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