WORLD ORGANIZATION                  FOOD AND AGRICULTURE ORGANIZATION  
    ORGANISATION MONDIALE DE LA SANTE   ORGANISATION POUR L'ALIMENTATION ET
                                        L'AGRICULTURE                           

                                                         VBC/DS/75.19
                                                         ORIGINAL:  ENGLISH

                              
   DATA SHEETS ON PESTICIDES No. 19
    
   1975

   HEPTACHLOR

    It must be noted that the issue of a Data Sheet for a particular 
    pesticide does not imply endorsement of the pesticide by WHO or FAO for 
    any particular use, or exclude its use for other purposes not stated. 
    While the information provided is believed to be accurate according to 
    data available at the time when the sheet was compiled, neither WHO nor 
    FAO are responsible for any errors or omissions, or any consequences 
    therefrom. 

    The issue of this document does     Ce document ne constitue pas une 
    not constitute formal               publication. Il ne doit faire 
    publication. It should not be       l'objet d'aucun compte rendu ou 
    reviewed, abstracted or quoted      résumé ni d'aucune citation sans 
    without the agreement of the        l'autorisation de l'Organisation 
    Food and Agriculture                des Nations Unies pour 
    Organization of the United          l'Alimentation et l'Agriculture ou 
    Nations or of the World Health      de l'Organisation Mondiale de la 
    Organization.                       Santé. 

        
                                   HEPTACHLOR

    Part 1 - General information

                                            CLASSIFICATION

                                            Primary use:  insecticide 

                                            Secondary uses:  none 
     
                                            Chemical group:  organochlorine 
                                                             compound 
    
                                            Data sheet No. 19 
    
                                            Date issued:  December 1975 

    1.1   COMMON NAME:  heptachlor (ISO)

          Identity: 1,4,5,6,7,8-heptachloro-3a,4,7,7a-tetrahydro-4-7-
    methanoindene.  The technical material contains about 72% heptachlor
    and 28% related substances.

    

          Synonyms:  OMS 193                          Local synonyms: 
                     Heptachlorodicyclopentadiene

    1.2   SYNOPSIS: a toxic organochlorine insecticide of moderate 
    mammalian toxicity which is stored in the fat as heptachlor epoxide. 

    1.3   SELECTED PROPERTIES

    1.3.1 Physical characteristics:  when pure, a white crystalline
    solid mp 95-96°C; the technical material is a soft waxy solid melting 
    range 46-74°C. 

    1.3.2 Solubility:  water at 20°C practically insoluble, alcohol at 26°C 
    slightly soluble (4.5%), soluble in benzene and acetone. 

    1.3.3 Stability:  stable towards heat to 150°C-160°C and towards light, 
    air, moisture, alkalies and acids, it is not readily dechlorinated, but 
    is susceptible to epoxidation.  Compatible with most other pesticides. 

    1.3.4 Vapour pressure (volatility): 3 x 10-4 mmHg at 25°C (estimated).

    1.4   AGRICULTURE, HORTICULTURE AND FORESTRY

    1.4.1 Common formulations

          Emulsifiable concentrates, usually 25%; wettable powders, 25%;
    dusts 1.5-2.5%; granules, 2.5, 5, 20 and 25%.  Some clays used as 
    carriers promote decomposition and this is prevented by adding a 
    deactivator.  There are FAO specifications for emulsifiable 
    concentrates, dispersible powders and dusts, and a draft specification 
    for granules. 

    1.4.2 Pests mainly controlled

          Effective as stomach and contact poison against a wide range of
    insects, notably spittlebugs, weevils, wireworms, cornborers, root 
    worms, boll weevils, leaf hoppers, cutworms, thrips, Japanese beetles, 
    grasshoppers, mosquitos, and plum curculio. 
          
    1.4.3 Use pattern

          Originally used on a broad scale on forage, cereal, oil seed,
    vegetable, sugar beet and some nut crops.  Uses have decreased as with 
    other persistent chlorinated pesticides. 

          Main uses are in the treatment of seeds and soil.  In Europe it 
    is used mainly for sugar beet seed treatment, with minor uses as seed 
    dressing for cereal grains and potatoes.  In Asia main use is for the 
    control of soil insects attacking sugar cane, cereals and vegetables. 
    There is a minor use for the protection of pineapple.  In South America 
    the main uses are on sugar cane and maize, with limited use on bananas. 
    In Africa and North America heptachlor is mainly used on maize and 
    small grains.  In some countries it has minor applications, with 
    restrictions on the access of livestock, to young pasture plants, 
    transplant water for seedlings, and ground cover under orchard trees. 

    1.4.4 Unintended effects

          Fish were poisoned as a result of granules being blown from 
    treated land into canals.  Bird losses have occurred in treated areas. 
    Heptachlor accumulates in soil, partly as metabolites of soil 
    microorganisms.  It is not generally phytotoxic but adverse effects on 
    hops have been reported, although the pure material is not toxic to 
    them.  It is toxic to some fungi. 

    1.5   PUBLIC HEALTH PROGRAMMES 
    
          Has been in limited use as a mosquito larvicide. 

    1.6   HOUSEHOLD USE
        
          Not recommended for household use due to its toxicity.

              
                                   HEPTACHLOR

    Part 2 - Toxicology and risks

                                                Common name:  heptachlor

                                                Data sheet No. 19 

                                                Date issued:  December 1975

    2.1   TOXICOLOGY - MAMMALS 

    2.1.1 Absorption route: absorbed by the intact skin as well as by 
    inhalation and from the gastrointestinal tract. 

    2.1.2 Mode of action: central nervous system stimulant producing 
    convulsions.

    2.1.3 Excretion products: in all mammals, heptachlor is converted to 
    heptachlor epoxide which is stored in the fat or is excreted in the 
    faeces or in the milk of lactating animals.  A minor hydroxylated 
    metabolite is also found in the faeces and in the urine. 

    2.1.4 Toxicity, single dose

          Oral:  LD50 rat (M) 100 mg/kg

                      rat (F) 162 mg/kg

          Dermal:  LD50 rat (M) 195 mg/kg

                        rat (F) 250 mg/kg

         Inhalation:    LC50 rat (4 hour exposure) 200 mg/l

    2.1.5 Toxicity, repeated doses

          Oral:  When heptachlor was fed orally, dissolved in corn oil, to
    groups of two and four dogs at levels of 5 mg/kg and 1 mg/kg body-
    weight respectively, all the animals at the higher dose level died 
    within 21 days.  At the lower dose level, three out of four dogs died 
    within 424 days but one was living at 455 days. 

          Inhalation:  No information.

          Dermal:  Cutaneous application in solution to rabbits at 20 mg/kg
    for 14 days caused the death of all animals. 

          Cumulation of compound:  Heptachlor accumulates in the fat of
    mammals mainly as the epoxide.

          Cumulation of effect:  The chronic toxicity of heptachlor is due
    to the cumulation of the compound in the body.

    2.1.6 Dietary studies

          Short-term:  The addition of heptachlor up to 45 ppm (2.25
    mg/kg/day) to the diet of rats for 140 days produced liver microsomal 
    changes, i.e., enlarged centrolobular cells showing big nuclei with 
    prominent nucleoli, cytoplasmic fat accumulation and occasional 
    aggregration of granules.  These changes regressed after withdrawal of 
    the pesticide. 

          Rats were given 0 (control), 5, 50 or 100 mg/kg per day of 
    heptachlor starting at four months of age and continuing for 200 days 
    or until all the animals died.  By the tenth day, all the animals in 
    the group fed 50 or 100 mg/kg had died.  In the group fed 5 mg/kg, 
    clinical abnormalities typical of central nervous system stimulation 
    were observed but not until after the fiftieth day.  At the end of the 
    experiment, four animals had died compared to only one in the controls. 
    Gross pathology revealed changes in the liver, kidney and spleen. 
                    
          Long-term:  There are no reports of long-term feeding studies
    having been conducted on heptachlor per se. There are, however, a 
    number of studies involving the primary metabolite heptachlor epoxide.  
    These studies are pertinent to the evaluation of the long-term toxicity 
    of heptachlor. 

          Rats were fed dietary levels of 5, 10, 20, 40, 60, 80, 160 or 300 
    ppm (0.25, 0.5, 1, 2, 3, 4, 8 or 15 mg/kg/day) of heptachlor epoxide 
    for up to two years.  All the animals receiving 80 ppm or more died 
    within 2-20 weeks. 

          Female animals given 40 ppm all died within a period of 54 weeks, 
    the male animals on this dose level survived to 104 weeks.  At 20 ppm 
    (1 mg/kg/day) or less, there was no sign of illness but there was an 
    increase in liver weight from diets containing more than 10 ppm (males) 
    or 5 ppm (females) (0.5 or 0.25 mg/kg/day respectively). 

    2.1.7 Supplementary studies of toxicity

          Carcinogenicity

          Rats were fed 5 or 10 ppm (0.25 or 0.5 mg/kg/day) of heptachlor 
    for eight months.  Examination of the liver cells of the groups fed 10 
    ppm (0.5 mg/kg/day) revealed an increase in the smooth endoplasmic 
    reticulum and mitochondria.  Earlier stages of the same development 
    were seen at 5 ppm (0.25 mg/kg/day).  There was a striking difference 
    between these changes and the hepatoma cells obtained from feeding 
    carcinogenic aminoazo compounds. 

          In a number of other studies, rats were fed varying dose levels 
    of heptachlor epoxide and compared to controls.  In all cases, the 
    incidence of tumours of all kinds was no greater in the experimental 
    groups and was not dependent on the level of heptachlor epoxide fed. 

          Reproduction

          When 10 ppm (0.5 mg/kg/day) of heptachlor or its epoxide was fed 
    to rats over three generations, there was no adverse effects on 
    reproductive capacity, growth or survival. 

          In a reproduction study covering three generations, rats were 
    given 6.9 mg/kg of heptachlor daily for three months before mating. The 
    only effect upon reproduction was decrease in litter size. However, 
    cataracts were found in 6.8% of the young and became obvious between 
    the nineteenth and twenty-sixth day.  Among the parents, 15.2% of the 
    animals were affected and the lesions appeared after four to nine 
    months. 

          Teratogenicity 

          When pregnant female rabbits were treated orally with 0 or 5
    mg/kg/day of heptachlor epoxide on days 6 to 11 of gestation, there 
    were no teratogenic effects attributable to the compound. 

          Mutagenicity 

          Male mice were treated with a single oral or intraperitoneal dose 
    of heptachlor at levels of 7.5 or 15.0 mg/kg.  Mating abilities of 
    treated males were unaffected.  Pre-implantation losses and percentages 
    of early resorption for the treated animals were similar to those of 
    controls. 

    2.1.8 Modifications of toxicity

          Pre-treatment of rats with 5 mg/kg/day of heptachlor for three 
    months increased the metabolism of the organophosphorus insecticide 
    fenitrothion. 

    2.2   TOXICOLOGY - MAN

    2.2.2 Dangerous doses

          Single:  It has been estimated that the minimum dermal dose
    required to produce symptoms in man is 46 g for a single dose.

          Repeated:  Repeated dermal exposure at 1.2 g per day has been
    estimated to be the minimum dose level required to produce symptoms.

    2.2.3 Observations of occupationally exposed workers

          No information.

    2.2.4 Observations on exposure of the general population

          From a total diet study in one country, a three-year average
    intake of heptachlor and its epoxide was 0.000031 mg/kg per person.  In 
    another country, the mean concentration of heptachlor epoxide in 
    adipose tissue-was 0.0085 ppm. 

    2.3   TOXICITY TO NON-MAMMALIAN SPECIES

          The entries in these sections are intended to draw attention to
    special risks and to give warnings of any needs for special 
    precautions. 

    2.3.1 Fish

          Toxic to fish.

    2.3.2 Birds

          Toxicity to birds varies.  Toxic to several species, but toxicity 
    to mallards is low (LD50 about 2000 mg/kg).

    2.3.3 Other species

          Toxic to bees.

                                   HEPTACHLOR

    Part 3 - For regulatory authorities

                                                Common name:  heptachlor

                                                Data sheet No. 19
                                                
                                                Date issued:  December 1975

    RECOMMENDATIONS ON REGULATION OF COMPOUND

    3.1   RECOMMENDED RESTRICTION ON AVAILABILITY

          (For definition of categories, see introduction.)

          Liquid formulations of 50% or above, category 3, and over 5%,
          category 4.  Solid formulations over 20%, category 4. All other 
          formulations, category 5. 

            
    3.2   TRANSPORTATION AND STORAGE

          All formulations, categories 3 and 4

          Should be transported or stored in clearly labelled rigid and
    leakproof containers, under lock and key, secure from access by 
    unauthorized persons and children. No food or drink should be stored in 
    the same compartment. 

          Formulations, category 5

          Should be stored in clearly labelled leakproof containers, out of 
    reach of children, away from food and drink. 

    3.3   HANDLING

          All formulations, categories 3 and 4
    
          Full protective clothing (see part 4) should be provided for all 
    handling of the compound.  Adequate washing facilities should be 
    available at all times during handling and should be close to the site 
    of handling.  Eating, drinking and smoking should be prohibited during 
    handling and before washing after handling. 

          Formulations, category 5

          No facilities other than those needed for the handling of any
    chemical need to be required.

    3.4   DISPOSAL AND/OR DECONTAMINATION OF CONTAINERS

          All formulations

          Container must either be burned or crushed and buried below
    topsoil.  Care must be taken to avoid subsequent contamination of water 
    sources.  Decontamination of containers in order to use them for other 
    purposes should not be permitted. 

    3.5   SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS

          All formulations, categories 3 and 4

          Pre-employment and periodic medical examination of workers
    desirable.  Special account should be taken of the workers' mental 
    ability to comprehend and follow instructions.  Training of workers in 
    techniques to avoid contact essential. 
                    
          Formulations, category 5

          Warning of workers to minimize contact essential.

    3.6   ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT

          All formulations

          Pilots and loaders should have special training in application
    methods and recognition of early symptoms of poisoning.  Use of flagmen 
    not recommended.  Flagmen, if used, should wear overalls and be located 
    well away from the dropping zone. 

    3.7   LABELLING

          Formulations

          All formulations, categories 3 and 4

          Minimum cautionary statement

          "Heptachlor is a toxic substance and may cause convulsions.  It 
    is poisonous if swallowed.  It may be absorbed through the skin or 
    inhaled as dusts or mists.  Avoid skin contact; wear protective gloves 
    and clean protective clothing while using the material.  Wash 
    thoroughly with soap and water after using.  Keep the material out of 
    reach of children and well away from foodstuffs, animal feed and their 
    containers." 

          Formulations

          Formulations, category 5

          Minimum cautionary statement

          "This formulation contains heptachlor, a toxic substance which is 
    poisonous if swallowed.  Keep the material out of reach of children and 
    well away from foodstuffs, animal feed and their containers." 

    3.8   RESIDUES IN FOOD

          Maximum residue limits for heptachlor have been recommended by
    the Joint FAO/WHO Meeting on Pesticide Residues.  As these are subject 
    to change at annual reviews, the latest data will be found in the 
    report of the 1972 Joint FAO/WHO Meeting on Pesticide Residues. 
                               
                                   HEPTACHLOR

    Part 4 - Prevention of poisoning in man and emergency aid

                                                Common name:  heptachlor

                                                Data sheet No. 19

                                                Date issued:  December 1975

    4.1   PRECAUTIONS IN USE

    4.1.1 General

          Heptachlor is an organochlorine pesticide of moderate toxicity
    which penetrates the intact skin and is also absorbed by inhalation and 
    from the gastrointestinal tract.  Concentrated formulations should be 
    handled by trained personnel wearing protective clothing. 

    4.1.2 Manufacture and formulation

          T.L.V.

          (A.C.G.I.H.) 0.5 mg/m3;  (USSR) 0.01 mg/m3

          Closed systems and forced ventilation may be required to reduce 
    as much as possible the exposure of workers to the chemical.

    4.1.3 Mixers and applicators

          When opening the container and when mixing, protective 
    impermeable boots, clean overalls, gloves and respirator should 
    be worn.  Mixing, if not mechanical, should always be carried out with
    a paddle of appropriate length.  When spraying tall crops or during
    aerial application, a face mask should be worn as well as an
    impermeable hood, clothing, boots and gloves.  The applicator
    should avoid working in spray mist and avoid contact with the
    mouth.  Particular care is needed when equipment is being washed
    after use.  All protective clothing should be washed immediately after 
    use, including the insides of gloves.  Splashes must be washed
    immediately from the skin or eyes with large quantities of water.  
    Before eating, drinking or smoking, hands and other exposed skin should 
    be washed.
    
    4.1.4 Other associated workers (including flagmen in aerial operations)
          
          Persons exposed to heptachlor and associated with its application 
    should wear protective clothing and observe the precautions described 
    above in 4.1.3 under "Mixers and applicators". 

    4.1.5 Other populations likely to be affected

          With good agricultural practice subject to 4.2 below, other
    populations should not be exposed to hazardous amounts of heptachlor.  
    Total diet studies in two countries have demonstrated that the intake 
    of heptachlor is significantly below the hazard level.  Detectable 
    levels of heptachlor epoxide are found in the fat of the general 
    population. 

    4.2   ENTRY OF PERSONS INTO TREATED AREAS

          Unprotected persons should be kept out of treated areas for at 
    least one day.

    4.3   SAFE DISPOSAL OF CONTAINERS AND SPILLAGE

          Residues in containers should be emptied in a diluted form
    into a deep pit taking care to avoid contamination of ground waters.  
    Decontamination of containers in order to use them for other purposes 
    should not be permitted.  Spillage should be removed as much as 
    possible into a deep dry pit and the remainder washed away with large 
    quantities of water. 

    4.4   EMERGENCY AID

    4.4.1 Early symptoms of poisoning

          Early symptoms of poisoning are headache, dizziness, nausea,
    vomiting, loss of appetite, general malaise and possibly insomnia. 
    Later, convulsions may occur. 

    4.4.2 Treatment before person is seen by a physician, if these symptoms 
          follow exposure

          The person should stop work immediately, remove contaminated
    clothing and wash the affected skin with soap and water, if available, 
    and flush the area with large quantities of water.  If swallowed, 
    vomiting should be induced, if the person is conscious. 

                                   HEPTACHLOR

    Part 5 - For medical and laboratory personnel

                                                Common name:  heptachlor   

                                                Data sheet No. 19          
                                    
                                                Date issued:  December 1975

    5.1   MEDICAL DIAGNOSIS AND TREATMENT OF CASES OF POISONING 

    5.1.1 General information

          An organochlorine pesticide of moderate toxicity which may be
    absorbed through the intact skin as well as by inhalation and from the 
    gastrointestinal tract.  Its mode of action is as a central nervous 
    system stimulant producing convulsions.  It is cumulative in body 
    tissues particularly fat. 

    5.1.2 Symptoms and signs

          There is little information on the symptoms of poisoning by
    heptachlor in man; based upon information with similar compounds, early 
    symptoms of acute poisoning would expect to include headache, nausea, 
    vomiting, general malaise and dizziness.  With more severe poisoning 
    clonic and tonic convulsions might occur with or without the symptoms 
    just mentioned.  Coma may or may not follow the convulsions.  
    Hyperexcitability and hyperirritability would be expected. 

    5.1.3 Laboratory

          Levels of heptachlor epoxide in blood are indicative of
    absorption but the level associated with toxic effects is not known.  
    The presence of heptachlor metabolites in the urine also indicates 
    absorption.  The electroencephalogram may show certain changes. 

    5.1.4 Treatment

          If the pesticide has been ingested, gastric lavage should be
    performed with 2-4 litres of tap water followed by saline purgatives 
    (30 g sodium sulfate in 250 ml of water).  Barbiturates (preferably 
    phenobarbitone or pentobarbitone) or diazepam should be given i.m. or 
    i.v. in sufficient dosage to control restlessness or convulsions.  It 
    may be necessary to give large doses over a period of two weeks in 
    connexion with the syndrome characterized by complete loss of appetite 
    and severe weight loss.  Mechanical respiratory assistance with oxygen 
    may be required.  Calcium gluconate, 10% in 10 ml, should be injected 
    i.v. four hourly. Contraindications are oily purgatives, epinephrine 
    and other adrenegic drugs and central stimulants of all kinds. 

    5.1.5 Prognosis

          If the convulsions are survived, the chances of complete
    recovery are good.  However, in very severe cases, there is a 
    possibility of permanent brain damage secondary to continued anoxia 
    resulting from prolonged convulsions. 

    5.1.6 References of previously reported cases

          The following reference gives methods of treatment used in cases 
    of poisoning: 

          Hayes, W. J. Jr. (1963) "Clinical Handbook of Economic Poisons",
          U.S. Dept. Hlth. Educ. Welfare, Publ. Hlth. Ser. Publ. No. 476, 
          pp. 49, 50, 66, 70.

     5.2  SURVEILLANCE METHODS

          There are no rapid methods for determining the extent of
    absorption of heptachlor prior to the appearance of symptoms.  Levels 
    of heptachlor epoxide in blood and the presence of heptachlor 
    metabolites in urine may possibly be used but no details appear to be 
    available. 

    5.3   LABORATORY METHODS

          References only are given.

    5.3.1 Detection and analysis

          Residues of heptachlor and its epoxide in foodstuffs can be
    determined by the multiresidue methods of the AOAC (U.S. Food and Drug 
    Administration, Pesticides Analytical Manual, 1971) and of de Faubert 
    Maunder et al. (1964), Wood (1969) and Abbott et al. (1969).  All these 
    are gas-chromatographic methods, but involve various clean-up 
    procedures. 

          Heptachlor and its epoxide may be determined in blood along with 
    other organochlorine pesticides, see Dale et al. (1966), Jain et al. 
    (1965). 

    5.3.2 Other tests in cases of poisoning
         
          None.

                                   REFERENCES

    U.S. Food & Drug Administration.
          Pesticide Analytical Manual, Vol. I, 1971, Sections 211, 212

    de Faubert Maunder, M. J., Egan, H., Godly, E. W., Hammond, E.W., 
          Roburn, J. & Thomson, J. Clean-up of Animal Fats and Dairy 
          Products for the Analysis of Chlorinated Pesticide
          Residues. Analyst, 1964, 89, 168

    Wood, N. F. 
          Extraction and Clean-up of Organochlorine Pesticide Residues by 
          Column Chomatrography.  Analyst, 1969, 94, 399

    Abbott, D. C., Holmes, D. C. & Tatton, J. O'G.
          Pesticide Residues in the Total Diet in England and Wales, 1966-
          1967. II. - Organochlorine Pesticide Residues in the Total Diet.   
          J. Sci. Fd Agric., 1969, 20, 245

    Dale, W. E., Curley, A. & Cueto, C.
          Hexane extractable chlorinated insecticides in human blood. Life 
          Sci., 1969, 5, 47

    Jain, N. C., Fontan, C. R. & Kirk, P. L.
          Simplified gas chromatographic analysis of pesticides from blood. 
          J. Pharm. Pharmacol., 1965, 17, 362

    See Also:
       Toxicological Abbreviations
       Heptachlor (EHC 38, 1984)
       Heptachlor (HSG 14, 1988)
       Heptachlor (ICSC)
       Heptachlor (PIM 578)
       Heptachlor (FAO Meeting Report PL/1965/10/1)
       Heptachlor (FAO/PL:CP/15)
       Heptachlor (FAO/PL:1967/M/11/1)
       Heptachlor (FAO/PL:1968/M/9/1)
       Heptachlor (FAO/PL:1969/M/17/1)
       Heptachlor (AGP:1970/M/12/1)
       Heptachlor (WHO Pesticide Residues Series 4)
       Heptachlor (WHO Pesticide Residues Series 5)
       Heptachlor (Pesticide residues in food: 1991 evaluations Part II Toxicology)