INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY

    ENVIRONMENTAL HEALTH CRITERIA 145

    METHYL PARATHION

    This report contains the collective views of an international group of
    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization.

    Published under the joint sponsorship of
    the United Nations Environment Programme,
    the International Labour Organisation,
    and the World Health Organization

    First draft prepared by Dr R.F. Hertel and co-workers,
    Fraunhofer Institute of Toxicology and Aerosol
    Research, Hanover, Germany

    World Health Orgnization
    Geneva, 1993

         The International Programme on Chemical Safety (IPCS) is a
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    WHO Library Cataloguing in Publication Data

    Methyl parathion.

        (Environmental health criteria ; 145)

        1.Environmental exposure 2.Methyl parathion - adverse effects
        3.Methyl parathion - poisoning 4.Methyl parathion - toxicity 
        I.Series

        ISBN 92 4 157145 4        (NLM Classification: WA 240)
        ISSN 0250-863X

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    CONTENTS

    ENVIRONMENTAL HEALTH CRITERIA FOR METHYL
    PARATHION

    1. SUMMARY AND EVALUATION, CONCLUSIONS, RECOMMENDATIONS

         1.1. Summary and evaluation
              1.1.1. Exposure
              1.1.2. Uptake, metabolism, and excretion
              1.1.3. Effects on organisms in the environment
              1.1.4. Effects on experimental animals and
                         in vitro test systems
              1.1.5. Effects on human beings
         1.2. Conclusions
         1.3. Recommendations

    2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

         2.1. Identity
              2.1.1. Primary constituent
              2.1.2. Technical product
                   2.1.2.1.  Purity
         2.2. Physical and chemical properties
         2.3. Conversion factors
         2.4. Analytical methods
              2.4.1. Sampling, extraction, clean-up
                   2.4.1.1   Plant material (tobacco,
                             fruits, vegetables, crops
                             with low oil (fat) content)
                   2.4.1.2   Dairy products, products with a
                             high fat content (edible fats)
                   2.4.1.3   Blood, body fluids
                   2.4.1.4   Soil, sediments
                   2.4.1.5   Water
                   2.4.1.6   Air
                   2.4.1.7   Formulations
              2.4.2. Instrumental analytical methods
                   2.4.2.1   Gas chromatography
                   2.4.2.2   High performance liquid chroma-
                             tography (HPLC)
                   2.4.2.3   Thin layer chroma-
                             tography (TLC)
                   2.4.2.4   Spectrophotometry
                   2.4.2.5   Polarography
                   2.4.2.6   Mass spectrometry
              2.4.3. Detection limits
              2.4.4. Confirmatory method

    3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

         3.1. Natural occurrence
         3.2. Man-made sources
              3.2.1. Production process
              3.2.2. Loss into the environment
              3.2.3. Production
              3.2.4.    World consumption
              3.2.5. Formulations
         3.3. Uses

    4. ENVIRONMENTAL TRANSPORTATION, DISTRIBUTION, AND TRANSFORMATION

         4.1. Transportation and distribution between media
              4.1.1. Air
              4.1.2. Water
              4.1.3. Soil
              4.1.4. Vegetation and wildlife
              4.1.5. Entry into the food-chain
         4.2. Biotransformation
              4.2.1. Degradation involving biota
              4.2.2. Abiotic degradation
                   4.2.2.1   Photodegradation
                   4.2.2.2   Hydrolytic degradation
              4.2.3. Bioaccumulation
         4.3. Interaction with other physical,
              chemical, and biological factors
         4.4. Ultimate fate following use

    5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

         5.1. Environmental levels
              5.1.1. Air
              5.1.2. Water
              5.1.3. Soil
              5.1.4. Food
              5.1.5. Terrestrial and aquatic organisms
         5.2. General population exposure
         5.3. Occupational exposure during
              manufacture, formulation, or use

    6. KINETICS AND METABOLISM

         6.1. Absorption
         6.2. Distribution
         6.3. Metabolic transformation
         6.4. Elimination and excretion in expired air,
              faeces, or urine
         6.5. Retention and turnover

    7. EFFECTS ON ORGANISMS IN THE ENVIRONMENT

         7.1. Microorganisms
              7.1.1. Bacteria and fungi
              7.1.2. Algae
         7.2. Aquatic animals
              7.2.1. Short-term toxicity in
                        aquatic invertebrates
                   7.2.1.1   Laboratory studies on
                             single species
                   7.2.1.2   Mesocosmic studies
              7.2.2. Fish
                   7.2.2.1   Laboratory studies on
                             single species
                   7.2.2.2   Mesocosmic studies
              7.2.3. Amphibians
    7.3. Terrestrial organisms
              7.3.1. Plants
              7.3.2. Invertebrates
              7.3.3. Birds
              7.3.4. Non-laboratory mammmals

    8. EFFECTS ON EXPERIMENTAL ANIMALS AND  IN VITRO TEST SYSTEMS

         8.1. Single exposure
         8.2. Skin and eye irritation, sensitization
         8.3. Short-term exposures
         8.4. Long-term exposures
         8.5. Reproduction, embryotoxicity,
              and teratogenicity
         8.6. Mutagenicity related end-points
         8.7. Carcinogenicity
         8.8. Special studies
         8.9. Factors toxicity
         8.10. Mode of action
              8.10.1. Inhibition of esterases
              8.10.2. Possible alkylation of
                        biological macromolecules
              8.10.3. General

    9. EFFECTS ON MAN

         9.1. General population exposure
              9.1.1. Acute toxicity
              9.1.2. Effects of short- and
                        long-term exposure,
                        controlled human studies
         9.2. Occupational exposure
              9.2.1. Epidemiological studies

    10. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

         REFERENCES

         ANNEX I

         RESUME

         RESUMEN

    WHO TASK GROUP ON ENVIRONMENTAL HEALTH
    CRITERIA FOR METHYL PARATHION

    Members

    Dr L.A. Albert, Consultores Ambientales Asociados, S.C.,
         Xalapa, Veracruz, Mexico  (Vice-Chairman)

    Dr S. Dobson, Ecotoxicology and Pollution Section, Institute of
         Terrestrial Ecology, Monks Wood Experimental Station, Abbots
         Ripton, Huntingdon, Cambridgeshire, United Kingdom

    Dr D.J. Ecobichon, Pharmacology and Therapeutics, McGill
         University, Montreal, Canada  (Chairman)

    Dr R.F. Hertel, Fraunhofer Institute of Toxicology & Aerosol
         Research, Hanover, Germany  (Co-rapporteur)

    Dr S.K. Kashyap, National Institute of Occupational Health,
         Meghaninagar, Ahmedabad, India

    Dr I. Nordgren, Department of Toxicology, Karolinska Institute,
         Stockholm, Sweden

    Dr K.C. Swentzel, Toxicology Branch II, Health Effects Division,
         US Environmental Protection Agency, Washington, DC, USA
          (Co-rapporteur)

    Dr M. Tasheva, Department of Toxicology, Institute of Hygiene and
         Occupational Health, Medical Academy, Sofia, Bulgaria

    Dr L. Varnagy, Department of Agrochemical Hygiene, University of
         Agricultural Sciences, Institute for Plant Protection,
         Keszthely, Hungary

    Observers

    Dr W. Flucke, Bayer AG, Fachbereich Toxikologie, Institut für
         Toxikologie Landwirtschaft, Wuppertal, Germany

    Secretariat

    Dr K.W. Jager, International Programme on Chemical Safety, World
         Health Organization, Geneva, Switzerland  (Secretary)

    Dr E. Matos, Unit of Carcinogen Identification and Evaluation,
         International Agency for Research on Cancer (IARC), Lyon,
         France

    NOTE TO READERS OF THE CRITERIA
    MONOGRAPHS

         Every effort has been made to present information in the
    criteria monographs as accurately as possible without unduly
    delaying their publication. In the interest of all users of the
    environmental health criteria monographs, readers are kindly
    requested to communicate any errors that may have occurred to the
    Director of the International Programme on Chemical Safety, World
    Health Organization, Geneva, Switzerland, in order that they may be
    included in corrigenda.

                                  * * *

         A detailed data profile and a legal file can be obtained from
    the International Register of Potentially Toxic Chemicals, Palais
    des Nations, 1211 Geneva 10, Switzerland (Telephone No. 7988400 -
    7985850).

    NOTE:  The proprietary information contained in this monograph
    cannot replace documentation for registration purposes, because the
    latter has to be closely linked to the source, the manufacturing
    route, and the purity/impurities of the substance to be registered. 
    The data should be used in accordance with paragraphs 82-84 and
    recommendations paragraph 90 of the Second FAO Government
    Consultation (1982).

    ENVIRONMENTAL HEALTH CRITERIA FOR METHYL
    PARATHION

         A WHO Task Group on Environmental Health Criteria for Methyl
    Parathion met at the World Health Organization, Geneva from 19 to
    23 August 1991. Dr K.W. Jager, IPCS, welcomed the participants on
    behalf of Dr M. Mercier, Director of the IPCS, and the three IPCS
    cooperating organizations (UNEP/ILO/WHO). The Group reviewed and
    revised the draft and made an evaluation of the risks for human
    health and the environment from exposure to methyl parathion.

         The first draft of the EHC on methyl parathion was prepared by
    Dr R.F. Hertel and his co-workers of the Fraunhofer Institute of
    Toxicology and Aerosol Research in Hanover, Germany. The same group
    assisted in the preparation of the second draft, incorporating
    comments received following circulation of the first drafts to the
    IPCS contact points for Environmental Health Criteria monographs.

         Dr K.W. Jager of the IPCS Central Unit was responsible for the
    scientific content of the monograph, and Mrs M.O. Head of Oxford
    for the editing.

         The efforts of all who helped in the preparation and
    finalization of the monograph are gratefully acknowledged.

    1.  SUMMARY AND EVALUATION, CONCLUSIONS, RECOMMENDATIONS

    1.1  Summary and evaluation

    1.1.1  Exposure

         Methyl parathion is an organophosphorus insecticide that was
    first synthesized in the 1940s. It is relatively insoluble in water, 
    poorly soluble in petroleum ether and mineral oils, and readily
    soluble in most organic solvents. Pure methyl parathion consists of
    white crystals; technical methyl parathion is a light tan colour with
    a garlic-like odour. It is thermally unstable and undergoes fast
    decomposition above pH 8.

         Gas chromatography, with either alkali flame ionization (AFID) or
    flame photometric (FPD) detectors, is the most common method for the
    determination of methyl parathion. Detection limits range from 0.01 to
    0.1 µg/litre in water, and from 0.1 to 1 ng/m3 in air. HPLC and TLC
    are also useful methods of detection.

         The distribution of methyl parathion in air, water, soil, and
    organisms in the environment is influenced by several physical,
    chemical, and biological factors.

         Studies using model ecosystems and mathematical modelling
    indicate that methyl parathion partitions mainly into the air and soil 
    in the environment with lesser amounts going to plants and animals.
    There is virtually no movement through soil and neither the parent
    compound nor its breakdown products will normally reach ground water.
    Methyl parathion in air mainly arises from the spraying of the
    compound, though some volatilization occurs with the evaporation of
    water from leaves and the soil surface. Background atmospheric levels
    of methyl parathion in agricultural areas range from not detectable to
    about 70 ng/m3. Air concentrations after spraying have been shown to
    decline rapidly over 3 days reaching background levels after about 9
    days. Levels in river water (in laboratory studies) declined to 80% of
    the initial concentration after 1 h and 10% after 1 week. Methyl
    parathion is retained longer in soil than in air or water, though
    retention is greatly influenced by soil type; sandy soil can lose
    residues of the compound more rapidly than loams. Residues on plant
    surfaces and within leaves decline rapidly with half lives of the
    order of a few hours; complete loss of methyl parathion occurs within
    about 6-7 days.

         Animals can degrade methyl parathion and eliminate the
    degradation products within a very short time. This is slower in lower
    vertebrates and invertebrates than in mammals and birds.
    Bioconcentration factors are low and the accumulated methyl parathion
    levels transitory.

         By far the most important route for the environmental degradation
    of methyl parathion is microbial degradation. Loss of the compound in
    the field and in model ecosystems is more rapid than that predicted
    from laboratory studies. This is because of the variety of
    microorganisms capable of degrading the compound in different habitats
    and circumstances. The presence of sediment or plant surfaces, which
    increases the microbial populations, increases the rate of breakdown
    of methyl parathion.

         Methyl parathion can undergo oxidative degradation, to the less
    stable methyl paraoxon, by ultraviolet radiation (UVR) or sunlight;
    sprayed films degrade under UVR with a half-life of about 40 h.
    However, the contribution of photolysis to total loss in an aquatic
    system has been estimated to be only 4%. Hydrolysis of methyl
    parathion also occurs and is more rapid under alkaline conditions.
    High salinity also favours hydrolysis of the compound. Half-lives of
    a few minutes were recorded in strongly reducing sediments, though
    methyl parathion is more stable when sorbed on other sediments.

         In towns in the centre of agricultural areas of the USA, methyl
    parathion concentrations in air varied with season and peaked in
    August or September; maximum levels in surveys were mainly in the
    range of 100-800 ng/m3 during the growing season. Concentrations in
    natural waters of agricultural areas in the USA ranged up to 0.46
    µg/litre, with highest levels in summer. There are only small numbers
    of published reports on residues of methyl parathion in food
    throughout the world. In the USA, residues of methyl parathion in food
    have generally been reported at very low levels with few individual
    samples exceeding maximum residue limits (MRLs). Only trace residue
    levels of methyl parathion were detected in the total dietary studies
    reported. Methyl parathion residues were highest in leafy (up to 2
    mg/kg) and root (up to 1 mg/kg) vegetables in market basket surveys in
    the USA between 1966 and 1969. Food preparation, cooking, and storage
    all cause decomposition of methyl parathion residues further reducing
    exposure of humans. Raw vegetables and fruits may contain higher
    residues after misuse.

         The production, formulation, handling, and use of methyl
    parathion as an insecticide are the principal potential sources of
    exposure of humans.  Skin contact and, to a lesser degree, inhalation
    are the main routes of exposure of workers.

         In a study on farm spray-men (with unprotected workers using
    ultra-low-volume (ULV) handsprays) an intake of 0.4-13 mg of methyl
    parathion per 24 h was calculated from the excreted  p-nitrophenol in
    the urine. Early re-entry into treated crops is a further source of
    exposure.

         The general population may be exposed to air-, water-, and
    food-borne residues of methyl parathion as a consequence of
    agricultural or forestry practices, the misuse of the agent resulting
    in the contamination of fields, crops, water, and air through
    off-target spraying.

    1.1.2  Uptake, metabolism, and excretion

         Methyl parathion is readily absorbed via all routes of exposure
    (oral, dermal, inhalation) and is rapidly distributed to the tissues
    of the body. Maximum concentrations in various organs were detected
    1-2 h after treatment. Conversion of methyl parathion to methyl
    paraoxon occurs within minutes of administration. A mean terminal
    half-life of 7.2 h was determined in dogs following intravenous (i.v.)
    administration of methyl parathion. The liver is the primary organ of
    metabolism and detoxification. Methyl parathion or methyl paraoxon are
    mainly detoxified in the liver through oxidation, hydrolysis, and
    demethylation or dearylation with reduced glutathione (GSH). The
    reaction products are  O-methyl  O-p-nitrophenyl phosphorothioate or
    dimethyl phosphorothioic or dimethylphosphoric acids and
     p-nitrophenol. Therefore, it is possible to estimate exposure by
    measuring the urinary excretion of  p-nitrophenol; urinary excretion
    of  p-nitrophenol by human volunteers was 60% within 4 h and
    approximately 100% within 24 h.  The metabolism of methyl parathion is
    important for species selective toxicity, and the development of
    resistance. The elimination of methyl parathion and metabolic products
    occurs primarily via the urine.  Studies conducted on mice with
    radiolabelled (32P-methyl parathion) revealed 75% of radioactivity in
    the urine and up to 10% radioactivity in the faeces after 72 h.

    1.1.3  Effects on organisms in the environment

         Microorganisms can use methyl parathion as a carbon source and
    studies on a natural community showed that concentrations of up to 5
    mg/litre increased biomass and reproductive activity. Bacteria and
    actinomycetes showed a positive effect of methyl parathion while fungi
    and yeasts were less able to utilize the compound. A 50% inhibition of
    growth of a diatom occurred at about 5 mg/litre. Cell growth of
    unicellular green algae was reduced by between 25 and 80 µg methyl
    parathion/litre. Populations of algae became tolerant after exposure
    for several weeks.

         Methyl parathion is highly toxic for aquatic invertebrates with
    most LC50s ranging from < 1 µg to about 40 µg/litre. A few
    arthropod species are less susceptible. The no-effect level for the
    water flea  (Daphnia magna) is 1.2 µg/litre. Molluscs are much less
    susceptible with LC50s ranging between 12 and 25 mg/litre.

         Most fish species in both fresh and sea water have LC50s of
    between 6 and 25 mg/litre with a few species substantially more or
    less sensitive to methyl parathion. The acute toxicity for amphibians
    is similar to that for fish.

         Population effects have been seen on communities of aquatic
    invertebrates in experimental ponds treated with methyl parathion. The
    concentrations needed to cause these effects would occur only with
    overspraying of water bodies and, even then, would last for only a
    short time. Population effects are, therefore, unlikely to be seen in
    the field. Kills of aquatic invertebrates would be unlikely to lead to
    lasting effects.

         Care should be taken to avoid overspraying of ponds, rivers, and
    lakes, when using methyl parathion. The compound should never be
    sprayed under windy conditions.

         Methyl parathion is a non-selective insecticide that kills
    beneficial species as readily as pests. Kills of bees have been
    reported following spraying of methyl parathion. Incidents concerning
    bees were more severe with methyl parathion than with other
    insecticides. Africanized honey bees are more tolerant of methyl
    parathion than European strains.

         Methyl parathion was moderately toxic for birds in laboratory
    studies, with acute oral LD50s ranging between 3 and 8 mg/kg body
    weight. Dietary LC50s ranged from 70 to 680 mg/kg diet. There is no
    indication that birds would be adversely affected from recommended
    usage in the field.

         Extreme care must be taken to time methyl parathion spraying to
    avoid adverse effects on honey bees.

    1.1.4  Effects on experimental animals and in vitro test systems

         Oral LD50 values of methyl parathion in rodents range from 3 to
    35 mg/kg body weight, and dermal LD50 values, from 44 to 67 mg/kg
    body weight.

         Methyl parathion poisoning causes the usual organophosphate
    cholinergic signs attributed to accumulation of acetylcholine at nerve
    endings. Methyl parathion becomes toxic when it is metabolized to
    methyl paraoxon. This conversion is very rapid. No indications of
    organophosphorous-induced, delayed neuropathy (OPIDN) have been
    observed.

         Technical methyl parathion was found not to have any primary eye
    or skin irritating potential.

         In short-term toxicity studies, using various routes of
    administration on the rat, dog, and rabbit, inhibition of plasma, red
    blood cell, and brain ChE, and related cholinergic signs were
    observed. In a 12-week feeding study on dogs, the no-observed-
    adverse-effect level (NOAEL) was 5 mg/kg diet (equivalent to 0.1 mg/kg
    body weight per day). In a 3-week dermal toxicity study on rabbits,
    the no-observed-effect-level (NOEL) was 10 mg/kg body weight daily. 
    Inhalation exposure for 3 weeks indicated a NOEL of 0.9 mg/m3 air. 
    At 2.6 mg/m3, only slight inhibition of plasma ChE was observed.

         Long-term toxicity/carcinogenicity studies were carried out on
    mice and rats. The NOEL for rats was 0.1 mg/kg body weight per day,
    based on ChE inhibition. There is no evidence of carcino genicity in
    mice and rats, following long-term exposure. In another 2-year study
    on rats, however, there was evidence of a peripheral neurotoxic effect
    at a dose of 50 mg/kg diet.

         Methyl parathion has been reported to have DNA-alkylating
    properties  in vitro.  The results of most of the  in vitro
    genotoxicity studies on both bacterial and mammalian cells were
    positive, while 6  in vivo studies using 3 different test systems
    produced equivocal results.

         In reproduction studies, at toxic dose levels (ChE inhibition),
    there were no consistent effects on litter size, number of litters,
    pup survival rates, and lactation performance. No primary teratogenic
    or embryotoxic effects were noted.

    1.1.5  Effects on human beings

         Several cases of acute methyl parathion poisoning have been
    reported. Signs and symptoms are those characteristic of systemic
    poisoning by cholinesterase-inhibiting organophosphorous compounds.
    They include peripheral and central cholinergic nervous system
    manifestations appearing as rapidly as a few minutes after exposure.
    In case of dermal exposure, symptoms may increase in severity for more
    than one day and may last several days.

         Studies on volunteers, following repeated, long-term exposures,
    suggest that there is a decrease in blood cholinesterase activities
    without clinical manifestations.

         No cases of organophosphorous-induced, delayed peripheral
    neuropathy (OPIDN) have been reported. Neuro-psychiatric sequelae have
    been reported in cases of multiple exposure to pesticides including
    methyl parathion.

         An increase in chromosomal aberrations has been reported in cases
    of acute intoxications.

         No human data were available to evaluate the teratogenic and
    reproductive effects of methyl parathion.

         The available epidemiological studies deal with multiple exposure
    to pesticides and it is not possible to evaluate the effects of
    long-term exposure to methyl parathion.

    1.2  Conclusions

         Methyl parathion is a highly toxic organophosphorus ester
    insecticide. Overexposure from handling during manufacture, use,
    and/or accidental or intentional ingestion may cause severe or fatal
    poisoning. Methyl parathion formulations may, or may not, be
    irritating to the eyes or to the skin, but are readily absorbed. As a
    consequence, hazardous exposures may occur without warning.

         Methyl parathion is not persistent in the environment. It is not
    bioconcentrated and is not transferred through food-chains. It is
    degraded rapidly by many microorganisms and other forms of wild life.
    This insecticide is likely to cause damage to ecosystems only in
    instances of heavy over-exposure resulting from misuse or accidental
    spills; however, pollinators and other beneficial insects are at risk
    from spraying with methyl parathion.

         Exposure of the general population to methyl parathion residues
    occurs predominantly via food.  If good agricultural practices are
    followed, the Acceptable Daily Intake (0-0.02 mg/kg body weight),
    established by FAO/WHO, will not be exceeded.  Dermal exposure may
    also occur through accidental contact with foliar residues in sprayed
    fields or in areas adjacent to spraying operations as a consequence of
    off-target loss of the chemical.

         With good work practices, hygienic measures, and safety
    precautions, methyl parathion is unlikely to present a hazard for
    those occupationally exposed.

    1.3  Recommendations

    *    For the health and welfare of workers and the general population,
         the handling and application of methyl parathion should be
         entrusted only to competently supervised and well-trained
         applicators, who must follow adequate safety measures and use the
         chemical according to good application practices.

    *    The manufacture, formulation, agricultural use, and disposal of
         methyl parathion should be carefully managed to minimize
         contamination of the environment.

    *    Regularly exposed workers should receive appropriate monitoring
         and health evaluation.

    *    To minimize risks for all individuals, a 48-h interval between
         the spraying and re-entry into any sprayed area is recommended.

    *    Pre-harvest intervals should be established and enforced by
         national authorities.

    *    In view of the high toxicity of methyl parathion, this agent
         should not be considered for use in hand-applied, ULV spraying
         practices.

    *    Do not overspray water bodies. Choose spraying times to avoid
         killing pollinating insects.

    *    Information on the health status of workers exposed only to
         methyl parathion (i.e.,  in manufacture, formulation) should be
         published, in order to better evaluate the risks of this chemical
         for human health.

    *    More definitive studies should be conducted on residues of methyl
         parathion in fresh foods.

    *    A more definitive genotoxic assessment of methyl parathion should
         be conducted.

    2.  IDENTITY, PHYSICAL AND CHEMICAL  PROPERTIES, ANALYTICAL METHODS

    2.1  Identity

    2.1.1  Primary constituent

    Molecular formula:  C8H10NO5PS

    Relative molecular mass:      263.23

    Common names:                 methyl parathion 
                                  accepted by
                                  ESA (Entomological Society of
                                  America)
                                  JMAF (Japanese Ministry of
                                  Agriculture, Fisheries and Food)
                                  WHO (World Health Organization)

                                  parathion-methyl
                                  accepted by
                                  BSI (British Standards Institution)
                                  ISO (International Organization for
                                  Standardization)

                                  metaphos
                                  accepted by the USSR

    CAS chemical name:             O,O-dimethyl  O-(4-nitro-phenyl)
                                  phosphorothioate

    IUPAC systematic name:         O,O-Dimethyl  O-4-nitrophenylphos-
                                  phorothioate

    CAS registry number:          298-00-0

    RTECS number:                 TG 0175000

    EINECS number:                206-050-1

    EEC number:                   015-035-00-7

    Common synonyms:

         Demethylfenitrothion; dimethyl  para-nitrophenyl
         monothiophosphate;  O,O-dimethyl O-( para-nitrophenyl)
         phosphorothioate; dimethyl  para-nitrophenyl phosphorothionate;
         dimethyl 4-nitrophenyl phosphorothionate;  O,O-dimethyl
          O-(para-nitrophenyl) thionophosphate; dimethyl
          para-nitrophenyl thiophosphate;
          O,O-dimethyl- O-(para-nitrophenyl) thiophosphate; dimethyl
         parathion; ENT 17292; metaphos; methyl-parathion; methylthiophos;
         MPT; NCI CO2971; parathion methyl homolog; phosphorothioic acid
          O,O-dimethyl  O-(4-nitro-phenyl) ester; phosphorothioic acid
          O,O-dimethyl  O-(para-nitrophenyl) ester BAY 11405; 8056 HC;
         E601

    2.1.2  Technical product

    Major trade names:

         A-Gro; Azofos; Azophos; Bladan M; Cekumethion; Dalf;  Divithion;
         Drexel Methyl Parathion 4E & 601; Dygun; Dypar; Ekatox; Folidol
         M, M40 & 80; Fosferno M50; Gearphos; Mepaton; Meptox; Metacid 50;
         Metacide; Metafos; Metaphos; Methyl-E 605; Methyl Fosferno; 
         Methylthiophos; Metron; M-Parathion; Niletar; Niran M-4; Nitran;
         Nitrox; Nitrox 80; Oleovofotox; Parapest M-50;  Parataf; Paratox;
         Paridol; Parton M; Penncap M & MLS;  Sinafid M-48; Sixty-Three
         Special E.C. Insecticide; Tekwaisa; Thiophenit; Thylpar M-50;
         Toll; Unidol; Vertac Methyl Parathion; technical product 80%,
         Wofatox; Wolfatox.

    2.1.2.1.  Purity

         Technical methyl parathion is available as a solution containing
    80% active ingredient (a.i.), 16.7% xylene, and 3.3% inert
    ingredients. 

         The following impurities were identified in one sample of
    technical-grade methyl parathion:  O,O-dimethyl- S-methyl
    dithiophosphate, nitroanisol, nitro-phenol, isomers of methyl
    parathion, and the dithio-analogue of methyl parathion (Warner, 1975).

    2.2  Physical and chemical properties

    Physical state:          pure: white crystalline solid or powder
                             (National Fire Protection Association, 1986)

                             technical (80%) pure: light to dark tan
                             liquid (Worthing & Walker, 1987)

    Melting point:           37-38 °C (The Merck Index, 1983)
                             35-36 °C (Worthing, 1983)

    Freezing point:          about 29 °C (technical product)
                             (Worthing & Walker, 1987)

    Density/specific gravity:

                             1.358 at 20 °C/40 °C (d204  1.358)
                             (The Merck Index, 1983)

    Vapour pressure:         1.3 mPa at 20 °C
                             (Worthing & Walker, 1987)

    Octanol/water partition coefficient:

                             log Kow = 2.68 (measured) 
                             log Kow = 1.81-3.43 (reported range) 
                             (Hansch & Leo, 1987)

    Water solubility:        55-60 mg/litre at 25 °C (pure)
                             (Midwest Research Institute, 1975;
                             National Research Council, 1977)
                             37.7 mg/litre at 19 °C (pure)
                             (Bowman & Sans, 1979)
                             57 mg/litre at 22 °C (anal. grade)
                             (Sanders & Seiber, 1983)

    Nonaqueous solubility:   soluble in ethanol, chloroform,
                             aliphatic solvents, and slightly
                             soluble in light petroleum

    Volatility (pure):       0.14 mg/m3 at 20 °C (Spencer, 1982)

    Odour:                   like rotten eggs or garlic (technical grade)
                             (Midwest Research Institute, 1975; Anon.,
                             1984)

    Odour threshold:         0.0125 mg/m3 (Akhmedov, 1968) 

    Other properties:        hydrolyses and isomerizes easily
                             (White-Stevens, 1971)

    Half-life in aqueous solution at 20 °C, pH 1-5:
                             175 days (Melnikov, 1971)

    2.3  Conversion factors

         1 ppm methyl parathion= 10.76 mg/m3 at 25 °C, 1066 mbar

         1 mg methyl parathion/m3 = 0.0929 ppm

    2.4  Analytical methods

    2.4.1  Sampling, extraction, clean-up

         Standardized methods for the determination of various residues
    are reported in the  Manual of pesticide residue analysis (Thier &
    Zeumer, 1987).

    2.4.1.1  Plant material (tobacco, fruits, vegetables, crops with low
    oil (fat) content)

    (a)    Extraction

         Three extraction methods have mainly been used, all of which are
    suitable for multiresidue analysis.

    (1)  Soxhlet extraction with chloroform - 10% methanol has been
         proposed for field-weathered crops by Bowman (1981).

    (2)  Acetonitrile combined with various amounts of water has been used
         by Mills et al. (1963), Wessel (1967), Osadchuk et al. (1971),
         Luke et al. (1975), and Stahr et al. (1979). The plant material
         is homogenized in a blender with acetonitrile, in some instances
         after the addition of Celite (Nelson, 1967; Funch, 1981;).
         High-moisture products (fruits and vegetables) are extracted with
         pure acetonitrile while samples of dry products (hays, grains,
         feedstuff) are blended with acetonitrile-water (65:35).
         Extraction is followed by solvent partitioning into petroleum
         ether with the addition of sodium chloride (Mills et al., 1963;
         Wessel, 1967; Nelson, 1967) into dichloromethane (Funch, 1981),
         and dichloromethane/hexane (10:200) (Osadchuk et al., 1971).

    (3)  Acetone was preferred as the solvent in particular in
         multiresidue analysis by Becker (1971), Pflugmacher & Ebing
         (1974), Sagredos & Eckert (1976), Becker (1979), Specht & Tillkes
         (1980), Miellet (1982), Sonobe et al. (1982), Luke & Doose
         (1983), Luke & Doose (1984), Ebing (1985), Andersson & Ohlin
         (1986), Vogelsang & Thier (1986), Gyorfi et al. (1987), Thier &
         Zeumer (1987), and Becker & Schug, (1990). In some instances,
         celite was added. Depending on the water content of the sample,
         water was added. In a second step, the acetone extracts were  
         further extracted with either dichloromethane, dichloro 
         methane/petroleum ether, or dichloromethane/ n-hexane. The  
         extract was dried over anhydrous sodium sulfate, reduced in  
         volume in a Kuderna-Danish concentrator, and subjected to  
         further clean-up.

         Extraction with acetone- o-xylene (19:1) (Ross & Harvey, 1981),
         toluene/hexane (75:25) (Johansson, 1978), chloroform (Ault et
         al., 1979), or supercritical fluid extraction using methanol
         (Capriel et al., 1986), has also been reported.

    (b)    Column clean-up 

         The published clean-up procedures are usually suitable for
    multiresidue analysis. For plant material with a low fat content, 3
    column clean-up procedures have been developed.

    (1)  The oldest method involves the use of chromatography on Florisil
         (often topped with anhydrous sodium sulfate) (Mills et al., 1963;
         Nelson, 1967; Schnorbus & Phillips, 1967; Wessel, 1967; Beckman
         & Garber, 1969; Osadchuk et al., 1971; Luke et al., 1975;
         Johansson, 1978; Gretch & Rosen, 1984, 1987). Although it has
         been claimed that organo phosphorous pesticides are partially
         lost during Florisil clean-up (Luke et al., 1975), high
         recoveries (usually > 80 %) have been reported for methyl
         parathion. Various solvents and solvent mixtures are used for
         chromatography on Florisil including: diethylether/petroleum
         ether, ethyl ether/hexane, and acetone/toluene,
         diethylether/petroleum ether being the most frequently used.
         Fractionation is achieved by increasing successively the
         diethylether content. Florisil clean-up is usually used for a
         combined clean-up of organochlorine and organophosphorous
         pesticides. Luke et al. (1975) reported that gas chromatography
         (GC) with a thermionic detector was sufficiently selective to
         detect organophosphorous pesticides without Florisil clean-up.

    (2)  Alternatively, clean-up of pesticides in multiresidue analysis
         has been achieved by chromatography on charcoal (Becker, 1971,
         1979; Miellet, 1982; Sonobe et al., 1982; Luke & Doose, 1984;
         Ebing, 1985; Gyorfi et al., 1987). To this end, charcoal is mixed
         with silica gel (1:15) (and sometimes also celite or magnesia).
         In most instances, elution is achieved with mixtures of
         dichloromethane/acetone/toluene (e.g., 5:1:1) (Ebing, 1985; Thier
         & Zeumer, 1987). Recoveries are high (often > 90 %). Charcoal
         clean-up is particularly suited for dry products (< 10 % water).
         The simultaneous clean-up of organochlorine and organo-
         phosphorous pesticides is also possible with chromatography on
         charcoal.

    (3)  In recent years, a clean-up of pesticides in multiresidue  
         analysis by gel permeation chromatography (GPC) has become
         popular (Pflugmacher & Ebing, 1974; Ault et al., 1979; Specht &
         Tillkes, 1980; Andersson & Ohlin, 1986; Vogelgesang & Thier,
         1986; Steinwandter, 1988). The stationary phase consists, in most
         instances, of Bio Beads SX3 (a polystyrene gel). Ethyl
         acetate/cyclohexane (1:1), dichloromethane/cyclohexane (1:1) and,
         more recently, acetone/cyclohexane (3:1) have been used as
         elution mixtures. Gel permeation chromatography is mainly used to 
         protect the GC column and the GC detector against contam- 
         ination. GPC removes material of higher relative molecular mass.
         Recoveries > 85% have been reported. Frequently, GPC is combined
         with the additional purification step of silica gel
         chromatography (Specht & Tillkes, 1980; Andersson & Ohlin, 1986;
         Vogelsaifng & Thier, 1986) where elution is achieved with
         toluene/hexane (35:65), followed by toluene and acetone/toluene,
         with increasing acetone content. However, while the additional
         clean-up by silica gel column chromatography is important when
         organo chlorine pesticides are present, it is not necessary for 
         organophosphorous pesticides if analysis is performed by gas
         chromatography with flame photometric detection.

    2.4.1.2  Dairy products, products with a high fat content (edible
    fats)

         Clean-up techniques for products with a high fat content have
    been reviewed by Waters (1990). Florisil column chromatography and gel
    permeation chromatography are also suited for a clean-up of samples
    with a high fat content. In addition, clean-up using normal phase HPLC
    has been reported (Gillespie & Waters, 1986). Fat is dissolved in
     n-hexane and fractionated on silica gel HPLC using
    dichloromethane/hexane as solvent. However, complete separation
    ofmethyl parathion from the fat is not achieved. As an alternative,
    fat is adsorbed on aluminum oxide (Luke & Doose, 1984) or on Calflo E
    (calcium silicate) (Specht, 1978; Thier & Zeumer, 1987). Finally, a
    sweep codistillation clean-up of edible oils has been reported by

    Storherr et al. (1967) and Watts & Storherr (1967). This method has
    been standardized also for plant material (Thier & Zeumer, 1987).
    After extraction of the sample with ethyl acetate, the concentrated
    extract is injected into a heated glass column packed with glass wool
    or glass beads followed by the injection of ethyl acetate or petroleum
    ether in a nitrogen stream. The nitrogen carrier gas sweeps the
    volatile component through the tube to a condensing bath and through
    an Arnakrom scrubber tube to a collection tube. Sweep codistillation
    may be followed by a further Florisil clean-up.

         The extraction and clean-up of vegetable oil can be speeded up by
    performing extraction and clean-up in one step using a system of three
    ready-to-use cartridges in series (Extralut-3, Sep-Pack silicade1 and
    Sep-Pack C18) where the assembled columns are eluted with
    acetonitril (saturated with  n-hexane) (Di Muccio et al., 1990).

    2.4.1.3  Blood, body fluids

         Methyl parathion is extracted from blood with hexane or benzene
    and analysed without further clean-up (Gabica et al., 1971; De Potter
    et al., 1978). No extraction is necessary if methyl parathion is
    determined by polarography (Zietek, 1976).

         Measurement of the urinary metabolites and the cholinesterase
    activity were used to supervise the exposure of workers coming into
    contact with methyl parathion or parathion and to observe their
    elimination in cases of poisoning (see section 5.3) (Elliot et al.,
    1960; Arterberry et al., 1961; Shafic & Enos, 1969; Wolfe et al.,
    1970; Ware et al., 1974b; NIOSH, 1976).

    2.4.1.4  Soil, sediments

         Methyl parathion is extracted from soil with acetone,
    acetone/ n-hexane or hexane/isopropanol (Schutzmann et al., 1971;
    Agishev et al., 1977; Garrido & Monteoliva, 1981; Wegman et al., 1984;
    Kjoelholt, 1985). It is partitioned in a second step into
    dichloromethane. While several authors determine the pesticides
    without further clean-up, additional silica gel adsorption
    chromatography has been used by Wegman et al., (1984) and Kjoelholt
    (1985). The recovery of methyl parathion is 70-85%.

         When sediments are analysed, elemental sulfur represents a
    particular problem. Kjoelholt et al. separated the sulfur by tetra
    butylammonium hydrogensulfate (Kjoelholt, 1985), while Schutzmann et
    al. (1971) refluxed the sediment extract with Raney copper.

         For the extraction, the sediment mixed with sand and sodium
    sulfate can be placed into a column and eluted using acetone :
    dichloromethane (1:1) (Belisle & Swineford, 1988).

    2.4.1.5  Water

         Extraction and concentration of methyl parathion from water is 
    achieved either by liquid/liquid extraction (Kawahara et al., 1967;
    Pionke et al., 1968; Mestres et al., 1969; Konrad et al., 1969; Zweig
    & Devine, 1969; Schutzmann et al., 1971; Coburn & Chau, 1974; Chmil et
    al., 1978; Chernyak & Oradovskii, 1980; Miller et al., 1981; Spingarn
    et al., 1982; Bruchet et al., 1984; Albanis et al., 1986; Li & Wang,
    1987; Brodesser & Schoeler, 1987), or by adsorption on polymeric
    material (Paschal et al., 1977; Le Bel et al., 1979; Agostiano et al.,
    1983; Xue, 1984; Clark et al., 1985). Various solvents have been used
    for solvent extractions including: diethyl ether/hexane (1:1),
    benzene, petroleum ether, hexane/isopropanol; chloroform,
    dichloromethane, and ethyl acetate. Recoveries have been  high (in
    most instances > 90 %). If the liquid/liquid extraction is scaled up
    using a "Goulden large sample extractor" and 120 litre of water,
    detection limits may be lower by a factor of about 150 compared with
    1-litre samples (i.e., a detection limit of 2.5 ng/litre (ppt) has
    been achieved for methyl parathion) (Foster & Rogerson, 1990). The
    extraction efficiency can be further improved by continuous
    liquid-liquid extraction, which allows the use of non-polar solvents
    as  n-pentane (Bruchet et al., 1984; Brodesser & Schoeler, 1987). 
    Water samples are frequently analysed for pesticides without further
    clean-up, while Florisil clean-up has been used in some instances
    (Mestres et al., 1969; Miller et al., 1981). 

         High concentration factors are achieved, if methyl parathion (and
    other pesticides) are adsorbed on polymeric material, such as XAD-2
    (Paschal et al., 1977; Le Bel et al., 1979), XAD-4 (Xue et al., 1984),
    Tenax (Agostiano et al., 1983) or Porapack Q (Clark et al., 1985).
    Elution from XAD is achieved with diethyl ether, acetone/hexane
    (15:85), diethyl ether-hexane (85:15). Recoveries are >90 %. If Tenax
    is used, both solvent elution (diethyl ether) or thermoelution can be
    used to desorb the pesticides. Solid-phase extraction (using C-18
    cartridges) will become the method of choice for the rapid extraction
    of organophosphorous insecticides from water (Swineford & Belisle,
    1989; Sherma & Bretschneider, 1990).

    2.4.1.6  Air

         Most methods for the determination of pesticides in air have been
    developed as multiresidue methods. Pesticides in air are either
    absorbed in liquids or adsorbed on polymeric material. Thus,
    pesticides may be trapped in ethylene glycol, which is subsequently
    extracted with dichloromethane (Tessari & Spencer, 1971; Sherma &
    Shafik, 1975) or they may be trapped on glass beads coated with
    cottonseed oil (Compton, 1973). Further clean-up is achieved by silica
    gel or Florisil column chromatography.

         Among the solid polymeric material used to trap pesticides,
    polyurethane foam (PUF) is by far the most popular (Lewis et al.,
    1977; Rice et al., 1977; Lewis & McLeod, 1982; Lewis & Jackson, 1982;
    Belashova et al., 1983; Beine, 1987). Air can be collected both with
    low-volume (approx. 4 litre/min) or high-volume samplers (up to 250
    litre/min). PUF can be reused after careful cleaning (e.g., with 5%
    diethyl ether in  n-hexane). In some instances, Tenax, Chromosorb
    102, or Porapack R is sandwiched between PUF plugs to enhance the
    collection efficiency. Collection efficiencies in excess of 80% have
    been reported for methyl parathion. A filter may be added to remove
    particulate matter (Lewis et al., 1977). Methyl parathion is usually
    determined without further clean-up. Finally, XAD-4 (Wehner et al.,
    1984) and silica gel (Klisenko & Girenko, 1980; Liang & Zhang, 1986)
    have been used as solid trapping materials.

    2.4.1.7  Formulations

         When analysing formulations, the determination of by-products and
    impurities is an important objective. A variety of instrumental
    techniques have been used for the analysis of formulations including:
    gas chromatography (Jackson, 1976; Jackson, 1977a), high performance
    liquid chromatography (Jackson, 1977b), infrared analysis (Goza,
    1972), P-31-nuclear magnetic resonance spectroscopy (Greenhalgh et
    al., 1983), and spectrophotometry after alkaline hydrolysis to
     p-nitrophenol (Blanco & Sanchez, 1989). An inter laboratory study
    has been carried out using both GC (Jackson, 1977a) and HPLC (Jackson,
    1977b). With both methods, coefficients of variation of 1.7% have been
    determined. The instrumental techniques are described below.

    2.4.2  Instrumental analytical methods

    2.4.2.1  Gas chromatography

         Gas chromatrophic (GC) methods for the determination of
    pesticides (including methyl parathion) have been reviewed by Ebing
    (1987).

         Organophosphorous pesticides, including methyl parathion, are
    sufficiently volatile and thermally stable to be amenable to gas
    chromatography and it is by far the most important method for the
    determination of methyl parathion. This technique provides the good
    resolution necessary for multiresidue analysis. Moreover, very
    sensitive and specific detectors are available, in particular for the
    analysis of organophosphorous pesticides.

    (a)    Detectors 

         The two most widely used detectors for organophosphorous
    pesticides are the alkali flame ionization detector (AFID) and
    variations of this detector (thermionic detector (Patterson, 1982),
    nitrogen-phosphorous detector) and the flame photometric detector
    (FPD) (Bowman, 1981). The AFID makes use of the phenomenon that the
    flame ionization detector yields enhanced response to nitrogen- and
    phosphorus-containing compounds, in the presence of alkali metal
    salts. The detection limit is in the low picogram range. The detector
    discriminates against other compounds 30-50 fold. The flame
    photometric detector (FPD) operates with a cool, hydrogen rich flame
    for the detection of phosphorus- and sulfur-containing compounds,
    which form POH and S2 species. These species emit light at 526 nm
    (POH) and 394 nm (S2), which is monitored by using interference
    filters and a photomultiplier. The detector is easy to operate and
    results are reproducible. The detector is highly specific. The
    response of 100 ng of parathion is 130 000 times greater than that of
    an equal amount of aldrin. Furthermore, It is of advantage that any
    solvent can be used with the detector. For the determination of methyl
    parathion the P mode is the method of choice, though the S mode can
    also be used (sensitivity 10 times lower) as methyl parathion contains
    both P and S atoms.

         Finally, the electron capture detector (ECD) is sometimes used
    for the analysis of methyl parathion as it responds not only to the
    P=S moiety, but in particular to the NO2 group.

    (b)     Columns

         A definite identification of a pesticide by its retention time on
    one column is not possible. Analysis on at least one further column
    with a stationary phase of different polarity is necessary to confirm
    the identity of a compound.

         Packed columns are frequently used for pesticide residue
    analysis, though resolution is substantially poorer compared with
    capillary columns and identification of the pesticides is less
    specific. Solid supports are usually of the Chromosorb W type. In some
    instances, Gaschrom Q has also been used. A large variety of
    stationary phases, used either alone or in admixture, have been
    employed.  The most frequently used phases are DC 200, QF-1, OV 17,
    OV-101, OV-210, and SE-30. Relative retention times for many
    stationary phases have been reported by several authors for a large
    variety of pesticides (up to 600 compounds including other industrial
    chemicals) (Bowman & Beroza, 1967; Ambrus et al., 1981b; Daldrup et
    al., 1981; Prinsloo & de Beer, 1987; Saxton, 1987; Suprock & Vinopal,
    1987; Omura et al., 1990).

         Packed column GC allows the separation of only a limited number
    of pesticides. Capillary columns exhibit a considerably better
    separation efficiency than packed columns. Such capillary columns have
    been used by several authors for methyl parathion analysis (Krijgsman
    & van den Kamp, 1976; Ripley & Braun, 1983; Stan & Goebel, 1983;
    Ebing, 1985; Andersson & Ohlin, 1986; Vogelsang & Thier, 1986). 
    Retention time data on a SE-30 capillary column have been reported
    (Ripley & Braun, 1983). Several injection techniques for capillary
    columns have been compared (Stan & Goebel, 1984; Stan & Mueller,
    1988). Cold splitless (PTV) injection appears to be best suited for
    organophosphorous pesticide analysis. The resolution can be further
    improved by applying two-dimensional capillary gas chromatography
    using two columns of different polarity (Stan & Mrowetz, 1983).

    2.4.2.2  High performance liquid chromatography (HPLC)

         The main advantage of HPLC is its ability to analyse compounds
    that are heat labile, such as phenylurea and carbamates. As stated
    above, organophosphorous pesticides including methyl parathion are
    sufficiently heat stable for analysis using gas chromatography and
    there is no direct need to use HPLC. Thus, relatively few studies
    dealing with the HPLC analysis of methyl parathion have been reported.

         HPLC analysis has been achieved using reversed phase
    chromatography, with acetonitrile/water (60:40) (Funch, 1981), or
    methanol/acetic acid/water (32:0.6:  47.4) as solvents, and UV-
    detection (Zhao & Wang, 1984). HPLC conditions for 166 pesticides
    including methyl parathion were reported by Lawrence & Turton (1978).
    Retention data of 560 pesticides and other industrial chemicals have
    been published by Daldrup et al. (1981, 1982) using two gradient
    systems.

         Sharma et al. (1990) developed a method for the rapid
    quantitative analysis of organophosphorus (including methyl parathion)
    and carbamate pesticides using HPLC and refractive index detection.

         HPLC appears to be particularly suited for the analysis of polar
    metabolites of methyl parathion (Abe et al., 1979).

         Fluorogenic labelling of organophosphorous pesticides leads to an
    improvement in sensitivity. Such labelling can be achieved by
    hydrolysis of the compounds to the corresponding phenols and
    derivatization with dansyl chloride (5-dimethylamino-naphthalene-1-
    sulfonyl chloride) (Lawrence et al., 1976). Besides the UV and
    fluorescence detector, electrochemical detectors have been used for
    the detection of methyl parathion using amperometric detection in the
    reductive mode (Bratin et al., 1981; Clark et al., 1985) or polaro-
    graphic detection (Koen & Huber, 1970). Acetonitrile/water with
    additional acetate buffer is used as solvent. The response is similar
    to the UV detector, but there is less interference from the plant
    material (Clark et al., 1985).

    2.4.2.3  Thin layer chromatography (TLC)

         Thin layer chromatography is well suited for the analysis
    organophosphorous pesticides, even if it is not as specific as GC
    (Kawahara et al., 1967; Schütz & Schindler, 1974; Thielemann, 1974;
    Katkar & Barve, 1976; Lawrence et al., 1976; Curini et al., 1980;
    Daldrup et al., 1981; Pfeiffer & Stahr, 1982; Korsos & Lantos, 1984).
    Usually, silica gel G plates are used with a variety of solvent or
    solvent mixtures. These include benzene, chloroform/cyclohexane,
     n-hexane/acetone, chloroform/benzene, dichloro-methane/acetone.
    Silver nitrate is frequently used as spray reagent, which, in the
    presence of organophosphorous pesticides, leads to white spots against
    a black background (Pfeiffer & Stahr, 1982).

         As an alternative, an enzymatic reaction has been frequently
    applied to detect organophosphorous compounds on TLC plates (Mueller,
    1973; Leshev & Talanov, 1977; Ambrus et al., 1981a; Bhaskar & Kumar,
    1981; Devi et al., 1982). This method makes use of the fact that
    cholinesterase (from horse serum or cow liver) hydrolises 1-naphthyl
    acetate to 1-naphthol, which reacts either with Fast Blue Salt B or
     p-nitrobenzenediazoniumfluoroborate to form a coloured complex. If
    methyl parathion is inhibiting the enzyme reaction, white spots on a
    red or orange background appear. The sensitivity may be enhanced if
    methyl parathion is oxidized to methylparaoxon by reaction with
    bromine or hydrogen peroxide.

    2.4.2.4  Spectrophotometry

         Colorimetric methods, which were of importance during the early
    years of organophosphorous pesticide analysis, have largely been
    replaced by chromatographic methods.

         The inhibition of cholinesterase by organophosphorous pesticides,
    described above, is also the basis of a photometric method (Archer &
    Zweig, 1959; Kumar & Ramasundari, 1980; Bhaskar & Kumar, 1982, 1984;
    Kumar, 1985). Sadar et al. (1970) made use of the fact that
    cholinesterase hydrolyses the non fluorescent  N-methyl-
    indoxylacetate to the highly fluorescent indoxyl. This reaction is
    again inhibited by methyl parathion.

         In another spectrophotometric method, methyl parathion is treated
    with hydroxylamine hydrochloride and sodium nitroprusside, under
    alkaline conditions, to form a water-soluble, coloured complex (Sastry
    & Vijaya, 1986). The method is rapid and accurate and can be used for
    formulations and for residues in fruits and vegetables.

    2.4.2.5  Polarography

         Polarography and various modifications of this method, i.e., the
    "differential pulse polarography" (DPP), have been used repeatedly to
    determine methyl parathion and other organophosphorous compounds with
    a nitro group (Nangniot, 1966; Gajan, 1969; Kheifets et al., 1976;
    Zietek, 1976; Smyth & Osteryoung, 1978; Kheifets et al., 1980; Khan,
    1988; Reddy & Reddy, 1989). The method allows the simultanous
    determination of parathion, methyl parathion, paraoxon, EPN, and the
    metabolite 4-nitrophenol (Zietek, 1976) in blood, without prior
    extraction. Polarography has been proposed as confirmatory method for
    the determination of methyl parathion (and three further pesticides).
    A collaborative study of 10 laboratories showed a coeffient of
    variation of 15-16% (Gajan, 1969). In addition the method was applied
    to water analysis (Kheifets et al., 1976, 1980; Bourquet et al.,
    1989). Bourquet et al. (1989) showed a 20-50 increase in sensitivity
    when "adsorptive stripping voltametry" was used instead of DPP.

    2.4.2.6  Mass spectrometry

         Coupled gas chromatography/electron impact mass spectrometry
    (GC/MS) is a particularly valuable method for confirming pesticide
    residues in various environmental samples. Methyl parathion shows an
    abundant m/z=109, 125, and 263 (M+.) under electron impact
    conditions (Mestres et al., 1977; Wilkins, 1990). Under positive ion
    chemical ionization mass spectrometry (methane), the protonatic
    molecule is the most abundant ion (m/z 264) while the structure
    specific fragment at m/z 125 is due to (CH3O)2 P=S+ (8.8%)
    (Holmstead & Casida, 1974). The negative ion chemical ionization
    spectrum shows the typical thiophenolate fragment at m/z=154
    (-S-C6H4-NO2) (Nielsen, 1985).

         In addition, field ionization (FI) and field desorption (FD) mass
    spectrometry have been applied repeatedly in the determination of of
    methyl parathion (Damico et al., 1969; Klisenko et al., 1981; Schulten
    & Sun, 1981; Golovatyi et al., 1982). The FD spectra show little
    fragmentation and, thus, are not well suited for environmental
    analysis. Among the newer mass spectrometric techniques, tandem mass
    spectrometry (MS/MS) shows more promise for organophosphorous
    pesticide analysis, as this technique enhances the selectivity of the
    method and thus may reduce the necessary clean-up. Under MS/MS
    conditions (chemical ionization), the protonated molecule forms an
    abundant fragment at m/z 125 ((CH3O)2 P=S+) (Hummel & Yost, 1986;
    Roach & Andrzejewski, 1987).

         HPLC/MS of methyl parathion has been demonstrated (De Wit et al.,
    1987; Betowski & Jones, 1988; Farran et al., 1990). As this method is
    more difficult to handle and less sensitive and reproducible than
    GC/MS, there is no need to use it in routine analysis, except when
    other thermally labile pesticides are to be determined together with
    organophosphorous compounds.

    2.4.3  Detection limits

         Detection limits are rarely reported. When plant material was
    analysed, the detection limit for the overall method (extraction,
    clean-up, analysis) was 10-100 µg/kg when gas chromatography with AFID
    or FPD was used. In water analysis, substantially better detection
    limits were achieved (usually 0.01-0.1 µg/litre), which may be further
    reduced if a large-scale extractor is used (Foster & Rogerson, 1990).
    In air analysis, detection limits have been reported to be 0.1-1
    ng/m3.

    2.4.4  Confirmatory method

         A confirmatory derivatization method was proposed by Lee et al.
    (1984). Following hydrolysis with KOH, 4-nitrophenol was derivatized
    with pentafluoro benzyl bromide to the corresponding ether. Analysis
    is carried out by GC with ECD. Levels as low as 0.01 ppb can be
    confirmed.

    
    Table 1. Sampling, extraction, clean-up, and determination of methyl parathiona

    Matrix          Sampling, extraction, clean-up      Analytical        Recovery (%)   Detection limitb    References
                                                        method                           (µg/kg or litre)

    fruits,         extr.: acetonitrile,                GC (ECD, TID)     86-92          n.r.                Wessel (1967)
    vegetables      part.: petroleum ether,             TLC
                    clean-up: Florisil

    plant material, extr.: propylene carbonate,         GC (ECD, TID)     82-95          n.r.                Schnorbus &
    dairy products  clean-up: Florisil                                                                       Phillips (1967)

    fruits,         extr.: acetonitrile,                GC (ECD)          90-98          n.r.                Osadchuck et al.
    vegetables,     part.: dichloromethane + hexane,                                                         (1971)
    fat, oil        clean-up: Florisil                  

    vegetables      extr.: acetone,                     GC (ECD, TID)     93 (celery)    n.r.                Luke et al. (1975)
                    part.: dichloromethane/petroleum
                    ether,
                    clean-up: Florisil

    apples          extr.: toluene +  n-hexane,          GC (ECD)          93             1-20                Johansson (1978)
                    clean-up: Florisil

    vegetables      autom. extraction +                 n.r.              91-104         n.r.                Gretch & Rosen 
                    clean-up: Florisil                                    (pepper)                           (1984)

    food            extr.: acetone,                     GC                n.r.           n.r.                Specht & Tillkes 
                    part.: dichloromethane,                                                                  (1980)
                    clean-up: GPC + silica gel

    Table 1 (continued)

    Matrix          Sampling, extraction, clean-up      Analytical        Recovery (%)   Detection limitb    References
                                                        method                           (µg/kg or litre)

    fruits,         extr.: acetone,                     GC (ECD,FPD,      > 80           10-100              Andersson &
    vegetables      part.: dichloromethane hexane,      TID)                                                 Ohlin (1986)
                    clean-up: GPC and silica gel

    vegetables,     extr.: trichloromethane,            GC (FPD)          93-105         n.r.                Ault et al.  (1979)
    fruits,         clean-up: GPC 
    crops

    vegetables      extr.: acetone,                     GC (TID)          85-95          n.r.                Pflugmacher &
                    part.: dichloromethane,                                                                  Ebing (1974)
                    clean-up: GPC

    -               clean-up: GPC                       n.r.              n.r.           n.r.                Steinwandter
                                                                                                             (1988)

    -               clean-up: cellulose column          n.r.              82             n.r.                Stahr et al. (1979)

    fruits,         extr.: acetonitrile,                HPLC (UV 280)     77-87          10                  Funch (1981)
    vegetables      part.: dichloromethane

    honey bees,     extr.: acetone  o-xylene             GC (FPD)          92-101         1                   Ross & Harvey
    beewax, pollen                                                                                           (1981)

    plants, soil    extr.: supercritical methanol       GC (ECD, AFID)    38             n.r.                Capriel et al.
                                                                                                             (1986)

    tobacco         extr.: hexane/acetone,              GC (FPD)          99-104         20                  Sagredos & Eckert
                    clean-up: alumina                                                                        (1976)

    Table 1 (continued)

    Matrix          Sampling, extraction, clean-up      Analytical        Recovery (%)   Detection limitb    References
                                                        method                           (µg/kg or litre)

    vegetables      extr.: acetone,                     GC (ECD,TID,      n.r.           n.r.                Gyorfi et al.
                    part.: dichloromethane,             FPD)                                                 (1987)
                    clean-up: charcoal

    plant material  extr.: acetone,                     GC (AFID, ECD)    92-103         n.r.                Becker (1971)
                    part.: dichloromethane

    plant material  extr.: acetone,                     GC (ECD, AFID)    92-103         n.r.                Becker (1979)
                    part.: dichloromethane, 
                    clean-up: charcoal

    plant material  extr.: acetone,                     HPLC              n.r.           n.r.                Miellet (1982)
                    clean-up: charcoal/Florisil

    barley, malt,   extr.: acetone or acetonitrile,     GC (FPD)          82             30                  Sonobe et al.
    hops            part.: hexane,                                                                           (1982)
                    clean-up: charcoal

    low moisture    extr.: acetone,                     GC (FPD)          93             n.r.                Luke & Doose
    products        part.: dichloromethane/petrol,                                                           (1983)
    (pepper)        ether,
                    clean-up: charcoal

    ready-to-eat    extr.: acetone                      GC (ECD, TID)     n.r.           0.7-1.8             Vogelsang & Thier
    foods           part.: dichloromethane,                                                                  (1986)
                    clean-up: + GPC silica gel

    honey bees      extr.: acetone                      GC (ECD)          91             15                  Ebing (1985)
                    clean-up: charcoal
                                                                                                                              
    Table 1 (continued)

    Matrix          Sampling, extraction, clean-up      Analytical        Recovery (%)   Detection limitb    References
                                                        method                           (µg/kg or litre)

    milk, oilseeds  fat adsorbed on alumina             GC (ECD, FPD)     n.r.           80                  Luke & Doose
                    extr.: acetonitrile,                                                                     (1984)
                    part.: petroleum ether

    fat             ad.: of fat on Calflo E                               n.r.           n.r.                Specht (1978)

    edible oils     sweep co-distillation               GC (TID)          95             10 (mg/kg)          Storherr et al. 
                                                                                                             (1967)

    edible oils     extr.: petroleum ether,             GC(FPD)           83-107         n.r.                Gillespie &
                    clean-up: HPLC                                                                           Walters (1989)

    milk            sweep co-distillation               GC (TID)          > 87           n.r.                Watts & Storherr 
                                                                                                             (1967)

    blood           extr.:  n-hexane                     GC (FPD)          n.r.           3                   Gabica et al.
                                                                                                             (1971)

    serum           extr.: benzene                      GC (AFID)         69             2                   De Potter et al.
                                                                                                             (1978)

    blood           no extr.                            polarography                     7x10-8 mol          Zietek (1976)

    soil            extr.: acetone/hexane               GC (TID)          n.r.           n.r.                Agishev et al.
                                                                                                             (1977)

    soil            extr.: acetone/hexane               TLC (silica       n.r.           n.r.                Garrido &
                                                        gel)                                                 Monteoliva (1981)

    Table 1 (continued)

    Matrix          Sampling, extraction, clean-up      Analytical        Recovery (%)   Detection limitb    References
                                                        method                           (µg/kg or litre)

    soil, sediment  extr.: acetone/hexane,              GC (AFID)         71             0.17                Kjoelholt (1985)
                    clean-up: ad. chrom.

    soil            extr.: acetone,                     GC (TID)          78-85          5                   Wegman et al.
                    part.: dichloromethane,                                                                  (1984)
                    clean-up: silica gel

    soil, water,    extr.: hexane/isopropanol,          GC (ECD)          45             n.r.                Schutzmann et al.
    sediment        desulfurization with Raney copper                                                        (1971)

    water           diethylether/hexane or benzene/     GC (ECD)          n.r.           n.r.                Kawahara et al.
                    n-C6,                                                                                    (1967)
                    clean-up: TLC

    water           extr.: benzene                      GC (TID)          95             n.r.                Pionke et al.
                                                                                                             (1968)

    water           extr.: benzene                      GC                92-101         0.001 (?)           Konrad et al.
                                                                                                             (1969)

    water           extr.: petroleum ether              GC                98             0.04                Zweig & Devine
                                                                                                             (1969)

    water           extr.: trichloromethane             TLC               60-95          1                   Chmil et al.
                                                                                                             (1978)

    water           extr.: trichloromethane             GC(TID)           n.r.           0.01                Chernyak &
                                                                                                             Oradovskii (1980)

    Table 1 (continued)

    Matrix          Sampling, extraction, clean-up      Analytical        Recovery (%)   Detection limitb    References
                                                        method                           (µg/kg or litre)

    water/          extr.: at pH 11: dichloromethane;   GC/MS             60-85          5                   Spingarn et al.
    wastewater      at pH 2: dichloromethane                                                                 (1982)

    water           extr.: dichloromethane/hexane,      GC (ECD)          n.r.           n.r.                Albanis et al.
                    clean-up: Florisil                                                                       (1986)

    water           extr.: ethylacetate                 GC (FPD)          85-91          0.08 ng(abs.)       Li & Wang (1987)

    wastewater      extr.: dichloromethane,             GC (FPD)          90             0.75                Miller et al.
                    clean-up: Florisil                                                                       (1981)

    water           extr.: petroleum ether,             GC (ECD)          n.r.           0.5                 Mestres et al.
                    clean-up: Florisil                                                                       (1969)

    water           extr.: dichloromethane              GC/MS             75             n.r.                Bruchet et al.
                    (continuous) liquid-liquid)                                                              (1984)

    water           extr.:  n-pentane (continous         GC (TID)          90             0.01                Brodesser &
                    liquid-liquid)                                                                           Schoeler (1987)

    water           hydrolysis KOH, derivat. penta      GC (ECD)          95             0.1                 Coburn & Chau
                    fluoro-benzylbromide,                                                                    (1974)
                    clean-up: silica gel

    water           ad.: on Tenax, thermoelution        GC (FID/ECD)      62             0.01                Agostiano et al.
                                                                                                             (1983)

    water, run-off  ad.: XAD-2,                         HPLC (rev.        99             2                   Paschal et al.
    water           elut.: diethylether                 phase, UV)                                           (1977)

    Table 1 (continued)

    Matrix          Sampling, extraction, clean-up      Analytical        Recovery (%)   Detection limitb    References
                                                        method                           (µg/kg or litre)

    water,          ad.: XAD-2,                         GC (TID, FID)     93-100         15 pg(abs.)         Le Bel et al.
    drinking-water  elut.: acetone/hexane                                                                    (1979)

    water           ad.: XAD-4,                         GC                n.r.           n.r.                Xue (1984)
                    elut.: diethylether/hexane

    water           ad.: Porapack Q,                    HPLC (rev.        96-105         < 1                 Clark et al. (1985)
                    elut.: acetonitrile                 phase
                                                        electro-chem.)

    water           ad.: C-18,                          TLC               n.r.           0.2 ng(abs.)        Sherma &
                    elut.: ethyl acetate                                                                     Bretschneider
                                                                                                             (1990)

    water           ad.: C-18, acetone                  GC (FPD)          > 79           n.r.                Swineford &
                                                                                                             Belisle (1989)

    water           extr.: dichloromethane              GC/MS             48             0.0025              Foster & Rogerson
                    (large-scale extractor)                                                                  (1990)

    air             ab.: ethylene-glycol,               GC (FPD)          87-97          n.r.                Sherma & Shafik
                    extr.: dichloromethane,                                                                  (1975)
                    clean-up: silica gel

    air             ab.: cotton seed oil coated glass   GC (FPD)          91             0.04 ng/m3          Compton (1973)
                    beads,
                    clean-up: Florisil

    air             clothscreen with ethylene glycol,   GC (ECD/FPD)      93             n.r.                Tessari & Spencer
                    extr.: acetone/hexane,                                                                   (1971)
                    clean-up: alumina + Florisil

    Table 1 (continued)

    Matrix          Sampling, extraction, clean-up      Analytical        Recovery (%)   Detection limitb    References
                                                        method                           (µg/kg or litre)

    air             ad.: silica gel, activated          GC (ECD/FPD)      n.r.           1 ng (abs.)         Klisenko &
                    charcoal                                                                                 Girenko (1980)

    air             ad.: silica gel                     GC (FPD)          101-104        30 pg (abs.)        Liang & Zhang
                                                                                                             (1986)

    air             ad.: XAD-4,                         GC (ECD, TID)     74             1-3 ng/m3           Wehner et al.
                    elut: ethylacetate,                                                                      (1984)
                    clean-up: HPLC

    air             ad.: PUF,                           GC (ECD)          100            n.r.                Rice et al. (1977)
                    elut: petroleum ether

    air             ad.: PUF (high volume sampler)      GC (ECD, FPD)     86             0.1 ng/m3           Lewis et al.
                                                                                                             (1977)

    air             ad.: PUF (low volume sampler),      GC (ECD, FPD)     80             20 ng/m3            Lewis & MacLeod
                    elut: diethylether/hexane                                                                (1982)

    air             ad.: PUF/other polymers (high       GC                72-91          n.r.                Lewis & Jackson
                    volume sampler)                                                                          (1982)

    air             ad.: PUF,                           n.r.              n.r.           n.r.                Belashova et al.
                    elut.: trichloromethane or                                                               (1983)
                    acetaldehyde

    air             ad.: Tenax,                         GC (FID)          n.r.           2.5 µg/m3           Beine (1987)
                    elut.: toluene

    formulations    -                                   GC or HPLC        -              -                   Jackson (1976)

    Table 1 (continued)

    Matrix          Sampling, extraction, clean-up      Analytical        Recovery (%)   Detection limitb    References
                                                        method                           (µg/kg or litre)

    formulations    -                                   GC                -              -                   Jackson (1977a)

    formulations    -                                   HPLC              -              -                   Jackson (1977b)

    formulations    -                                   IR                -              -                   Goza (1972)

    formulations    -                                   P-31 NMR          -              -                   Greenhalgh et al.
                                                                                                             (1983)

    formulations    hydrolysis to  p-nitrophenol         Spectr.           -              -                   Blanco & Sanchez
                                                                                                             (1989)

    a    Abbreviations: GC = gas chromatography, TLC = thin-layer chromatography, GPC = gel
         permeation chromatography, MS = mass spectrometry, HPLC = high performance liquid
         chromatography, NMR = nuclear magnetic resonance, IR = infrared spectroscopy,
         ECD = electron capture detector, FID = flame ionization detector, AFID = alkali flame
         ionization detector, FPD = flame photometric detector, TID = thermionic detector,
         UV = ultraviolet detector, spectr. = spectrophotometry, extr. = extraction, part. = partitioning,
         ad. = adsorption, ab. = absorption, elut. = elution, n.r. = not reported, (abs.) =  absolute.

    b    µg/kg or litre unless stated otherwise.

    Table 2.  Methods used in the determination of methyl parathion

    Method                       Detection limit        Remarks                    References

    HPLC (UV)                    n.r.                   analysis                   Abe et al. (1979)
                                                        of metabolism

    HPLC (UV)                    n.r.                   in mixtures                Zhao & Wang
    (rev. phase, methanol/                                                         (1984)
    acetic acid)

    HPLC                         n.r.                   review on HPLC             Lawrence & Turton (1978)
                                                        methods

    HPLC (fluorescence)          10-20 µg (abs.)-       deriv. with dansyl         Lawrence et al. (1976)
                                                        chloride

    HPLC 1. acetonitrile         n.r.                   retention times of         Daldrup et al. (1982)
    2 acetonitrile/phosphoric                           560 compounds
    acid KH2PO4/H2O

    HPLC 1. acetonitrile         n.r.                   retention times of         Daldrup et al. (1981)
    2 acetonitrile/phosphoric                           570 compounds
    acid KH2PO4/H2O

    HPLC (rev. phase,            10 µg/kg               fruits and vegetables      Funch (1981)
    acetonitrile/H2O)

    Table 2 (continued)

    Method                       Detection limit        Remarks                    References

    HPLC (rev. phase,            1 µg/kg                reduction amperometric     Clark et al. (1985)
    acetonitrile/0.01 KC1                               detection
    0.03 M potassium                                    (vegetables, water)
    acetate/H20)

    HPLC (rev. phase,            n.r.                   electrochemical            Bratin et al. (1981)
    acetonitrile/sodium                                 detection
    acetate/H2O)

    HPLC rev. phase (H2O         30 µg/kg               polarographic              Koen & Huber (1970)
    ethyl alcohol/acetic                                detection
    acid/NaOH)

    GC                           < 2 ng                 TID                        Patterson (1982)

    GC                           n.r.                   retention times of         Daldrup et al. (1981)
                                                        570 compounds

    GC (TID)                     20 µg/kg               retention times            Ambrus et al. (1981a,b)

    GC                           n.r.                   retention times of         Saxton (1987)
                                                        600 compounds

    GC                           n.r.                   retention times of         Prinsloo & de Beer (1987)
                                                        42 pesticides

                                 n.r.                   retention times of         Suprock & Vinopal (1987)
                                                        78 pesticides

    Table 2 (continued)

    Method                       Detection limit        Remarks                    References

    GC                           n.r.                   retentions times of        Bowman & Beroza (1967)
                                                        20 OP-pesticides
                                                        (milk, corn silage)

    GC                           n.r.                   two dimensional            Stan & Mrowetz (1983)
                                                        GC

    GC (FPD)                     100 pg                 capillary columns,         Krijgsman & Van de Kamp (1976)
                                                        relative retention
                                                        times

    GC (ECD, TID)                n.r.                   capillary columns,         Stan & Goebel (1983)
                                                        simultaneous
                                                        detection of ECD, TID

    GC                           n.r.                   retention times            Ripley & Braun (1983)
                                                        of 194 pesticides

    GC                           < 0.1 ng               relative retention         Omura et al. (1990)
                                                        times of 40 pesticides
                                                        on 11 phases

    Table 2 (continued)

    Method                       Detection limit        Remarks                    References

    GC (ECD)                     n.r.                   hydrolysis of              Lee et al. (1984)
                                                        methyl parathion
                                                        to 4-nitrophenol,
                                                        derivat.
                                                        penta-fluorobenzylbromide
                                                        Clean-up: silica gel

    TLC (silica gel G)           n.r.                   detection with GC          Kawahara et al. (1967)

    TLC (silica gel)             0.1 µg                 4 solvent mixtures,        Schütz & Schindler (1974)
                                                        reduct. to amines

    TLC (silica gel)             0.06-0.6 µg            saponification and         Thielemann (1974)
                                                        reduct. to
                                                         p-amino-phenol

    TLC (silica gel G)           n.r.                   elut.:  n-hexane/acetone    Katkar & Barve (1976)

    TLC (silica gel)             n.r.                   17 solvent systems,        Curini et al. (1980)
                                                        spray reagent: AgNO3

    TLC (silica gel)             n.r.                   elut.: 1.methanol/NH3H2O   Daldrup et al. (1981)
                                                        2. dichloromethane/
                                                        acetone

    TLC (silica gel)             n.r.                   elut.:  n-heptane/acetone   Pfeiffer & Stahr (1982)

    Table 2 (continued)

    Method                       Detection limit        Remarks                    References

    TLC (silica gel)                                    elut.: petroleum ether/    Korsos & Lantos (1984)
                                                        diethylether, two
                                                        dimensional TLC

    TLC                          n.r.                   elut.: benzene/acetone,    Mueller (1973)
                                                        detect. enzymatic
                                                        reaction

    TLC (silica gel/                                    elut.: 4 solvent           Leshchev & Talanov (1977)
    starch)                                             mixtures, milk,
                                                        feed, animal tissue,
                                                        extr: acetone, detect.
                                                        enzymatic reaction

    TLC (silica gel G)           n.r.                   detect. enzymatic          Bhaskar & Kumar (1981)
                                                        reaction

    TLC (silica gel G)           5 µg (abs.)            elut.: dichloromethane     Ambrus et al. (1981a,b)
                                                        or ethyl acetate,
                                                        detect. enzymatic
                                                        reaction

    TLC                          n.r.                   detect. enzymatic          Devi et al. (1982)
                                                        reaction

    Table 2 (continued)

    Method                       Detection limit        Remarks                    References

    polarography                 140 µg/kg              oscillographic             Nangniot (1966)
                                                        polarography,
                                                        pesticide
                                                        residues

    polarography                 10 µg/kg               single sweep               Gajan (1969)
                                                        oscillographic
                                                        polarography,
                                                        non-fatty foods

    polarography                 n.r.                   differential               Kheifets et al. (1976)
                                                        oscillographic
                                                        polarography
                                                        (water)

    polarography                 7x10-6 mol/litre       methyl parathion and       Zietek (1976)
                                                        metabolites in blood

    polarography                 10-8 mol/litre         -                          Smyth & Osteryoung (1978)

    polarography                 n.r.                   adsorptive stripping       Bourquet et al. (1988)

    polarography                 n.r.                   -                          Kahn (1988)

    polarography                 3.9.10-9 mol/litre     polargaraphy, diff.        Reddy & Reddy (1989)
                                                        pulse polargraphy
                                                        cyclic voltametry

    Table 2 (continued)

    Method                       Detection limit        Remarks                    References

    differ.                      n.r.                   water                      Kheifets et al. (1980)
    chronoamperometry

    spectrophotometry            n.r.                   enzymatic reaction         Kumar (1985)
                                                        (cholinesterase,
                                                        Fast Blue B)

    spectrophotometry            n.r.                   reduction to amine,        Sastry & Vijaya (1986)
                                                        formation of a
                                                        coloured complex

    spectrophotometry            n.r.                   reaction with 3-methyl-    Sastry & Vijaya (1987)
                                                        2-benzothiazolinone

    spectrophotometry            n.r.                   hydrolysis to              Ramakrishna & Ramachandran
                                                        4-nitro-phenol             (1978)

    a    Abbreviations: GC = gas chromatography, HPLC = high performance liquid chromatography, TLC= thin layer chromatography,
         ECD = electron capture detector, TID = thermionic detector, FPD = flame photometric detector, UV = ultraviolet
         detector, elut. = elution, n.r. = not reported, (abs.) = absolute.

    3.  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

    3.1  Natural occurrence

    Natural occurrence of methyl parathion is unlikely.

    3.2  Man-made sources

    3.2.1  Production process

         Methyl parathion is a representative of the highly active
    insecticides, the thiophosphorus esters, developed in the 1940s by
    Schrader, a German chemist. Methyl parathion was introduced as a
    commercial chemical in 1949. It is synthesized by the reaction of
     O,O-dimethyl phosphoro-chloridothioate with the sodium salt of 4-
    nitrophenol (Schrader, 1963).

    3.2.2  Loss into the environment

         Emissions of methyl parathion during the production process can
    be disregarded when compared with those from its use as an
    insecticide. The air emission from a factory in the USA was reported
    to be around 0.1% of the production level (Archer et al., 1978). The
    major losses of this insecticide are directly caused by spraying, and
    evaporation from water surfaces, leaves, and from the soil (Woodrow et
    al., 1977).

    3.2.3  Production

         According to the European Directory of Agrochemical Products
    (1986) and the Directory of World Chemical Producers (1990), methyl
    parathion is produced throughout the world by many companies. World
    production in 1966 was 31 700 tonnes, including 14 800 tonnes produced
    in the USA.

         In Table 3, selected countries producing methyl parathion are
    listed together with their production capacities (Bayer, 1988).

    Table 3.  Methyl parathion production capacities in different
    countriesa

    Country                                             Production capacity in
                                                        tonnes/year
                                                                                  
    Brazil                                                 3000

    Denmark                                              15 000

    German Democratic Republic                             3500

    Mexico                                                 8000

    India                                                  3000

    China                                                40 000

    USSR                                                5000-10 000

    a From: Bayer (1988).
    
    3.2.4  World consumption

         Recent data from Bayer concerning the consumption of the active
    ingredient only are reported in Table 4 (Bayer, 1988).

    Table 4.  Methyl parathion consumption in tonnes in some areas of the
    worlda

    Region                              1984           1985           1986

    Africa                               191            308            152

    North America                      2 045          2 776          2 932

    South America                      9 135          6 555          5 587

    Asia, New Zealand,                 2 757          3 028          2 620
    Australia

    Western Europe                       894          1 087          1 019

    Total                             15 022         13 754         12 310

    aFrom: Bayer (1988).
    
         In 1984, the USA exported 3010 tonnes of methyl parathion (HSDB,
    1990).

    3.2.5  Formulations

    Methyl parathion is used in following formulations:

    (1)  emulsifiable concentrates (EC) with 19.5%, 40%, 50%, 60% active
         ingredient (a.i.)
    (2)  wettable powders containing 40% a.i.
    (3)  dusts 1.5%, 2%, and 3% methyl parathion,
    (4)  microencapsulated methyl parathion, and
    (5)  ready-to-use liquid (less than 1% a.i.).

         The usual carriers are: petroleum solvents and clay carriers
    (such as propargite).

         Combinations are available containing parathion, omethoate,
    tetradifon, prothoate, and petroleum oil.

    3.3  Uses

         Methyl parathion is a broad-spectrum insecticide with
    non-systemic contact and stomach action. The normal method of
    application is foliar spraying by aircraft or ground equipment. Data
    from 1971 show that most methyl parathion was used for protecting
    cotton fields (Table 5).

    Table 5.  Methyl parathion consumption pattern (1971)a

    Protection of                                               consumption (%)

    cotton                                                      83

    soybeans                                                     8

    grain including corn                                         5

    wheat                                                        2

    tobacco, peanuts, vegetables, and citrus fruits              2

    aFrom: HSDB (1990).
    
         Only foliar application of methyl parathion is known. It is used 
    as a contact insecticide and acaricide. There are different routes of
    application depending on the type of plant to be protected and the
    organisms killed. The recommended application rate is 0.5-1 kg a.i./ha
    for vegetables, 1-2 kg/ha for cereals, 1.5-6 kg/ha for fruit trees,
    2-5 kg/ha for citrus fruits, and 0.12-1.0 kg/ha for cotton.

    4.  ENVIRONMENTAL TRANSPORTATION, DISTRIBUTION, AND TRANSFORMATION

    4.1  Transportation and distribution between media

         The transportation and distribution of methyl parathion in air,
    water, soil, fauna, and flora are influenced by several physical,
    chemical, and biological parameters. The transportation and fate of
    methyl parathion were studied by Gile & Gillett (1981). They used the
    simulated ecosystem developed at the Corvallis Environmental Research
    Laboratory of the US EPA (Gillett & Gile, 1976). A 16-h daily light
    cycle with an average of 27 000 lx at the soil surface was used. The
    temperatures varied from 18 °C at night to 30 °C during the day. The
    ecological compartment was ventilated with 10 litre air/min. The
    simulated ecosystem included alfalfa  (Medicago sativa) and
    perennial ryegrass  (Lolium perenne). Twenty days after planting,
    different representative kinds of invertebrates (earthworms,
    nematodes, garden snails) were added to the microcosms. Ten days
    later, radioactive labelled 14C-methyl parathion (50 µCi) was
    applied at rates of 0.3, 0.6, and 2.4 kg/ha. One week following the
    methyl parathion application, a gravid gray-tailed vole  (Microtus
     canicaudus)  was placed in the model ecosystem. The relative 14C
    mass balance of the study is shown in the Table 6.

         Most radioactivity was found in the upper 5 cm of soil. A
    comparable experiment with  p-nitrophenol showed a lower soil content
    and no residues in the groundwater as well.

         Crossland & Elgar (1983) used a mathematical model to predict the
    dispersion and degradation of methyl parathion in freshwater ponds.
    Basic assumptions of the model were that loss processes could be
    adequately described in terms of simple partition phenomena and
    first-order rate kinetics. Predictions of the model were compared with
    experimentally-obtained data for concentrations of methyl parathion in
    water and sediment. They started with a concentration of 100 µg methyl
    parathion/litre pond water. At the limit of the analytical method
    (0.005 µg/g), they could not find any residues of methyl parathion, 16
    days after treatment. The authors described the degradation by a
    pseudo first order rate constant that was temperature-dependent. 
    Since the degradation of methyl parathion in distilled water (pH not
    given) was faster than expected and the bacteria concentration was
    only 106/litre, a sediment-catalysed hydrolysis was supposed.
    Crossland & Bennett (1984) compared degradation of methyl parathion in
    experimental ponds and laboratory aquaria. Degradation was faster in
    the natural ponds and faster than predicted from simple mathematical
    models. Addition of plants, sediment, or sediment with plants, to the
    laboratory aquaria increased the rate of breakdown of methyl
    parathion; sediment had the greatest effect reducing half-life from
    300 h in water alone to 90-140 h. These findings support the
    investigation of Goedicke & Winkler (1976), who considered, from their
    testing of the persistence of different formulations of methyl
    parathion in soils, that the compound would not contaminate
    groundwater, if applied at suggested rates and intervals.

    Table 6.  14C mass balance of methyl parathion in a model ecosystema

    Samples                            Application rate of methyl parathion

                                       0.3 kg/ha       0.6 kg/ha       2.4 kg/ha

    air                                    57b           46              33

    soil                                   30            30              28

    groundwater                             0.0           0.1             0.0

    plants                                 12            23              38

    animals                                 1.0           0.6             1.1

    a From: Gillett & Gile (1976).
    b %.
    
    4.1.1  Air

         Most of this insecticide is directly liberated by spraying.
    However, a perceptible amount is released simultaneously with
    evaporation from water surfaces, leaves, or soil (Woodrow et al.,
    1977).

         Air samples were analysed after the application of methyl
    parathion at a concentration of 1.12 kg/ha (Jackson & Lewis, 1978). 
    The conventional emulsifiable concentrate was compared with an
    encapsulated formulation. The filter collection efficiency was
    determined to be 105% and the extraction efficiency was 92%. During
    the experimental period, the temperature varied from 18 to 34 °C at an
    average relative humidity of 72%. The results of the analysis of the
    air samples collected in tobacco-growing areas of North Carolina are
    shown in Table 7.

    Table 7.  Concentration of methyl parathion in the air after applicationa

    Time (days)                            Methyl parathion (mg/m3)

                               emulsifiable concentrate    encapsulated formulation

    0                          7.408                       3.783

    1                          3.338                       0.330

    3                          0.584                       0.107

    6                          0.036                       0.025

    6                          0.054                       0.019

    9                          0.013                       0.016

    a From: Jackson & Lewis (1978).
    
         Since the usual atmospheric levels of methyl parathion in the
    surroundings of agricultural areas range from not detectable to 71
    ng/m3, Jackson & Lewis (1978) discussed the possibility that the
    concentrations measured on day 9 may have been the result of the
    background level in the air of the heavily treated areas

         The atmospheric concentration of methyl parathion after spraying
    in the Kalinin District, Tashkent Province of the Uzbek USSR, during
    July and August, was determined by Akhmedov (1968). He found that the
    concentrations measured were dependent on the size of the area of
    methyl parathion application, the time of application, the
    temperature, and the wind velocity. In addition, the odour threshold
    was estimated, and effects on the brain electrical activity,
    resorption action, dark adaptation, and the light sensitivity of the
    eyes were studied.

         After the aerial treatment of forests, Vrochinsky & Makovsky
    (1977) measured the following concentrations of methyl parathion in
    the air (Table 8).

         The concentrations of methyl parathion increased in foggy
    conditions because of the adsorption of the compound on the surface of
    water aerosols (Goncharuk et al., (1988).

    Table 8.  Methyl parathion in air after spraying forestsa

    Time (days)                          Methyl parathion (mg/m3)

    0                                       0.12

    1                                       0.05

    5                                       0.024

    10                                      0.0015

    a From: Vrochinsky & Makovsky (1977).
    
         14C-Methyl parathion was subjected to simulated rainfall (total
    amount: 2.5, 25, and 38 mm/h) after application of 177 µg ai/cm2 to
    an octadecylsilane/trimethylsilane-treated glass slide. The amounts of
    14C remaining after washoff were 56%, 6%, and 2% respectively; thus,
    methyl parathion shows a high rate of washoff (Cohen & Steinmetz,
    1986).

    4.1.2  Water

         Various mechanisms exist for the transportation of methyl
    parathion following its application to aquatic environments,
    including: application-associated losses, volatilization, wind
    erosion, rinsing by rain into groundwater, and transportation as a
    soil-methyl parathion complex. 

         Eichelberger & Lichtenberg (1971) estimated the water pollution
    factor by investigating the persistence of methyl parathion in river
    water. They used a sealed glass jar containing river water and methyl
    parathion and applied sunlight and artificial fluorescent light. The
    initial concentration of methyl parathion was 10 µg/litre (Table 9):

         Badawy & El-Dib (1984) found that methyl parathion was more
    stable in water of high salinity, such as sea water, than in fresh
    water.

    Table 9.  Persistence of methyl parathion in river watera

    Time                        % of the initial concentration (10 µg/litre)

    1 hour                                80b

    1 week                                25

    2 weeks                               10

    4 weeks                                0

    a Adapted from: Eichelberger & Lichtenberg (1971).
    b Recoveries were rounded off to the nearest 5%.
    
         Because of a collision between two ships in the Mediterranean Sea
    near Port-Said, Egypt, the sea became contaminated with more than
    10 000 kg methyl parathion. Maximum methyl parathion concentrations
    (96 µlitre/litre) were found 50 m in the drifting direction (surface
    current, wind). In general, the concentration decreased with distance
    and time and reached the detection limit up to 80 days after the
    accident. The residues in sediment gradually increased during the
    first 20 days (concentration factor 49.5) (Badawy et al., 1984).

         Crossland et al. (1986) gave mathematical tools for calculating
    the fate of chemicals in aquatic systems (because of the importance of
    the degradation of methyl parathion in water, see also section 4.2).

    4.1.3  Soil

         Lichtenstein (1975) incorporated an emulsifiable concentration of
    methyl parathion into the upper 5 inches of a silt loam at a rate of
    3.1 mg/kg). One month after treatment, 3.5% of the methyl parathion
    could be detected in the soil. The author showed that percolating
    water transported metabolites vertically as well as horizontally.
    Methyl parathion moved less than 20 cm in a loamy soil following an
    annual precipitation of 1500 mm (Haque & Freed, 1974).

         Bound residues of [ring-14C] methyl parathion in a silt loam
    were monitored during an incubation period of 49 days (Gerstl &
    Helling, 1985). After this period, 54% of the initial 14C remained
    in the soil; of this, 13% was soxhlet-extractable with methanol and
    87% was bound residue. Several treatments indicated that bound
    residues of methyl parathion are not easily released (i.e., converted
    to an extractable form), but that they are slowly mineralized to
    CO2.

         A simulated spillage of emulsifiable or microencapsulated
    formulations of methyl parathion on soil (sandy loam; pH ranging from
    6.6 to 7.8, with a mean of 7.2) was studied for 45 months by Butler
    and coworkers (1981). The uptake of the insecticide was studied in
    five different experiments. The soil was contaminated with: a) 51%
    emulsifiable concentrate formulation (E.C.), b) dilute drum rinse of
    E.C., c) 22% microencapsulated formulation (M.C.), d) dilute drum
    rinse of M.C., and e) a solid cake of M.C. microencapsulated
    formulation of the initial values (Table 10). At 45 months, soil
    residues of methyl parathion had decreased by 64% for emulsifiable
    concentrate spills, and 68% for the soil beneath the microencapsulated
    cake; the residue in the cake itself only decreased by 31% (Table 10).
    Soil residue concentrations from the simulated drum rinses (Table 10)
    were very low by 45 months (emulsifiable concentrate) and by one year
    (microencapsulated formulation).

         Performing laboratory experiments, Davidson et al. (1980) showed
    that, at low application rates (24.5 mg/kg), methyl parathion was
    non-persistent in soils (Webster & Cecil) but was persistent following
    application of large quantities (10015 mg/kg). Therefore, it is
    impossible to predict the behaviour of methyl parathion at high
    applications rates on the basis of results following low application
    rates.

    4.1.4  Vegetation and wildlife

         Residue levels of methyl parathion on foliage depend on the
    formulation, the method of application, humidity, rain, temperature,
    dust levels etc. Kido et al. (1975) investigated surface and internal
    residue levels of methyl parathion on grape leaves treated with methyl
    parathion sprays (at the rate of 0.84 kg a.i./ha.); 90.2% of the
    initial surface residue was lost from the leaves one day after
    application. The major portion, over 60%, of the total residues was
    found in the internal portion of the leaves, and over 99% of the total
    residues had been lost, 5 days after application. Overhead sprinkler
    irrigation of the vines had only a slight, or no, effect on the
    reduction of methyl parathion residues (Kido et al., 1975). The
    residual life of methyl parathion on cotton can be extended by

    Table 10. Persistence of methyl parathion in sandy loam soil and
              in solid cake material following contamination of the soil
              with different formulations of methyl parathiona

    Time                   Mean concentrations of Methyl parathion (mg/kg)
    (months)                                                                  

                      E.C.b      E.C.      M.C.c      M.C.        M.C.
                      (51%)      (rinse)   (22%)      (rinse)     (cake)

    0                 48 900     17 600    30 800     2 140       379 000

    1                 33 700     10 800    14 200       940       258 000

    3                 25 300     7 000     17 100       550       305 000

    12                20 900     3 800     20 000         0.15     87 500

    20                20 800     1 400     13 300       230       149 000

    45                17 500       130     9 800      n.r.d       262 000

    a Modified from: Butler et al. (1981).
    b E.C. = emulsifiable concentrate.
    c M.C. = microencapsulated formulation.
    d n.r. = not recorded.
    
    application at dusk rather than dawn. For example, methyl parathion
    decreased to less than 50% after 4 h in sunlight, but only to 84%
    after the same time at night (Ware et al., 1980). The persistence of
    methyl parathion following application to cotton was also increased by
    combining it with molasses (Ware et al., 1980), toxaphene (Buck et
    al., 1980; Ware et al., 1980; Bigley et al., 1981), camphene (Bigley
    et al., 1981), or cedar oil (Bigley et al., 1981).  Ware et al. (1983)
    compared surface residues of methyl parathion on cotton foliage. When
    applied to cotton fields (at 1.1 kg/ha) as a typical, low-volume spray
    diluted with water versus ultra-low-volume (ULV) application using
    vegetable oil as the carrier. Forty-eight hours after application as
    an aqueous dilution, 1.8 % of the initial residue remained compared
    with 7.2 % after application as ULV. Cole et al. (1986) sprayed methyl
    parathion 4E (EC) in either water or water-crop oil (6:1) at 8 litres
    of a 1.8% dilution/ha on a 5 ha plot of cotton using a pawnee
    airplane. The residues found in the leaves sprayed with the mixture
    containing crop oil were higher than those in water-sprayed leaves in
    all samples collected after the treatment (Table 11).

    Table 11. Comparison of methyl parathion residues in cotton leaves
              treated with water sprays and with water-oil spraysa

    Days after treatment                Methyl parathion concentration

                                water                   water-oil formulation

    1                           14.80±8.74b             27.70±7.99

    2                            9.17±7.15               9.68±4.29

    3                            2.30±0.89               7.48±2.85

    4                            1.52±0.31               8.70±4.58

    5                            1.96±1.49               5.97±2.61

    a From: Cole et al. (1986).
    b mg/kg mean ± SE.
    
         The drift from a commercial aerial application of methyl
    parathion was quantified by Draper & Street (1981) by determining leaf
    surface residues of methyl parathion in a treated alfalfa field and an
    adjoining non-target pasture (with quackgrass, Agropyron repens, as
    predominant species). Four hours after the pesticide spraying by plane
    (0.27 kg/litre emulsifiable concentrate; 0.7 litre/ha; in the morning)
    2.8 mg methyl parathion/kg were present as foliar residues in the
    target field, and 0.26 mg/kg, in the untreated non-target pasture. At
    both places, the foliar residues of the parent compound dissipated
    rapidly with time.

         The time-dependent decrease in the residues of 2 different
    formulations of methyl parathion applied to tobacco plants was
    evaluated. Methyl parathion in either the emulsifiable or the
    encapsulated form was applied at rates of 0, 0.56, and 1.12 kg/ha.
    Samples were collected before spraying and within 10 min of the
    application. It was observed that the encapsulated formulation of
    methyl parathion did not decompose as fast as the emulsifiable form
    (Leidy et al., 1977). Varis (1972) tried to determine the influence of

    plant growth on the loss of methyl parathion residues in sugar beet
    seedlings. Methyl parathion was applied as a dust formulation (1.5%)
    at 20 kg/ha, 14 days after sowing. The residue methyl parathion
    concentration in the plants decreased to about 50% within 24 h. Within
    6 days, the methyl parathion residue was reduced by 90%, 73% reduction
    being due to plant growth.

         Fuhremann & Lichtenstein (1978) performed experiments with
    unextractable, soil-bound residues of radioactive labelled methyl
    parathion and measured the potential pick up of the 14C-containing
    residues. Earthworms  (Lumbricus spp.) and oat  (Avena sativa L.)
    plants were able to release and incorporate some soil-bound,
    14C-ring-labelled methyl parathion. Oat plants were found to release
    more chemical from the soil than the earthworms.

         Following applications of insecticides (including methyl 
    parathion) to nearby sugarcane or cotton fields, alterations in brain 
    acetylcholinesterase activity were found in birds living in brushland 
    within the Lower Rio Grande Valley of South Texas (Custer & Mitchell,
    1987). These alterations might have resulted from exposure during the
    use of agricultural fields as feeding or resting sites.

    4.1.5  Entry into the food-chain

         Methyl parathion hydrolyses faster than parathion. Because of the
    physical and chemical properties of methyl parathion, its pollution
    potential seems to be very small. Therefore, the most probable entry
    into the food-chain seems to be directly via residues on vegetables or
    crops.

         Since animals can degrade methyl parathion and excrete the
    degradation products within a very short time, a risk from eating meat
    seems to be unlikely. However, there may be an additional hazard from
    methyl parathion bound to glucosides (Dorough, 1978).

    4.2  Biotransformation

    4.2.1  Degradation involving biota

         Both field and laboratory studies have been conducted on the
    degradation of methyl parathion were. Data suggest that biodegrad
    ation is the major degradative pathway in eutrophic systems, whereas
    absorption, photolysis, and hydrolysis are more important in
    oligotrophic systems.

         The half-lives of methyl parathion residues reported in the
    literature for plants were relatively short, but varied with ambient
    conditions (see also section 4.1.4).

         Singh et al. (1978) recorded half-lives of methyl parathion
    applied to urd  (Phaseolus mungo Roxb.) and pea ( Pisum sativum (L)
    var.  arvense Poir.) at the rate of 0.63 and 1.25 kg a.i. per ha,
    respectively. Half-lives were 1.7 and 2.5 days for urd and 2.0 and 2.7
    days for pea, respectively. Foliar residues of methyl parathion on
    alfalfa treated by aircraft (0.27 kg/litre, emulsifiable concentrate)
    dissipated showing a first-order half-life of 12 h. This calculation
    is based on initial slopes of semi-logarithmic plots (Draper & Street,
    1981). The authors, however, noted that dissipation kinetics appeared
    to be greater than first-order. The times required for a 50% reduction
    in methyl parathion residues in cotton foliage were determined to be
    4.4-5.4 h (emulsifiable concentrate) or 28.1 h (encapsulated
    formulation) following application at a rate of 0.28 kg/ha (Smith et
    al., 1987). Based on data previously reported by Ware et al. (1974a)
    following application of methyl parathion to cotton (1.12 kg/ha),
    half-lives of 12 h (emulsifiable concentrate) and 70 h (encapsulated
    formulation) were calculated (Smith et al., 1987). In another study
    using emulsifiable concentrate formulations of methyl parathion at a
    rate of 1.15 kg/ha, a 50% disappearance time of 2-4 h was calculated
    for methyl parathion on cotton plants (Willis et al., 1985). A
    half-life of 0.96 days was described for methyl parathion residues
    (initial concentration = 0.4 µg/cm) on apple leaf surfaces (Goedicke,
    1989).

         A single report is available on the persistence of methyl
    parathion in a submerged aquatic macrophyte  (Hydrilla verticilla)
    and a fish (carp), both initially exposed to 3.8 mg methyl
    parathion/litre. The first order half-lives were 7.9 and 5.4 days,
    respectively (Sabharwal & Belsare, 1986).

         The half-life of methyl parathion in a soil (not characterized in
    detail) has been reported to be about 45 days (Menzie, 1972). In
    another study it was calculated to be as short as 2.7 days (Singh et
    al., 1978), possibly due to the high pH of the soil (pH = 8.6) and
    temperature (28 °C-33 °C). Half-lives of 12 and 22 days were measured
    for methyl parathion in 2 soils (pH = 6.1 and 5.5, respectively) when
    incubated at 22 °C (Möllhoff, 1981). Concentrations of methyl
    parathion in a loamy sand soil (pH = 5.3) decreased from a level of
    about 5 mg/kg to 0.3 mg/kg during a period of 57 days (Goedicke &
    Winkler, 1976). Thirty days following treatment, 3.1% of initial
    residues of methyl parathion were found in a soil (clay?) of a field
    treated with 5.6 kg/ha (Lichtenstein & Schulz, 1964) (see also section
    4.1.3).

         During an incubation study under aerobic conditions, methyl
    parathion was degraded mainly to CO2 and 4-nitrophenol, and, to a
    minor extent, to desmethyl parathion (Möllhoff, 1981). Methyl
    parathion may be degraded in the environment by:  a ) hydrolysis to
     p-nitrophenol and dimethylthiophosphoric acid; or  b ) nitro-group
    reduction to methyl aminoparathion (e.g., Sharmila et al., 1988).

    Hydrolysis can be both chemical and microbial while nitro-group
    reduction is essentially microbial. Generally, hydrolysis is the major
    pathway in nonflooded soil while methyl parathion is degraded mainly
    by nitro-group reduction in predominantly anaerobic systems, such as
    flooded soil (Ou et al., 1983; Ou, 1985; Adhya et al., 1987).

         In a few instances, hydrolysis is the major or only pathway of
    methyl parathion degradation in soils, even under flooded conditions
    (Ou, 1985). Adhya et al. (1987) evaluated the influence of different
    physical and chemical characteristics on the persistence of methyl
    parathion in 5 tropical soils under flooded and nonflooded conditions.
    They found that nitro-group reduction was the major pathway of methyl
    parathion degradation in 4 out of 5 of the soils under flooded
    conditions, while, in one soil (Sukinda-soil), degradation of methyl
    parathion proceeded exclusively by hydrolysis, even under flooded
    conditions. The latter finding was confirmed by Sharmila et al.
    (1989a).

         A temperature-dependent shift from nitro-group reduction (at
    25 °C) to predominantly hydrolysis (at 35 °C) occurred in a flooded
    alluvial soil; both pathways were mediated microbially (Sharmila et
    al., 1988). The addition of yeast extract also influenced the
    degradation pathway of methyl parathion by bacterial cultures in
    enriched flooded alluvial and laterite (Sukinda) soils (Sharmila et
    al., 1989b). Low redox potential in a flooded soil favoured
    degradation by nitro-group reduction, whereas hydrolysis was
    concomitant with a more positive potential (Adhya et al., 1981a).

         Adhya et al. (1981b) reported studies on sulfur-containing
    anaerobic ecosystems, such as oceanic sediments, which they supposed
    could serve as a potential sink for pesticides. They found that methyl
    parathion was decomposed in acid, sulfur-containing soils and soils
    with a low sulfate content to aminomethyl parathion; however, no
    decomposition occurred under aerobic conditions. Demethylation could
    be demonstrated in anaerobic sulfate soils.

         Evidence for microbial participation was provided by the fact
    that sterilization of the enriched soil samples increased the
    stability of methyl parathion in soil (Adhya et al., 1981a). The
    authors reported a very rapid reduction of the nitro group of methyl
    parathion by equilibration with a soil incubated with rice straw under
    flooding. Sterilization of this soil preparation prevented this rapid
    reduction. The degradation of methyl parathion and its metabolite
     p-nitrophenol in flooded alluvial soil is given in Table 12.

         It appeared from this study, that the degradation of the
    metabolite  p-nitrophenol is more rapid than the decomposition of
    methyl parathion.

    Table 12. Degradation of methyl parathion and its metabolite  p-nitrophenol
              in flooded alluvial soila

    Days after methyl            µg of compound recovered/20 g of soil
    parathion addition                                                            

                               methyl parathion         p-nitrophenol

    0                           485.3                  0

    0.5                         428.1                  trace

    1                           333.7                  120.0

    2                           219.8                  98.6

    3                           185.6                  72.0

    6                            95.5                  0

    12                           58.2                  0

    a From: Adhya et al. (1981a).
    
         Isolated mixed bacterial cultures from soil utilized methyl
    parathion and parathion as a sole carbon source (Chaudhry et al.,
    1988).  Pseudomonas sp. was capable of hydrolysing methyl parathion
    and parathion to  p-nitrophenol but needed another carbon source for
    growth. The optimum pH range for enzymatic hydrolysis  by this
    bacterium was from 7.5 to 9.5. In view of the instability of methyl
    parathion in alkaline solutions, it is not clear whether the
    hydrolysis noted was or was not partially due to the pH of the
    solution rather than wholly due to bacterial action. The thermal
    optimum was between 35 °C and 40 °C.  Flavobacterium sp. culture was
    able to metabolize  p-nitrophenol by degrading it to nitrite and to
    use it for growth. The DNAs from  Pseudomonas sp. and from the mixed
    culture showed homology with the organophosphate degradation gene from
    a previously reported parathion-hydrolysing bacterium,  Flavobacterium
    sp. Ou & Sharma (1989) showed that methyl parathion is extensively
    degraded by a mixed bacterial culture and a  Bacillus sp. to its
    final oxidation products carbon dioxide and water, whilst a
     Pseudomonas sp. isolated from the mixed culture could degrade the

    hydrolysis product  p-nitrophenol. A  Flavobacterium sp. isolated
    from flooded soil was able to hydrolyse methyl parathion, but a
     Pseudomonas sp. from flooded soil was not (Adhya et al., 1981c). The
    transformation of methyl parathion by pure cultures of  Flavobacterium
    sp. followed multiphasic kinetics (Lewis et al., 1985).

         A different result was described by Arndt et al. (1981) for
    microorganisms in compost. They added 70 mg of methyl parathion
    dissolved in 20 ml ethyl acetate to 1.2 kg of grass (40%), apples
    (23%), potatoes (17%), yoghourt (13%), and bread (7%). After
    composting this mixture for 7 days, no degradation product of methyl
    parathion was found. The recovery rate was 95%. The authors concluded
    that the insecticide could accumulate in the compost under the
    conditions tested, but it could not be excluded that this result was
    affected by the ethyl acetate.

         The concentration of methyl parathion (applied at 0.28 kg/ha) in
    a lake (Clear Lake, California, USA) dropped from 0.50 µg/litre to
    0.28 µg/litre, measured 8 and 48 h, respectively, after treatment
    (Apperson et al., 1976). After a third application (total 3 X 0.28
    kg/ha) the residue level of methyl parathion was 5.4 µg/litre, and 7
    days later, 2 µg/litre (Apperson et al., 1976). Eichelberger &
    Lichtenberg (1971) found that 90% of methyl parathion in river water
    was degraded during a period of 2 weeks, whereas there was no
    degradation in distilled water. The latter finding may be pH related,
    since Cowart et al. (1971) noted 50% hydrolysis of the pesticide after
    14 days in distilled water at pH 6. Under field conditions, in the
    presence of sediment and aquatic plants, degradation is accelerated
    and persistence is lower. Dortland (1980) showed that persistence
    decreased by a factor of 2-3 when sediment and plants were added to
    the aquatic microcosm. When considering the aquatic ecosystem as a
    whole (which includes adsorption on sediments and adsorption on, and
    incorporation in, aquatic biota) a fair estimate of the persistence of
    methyl parathion in the water column seemed to be 2-3 days (Walker,
    1978). This value was recorded in microcosm studies and field
    experiments in both freshwater and estuarine aquatic environments.
    Predicted half-life values in rivers, ponds, eutrophic lakes, and
    oligotrophic lakes were reported to be 0.6, 27.3, 28.3, and 151.6 h,
    respectively (Smith et al., 1978). Methyl parathion was degraded with
    a half-life of 28 h in sediment collected from a field site and with
    a half-life of 7 h in microbial mats derived from laboratory mesocosms
    (Newton et al., 1990). The half-lives of methyl parathion in the water
    and sediment of a carp pond were 5.7 days and 5.0 days, respectively
    (initial residues: 3.77 mg/litre in water and 0.52 mg/kg in soil)
    (Sabharwal & Belsare, 1986). It should be emphasized that the
    persistence values reported depend not only on the type of biotope but
    also on the abiotic conditions, i.e., temperature, pH, and salinity,
    as pointed  out, for example, by Badawy & El-Dib (1984).

         Holm et al. (1983) found in their model ecosystem that the
    sediment type had no observable effect on the degradation of methyl
    parathion and that it depended primarily on the communities of
    microorganisms. These communities and their ability to degrade methyl
    parathion did not change with different sediment types. The microbial
    degradation rate constants in an aquatic channel microcosmos ranged
    from 2.7 X 10-6/s to 6.9 X 10-6/s. This was significantly higher
    than the rate constants determined for abiotic degradation. Cripe et
    al. (1987) modified the river die-away test for determining the
    biodegradability of organic substances and tested the degradation
    products for their toxicity. Because of their sensitivity, mysids and
    daphnids were used for testing the toxicity of the degradation
    products. This test showed a rapid, sediment-mediated biodegradation
    of methyl parathion.

         The biodegration rate of methyl parathion was compared in 3 types
    of test systems composed of sediment and water collected from various
    estuarine sites (Van Veld & Spain, 1983). Generally, methyl parathion
    degradation was fastest in intact sediment/water cores, followed by
    sediment/water shake flasks, and was slowest in water shake flasks.

         Lewis & Holm (1981) determined the transformation rate of methyl
    parathion by "aufwuchs" microorganisms, i.e., aquatic microbial growth
    attached to submerged surfaces or suspended in streamers or mats.
    "Aufwuchs" fungi, protozoa, and algae did not transform methyl
    parathion, but bacteria rapidly transformed it.

         Lewis et al. (1984) examined the effects of microbial community
    interactions on methyl parathion transformation rates. They found
    either stimulation or inhibition of bacterial transformation rates in
    the presence of various cultures, filtrates, or exudates of algae,
    fungi, or other bacteria.

         The biotic and abiotic degradation rates of methyl parathion in
    water and sediment samples over a 3-year period was studied by
    Pritchard et al. (1987). The aim of their study was to find the reason
    for the different degradation rates reported for methyl parathion, but
    the divergences in biodegration could not be assigned to any single
    factor. The predominant degradation in an aerobic system appears to be
    the biological hydrolysis, producing  p-nitrophenol.

         Phosphatases are an important group of enzymes involved in the
    breakdown of methyl parathion (Portier & Meyers, 1982; Portier et al.,
    1983). A proposed pathway for the breakdown of methyl parathion in
    aquatic systems is given by Bourquin et al. (1979) in  Fig. 1.

         Methyl parathion is degraded by bacteria in soil, but more slowly
    by bacteria in water. Crossland et al. (1986) estimated the rate of
    biodegradation of methyl parathion using a mathematical model.
    Sorption on sediment was the dominant process for loss of methyl
    parathion from the water compartment. The rate of biodegradation in
    sediment (4.0 µmol/litre per h) greatly exceeded that of sorption on
    sediment (0.02-0.05 µmol/litre per h) and, therefore, the sediment
    compartment may be considered a sink for methyl parathion.

         The complete decomposition of methyl parathion into innocuous
    compounds can be realized by planktonic and attached microorganisms
    (Lassiter et al., 1986). The metabolite  p-nitrophenol can be further
    metabolized by algae, as reported by Werner & Pawlitz (1978).

    4.2.2  Abiotic degradation

         Data on the abiotic degradation of methyl parathion are presented
    in Table 13.

    4.2.2.1  Photodegradation

         When exposed to UV radiation or sunlight, methyl parathion
    undergoes oxidative degradation. The degradation rate constant of
    methyl parathion sprayed as a film (0.67 µg/cm2) and exposed to 300
    nm light was reported to be 46.6 X 10-7/s, corresponding to a
    half-life of 41.2 h (Chen et al., 1984). In a stationary reactor, the 
    half-life of methyl parathion dissolved in an aqueous solution (pH=7)
    was 72 min after radiation with a Hg low pressure lamp (at 254 nm)
    (Hicke & Thiemann, 1987). Methyl parathion has been shown to be one of
    the most light-sensitive insecticides. Baker & Applegate (1970, 1974)
    showed photodegradation of methyl parathion using light in the
    spectral range 300-400 nm (Table 13); methyl paraoxon, the active
    cholinesterase inhibitor, was produced. Although photodegradation of
    methyl parathion in the terrestrial compartment of the environment may
    be important, it plays only a minor role in aquatic media (Env. Res.
    Lab., 1981). The first-order transformation rate for photolysis upon
    exposure to daylight fluorescent lamps was low compared to hydrolysis
    and, in particular, compared to microbial degradation in an aquatic
    channel microcosm (Holm et  al., 1983). The loss of methyl parathion
    through photolysis was estimated to be 4%.

         Nevertheless, it seems that sunlight may reduce the half-life of
    methyl parathion considerably. Schimmel et al. (1983) reported a
    half-life of 6.3 days for a 1 mg methyl parathion/litre solution
    exposed to sunlight. In darkness, with the same test conditions, the
    half-life was 18 days. Like parathion, the photoreaction of methyl
    parathion was accelerated in the presence of green and blue green
    algae (Zepp & Schlotzhauer, 1983).

    
    Table 13. Abiotic degradation of methyl parathion

    Transformation     Time       Experimental conditions    Light    Initial concentration  Conversion  References
    process                                             
                                  temp (°C)        pH                   (mg/litre)           (%)         

    Hydrolysis in      24 h       a                6                     0.26                  8.8       Cowart et al. (1971)
    distilled water    7 days     a                6                     0.26                 32.0       Cowart et al. (1971)
                       14 days    a                6                     0.26                 50.5       Cowart et al. (1971)
                       21 days    a                6                     0.26                 73.8       Cowart et al. (1971)
                       28 days    a                6                     0.26                100         Cowart et al. (1971)

    Hydrolysis in      31.7 days  10               1-5                   a                    50         Mühlmann & Schrader
    distilled water    12.5 h     40               1-5                   a                    50         (1957)
                                                                                                         Mühlmann & Schrader
                                                                                                         (1957)

    Hydrolysis in      8.4 h      70               6                     6                    50         Ruzicka et al. (1967)
    ethanol buffer

    Hydrolysis in      4 h        37.5             12                    a                   64-73       Jaglan & Gunther
    0.01 M NaOH                                                                                          (1970)

    Table 13 (continued)

    Transformation     Time       Experimental conditions    Light    Initial concentration  Conversion  References
    process                                             
                                  temp (°C)        pH                   (mg/litre)           (%)         

    UV-degradation     2 h        30                         350 nm      0.1                 39          Baker & Applegate
    of pure product    4 h        30                         350 nm      0.1                 65          (1974)
                       6 h        30                         350 nm      0.1                 82          Baker & Applegate
                       8 h        30                         350 nm      0.1                 91          (1974)
                                                                                                         Baker & Applegate
                                                                                                         (1974)
                                                                                                         Baker & Applegate
                                                                                                         (1974)
    Temperature-       2 h        35                         dark        0.1                  9          Baker & Applegate
    degradation of     4 h        35                         dark        0.1                  8          (1974)
    pure product       6 h        35                         dark        0.1                 24          Baker & Applegate
                       8 h        35                         dark        0.1                 31          (1974)
                                                                                                         Baker & Applegate
                                                                                                         (1974)
                                                                                                         Baker & Applegate
                                                                                                         (1974)

    a  No data given.

         Exposure of methyl parathion to sunlight resulted in the
    formation of trace levels of  O, O, S-trimethyl phosphorothioate and
    trimethylphosphate (Chukwudebe et al., 1989).

         According to Sauvegrain (1980), methyl parathion seems to be
    oxidized by oxidizing agents, i.e., ozone and chlorine. Methyl
    parathion treatment with ozone eliminated 80-100% of the compound. The
    oxidation of methyl parathion leads to methyl paraoxon, which is
    further transformed into  p-nitrophenol.

    4.2.2.2  Hydrolytic degradation

         The half-life of methyl parathion in an aqueous solution (20 °C,
    pH 1-5) was reported to be 175 days (Melnikov, 1971). At a
    concentration of 0.03 mol/litre (pH 10), sodium perborate greatly
    accelerated the degradation of methyl parathion (Qian et al., 1985).
    The half-life in the presence of perborate was 12 min, while the rate
    was too slow to be measurable when the same concentration of sodium
    carbonate was added. Badawy & El-Dib (1984) also found that the
    degradation of methyl parathion occurred much more rapidly under
    alkaline (pH 8.5) than under neutral (pH 7.0) or acidic (pH 0.5)
    conditions. The rate of degradation was also positively correlated
    with salinity.

         Although chemical hydrolysis occurs in the aquatic environment,
    this degradation reaction plays only a limited role in the
    disappearance of methyl parathion. In an aquatic channel microcosm,
    only 7% of degradation of the pesticide was attributed to chemical
    hydrolysis (Holm et al., 1983). In a sterile, seawater-sediment
    system, methyl parathion remained for 7 days whereas, in a
    corresponding nonsterile system, 100% of the compound was degraded
    within this period (Env. Res. Lab., 1981).

         Methyl paraoxon, the more toxic oxygen analogue of methyl
    parathion is also chemically hydrolysed. According to Jaglan & Gunther
    (1970), the chemical hydrolysis of methyl paraoxon is much faster than
    that of methyl parathion, because of the presence of oxygen in the
    oxon, which makes the phosphorus more susceptible to attack by the
    hydroxide ion. At pH 8.5 (37.5 °C), approximately 35% of methyl
    paraoxon was hydrolysed within 16 h compared with about 5% for methyl
    parathion.

         The hydrolysis products of methyl parathion and methyl paraoxon
    are dimethyl phosphorothioic acid or dimethyl phosphoric acid and
     p-nitrophenol. These compounds are less toxic than the parent
    compounds, thus hydrolysis is detoxifying (Thuma et al., 1983).

         Pritchard et al. (1987) reported that there was no biotic
    degradation of methyl parathion in seawater, i.e., "the rate resulting
    from the substraction of the sterile rate from the nonsterile rate was
    not significantly different from zero".

         Several research groups investigated the binding of methyl
    parathion on soils as well as the soil catalysed degradation of methyl
    parathion. Saltzman et al. (1976) and Mingelgrin et al. (1977)
    analysed the influences of different water contents and cations on the
    kaolinite-catalysed degradation of methyl parathion; when adsorbed on
    kaolinite, methyl parathion seems to be more stable than  parathion.
    A concentration of 10% Ca-kaolinite catalysed the  degradation of
    methyl parathion most efficiently.

         Wolfe et al. (1986) studied the influences of pH and redox
    transformations on the detoxification of methyl parathion in soils,
    quantitatively. The disappearence of methyl parathion could be
    described by first-order kinetics. Amino methyl parathion was
    identified as a reaction product. Half-lives in the range of a few
    minutes were measured in strongly reducing sediments, thus, confirming
    the data of Gambrell et al. (1984). It was suggested that more
    information about the effect of sediment sorption was needed for
    further studies on the reaction kinetics.

    4.2.3  Bioaccumulation

         Temporary accumulation (up to 10 days) occurred following an
    aerial spraying of pine and deciduous forest with methyl parathion (3
    kg 20% solution/ha in April and 1 kg 40% solution/ha in September),
    which led to higher levels of methyl parathion in the tissues of a
    variety of vertebrates compared with the concentrations in soil,
    water, and plants (Fedorenko et al., 1981).

         Takimoto et al. (1984) reported bioaccumulation of methyl
    parathion in killifish  (Oryzias latipes). Bioaccumulation factors
    of 88-fold (postlarva) to 540-fold (female adult) were found in the
    killifish. Residues in the bluegill sunfish  (Lepomis macrochirus),
    exposed to methyl parathion treatments in a lake, varied from 11 to
    110 µg/kg, corresponding to bioaccumulation factors of 28-39 (Apperson
    et al., 1976).

         Sabharwal & Belsare (1986) added 4 mg methyl parathion/litre to
    the water of a carp-rearing pond and measured the methyl parathion
    concentrations in the water, soil, macrophytes, and carps over a
    period of 35 days. The methyl parathion limits of detection in water,
    soil, macrophytes, and fish were 0.0066, 0.12, 0.0478, and 0.0746
    mg/kg respectively (see Table 14).

         There was an accumulation of methyl parathion in the soil,
    macrophytes, and fish, whereas the compound degraded immediately in
    water. The bioaccumulation in the carp peaked at 3 days.

    Table 14.  The persistence of methyl parathion in water, soil,
    macrophytes, and fisha

    Time (days)              methyl parathion concentration (mg/kg)

                       water       soil         macrophytes      fish

    0                  3.77        0.52           1.2             0.52

    1                  3.15        2.28          14.41           10.26

    3                  2.16        1.5           11.73           26.17

    7                  1.50        -              8.98           11.74

    14                 0.60        -              4.16            5.67

    21                 0.28        -              2.24            2.06

    28                 ndb         ndb            1.42            0.83

    35                 ndb         ndb            0.73            0.48

    a  From: Sabharwal & Belsare (1986).
    b  nd = not detectable.
    
         Using a mean Kow value of 2.55, and on the basis of the log
    Kow/log bio-concentration regression curve for fathead minnows, the
    estimated bioconcentration factor was reported to be 22 (Env. Res.
    Lab., 1981). According to Zitko & McLeese (1980), the expected
    bioconcentration factor in aquatic biota for methyl parathion is
    estimated to be 20.

         Crossland & Bennett (1984) using a range of published log Kow
    values estimated that bioaccumulation factors would be between 2.5 and
    84.
         Accumulation of methyl parathion does not occur in the blood of
    mammals. After ingestion, it is rapidly absorbed and the blood
    concentration reaches a maximum 1-3 h following ingestion and,
    thereafter, decreases. Although a significant portion of methyl
    parathion is found in the bile, it is present in all organs (see also
    section 6.2).

    4.3  Interaction with other physical, chemical, and biological
    factors

         Methyl parathion shows interactions with the following
    substances:  adrenocorticoids, anaesthetics, tricyclic antidepressive
    agents, antihistamines, atropine, barbiturates, clofibrate,
    colistimethate, corticosteroids, curare, decamethonium, dexpanthenol,
    fluorophosphate, hexamethonium, kanamycin, morphine, muscle relaxants,
    anticholinesterases, neomycin, parasympathomimetics, phenothiazines,
    polymyxin, pralidoxime, procainamide, streptomycin, succinylcholin,
    sympathomimetics, d-tubocurarine (Martin, 1978).

         A significant increase in the toxicity of oxygen analogues of
    organophosphorus insecticides to house flies was observed following
    treatment with polychlorinated biphenyl (PCB) (Aroclor 1248)
    (Fuhremann, 1980). Detergents increased the hydrolysis of
    organophosphates, such as methyl parathion (Peterka & Cerna, 1988).
    Yang & Sun (1977) found an inversely proportional correlation between
    fish toxicity and the partition coefficient of different insecticides,
    including methyl parathion.

         DEF ( S,S,S-tributyltrithiophosphate), a defoliant, enhanced the
    toxic effect of methyl parathion in the fish  (Gambusia affinis)
    (Fabacher, 1976).

    4.4  Ultimate fate following use

         The ultimate fate of methyl parathion depends on the degradation
    pathways. The most important one is chemical as well as biological
    hydrolysis; the others are oxidative desulfurisation, nitro reduction,
    and photodegradation. Important degradation products are methyl
    paraoxon, dimethylthiophosphoric acid, dimethylphosphoric acid, and
     p-nitrophenol.

    5.  ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

    5.1  Environmental levels

    5.1.1  Air

         In a pilot study, Stanley et al. (1971) measured methyl parathion
    concentrations of up to 129 ng/m3 in air samples collected in the
    USA (Stoneville). The technique used for air sampling was that of
    Miles et al. (1970).

         In Tennessee, USA, average hourly concentrations of methyl
    parathion in air were < 0.57 ng/m3 (maximum, 2.9 ng/m3) at a site
    located one mile south-east of a methyl parathion plant and one mile
    west of a plant producing the nematocide ethoprophos
    ( O-ethyl- S,S-dipropyl phosphorodithioate), and < 0.64 ng/m3
    (maximum, 5.1 ng/m3) at another site located one mile north of a
    methyl parathion plant. Particulate samples collected from the 2 sites 
    contained < 0.086 ng methyl parathion/m3 (Foster, 1974).

         In the USA, maximum atmospheric levels were detected of 29.6
    ng/m3 in Alabama, 5.4 ng/m3 in Florida, and 129 ng/m3 in
    Mississippi (Midwest Research Institute, 1975). Methyl parathion was
    found in air samples in the Mississippi Delta, one of the highest
    pesticide usage areas in the USA, because of the intensive cotton
    production, at a maximal concentration of 2060 ng/m3 (Arthur et al.,
    1976). The average monthly concentrations of methyl parathion peaked
    in August or September with levels varying from 111.7 ng/m3
    (September 1972) to 791.1 ng/m3 (September 1973).

         In another study, airborne residues of methyl parathion and
    methyl paraoxon were determined after the use of methyl parathion on
    rice in the Sacramento valley in California, USA (Seiber et al.,
    1989). Sampling was conducted on the roof tops of public buildings in
    4 towns in 2 counties where methyl parathion was used in significant
    quantities, and in a reference area where no use occurred. Daily
    maximum average concentrations were 25.7 ng/m3 for methyl parathion
    and 3.1 ng/m3 for methyl paraoxon. The range in averages for all
    sites in the vicinity of usage during springtime 1986 was 0.2-6.2
    ng/m3 for methyl parathion and < 0.5-0.8 ng/m3 for methyl
    paraoxon. With one exception, the background samples did not show any
    methyl parathion above the detection limit.

         Methyl parathion and methyl paraoxon concentrations measured in
    the condensate from coastal fog near Monterey (California, USA) ranged
    between 0.046 and 0.43 µg/litre and between 0.039 and 0.49 µg/litre,
    respectively. The oxon to thion ratios were 0.28-2.6, and thion to
    oxon conversion appeared to take place during atmospheric transport
    from agricultural to the nonagricultural areas (Schomburg et al.,
    1991).

         In the Kalinin District, Tashkent Province, the Uzbek SSR (USSR),
    during July and August, the concentrations of methyl parathion in the
    air after spraying with 30% emulsion, measured at  500, 750, and 1000
    m from the place of the treatment, were 0.055- 0.08, 0.01-0.02, and
    0-0.008 mg/m3, respectively (Akhmedov, 1968).

         Tessari & Spencer (1971) analysed indoor and outdoor air samples,
    collected monthly for a year, at the homes of families where the head
    of the household was occupationally exposed to pesticides. A nylon
    chiffon cloth screen was exposed to the atmosphere for 5 days and the
    absorbed pesticides were extracted and analysed using a column
    chromatography method. The authors found methyl parathion in 13 out of
    52 samples, at an average concentration of 1.04 µg/m3. The range was
    0.04-9.4 µg/m3. The values obtained from outdoor sampling were much
    smaller, 3 out of 53 samples containing 0.35 µg methyl parathion/m3
    with a range of 0.15-0.71 µg/m3.

    5.1.2  Water

         Methyl parathion concentrations of up to 0.23 µg/litre were found
    in selected Western streams of the USA in 1968-71 (Schulze et al.,
    1973).

         In 1970, methyl parathion was detected in 3 out of 18 surface
    drain effluent water samples in California, USA, at concentrations of
    10-190 ng/kg, and, in 8 out of 60 subsurface drain effluent water
    samples, at concentrations of 10-170 ng/kg (Midwest Research
    Institute, 1975).

         In water samples from 10 sites in the Cape Fear River Basin in
    North Carolina, USA, taken monthly between July 1974 and June 1975
    (except October), maximum concentrations of methyl parathion in
    dissolved fractions and in particulate-associated fractions were 468
    ng/litre and 123 ng/litre, respectively (Pfaender et al., 1977).
    Methyl parathion was detected in waste water from a parathion
    production plant in the USA at levels of 2.0 mg/litre in pre-treatment
    water and < 0.004 mg/litre in post-treatment water (Marcus et al.,
    1978).

         Methyl parathion residues in major Mississippi stream systems
    (USA), monitored during 1972-73, ranged between 0.08 and 0.46 µg/litre
    (Leard et al., 1980).

         In one station at the Negro River Basin (Argentina), methyl
    parathion was detected at a concentration of 0.034 µg/litre in March
    1986, which is the end of the summer season in South America (Natale
    et al., 1988).

         In a study on the Ionnina basin and Kalamas river (Greece), from
    September 1984 to October 1985, a seasonal fluctuation was found in
    the concentration of methyl parathion, with a maximum during the
    summer and a minimum during the winter (Albanis et al., 1986). The
    mean concentration in the lake Pamvotis (Greece) was 7.7 ng methyl
    parathion/litre in July. The natural outlet of the lake is the Kalamas
    River, where a maximum concentration of 32 ng methyl parathion/litre
    was found. With the exception of the river, the other analyses showed
    much lower concentrations of methyl parathion. The results of this
    study show very clearly the seasonal influence of the application of
    this pesticide on natural water concentrations.

         Normally, the methyl parathion concentration in the River Rhine
    is below the limit of detection and the Sandoz accident on 1 November
    1987 did not affect the wells of the waterworks. A maximum value
    measured in the Rhine during the second half of 1986 was higher (<
    0.05 mg/m3) than that following this accident (Winter & Lindner,
    1987).

         Methyl parathion was detected in Hungarian surface waters only
    once between 1977 and 1986 (concentration not given), which
    corresponded to a sampling frequency of 0.14% (Csernatoni et al.,
    1988).

    5.1.3  Soil

         In 1969, 76 samples of onions and the soils in which they had
    been grown were collected in the 10 major onion-producing states of
    the USA for analysis of the pesticide residues. The limit of
    quantification of methyl parathion was 0.01 mg/kg. Methyl parathion
    was found in a range of 0.09-1.9 mg/kg in 11.8% of the soil samples.
    No residues were detected in the onion samples (Wiersma et al., 1972).

         Methyl parathion was found at levels of 0.09-1.90 mg/kg in soil
    samples from onion-producing States in the USA (Midwest Research
    Institute, 1975). In cropland soil (South Dakota, USA), the
    concentration of methyl parathion was 0.01 mg/kg soil (Carey et al.,
    1979).

    5.1.4  Food

         Renvall et al. (1975) reported pesticide analyses of fruits and
    vegetables on the Swedish market from July 1967 to April 1973. Methyl
    parathion belonged to the most frequently occurring pesticides with a
    rate of 6%. Levels in 4 out of 207 oranges analysed, 1 out of 37
    lemons, 4 out of 69 grapefruits, and, 2 out of 29 clementines or
    mandarins exceeded 0.11 mg/kg. In a more recent study, in the Swedish
    monitoring programme during the period 1981-84, methyl parathion was

    found in apples, celery, grapes, lemons, lettuce, limes, mandarins,
    oranges, pears, and plums. One out of 74 celeries analysed (imported),
    1 out of 238 lemons (imported), 1 out of 248 lettuces (domestic), 5
    out of 421 mandarins (imported), and, 8 out of 917 oranges (imported)
    exceeded the Swedish maximum residue limits of 0.1-0.5 mg methyl
    parathion/kg (Andersson, 1986).

         In a study on the presence of organophosphorus insecticide
    residues in Mexican food, methyl parathion residues were found in
    market samples of avocados, rice, strawberries, and tomatoes, with
    respectively 6, 4, 3, and 5 positive samples out of 10. The average
    concentrations were 0.3, 0.8, 0.5, and 0.5 mg/kg, respectively (Albert
    et al., 1979).

         A report on pesticide residues in the United Kingdom (1982-85)
    gave a residue level for methyl parathion in lemons of 0.3 mg/kg
    (MAFF, 1986). In a more recent report, no methyl parathion was found
    in cooking apples and in imported apples with a reporting limit of
    determination of 0.1 mg/kg; however, a concentration of 0.08 mg methyl
    parathion/kg was found in one sample of lemons from Spain (MAFF,
    1990).

         Methyl parathion was detected in citrus fruits in France at
    levels of 0.003-1.25 mg/kg (Mestres et al., 1977). Lamontagne (1978)
    found methyl parathion in concentrations of 0.311 mg/kg in fruit and
    0.87-2.12 mg/kg in greenhouse plants in France. Branca & Quaglino
    (1988) found methyl parathion at a residue level of 0.036 mg/kg in one
    out of 34 samples of French potatoes imported into Italy.

         Pesticide residue levels were analysed during 1968-69 in samples
    of ready-to-eat foods from 30 markets in 24 different cities with
    populations of between 50 000 and more than 1 000 000 in the USA. The
    limit of determination was 0.05 mg/kg. Methyl parathion was found
    infrequently (1 X Boston, 1 X Los Angeles, 2 X Minneapolis) in
    concentrations of 0.008, traces, 0.001, and 0.025 mg/kg in leafy
    vegetables and 0.033 mg/kg in grain (Boston) (Corneliussen, 1970). 
    From June 1971 to July 1972, methyl parathion was detected in 7 out of
    420 samples of ready-to-eat foods. The concentrations found in leafy
    vegetables ranged from a trace to 0.010 mg/kg. In one sample of fruit
    (type not given), a concentration of 0.007 mg/kg was found (Boston)
    (Manske & Johnson, 1975). In the report of the Food and Drug
    Administration, 5 samples of leafy vegetables containing methyl
    parathion residues are mentioned. The concentrations ranged from a
    trace to 0.003 mg/kg (Johnson & Manske, 1976). In "market-basket"
    surveys conducted by the US Food and Drug Administration in 1966-69,
    methyl parathion was detected in leafy and stem vegetables at levels
    of 0-2.00 mg/kg, and, in root vegetables, at levels of 0-1.0 mg/kg
    (Midwest Research Institute, 1975). Johnson et al. (1981) did not find
    any methyl parathion in infant and toddler Total Diet Studies (TDS) in

    the USA in 1975-76. In the adult TDS in the USA in 1973-74, trace
    residue levels were found in leafy vegetables, but none in fruit
    (Manske & Johnson, 1977). "Dislodgable" methyl parathion residues were
    found on sweet corn in the USA at levels of 0-0.14 µg/cm2, one and
    two days after application of the pesticide (Wicker et al., 1979).
    Soybeans analysed in 1979 showed levels of 1-40 mg methyl parathion/kg
    and soybean forage analysed at intervals of 1-14 days after treatment,
    0.3-6.6 mg methyl parathion/kg. Levels of 0.1-0.3 mg methyl
    parathion/kg were  measured in 12 samples of cottonseed (FAO, 1985).

         Samples of standing agricultural crops were analysed in 1971
    during the National Pesticide Monitoring Programme in the USA (Carey
    et al., 1978). Levels of methyl parathion detected in samples of
    alfalfa, field orn (kernels), cotton, cotton stalks, and mixed hay
    ranged from 0.02 to 4.57 mg/kg dry weight.

         During a TDS in Canada in 1972, Smith et al. (1975) found methyl
    parathion residues in leafy vegetables from Winnipeg at an average
    level of 0.012 mg/kg.

         In a TDS in New Zealand during 1971-73, methyl parathion was
    found in one sample of leafy vegetables at a level of 0.15 mg/kg in
    1973, in one sample of root vegetables at the level of 0.26 mg/kg in
    1972, and in 4 samples of citrus fruit at an average level of 0.20
    mg/kg and a maximum level of 1.4 mg/kg during each of the years
    1971-73. In 1971, 3 samples of pip fruit contained, on average, 0.03
    mg/kg, and, in 1972, one sample of stone fruit contained 0.25 mg/kg.
    Some of these figures exceeded the New Zealand tolerances (Love et
    al., 1974). In 1974, methyl parathion was detected at levels of
    0.003-0.007 mg/kg in fruit and 0.002-0.008 mg/kg in tinned food from
    Auckland and Wellington, New Zealand (Dick et al., 1978).

         The loss of methyl parathion in food during heating and storage
    was confirmed by Elkins et al. (1972). The samples were analysed
    before, and after, standardized heat treatment. Spinach and apricots
    were fortified separately with methyl parathion. The spinach samples
    were heated for 66 min at 122 °C and the apricot samples were heated
    for 50 min at 103 °C. The initial concentration of methyl parathion in
    the spinach samples was 0.88 mg/kg. It disappeared completely after
    heating. The methyl parathion level in the apricot samples was 0.85
    mg/kg, but this decreased to 46% of this level after heating. The
    detection limit was less than 0.005 mg/kg. A further decomposition can
    be expected during the storage of preserved food. Generally, methyl
    parathion residues in fruit decomposed very rapidly, except in the
    waxy skin of apples and in the oil vessels of olives (Stoll, 1982).

         Rippel et al. (1970) found remarkable differences in the
    degradation of methyl parathion in packaged citrus juice, depending on
    the kind of package surface. The rate of decrease of the methyl
    parathion residues was insignificant in glass containers. It was
    substantially higher in packages with tin-layer surfaces than in
    packages with painted protective surfaces, since the tin layers
    reduced the nitro group of the methyl parathion.

    5.1.5  Terrestrial and aquatic organisms

         Methyl parathion is rapidly metabolized in most organisms,
    resulting in low bioconcentration factors after acute exposure. There
    are few studies of residues of methyl parathion in organisms in the
    environment, but those conducted have consistently shown low methyl
    parathion residues.

         Methyl parathion was detected in tissue samples from estuarine
    fish at a mean level of 47 µg/kg (Butler & Schutzmann, 1978). It has
    been detected at a concentration of 59 µg/kg in the ovaries of spotted
    sea trout  (Cynoscion nebulosus), collected in Texas, USA (Midwest
    Research Institute, 1975).

         Methyl parathion was detected in 34 out of 55 suspectedly
    poisoned apiaries examined in Connecticut (USA) in 1983-85 (Anderson
    & Wojtas, 1986). Concentrations of methyl parathion found in dead bees
    and in brood comb ranged from 0.04 to  5.8 mg/kg.

    5.2  General population exposure

         The general population can come into contact with methyl
    parathion via air, water, or food. Average methyl parathion intake
    from food in the USA during 1988 was estimated to range from 0.1 to
    0.2 ng/kg per day in 3 different age groups (FDA, 1989). Draper &
    Street (1981) estimated that a 70-kg male living in a residence
    adjacent (50 yards) to an alfalfa field sprayed with methyl parathion
    at a rate of 0.19 kg a.i./ha would be exposed to a total dermal dose
    of 0.38 mg. Within a pesticide monitoring programme in the USA, based
    on the analysis of 6990 samples collected from the general population
    via the National Center for Health Statistics 1976-80,
     para-nitrophenol as an indicator for exposure to methyl and ethyl
    parathion was detected in 2.4% of urine samples from 12 to 74-year-old
    persons (Carey & Kutz, 1985).

    5.3  Occupational exposure during manufacture, formulation, or use

         There is a special risk for farm workers, since incidents of
    poisonings and illnesses during the mixing, loading, and application
    of methyl parathion have been reported. Exposure may also occur during
    the cleaning and repair of equipment and during early re-entry into
    fields. According to NIOSH (1976), 150 000 workers in the USA (field

    workers, aerial application personnel, mixer and blender operators,
    tractor tank loaders, ground applicator vehicle drivers, field
    inspectors, and warehouse personnel) are conceivably exposed to methyl
    parathion. A maximum air concentration of methyl parathion was
    estimated to be 1.77 µg/m3. The exposure to methyl parathion was
    estimated by Hayes (1971) for workers checking cotton for insect
    damage as 0.7 mg/h via skin contact and < 0.01 mg/h through
    inhalation (NIOSH, 1976).

         Davis et al. (1981) estimated that workers in apple orchards
    sprayed with methyl parathion would be exposed to dermal doses ranging
    from 0.055 mg to 3.1 mg, with the amount varying with time after
    spraying and the formulation of the pesticide. Two field studies were
    carried out by Kummer & Van Sittert (1986) to evaluate the health risk
    for the farm workers. In a number of cases, the men involved in
    hand-held ULV-spraying wore very little clothing and did not stop
    spraying, when it was too windy. Another possible contamination risk
    was the filling of bottles from larger (25-litre) containers, and the
    repairing and cleaning of the equipment with unprotected hands.
    However, no signs of acute poisoning could be observed in any of the
    persons involved in these studies. The urine was collected in spot
    samples in one of the studies and in 24-h samples in the other. 
    Methyl parathion absorption could be verified from its metabolites in
    the spraymen's urine. Average levels of urinary nitrophenol (mg/g
    creatinine) for 6 supervisors and 2 groups of sprayers were reported
    to be 0.08 (range of 0.05-0.20), 0.38 (range of 0.04-1.38), and 0.13
    (range of 0.06-0.44), respectively. An intake of 0.4-13 mg methyl
    parathion was calculated from the excreted  p-nitrophenol.

         Since investigations showed that clothing worn by agricultural
    workers became contaminated with methyl parathion following
    application and that the laundering of contaminated clothing with
    uncontaminated fabrics resulted in the transfer of the methyl
    parathion residue, recommendations were made that contaminated fabrics
    should not be washed with regular family laundry. Suggestions for the
    procedure of laundering were made by Easley et al. (1981) and Laughlin
    et al. (1981). The most effective procedure was using a pre-rinse
    programme and a detergent together with sodium hypochlorite (NaOCl) as
    a bleach. Laughlin & Gold (1989) discussed further aspects of
    laundering protective clothing contaminated with methyl parathion. 
    Fluorocarbon soil repellent finishes on such protective clothing
    decrease pesticide absorption, but may hinder pesticide removal in
    laundering. Storage of laundered garments at 20 °C with air flow
    and/or at high humidity levels was recommended to dissipate residues
    of methyl parathion.

         Ware et al. (1974b) suggested that serum insecticide levels,
    serum and red blood cell cholinesterase activities, and urinary
    excretion of  p-nitrophenol should be investigated, because they are
    more effective for evaluating the possible potential poisoning hazard
    than the analysis of skin and clothing contamination. The safety of

    re-entering cotton fields 24 h following application of methyl
    parathion was tested. Methyl parathion was applied at 1.12 kg a.i./ha.
    During the application, the temperature ranged from 30 to 38 °C. The
    foliar residues decreased from 1.6 mg/m2, 24 h following methyl
    parathion treatment, to 0.9 mg/m2, 6 h later. No methyl parathion
    was detectable in the serum of the volunteers. The 48-h urinary
    excretion of p-nitrophenol ranged from 0.15 to 1.20 mg. Serum
    cholinesterase levels varied within normal intervals whereas the red
    blood cell cholinesterase levels showed a temporary, but not
    pronounced, depression of about 5-7%. The amounts of methyl parathion
    and methyl paraoxon extracted from clothing and hand surfaces are
    shown in Table 15.

         During the working period, the mean air concentration was 0.2 ng
    methyl parathion/litre, of which, 1.2 µg methyl parathion was inhaled
    over 5 h. From all these data, it was concluded that a 24-h interval
    is safe for methyl parathion in this form of application.

         Munn et al. (1985) collected human exposure samples from workers
    and dependants wearing nylon gloves, as well as environmental samples,
    during the onion harvest season of 1982 in Colorado, USA. Children in
    agricultural settings normally accompany their parents to the fields,
    as part of a family unit, the young children playing in this
    environment and older children helping their parents in the fields. 
    Munn et al. (1985) recorded the length of time the gloves were worn,
    and the age and sex of the participants. No association between age
    and methyl parathion levels was found. The urine samples collected
    prior to their leaving the field did not contain detectable levels of
    methyl parathion. This could be because the nylon gloves reduced the
    absorption of organophosphate residues by about 90%.

    Table 15. Extracted residues of methyl parathion and methyl paraoxon
              following a 5-h working perioda

    Extract from:             Methyl parathion          Methyl paraoxon
                              residue (mg)              residue (mg)

    Hands                         0.2                      0.5

    Shirts                        0.2                      4.0

    mep.5s                        1.7                     39.0

    a From: Ware et al. (1974b).
    
    6.  KINETICS AND METABOLISM

    6.1  Absorption

         Methyl parathion can be absorbed through the digestive tract, the
    skin, and the respiratory tract (White-Stevens, 1971).

         The primary routes of exposure are via skin contact with
    contaminated plants or material, and via inhalation. Severe accidental
    intoxications of humans have occurred.

         The absorption of methyl parathion from the digestive tract is
    rapid, and it appears in the bloodstream immediately after oral
    intake. Studies on guinea-pigs were performed to analyse the rate of
    absorption of radioactive labelled (32P) methyl parathion. One
    minute after dosage, it could be detected in various organs. The
    maximum level was found 1-2 h after treatment. The liver showed a
    remarkably high concentration (Gar et al., 1958).

         Miyamoto et al. (1963) administered 50 mg 32P-labelled methyl
    parathion/kg body weight to guinea-pigs or 1.5 mg/kg body weight to
    rats, by stomach tube. Maximum concentrations in the blood and brain
    were reached 1-3 h after treatment. An oral dose of 50 mg methyl
    parathion/kg resulted in no detectable levels of methyl parathion in
    either the brain or blood after 3 min, but, after 6-8 min, at which
    point lethal effects occurred, levels of methyl parathion increased to
    182 ng/ml in plasma and to 137 ng/g in brain (Yamamoto et al., 1981).

    6.2  Distribution

         Accumulation of methyl parathion was observed in tissues. The
    highest concentrations were found in the lung and the liver (NRC,
    1977). Transplacental transport of methyl parathion is discussed in
    section 8.5.

         Total radioactive residues recovered in the 12 tissues analysed
    (excluding the gastrointestinal tract) from rats given a single oral
    dose of 5 mg C-14-methyl parathion/kg body weight were about 11% of
    the administered dose, 1 h after treatment, declining to 0.3% at 24 h,
    about 0.1% at 48 h, and to only 0.04%, 6 days later. The kidney had
    the highest relative activity up to 8 h after treatment. The
    14C-activity in the plasma was initially about 5 times higher than
    that in the erythrocytes. However, from day 2 to day 6 after dosing,
    the 14C-activity in the erythrocytes was greater than that in plasma
    and remained constant (Weber et al., 1979).

         Sultatos et al. (1990) measured the partition coefficient for
    methyl parathion between mouse liver and blood by either equilibrium
    dialysis or a perfusion technique and obtained values of 9.5 and 16.4
    respectively.

         In a kinetic study on mongrel dogs of both sexes, Braeckman et
    al. (1980) found a rapid decrease in serum methyl parathion
    concentrations during the first few hours. The authors injected methyl
    parathion intravenously in doses of 1, 3, 10, and 30 mg/kg body
    weight. The dogs were pretreated with 1-5 mg atropine/kg body weight,
    10 min before injecting methyl parathion. The blood samples were taken
    for up to 160 h. Besides quantifying serum levels of methyl parathion,
    the authors also measured serum cholinesterase activity at the 2
    highest concentrations of methyl parathion. The determination of serum
    methyl parathion concentrations was performed according to De Potter
    et al. (1978). The cholinesterase activity decreased within 30 min to
    its lowest value, i.e., 40% of the normal level in dogs receiving 10
    mg/kg body weight and 25% in dogs receiving 30 mg/kg. The first rapid
    fall in the methyl parathion concentration after injection was due to
    distribution and elimination. A slower decrease in serum methyl 
    parathion concentrations at higher doses was the result of dee
    compartment linear kinetics. This is in line with observations of
    Tilstone et al. (1979), who found a rebound effect after a 
    haemoperfusion.

    6.3  Metabolic transformation

         Organic nitro compounds, orally administered to ruminants, will
    undergo reduction of the nitro groups to amino groups. This reaction
    takes place in the rumen (Karlog et al., 1978).

         The metabolism of methyl parathion in rodents is illustrated in
    Fig. 2.

         Because of the importance of a first pass through the liver for
    the metabolism of methyl parathion, there is a distinct difference
    between the oral and intravenous toxicity (Morgan et al., 1977;
    Braeckman et al., 1983). Conversion of methyl parathion to its toxic
    metabolite, methyl paraoxon, may occur within minutes following oral
    administration (Yamamoto et al., 1983).

         Mouse liver, perfused with methyl parathion, released the toxic
    metabolite methyl paraoxon into the effluate. Mouse whole blood
    rapidly detoxified the methyl paraoxon formed (Sultatos, 1987).

         A reduction of the cellular concentration of reduced glutathione
    (GSH) influences mitosis, mobility, and other GSH-dependent cell
    functions. Glutathione  S-transferases are mainly located in the
    cytosol and display overlapping substrate specificity. They also show
    peroxidase activity and prevent the peroxidation of membrane lipids.
    The interaction of methyl parathion with GSH or with the glutathione
     S-transferases therefore is important not only for the non-oxidative
    detoxification of the insecticide, but also for species-selective
    toxicity, and the development of resistance. Placental and fetal human
    glutathione  S-transferase catalysed the dealkylation of methyl
    parathion exclusively to demethyl parathion via  O-dealkylation
    (Radulovic et al., 1986; 1987).

         Only after the metabolic formation of methyl paraoxon by liver
    microsomal oxidases does the substance become toxic. Therefore, this
    is an activation reaction. Methyl parathion and methyl paraoxon are
    mainly detoxified by conjugation with GSH (Hennighausen, 1984).

         Detoxification is achieved by degradation reactions, that involve
    either demethylation or dearylation. The resulting desmethyl compounds
    and dimethyl phosphoric acids are essentially nontoxic (NRC, 1977).

    These detoxification reactions are due to the glutathione-dependent
    alkyl and aryl transferases; the reaction products are
     O-methyl- O-p-nitrophenyl phosphorothioate (or
     O-methyl- O-p-nitrophenyl phosphate) or dimethyl phosphorothioic
    acid (or dimethyl phosphoric acid) and  p-nitrophenol. In addition,
    hydrolysis of methylparaoxon by tissue arylesterases may occur. Thus,
    it is possible to follow an exposure to methyl parathion by measuring
    the urinary excretion of  p-nitrophenol (Benke & Murphy, 1975).

         However, prior depletion of glutathione by acetaminophen (Costa
    & Murphy, 1984) or diethyl maleate (Sultatos & Woods, 1988) has little
    effect on the toxicity of methyl parathion in the mouse, indicating
    that perhaps glutathione does not play a significant role in the
    detoxification of methyl parathion.

         The amount of the active toxic compound (methyl paraoxon) that
    will be produced after exposure to methyl parathion, depends on the
    kinetics of the oxidation of methyl parathion and on the kinetics of
    the detoxification reactions. Dealkylation is important at high
    dosages (Plapp & Casida, 1958). This enzyme system was found in the
    supernatant of the liver homogenate. The main metabolites were
    demethyl parathion (80%) and demethyl paraoxon (Fukami & Shihido,
    1963; Shihido & Fukami, 1963).

         The same major metabolites were generated when rat liver
    microsomes metabolized methyl parathion: demethyl paraoxon, methyl
    paraoxon, i.e., dimethyl phosphate, dimethyl phosphorothioate, and
     p-nitrophenol. When rats were treated with methyl parathion,
    dimethyl phosphoric acid was excreted in the urine together with
     O-methyl and  O,O-dimethyl paraoxon (Menzie, 1974).

         Adult rats have an increasing capacity to metabolize the oxygen
    analogue by both oxidative and hydrolytic pathways (Benke & Murphy,
    1975).

         Willems et al. (1980) calculated the high serum clearance of
    methyl parathion from their intravenous studies on dogs to be  2.1
    litre/kg per h.

         Malaysian prawns (Macrobrachium rosenbergii) as well as ridgeback
    prawns  (Sicyonia ingentis) decomposed methyl parathion readily to
     p-nitrophenol and  p-nitrophenyl conjugates. The dominant way of
    detoxification was the formation of ß-glycosides and sulfate esters
    (Foster & Crosby, 1987).

         The metabolism of methyl parathion in humans is similar to that
    reported in experimental animals (Fig. 3) (Benke & Murphy, 1975;
    Morgan et al., 1977). The liver is the primary organ for
    detoxification and metabolism (Nakatsugawa et al., 1968, 1969). The

    main metabolites recovered from urine following administration of
    methyl parathion to human subjects were also  p-nitrophenol and
    dimethyl phosphate. Eight hours after application,  p-nitrophenol
    excretion was nearly complete. Methyl paraoxon was hydrolysed to
    dimethyl phosphate and an amount representing 12% of the administered
    dose was excreted. Its excretion was more protracted than that of
     p-nitrophenol (Morgan et al., 1977). 

         Rao & McKinley (1969) found remarkable differences in the rates
    of metabolism of methyl parathion by liver homogenates from male and
    female chickens. The rate of the oxidative desulfurating system of the
    male liver homogenates was substantially higher than that of the
    homogenates of female chicken livers; however, the rates of the
    demethylating system showed no differences. Also no sexually
    determined differences of the oxidative or the demethylating system
    were found in the liver homogenates of rats, guinea-pigs, or monkeys.

    6.4  Elimination and excretion in expired air, faeces, urine

         After an oral dose of 32P-methyl parathion to mice (17 mg/kg),
    75% of the radioactivity was found after 72 h as metabolites in the
    urine and up to 10% was eliminated in the faeces (Hollingworth et al.,
    1967).

         In male rats, treated with a single oral dose of 14C-methyl
    parathion (benzene ring-labelled) at 0.1, 1 or 5 mg/kg body weight and
    in female rats given a single oral dose of 1 mg/kg body weight, over
    99% of the administered dose was eliminated in the urine and the
    faeces within 48 h. Elimination in the faeces accounted for only  5-7%
    after 1 or 5 mg/kg body weight, but amounted to about 20% after 0.1
    mg/kg body weight  Male rats treated with an intravenous dose of 1 mg
    methyl parathion/kg body weight eliminated about 99% of the
    administered radioactivity in the urine within 48 h, and 
    approximately 1% of the dose in the faeces (Table 16, Weber et al.,
    1979).

        Table 16.  Elimination of 14C-labelled methyl parathion in ratsa,b

    Doses      Route of          No. of     Urine        Faeces        Balance
    (mg/kg)    administration    rats       (%)          (%)           (%)

    0.1        oral              5          79.8±11      19.4±5.       99.2
                                                            3 

    1          oral              4          93.6±2.6     6.3±1.1       99.9

    1          iv                5          99.0±3.8     0.8±0.1       99.8

    1          oral              4          93.3±5.1     6.6±2.7       99.9

    5          oral              5          94.7±6.0     5.1±0.5       99.8

    a Adapted from: Weber et al. (1979).
    b iv = intravenously.
    
         The kinetics of the toxic metabolite of methyl parathion, methyl
    paraoxon, were studied in conscious dogs (De Schryver et al., 1987).
    Thirty min before performing the test, the dogs received atropine as
    protection against intoxication. Methyl paraoxon was administered
    intravenously (2.5 mg/kg body weight) or orally (15 mg/kg body
    weight). The distribution of an intravenous dose was very fast.

         The elimination was fitted by using a one-compartment model. The
    average half-life was determined to be 9.7 min, the average volume of
    distribution 1.76 litre/kg, and the average plasma clearance 126 ml/kg
    per min. Within 3-16 min, the maximal plasma concentration (927-2905
    µg/litre) was reached following oral application. The bioavailability
    ranged from 5 to 71%. The hepatic extraction in anaesthetized dogs
    varied at a high level of 70-92%. From comparison of the urinary
    excretion as  p-nitrophenol after intravenous (87 and 97%) and oral
    (63 and 60%) administration of methylparaoxon, the gastrointestinal
    absorption seemed to be about 60%. It was assumed, that the kinetics
    were linear in this dose range.

         The concentration of the main metabolites paranitrophenol (PNP)
    and dimethylphosphate (DMP) in the urine of 4 human volunteers,
    following 2 days of ingestion of 2 or 4 mg methyl parathion, is shown
    in Table 17. Unmetabolized traces of methyl parathion were also found
    in the urine, which was collected after 4-, 8-, and 24-h (Morgan et
    al., 1977). The urinary excretion of nitrophenol was  60%  within 4 h, 
    86% within 8 h, and approximately 100% within 24 h following
    ingestion. Table 17 shows the dependence of urinary metabolite
    excretion on methyl parathion dosage.

        Table 17.  p-Nitrophenol (PNP) and dimethylphosphate (DMP) concentrations in
              24-h urine samples collected from human volunteers following
              administration of 2 or 4 mg methyl parathiona

                                  PNP                        DMP
                                                                       
                             mean        range        mean        range

     a) 2 mg methyl parathion

    urinary                  0.13        0.08-0.20    0.06        0.02-0.11
    concentration
    (mg/litre)

    24-h excretion (mg)      0.29        0.14-0.43    0.12        0.07-0.16

    excretion per g          0.16        0.10-0.23    0.06        0.03-0.10
    creatinine (mg/g)

     b) 4 mg methyl parathion

    urinary                  0.34        0.16-0.61    0.14        0.05-0.23
    concentration
    (mg/litre)

    24-h excretion (mg)      0.58        0.34-0.88    0.23        0.12-0.41

    excretion per g          0.31        0.15-0.42    0.13        0.06-0.20
    creatinine (mg/g)

    a  Adapted from: Morgan et al. (1977).
    
    6.5  Retention and turnover

         Braeckman et al. (1980) injected 10 mg methyl parathion per kg
    body weight intravenously into dogs, recorded the uptake of methyl
    parathion, and determined a harmonic mean terminal half-life of 7.2 h.
    Five hours after the injection, the concentration decreased to 30% of
    the initial value. Primarily, the peripheral body compartments
    contained this residual methyl parathion. The excretion was completed
    within 35 h.

         The velocity of the excretion of the main metabolites after oral
    or intravenous application was similar. However, the bioavaibility
    after oral intake was reduced by first-pass extraction by the liver
    compared with the intravenous application. Methyl parathion was shown
    to bind to a great extent (90%) to plasma proteins in both dogs and
    humans (Braeckman et al., 1983).

    7.  EFFECTS ON ORGANISMS IN THE ENVIRONMENT

    7.1  Microorganisms

    7.1.1  Bacteria and fungi

         Soil concentrations of methyl parathion of 5 mg/kg or more were
    found to reduce microbial reductive potential (Reddy & Gambrell,
    1985).

         In biotests for sanitary control of water samples, growth
    inhibition of  Escherichia coli by several toxicants was studied in
    a liquid medium (Vogel-Bonner medium, supplemented with thymine and
    glucose at 37 °C). The minimal concentrations of methyl parathion that
    significantly increased growth rate and doubling time of  E. coli
    were reported to be 62.5 mg/litre and 125 mg/litre; the bacterium
    used the compound as a carbon source (Espigares et al., 1990).

         Portier et al. (1983) tested the effects of methyl parathion (1.5
    or 5 mg/litre) on the reproduction of aquatic microorganisms from
    drainage basins in laboratory experiments, using static or
    flow-through approaches (28 °C; pH 7.5; 22%; 22 days; or 28 °C; pH
    7.2; 0%; 24 days). In bacteria and  Actinomycetes , methyl parathion
    had a positive effect on the development. In fungi and yeasts, slight
    negative effects were found that were related to the test conditions
    rather than to the toxicant concentration. In general, a concentration
    of up to 5 mg methyl parathion/litre resulted in increased activity
    and biomass production in a microbial community, being used as carbon
    source by the microorganisms (Portier & Meiers, 1982).

         Bhunia et al. (1991) cultured  Nostoc muscorum , a blue-green
    alga  (Cyanobacterium), which is a major nitrogen-fixing organism in
    tropical soil, with methyl parathion at 5, 10, 20, or 35 mg/litre.
    Only the highest concentration significantly reduced the growth of the
    cells in culture. However, the chlorophyll- a contents of the
    cultures were marginally reduced at 5 mg methyl parathion/litre and
    substantially reduced at 10 mg/litre. Nitrogenase activity was reduced
    to < 50% of control levels at 10 mg/litre.

    7.1.2  Algae

         The 96-h EC50, i.e., the calculated concentration of methyl
    parathion that would inhibit growth by 50% of the diatom  Skeletonema
     costatum , ranged between 5.0 and 5.3 mg/litre (Walsh & Alexander,
    1980; Walsh et al., 1987).

         Exposure of cultures of  Chlorella protothecoides to 26-80 µg
    methyl parathion/litre resulted in decreases in cell growth, as
    measured by cell count, and chlorophyll and protein contents (Saroja-
    Subbaraj & Bose, 1982; Saroja-Subbaraj & Bose, 1983a). These effects

    were correlated with a reduction in photosynthetic electron transfer
    (Saroja-Subbaraj & Bose, 1983a; Saroja-Subbaraj & Bose, 1983b).
    Recovery from the effect on photosynthesis occurred after removal of
    the pesticide. Tolerance to the effect of methyl parathion on cell
    growth occurred for several weeks after exposure (Saroja-
    Subbaraj & Bose, 1984).

         In a natural phytoplankton community, addition of 1 mg methyl
    parathion/litre led to a 5% decrease in the productivity (Butler,
    1964).

         An algal bloom (species not specified) in a methyl
    parathion-treated pond was suggested to have been induced by the
    mortality of herbivorous mayfly larvae and Daphnia (Crossland & Elgar,
    1983).

    7.2  Aquatic animals

         The acute effects of methyl parathion on aquatic animals in
    laboratory studies are presented in Table 18. The data show that the
    sensitivity of aquatic animals to methyl parathion varies considerably
    between species.

         LC50 values of more than 1 mg/litre have been found for some 
    freshwater biota (molluscs, fish, and amphibians). Insect sensitivity 
    to methyl parathion depends not only on the species but on the life 
    stage. In general, instar I larvae are more affected than instar IV 
    larvae. Apperson et al. (1978) showed that larvae may develop a 
    resistance to methyl parathion. Both freshwater and marine 
    crustaceans are sensitive to methyl parathion with EC50 values 
    ranging from 0.002 to 0.050 mg/litre. In general, copepods were less
    sensitive than decapods in laboratory tests.

         Many laboratory studies have been performed on the acute toxicity
    of methyl parathion for fish. The following symptoms of methyl
    parathion poisoning can be expected to occur in fish: darkening of the
    skin, hyperactivity, body tremors, lethargy, jerky swimming, scalosis,
    loss of equilibrium, opercular or gaping paralysis, and death (Rao et
    al., 1967; Anees, 1975; Midwest Research Institute, 1975). One
    response that may be considered to be somewhat characteristic of acute
    methyl parathion poisoning in fish is the extreme forward position of
    the pectoral and pelvic fins (Midwest Research Institute, 1975;
    Srivastava & Singh, 1981).

    
    Table 18. Acute effects of methyl parathion on aquatic animals in laboratory studies

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda
                                                                                                                                           
        MOLLUSCA

    Freshwater mussel

     Lamellidens                           48            st.c                  m, LC50       20 000          -               Moorthy et al. (1983)
     marginalis

     Lamellidens                                                               m, LC50       25 000          -               Moorthy et al. (1983)
     marginilis

     Lamellidens              20 g         48            st.                   m, LC50       23 400          -               Rao et al. (1983)
     marginalis

    Eastern oyster

     Crassostrea              larvae       48            st.; natural seawater d, EC50       12 000          P: 99%          Mayer (1997)
     virginice                                           25 °C                                               s: TEG

    Marine hard clam

     Mercenaria               adult        96            St.: wellwater;       no effect     25 000          s: acetone      Mayer (1987)
     mercenaria                                          24°/oo d 20 °C
                                                         pH8

     Nassa dosoleta           adult        96            st.; wellwater;       no effect     25 000          s: acetone      Meyer (1987
                                                         24°/oo d 20 °C
                                                         pH8

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

      ANNELIDA
      (Estuerine)

     Branchiura               -            72            st.; 4.4 °C           m, 100%       4000            P: techn.gr.    Naqvi (1973)
     sowerbyi                                                                                                s: acetone

     Branchiura               -            72            st.; 21 °C            m, 0%         4000            P: techn.gr.    Naqvi (1973)
     sowerbyi                                                                                                s: acetone

                              -            72            st.; 32.2 °C          m, 100%       4000            P: techn.gr.    Naqvi (1973)
                                                                                                          s: acetone

      CRUSTACEA
      (Freshwater)

    Water flea

     Daphnia                  adult        24            st.; dechlorinated    i, LC50       2.4             P: 93.8%        Stephenson &
     longispira                                          tap-water;                                          s: acetone      Kane (1984)
                                                         19.5 °C; H 250e

     Daphnia                  < 24 h       24            st.; dechlorinated    i, LC50       4.1             P: 93.8%        Stephenson &
     magna                    old                        tap-water;                                          s: acetone      Kane (1984)
                                                         19.5 °C; H 250

     Daphnia                  adult        24            -                     i, LC50       5.4             P: 93.8%        Stephenson &
     magna                                                                                   s: acetone                      Kane (1984)

     Daphnia                  < 24 h       48            st.; artificial       i, LC50       7.8-9.1         P: 99%          Dortland (1980)
     magna                    old                        water; 18 °C                                        s: acetone

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Daphnia                  first        48            st.; reconst.         i. LC50       0.14            P: 98.7         Mayer & Ellersieck
     magnia                   instar                     water; 21 °C                                        s: acetone      (1986)
                                                         pH 7.2-7.5;
                                                         H40-50

     Daphnia                  -             3            st.; 24 °C            m, LC50       8.5             -               Nishiuchi & Hashimoto,
     pulex                                                                                                                   (1967)

     Moira macrocopa          -             3            st.; 24 °C            m, LC50       5.5             -               Nishiuchi &
                                                                                                                          Hashimoto (1967)

     Simocephalus             first        48            st.; reconst.         i, LC50       0.37            P: 98.7%        Mayer & Ellersieck
     secrultus                instar                     water; 15 °C                                        s: acetone      (1986)
                              larva                      pH 7.2-7.5
                                                         H 40-50

    Scud

     Gammarus                 adult        96            st.; reconst.         m, LC50       3.8             P: 98.7%        Mayer & Ellersieck
     fasciatus                                           water; 15 °C                                        s: acetone      (1986)
                                                         pH 7.2-7.5;
                                                         H 40-50

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Field crab

     Oziotelphusa             -            48            st.; tap-water;       m, LC50       1000            P: techn.gr.    Reddy et al. (1986a)
     senex senex                                         pH 7.3; 30 °C                                                     s: acetone
                                                          DO 6.2g; H 38

    Crayfish

     Orconectes               adult        96            st.: reconst.         m, LC50       15              P: 98.7%        Mayer & Ellersieck
     nais                                                water; 15 °C                                        s: acetone      (1986)
                                                         pH 7.2-7.5;
                                                         H 162-272

     Procambarus              2.5-         96            st.; tap-water;       m, LC50       3               P: techn.gr.    Cheeh et al. (1980)
     acutus                   3.5 cm                     pH 8.4; H 100

    from clean area           1.2-         48            st.; tap-water;       m, LC50       2.4             P: techn.gr.    Albaugh (1972)
                              1.5 cm                     pH 8.7; H 10                                        as acetone

    from treated              1.2-         48            st.; tap-water;       m, LC50       3.4             P: techn.gr.    Albaugh (1972)
    area                      1.5 cm                     pH 8.7; H 10                                        s: acetone

     Procambarus              8.9 cm       36            st.; distilled        m, LC50       41              P: 51%          Chang & Lange (1967)
     clarkii                                             water
                                                         22.2-25-5 °C

     Procambarus              8.9 cm       24            at.; tap-water        m, LC50       50              P: tech.gr.     Muncy & Oliver (1963)
     clarkii                                             16-32 °C
                                                         pH 7.6

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Procambarus              8.9 cm       48            st.; tap-water        m, LC50       40              P: tech.gr      Muncy & Oliver (1963)
     clarkii                                             16-32 °C
                                                         pH 7.6

     Procambarus              8.9 cm       72            st.; tap-water        m, LC50       40              P: tech.gr.     Muncy & Oliver (1963)
     clarkii                                             16-32 °C
                                                         pH 7.6

      ESTUARINE
      AND MARINE

    Copepod

     Acartia tonsa            -            96            st.; natural          m, LC50       28              P: 99%          Mayer (1987)
                                                         seawater; 22°/oo                                    s: TEG
                                                         22 °C; pH 8.1-
                                                         8.2; DO 7-7.6

     Acartia tonsa            adult        96            st.; syntheric        m, LC50       890             P: 80%          Khattat & Farley
                                                         seawater; 22°/oo                                                    (1976)
                                                         17 °C

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Sand shrimp

     Crangon                  2.6 cm       24            st.; wellwater        m, LC50       11              s: acetone      Eisler (1969)
     septemspinosa            0.25 g                     24°/oo; 20 °C; pH 8
                                                         DO 7.1-7.7

     Crangon                  2.6 cm       48            st.; wellwater        m. LC50       3               s: acetone      Eisler (1969)
     septemspinosa            0.25 g                     24°/oo; 20 °C; pH 8
                                                         DO 7.1-7.7

     Crangon                  2.6 cm       96            st.; wellwater        m, LC50       2               s: acetone      Eisler (1969)
     septemspinosa            0.25 g                     24°/oo; 20 °C; pH 8
                                                         DO 7.1-7.7

    Mysid shrimp

     Mysidopsis               24 h         96            st.; natural          m, LC50       0.98            P: 99%          Mayer (1987)
     bahia                    old                        seawater; 20°/oo;                                   s: TEG
                                                         25 °C;
                                                         DO 4.3-5.5

     Mysidopsis               24 h         96            st.; natural          no effect     0.32            P: 99%          Mayer (1987)
     bahia                    old                        seawater; 20°/oo;                                   s: TEG
                                                         25 °C;
                                                         DO 4.3-5.5

     Mysidopsis               24 h         96            flow-through          m, LC50       0.77            P: 99%          Mayer (1987)
     bahia                    old                        natural seawater;                                   s: TEG
                                                         20°/oo; 25 °C;
                                                         DO 4.3-5.5

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Mysidopsis               < 24 h       96            flow-through          m, LC50       0.78            P: 99%          Mayer (1987)
     bahia                    old                        14°/oo; 19.5 °C;                                    s: TEG

     Mysidopsis               juvenile     96            flow-through          m, LC50       0.77            s: TEG          Nimmo et al. (1981)
     bahia                                               22-28 °C

     Mysidopsis               juvenile     96            flow-through          MATCg         0.11-0.16       s: TEG          Nimmo et al. (1981)
     bahia                                               22-28 °C

    Hermit crab

     Pagurus                  3.5 mm       24            st.; wellwater        m, LC50       23              s: acetone      Eisler (1969)
     longicarpus              0.28 g                     24°/oo; 20 °C; ph 8;
                                                         DO 7.1-7.7

     Pagurus                  3.5 mm       48            st.; wellwater        m, LC50        7              s: acetone      Eisler (1969)
     longicarpus              0.28 g                     24°/oo; 20 °C; ph 8;
                                                         DO 7.1-7.7

     Pagurus                  3.5 mm       96            st.; wellwater        m, LC50        7              s: acetone      Eisler (1969)
     longicarpus              0.28 g                     24°/oo; 20 °C; ph 8;
                                                         DO 7.1-7.7

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Crab

     Portunus                 Zo÷e IV      24            25 °C                 m, LC50       0.17-0.5        -               Hirayama & Tamaoi
     trituberculatus          stage                                                                                          (1980)

    Grass shrimp

     Palaemonetes             31 mm        24            st.; wellwater;       m, LC50       15              s: acetone      Eisler (1969)
     vulgaris                 0.47 g                     24°/oo; 20 °C; ph 8;
                                                         DO 7.1-7.7

     Palaemonetes             31 mm        48            st.; wellwater;       m, LC50       10              s: acetone      Eisler (1969)
     vulgaris                 0.47 g                     24°/oo; 20 °C; ph 8;
                                                         DO 7.1-7.7

     Palaemonetes             31 mm        96            st.; wellwater;       m, LC50       3               s: acetone      Eisler (1969)
     vulgaris                 0.47 g                     24°/oo; 20 °C; ph 8;
                                                         DO 7.1-7.7

    Brown shrimp

     Penaeus aztecus          adult        24            flow-through          m, LC50       5.5             s: acetone      Butler (1964)
                                                         29°/oo; 25 °C

     Penaeus aztecus          adult        48            flow-through          m, LC50       5.5             s: acetone      Butler (1964)
                                                         29°/oo; 25 °C

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Pink shrimp

     Penaeus duorerum         -            -             flow-through          m, LC50       1.9             s: acetone      Schoor & Brausch,
                                                         17-31 °/oo                                          + TEG           (1980)
                                                         7.6-28.8 °C

     Penaeus duorarum         post-        96            flow-through          m, LC50       1.2             s: TEG          Mayer (1987)
                              larvae                     natural seawater                                    P: 99%
                                                         20 °/oo; 25 °C

    Japanese shrimp

     Peneaus                  post-        24            25 °C                 m, LC50       0.5-0.9         -               Hirayama & Tamaoi
     japonicus                larve                                                                                          (1980)

    Shrimp

     Penaeus                  post-        96            st.; natural seawater               m, LC50         1.4             s: TEG Mayer (1987)
     stylirostris             larvae                     20 °/oo; 25 °C;                                     P: 99%
                                                         DO 5.6-6.3

     Penaeus                  adult        96            st.; 15 °/oo;         m, LC50       148             -               Reddy & Rao (1986)
     monodon                                             23 °C; pH 7.3

     Penaeus                  adult        96            st.; 15 °/oo;         m, LC50       98              -               Reddy & Rao (1986)
     indicus                                             23 °C; pH 7.3

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Penaeus                  (inter-molt)               48                    st.; seawater;                m, LC50         95-Reddy & Rao (1986)
     indicus                  2.5 g                      15 °/oo; 23 °C
                                                         pH 7.1

     Metapenaeus              adult        96            st.; 15 °/oo          m, LC50       102             -               Reddy & Rao (1986)
     monoceros                                           23 °C; pH 7.3

     Metapenaeus              (inter-molt)               48                    st.; seawater;                m, LC50         120- Reddy & Rao (1988)
     monoceros                2.5 g                      15 °/oo; 23 °C;
                                                         pH 7.1

     Metapenaeus              adult        96            st.; 15 °/oo          m, LC50       115             -               Reddy & Rao (1986)
     dopsoni                                             23 °C; pH 7.3

      INSECTA

    Mosquito

     Culex piplens            4th          24            st.; 28 °C;           m, LC50       30              P: 98.2%        Yasuno et al. (1965)
                              instar                     deionized                                           s: ethanol
                              larva                      water

     Culex piplens            4th          24            st.; 28 °C;           m, LC50       2000            P: 98.2%        Yasuno et al. (1965)
                              instar                     polluted                                            s: ethanol
                              larva                      water

     Culex piplens            4th          96            st.; 28 °C;           m, LC50       30              P: 98.2%        Yasuno et al. (1965)
                              instar                     deionized                                           s: ethanol
                              larva                      water

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Culex pipiens            4th          96            st.; 28 °C;           m, LC50       80 000          P: 98.2%        Yasuno et al. (1965)
                              instar                     polluted                                            s: ethanol
                              larva                      water

     Chactorus                1st          24            st.; lake             m, LC50       1.6             P: techn.gr.    Apperson et al.
     astictopus               instar                     water; 25 °C                                        s: acetone      (1978)
                              larva                                                                          (1962 exper.)

     Chactorus                4th          24            st.; lake             m, LC50       30              P: techn.gr.    Apperson et al.
     astictopus               instar                     water; 25 °C                                        s: acetone      (1978)
                              larva                                                                          (1962 exper.)

     Chactorus                1st          24            st.; lake             m, LC50       18              P: techn.gr.    Apperson et al.
     astictopus               instar                     water; 25 °C                                        s: acetone      (1978)
                              larva                                                                          (1978 exper.)

     Chactorus                4th          24            st.; lake             m, LC50       85              P: techn.gr.    Apperson et al.
     astictopus               instar                     water; 25 °C                                        s: acetone      (1978)
                              larva                                                                          (1978 exper.)

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Damselfly

     Ischnura                 larva        96            st.; reconst.         m, LC50       33              P: 98.7%        Mayer & Ellersiack
     venticalus                                          water; 15 °C                                        s: acetone      (1987)
                                                         pH 7.2-7.5
                                                         H 167-272

      FISH
      (Freshwater)

     Betta                    adult        120           tap-water; 25 °C      m, LC50       7500-8000       s: haxana       Walsh & Hanselka
     splendens                                           pH 7-7.4                                                            (1972

    Goldfish

     Carassius                0.6-         96            st.; reconst.         m, LC50       9000            P: 80%          Mayer & Ellersieck
     auratus                  1.7 g                      water; 18 °C;                                       s: acetone      (1986)
                                                         pH 7.1

     Carassius                4.6 cm       24            st.; dest.            m, LC50       14 000          P: 80%          Pickering et al.
     auratus                  1.2 g                      water; 25 °C;                                       s: acetone      (1962)
                                                         pH 7.4-7.5
                                                         H 20; DO 4-8
                          
     Carassius                4.6 cm       48            st.; distilled        m, LC50       12 000          P: 80%          Pickering et al.
     auratus                  1.2 g                      water; 25 °C;                                       s: acetone      (1962)
                                                         pH 7.4-7.5
                                                         H 20; DO 4-8

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Carassius                4.6 cm       96            st.; distilled        m, LC50       12 000          P: 80%          Pickering et al.
     auratus                  1.2 g                      water; 25 °C;                                       s: acetone      (1962)
                                                         pH 7.4-7.5
                                                         H 20; DO 4-8

    Golden carp

     Cyprinus                 -            48            st.; 24 °C            m, LC50       > 10 000        P: 80%          Nishiuchi &
     auratus                                                                                                 s: acetone      Hashimoto (1967)

    Carp

     Cyprinus                 < 1 year     24            st.; 20 °C            m, LC50       27 600          P: 80%          Rehwoldt et al.
     carpio                                              pH 7.2; DO 6;                                       s: acetone      (1977)
                                                         H 50

     Cyprinus                 < 1 year     48            st.; 20 °C            m, LC50       21 200          P: 80%          Rehwoldt et al.
     carpio                                              pH 7.2; DO 6;                                       s: acetone      (1977)
                                                         H 50

     Cyprinus                 < 1 year     96            st.; 20 °C            m, LC50       14 800          P: 80%          Rahwoldt et al.
     carpio                                              pH 7.2; DO 6;                                       s: acetone      (1977)
                                                         H 50

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Cyprinus                 35 g         48            st.; 20 °C            m, LC50       12 000          P: 80%          Nagaratnamma &
     carpio                                              pH 7.2; DO 6;                                       s: acetone      Ramamurthi (1982)
                                                         H 50

     Cyprinus                 0.6-         96            st.; reconst.         m, LC50       7130            P: 80%          Mayer & Ellersieck
     carpio                   1.7 g                      water; 18 °C                                        s: acetone      (1986)
                                                         pH 7.1

     Cyprinus                 0.6 g        96            st.; reconst.         m, LC50       8900            P: techn.gr.    Johncon & Finley
     carpio                   1.7 g                      water; 18 °C                                        s: acetone      (1980)
                                                         pH 7.2-7.5
                                                         H 40-50

     Cyprinus                 0.6 g        48            st.; 24 °C            m, LC50       > 10 000        P: techn.gr.    Nishiuchi &
     carpio                                                                                                  s: acetone      Hashimoto (1967)

    Banded killifish

     Fundulus                 < 1 year     24            st.; 20 °C            m, LC50       24 900          P: techn.gr.    Rehwoldt et al.
     diaplanus                                           pH 7.2; DO 6;                                       s: acetone      (1977)
                                                         H 50

     Fundulus                 < 1 year     48            st.; 20 °C            m, LC50       18 600          P: techn.gr.    Rehwoldt et al.
     diaplanus                                           pH 7.2; DO 6;                                       s: acetone      (1977)
                                                         H 50

     Fundulus                 < 1 year     96            st.; 20 °C            m, LC50       15 200          P: techn.gr.    Rehwoldt et al.
     diaplanus                                           pH 7.2; DO 6;                                       s: acetone      (1977)
                                                         H50

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Mosquito fish

     Gambusia                 adult        48            st.; dechlorinated    m, LC50       13 480          P: 99%          Chambers &
     affinis                  non                        tap-water                                           s:              Yarbrough (1974)
                             resistent                                                                      methoxy-ethanol

     Gambusia                 adult        48            st.; dechlorinated    m, LC50       17 480          P: 99%          Chambers &
     affinis                  non                        tap-water                                           s:              Yarbrough (1974)
                            resistent                                                                      methoxy-ethanol

    Catfish

     Heteropneustes           adult        96            24 °C; pH 7,7;        m, LC50       7000            s: acetone      Srivastava & Singh
     fossilis                 (fem)                      DO 6; H 117                                                         (1981)

     Heteropneustes           16 cm        24            st.; 23 °C;           m, LC50       9400            s: acetone      Singh & Srivastava
     fossilis                 35 g                       pH 7.7; DO                                                          (1982)
                                                         6.1; H 115
  
     Heteropneustes           16 cm        48            st.; 23 °C;           m, LC50       8600            s: acetone      Singh & Srivastava
     fossilis                 35 g                       pH 7.7; DO                                                          (1982)
                                                         6.1; H 115

     Heteropneustes           16 cm        72            st.; 23 °C;           m, LC50       8000            s: acetone      Singh & Srivastava
     fossilis                 35 g                       pH 7.7; DO                                                          (1982)
                                                         6.1; H 115

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Heteropneustes           16 cm        96            st.; 23 °C;           m, LC50       7000            s: acetone      Singh & Srivastava
     fossilis                 35 g                       pH 7.7; DO                                                          (1982)
                                                         6.1; H 115

    Black Bullhead

     Ictalurus melas          0.6-         96            st.; reconst.         m, LC50       6640            P: 80%          Mayer & Ellersieck
                              1.7 g                      water; 18 °C                                        s: acetone      (1986)
                                                         pH 7.1

    Catfish

     Mystus cavasius          6-8 cm       96            26-30 °C              m, LC50       5900            -               Murty & Ramani (1982)
                              7g

    Channel Catfish

     Ictalurus                1.4 g        96            st.; reconst.         m, LC50       5240            P. techn.gr.    Mayer & Ellersieck
     punctatus                                           water; 18 °C                                        s: acetone      (1986)
                                                         pH 7.2-7.5; H 40-50

     Guppy (Poecilia
     reticulata)

     Lebistes                 6 mon.       24            st.; distilled        m, LC50       11 000          P. 80%          Pickering et al.
     reticulatus                                         water; 25 °C                                        s: acetone      (1962)
                                                         pH 7.4-7.5;
                                                         H 20, DO 4-8

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Lebistes                 6 mon.       48            st.; distilled        m, LC50       9800            P. 80%          Pickering et al.
     reticulatus                                         water; 25 °C                                        s: acetone      (1962)
                                                         pH 7.4-7.5;
                                                         H 20, DO 4-8

     Lebistes                 6 mon.       96            st.; distilled        m, LC50       9800            P. 80%          Pickering et al.
     reticulatus                                         water; 25 °C                                        s: acetone      (1962)
                                                         pH 7.4-7.5;
                                                         H 20, DO 4-8

     Lebistes                 < 1 year     24            st.; 20 °C            m, LC50       12 200          P. 80%          Rehwoldt et al.
     reticulatus                                         pH 7.2; DO 6                                        s: acetone      (1977)
                                                         H 20

     Lebistes                 < 1 year     48            st.; 20 °C            m, LC50       9400            P. 80%          Rehwoldt et al.
     reticulatus                                         pH 7.2: DO 6                                        s: acetone      (1977)
                                                         H 20

     Lebistes                 < 1 year     96            st.; 20 °C            m. LC50       6200            P. 80%          Rehwoldt et al.
     reticulatus                                         pH 7.2; DO 6                                        s: acetone      (1977)
                                                         H 20

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Green sunfish

     Lepomis                  0.8 g        96            st.; reconst.         m, LC50       6860            P: techn.gr.    Mayer (1987)
     cyanellus                                           water; 17 °C                                        s: acetone
                                                         pH 7.2-7.5;
                                                         H 40-50

     Lepomis                  0.8 g        48            st.; tap-water        m, LC50       > 5000          P: techn.gr.    Minchew & Ferguson
     cyanellus                                           20 °C                                               s: acetone      (1969)

    Pumpkinseed

     Lepomis                  40-50 g      24            injection, st.        m, LD50       > 2500          P: 99%          Benke et al. (1974)
     gibbosus                                                                                                s: corn oil

     Lepomis                  < 1 year     24            st.: 20 °C            m, LD50       4900            P: 99%          Rehwoldt et al.
     gibbosus                                            pH 7.2; DO 6;                                       s: corn oil     (1977)
                                                         H 50

     Lepomis                  < 1 year     48            st.: 20 °C            m, LD50       3600            P: 99%          Rehwoldt et al.
     gibbosus                                            pH 7.2; DO 6;                                       s: corn oil     (1977)
                                                         H 50

     Lepomis                  < 1 year     96            st.: 20 °C            m, LD50       3600            P: 99%          Rehwoldt et al.
     gibbosus                                            pH 7.2; DO 6;                                       s: corn oil     (1977)
                                                         H 50

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Bluegill sunfish

     Lepomis                  fingerling   24            st.; reconst.         m, LC50       6470            P: 44.6%        McCann & Jasper
     machrochirus                                        water; 18 °C                                        s: water        (1972)
                                                         pH 7; H 17

     Lepomis                  0.6-         96            st.; reconst.         m, LC50       5720            P: 80%          Macak & McAllister
     machrochirus             1.7 g                      water; 18 °C                                        s: acetone      (1970)
                                                         pH 7.1

     Lepomis                  4-6 cm       24            st.; distilled        m, LC50       9800            P: 80%          Pickering et al.
     machrochirus             1.2 g                      water; 25 °C                                        s: acetone      (1962)
                                                         pH 7.4-7.5
                                                         H 20; DO 4-8
                                                   
     Lepomis                  4-6 cm       48            st.; distilled        m, LC50       8600            P: 80%          Pickering et al.
     machrochirus             1.2 g                      water; 25 °C                                        s: acetone      (1962)
                                                         pH 7.4-7.5
                                                         H 20; DO 4-8

     Lepomis                  4-6 cm       96            st.; distilled        m, LC50       2400            P: 80%          Pickering et al.
     machrochirus             1.2 g                      water; 25 °C                                        s: acetone      (1962)
                                                         pH 7.2-7.5;
                                                         H 20; DO 4-6

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Lepomis                  1 g          96            st.; reconst.         m, LC50       4380            P: techn.gr.    Mayer & Ellersieck
     machrochirus                                        water; 17 °C                                        s: acetone      (1986)
                                                         pH 7.2-7.5
                                                         H 40-50

     Lepomis                  0.6-         96            st.; reconst.         m, LC50       5170            P: 80%          Macek & McAllister
     machrochirus             1.7 g                      water; 18 °C                                        s: acetone      (1970)
                                                         pH 7.1

    Largemouth bass

     Micropterus              0.6-         96            st.; reconst.         m, LC50       5220            P: 80%          Mayer & Ellersieck
     salmoides                1.7 g                      water; 18 °C                                        s: acetone      (1986)
                                                         pH 7.1

     Mystus cavasius          -            96            -                     m, LC50       5900            -               Murty & Ramani
                                                                                                                          (1982)

    Golden shiner

     Notamigonus              -            48            st.; tap-water:       m, LC50       > 5000          P: techn.gr.    Minchew & Ferguson
     chrysoleuces                                        20 °C                                               s: acetone      (1969)

    Coho salmon

     Oncorhynchus             0.6-         96            st.; reconst.         m, LC50       5300            P: 80%          Meyer & Ellersieck
     kisutch                  1.7 g                      water; 13 °C                                        s: acetone      (1986)
                                                         pH 7.1

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Medaka

     Oryzias latipes          -            48            er.; 24 °C            m, LC50       7500            P: techn.gr,    Nishiuchi &
                                                                                                           s: acetone      Hashimoto (1967)

    Yellow perch

     Perca                    1.4 g        96            st.; reconst.         m, LC50       3060            P: techn.gr.    Mayer & Ellersieck
     flavescens                                          water; 18 °C                                        s: acetone      (1986)
                                                         pH 7.2-7.5;
                                                         H 40-50

    Punti

     Puntius                  6-           24            st.; 27.9 °C          m, LC50       2900            P: 50%          Rao et al. (1967)
     puckelli                 8.5 cm                     pH 8.3; H 130

     Puntius                  6-           48            st.; 27.9 °C          m, LC50       2700            P: 50%          Rao et al. (1967)
     puckelli                 8.5 cm                     pH 8.3; H 130

     Puntius                  6-           96            st.; 27.9 =C          m, LC50       2100            P: 50%          Rao et al. (1967)
     puckelli                 8.5 cm                     pH 8.3; H 130

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Fathead minnow

     Pimephales               1.2 g        96            st.; reconst.         m, LC50       8300            P: techn.gr.    Mayer & Ellersieck
     promelas                                            water; 18 °C                                        s: acetone      (1986)
                                                         pH 7.2-7.5; H40-50

     Pimephales               -            48            flow-through          m, LC50       7400            P: 98.5%        Solon & Nair (1970)
     promelas                                                                                s: acetone

     Pimephales               -            96            flow-through          m, LC50       3750            P: 98.5%        Solon & Nair (1970)
     promelas                                                                                s: acetone

     Pimephales               newly        96            st.; sterilized       m, LC50       4460            P: 80%          Jarvinen & Tanner
     promelas                 hatched                    water; 25 °C                                                        (1982)
                              larvae                     pH 7.4-7.8;
                                                         DO 6.5-8.4; H 64

     Pimephales               newly        96            st.; sterilized       m, LC50       1220            P: 80%          Jarvinen & Tanner
     promelas                 hatched                    water; 25 °C          DO 6.5-8.4; H                                 stock (1982)
                              larvae                     pH 7.4-7.8;           64                            solution aged
                                                                                                          11 weeks

     Pimephales               newly        96            st.; sterilized       m, LC50       8170            P: 80%          Jarvinen & Tanner
     promelas                 hatched                    water; 25 °C                                        controlled-     (1982)
                              larvae                     pH 7.4-7.8;                                         release
                                                         DO 6.5-8.4; H 64                                    formulation

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Pimephales               newly        96            st.; sterilized       m, LC50       3470            P: 80%          Jarvinen & Tanner
     promelas                 hatched                    water; 25 °C                                        controlled      (1982)
                              larvae                     pH 7.4-7.8;                                         release
                                                         DO 6.5-8.4; H 64                                    formulation
                                                                                                          for 11 weeks

     Pimephales               newly        96            flow-through;         m, LC50       5360            P: 80%          Jarvinen & Tanner
     promelas                 hatched                    sterilized water                                                    (1982)
                              larvae                     25 °C; pH 7.4-
                                                         7.8; DO 6.5-8.4;
                                                         H 64

     Pimephales               newly        96            flow-through;         m, LC50       6910            P: 80%          Jarvinen & Tanner
     promelas                 hatched                    sterilized water                                    controlled      (1882)
                              larvae                     25 °C; pH                                           release
                                                         7.4-7.8;                                            formulation
                                                         DO 6.5-8.4;
                                                         H 64

     Pimephales               4-6 cm       24            st.; distilled        m, LC50       13 000          P: 80%          Pickering et al.
     promelas                 1-2 g                      water; 25 °C                                        s: acetone      (1862)
                                                         pH 7.4-7.5;
                                                         H 20; DO 4-8

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Pimephales               4-6 cm       48            st.; distilled        m, LC50       9800            P: 80%          Pickering et al.
     promelas                 1-2 g                      water; 25 °C                                        s: acetone      (1962)
                                                         pH 7.4-7.5;
                                                         H 20; DO 4-8

     Pimephales               4-6 cm       96            st.; distilled        m, LC50       9500            P: 80%          Pickering et al.
     promelas                 1-2 g                      water; 25 °C                                        s: acetone      (1962)
                                                         pH 7.4-7.5;
                                                         H 20; DO 4-8

    White perch

     Roccus                   < 1 year     24            st.; 12 °C            m, LC50       22 400          P: 80%          Rehwoldt et al.
     americanus                                                                pH 7.2                        s: acetone      (1977)

     Roccus                   < 1 year     46            st.; 12 °C            m, LC50       18 600          P: 80%          Rehwoldt et al.
     americanus                                          pH 7.2                                              s: acetone      (1977)

     Roccus                   < 1 year     96            st.; 12 °C            m, LC50       14 000          P: 60%          Rehwoldt et al.
     americanus                                          pH 7.2                                              s: acetone      (1977)

    Cutthroat trout

     Salmo clarki             0.2 g        96            st.; reconst.         m, LC50       1850            P: techn.gr.    Mayer & Ellersieck
                                                         water; 12 °C                                        s: acetone      (1996)
                                                         pH 7.2-7.5;
                                                         H 162-272

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Rainbow trout
    (Oncorhynchus
    mykiss)

     Salmo                    1.1 g        96            st.; reconst.         m, LC50       3700            P: techn.gr.    Mayer & Ellersieck
     gairdneri                                           water; 12 °C;                                       s: acetone      (1986)
                                                         pH 7.2-7.5;
                                                         H 162-272

     Salmo                    0.6-         96            st.; reconst.         m, LC50       2750            P: 80%          Macek & McAllister
     gairdneri                1.7 g                      water; 13 °C;                                       s: acetone      (1970)
                                                         pH 7.1

     Salmo                    24 mm        96            st.; 12 °C            m, LC50       2800            P: 76.8%        Palawski et al.
     gairdneri                                                                                                               (1983)

    Brown trout

     Salmo trutta             0.6-         96            st,; reconst,         m, LC50       4750            P: 80%          Mayer & Ellersieck
                                           1.7 g         pH 7.1                                              s: acetone      (1986)
                                                         water; 13 °C

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Brook trout

     Salvelinus               0.5 g        96            st.; reconst.         m, LC50       3780            P: techn.gr.    Mayer & Ellersieck
     fontinalis                                          water; 12 °C                                        s: acetone      (1986)
                                                         pH 7.2-7.5;
                                                         H 40-50

    Northern pike

     Esox lucius              0.4 g        24            st.; 18 °C            m, LC50       760             P: techn.gr.    Mayer & Ellersieck
                                                         pH 7.1; H 44                                        s: acetone      (1986)

    Tilapia

     tilapia                  -            48            st.; 26-28 °C         m, LC50       266             P: techn.gr.    Rao & Rao (1983)
     mossambica                                          pH 7; H 140                                       s:
                                                                                                          2-methoxyethanol
    ESTUARINE
    AND MARINE

    American eel

     Anguilla                 59           24            st.; underground      m, LC50       27 600          P: act,         Eisler (1970a)
     rostrata                 mm-0.14 g                  wellwater;                                          ingredient
                                                         24%0; 20 °C;                                        s: acetone
                                                         pH 8; DO 7.1-7.7

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Anguilla                 59           48            st.; underground      m, LC50       22 400          P: act.         Eisler (1970a)
     rostrata                 am-0. 14 g                 wellwater;                                          ingredient
                                                         24°/oo; 20 °C;                                      s: acetone
                                                         pH 8; DO 7.1-7.7

     Anguilla                 59           96            st.; underground      m, LC50       16 900          P: act.         Eisler (1970e)
     rostrate                 am-0.14 g                  wellwater;                                          ingredient
                                                         24°/oo; 20 °C;                                      s: acetone
                                                         pH 8; DO 7.1-7.7

     Anguilla                 < 1 year     24            st.; 20 °C.           m, LC50       42 600          P: act.         Rehwoldt et al.
     rostrata                                            pH 7.2; DO 6;                                       ingredient      (1977)
                                                         H 50                                                s: acetone

     Anguilla                 < 1 year     48            st.; 20 °C.           m, LC50       37 200          P: act.         Rehwoldt et al.
     rostrata                                            pH 7.2; DO 6;                                       ingredient      (1977)
                                                         H 50                                                s: acetone

     Anguilla                 < 1 year     96            st.; 20 °C.           m, LC50       6300            P: act.         Rehwoldt et al.
     rostrata                                            pH 7.2; DO 6;                                       ingredient      (1977)
                                                         H 50                                                s: acetone

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Sheephead
    minnow

     Cyprinodon               28 days      96            st.; natural          m, LC50       12 000          P: 99%          Mayer (1987)
     variegatus               old                        sea-water;                                          s: TEG
                                                         20°/oo; 25 °C;
                                                         DO 4.6-5.7

     Cyprinodon               28 days      96            st.; natural          no effect     10 000          P: 99%          Mayer (1987)
     variegatus               old                        sea-water;                                          s: TEG
                                                         20°/oo; 25 °C;
                                                         DO 4.6-5.7

    Mummichog

     Fundulus                 55 mm        24            st.; underground      m, LC50       > 85 100        P: act.         Eisler (1970a)
     heteroclitus             1.7 g                      wellwater; 24°/oo;                  ingredient
                                                         20 °C; pH 8;                                        s: acetone
                                                         DO 7.1-7.7

     Fundulus                 55 mm        48            st.; underground      m, LC50       85 200          P: act.         Eisler (1970a)
     heteroclitus             1.7 g                      wallwater; 24°/oo;                  ingredient
                                                         20 °C; pH 8;                                        s: acetone
                                                         DO 7.1-7.7

     Fundulus                 55 mm        96            st.; underground      m, LC50       58 000          P: act.         Eisler (1970a)
     heteroclitus             1.7 g                      wellwater; 24°/oo;                  ingredient
                                                         20 °C; pH 8;                                        s: acetone
                                                         DO 7.1-7.7

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Fundulus                 42 mm        96            st.: underground      m, LC50       8000            P: act.         Eisler (1970b)
     heteroclitus                                        wellwater; 24°/oo;                                  ingredient
                                                         20 °C; pH 8;                                        s: acetone
                                                         DO 7.1-7.7

     Fundulus                 42 mm        96            st.; underground      m, LC50       4000            P: act.         Eisler (1970b)
     heteroclitus                          ( + 240h      wellwater; 24°/oo;                                  ingredient
                                         observation)    20 °C; pH 8;                                        s: acetone
                                                         DO 7. 1-7.7

     Fundulus                 42 mm        96            st.; underground      m, LC50       1210            solution        Eisler (1970b)
     heteroclitus                                        wellwater; 24°/oo;                                  aged for
                                                         20 °C; pH 8;                                        96 h
                                                         DO 7.1-7.7

     Fundulus                 42 mm        96            10 °C                 20% M         8000            P: act.         Eisler (1970b)
     heteroclitus                                                                                            ingredient
                                                                                                           s: acetone

     Fundulus                 42 mm        96            15 °C                 10% M         8000            P: act.         Eisler (1970b)
     heteroclitus                                                                                            ingredient
                                                                                                           s: acetone

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Fundulus                 42 mm        96            36 °/oo               100% M        8000            P: act.         Eisler (1970b)
     heteroclitus                                                                                            ingredient
                                                                                                           s: acetone

    Striped killifish

     Fundulus                 84 mm        24            st.; underground      m, LC50       29 000          P: act.         Eisler (1970a)
     majalis                  6.5 g                      wellwater; 24°/oo;                                  ingredient
                                                         20 °C; pH 8;                                        s: acetone
                                                         DO 7.1-7.7
        
     Fundulus                 84 mm        48            st.; underground      m, LC50       19 400          P: act.         Eisler (1970a)
     majalis                  6.5 g                      wellwater; 24°/oo;                                  ingredient
                                                         20 °C; pH 8;                                        s: acetone
                                                         DO 7.1-7.7

     Fundulus                 84 mm        24            st.; underground      m, LC50       13 800          P: act.         Eisler (1970a)
     majalis                  6.5 g                      wellwater; 24°/oo;                                  ingredient
                                                         20 °C; pH 8;                                        s: acetone
                                                         DO 7.1-7.7

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Fundulus                 42 mm        96            20 °C                 50% M         8000            P: act.         Eisler (1970b)
     heteroclitus                                                                                            ingredient
                                                                                                           s: acetone

     Fundulus                 42 mm        96            25 °C                 100% M        8000            P: act.         Eisler (1970b)
     heteroclitus                                                                                            ingredient
                                                                                                           s: acetone

     Fundulus                 42 mm        96            30 °C                 100% M        8000            P: act.         Eisler (1970b)
     heteroclitus                                                                                            ingredient
                                                                                                           s: acetone

     Fundulus                 42 mm        96            12 °/oo               0% M          8000            P: act.         Eisler (1970b)
     heteroclitus                                                                                            ingredient
                                                                                                           s: acetone

     Fundulus                 42 mm        96            18 °/oo               0% M          8000            P: act.         Eisler (1970b)
     heteroclitus                                                                                            ingredient
                                                                                                           s: acetone

     Fundulus                 42 mm        96            24 °/oo               10% M         8000            P: act.         Eisler (1970b)
     heteroclitus                                                                                            ingredient
                                                                                                           s: acetone

     Fundulus                 42 mm        96            30 °/oo               70% M         8000            P: act.         Eisler (1970b)
     heteroclitus                                                                                            ingredient
                                                                                                           s: acetone

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Spot

     Leiostomus               84 mm        96            st.; natural          m, LC50       93              P: 99%          Mayer (1987)
     xanthurus                6.5 g                      seawater; 2°/oo;                                    s: TEG
                                                         25 °C; DO 3.2-4.5

     Leiostomus               84 mm        96            st.; natural          no effect     56              P: 99%          Mayer (1987)
     xanthurus                6.5 g                      seawater; 2°/oo;                                    s: TEG
                                                         25 °C; DO 3.2-4.5

     Leiostomus               84 mm        96            flow-through          m, LC50       59              P: 99%          Mayer (1987)
     xanthurus                6.5 g                      20°/oo; 25 °C                                       s: TEG

    Atlantic silverside

     Menidia                  50 mm        24            st.; underground      m, LC50       24 800          P: act.         Eisler (1970a)
     menidia                  0.8 g.                     wellwater; 24°/oo;                                  ingredient
                                                         20 °Cr pH 8r                                        s: acetone
                                                         DO 7.1-7.7

     Menidia                  50 mm        48            at.; underground      m, LC50       21 900          P: act.         Eisler (1970a)
     menidia                  0.8 g                      wellwater; 24°/oo;                                  ingredient
                                                         20 °Cr pH 8;                                        s: acetone
                                                         DO 7.1-7.7

     Menidia                  50 mm        96            st.; underground      m, LC50       5700            P: act.         Eisler (1970a)
     menidia                  0.8 g                      wellwater; 24°/oo;                                  ingredient
                                                         20 °C; pH 8;                                        s: acetone
                                                         DO 7.1-7.7

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Striped bass

     Morone                   1 year       24            st.; 20 °C;           m, LC50       16 800          P: act.         Rehwoldt et al.
     saxatilis                                           pH 7.2; DO 6;                                       ingredient      (1977)
                                                         H 50                                                s: acetone

     Morone                   1 year       48            st.; 20 °C;           m, LC50       14 200          P: act.         Rehwoldt et al.
     saxatilis                                           pH 7.2; DO 6;                                       ingredient      (1977)
                                                         H 50                                                s: acetone

     Morone                   1 year       96            st.; 20 °C;           m, LC50       14 000          P: act.         Rehwoldt et al.
     saxatilis                                           pH 7.2; DO 6;                                       ingredient      (1977)
                                                         H 50                                                s: acetone

     Morone                   adult        96            interm. flow          m, LC50       790             P: 99%          Earnest (1970)
     saxatilis                                           12.8 °

     Morone                   juvenile     96            flow-through          m, LC50       790             P: 86%          Korn & Earnest
     saxatilis                                           13 °C; 30 °/oo                                      s: ethanol      (1974)

    Black mullet

     Mugil cephalus           48 mm        24            st.: underground      m, LC50       39 000          P: act.         Eisler (1970a)
                              0.78 g                     wellwater; 24 °/oo                                  ingredient
                                                         20 °C; pH 8;                                        acetone
                                                         DO 7.1-7.7

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

     Mugil cephalus           48 mm        48            st.: underground      m, LC50       26 300          P: act.         Eisler (1970a)
                              0.78 g                     wellwater; 24 °/oo                                  ingredient
                                                         20 °C; pH 8;                                        acetone
                                                         DO 7.1-7.7

     Mugil cephalus           48 mm        96            st.: underground      m, LC50       5200            P: act.         Eisler (1970a)
                              0.78 g                     wellwater; 24 °/oo                                  ingredient
                                                         20 °C; pH 8;                                        acetone
                                                         DO 7.1-7.7

    Northern puffer

     Sphaeroides              196 mm       24            st.; underground      m, LC50       100 000         P: act..        Eisler (1970a)
     maculatus                153 g                      wellwater; 24 °/oo                                  ingredient
                                                         20 °C; pH 8;                                        s: acetone
                                                         DO 7.1-7.7

     Sphaeroides              196 mm       48            st.; underground      m, LC50       91 000          P: act.         Eisler (1970a)
     maculatus                153 g                      wellwater; 24 °/oo                                  ingredient
                                                         20 °C; pH 8;                                        s: acetone
                                                         DO 7.1-7.7

     Sphaeroides              196 mm       96            st.; underground      m, LC50       75 800          P: act.         Eisler (1970a)
     maculatus                153 g                      wellwater; 24 °/oo                                  ingredient
                                                         20 °C; pH 8;                                        s: acetone
                                                         DO 7.1-7.7

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Bluehead

     Thalassoma               90 mm        24            st.; underground      m, LC~        98 000          P. act.         Eisler (1970a)
     bifasciatum              7 g                        wellwater; 24 °/oo                                  ingredient
                                                         20 °C; pH 8;
                                                         DO 7.1-7.7

     Thalassoma               90 mm        48            st.; underground      m, LC50       88 000          P. act.         Eisler (1970a)
     bifasciatum              7 g                        wellwater; 24 °/oo                                  ingredient
                                                         20 °C; pH 8;
                                                         DO 7.1-7.7

     Thalassoma               90 mm        96            st.; underground      m, LC50       12 300          P. enct.        Eislar (197Oa)
     bifasciatum              7 g                        wellwater; 24 °/oo                                  ingredient
                                                         20 °C; pH 8;                                        s: acetone
                                                         DO 7.1-7.7

      AMPHIBIA

     Rana                     adult        96            st.; tap-water:       m, LC50       8000                            Mudgall & Patil
     cyanophlyctis                                       23 °C; pH 7.3-7.8;                                                   (1987)
    (male)                                               H 60-70; DO 6.7-7.9

     Rana                     adult        96            st.; tap-water:       m, LC50       11 500                          Mudgall & Patil
     cyanophlyctis                                       23 °C; pH 7.3-7.8;                                                   (1987)
    (female)                                             H 60-70; DO 6.7-7.9

    Table 18 (continued)

    Species                Life         Test          Experimental          Criterion     Concentration   Remarksb        References
                           stage        period        conditions            effect        (µg/litre)
                                        (h)                                 measureda

    Western chorus

    frog

     Bendacris                tadpole      96            st.; 15 °C;           m, LC50       3700                            Mayer & Ellersieck
     triseriata                                          pH 7.1; H 44                                                        (1986)

    a Criterion: m = mortality; i = immobilization; d = development; % M = % mortality.
    b P = purity; s = solvent; TEG = triethyiene glycol; techn.gr. = technical grade.
    c st. = static.
    d °/oo  = salinity.
    e H = hardness in mg/litre CaCO3.
    f DO = dissolved oxygen in mg O2/litre.
    g MATC = maximum acceptable toxic concentration.

         Murty et al. (1984) state that the lowest concentration causing
    irreversible effects in the fish Mystus carasius after a 1-h exposure
    was 15 mg/litre.

    7.2.1  Short-term toxicity in aquatic invertebrates

    7.2.1.1  Laboratory studies on single species

         Exposure of the freshwater mussel  (Lamellidens marginalis) to
    sublethal (8 mg/litre) concentrations resulted in a transient increase
    (at 12 h) followed by a decrease (at 24-72 h) in the rate of
    respiration (Moorthy et al., 1984). Exposure of this species to
    concentrations ranging from 10 to 50 mg/litre resulted in a
    concentration-dependent decrease in heart rate (Rao et al., 1983a).

         For crustaceans, long-term toxicity levels appear to be of the
    same magnitude as acute: a no-effect level on the reproduction of
     Daphnia magna was 0.0012 mg methyl parathion/litre after 21 days
    (artificial water, 18 °C; Dortland, 1980).

         Exposure of the freshwater crab  (Oziotelphusa senex senex) to
    sublethal levels of methyl parathion (0.1-1 mg/litre) resulted in
    complete inhibition of molt, a delay in the onset of molt, or a
    decrease in the percentage of molting animals (Reddy et al., 1985). A
    decrease in the carbohydrate content and increase in acid phosphatase
    activity in both the hepatopancreas and muscle also occurred (Reddy et
    al., 1986a; 1986b).

         Eisler (1970a,b) found a 20% increase in mortality in  Nassa
     docoleta after 10 days' exposure to 25 mg/litre (well water with a
    salinity of 24o/oo, 20°C, pH 8) in.

         Exposure of prawns  (Penaeus indicus or  Metapenaeus monoceros)
    to sublethal concentrations of methyl parathion resulted in a
    concentration-dependent inhibition of acetylcholinesterase activity,
    which recovered in 7 days (Reddy & Rao, 1988). An increase in tissue
    levels of ammonia, urea, and glutamine, apparently resulted from the
    increased production of ammonia from purines and glutamate (Reddy et
    al., 1988; Reddy & Rao, 1990a). There was also an increase in tissue
    levels of fatty acids and cholesterol (Reddy  & Rao, 1989), while the
    activity of alkaline phosphatase in the hepatopancreas was inhibited,
    and the acid phosphatase activity, enhanced (Reddy & Rao, 1990b).
    Changes in hepatic glycogen content and haemolymph glucose levels were
    observed after 5 days of sublethal methyl parathion exposure (Reddy &
    Rao, 1990b).

         Cripe et al. (1981) tested the stamina of mysid shrimp
     (Mysidopsis bahia) in swimming against a water current in the
    presence of methyl parathion. Concentrations of 0.10 and 0.31 µg/litre
    did not affect maximum sustained speeds of the shrimp, but they
    were significantly reduced on exposure to 0.58 µg/litre.

    7.2.1.2  Mesocosmic studies

         After treatment of ponds with methyl parathion, the effects on
    daphnids were similar to those observed in the laboratory. However,
    indirect biological effects occurred that could not be predicted on
    the basis of laboratory tests. For example, the observed increase in
    populations of the crustacean  Diaptomus sp. in treated ponds was
    attributed to the mortality of competitors  (Daphnia spp.) and
    predators ( Cyclops and aquatic insects) (Crossland & Elgar, 1983).
    Generally, recovery of zooplankton occurred soon after the end of
    treatment of ponds (Apperson et al., 1976; Crossland & Elgar, 1983).
    The numbers of free-swimming  Diptera and  Ephemeroptera were
    significantly reduced compared with controls, as were the benthic
    chironomid larvae in ponds treated at 100 µg/litre. Seventy days after
    treatment, there was evidence of recovery of populations of
    chironimids and  Ephemeroptera , with full recovery 90 days after
    treatment (Crossland & Elgar, 1983).

    7.2.2  Fish

    7.2.2.1  Laboratory studies on single species

         Jarvinen & Tanner (1982) conducted a long-term mortality study on
    the fish  Pimephales promelas (flow through conditions, sterile
    water, 25 °C, pH 7.4-7.8, 46 mg CaCO3/litre, 6.5-8.4 mg dissolved
    O2/litre). Methyl parathion concentrations of 0.59-0.77 mg/litre
    induced increased mortality after 32 days. No effects on mortality
    were found at 0.38 mg/litre for the technical grade product and 0.59
    mg/litre for the controlled release formulation. Mortality in rainbow
    trout  (Salmo gairdneri) increased to 98% after exposure to 2.8 mg
    technical grade methyl parathion/litre (wellwater, 12 °C, pH 7.5, 272
    mg CaCO3/litre) for 96 h, followed by 7 days of observation
    (Palawski et al., 1983).

         Exposure of the tilapia fish  (Tilapia mossambica) to methyl
    parathion at a concentration of 0.09 mg/litre for 48 h resulted in a
    decrease in various anions and cations in tissues (Rao et al., 1983b),
    and in inhibition of acetylcholinesterase (20-60%) and ATPase (10-14%)
    activities. The activities of aspartate and alanine amino-transferase
    in muscle, gill, liver, and brain increased by 12-31% and 9-31%,
    respectively (Rao & Rao, 1984a; 1984b). Concentrations of 
    carbohydrate and glycogen decreased in the tissues examined (Rao & 
    Rao, 1983). Levels of soluble protein and the activity of

    glucose-6-phosphate dehydrogenase, a key enzyme of the hexose
    monophosphate shunt, in muscle, gill, and liver, were increased (Rao
    & Rao, 1987). Changes in carbohydrate metabolism were also observed in
    the freshwater fish  Clarias batrachus , when exposed to sublethal
    concentrations of methyl parathion (7 mg/litre) for 48 and 96 h (Rani
    et al., 1989). There were significant decreases in glycogen (liver)
    and in pyruvate (liver, brain, gill) contents and increases in glucose
    (gill) and lactate (liver, brain, gill) levels, and the specific
    activities of several enzymes were inhibited.

         Exposure of the catfish  (Channa punctatus) to 52 µg methyl
    parathion/litre resulted in the elevation of serum triiodothyronine
    (T3) as well as depression of brain acetylcholinesterase activity
    (Ghosh et al., 1989). This low dose of methyl parathion also impaired
    the regulation of gonadal function by gonadotropic hormone and gonado
    tropin-releasing hormone in  Channa punctatus (Ghosh et al., 1990).
    The inhibiting effect was also seen under field conditions where water
    concentrations of methyl parathion amounted to 0.239 µg/litre (Ghosh
    et al., 1990).

         Exposure to sublethal doses of 0.1 mg methyl parathion/litre
    (corresponding to 1/5th of the LC50 values) for 75 days produced
    severe ovarian damage in the carp minnow  (Rasbora daniconius)
    (Rastogi & Kulshrestha, 1990). Effects included diminished growth of
    ovaries and histopathological changes in immature, maturing, and
    mature oocytes.

         Sublethal concentrations of methyl parathion (1.2 mg/litre)
    induced behavioural abnormalities in the juveniles of the fish
     Cyprinus carpio , such as imbalance, increased opercular movement
    and irritation (Babu et al., 1986). Exposed juveniles, when
    transferred to pesticide-free medium, showed rapid recovery.

         Little et al. (1990) exposed rainbow trout  (Oncorhynchus mykiss)
    to methyl parathion at 0.01 or 0.1 mg/litre and measured various 
    behavioural parameters. Swimming capacity (as cm/s) was unaffected at
    any concentration tested, though spontaneous swimming activity was
    significantly reduced at both exposures. Number of prey  (Daphnia)
    consumed was reduced, even at the lower exposure (0.01 mg/litre), but
    the percentage of daphnia consumed and the strike frequency of the
    fish on daphnia were only affected at 0.1 mg/litre. The capacity of
    the trout to escape from a predator was only reduced at 0.1 mg/litre.

         In a static system (well water, salinity: 24o/oo, 20 °C, pH 8),
    with the fish Fundulus heteroclitus, the LC50 was 0.96 mg/litre
    after exposure for 10 days or 4 mg/litre after exposure for 4 days
    followed by 10 days in clean water (Eisler, 1970b).

    7.2.2.2  Mesocosmic studies

         In a methyl parathion-treated experimental pond, a high mortality
    rate was observed in rainbow trout, 37 days after treatment, which was
    associated with depression of the concentration of dissolved oxygen to
    less than 3 mg/litre, and decay of large amounts of algal biomass
    (Crossland & Elgar, 1983; see also section 7.3). 

    7.2.3  Amphibians

         After application of methyl parathion to  Rana cyanophlyctis,
    Mudgall & Patil (1987) found increased levels of glycogen in muscles,
    liver, and kidney, compared with control animals. On the basis of the
    marked elevated glycogen concentration in the kidney, it was concluded
    that the kidneys were the main target organ.

         The effects of metacid (DDT + 50% w/w methyl parathion) on the
    development of the Indian bullfrog  (Rana tigrina) were determined
    by Mohanty-Hejmadi & Dutta (1981). Threshold concentrations for
    adverse effects on eggs, feeding stage, and limb bud stage tadpoles
    ranged from 0.00005% to 0.004% metacid. These levels were much lower
    than the recommended dosage for the field application of metacid
    (0.15%).

    7.3  Terrestrial organisms

    7.3.1  Plants

         Methyl parathion has been found to have phytotoxic effects in
    diverse crops, such as cotton  (Gossypium hirsutum) (Brown et al.,
    1962; Roark et al., 1963; Youngman et al., 1989, 1990) and lettuce
     (Lactuca sativa) (Toscana et al., 1982; Johnson et al., 1983;
    Youngman et al., 1989).

         Swamy & Veeresh (1987) found a reduction in lipid synthesis in
    methyl parathion-treated seeds of  Sorghum sp., 24 h after
    germination. An increase in lipid production with a substantial
    elevation in unsaturated fatty acids was observed in methyl
    parathion-treated sorghum, 120 h after germination. The same effect
    occurred in 48-h seedlings, which were treated with the degradation
    products of methyl parathion. From this, it was concluded that the
    time-related reversal effect of methyl parathion is triggered by the
    pesticide degradation products themselves.

         Exposure of sorghum seeds to methyl parathion for 1 h before
    germination resulted in an accumulation of proline in the seedlings
    and a reduction in growth, without affecting the water content.
    Residues of methyl parathion in the soil also influenced seed
    germination and seedling growth (Deshpande & Swamy, 1987).

    7.3.2  Invertebrates

         Poisoning of bees has been reported after incorrect application
    of methyl parathion on windy days (Bubien, 1971).

         Analysis of dead honey bees  (Apis mellifera; Hymenoptera) for
    pesticide residues, during 1983-85 in the USA, showed that the health
    of colonies, poisoned with methyl parathion (Penncap-M) or with a
    combination of methyl parathion and other insecticides, was often
    severely affected, whereas colonies contaminated by insecticides other
    than methyl parathion often recovered (Anderson & Wojtas, 1986).

         Acute toxicity values were established for acetone formulations
    of methyl parathion applied topically to workers of Africanized and
    European honey bees  (Apis mellifera) (Danka et al., 1986). The
    LC50 values of 0.32 µg and 0.17 µg/bee, respectively, showed the
    greater tolerance to methyl parathion of Africanized bees compared
    with European bees.

         Jepson (1989) calculated a hazard ratio (ratio of contact LD50
    at 0.11 µg/bee to the application rate of the pesticide at 500 g
    a.i./ha) for methyl parathion in honey bees of 8937 (using the method
    of Smart & Stevenson, 1982). Values of the hazard ratio greater than
    50 are usually considered to indicate danger for bees. Along with
    azinphos methyl, methyl parathion has a very high indication of 
    danger for bees from field spraying. Although the intrinsic toxicity
    for bees is as high for other pesticides, such as the pyrethroids, the
    hazard ratio is lower, since application rates of these pesticides are
    also lower.

         Methyl parathion applied to small barriered plots of spring wheat
    at 1000 g a.i./ha did not have any apparent adverse effects on leaf
    litter decomposition and on earthworm populations (species not
    differentiated). Effects on individual earthworm species could not be
    demonstrated, because of statistically insufficient numbers of mature
    specimens collected (Shires, 1985).

         Methyl parathion has adverse effects on many different beneficial
    insects. It was placed in the highest class of toxicity (score 4 in a 
    classification of 1-4) for  Chrysopa (Plannipennia), Coccinellidae
    (Coleoptera), and Hymenoptera  (Entomophaga) (Höbaus, 1987). Side
    effects on the predator mite  Phytoseiulus persimilis were placed in
    class 3 (Kniehase & Zoebelein, 1990).

         Thompson & Gore (1972) assessed the toxicity of methyl parathion
    (95-99% purity) for  Folsomia candida (Collembola) by direct contact
    in a spray tower and when applied to soil. In the direct-contact
    study, a 0.01% methyl parathion solution caused a 100% mortality of
    the collembola, 24 h after being treated. A 100% mortality rate also
    occurred in soil (Plainfield sand) treated with 0.5 mg methyl
    parathion/kg dry weight soil after a 24-h exposure.

         Methyl parathion (0.05%) sprayed on coconut leaflets was found to
    be highly toxic to the parasitoid fauna (Hymenoptera;  Ento-mophaga )
    of a coconut coccid  (Opisina arenosella; Homoptera). The mortality
    of the caged insects was assessed 24 h after introduction of leaflets
    and after longer periods (Jalaluddin & Mohanasundaram, 1989).

         Flanders et al. (1984) conducted a field study of methyl
    parathion (sprayed at recommended rates of 0.84 kg a.i./ha, in an
    encapsulated formulation, on soybeans) effects on  Pediobius
     foveolatus , a parasitoid of the Mexican bean beetle  Epilachnia
     varivestis . The pupae within parasitized beetles were unaffected by
    the insecticide and emerged normally. However, residues of methyl
    parathion on the plants killed 100% of the adult parasites emerging
    within 1 day, and 50% of those emerging within 3 days of the spraying.
    By 9 days after spraying, the mortality of emerging parasite adults
    was no longer affected by residues.

         Walker et al. (1985) examined the effects of methyl parathion,
    used at 0.6 kg a.i./ha on rice fields in Louisiana, on the survival
    and reproduction of parasitic nematodes  (Romanomermis culcivorax),
    introduced into the fields to control mosquito larvae. There were not
    any adverse effects of the insecticide on the nematodes.

         Only a few cases of resistance to methyl parathion have been
    reported among arthropod parasites or predators. The reports refer to
    the braconid  Bracon mellitor (Hymenoptera), a parasite of the boll
    weevil  (Anthonomous grandii), which developed low levels of
    resistance after 5 or more generations of selection in the laboratory,
    and to field populations of the coccinellid  Coleomegilla maculata
    (Coleoptera) taken from cotton fields, treated extensively with methyl
    parathion for 2 decades (Croft, 1977).

         One week after application of methyl parathion (1000 g a.i./ha)
    on small barriered plots of spring wheat, the number of predatory
    beetles (mainly 4 species of Carabidae and 3 genera of Staphylinidae)
    fell to about 10% of that in the untreated control plot. Recovery
    occurred between 4 and 6 weeks after application, but a further fall
    in numbers of predatory beetles was observed 8-12 weeks after
    application (Shires, 1985). This second reduction was attributed to an
    indirect effect of the treatments, causing removal of the predators'
    food supply (mainly cereal aphids).

    7.3.3  Birds

         The acute lethal toxicities of methyl parathion for birds are
    compiled in Table 19.

         Percutaneous administration of methyl parathion was more toxic
    for young mallard ducks  (Anas platyrhynchos) than oral (dietary)
    administration (Hudson et al., 1979).

         Studies on mallard ducks  (Anas platyrhynchos) have shown that
    methyl parathion can affect the brood-rearing phase by increasing
    mortality and causing behavioural changes (Fairbrother et al., 1988).
    At least 40% of young ducklings exposed to sub-lethal oral doses of
    methyl parathion (4 mg/kg body weight) died within 40 min in outdoor
    enclosures. Several activities (swimming, preening, feeding) of
    mothers and ducklings were changed in treated broods. Ducks  (Anas
     platyrhynchos; A. discors; Aix sponsa) nesting in agricultural
    fields aerially treated with methyl parathion (1.4 kg a.i./ha) had a
    higher average daily rate of duckling losses than those nesting in
    untreated fields (Brewer et al., 1988).

         Spraying of methyl parathion at 1.4 kg a.i./ha did not
    significantly reduce the hatchability of starling  (Sturnus vulgaris)
    eggs and the number of young fledglings per nest. However,
    collectively, the number of fledglings from the treated field was
    significantly lower than that from the control field (Robinson et al.,
    1988).

         Buerger et al. (1991) dosed wild bobwhite quail  (Colinus
     virginianus) with methyl parathion at 0, 2, 4, or 6 mg/kg body
    weight by oral intubation and then released them into the wild. The
    birds were monitored for 14 days by radio telemetry. Only the birds
    receiving 6 mg methyl parathion/kg body weight showed significantly
    reduced survival and this was the result of predation rather than
    overt toxicity. Activity was not affected by any treatment. Survivors
    did not show any inhibition of brain cholinesterase activity after 14
    days, compared with controls.

         Bennett et al. (1991) examined parameters of reproductive success
    in mallard ducks exposed to a dietary concentration of methyl
    parathion of 400 mg/kg. The female mallards were fed the methyl
    parathion diet at different stages of egg laying and incubation.
    Numbers of hatchlings per nest were 61%, 43%, and 58% of controls for
    birds exposed during egg laying, early incubation, and late
    incubation, respectively. Daily egg production was reduced during the
    treatment period, though 4 out of 10 hens resumed egg laying after
    treatment was terminated.

         A dose-dependent inhibition of brain and plasma cholinesterase,
    hyperglycaemia, and elevated corticosterone concentrations were
    observed in the American kestrel  (Falco sparverius) exposed to oral
    doses of up to 3 mg methyl parathion/kg body weight (Rattner &
    Franson, 1984).

    
    Table 19.  Acute lethal toxicities of methyl parathion for birds

    Species                          Age           Oral LD50                Dietary LC50    References
                                                   (mg/kg body weighta)     mg/kgb

    Mallard duck                     5 days        8                                        Fairbrother et al.
     (Anas platyrhynchos)                                                                     (1988)

                                     3 months      10                                       Hudson et al. (1984)

                                     adult         6.6

    Mallard duck                     10 days                                682             Hill et al. (1975)
     (Anas platyrhynchos)

    Mallard duck                     5 days                                 336             Hill et al. (1975)
     (Anas platyrhynchos)

    Kestrel                          > 8          3.08                                     Rattner & Franson
     (Falco sparverius)                months                                                 (1984)

    Bobwhite quail                   14 days                                90              Hill et al. (1975)
     (Colinus virginianus)

    Table 19 (continued)

    Species                          Age           Oral LD50                Dietary LC50    References
                                                   (mg/kg body weighta)     mg/kgb

    Bobwhite quail                   14 days                                91              Bennet (1989)
     (Colinus virginianus)

    Japanese quail                   14 days                                79              Hill et al. (1975)
     (Coturnix coturnix japonica)

    Japanese quail
     (Coturnix coturnix japonica)    14 days                                69              Hill & Camardese
                                                                                            (1986)

    Ring-necked pheasant             10 days                                91              Hill et al. (1975)
     (Phasianus colchicus)

    Red-winged blackbird             -             10                                       Schafer (1972)
     (Agelaius phoeniceus)

    a  intubation of a single dose.
    b  8 days - standard test. 5 days feeding followed by 3 days observation.

         Egg production in Japanese quail was inhibited and hatchability
    reduced at 60 mg/kg (NRC, 1977).

         Methyl parathion-induced mortality following long-term ingestion
    was generally due to anorexia. Grackles  (Quiscalus quiscula) had
    lost 28-36% of their initial body weight, when they died. No fat was
    visible and the muscles were reduced on the sternum. There was an
    increase in mortality at relatively constant intake rate of methyl
    parathion observed between May and August, which was related to an
    increase in natural activity within this time. It was concluded, that
    median lethal dietary concentrations are relative and depend on the
    anorexic and physiological condition of wild birds (Grue, 1982). The
    mean brain AChE activity of grackles  (Quiscalus mexicanus) was
    significantly inhibited more than that of white-winged doves  (Zenaida
     asiatica) and that of mourning doves  (Zenaida macroura) after
    applications of EPN (phenylphosphonothioic acid  O-ethyl  O-p-nitro-
    phenyl ester) and methyl parathion (Custer & Mitchell, 1987).

         Free-living, female red-winged blackbirds  (Agelaius phoeniceus)
    were captured on their nests and given oral doses of 2.4 or 4.2
    methyl parathion mg/kg body weight and released immediately after
    dosing. Although methyl parathion caused ataxia, lacrimation, and
    lethargy and significantly depressed cholinesterase activity (> 35%)
    at 4.2 mg/kg, there were no apparent adverse effects on incubation
    behaviour and nesting success (Meyers et al., 1990).

         Depressed brain acetylcholinesterase activity was also observed
    in 2 bird species (red-winged blackbird,  (Agelaius phoeniceus), and
    dickcissel  (Spiza americana)) inhabiting wheat fields treated with
    methyl parathion (0.67 kg a.i./ha). Maximal inhibition occurred 5 days
    after pesticide application. Enzyme activity levels returned to near
    normal levels by the tenth day following application. Cholinesterase
    inhibition for dickcissels and red-winged blackbirds differed 
    significantly (74% versus 40%), and these differences could not be
    explained by the diets of the 2 species, as they were similar
    (Niethammer & Baskett, 1983).

         A subacute oral dose of 3.5 mg methyl parathion/kg per day
    resulted in inhibition of brain cholinesterase (average decrease of
    36%) in nuthatches  (Sitta carolinensis) after 3-7 days exposure
    (Herbert et al., 1989).

    7.3.4  Non-laboratory mammmals

         Two wild rodent species  (Sigmodon hispudus and  Mus musculus)
    were found to have a higher mortality rate and to recover more slowly
    from exposure to methyl parathion at oral doses of 14-80 mg/kg,
    compared with laboratory rodents (Roberts et al., 1988). Clark (1986)
    reported a greater tolerance to methyl parathion in little brown bats
     (Myotis lucifugus) compared with wild mice  (Mus musculus): the

    24-h oral LD50 value (372 mg/kg body weight) of methyl parathion for
    little brown bats was 8.5 times the LD50 value for mice (44 mg/kg
    body weight). A loss of coordination was observed in 50% of the
    animals that were still alive 24 h after the treatment. The poisoned
    bats could be more easily captured by  predators. The threshold of the
    coordination loss was about 1/3 of the LD50 value. In toxicity
    tests, mink (Mustela vison) rejected methyl parathion-treated diets
    and appeared to die from starvation rather than from methyl parathion
    poisoning (Aulerich et al., 1987).

    8.  EFFECTS ON EXPERIMENTAL ANIMALS AND IN VITRO TEST SYSTEMS

         The inhibition by methyl parathion of acetylcholinesterase at
    nerve endings results in an accumulation of endogenous acetylcholine,
    as evidenced by peripheral and central cholinergic nervous system
    signs (Taylor, 1980).

         Toxic effects include profuse salivation, lacrimation, nasal
    discharge, colic, diarrhoea, pupil constriction, excessive sweating,
    coughing, vomiting, frequent urination, anxiety, restlessness,
    hyperactivity, and hyperkinesis.

         A more complete treatise on the effects of organophosphorus
    insecticides in general, especially their short- and long-term effects
    on the nervous system, can be found in  Environmental Health Criteria
     63: Organophosphorus insecticides - A general introduction (WHO,
    1986).

    8.1  Single exposure

         Toxicological data on methyl parathion are summarized by Taylor
    (1980) and Flucke (1984).

         The acute toxicity values in a number of species following the
    oral (Table 20), dermal (Table 21), inhalational (Table 22), and
    intraperitoneal (Table 23) administration of methyl parathion show
    lethal doses of about 3-400 mg/kg for the oral route, 40-300 mg/kg for
    the dermal route, 3.5-72 mg/kg for the intraperitoneal route, and
    30-300 mg/m3 for inhalation exposure. The acute subcutaneous LD50s
    for methyl parathion in rats and mice were 6 and 18 mg/kg body weight,
    respectively (Krueger & Casida, 1957; RTECS, 1991); the acute
    intravenous LD50 was reported to be 4.1-14.5 mg/kg body weight in
    rats, 2.3-13 mg/kg body weight in mice, and 50 mg/kg body weight in
    guinea-pigs (NIOSH, 1976).

         Izmirova et al. (1984) found an abrupt reduction in the blood and
    brain cholinesterase and acetylcholinesterase activities in albino
    rats in the 30th and 90th min after a single oral administration of 32
    mg methyl parathion/kg. The blood cholinesterase activity was reduced
    by 71% and the brain acetylcholinesterase activity by 54%. Twenty-four
    hours after administration, the cholinesterase activity was higher
    than that in the controls.

    Table 20.  Acute oral toxicity

    Animal (sex)a                  LD50 (mg/kg body       References
                                   weight)

    rat (m) fasted                 2.9                    Heimann (1982)

    rat (f) fasted                 3.2                    Heimann (1982)

    rat                            6                      Bayer AG (1988); RTECS
                                                          (1991)

    rat (m)                        7.4                    Flucke & Kimmerle (1977)

    rat (f) nonfasted              9.3                    Heimann (1982)

    rat (m) nonfasted              10.8                   Heimann (1982)

    rat (m)                        11.7                   Kimmerle (1975)

    rat (m)                        14                     Gaines (1960, 1969)

    rat (f)                        24                     Gaines (1960, 1969)

    rat                            35                     Kagan (1971)

    mouse                          23                     RTECS (1991)

    mouse                          14.5                   Haley et al. (1975)

    mouse                          33.1                   Mundy et al. (1978)

    mouse                          21.8                   Mundy et al. (1978)

    mouse                          19.5                   Haley et al. (1975)

    rabbit (m) fasted              19                     Heimann (1982)

    rabbit (f) fasted              19.4                   Heimann (1982)

    rabbit                         420                    RTECS (1991)

    Table 20. (cont'd)  Acute oral toxicity

    Animal (sex)a                  LD50 (mg/kg body       References
                                   weight)

    guinea-pig                     1270                   RTECS (1991)

    guinea-pig                     417                    NIOSH (1976)

    dog                            90                     Hirschelmann & Bekemeier
                                                          (1975)

    a  m= male, f= female.

    Table 21.  Acute dermal toxicity

    Animal,         Duration of      Ld50 (mg/kg    Ld100            References
    sexa            exposure (h)     body weight)

    rat             1b               63                              RTECS
                                                                     (1991)

    rat (m,f)       -                67                              Gaines
                                                                     (1960,
                                                                     1969)

    rat (m)         24               46                              Heimann
                                                                     (1982)

    rat (f)         24               44                              Heimann
                                                                     (1982)

    rabbit (m)       6                               1270 (pure)     Deichmann
                                                                     et al. (1952)

    rabbit (m)       6                               350-780
                                                     (technical      Deichmann
                                                     grade)          et al. (1952)

    rabbit (m)       6                               420 (pure, in   Deichmann
                                                     corn oil)       et al. (1952)

    rabbit (m)       6                               2500 (pure,     Deichmann
                                                     suspended in    et al. (1952)
                                                     water)

    rabbit           -                300                            RTECS
                                                                     (1991)

    a  m = male, f = female.
    b  no data given.

    Table 22.  Acute inhalation toxicity

    Animal           Duration of         LC50           References
    (sex)a           exposure (h)        (mg/m3 air)

    rat              1                   120              RTECS (1991)

    rat              1                   34               Molnar & Paksy
                                                          (1978)

    rat (m)          1                   200              Kimmerle & Lorke 
                                                          (1968)

    rat (m)          1                   260              Thyssen (1979)

    rat (f)          1                   320              Thyssen (1979)

    rat (m)          4                   120              Kimmerle & Lorke 
                                                          (1968)

    rat (m)          4                   185              Thyssen (1979)

    rat (f)          4                   170              Thyssen (1979)

    mouse            4                   120              RTECS (1991)

    a  m = male  f= female.

    Table 23.  Acute intraperitoneal toxicity

    Animal                  LD50(mg/kg body weight)        References

    rat                         3.5                        Du Bois & Coon (1952)

    rat adult                   5.8                        Brodeur & Du Bois (1963)

    rat juvenile                3.5                        Brodeur & Du Bois (1963)

    rat                         7                          Kimmerle (1975)

    mouse                       9.3                        Kimmerle (1975)

    mouse                      11.0                        Benke et al. (1974)

    mouse                       6.4                        Kamienski & Murphy (1971)

    mouse                       8.2                        Mirer et al. (1977)

    mouse                      72                          Goyer & Cheymol (1967)

         Dogs that received 10 or 30 mg methyl parathion/kg body weight
    intravenously showed minimal activity of the plasma cholinesterases,
    30 min after treatment. Sixteen hours after the injection of 10 mg
    methyl parathion/kg body weight, the enzyme activities had returned to
    their pre-injection values. However, following treatment with 30 mg
    methyl parathion/kg body weight, it took 7 days for complete recovery
    (Braeckman et al., 1980).

         After i.p. injection of 2.4 mg Wofatox (methyl parathion), Karcsu
    et al. (1981) observed complete inhibition of the histochemically
    detectable acetylcholinesterase activity in the central nervous system
    of the rat. Partial enzyme inhibition was found in the motor neurons
    and in the striated muscles. Ultrastructural changes in the myocardium
    of the rats were also confirmed.

    8.2  Skin and eye irritation, sensitization

         The skin of rabbits exposed to methyl parathion for 4 or 6 h did
    not show perceptible signs of irritation (concentrations up to
    LD100, Table 21, Deichmann et al., 1952). Similar results were
    obtained by Hecht & Wirth (1950) and by Heimann (1982) in their
    studies on rats.

         The irritation potential of methyl parathion on the rabbit skin
    and eye was studied according the OECD guidelines for the testing of
    chemicals (Nos. 404 and 405). It was concluded that methyl parathion
    had no primary irritating potential (Pauluhn, 1983).

    8.3  Short-term exposures

         Groups of Wistar albino rats were exposed to methyl parathion
    aerosol concentrations of 0.9, 2.6, and 9.7 mg/m3 air for 6 h/day,
    5 days/week for 3 consecutive weeks. No mortality occurred. Plasma and
    brain cholinesterase levels were significantly depressed in the
    highest dose group. At 2.6 mg/m3, slight inhibition of plasma ChE
    occurred (Thyssen & Mohr, 1982).

         Groups of New Zealand white rabbits were administered methyl
    parathion (purity 96.3%) dermally at dose levels of 10, 50, and 250
    mg/kg body weight, applied for 5 days/week over 3 weeks. The site was
    left uncovered for 6 h and then it was cleaned with soap and water.
    There was a dose-related inhibition of erythrocyte and brain
    cholinesterases in the 50 and 250 mg/kg dose groups. Plasma ChE was
    also significantly depressed in the highest dose group; these animals
    presented signs of cholinergic poisoning and 5 out of 6 animals died
    (Mihail & Vogel, 1984).

         A 12-week dietary study at 5, 20, and 50 mg methyl parathion/kg
    was performed on male and female dogs. The doses corresponded to 0.1,
    0.4, and 1.0 mg/kg body weight per day. A significant decrease in
    plasma cholinesterase activity was observed only at 50 mg/kg diet
    (Williams et al., 1959). 

    8.4  Long-term exposures

         Kazakova et al. (1974) fed chicken and cattle daily with 2.5 mg
    methyl parathion/kg body weight for one year. No changes in health
    status and food intake were observed. In pigs and cows, 10 mg/kg body
    weight led to irritation, depression, miosis, salivation, intensified
    peristaltics, and diarrhoea.

         Rats fed diets containing 40 mg methyl parathion/kg for 2 years,
    and mice (females: fed up to 125 mg/kg, males: fed up to 77 mg/kg) did
    not display any cholinergic toxicity (NCI, 1979).

         In a 2- year study (combined long-term/carcinogenicity), 500 rats
    (50 male, 50 female per dose, 100 controls) were fed diets containing
    0, 2, 10, or 50 mg methyl parathion/kg. The intake of active
    ingredient was 0, 0.144, 0.713, 4.917 mg/kg body weight per day
    (females). The highest dose led to retardation of growth, increase in
    mortality, inhibition of cholinesterase-activity in plasma,
    erythrocytes, and brain, reduction of haemoglobin, and haematocrit,
    and an increase in reticulocytes, after 2 years. Female rats showed a

    reduction in plasma proteins and a reversible increase in urea in
    plasma and protein in urine. At 10 mg/kg diet, the cholinesterase
    activity in plasma and red blood cells was inhibited. Male rats also
    showed reduced cholinesterase activity in the brain. Extensive
    histopathological examinations (cardiovascular, respiratory, and
    urogenital systems, digestive tract, organs, and glands) did not
    exhibit any substance-related changes. No toxic effects were found at
    the lowest dose (Bomhard et al., 1981; Schilde & Bomhard, 1984).

         Sixty rats per sex and group were fed diets containing methyl
    parathion at concentrations of 0.5, 5, or 50 mg/kg for 2 years.
    Sciatic nerve preparations from 1 out of 5 males in the low-dose group
    and 1 out of 5 in the mid-dose group reportedly showed moderate
    degenerative changes. In the high-dose group (50 mg/kg diet), sciatic
    nerve preparations from treated males showed a loss of myelinated
    fibres. These animals also showed more myelin degeneration and Schwann
    cell proliferation. Similar, less severe changes were seen with a
    lower incidence, in males fed 5.0 or 0.5 mg/kg per day males and in
    the controls. Only 1 rat in the low-dose group and 1 in the mid-dose
    group had more severe changes than the controls; however, 4 high-dose
    males showed more severe changes. No obvious differences were seen in
    the females. Haemoglobin, haematocrit, and RBCs were slightly reduced
    in mid-and high-dose males, and moderately reduced in high-dose
    females (Daly, 1983).

    8.5  Reproduction, embryotoxicity, and teratogenicity

         Dosages of 4 or 6 mg methyl parathion/kg body weight were
    injected intraperitoneally into pregnant, female albino Holzmann rats.
    The injection was made on day 9 or day 15 using an ethanol-propylene
    glycol vehicle. It was found, that the fetal, cerebral, cortical
    cholinesterase activity was reduced, indicating the transplacental
    passage of the organophosphate. Large subcutaneous haematomas also
    occurred; however, no significant developmental defects were noticed
    (Fish, 1966). Ackermann (1974) also reported that there was no
    placental barrier for methyl parathion.

         A 3-generation study was performed by the Woodard Research
    Corporation in 1966. This unpublished report was reviewed by  Anon.,
    FAO/WHO (1969). Rats received diets of 0, 10, or 30 mg methyl
    parathion per kg diet. A sporadic reduction in the litter size of
    groups was observed (30 mg/kg: F2alpha, F2ß, F3alpha; 10 mg/kg:
    F1ß), also a delayed growth of litters until weaning (30 mg/kg:
    F2alpha, F3alpha, F3ß; 10 mg/kg: F1ß), a reduced rate of
    survival of the litters (30 mg/kg: F1alpha, F1ß, F2alpha); 10
    mg/kg: F3alpha), and an increased rate of  stillbirths (30 mg/kg:
    F1ß, F3alpha).

         Another 3-generation study was performed by the Midwest Research
    Institute (1975). Rats received 0, 10, or 30 mg methyl parathion/kg
    diet (corresponding to 0, 0.5, or 1.5 mg methyl parathion/kg body
    weight); 2 litters of each generation were  evaluated. No adverse
    effects on growth, survival, or reproduction were observed at the 30
    mg/kg level, however, the 10 mg/kg level caused a reduction in the
    postnatal survival in weaning rats in the F1ß and F3alpha
    generations. Similar results were found in the 3-generation study of
    Löser & Eiben (1982). Rats (male and female, SPF-Wistar W 74 strain,
    5-6 weeks old) were fed a diet containing technical  methyl parathion
    (95% pure) at 2, 10, or 50 mg/kg for 77 days and then mated. The
    no-effect level in this study was 2 mg/kg diet. A dose of 50 mg methyl
    parathion/kg caused reductions in neonatal weights and litter size,
    and delayed body weight gains, while 10 mg/kg caused sporadic
    reductions in litter size (F2alpha, F3alpha), delayed growth of
    litters until weaning (F1alpha, F2alpha, F2ß), and a reduced
    rate of survival of the litters.

         Single doses of 3, 30, or 100 µg methyl parathion (in 10%  DMSO)
    were administered subgerminally into chicken eggs on day 2 and
    intra-amniotically on days 3 and 4. These doses did not induce any
    specific malformations. Embryotoxicity was noted at the 2 higher doses
    (30 and 100 µg) (Benes & Jelinek, 1979). These findings were confirmed
    by estimating the embryotoxicity range and parameters (Jelinek et al.,
    1985). Doses of up to 55 µlitre Wofatox 50EC/kg egg reduced
    haematocrit, glucose, cholesterol, and AChE activity and increased
    aspartate aminotransferase and lactate dehydrogenase values in blood
    samples of chicken embryos (Somlyay et al., 1989). The injection of 2
    different concentrations of methyl  parathion (13 and 135 mg/kg egg)
    into pheasant eggs resulted in increased mortality and in an increased
    incidence of skeletal deformities in the survivors (Varnagy et al.,
    1984; Déli & Varnagy, 1985; Varnagy & Déli, 1985). Biochemical studies
    on muscle  samples from chicken embryos (eggs treated with 0.4% or
    4.0%  solution of Wofatox 50EC) showed decreased creatine kinase
    activity, decreased creatine, creatine-phosphate, and Mg2+ (in
    cervical muscle only) contents, and increased creatinine, Ca2+, and
    Mg2+ (in femoral muscle only) values (Déli et al., 1985). Scanning
    electron microscopic examination of the cartilage in chicken embryos
    showed degeneration of collagen structure and chondrocytes at a high
    insecticide concentration (eggs treated with 0.4% or 4.0% solution of
    Wofatox 50EC) (Varnagy et al., 1988). Analysis of the protein pattern
    of the cervical muscles of 18-day-old embryos, treated with 0.4%
    methyl parathion solution showed decreases in alpha-actinin,
    alpha-tubulin, ß-tubulin, and gamma-proteins (Déli & Kiss, 1988).

         Studies on chickens showed that methyl parathion at 1-10
    µmol/litre had no or only little effect on the adenylate cyclase in
    the embryo muscle. Comparable results were obtained with rats using
    the plasma membrane adenylate cyclase in rat livers, even at 100
    µmol/litre. In the presence of adenylate cyclase-stimulating agents,

    additional activation of methyl parathion was observed; it enhanced
    the stimulating activity of GTP and isoproterenol together, but not
    alone. Methyl parathion is soluble, but not metabolized, in plasma
    membranes, so it may alter cellular levels of cAMP, and, thus, cell
    growth (Déli & Kiss, 1986).

         At very high doses (20 or 60 mg/kg body weight), methyl parathion
    injected intraperitoneally in ICR-CL mice on day 10 of pregnancy,
    caused convulsions, hypersalivation, ataxia, and tremor. At the higher
    dose, 5 out of the 14 litters died. This dose caused reduced neonatal
    weight, an increase in the occurrence of cleft palate, and an
    increased incidence of cervical ribs in the fetuses. At the lower
    dose, cleft palate, and a statistically non-significant increase in
    the number of cervical ribs and underdeveloped sternebrae were
    observed (Tanimura et al., 1967).

         A single intraperitoneal injection of 5, 10, or 15 mg/kg body
    weight was administered to Wistar rats on day 12 of pregnancy; signs
    of toxicity and reduced body weight were observed with 15 mg/kg, but
    there was no evidence of teratogenicity at any of the doses (Tanimura
    et al., 1967).

         On 6 alternate days between days 5 and 15 of pregnancy, 3 groups
    of rats received orally 0.1, 1, or 3 mg methyl parathion/kg body
    weight. Another group of rats received 3 mg methyl parathion/kg body
    weight on 8 alternate days between days 5 and 19 of pregnancy. No
    teratogenic effects were observed; however, the high doses caused
    increased resorptions and decreased fetal body weight (Fuchs et al.,
    1976).

         Methyl parathion was administered orally by gavage, to groups of
    female rats from day 6 to day 15 of gestation at dose levels of 0.1,
    0.3, or 1 mg/kg body weight. Weight gain in the mothers and a slight
    retardation in growth in the fetuses were noted at the highest dose
    level. Methyl parathion was not toxic for the embryo or fetus and no
    teratogenic effects were apparent (Machemer, 1977a).

         Groups of 24-26 rats received intravenous injections of 0, 0.03,
    0.1, or 0.3 mg methyl parathion/kg body weight per day from day 6 to
    day 15 of pregnancy. On day 20, the fetuses were evaluated. No
    treatment-related effects were found (Machemer, 1977b). 

         No signs of embryotoxicity or teratogenicity were found in
    rabbits that received 0.3, 1.0, or 3.0 mg methyl parathion/kg body
    weight on days 6-18 of pregnancy (Renhof, 1984).

         Daily intraperitoneal administration of methyl parathion (1 or
    1.5 mg/kg body weight) to rats during days 6-19 of gestation resulted
    in decreases in both maternal and fetal protein synthesis (Gupta et
    al., 1984). The effect was dose dependent, and was greater on day 19
    than on day 15 of gestation; it was also greater in fetal than in
    maternal tissues. The same dosage regimen resulted in a postnatal
    decrease in acetylcholinesterase activity and muscarinic receptor
    binding. Recovery of acetylcholinesterase activity to near normal
    levels occurred by day 28 in the low-dose offspring, but not in the
    high-dose weanlings (Gupta et al., 1985).

    8.6  Mutagenicity and related end-points

         Methyl parathion has been reported to have DNA-alkylating
    properties. Mutagenicity test results have been both positive and
    negative. The results of most of the  in vitro mutagenicity studies
    with both bacterial and mammalian cells were positive; the  in vivo
    studies produced equivocal results. A survey is given in Table 24.

    8.7  Carcinogenicity

         The carcinogenicity of methyl parathion was studied in mice by
    the National Cancer Institute (NCI) in 1979. Groups of 50,
    six-week-old female B6C3F1 mice received diets containing either
    62.5 or 125 mg methyl parathion/kg for 102 weeks. For 37 weeks, 2
    groups of 50 male mice received diets containing either 62.5 or 125 mg
    methyl parathion/kg, which was reduced then to 20 or 50 mg/kg for
    another 65 weeks. Untreated matched groups of 20 males and 20 females
    were used as a control. From all groups, 80-86% were still alive at
    the end of the study. There was no statistically significant increase
    in tumour incidence.

         The NCI (1979) also studied the carcinogenicity of methyl
    parathion in rats. Groups of 50 female and male Fischer 344 rats (6
    weeks old) received separate diets containing 20 or 40 mg methyl
    parathion/kg for 105 weeks. As matched controls, 20 male and 20 female
    rats remained untreated. Only 46% of the high-dose females survived,
    but 78% high-dose males, 74% low-dose males, 82% low-dose females, 85%
    control males, and 95% control females were still alive at the end of
    the study. No statistically significant increase in tumour rates was
    found.

         Male and female rats in groups of 50 were fed for 2 years with
    diets containing 2, 10, or 50 mg methyl parathion/kg. No toxic effects
    were found at the low dose (see section 8.4). No morphological changes
    due to the insecticide were detected. No carcinogenic effects of
    methyl parathion were observed (Bomhard et al., 1981; Schilde &
    Bomhard, 1984).

    
    Table 24. Mutagenicity tests of methyl parathion

    Test                          Species              Dose levels                 Metabolic       Results   Reference
                                                                                   activation

                                  Microorganism

    Gene mutation tests            S. typhimurium         _a                          +/-             -         Simmon et al. (1977)
    Ames                          TA100, TA1535                                      +/-                       Carrere et al. (1978)
                                  TA1536, TA1537
                                  TA 1538

    Ames                           S.typhimurium          250-1250 µg/plate           +               -         Rashid & Mumma (1984)
                                  TA100

    Ames                           S. typhimurium         250-1250 pg/plate           +               -         Rashid & Mumma (1984)
                                  TA98, TA1535,
                                  TA1537, TA1538

    Ames                           S. typhimurium                                                               Herbold (1986)
                                  TA1535                 > 1000/µg/plate             +/-             +
                                  TA 100                 > 500/µg/plate              +/-             +
                                  TA1537, TA1538         20-2500/µg/plate            +/-

    Reverse mutations              E. coli  WP2 and      1 crystal or microdrop      -               -         Dean (1972)
                                  WP2uvrA                250-2500/µg/plate           +/-             -         Simmon et al. (1977)
                                                                                                             Rashid & Mumma (1984)

    Forward mutations              E. coli               1 x 10-2mol/litre           -               +         Mohn (1973)
    streptomycin/                                                                                            Wild (1975)
    5-methyl-tryptophane
    resistance

    Table 24 (continued)

    Test                          Species              Dose levels                 Metabolic       Results   Reference
                                                                                   activation

    ade-6 forward mutation         Sacharomyces           11-228 mmol/litre           -               -         Gilot-Delhalle et al.
                                   pombe                                                                        (1983)

    Recombinogenic                 Aspergillus            2 mg                        -               -         Morpugo et al. (1977)
    activity/point                 nidulans
    mutation
    (8-Aza-guanine resistance

                                   Streptomyces           _a                          -               -         Carere et al. (1978)
                                   coelicolor

                                  Insects

    Sex link recessive             Drosophila             1.25 x 10-5% w/w                            +         Tripathy et al. (1987)
    lethal test                    melanogaster           6.3 x 10-6% w/w
                                  Larvae 24,48,72 h     24-48 and 72 h
                                  old                   exposure

                                  Mammals

    Thymidine kinase              Mouse Iymphoma        _a                         -/+             +         Jones et al. (1982)
    locus                         ceils L51784

    DNA effects                   Chinese hamster       20 and 40 µg/ml            _a              +         Chen et al. (1981 )
    chromatid                     ovary cells V79       28-72 h
    exchange                       (in vitro) 

    Table 24 (continued)

    Test                          Species              Dose levels                 Metabolic       Results   Reference
                                                                                   activation

                                  Human lymphold       20 µg/ml                    -               +         Sobti et al. (1982)
                                  cells (LAZ-007)

                                  Human lymphold       20 and 40/µg/ml             _a              + (for    Chen et al. (1981)
                                  cells 835 M and      28-72 h                                     20/µg/ml)
                                  Jeff cells

    Sister chromatid              Human lymphocytes    36-181.8 µmol/litre         -               + (dose   Singh et al. (1987)
    exchange (SCE)                                                                                 dependent)

    Unscheduled DNA               Human fetal lung     _a                          +/-             -         Simmon et al. (1977)
    synthesis                     WI 38 fibroblast

                                  Human lymphoid                                   -               -         Huang (1973)
                                  cells                up to 50/µg
                                  B411-4               6-50 h
                                  RMPI - 1788
                                  RMPI - 7191

                                  Mouse  (in vivo)       10 mg/kg ip                                 -         Degraeve & Moutschen
                                  bone marrow                                                                (1984)
                                  germ cells

                                  Mouse, Swiss         9.4, 18.8, 37.5,                            + (dose   Mathew et al. (1990)
                                  bone marrow          75 mg/kg body weight, oral                  dependent)

    Table 24 (continued)

    Test                          Species              Dose levels                 Metabolic       Results   Reference
                                                                                   activation

    Chromosomal aberrations       Rat bone marrow      0.5 mg/kg body weight                       + (dose   Malhi & Grover (1987)
                                  cells  (in vivo)       1 mg/kg                                     1.95%
                                                       2 mg/kg                                     9.26%
                                                       5 days/week for                             16.86%
                                                       7 weeks                                     dependent)

    Micronucleus                  Wistar rat           1, 2 and 4 mg/kg ip                         + (dose   Grover & Mahli (1985)
                                   (in vivo)                                                         dependent)

    Micronucleus                  Mouse                5-10 mg/kg body weight,                     -         Herbold (1986)
                                                       orally, daily,
                                                       for 2 days

    Micronucleus                  Mouse, Swiss         9.4, 18.8, 37.5, 75                         + (dose   Mathew et al. (1990)
                                                       mg/kg body weight, orally                   dependent)

    Dominant lethal               Mouse, male          20 mg/kg diet                               -         Simmon et al. (1977)
                                  ICR/SIM              40 mg/kg for
                                                       80 mg/kg 7 weeks

    Dominant lethal               Mice, male Q         0.15 mg/litre (daily) in                    -         Degraeve et al. (1984)
                                  strain               drinking-water, 5-7
                                                       weeks

    a = no information given.

    8.8  Special studies

         Seven white New Zealand rabbits per group were fed 0, 0.036,
    0.162, 0.519, or 1.479 mg methyl parathion/kg body weight per day, for
    8 weeks. A dose-dependent increasing atrophy of the thymus cortex and
    a reduced, delayed-type hypersensitivity response (DTH) were found
    (Street & Sharma, 1975). In a preliminary study, Fan et al. (1981)
    examined the effects of methyl parathion on immunological responses to
     S. typhimurium infection in mice. Mortality rates among infected
    animals fed 0.08, 0.3, or 0.7 mg methyl parathion/kg body weight
    (duration "extending beyond 2 weeks") were determined and protection
    by vaccination was examined. Dose-related increases in mortality were
    seen in unvaccinated mice and protection by immunization was
    decreased. These limited findings were reviewed by Sharma & Reddy
    (1987) and Thomas & House (1989).

         Methyl parathion was found by Barnes & Denz (1953) not to cause
    delayed neuropathy in their hen test. However, Nagymajitenyi et al.
    (1988) found neurotoxic effects on the central and peripheral nervous
    systems in both acute and short-term studies on CFY rats, in which the
    conduction velocity of the peripheral nerves, muscle function
    (ischidiacus nerve/gastrocnemius muscle), and EEG activity were
    measured. In the short-term studies, the rats were given 0.44 mg
    methyl parathion/kg body weight for 5 days/week for 6 weeks; in the
    acute study, the rats received 0.4 mg/kg, orally.

         Lipid metabolism in rats was investigated by Hasan & Ahmad Khan,
    (1985). The rats received daily intraperitoneal doses of 1.0, 1.5, or
    2.0 mg methyl parathion/kg body weight for 7 days. The concentrations
    of total lipids, phospholipids, and cholesterol increased in a
    dose-related manner in the cerebral hemisphere, cerebellum, brain
    stem, and spinal cord. Lipid peroxidation increased in the CNS with
    the exception of the cerebellum.

         Khan & Hasan (1988) studied changes in the levels of ganglio
    sides and glycogen of the cerebral hemisphere, cerebellum, brain stem,
    and spinal cord following intraperitoneal injection of methyl
    parathion (1, 1.5, or 2 mg/kg body weight) in 24 rats for 7 days. A
    dose-related depletion in the concentration of gangliosides and
    glycogen content were discernible in all regions of the CNS.

         Preweanling, male, rat pups were exposed daily through 
    subcutaneous injection to parathion (1.3 or 1.9 mg/kg body weight) or
    the vehicle (corn oil) on postnatal days 5-20, a period critical for
    the development of behavioural and biochemical parameters of the
    cholinergic nervous system. This exposure resulted in dose-dependent
    reductions in acetylcholinesterase activity and muscarinic receptor

    binding in the cortex. During the preweanling period, there were no
    differences among the groups in most reflex measures, eye opening, or
    incisor eruption. Postweanling behavioural assessment revealed small
    deficits in tests of spatial memory in both the T-maze and radial arm
    maze. There were no differences in neuromuscular abilities or
    spontaneous activity measures (Stamper et al., 1988).

         The behavioural effects of short-term exposure of male Wistar
    rats to methyl parathion (1/50 or 1/100 of LD50, orally, for 6
    weeks) were studied. Open-field (OF) and elevated plus-maze (EPM)
    tasks were used to decide whether or not the compound could affect
    behaviour. Significant effects were measured in OF activity during the
    first minute, on the activity of crossing outer squares, increasing
    latencies to leave centre, start of rearing, grooming, and defecation. 
    EPM parameters showed an increased amount of time spent in the open
    arms and a clear tendency to enter open arms more frequently. The
    defecation rate in the EPM was significantly decreased (Schultz et
    al., 1990).

    8.9  Factors modifying toxicity

         Methyl parathion becomes toxic only after metabolic
    transformation to the oxon analogue, methyl paraoxon, by liver
    microsomal oxidation. The microsomal enzymes metabolize methyl
    parathion in 2 ways  in vitro :  a) oxidation to methyl paraoxon,
    and  b) degradation to dimethyl phosphorothiotic acid and
     p-nitrophenol. NADPH and O2 are necessary for both reactions,
    indicating that these are oxidative processes (Nakatsugawa et al.,
    1968).

         Piperonyl butoxide inhibits the mixed function oxidase activity
    of the microsomal fraction of liver cells. Therefore, it inhibits both
    oxidative activation of methyl parathion and detoxification, but not
    the dealkylation reactions due to glutathione- S-alkyltransferase. At
    a dosage of 400 mg/kg body weight, piperonyl butoxide antagonized the
    toxic effects of methyl parathion in mice when given 1 h before the
    mice received the insecticide. The intraperitoneal toxicity of methyl
    parathion was reduced 40-fold (Kamienski & Murphy, 1971; Levine &
    Murphy, 1977a,b; Mirer et al., 1977). Diethyl maleate reduced the
    glutathione content of the liver by 80%. This agent increased the
    acute toxicity of methyl parathion by the inhibition of
    glutathione-dependent detoxification (Mirer et al., 1977).

         Pap et al. (1976) showed that methyl parathion was less toxic in
    rats with a thioacetamide-induced liver cirrhosis than in normal rats.
    After activating the microsomal enzymes in the liver with sodium
    phenobarbital or norandrostenolone phenylpropionate, the cirrhotic
    rats showed a normal susceptibility to methyl parathion, indicating
    the involvement of liver microsomes in the activation of methyl
    parathion. Treatment of normal rats with chloramphenicol could
    increase their survival time after poisoning with methyl parathion.

         Lead nitrate (Pb(NO3)2) reduced the toxicity of methyl
    parathion due to an increase in the carboxylesterase-dependent
    metabolism of the insecticide (Hapke et al., 1978).

         A single oral dose of 5 or 10 mg methyl parathion/kg body weight
    resulted in decreases in the cholinesterase activity in rats of 43.6%
    or 72.3%, respectively. However, rats pretreated on 5 successive days
    with a combination of 7 mg gentamycin/kg body weight and 20 mg
    rifamycin/kg body weight showed a remarkable protection against the
    toxic effects of methyl parathion. The toxic signs were minimal; the
    rats showed no, or only transient, signs of poisoning, and no
    convulsions were be observed in the rats that had been pretreated. The
    combination of these 2 drugs significantly prevented the methyl
    parathion-induced inhibition of cholinesterase in plasma and of the
    liver carboxylesterase. Gentamycin or rifamycin alone did not have any
    effect. Youssef et al. (1987) demonstrated, that gentamicin and
    rifamycin inhibited the formation of the oxidation product of methyl
    parathion, methyl paraoxon, in the liver and skeletal muscle. Both
    substances potentiated the rate of urinary  p-nitrophenol excretion
    within 48 h of the methyl parathion application. Pretreatment with
    rifamycin influenced the rate of liver glutathion reduction, whereas
    gentamicin did not show this effect.

         Male rats were treated with a single i.p. dose of 5 mg methyl
    parathion/kg. Pretreatment with memantine hydrochloride (18 mg/kg,
    i.p.), 30 min before methyl parathion administration, and atropine
    sulfate (16 mg/kg, i.p.), 15 min before, significantly reduced
    (P <0.01) the inhibition of acetylcholinesterase (Gupta &  Kadel,
    1990).

         Pretreatment with cimetidine, which suppresses the hepatic
    microsomal oxidative metabolism, decreased the toxicity of methyl
    parathion in rats and mice (Joshi & Thornburg, 1986).

         Fuchs et al. (1986) showed that the LD50 in rats increased by
    19-24% after simultaneous oral administration of 0.5 g humic acids/kg
    body weight and methyl parathion. It was supposed that the absorption
    of methyl parathion from the digestive tract decreased as a result of
    the intake of the humic acids.

         Sultatos (1987) perfused mouse livers  in situ with methyl
    parathion. The acute toxicity of methyl parathion in mice was
    antagonized by pretreatment with phenobarbital, daily, for 4 days (80
    mg/kg, i.p.). This effect was due to hepatic microsomal activation and
    resulted in an increased clearance of methyl parathion. Similar
    results were obtained by Du Bois & Kinoshita (1968), Du Bois (1969,
    1971), and Murphy (1980).

         The influence of temperature on the toxicity of methyl parathion
    in mice was studied by Nomiyama et al. (1980). They found median
    lethal doses (i.p.) of 14 mg/kg body weight at 8 °C, 44 mg/kg body
    weight at 22 °C, and 35 mg/kg body weight at 38 °C.

         An influence of age on the toxicity and metabolism of methyl
    parathion was observed by Benke & Murphy (1975) in rats. Rats became
    much less sensitive to poisoning with methyl parathion with increasing
    age. The effect was explained by a presumable increase in the
    detoxification processes as the GSH-dependent (glutathion-dependent)
    dealkylation. Methyl parathion dealkylation rates increased directly
    with age for both sexes.

         Carbon disulfide pretreatment, 1 h before administration of 10 mg
    methyl parathion/kg body weight to mice did not significantly affect
    the methyl parathion toxicity (Yasoshima & Masuda, 1986). 

         Prior depletion of glutathione by acetaminophen (600 mg/kg, i.p.,
    Costa & Murphy, 1984) or by diethyl maleate (1 ml/kg, i.p., Sultatos
    & Woods, 1988) had little effect on the toxicity of methyl parathion
    (2.5 mg/kg body weight and up to 55 mg/kg body weight i.p.,
    respectively) in the mouse.

         Interactions of organophosphorus pesticides and several
    pyrethroid insecticides were reported by Gaughan et al. (1980).
    Following an intraperitoneal injection of organophosphorus pesticides
    in mice, they found pronounced inhibition of the liver microsomal
    esterase, which hydrolyses trans-permethrin. Methyl parathion did not
    potentiate the toxicity of deltamethrin (Audegond et al., 1989). 
    Equitoxic oral or i.p. combinations of methyl parathion with other
    organophosphorus insecticides (amiton, coumaphos, crufomat,
    dimethoate, dioxathion, disulfoton, fensulfothion, ethyl parathion,
    phosphamidon, trichlofon) caused only subadditive or additive effects
    on the LD50 values (Du Bois, 1961; West et al., 1961; Du Bois &
    Kinoshita, 1963; Frawley et al., 1963; Sanderson & Edson, 1964;
    McCollister et al., 1968; Flucke & Kimmerle (1977). Williams et al.
    (1957) found additive effects in their testing of oral combinations of
    methyl parathion with demeton, EPN, malathion, or ethyl parathion in
    dogs.

         Mice pretreated with 50-300 mg diethyl dithiocarbamate per kg
    body weight displayed a remarkable reduction in the acute toxicity of
    methyl parathion. The toxicity was up to 10 times less. Lange &
    Wiezorek (1975) explained this observation by an effect of the
    dithiocarbamate on the microsomal oxidases and, thus, on the
    metabolism of methyl parathion. Another explanation is that compounds
    that temporarily occupy the active site of acetylcholinesterase
    prevent phosphorylation of the enzyme until there has been time for
    destruction of the organic phosphorus compound by A-esterases (Hayes
    & Laws, 1991).

         Dithiocarb reduced the toxicity of methyl parathion in mice
    markedly, when applied 30 min before the methyl parathion. No effect
    was observed when dithiocarb and methyl parathion were applied
    simultaneously (Lange et al., 1977).

         Orlando et al. (1972) found that pretreatment with quinidine
    sulfate had an inhibitory effect on the toxic action of i.v. injection
    of methyl parathion in rabbits.  This could be demonstrated by
    electrocardiography. Quinidine sulfate reduced the influence of methyl
    parathion on the nicotinic-and muscarinic-type receptors.

         The effect of methyl parathion on monoamine oxidase activity
    (MAO) in rat brain mitochondria was investigated by Nag & Nandi
    (1987).  In vitro methyl parathion reduced the MAO significantly;
    however,  in vivo , the effect was negligible.

         Methyl parathion is an inhibitor of malate dehydrogenase in the
    mitochondria of liver and skeletal muscle. There was also an
    inhibitory effect on plasmatic malate dehydrogenase and lactate
    dehydrogenase in the liver (Tripathi & Shukla, 1988).

    8.10  Mode of action

         The mode of action of organophosphorus insecticides, such as
    methyl parathion, is described in Environmental Health Criteria 63
    (WHO, 1986).

    8.10.1  Inhibition of esterases

         The primary biochemical effect associated with toxicity caused by
    organophosphorus pesticides is inhibition of acetylcholinesterase
    (AChE). The normal function of AChE is to terminate neurotransmission
    due to acetylcholine, liberated at cholinergic nerve endings in
    response to nervous stimuli. Loss of AChE activity may lead to a range
    of effects resulting from excessive nervous stimulation and
    culminating in respiratory failure and death. The chemistry of the
    inhibition of AChE and of many other esterases (e.g., NTE and liver
    carboxyesterases, which are discussed elsewhere) by these chemicals is
    similar and is given in schematic form in Fig. 4. Following the
    formation of a Michaelis complex (reaction 1), a specific serine
    residue in the protein is phosphorylated with loss of the leaving
    group X (reaction 2). Two further reactions are possible: reaction 3
    (reactivation) may occur spontaneously at a rate that is dependent on
    the nature of the attached group and on the protein and is also
    dependent on the influence of pH and of added nucleophilic reagents,
    such as oximes, which may catalyse reactivation.  Reaction 4 ("aging")
    involves cleavage of an R-O-P-bond with the loss of R and the
    formation of a charged monosubstituted phosphoric acid residue still

    attached to protein. The reaction is called "aging" because it is time
    dependent, and the product is no longer responsive to nucleophilic
    reactivating agents, such as some oximes. Since therapy of
    organophosphorus compound poisoning is, in part, dependent on the
    reactivating power of oximes, understanding of the "aging" reaction is
    important. Pseudocholinesterase (ChE), which is present in blood
    plasma and nervous tissue, but has no known physiological function, is
    inhibited by organophosphorus compounds in a similar way to AChE, but
    the specificity of the 2 enzymes is different. Though no toxic effect
    arises as a result of inhibition of pseudoChE, measures of its
    inhibition can be made for monitoring purposes.

    8.10.2  Possible alkylation of biological macromolecules

         It has been shown, under laboratory conditions, that some
    organophosphates can react with, and alkylate, the reagent
    4-nitro-benzylpyridine (Preussmann et al., 1969). The study was
    interpreted to imply that the  in vivo alkylating potential of some
    pesticides was similar to that of the known mutagens, dimethyl sulfate
    and methyl methanesulfonate. Furthermore, Löfroth et al. (1969)
    derived a substrate constant (a logarithmic measure of alkylating
    ability) of 0.75 for dichlorvos, which is intermediate between those
    known for methyl and ethyl methanesulfonates. Concern over the
    possible mutagenic and carcinogenic potential of organophosphorus
    compounds on the basis of the above data was misplaced, since
    alternative reactions were not considered. Compared with the carbon
    atom of the alkyl group, the phosphorus atom is markedly more
    electron-deficient and susceptible to attack by nucleophiles. Analysis
    by Bedford & Robinson (1972) of the data of Löfroth et al. (1969)

    revealed that the proposed rates of alkylation by hard nucleophiles
    were probably combined rates of phosphorylation and alkylation, and
    that phosphorylation was the totally dominant reaction in the case of
    the hydroxide ion. The comparison with known mutagens was therefore
    inappropriate. Two factors detract further from the toxicological
    significance of the alkylation studies. The first is that mammalian
    tissues (plasma, liver, etc.) contain active enzymes that catalyse the
    phosphorylation of water by the organophosphorus esters. Viewed
    inversely, these enzymes (often called A-esterases) catalyse the
    hydrolysis of the organophosphorus esters, thereby rapidly reducing
    circulating levels of hazardous material. Secondly, the comparative
    rate of reaction of most of these pesticides with AChE is many orders
    greater than their rate of alkylation of the typical nucleophile
    4-nitrobenzylpyridine: for dichlorvos, the ratio of rates was
    1 x 107 in favour of the inhibitory phosphorylation of AChE
    (Aldridge & Johnson, 1977). It follows that, at low exposure levels,
     in vivo phosphorylation of AChE and other esterases will be the
    dominant reaction with negligible uncatalysed alkylation of genetic
    material. Indeed, no such alkylation has been detected in sensitive
    in vivo studies designed to check this point (Wooder et al., 1977).
    Some catalysed alkylations of glutathione by organosphorus compounds
    are known to occur  in vivo , but these are essentially
    detoxification reactions.

    8.10.3  General

         Following lethal amounts of methyl parathion, hypotension,
    bradycardia, bronchoconstriction, and bronchial fluid accumulation
    occur with the inability of respiratory muscles to work. Cyanosis and
    central respiratory depression can be observed. In less severe cases
    of intoxication, bradycardia, muscle rigidity, muscle hypotonia,
    bronchial spasm, and constriction dominate (Meyer-Jones et al., 1977).

    9.  EFFECTS ON MAN

         The only confirmed effects on humans of exposure to methyl
    parathion are the signs and symptoms characteristic of systemic
    poisoning by cholinesterase-inhibiting organophosphorus compounds,
    observed in case studies. The results of oral ingestion studies
    performed by Rider et al. (1969, 1970, 1971) suggest that
    manifestations of acute methyl parathion toxicity are absent in humans
    whose erythrocyte cholinesterase activity has been reduced to as
    little as 45% of their pre-exposure baselines (see section 9.1.2).

         The effects of methyl parathion exposure on human beings were
    compiled in 1976 by NIOSH. Details are given by Hayes & Laws (1991).

         WHO (1986) summarized the signs and symptoms of organo-phosphate
    insecticide poisoning as follows:

         (a)  Muscarinic manifestations

              -    increased bronchial secretion, excessive sweating,
                   salivation, and lacrimation;

              -    pinpoint pupils, bronchoconstriction, abdominal cramps
                   (vomiting and diarrhoea); and

              -    bradycardia.

         (b)  Nicotinic manifestations

              -    fasciculation of fine muscles and, in more severe
                   cases, of the diaphragm and respiratory muscles; and

              -    tachycardia.

         (c)  Central nervous system manifestations

              -    headache, dizziness, restlessness, and anxiety;

              -    mental confusion, convulsions, and coma; and

              -    depression of the respiratory centre.

         All these signs and symptoms can occur in different combinations
    and can vary in time of onset, sequence, and duration, depending on
    the chemical, dose, and route of exposure. Mild poisoning might
    include muscarinic and nicotinic signs only. Severe cases always show
    central nervous system involvement; the clinical picture is dominated
    by respiratory failure, sometimes leading to pulmonary oedema, due to
    the combination of the above-mentioned signs and symptoms.

    9.1  General population exposure

         The general population may be exposed to air-, water-, and
    food-borne residues of methyl parathion as a consequence of
    agricultural/forestry practices, the misuse of the agent, and
    contamination of field crops, water, and air by off-target loss. 

         Lisi et al. (1986, 1987) studied the allergic potential of methyl
    parathion in 200 persons. No significant sensitization to methyl
    parathion was found.

    9.1.1  Acute toxicity

         Several cases of methyl parathion poisoning have been reported
    throughout the world; these have been reviewed by Hayes & Laws (1991).

         Human manifestations of acute poisoning by methyl parathion are
    comparable with those described in experimental animals (Durham &
    Hayes, 1962; Fazekas & Rengei, 1965; Hayes & Laws, 1991).

         In cases of fatal methyl parathion poisoning, gross and
    microscopic alterations occur in all the organs (brain, lung, heart,
    liver, kidneys, spleen, vascular walls, perivascular areas). Fazekas
    (1971) already saw alterations due to methyl parathion-poisoning, 2 h
    after the poisoning. Ember et al. (1970) found a high content of
    vitamin A in the liver in 5 cases of suicide with methyl parathion.

         Van Bao et al. (1974) reported an increase in chromosome
    aberrations in the lymphocytes of 4 patients who had suffered acute
    methyl parathion poisoning as a result of attempted suicide. The
    increase in chromosome aberrations was detected only in cell cultures
    carried out 1 month after their admission to hospital. No significant
    changes were found, compared with controls, 6 months later.

    9.1.2  Effects of short- and long-term exposure, controlled human
    studies

         Five male volunteers received 3.0 mg methyl parathion per day for
    28 days, then 3.5 mg methyl parathion for 28 days, and 4.0 mg methyl
    parathion for 43 days. No symptoms of poisoning or effects on the
    plasma or red blood cell cholinesterases could be noticed (Moeller &
    Rider, 1961).

         In another study, 3 groups of 5 volunteers each received 4.5 mg
    methyl parathion daily, for 30 days, then 5.0 g for 29 days or 5.5 mg
    for 28 days, followed by 6.0 mg for 29 days or 6.5 mg for 35 days, and
    finally 7.0 mg for 24 days. In no case was significant inhibition of
    the plasma or red blood cell cholinesterase activity found (Moeller &
    Rider, 1962).

         Morgan et al. (1977) studied the cholinesterase activities in 4
    human volunteers, who received 2 or 4 mg methyl parathion on 5
    successive days. These doses did not cause any depression of plasma
    and red blood cell cholinesterase activity.

         Rider et al. (1969) reported studies on human volunteers to
    determine the level of minimal toxicity of methyl parathion. For 30
    days, 5 volunteers received capsules containing methyl parathion, with
    the dose increasing daily, and 2 received capsules containing corn
    oil. Depression in plasma cholinesterase activity (15%) was observed
    at an oral dosage of 11.0 mg per day, while, at higher dosages up to
    and including 19 mg per day, no significant cholinesterase depression
    was observed. No significant changes in the blood cell count, urine
    analysis, or the prothrombin times occurred, nor was there any
    evidence of toxic effects.

         After 4 weeks with daily doses of 24 mg methyl parathion, 2 out
    of 5 volunteers showed inhibition of plasma and red blood cell
    cholinesterase activities with decreases of 24 or 23% for plasma and
    27 or 55% for red blood cells (Rider et al., 1970).

         Five volunteers received doses increasing from 14 to 20 mg methyl
    parathion per day, orally, for 6 days. No inhibition of the
    cholinesterases was found. However, doses of 28 or 30 mg methyl
    parathion caused a decrease in the cholinesterase activities of about
    37% (Rider et al., 1971).

         Two male volunteers received, orally, 2 or 4 mg methyl parathion
    per day. No influence of methyl parathion on neurophysiological
    parameters was found, and there was no inhibition of the plasma or red
    blood cell cholinesterase activity (Rodnitzky et al., 1978).

    9.2  Occupational exposure

         The production, formulation, handling, and use as an insecticide
    of methyl parathion are potential sources of exposure. Skin contact or
    inhalation are the main hazards for workers. The main hazard for the
    general population is the ingestion of contaminated food. Wind-drift
    during spraying may be a health risk, since Kummer & Van Sittert
    (1986) observed that, in a number of cases, the spraymen did not stop
    spraying, when it was too windy.

         The analysis of 375 pesticide poisonings in Bulgaria during
    1965-68 showed that 82.5% of all cases were due to organophosphates.
    Six of the intoxications were attributed to methyl parathion. A large
    number of poisonings, usually mild, occurred not in applicators
    directly engaged in plant protection but in other agricultural workers
    when they entered a previously sprayed crop area for further
    cultivation and hand-harvesting (Kaloyanova-Simeonova, 1970).

         Hatcher & Wiseman (1969) reported 16 cases of methyl parathion
    intoxication among 118 organophosphorus insecticide poisonings of farm
    workers that occurred in the lower Rio Grande Valley (Texas) in 1968.
    Toxicity following dermal exposure was predominant.

         Neuropsychiatric sequelae from occupational exposure to
    organophosphorus pesticides have been reported (Dille & Smith, 1964).
    However, the patients had been exposed to other pesticides besides
    methyl parathion.

         Data on chromosomal aberrations due to methyl parathion are
    scarce. Data from persons who had worked with various pesticides were
    presented by Yoder et al., 1973 (positive finding); Rupa et al., 1989
    (positive finding); and Nehéz et al., 1988 (positive finding in farm
    workers in the open field, but not in those in enclosed spaces like
    greenhouses). Van Bao et al. (1974) found chromosome aberrations in
    one case of an agricultural worker, accidentally exposed to methyl
    parathion (without exposure data).

         De Cassia Stocco et al. (1982) reported data from subjects
    exposed to methyl parathion and DDT at a formulation plant near of Sao
    Paulo, Brazil. No increased frequency of chromosome aberrations was
    found in the lymphocyte cultures of 15 healthy male workers (with
    blood cholinesterase level < 75% of presumably the normal mean
    levels), who were exposed repeatedly or long-term to methyl parathion
    for durations ranging from 1 week to 7 years, but who had intermittent
    periods of non-exposure.

         Richter et al. (1986) investigated the risk of exposure to methyl
    parathion spray drift in the workers in 3 kibbutzim. The
    cholinesterase levels were measured in 36 agricultural workers and 25
    residents from the same kibbutzim. No effects due to the methyl
    parathion spray drift exposure were observed in the field workers or
    in the residents.

    9.2.1  Epidemiological studies

         There are no epidemiological studies on effects related only to
    methyl parathion exposure.

    10.  PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

         The FAO/WHO Joint Meeting on Pesticide Residues (JMPR) evaluated
    methyl parathion in 1968, 1972, 1975, 1979, 1980, and 1984 (FAO/WHO,
    1969, 1973, 1976, 1980, 1981 and 1985). The acceptable daily intake
    for man (ADI) was estimated at 0-0.02 mg/kg body weight in 1984. This
    was based on levels causing no toxicological effects of:

         -    2 mg/kg diet, equivalent to 0.1 mg/kg body weight in the
              rat; and

         -    0.3 mg/kg body weight per day in man.

         The FAO/WHO Codex Alimentarius Commission (FAO/WHO, 1986)
    recommended Maximum Residue Limits (MRLs) in several food commodities,
    ranging from 0.05 to 0.2 mg/kg as follows:

              Commodity                          MRL (mg/kg)

              Cantaloupe                         0.2

              Cole crops                         0.2

              Cottonseed oil                     0.05

              Cucumbers                          0.2

              Fruit, other                       0.2

              Hops (dry cones)                   0.05a

              Melons                             0.2

              Sugar beets                        0.05a

              Tea (fermented and dried)          0.2

              Tomatoes                           0.2

              a Levels at, or about, the limit of determination. 

         The International Agency for Research on Cancer (IARC) evaluated
    methyl parathion in 1982 and in 1987 (IARC, 1983, 1987), and concluded
    that the available data do not provide evidence that methyl parathion
    is carcinogenic to experimental animals. No data on humans were
    available. The available data provide no evidence that methyl
    parathion is likely to present a carcinogenic risk for humans.

         WHO (1990) classified technical methyl parathion as "extremely
    hazardous" in normal use, based on an oral LD50 in the rat of 14
    mg/kg. WHO/FAO (1975) issued a data sheet on methyl parathion (No. 7).

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    ANNEX I.  TREATMENT OF ORGANOPHOSPHATE INSECTICIDE POISONING IN MAN

    (From EHC 63:  Organophosphorus insecticides - a general introduction)

         All cases of organophosphorus poisoning should be dealt with as
    an emergency and the patient sent to hospital as quickly as possible.
    Although symptoms may develop rapidly, delay in onset or a steady
    increase in severity may be seen up to 48 h after ingestion of some
    formulated organophosphorus insecticides.

         Extensive descriptions of treatment of poisoning by
    organophosphorus insecticides are given in several major references
    (Kagan, 1977; Taylor, 1980; UK DHSS, 1983; Plestina, 1984) and will
    also be included in the IPCS Health and Safety Guides to be prepared
    for selected organophosphorus insecticides.

         The treatment is based on:

         (a)  minimizing the absorption;

         (b)  general supportive treatment; and

         (c)  specific pharmacological treatment.

    I.1  Minimizing the absorption

         When dermal exposure occurs, decontamination procedures include
    removal of contaminated clothes and washing of the skin with alkaline
    soap or with a sodium bicarbonate solution. Particular care should be
    taken in cleaning the skin area where venepuncture is performed. Blood
    might be contaminated with direct-acting organophosphorus esters and,
    therefore, inaccurate measures of ChE inhibition might result.
    Extensive eye irrigation with water or saline should also be
    performed. In the case of ingestion, vomiting might be induced, if the
    patient is conscious, by the administration of ipecacuanha syrup
    (10-30 ml) followed by 200 ml water. This treatment is, however,
    contraindicated in the case of pesticides dissolved in hydrocarbon
    solvents. Gastric lavage (with addition of bicarbonate solution or
    activated charcoal) can also be performed, particularly in unconscious
    patients, taking care to prevent aspiration of fluids into the lungs
    (i.e., only after a tracheal tube has been put into place).

         The volume of fluid introduced into the stomach should be
    recorded and samples of gastric lavage frozen and stored for
    subsequent chemical analysis. If the formulation of the pesticide
    involved is available, it should also be stored for further analysis
    (i.e., detection of toxicologically relevant impurities). A purgative
    can be administered to remove the ingested compound.

    I.2  General supportive treatment

         Artificial respiration (via a tracheal tube) should be started at
    the first sign of respiratory failure and maintained for as long as
    necessary.

         Cautious administration of fluids is advised, as well as general
    supportive and symptomatic pharmacological treatment and absolute
    rest.

    I.3  Specific pharmacological treatment

    I.3.1  Atropine

         Atropine should be given, beginning with 2 mg iv and given at
    15-30-min intervals. The dose and the frequency of atropine treatment
    varies from case to case, but should maintain the patient fully
    atropinized (dilated pupils, dry mouth, skin flushing, etc.).
    Continuous infusion of atropine may be necessary in extreme cases and
    total daily doses up to several hundred mg may be necessary during the
    first few days of treatment.

    I.3.2  Oxime reactivators

         Cholinesterase reactivators (e.g., pralidoxime, obidoxime)
    specifically restore AChE activity inhibited by organophosphates. This
    is not the case with enzymes inhibited by carbamates. The treatment
    should begin as soon as possible, because oximes are not effective on
    "aged" phosphorylated ChEs. However, if absorption, distribution, and
    metabolism are thought to be delayed for any reasons, oximes can be
    administered for several days after intoxication. Effective treatment
    with oximes reduces the required dose of atropine. Pralidoxime is the
    most widely available oxime. A dose of 1 g pralidoxime can be given
    either im or iv and repeated 2-3 times per day or, in extreme cases,
    more often. If possible, blood samples should be taken for AChE
    determinations before and during treatment. Skin should be carefully
    cleansed before sampling. Results of the assays should influence the
    decision whether to continue oxime therapy after the first 2 days.

         There are indications that oxime therapy may possibly have
    beneficial effects on CNS-derived symptoms.

    I.3.3  Diazepam

         Diazepam should be included in the therapy of all but the mildest
    cases. Besides relieving anxiety, it appears to counteract some
    aspects of CNS-derived symptoms that are not affected by atropine. 
    Doses of 10 mg sc or iv are appropriate and may be repeated as
    required (Vale & Scott, 1974). Other centrally acting drugs and drugs
    that may depress respiration are not recommended in the absence of
    artificial respiration procedures.

    I.3.4  Notes on the recommended treatment

    I.3.4.1  Effects of atropine and oxime

         The combined effect far exceeds the benefit of either drug
    singly.

    I.3.4.2  Response to atropine

         The response of the eye pupil may be unreliable in cases of
    organophosphorus poisoning. A flushed skin and drying of secretions
    are the best guide to the effectiveness of atropinization. Although
    repeated dosing may well be necessary, excessive doses at any one time
    may cause toxic side-effects. Pulse-rate should not exceed 120/min.

    I.3.4.3  Persistence of treatment

         Some organophosphorus pesticides are very lipophilic and may be
    taken into, and then released from, fat depots over a period of many
    days. It is therefore quite incorrect to abandon oxime treatment after
    1-2 days on the supposition that all inhibited enzyme will be aged.
    Ecobichon et al. (1977) noted prompt improvement in both condition and
    blood-ChEs in response to pralidoxime given on the 11th-15th days
    after major symptoms of poisoning appeared due to extended exposure to
    fenitrothion (a dimethyl phosphate with a short half-life for aging of
    inhibited AChE). 

    I.3.4.4  Dosage of atropine and oxime

         The recommended doses above pertain to exposures, usually for an
    occupational setting, but, in the case of very severe exposure or
    massive ingestion (accidental or deliberate), the therapeutic doses
    may be extended considerably. Warriner et al. (1977) reported the case
    of a patient who drank a large quantity of dicrotophos, in error,
    while drunk. Therapeutic dosages were progressively increased up to 6
    mg atropine iv every 15 min together with continuous iv infusion of
    pralidoxime chloride at 0.5 g/h for 72 h, from days 3 to 6 after
    intoxication. After considerable improvement, the patient relapsed and
    further aggressive therapy was given at a declining rate from days 10
    to 16 (atropine) and to day 23 (oxime), respectively. In total, 92 g
    of pralidoxime chloride and 3912 mg of atropine were given and the
    patient was discharged on the thirty-third day with no apparent
    sequelae.

    References to Annex I.

    ECOBICHON, D.J., OZERE, R.L., REID, E., & CROCKER, J.F.S (1977) Acute
    fenitrothion poisoning.  Can. Med. Assoc. J., 116: 377-379.

    KAGAN, JU.S. (1977) [ Toxicology of organophosphorus pesticides,]
    Moscow, Meditsina, pp. 111-121, 219-233, 260-269 (in Russian).

    PLESTINA, R. (1984)  Prevention, diagnosis, and treatment of
     insecticide poisoning, Geneva, World Health Organization
    (Unpublished document VBC/84.889).

    TAYLOR, P. (1980) Anticholinesterase agents. In: Goodman, L.S. &
    Gilman, A., ed.  The pharmacological basis of therapeutics, 6th ed.,
    New York, Macmillan Publishing Company, pp. 100-119.

    UK DHSS (1983)  Pesticide poisoning: notes for the guidance of medical
    practitioners, London, United Kingdom Department of Health and Social
    Security, pp. 41-47.

    VALE, J.A. & SCOTT, G.W. (1974)  Organophosphorus poisoning.  Guy's
     Hosp. Rep., 123: 13-25.

    WARRINER, R.A., III, NIES, A.S., & HAYES, W.J., Jr (1977) Severe
    organophosphate poisoning complicated by alcohol and terpentine
    ingestion.  Arch. environ. Health, 32: 203-205.

    RESUME ET EVALUATION, CONCLUSIONS, RECOMMANDATIONS

    1  Résumé et évaluation

    1.1  Exposition

         Le parathion-méthyl est un insecticide organophosphoré dont la
    première synthèse remonte aux années 1940. Il est relativement
    insoluble dans l'eau, peu soluble dans l'éther de pétrole et les
    huiles minérales et facilement soluble dans la plupart des solvants
    organiques. A l'état pur, il se présente sous la forme de cristaux
    blancs; le parathion-méthyl technique est légèrement jaunâtre et
    dégage une odeur alliacée. Il est instable à la chaleur et se
    décompose rapidement au-dessus de pH 8.

         La chromatographie en phase gazeuse avec détection par ionisation
    de flamme alcaline (AFID) ou photométrie de flamme (FPD) est la
    méthode la plus couramment utilisée pour le dosage du
    parathion-méthyl. Les limites de détection dans l'eau vont de 0,01 à
    0,1 µg/litre; dans l'air, elles vont de 0,1 à 1 ng/m3. La
    chromatographie en phase liquide à haute performance et la
    chromatographie en couche mince sont également utiles pour la
    recherche du parathion-méthyl.

         La distribution du parathion-méthyl dans l'air, l'eau, le sol et
    les êtres vivants dépend de plusieurs facteurs physiques, chimiques et
    biologiques.

         Les études utilisant des modèles d'écosystèmes ainsi que des
    modèles mathématiques montrent que le parathion-méthyl se partage
    principalement entre l'air et le sol dans l'environnement, une plus
    faible proportion se répartissant entre les végétaux et les animaux.
    Il ne se déplace pratiquement pas dans le sol et ni le composé
    initial, ni ses produits de décomposition n'atteignent normalement les
    eaux souterraines. Le parathion-méthyl présent dans l'air provient
    principalement de l'épandage de ce composé, encore qu'il puisse se
    volatiliser en partie lorsque l'eau qui le contient s'évapore de la
    surface des feuilles et du sol. Les niveaux atmosphériques de fond
    dans les zones agricoles vont de zéro (non décelable) à environ 70
    ng/m3. Les concentrations dans l'air après épandage diminuent
    rapidement en trois jours pour atteindre le niveau de fond au bout
    d'environ neuf jours. Dans les cours d'eau, les concentrations (études
    de laboratoire) tombent à 80% de la concentration initiale au bout
    d'une heure et à 10 % au bout d'une semaine. Le parathion-méthyl
    demeure plus longtemps dans le sol que dans l'air ou l'eau encore que
    sa rétention dépende en grande partie du type de sol; dans les sols
    sableux, les résidus de parathion-méthyl disparaissent plus rapidement
    que dans le terreau. Les résidus présents à la surface des plantes ou
    dans les feuilles diminuent rapidement avec une demi-vie de l'ordre de
    quelques heures; la disparition totale du parathion-méthyl s'effectue
    en six à sept jours environ.

         L'organisme animal est capable de décomposer le parathion-méthyl
    et d'en éliminer les produits de dégradation en très peu de temps. Ce
    processus est plus lent chez les vertébrés inférieurs et les
    invertébrés que chez les mammifères et les oiseaux. Les facteurs de
    bioconcentration sont faibles et le parathion-méthyl ne s'accumule que
    temporairement.

         C'est la dégradation microbienne qui est de loin la voie la plus
    importante de dégradation du parathion-méthyl dans le milieu. Le
    composé disparaît plus rapidement sur le terrain ou dans des modèles
    d'écosystèmes que ne l'avaient laissé entrevoir les études de
    laboratoire. Cela tient au fait qu'il existe plusieurs microorganismes
    capables de décomposer cette substance dans diverses circonstances et
    dans différents biotopes. La présence de sédiments ou de surfaces
    végétales qui accroît les populations microbiennes, augmente la
    vitesse de décomposition du parathion-méthyl.

         Sous l'action du rayonnement ultra-violet ou de la lumière
    solaire, le parathion-méthyl peut subir une décomposition oxydante en
    paraoxon-méthyl, moins stable; après pulvérisation, le temps de
    demi-décomposition par le rayonnement ultra-violet est d'environ 40
    heures. Toutefois, la contribution de la photolyse à l'élimination
    totale dans un système aquatique, n'est, selon les estimations, que de
    4 %. L'hydrolyse du parathion-méthyl se produit également plus
    rapidement en milieu alcalin. Une forte salinité favorise aussi
    l'hydrolyse. En présence de sédiments fortement réducteurs, on a noté
    des demi-vies de quelques minutes, encore que la sorption à d'autres
    sédiments accroisse la stabilité du composé.

         Dans des villes situées au centre de zones agricoles des
    Etats-Unis d'Amérique, on a observé que les concentrations de
    parathion-méthyl dans l'air variaient avec la saison et culminaient en
    août ou septembre; les enquêtes ont révélé que les teneurs maximales
    se situaient principalement dans les limites de 100 à 800 ng/m3 au
    cours de la période de végétation. Dans les eaux naturelles de ces
    mêmes régions des Etats-Unis, on a observé des concentrations allant
    jusqu'à 0,46 µg/litre, les maxima étant atteints en été. Il n'existe
    qu'un petit nombre de publications sur les résidus alimentaires de
    parathion-méthyl dans le monde. Aux Etats-Unis, ces résidus se situent
    en général à un très faible niveau, même si quelques échantillons
    dépassent les limites maximales de résidus (LMR). Les études de ration
    totale dont il est fait état dans la littérature ne font état que de
    traces de résidus. C'est dans les légumes-feuilles (jusqu'à 2 mg/kg)
    et les légumes racines (jusqu'à 1 mg/kg) que l'on a constaté les
    résidus les plus élevés lors d'enquêtes sur le panier de la ménagère
    effectuées aux Etats-Unis entre 1966 et 1969. La préparation, la
    cuisson et la conservation des aliments entraînent la décomposition
    des résidus de parathion-méthyl, ce qui réduit encore l'exposition des

    consommateurs. En cas d'erreurs de manipulation du parathion-méthyl,
    on peut trouver des résidus plus élevés dans les légumes et les fruits
    crus. la production, la formulation, la manipulation et l'utilisation
    du parathion-méthyl comme insecticide sont les principales sources
    potentielles d'exposition humaine. C'est principalement par contact 
    cutané et, dans une moindre proportion, par inhalation que les
    travailleurs sont exposés à cette substance.

         Lors d'une étude sur des ouvriers agricoles qui pulvérisaient du
    parathion-méthyl (les ouvriers non protégés procédant à un épandage
    manuel de cette substance à très bas volume), on a calculé que ces
    personnes absorbaient 0,4 à 13 mg de parathion-méthyl par 24 heures en
    se fondant sur le dosage du  p-nitrophénol dans les urines. Si les
    ouvriers reviennent trop tôt sur les lieux après le traitement, ils se
    trouvent encore davantage exposés.

         La population générale peut être exposée à des résidus présents
    dans l'air, l'eau et les aliments par suite de traitements sur les
    cultures ou les forêts ou d'erreurs de manipulation (épandage en
    dehors de la zone à traiter) qui entraînent la contamination des
    champs, des cultures, de l'eau et de l'air.

    1.2  Fixation, métabolisme et excrétion

         Le parathion-méthyl est facilement absorbé par toutes les voies
    d'exposition (orale, percutanée, respiratoire) et il se répand
    rapidement dans les tissus de l'organisme. Les concentrations
    maximales dans les divers organes ont été observées une à deux heures
    après le traitement. La conversion du parathion-méthyl en
    paraoxon-méthyl se produit dans les minutes qui suivent
    l'administration. Après administration de parathion-méthyl par voie
    intraveineuse à des chiens, on a observé une demi-vie terminale
    moyenne de 7,2 heures. C'est le foie qui joue le principal rôle dans
    le métabolisme et la détoxication du parathion-méthyl. Le mode
    principal de détoxication du parathion-méthyl et du paraoxon-méthyl au
    niveau du foie consiste en oxydation, hydrolyse et déméthylation ou
    désarylation en présence de glutathion réduit (GSH). Les produits de
    réaction sont le thiophosphate de  o-méthyle et de  o-nitrophényle
    ainsi que les acides diméthylphosphorothioïque ou
    diméthyl-phosphorique et le  p-nitrophénol. Il est donc possible
    d'évaluer l'exposition en mesurant l'excrétion urinaire du
     p-nitrophénol. Chez des volontaires, l'excrétion urinaire de
     p-nitrophénol était de 60 % quatre heures après l'administration et
    d'environ 100 % au bout de 24 heures. Le métabolisme du
    parathion-méthyl joue un rôle important dans la toxicité sélective de
    ce composé pour les différentes espèces et l'apparition éventuelle

    d'une résistance. L'élimination du parathion-méthyl et de ses
    métabolites s'effectue principalement par la voie urinaire. Des études
    menées sur des souris avec du parathion-méthyl radiomarqué au 32P
    ont montré qu'au bout de 72 heures, 75 % de la radio-activité se
    retrouvaient dans les urines et jusqu'à 10 % dans les matières
    fécales.

    1.3  Effets sur les êtres vivants dans leur milieu
    naturel

         Certains microorganismes peuvent utiliser le parathion-méthyl
    comme source de carbone et l'étude d'une communauté naturelle a montré
    que des concentrations allant jusqu'à 5 mg/litre augmentaient la
    biomasse et l'activité reproductrice. L'effet est positif dans le cas
    des bactéries et des actinomycètes; par contre, les champignons et les
    levures sont moins capables d'utiliser ce composé. Chez une diatomée,
    on a constaté une inhibition de 50 % de la croissance à une
    concentration d'environ 5 mg/litre. Chez des algues vertes
    unicellulaires, la croissance a été réduite par des concentrations
    comprises entre 25 et 80 µg de parathion-méthyl par litre. Les
    populations d'algues devenaient tolérantes au parathion-méthyl après
    quelques semaines d'exposition.

         Le parathion-méthyl est extrêmement toxique pour les invertébrés
    aquatiques, la CL50 étant plupart du temps comprise entre <1 µg et
    environ 40 µg/litre. Quelques espèces d'arthropodes sont moins
    sensibles. Pour la daphnie  (Daphnia magna) la concentration sans
    effet observable est de 1,2 µg/litre. Les mollusques sont beaucoup
    moins sensibles, puisque leur CL50 varie de 12 à 25 mg/litre.

         La plupart des espèces de poissons d'eau douce ou de mer ont une
    CL50 comprise entre 6 et 25 mg/litre, quelques espèces étant
    nettement plus ou nettement moins sensibles au composé. La toxicité
    aiguë est comparable chez les amphibiens et les poissons.

         Le traitement au parathion-méthyl de mares expérimentales a
    permis d'en observer les effets sur l'effectif des communautés
    d'invertébrés aquatiques. Seul un épandage sur les étendues d'eau
    serait susceptible d'engendrer les concentrations nécessaires à
    l'apparition de ces effets et encore, seraient-ils de courte durée.
    Une décimation des populations d'invertébrés est donc improbable en
    situation réelle. En cas de mortalité chez les invertébrés, les effets
    ne seraient probablement pas de longue durée.

         Il convient dont de veiller à ne pas procéder à des épandages sur
    les mares, cours d'eau et lacs. Le parathion-méthyl ne doit jamais
    être épandu lorsque le vent souffle.

         Le parathion-méthyl est un insecticide non-sélectif qui détruit
    les espèces utiles tout autant que les ravageurs. On a fait état de
    mortalité parmi des abeilles à la suite d'épandages de
    parathion-méthyl. Ce genre d'accidents est plus grave avec le
    parathion-méthyl qu'avec d'autres insecticides. Les abeilles adaptées
    à l'Afrique supportent mieux le parathion-méthyl que les souches
    européennes.

         Le parathion-méthyl s'est révélé modérément toxique pour les
    oiseaux au laboratoire, la DL50 aiguë par voie orale allant de 3 à
    8 mg/kg de poids corporel. Par la voie alimentaire, la CL50 allait
    de 70 à 680 mg/kg de nourriture. Rien n'indique que les oiseaux aient
    à souffrir du parathion-méthyl lorsqu'il est épandu conformément aux
    recommandations.

         On veillera tout particulièrement à l'horaire des épandages pour
    éviter tout effet nocif sur les abeilles.

    1.4  Effets sur les animaux d'expérience et les systèmes d'épreuve
     in vitro

         La DL50 par voie orale varie chez les rongeurs de 3 à 35 mg/kg
    de poids corporel et la DL50 par voie percutanée, de 44 à 67 mg/kg
    de poids corporel.

         L'intoxication par le parathion-méthyl engendre les effets
    cholinergiques habituels des organophosphorés que l'on peut attribuer
    à l'accumulation d'acétylcholine au niveau des terminaisons nerveuses.
    La toxicité du parathion-méthyl est due à sa métabolisation en
    paraoxon-méthyl. Cette conversion est très rapide. Aucun signe de
    neuropathie retardée induite par les organophosphorés n'a été relevé.

         Le parathion-méthyl technique n'a aucun effet irritant sur l'oeil
    ni la peau.

         Lors d'études de toxicité à court terme utilisant diverses voies
    d'administration et portant sur des rats, des chiens et des lapins, on
    a observé une inhibition de la cholinestérase du plasma, des
    érythrocytes et du cerveau ainsi qu'un certain nombre de signes liés
    aux effets cholinergiques. Lors d'une étude d'alimentation de 12
    semaines sur des chiens, on a obtenu, pour la dose sans effet nocif
    observable, une valeur de 5 mg/kg de nourriture (soit l'équivalent de
    0,1 mg/kg de poids corporel par jour). Lors d'une étude de toxicité
    par voie percutanée, effectuée pendant trois semaines sur des lapins,
    on a obtenu une dose sans effet observable de 10 mg/kg de poids
    corporel par jour. Lorsque les animaux étaient exposés par la voie
    respiratoire pendant trois semaines, la dose sans effet observable
    était de 0,9 mg/m3 d'air. A la dose de 2,6 mg/m3, on n'a observé
    qu'une légère inhibition de la cholinestérase plasmatique.

         Des études de cancérogénicité et de toxicité à long terme ont été
    effectuées sur des souris et des rats. Pour les rats, la dose sans
    effet observable basée sur l'inhibition de la cholinestérase était de
    0,1 mg/kg de poids corporel par jour. Les résultats de ces études
    n'ont fait ressortir aucun signe de cancérogénicité, ni chez les
    souris ni chez les rats. Dans une autre étude de deux ans effectuée
    sur des rats, on a toutefois relevé les signes d'un effet neurotoxique
    périphérique à la dose de 50 mg/kg de nourriture.

         Le parathion-méthyl serait capable de provoquer l'alkylation de
    l'ADN  in vitro. La plupart des études de génotoxicité  in vitro
    portant sur des cellules bactériennes et mammaliennes ont donné des
    résultats positifs, alors que six études  in vivo portant sur trois
    systèmes d'épreuve différents ont donné des résultats ambigus.

         Les études portant sur la reproduction avec administration de
    doses toxiques (inhibition de la cholinestérase) n'ont pas produit
    d'effets systématiques sur la taille des portées et leur nombre, le
    taux de survie des petits ni la lactation. Aucun effet tératogène ou
    embryotoxique direct n'a été observé.

    1.5  Effets sur l'homme

         Plusieurs cas d'intoxication aiguë par le parathion-méthyl ont
    été signalés. Les symptômes sont caractéristiques d'une intoxication
    générale par les anticholinestérasiques organophosphorés. Il s'agit
    d'effets nerveux cholinergiques au niveau périphérique et au niveau
    central qui apparaissent dans les minutes qui suivent l'exposition. En
    cas d'exposition par voie percutanée, les symptômes peuvent s'aggraver
    pendant plus d'une journée et durer plusieurs jours.

         Des études sur des volontaires soumis à des expositions répétées
    de longue durée ont montré que l'activité cholinestérasique du sang
    diminuait sans provoquer de manifestations cliniques. 

         Aucun cas de neuropathie périphérique retardée induite par les
    organophosphorés n'a été signalé. Dans un certain nombre de cas
    d'exposition multiple à des pesticides et notamment à du
    parathion-méthyl, on a observé des séquelles neurospychiatriques.

         Une augmentation du nombre des aberrations chromosomiques a été
    signalée dans des cas d'intoxication aiguë.

         On ne possède aucune donnée obtenue sur l'homme qui puisse
    permettre d'évaluer les effets tératogènes du parathion-méthyl ou ses
    effets sur la reproduction.

         Les études épidémiologiques disponibles sont consacrées à des
    expositions multiples aux pesticides et il n'est pas possible d'en
    déduire les effets qu'une exposition de longue durée au
    parathion-méthyl pourrait entraîner.

    2  Conclusions

         Le parathion-méthyl est un insecticide organophosphoré très
    toxique. Une exposition excessive due à la manipulation de ce produit
    au cours de la production, de l'utilisation ou par suite d'ingestion
    accidentelle ou intentionnelle peut entraîner une intoxication grave
    voire mortelle. Certaines formulations de parathion-méthyl peuvent,
    selon le cas, entraîner une irritation des yeux ou de la peau mais de
    toute façon, elles sont toutes facilement absorbées. On peut donc être
    dangereusement exposé à cet insecticide sans s'en rendre compte.

         Le parathion-méthyl ne subsiste pas dans l'environnement. Il ne
    subit pas de bioconcentration et ne se transmet pas le long de la
    chaîne alimentaire. Il est rapidement décomposé par un grand nombre de
    microorganismes et autres éléments de la faune sauvage. Cet
    insecticide peut provoquer des dégâts dans les écosystèmes, mais
    seulement en cas d'exposition excessive dues à une utilisation
    défectueuse ou à des déversements accidentelles. Toutefois les
    insectes utiles et notamment les insectes pollinisateurs peuvent
    souffrir des épandages de parathion-méthyl.

         C'est principalement par l'intermédiaire des denrées alimentaires
    que la population générale peut être exposée à des résidus de
    parathion-méthyl. Si l'on respecte les règles de bonne pratique
    agricole, il n'y a pas de raison que la dose journalière admissible
    fixée par le Comité d'experts FAO/OMS soit dépassée (0-0,02 mg/kg de
    poids corporel)). Il peut également y avoir exposition par voie
    percutanée lors de contacts accidentels avec des résidus foliaires
    dans des champs traités ou des zones voisines contaminées par des
    embruns de pesticides.

         Moyennant de bonnes méthodes de travail et des précautions
    suffisantes en matières d'hygiène et de sécurité, le parathion-méthyl
    de devrait pas présenter de danger pour ceux qui lui sont exposés de
    par leur profession.

    3  Recommandations

    *    Afin de protéger la santé et le bien-être des travailleurs et de
         la population générale il ne faut confier la manipulation et
         l'épandage du parathion-méthyl qu'à des personnes bien encadrées
         et bien formées qui utiliseront l'insecticide en prenant les
         mesures de sécurité nécessaires et se conformeront aux règles de
         bonne pratique en la matière.

    *    La fabrication, la formulation, l'utilisation agricole et
         l'élimination du parathion-méthyl doivent être conduites avec
         soin afin de réduire au minimum la contamination de
         l'environnement.

    *    Les travailleurs qui sont régulièrement exposés au parathion-
         méthyl doivent bénéficier d'un suivi médical approprié. 

    *    Afin de réduire les risques pour l'ensemble de la population, il
         est recommandé de ne pas revenir sur une zone traitée avant 48
         heures.

    *    Les autorités nationales devront fixer les délais pour les
         épandages avant récolte et les faire respecter.

    *    En raison de la forte toxicité du parathion-méthyl, cet
         insecticide ne doit pas être épandu à très bas volume à l'aide de
         dispositifs à main.

    *    Ne pas pulvériser sur les étendues d'eau.  Choisir les horaires
         de manière à éviter de détruire les insectes pollinisateurs.

    *    Les données sur l'état de santé des travailleurs exposés
         uniquement au parathion-méthyl (c'est-à-dire employés à la
         fabrication et à la formulation de cet insecticide) devront être
         publiées afin que l'on puisse mieux en évaluer les risques pour
         la santé humaine.

    *    Des études à caractère plus définitif devront être menées sur les
         résidus de parathion-méthyl dans les denrées alimentaires
         fraîches.

    *    Il faudrait procéder à une évaluation plus concluante de la
         génotoxicité du parathion-méthyl.

    RESUMEN Y EVALUACION, CONCLUSIONES Y RECOMENDACIONES

    1  Resumen y evaluación

    1.1  Exposición

         El metilparatión es un insecticida organofosforado que
    sesintetizó por primera vez en la década de 1940. Es
    relativamenteinsoluble en agua, poco soluble en éter de petróleo y
    aceitesminerales y fácilmente soluble en la mayoría de los
    disolventesorgánicos. El metilparatión puro se encuentra en forma de
    cristalesblancos; el de calidad técnica tiene un color tostado claro
    y olorparecido al del ajo. Es térmicamente inestable y se descompone
    conrapidez a un pH superior a 8.

         El método más común para la determinación del metilparatión esla
    cromatografía de gases con un detector de ionización de llama enálcali
    o bien con uno fotométrico de llama. Los límites de detecciónen el
    agua oscilan entre 0,01 y 0,1 µg/litro, y en el aire entre 0,1 y 1
    ng/m3. También son útiles como métodos de detección lacromatografía
    líquida de alta resolución y la cromatografía en capafina.

         En la distribución del metilparatión en el aire, el agua, el
    sueloy los organismos del medio ambiente influyen varios factores
    físicos,químicos y biológicos.

         Los estudios realizados utilizando modelos de ecosistemas y
    laelaboración de modelos matemáticos indican que en el medioambiente
    el metilparatión se reparte principalmente entre el aire y elsuelo,
    con cantidades menores en las plantas y los animales.Prácticamente no
    hay desplazamiento a través del suelo, y ni elcompuesto original ni
    los productos derivados de su degradaciónllegan normalmente al agua
    subterránea. El metilparatión presente enel aire procede sobre todo
    del rociado del compuesto, aunque seproduce cierta volatilización con
    la evaporación del agua de las hojasy de la superficie del suelo. Los
    niveles habituales de metilparatiónen la atmósfera en las zonas
    agrícolas oscilan entre una cantidad nodetectable y unos 70 ng/m3.
    Se ha observado que las concentracionesen el aire después del rociado
    disminuyen con rapidez en tres días,alcanzando los niveles habituales
    en unos nueve días. Laconcentración en el agua fluvial (en estudios de
    laboratorio)descendió al 80% de la inicial después de una hora, y
    transcurridauna semana era del 10%. El metilparatión se mantiene en el
    suelomás tiempo que en el aire o el agua, aunque en la retención
    influyemucho el tipo de suelo; el arenoso pierde los residuos del
    compuestocon mayor rapidez que las margas. Los residuos de la
    superficie delas plantas y del interior de las hojas disminuyen
    rápidamente, conuna semivida del orden de unas horas; el metilparatión
    desaparecetotalmente en unos 6-7 días.

         Los animales pueden degradar el metilparatión y eliminar
    losproductos de degradación en un período muy breve de tiempo.
    Elproceso es más lento en los vertebrados inferiores y en
    losinvertebrados que en los mamíferos y las aves. Los factores
    debioconcentración son bajos y los niveles acumulados de
    metilparatióntransitorios.

         La descomposición microbiana es con diferencia el mecanismomás
    importante de degradación del metilparatión en el medioambiente. La
    desaparición del compuesto en el campo y enecosistemas utilizados como
    modelo es más rápida de lo que habíanpermitido suponer los estudios de
    laboratodeloorio. Esto se debe a lavariedad de microorganismos que son
    capaces de degradarlo endistintos hábitats y circunstancias. La
    presencia de sedimentos o desuperficies de plantas, que aumenta la
    población microbiana, acelerael ritmo de degradación del
    metilparatión.

         El metilparatión puede sufrir degradación oxidativa por acciónde
    la radiación ultravioleta o la luz solar, convirtiéndose enmetil
    paraoxón, que es menos estable; las películas de rociado sedegradan
    por acción de la radiación ultravioleta con una semivida aproximada de
    40 horas. Sin embargo, se ha estimado que lacontribución de la
    fotolisis a la desaparición total en un sistema acuático es sólo de un
    4%. También se produce hidrólisis delmetilparatión en condiciones
    alcalinas, en las que es más rápida. Lasalinidad elevada favorece
    asimismo la hidrólisis del compuesto. Ensedimentos muy reductores se
    registraron semividas de unos minutos, aunque el metilparatión  es más
    estable cuando está adsorbido sobreotros sedimentos.

         En las ciudades situadas en el centro de las zonas agrícolas
    delos Estados Unidos, las concentraciones de metilparatión en el
    airevariaban con las estaciones y alcanzaban el punto más alto en
    agostoo septiembre; los niveles máximos registrados durante los
    estudios fueron fundamentalmente del orden de 100-800 ng/m3 durante
    elperíodo vegetativo. Las concentraciones en el agua natural de
    laszonas agrícolas de los Estados Unidos llegaron a 0,46 µg/litro,
    conlos niveles más altos en el verano. Son muy pocos los
    informespublicados en todo el mundo sobre los residuos de
    metilparatión enlos alimentos. En los Estados Unidos, se han
    notificado en generalniveles muy bajos de residuos de metilparatión 
    en los productos alimenticios, con un pequeño número de muestras
    aisladas porencima de los límites máximos de residuos (LMR). En todos
    losestudios publicados sobre la alimentación sólo se detectaron
    niveles ínfimos de metilparatión. En las encuestas sobre la cesta de
    lacompra realizadas en los Estados Unidos entre 1966 y 1969,
    lascantidades mayores de residuos de metilparatión se encontraron en

    lashortalizas de hoja (hasta 2 mg/kg) y en las de raíz (hasta 1
    mg/kg). En la preparación, cocción y almacenamiento de los alimentos
    se descomponen los residuos de metilparatión, reduciéndose
    ulteriormente la exposición humana. Las frutas y hortalizas
    sinelaborar pueden contener más residuos después de un uso indebidodel
    producto.

         La producción, formulación, manipulación y uso delmetilparatión
    como insecticida pueden ser, en principio, fuente deexposición para
    las personas. Las principales vías de exposición delos trabajadores
    son el contacto cutáneo y, en menor medida, lainhalación.

         En un estudio sobre personas encargadas del rociado en fincas
    (trabajadores no protegidos que utilizaban rociadores manuales
    devolumen ultrabajo), a partir del  p-nitrofenol excretado en la
    orina secalculó una ingestión de 0,4-13 mg de metilparatión cada 24
    horas. También se puede sufrir exposición si se entra en los
    cultivosdemasiado pronto después de tratarlos.

         La población general puede estar expuesta a residuos
    demetilparatión presentes en el aire, el agua y los alimentos como
    consecuencia de prácticas agrícolas y forestales con un uso
    indebidodel producto, que provoca la contaminación de los campos,
    loscultivos, el agua y el aire debido al rociado parcial fuera del
    objetivo.

    1.2  Ingestión, metabolismo y excreción

         El metilparatión se absorbe fácilmente por todas las vías de
    exposición (oral, cutánea, respiratoria) y se distribuye con rapidez
    por los tejidos del cuerpo. Se detectaron concentraciones máximas en
    diversos órganos 1-2 horas después del tratamiento. Después de la
    administración, la transformación del metilparatión en metilparaoxón
    se produce en unos minutos. En perros se determinó una semivida
    terminal media de 7,2 horas tras la administración intravenosa de
    metilparatión. El hígado es el principal órgano de metabolización y
    desintoxicación. El metilparatión o el metilparaoxón se destoxifican
    en el hígado sobre todo mediante oxidación, hidrólisis y desmetilación
    o desarilación con glutatión reducido. Los productos de la reacción
    son el  O-metil  O-p-nitrofenilfosfotioato, o bien los ácidos
    dimetilfosfotioico o dimetilfosfórico, y el  p-nitrofenol. Por
    consiguiente, se puede estimar la exposición midiendo la excreción
    urinaria de  p-nitrofenol; en voluntarios humanos fue del 60% en
    cuatro horas y prácticamente del 100% en 24 horas. El metabolismo del
    metilparatión es importante para la toxicidad específica selectiva y
    la aparición de resistencia. Le eliminación de esta sustancia y sus
    productos derivados tiene lugar primordialmente por la orina. En
    estudios realizados en ratones con 32P-metilparatión (marcado
    radiactivamente) se observó un 75% de radiactividad en la orina y
    hasta un 10% en las heces después de 72 horas. 

    1.3  Efectos en los seres vivos del medio ambiente

         Los microorganismos pueden utilizar el metilparatión como fuente
    de carbono, y en el estudio de una comunidad natural se vio que
    concentraciones de hasta 5 mg/litro aumentaban la biomasa y la
    actividad reproductora. En las bacterias y los actinomicetos se
    observó un efecto positivo del metilparatión, mientras que los hongos
    y las levaduras tenían menor capacidad para utilizar la sustancia. Con
    una concentración aproximada de 5 mg/litro se produjo una inhibición
    del 50% del crecimiento de una diatomea. Concentraciones de
    metilparatión comprendidas entre 25 y 80 µg/litro redujeron el
    crecimiento celular de las algas clorofíceas unicelulares. Las
    poblaciones de algas adquirieron tolerancia tras varias semanas de
    exposición.

         El metilparatión es muy tóxico para los invertebrados acuáticos,
    oscilando casi siempre la CL50 entre < 1 µg y alrededor de 40
    µg/litro. Hay un pequeño número de especies de artrópodos que son
    menos susceptibles. El nivel sin efecto para  Daphnia magna es de 1,2
    µg/litro. Los moluscos son mucho menos susceptibles, con CL50 entre
    12 y 25 mg/litro.

         La mayoría de las especies de peces, tanto de agua dulce como de
    mar, tienen una CL50 de 6 a 25 mg/litro, pero hay un pequeño número
    de especies cuya sensibilidad al metilparatión es considerablemente
    mayor o menor. La toxicidad aguda para los anfibios es análoga a la de
    los peces.

         Se han observado los efectos sobre poblaciones en las comunidades
    de invertebrados acuáticos de estanques experimentales tratados con
    metilparatión. Las concentraciones necesarias para producir esos
    efectos se alcanzarían sólo con un rociado excesivo de las masas de
    agua, e incluso en este caso durarían muy poco tiempo. Por
    consiguiente, en condiciones normales no es probable que se observen
    efectos sobre las poblaciones. Tampoco los es que la acción letal
    sobre los invertebrados acuáticos provoque efectos duraderos.

         Hay que tener cuidado para evitar un rociado excesivo de
    estanques, ríos y lagos al utilizar el metilparatión. Nunca se debe
    efectuar la operación con viento.

         El metilparatión es un insecticida no selectivo que mata especies
    beneficiosas tan fácilmente como las plagas. Se ha notificado la
    muerte de abejas después de su aplicación. Sus efectos sobre esta
    especie fueron más graves que los de otros insecticidas. Las abejas
    africanizadas son más tolerantes al metilparatión que las razas
    europeas.

         El metilparatión fue moderadamente tóxico para las aves en
    estudios de laboratorio, con una DL50 oral aguda comprendida entre
    3 y 8 mg/kg de peso corporal. La CL50 en la dieta osciló entre 70 y
    680 mg/kg de alimentos. No hay indicios de que las aves puedan verse
    afectadas negativamente con la utilización recomendada en el campo.

         Hay que tener el máximo cuidado al programar el rociado con
    metilparatión, a fin de evitar los efectos adversos sobre las abejas.

    1.4  Efectos en los animales de experimentación y en sistemas de
    prueba  in vitro

         Los valores de la DL50 del metilparatión por vía oral en
    roedores oscilan entre 3 y 35 mg/kg de peso corporal, y los valores
    por vía cutánea entre 44 y 67 mg/kg de peso corporal.

         El envenenamiento por metilparatión provoca los signos
    colinérgicos habituales de los organofosfatos, atribuidos a la
    acumulación de acetilcolina en la terminaciones nerviosas. El
    metilparatión adquiere la toxicidad al metabolizarse a metilparaoxón,
    en un proceso que es muy rápido. No se han observado indicios de
    neuropatía retardada inducida por compuestos organofosforados.

         Se ha comprobado que el metilparatión de calidad técnica no tiene
    potencial de irritación primaria de los ojos o la piel.

         En estudios de toxicidad de corta duración, utilizando diversas
    vías de administración en ratas, perros y conejos, se observó
    inhibición de la colinesterasa del plasma, los eritrocitos y el
    cerebro, así como signos colinérgicos conexos. En un estudio de
    alimentación durante 12 semanas con perros, el nivel sin efectos
    adversos observados (NOAEL) fue de 5 mg/kg de la dieta (equivalente a
    0,1 mg/kg de peso corporal al día). En un estudio de toxicidad cutánea
    de tres semanas en conejos, el nivel sin efectos observados (NOEL) fue
    de 10 mg/kg de peso corporal al día. La exposición por inhalación
    durante tres semanas dio como resultado un NOEL de 0,9 mg/m3 de
    aire. Con 2,6 mg/m3 solamente se observó una ligera inhibición de la
    colinesterasa del plasma.

         Se realizaron estudios de toxicidad/teratogenicidad de larga
    duración con ratones y ratas. El NOEL para las ratas fue de 0,1 mg/kg
    de peso corporal al día, basado en la inhibición de la colinesterasa.
    No hay pruebas de carcinogenicidad en ratones y ratas tras una
    exposición de larga duración. Sin embargo, en otro estudio de dos años
    con ratas se detectó un efecto neurotóxico periférico con una dosis de
    50 mg/kg de la dieta.

         Se ha informado que el metilparatión tiene propiedades
    alquilizantes del ADN  in vitro. Los resultados de la mayoría de los
    estudios de genotoxicidad  in vitro con células tanto bacterianas
    como de mamífero fueron positivos, mientras que en seis estudios in
    vivo, utilizando tres sistemas de prueba distintos, los resultados
    fueron equívocos.

         En estudios de reproducción con niveles de dosificación tóxicos
    (inhibición de la colinesterasa), no se observaron efectos constantes
    sobre el tamaño de la camada, el número de partos, la tasa de
    supervivencia de las crías y el rendimiento de la lactación. No se
    detectó ningún efecto teratogénico o embriotóxico primario.

    1.5  Efectos en la especie humana

         Se han registrado varios casos de intoxicación aguda por
    metilparatión. Los signos y síntomas son los característicos de la
    intoxicación sistémica por compuestos organofosforados inhibidores de
    la colinesterasa. Cabe mencionar entre ellos las manifestaciones del
    sistema nervioso colinérgico periférico y central, que aparecen apenas
    unos minutos después de la exposición. En el caso de la exposición
    cutánea, la gravedad de los síntomas puede ir en aumento durante más
    de un día y pueden durar varios días.

         Los estudios con voluntarios sometidos a exposiciones repetidas
    de larga duración parecen indicar que hay una disminución de la
    actividad de la colinesterasa de la sangre, sin manifestaciones
    clínicas.

         No se ha informado de ningún caso de neuropatía periférica
    retardada inducida por compuestos organofosforados. Se han descrito
    secuelas neuropsiquiátricas en casos de exposición múltiple a
    plaguicidas, entre ellos el metilparatión.

         En casos de intoxicaciones agudas, se ha detectado un aumento de
    las aberraciones cromosómicas.

         No se dispone de datos relativos al metilparatión en la especie
    humana que permitan evaluar los efectos teratogénicos y sobre la
    reproducción.

         Los estudios epidemiológicos disponibles se refieren a una
    exposición múltiple a plaguicidas, y no es posible evaluar los efectos
    de una exposición de larga duración al metilparatión.

    2  Conclusiones

         El metilparatión es un éster organofosfórico muy tóxico,
    utilizado como insecticida. Una exposición excesiva al manejarlo
    durante su fabricación y uso o por ingestión accidental o intencionada
    puede ocasionar una intoxicación grave o letal. Las formulaciones de
    metilparatión unas veces son irritantes y otras no para los ojos o la
    piel, pero se absorben fácilmente. Por consiguiente, pueden producirse
    exposiciones peligrosas sin advertirlo.

         El metilparatión no se mantiene mucho tiempo en el medio
    ambiente, no se produce bioconcentración y no se desplaza a través de
    la cadena alimentaria. Lo degradan con rapidez numerosos
    microorganismos y otros tipos de seres vivos presentes en el medio
    ambiente. Este insecticida puede ocasionar daños a ecosistemas
    solamente en casos de una exposición muy intensa causada por el uso
    indebido o escapes accidentales; sin embargo, el rociado con
    metilparatión representa un riesgo para los insectos polinizadores y
    otros que son beneficiosos.

         La exposición de la población general a los residuos del
    metilparatión tiene lugar fundamentalmente por medio de los alimentos.
    Si se siguen buenas prácticas agrícolas, no se supera la ingesta
    diaria admisible (0-0,02 mg/kg de peso corporal) establecida por la
    FAO/OMS. Puede haber exposición cutánea accidental por contacto con
    residuos foliares en campos rociados o en zonas adyacentes a los
    lugares que se están rociando, como consecuencia de pérdidas del
    producto que no llegan a su objetivo.

         Con buenas prácticas de trabajo, medidas higiénicas y
    precauciones de seguridad, no es probable que el metilparatión
    represente un riesgo para las personas con exposición profesional.

    3  Recomendaciones

    *    Para salvaguardar la salud y el bienestar de los trabajadores y
         de la población general, el manejo y la aplicación del 
         metilparatión sólo se debería encomendar, bajo una atenta
         supervisión, a personas bien capacitadas que se ajusten a las 
         medidas de seguridad adecuadas y utilicen el producto de acuerdo 
         con las buenas prácticas de aplicación.

    *    Se debe prestar particular atención a la fabricación, la
         formulación, el uso agrícola y la eliminación del metilparatión,
         a fin de reducir al mínimo la contaminación del medio ambiente.

    *    Los trabajadores regularmente expuestos deberían ser objeto de
         vigilancia y exámenes médicos adecuados.

    *    A fin de reducir al mínimo el riesgo para todas las personas, se 
         recomienda esperar 48 horas después del rociado antes de entrar
         de nuevo en cualquier zona tratada.

    *    Las autoridades nacionales deberían establecer intervalos sin
         tratamiento antes de la recolección y obligar a respetarlos.

    *    A la vista de la elevada toxicidad del metilparatión, se debe
         excluir este producto de la aplicación mediante rociado de
         volumen ultrabajo aplicado manualmente.

    *    No se han de rociar masas de agua. Hay que elegir los momentos de
         la aplicación de manera que se evite la muerte de insectos
         polinizadores.

    *    Se debe hacer pública la información relativa al estado de salud 
         de los trabajadores expuestos exclusivamente al metilparatión (es
         decir, en la fabricación, la formulación), con objeto de evaluar
         mejor los riesgos de este producto químico para la salud humana.

    *    Deberían llevarse a cabo estudios más definitivos sobre los
         residuos de metilparatión en los alimentos frescos.

    *    Debería realizarse una evaluación genotóxica más definitiva del 
         metilparatión.
    See Also:
       Toxicological Abbreviations
       Methyl parathion (HSG 75, 1992)
       Methyl parathion (ICSC)
       Methyl Parathion (FAO Meeting Report PL/1965/10/1)
       Methyl Parathion  (IARC Summary & Evaluation, Supplement7, 1987)
       Methyl Parathion (IARC Summary & Evaluation, Volume 30, 1983)