Heptachlor
| 1. Heptachlor |
| 1.1 Substance |
| 1.2 Group |
| 1.3 Synonyms |
| 1.4 Identification numbers |
| 1.4.1 CAS number |
| 1.4.2 Other numbers |
| 1.5 Main brand names, Main trade names |
| 1.6 Main manufacturers, main importers |
| 2. SUMMARY |
| 2.1 Main risks and target organs |
| 2.2 Summary of clinical effects |
| 2.3 Diagnosis |
| 2.4 First aid measures and management principles |
| 3. PHYSICOCHEMICAL PROPERTIES |
| 3.1 Origin of the substance |
| 3.2 Chemical structure |
| 3.3 Physical properties |
| 3.3.1 Colour |
| 3.3.2 State/Form |
| 3.3.3 Description |
| 3.4 Hazardous characteristics |
| 4. USES |
| 4.1 Uses |
| 4.1.1 Uses |
| 4.1.2 Description |
| 4.2 High risk circumstance of poisoning |
| 4.3 Occupationally exposed populations |
| 5. ROUTES OF EXPOSURE |
| 5.1 Oral |
| 5.2 Inhalation |
| 5.3 Dermal |
| 5.4 Eye |
| 5.5 Parenteral |
| 5.6 Other |
| 6. KINETICS |
| 6.1 Absorption by route of exposure |
| 6.2 Distribution by route of exposure |
| 6.3 Biological halflife by route of exposure |
| 6.4 Metabolism |
| 6.5 Elimination and excretion |
| 7. TOXICOLOGY |
| 7.1 Mode of action |
| 7.2 Toxicity |
| 7.2.1 Human data |
| 7.2.1.1 Adults |
| 7.2.1.2 Children |
| 7.2.2 Relevant animal data |
| 7.2.3 Relevant in vitro data |
| 7.2.4 Workplace standards |
| 7.2.5 Acceptable daily intake (ADI) |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS |
| 8.1 Material sampling plan |
| 8.1.1 Sampling and specimen collection |
| 8.1.1.1 Toxicological analyses |
| 8.1.1.2 Biomedical analyses |
| 8.1.1.3 Arterial blood gas analysis |
| 8.1.1.4 Haematological analyses |
| 8.1.1.5 Other (unspecified) analyses |
| 8.1.2 Storage of laboratory samples and specimens |
| 8.1.2.1 Toxicological analyses |
| 8.1.2.2 Biomedical analyses |
| 8.1.2.3 Arterial blood gas analysis |
| 8.1.2.4 Haematological analyses |
| 8.1.2.5 Other (unspecified) analyses |
| 8.1.3 Transport of laboratory samples and specimens |
| 8.1.3.1 Toxicological analyses |
| 8.1.3.2 Biomedical analyses |
| 8.1.3.3 Arterial blood gas analysis |
| 8.1.3.4 Haematological analyses |
| 8.1.3.5 Other (unspecified) analyses |
| 8.2 Toxicological Analyses and Their Interpretation |
| 8.2.1 Tests on toxic ingredient(s) of material |
| 8.2.1.1 Simple Qualitative Test(s) |
| 8.2.1.2 Advanced Qualitative ConfirmationTest(s) |
| 8.2.1.3 Simple Quantitative Method(s) |
| 8.2.1.4 Advanced Quantitative Method(s) |
| 8.2.2 Tests for biological specimens |
| 8.2.2.1 Simple Qualitative Test(s) |
| 8.2.2.2 Advanced Qualitative Confirmation Test(s) |
| 8.2.2.3 Simple Quantitative Method(s) |
| 8.2.2.4 Advanced Quantitative Method(s) |
| 8.2.2.5 Other Dedicated Method(s) |
| 8.2.3 Interpretation of toxicological analyses |
| 8.3 Biomedical investigations and their interpretation |
| 8.3.1 Biochemical analysis |
| 8.3.1.1 Blood, plasma or serum |
| 8.3.1.2 Urine |
| 8.3.1.3 Other fluids |
| 8.3.2 Arterial blood gas analyses |
| 8.3.3 Haematological analyses |
| 8.3.4 Interpretation of biomedical investigations |
| 8.4 Other biomedical (diagnostic) investigations and their interpretation |
| 8.5 Overall interpretation of all toxicological analyses and toxicological investigations |
| 8.6 References |
| 9. CLINICAL EFFECTS |
| 9.1 Acute poisoning |
| 9.1.1 Ingestion |
| 9.1.2 Inhalation |
| 9.1.3 Skin exposure |
| 9.1.4 Eye contact |
| 9.1.5 Parenteral exposure |
| 9.1.6 Other |
| 9.2 Chronic poisoning |
| 9.2.1 Ingestion |
| 9.2.2 Inhalation |
| 9.2.3 Skin exposure |
| 9.2.4 Eye contact |
| 9.2.5 Parenteral exposure |
| 9.2.6 Other |
| 9.3 Course, prognosis, cause of death |
| 9.4 Systematic description of clinical effects |
| 9.4.1 Cardiovascular |
| 9.4.2 Respiratory |
| 9.4.3 Neurological |
| 9.4.3.1 Central nervous system (CNS) |
| 9.4.3.2 Peripheral nervous system |
| 9.4.3.3 Autonomic nervous system |
| 9.4.3.4 Skeletal and smooth muscle |
| 9.4.4 Gastrointestinal |
| 9.4.5 Hepatic |
| 9.4.6 Urinary |
| 9.4.6.1 Renal |
| 9.4.6.2 Other |
| 9.4.7 Endocrine and reproductive systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, ear, nose, throat: local effects |
| 9.4.10 Haematological |
| 9.4.11 Immunological |
| 9.4.12 Metabolic |
| 9.4.12.1 Acid-base disturbances |
| 9.4.12.2 Fluid and electrolyte disturbances |
| 9.4.12.3 Others |
| 9.4.13 Allergic reactions |
| 9.4.14 Other clinical effects |
| 9.4.15 Special risks |
| 9.5 Other |
| 9.6 Summary |
| 10. MANAGEMENT |
| 10.1 General principles |
| 10.2 Life supportive procedures and symptomatic/specific treatment |
| 10.3 Decontamination |
| 10.4 Enhanced Elimination |
| 10.5 Antidote treatment |
| 10.5.1 Adults |
| 10.5.2 Children |
| 10.6 Management discussion |
| 11. ILLUSTRATIVE CASES |
| 11.1 Case reports from literature |
| 12. ADDITIONAL INFORMATION |
| 12.1 Specific preventive measures |
| 12.2 Other |
| 13. REFERENCES |
| 14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES) |
HEPTACHLOR
International Programme on Chemical Safety
Poisons Information Monograph 578
Chemical
1. Heptachlor
1.1 Substance
Heptachlor
1.2 Group
Chlorinated "cyclodiene" insecticide
1.3 Synonyms
Agroceres;
3-Chlorochlordene;
Drinox;
Drinox H-34;
E 3314;
ENT 15,152;
Eptachloro;
GPKh;
H-34;
Heptachloor;
Heptachlore;
Heptagran;
Heptomul;
Rhodiachlor;
1.4 Identification numbers
1.4.1 CAS number
76-44-8
1.4.2 Other numbers
RTECS PC 0700000
ICSC 0743
UN 2761
EC 602 - 046 - 00 - 2
NCI C - 00180
Standard Transportation Number 4960630
RCRA Waste Number: P 059
DOT ID & Guide: 2761 151
Transport Emergency Card: TEC (R) - 61 641b
1.5 Main brand names, Main trade names
Drinox;
Heptagram;
Heptamul;
1.6 Main manufacturers, main importers
Velsicol Chemical Corp.
2. SUMMARY
2.1 Main risks and target organs
Heptachlor is a central nervous system stimulant. The
liver is the other organ significantly affected by
heptachlor.
2.2 Summary of clinical effects
Poisoning by the heptachlor and other cyclodiene
insecticides is more likely to begin with the sudden onset of
convulsions preceeded by vomiting. Seizures caused by
cyclodienes may appear as long as 48 hours after exposure,
and then may recur periodically over several days following
the initial episode. Tonic-clonic convulsions usually are
accompanied by confusion, incoordination, excitability, or,
in some instances coma and hypotension. Respiratory failure
may also occur. At non-lethal acute exposures, heptachlor is
hepatotoxic.
2.3 Diagnosis
The diagnosis is based on the history of exposure
(dermal, inhalational or gastrointestinal) and signs of
central nervous system hyperexcitability including
seizures.
Blood levels are not clinically useful, but could help to
confirm the exposure, although treatment will be determined
by clinical status.
The principal method for its qualitative and quantitative
determination is gas-liquid chromatography with electron
capture detection.
2.4 First aid measures and management principles
Treatment is symptomatic. It is aimed at controlling
convulsions, coma, and respiratory depression.
Cardio-vascular function must be observed.
To control convulsions use clonazepam IV or diazepam IV or
per rectum. Intravenous barbiturates may also be used. Once
convulsions are controlled further treatment with Phenytoin
or Sodium Valproate should be continued as long as
required.
Do not give fats, oils or milk since these will enhance
absorption from the intestinal tract.
If the patient is conscious and a large quantity of
heptachlor has been ingested not more than 1 hour ago perform
gastric lavage only after tracheal intubation. This should be
followed by intragastic administration of a large amount of
activated charcoal slurry and a laxative.
In the case of skin contact remove and discard contaminated
clothing and wash exposed skin including hair and nails with
(soap and) copious amounts of water.
Opiates, adrenaline and nor-adrenaline should only be
given with extreme caution. Aminophylline, atropine or
oily laxatives should not be administered.
Rescuers must take precautions to avoid personal
exposure.
3. PHYSICOCHEMICAL PROPERTIES
3.1 Origin of the substance
A synthetic product (Budavari et al., 1996)
3.2 Chemical structure
Structural names
1, 4, 5, 6, 7, 8, 8 - Heptachloro - 3a, 4, 7, 7a - tetrahydro
- 4, 7 - methanoindene (IUPAC)
1, 4, 5, 6, 7, 8, 8 - Heptachloro - 3a, 4, 7, 7a -
tetrahydro - 4, 7 - methano - 1H - indene
Molecular formula C10H5CL7
Molecular weight 373.4
3.3 Physical properties
3.3.1 Colour
White to light tan
3.3.2 State/Form
Solid crystals
3.3.3 Description
Heptachlor is a white to light tan color solid
crystals.
It has a camphor - like odor (NIOSH, 1998)
Solubility: In water 0.056 mg/L
( 25 - 29°C)
Soluble in many organic solvents, e.g. in acetone 75,
benzene 106, xylene 102, cyclohexanone 119,
carbontetrachloride 113, ethanol 4.5 ( all in
g/100mL) (Tomlin, 1994).
Boiling Point: at 0.2 kPa: 135 to 145°C
(IPCS/CEC, 1999)
Melting Point : 95 to 96°C (IPCS/CEC,
1999)
Relative Density: (water = 1): 1.65 to 1.67
Vapour Pressure: Pa at 25°C: 0.053
Octanol/water partition coefficient as log Pow: 5.27
to 5.44
3.4 Hazardous characteristics
The substance decomposes on heating above 160°C
producing toxic fumes including hydrogen chloride and other
chlorine fumes. Reacts with strong oxidants. Attacks metals
(IPCS/CEC,1999).
4. USES
4.1 Uses
4.1.1 Uses
Pesticide for use against invertebrate animals
4.1.2 Description
Heptachlor is a non-systemic insecticide with
contact, stomach, and some respiratory action. It is
used to control termites, ants and soil insects in
cultivated and non cultivated soils. Applied as a seed
treatment, soil treatment, or directly to foliage.
Also used for control of household insects (Tomlin,
1994).
Heptachlor is registered in the United States only
for underground use in power lines for fire ants
(Reigart and Roberts, 1999).
Heptachlor is on the list of 12 persistent
organochlorine pesticides (POP) identified by UNEP
Governing Council, for which international action is
required to reduce the risks to human health and the
environment. It is also subject to the prior informed
consent procedure of UNEP and FAO.
4.2 High risk circumstance of poisoning
Accidental poisoning of children by heptachlor stored in
the home or garage.
Accidental exposure among formulating plant workers.
Suicide attempts.
Exposure of the general population may occur in dwellings
treated with heptachlor for termite control.
Individuals with a history of convulsive disorders would be
expected to be at increased risk from exposure (Mackison et
al., 1981).
Individuals with diseases of kidney, liver and lung
(ITII,1988).
4.3 Occupationally exposed populations
Factory workers involved in syntheses of heptachlor.
Workers involved in formulating and dispensing
heptachlor.
Public health workers involved in pest control.
5. ROUTES OF EXPOSURE
5.1 Oral
Ingestion occurs through accidental or deliberate
ingestion or accidental ingestion of contaminated
foodstuffs.
5.2 Inhalation
Heptachlor vapor is absorbed by inhalation.
5.3 Dermal
Heptachlor is readily absorbed after dermal contact, and
the absorbtion is variable depending on the type on the type
of solvent used.
5.4 Eye
Exposure to vapors, dust and aerosols.
5.5 Parenteral
Accidental or intentional.
5.6 Other
No data available.
6. KINETICS
6.1 Absorption by route of exposure
Heptachlor is readily absorbed by the skin as well as by
the lungs and gastrointestinal tract. It is only about twice
as toxic orally as dermally. Rats retained 77% of heptachlor
that they inhaled during a 30-minute period (Stubblefiled &
Dorough, 1979).
6.2 Distribution by route of exposure
Heptachlor is readily metabolized into heptachlor
epoxide in mammals. Heptachlor epoxide is the most persistent
metabolite. It is mainly stored in adipose tissue, but also
in liver, kidney and muscle. In rats, heptachlor epoxide was
found in tissues, urine and faeces while the hydrophilic
metabolite (1-exohydroxychlordene epoxide) was only detected
in urine. Rats fed diets containing 30 mg heptachlor/kg were
shown to have a maximum heptachlor epoxide concentrations in
adipose tissue within 2 to 4 weeks. Twelve weeks after
cessation of exposure, heptachlor completely disappeared from
the adipose tissue. The highest concentration of heptachlor
epoxide was found in adipose tissue; markedly lower amounts
were found in the liver, kidney and muscle; and none in the
brain (FAO/WHO, 1967). A similar pattern of distribution was
found in the dog (Radomski & Davidow, 1953).The accumulation
of heptachlorepoxide in the adipose tissue of laying hens
was demonstrated by Kan & Tuinstra (1976). The accumulation
ratio (level in adipose tissue/level in feed) was 6 for
heptachlor.
6.3 Biological halflife by route of exposure
When broiler chickens were fed heptachlor in
concentrations of 0.01, 0.03, 0.1 and 0.3 mg/kg diet for the
first 8 weeks of life, residue concentrations decreased by
about half in the first 4 weeks after cessation of exposure
(Walgstaff et al., 1980).
6.4 Metabolism
Heptachlor is metabolized readily to heptachlor epoxide
in mammals (Hayes, 1963). Heptachlor epoxide is metabolized
quickly and is the most persistent metabolite. Klein et al,
(1968) showed that the metabolism of heptachlor in rats gave
rise to heptachlor epoxide and hydrophilic metabolite,
1-exo-hydroxychlorene epoxide. Another metabolite of
heptachlor, a dehydrogenated derivative of 1-hydroxy -2,
3 - epoxy chlordene was identified in rat faeces by
(Matsumura & Nelson, 1971).
6.5 Elimination and excretion
Heptachlor epoxide is excreted in faeces and urine while
the hydrophilic metabolite is detected only in urine. In
rabbits, approximately 80% of the urinary radioactivity was
derived from the hydrophilic metabolite and 20% from the
epoxide (IPCS, 1984).
7. TOXICOLOGY
7.1 Mode of action
Chlorinated hydrocarbon insecticides act by altering the
electrophysiological and associated enzymatic properties of
nerve cell membranes, causing a change in the kinetics of Na+
and K+ ion flow through the membrane. Disturbances of calcium
transport of Ca+2-ATPase activity may also be involved, as
well as phosphokinase activities (Hayes & Laws, 1991).
The cyclodiene compounds antagonize the action of the
neurotransmitter gamma-aminobutyric acid (GABA), which
induces the uptake of chloride ions by neurons. The blockage
of this activity by cyclodiene insecticides results in only
partial repolarization of the neuron and a state of
uncontrolled excitation (Klassen & Watkins, 1999).
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
There is no information on cases of
accidental or suicide poisoning with
heptachlor.
7.2.1.2 Children
There is no information on the case
of accidental or suicide poisoning with
heptachlor.
7.2.2 Relevant animal data
Acute oral LD50 for rats100 mg/kg (IPCS, 1998)
Acute oral LD50 for guinea pigs116 mg/kg
(Tomlin, 1994)
Acute oral LD50 for mice 68 mg/kg (Tomlin, 1994)
Acute percutaneous LD50 for rabbits >2000 mg/kg
Acute percutaneous LD50 for rats 119-250 mg/kg
Inhalation LC50 (4 hour) (for rats exposed to
heptachlor in an aerosol > 2.0 but <200 mg/L
air.
NOEL in rats 7 mg/kg diet
in dogs 1 mg/kg diet
( 2 generation reproduction
study)
7.2.3 Relevant in vitro data
Heptachlor induced human myeloblastic leukemia
has been studied. Similar to 12 - 0
- tetradecanoylphorbol, 13 - acetate, a known tumor
promoter, heptachlor induced cell adherence and
formation of extended cytoplasmic pseudopodia in ML -
1 cells. The growth of ML -1 was slightly stimulated
by low concentrations (<30 nM) of heptachlor. A dose
responsive cell death was also observed with ML - 1
cells were treated with heptachlor at concentrations
greater than 80 uM. Examination by light microscopy of
the cells treated with 80 uM heptachlor revealed a
gradual appearance of differentiation characteristics
in the culture. On day 3 of the treatment, 41% of the
cells remained unchanged as ML -1, 39% of the cells
showed changes and apparent cells differentiation, and
20% of the cells were induced to differentiate to
monocyte- or macrophage- like cell type. Electron
microscopy also revealed cellular differentiation and
the presence of monocyte - and macrophage-like cell
types (22%) was confirmed by positive esterase
staining (Chuang et al., 1991)
7.2.4 Workplace standards
OSHA PEL TWA 0.5 mg/m3 (skin) (ACGIH 2000)
TLV 0.05 mg/m3 (as TWA)
NIOSH REL Ca TWA 0.5 mg/m3 skin
NIOSH IDLH Potential occupational
carcinogen 35 mg/m3
7.2.5 Acceptable daily intake (ADI)
ADI 0.0001 (PTDI) (IPCS, 1997)
7.3 Carcinogenicity
Case reports of leukaemia and other blood dyscrasias
have been associated with exposure to chlordane/heptachlor,
primarily in domestic situations (Furie & Trubowitz,
1976).
Mortality from lung cancer was slightly elevated in two
cohort studies of pesticide applicators; and one of
chlordane/heptachlor manufacturers. Termite control operators
probably have greater exposure to chlordane than other
pesticide applicators. However, in one study of applicators,
the excess occurred only among workers who were not engaged
in termite control (Mac Mahon et al., 1988). In the other
study of applicators, the relative risk for lung cancer among
workers engaged in termite control was similar to that of
workers engaged in other pest control. Inconsistencies in
these findings make it difficult to ascribe the excesses to
exposure to chlordane.
Small excess risks for other cancers, including leukaemia,
non-Hodgkin's lymphoma and soft tissue sarcoma and cancers of
the brain, skin, bladder and stomach were observed, with
little consistency among studies (IARC, 1991).
Chlordane, technical-grade chlordane, heptachlor,
technical-grade heptachlor, heptachlorepoxide and a mixture
of heptachlor and heptachlorepoxide have been tested for
carcinogenicity by oral administration in several strains of
mice and rats. These studies uniformly demonstrated increases
of hepatocellular neoplasms in mice of each sex. Increases in
the incidence of thyroid follicular-cell neoplasms were
observed in rats treated with chlordane and technical-grade
heptachlor. An increased incidence of malignant fibrous
histiocytomas was observed in one study in male rats treated
with chlordane. A small increase in the incidence of liver
adenomas was seen in one study in male rats treated with
technical grade chlordane.
Heptachlor has been evaluated by the International Agency for
Research on Cancer (IARC, 1979; 1987; 1991). It was concluded
that there is inadequate evidence in humans for the
carcinogenicity of heptachlor and sufficient evidence in
experimental animals for the carcinogenicity of heptachlor.
The overall evaluation of IARC on heptachlor is Group 2B
(possibly carcinogenic to humans).
7.4 Teratogenicity
Heptachlor was not tetratogenic in the tests conducted
but at higher exposure levels it may interfere with
reproduction and the viability of the offspring (IPCS,
1984).
7.5 Mutagenicity
Gene mutation assays indicate that heptachlor is not
mutagenic in bacteria (Probst et al, 1981; Shirasu et al,
1976; Moriya et al., 1983) or mammalian liver cells (Telang
et al., 1982). Negative results were reported in two dominant
lethal assays using male germinal cells (Epstein et al.,
1972; Arnold et al., 1977). DNA repair assays indicate that
heptachlor is not genotoxic in rodent hepatocytes (Maslansky
& Williams, 1987; Probst et al., 1981) but showed qualitative
evidence of unscheduled DNA synthesis in human fibroblasts
(Ahmed et al., 1977).
7.6 Interactions
Phenobabital pretreatment significantly enhance the
metabolism of heptachlor in rats. It causes a 6 to 11-fold
increase in the liver heptachlor epoxidase (Miranda et al.,
1973).
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative ConfirmationTest(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their
interpretation
8.5 Overall interpretation of all toxicological analyses and
toxicological investigations
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Heptachlor is a potent stimulant of the central
nervous system. Poisoning by the cyclodienes is more
likely to begin with the sudden onset of convulsions,
and is often not preceded by the premonitory
manifestations seen with DDT. Seizures caused by
cyclodienes may appear as late as 48 hours after
exposure, and then may recur periodically over several
days following the initial episode (Reigart & Roberts,
1999).
9.1.2 Inhalation
Heptachlor may be absorbed by inhalation.
Symptoms are basically the same as by
ingestion.
9.1.3 Skin exposure
Is a significant route of exposure. Symptoms
are basically the same as by ingestion.
9.1.4 Eye contact
Heptachlor is an eye irritant.
9.1.5 Parenteral exposure
No data available.
9.1.6 Other
No data available.
9.2 Chronic poisoning
9.2.1 Ingestion
No data available.
9.2.2 Inhalation
No data available
9.2.3 Skin exposure
No data available
9.2.4 Eye contact
No data available
9.2.5 Parenteral exposure
No data available
9.2.6 Other
No data available.
9.3 Course, prognosis, cause of death
Typical, severe poisoning by heptachlor is characterised
by onset of violent convulsions within 0.5 to 3 hours and
either death or the start of recovery within a few hours to a
day (Hayes & Laws, 1991). Seizures caused by heptachlor may
appear as long as 48 hours after exposure, and then may recur
periodically over several days following the initial episode
(Reigart & Roberts, 1999). Nausea and vomiting occur before
signs of central nervous system activity has appeared.
Convulsions may and may not be the first clear indication of
illness. Convulsions usually are accompanied by confusion,
incoordination, excitability, or, in some instances, coma.
Respiratory failure may also occur. Death may follow
respiratory failure (IPCS, 1984).
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Arrhythmias may occur owing to myocardial
sensivity to catecholamines (Olson, 1999).
9.4.2 Respiratory
The effects of heptachlor on the respiratory
system are secondary to the effects on the nervous
system (Hayes & Laws, 1991).
9.4.3 Neurological
9.4.3.1 Central nervous system (CNS)
Central nervous system excitation is
the primary toxic effect seen in humans.
Convulsions can occur suddenly after a
massive overdose. Convulsions often last
about a minute and may recur at intervals of
about 5 min. Convulsions usually are
accompanied by confusion, incoordination,
excitability, or, in some instances, coma.
9.4.3.2 Peripheral nervous system
Paraesthesia, No further data
available.
9.4.3.3 Autonomic nervous system
No data available.
9.4.3.4 Skeletal and smooth muscle
Rhabdomyolysis may occur.
9.4.4 Gastrointestinal
Nausea and vomit may occur.
9.4.5 Hepatic
Heptachlor is a potent inducer of hepatic
microsomal enzymes (Hart et al., 1963).
Proliferation of the smooth endoplasmatic reticulum
and induction of the mixed-function oxidases in liver
cells is one of the earliest indications of prolonged
exposure to heptachlor (IPCS, 1984).
9.4.6 Urinary
9.4.6.1 Renal
After ingestion renal injury may
develop (Olson, 1999)
9.4.6.2 Other
No data available.
9.4.7 Endocrine and reproductive systems
A dosage of 6.9 mg/kg/day for 3 days
significantly reduced fertility of rats and also the
survival of young during the first weeks by about one
third; this effect was found more sensitive than tests
of the liver and kidney function (Mestizovā & Beno,
1966, Mestitzovā 1967). Essentially similar results
were reported for dosages of 5 and 10 mg/kg/day, and
some fetal anomalies as well as resorptions were
encountered. A dosage of 1 mg/kg/day apparently was
harmless to reproduction (Rosival et al., 1972)
Yamaguchi et al, (1987) found no increases in fetal
mortality or malformation when heptachlor was
administered to pregnant rats (days 7 - 17) at doses
up to 20 mg/kg/day.
Induction of hepatic microsomal enzymes may result in
hormonal disturbances because of accelerated
metabolism of endogenous steroids (Street et
al.,1969).
Accumulation of heptachlor, a major component of a
technical chlordane in ovary, uterus and adrenals in
non-pregnant rats within 30 after an oral dose of 120
mg/kg heptachlor. In pregnant rats, levels were
markedly elevated in the uterus compared to non
pregnant rats; the higher accumulation is believed to
be a result of a slower metabolic turnover of
heptachlor. These results indicate that chlordane or
some of its components/metabolites have an increased
affinity towards reproductive organs during pregnancy
and may have potential to adversely affect
reproductive processes (Rani et al., 1992).
9.4.8 Dermatological
Skin irritation results from extensive contact
with organochlorine pesticides or with the white
petroleum distillate vehicles.
9.4.9 Eye, ear, nose, throat: local effects
It was reported by Mestitzova (1967) that
heptachlor at a dosage of 6.9 mg/kg/day increased the
incidence of cataracts in rats, especially young once
born to treated mothers.
9.4.10 Haematological
Blood disorders (leukemias, production
defects, and thrombocytopenie purport) have been
catalogued following home termite treatment with
chlordane and heptachlor, but proof of a direct effect
is lacking (Epstein & Osonoff, 1987).
9.4.11 Immunological
No data available
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
Metabolic acidosis may
occur.
9.4.12.2 Fluid and electrolyte disturbances
No data available
9.4.12.3 Others
No data available
9.4.13 Allergic reactions
No data available
9.4.14 Other clinical effects
9.4.15 Special risks
Pregnancy
In one study with rats chlordane or some of its
components/metabolites show an increased affinity
towards reproductive organs during pregnancy and may
have potential to adversely affect reproductive
processes. See 9.4.7 (Rani et al., 1992)
Breast feeding
Several investigators detected heptachlor epoxide
levels ranging from non-detectable to 0.46 ppm in
human milk (Kroger,1972; Polishuk et al., 1977;
Strassman & Kutz, 1977; Savage et al., 1981)
Concentrations of heptachlor in the milk of women in
various populations have been reported. Restrictions
on the use of the organochlorine insecticides (DDT,
aldrin, dieldrin, heptachlor and chlordane) have
resulted in reduced concentrations of these chemicals
in breast milk and adipose tissue as compared with
previous studies. The concentration of heptachlor in
breast milk did not pose a hazard to breast fed
infants (Stevens et al., 1993). In one study of 1436
women residing in the United states heptachlor was
found in less than 2%, but heptachlor epoxide, its
metabolite, was found 63% of the samples (detection
limit 91.4 ppb for heptachlor epoxide) (Savage et
al., 1981).
9.5 Other
No data available
9.6 Summary
10. MANAGEMENT
10.1 General principles
The condition of the patient in a particular case is
decisive whether the first attention should be given to
removal of the poison or to sedation of the patient.
Treatment is symptomatic, aimed at controlling convulsions,
coma, and respiratory depression.
Cardiovascular function needs to be observed. If heptachlor
has been ingested less than one hour ago, gastric lavage may
be indicated preceded by endotracheal intubation followed by
activated charcoal slurry.
Opiates should only be administered with extreme caution
because of their depressive effects on the respiratory
centre. Adrenaline and nor-adrenaline should only be
administered with extreme caution, because they may sensitise
the myocardium and thus provoke serious cardiac arrhythmias.
Aminophylline, atropine or oily laxatives should not be
administered.
10.2 Life supportive procedures and symptomatic/specific treatment
Make a proper assessment of airway, breathing,
circulation and neurological status of the patient.
Monitor vital signs.
Maintain a clear airway. Support ventilation using
appropriate mechanical device. Administer oxygen.
Open and maintain at least one IV route. Administer IV fluids
if necessary.
To control convulsions use clonazepam IV or diazepam IV or
per rectum. Intravenous barbiturates may also be used.Once
convulsions are controlled further treatment with Phenytoin
or Sodium Valproate should be continued for a further two
to four weeks. (See the Treatment Guide on Convulsions).
Monitor blood pressure and ECG. Control cardiac dysrrhythmias
with proper drug regimen and/or electrophysiologic
procedures.
If the patient vomited spontaneously, monitor respiratory
functions and watch for signs of pulmonary aspiration.
10.3 Decontamination
Skin contact
Remove and discard contaminated clothing. Wash exposed skin
including hair and nails with (soap and) copious amounts of
water.
Eye contact
Irrigate exposed eyes with copious amounts of water or
saline. Saline is preferable but do not delay the irrigation
if only water is readily available.
Ingestion
Inducing vomiting is contraindicated because of the risk of
abrupt onset of seizures. If the patient is conscious perform
gastric lavage for large ingestion, avoiding aspiration into
the lungs. This should be followed by intragastric
administration of a large amount of activated charcoal slurry
containing 50 to 200g of powder . Do not give fats, oils or
milk as these will enhance poison absorption from the
intestinal tract.
Gastric lavage is indicated if patient seen within 1 hour of
ingestion.
In the case of ingestion of a solution, or an emulsifiable
concentrate, a risk of chemical pneumonitis following
aspiration exist.
10.4 Enhanced Elimination
Enhanced elimination is not indicated because of the
large volume of distribution of chlorinated hydrocarbon
insecticides.
10.5 Antidote treatment
10.5.1 Adults
There is no specific antidote
10.5.2 Children
There is no specific antidote.
10.6 Management discussion
Clonazepam or diazepam are drugs of first choice, but
also barbiturates may be helpful administered slowly by
intravenous or intramuscular injection , e.g. phenobarbitone
(Shell Agriculture, 1990). Major side effects of the
treatment with barbiturates are sedation, respiratory
depression, hypotension, shock, apnoea and laryngospasm
(KNMP, 1996).
When convulsions are under control and do not recur, it is
recommended that treatment be continued with regular
antiepileptic drugs such as Phenytoin (or Sodium
Valproate), for 2 to 4 weeks (Shell Agriculture,
1990).
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
12. ADDITIONAL INFORMATION
12.1 Specific preventive measures
Rescuers must take precautions not to contaminate
themselves.
The manufacture of heptachlor has ceased in many countries.
Disposal of any remaining stocks should be done with care to
avoid contamination of the environment. Disposal can be done
by burning the remaining stock in a proper incinerator
designed for chlorinated hydrocarbon insecticide waste
disposal. Seek further advice from the local distributor or
poisons centre.
12.2 Other
Heptachlor is fairly stable to light and moisture and
it is not readily dehydrochlorinated. Its half-life in the
soil in temperate region ranges between 3/4 - 2 years,
depending on the type of soil, and may be less in tropical
regions. It is not likely to penetrate into groundwater but
contamination of surface water and sludge can occur. Several
metabolites, formed by microbial action, have been found in
soil, sludge and water. Epoxidation is an important
metabolic route leading to heptachlor epoxide, which is of
comparable toxicity to heptachlor but more stable in
biological systems.
Bioaccumulation and biomagnification occur and
bioconcentration factors of 200 - 37000X have been reported
from water into hydrobiota.
Heptachlor has been shown to be a toxic for aquatic life, but
its toxicity is highly species variable. Marine crustacea and
younger life stages both fish and invertebrates are most
sensitive. Insufficient information is available on its
toxicity for terrestrial species (IPCS, 1984).
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14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Author:
Dr Nida Besbelli
IPCS
World Health Organization
CH-1211 Geneva 27,
Switzerland
Telephone 41 22 791 4287
Facsimile 41 22 791 4848
E-mail besbellin@who.ch
Prepared: June 2000
Review:
Janusz Szajewski, MD
Warsaw Poisons Centre
Poland
Telephone 48 22 839 0677
Facsimile 48 22 839 0677
E-mail szajewsk@waw.pdi.net
Peer review: INTOX 12 Meeting, 7 - 11 November 2000
Drs J. Szajewski, C.Alonzo, R. Fernando.