| 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|
| 2.1 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|
| 4.1 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|
| 6.1 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|
| 7.1 Mode of action|
| 7.2 Toxicity|
| 7.2.1 Human data|
| 18.104.22.168 Adults|
| 22.214.171.124 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|
| 126.96.36.199 Toxicological analyses|
| 188.8.131.52 Biomedical analyses|
| 184.108.40.206 Arterial blood gas analysis|
| 220.127.116.11 Haematological analyses|
| 18.104.22.168 Other (unspecified) analyses|
| 8.1.2 Storage of laboratory samples and specimens|
| 22.214.171.124 Toxicological analyses|
| 126.96.36.199 Biomedical analyses|
| 188.8.131.52 Arterial blood gas analysis|
| 184.108.40.206 Haematological analyses|
| 220.127.116.11 Other (unspecified) analyses|
| 8.1.3 Transport of laboratory samples and specimens|
| 18.104.22.168 Toxicological analyses|
| 22.214.171.124 Biomedical analyses|
| 126.96.36.199 Arterial blood gas analysis|
| 188.8.131.52 Haematological analyses|
| 184.108.40.206 Other (unspecified) analyses|
| 8.2 Toxicological Analyses and Their Interpretation|
| 8.2.1 Tests on toxic ingredient(s) of material|
| 220.127.116.11 Simple Qualitative Test(s)|
| 18.104.22.168 Advanced Qualitative Confirmation Test(s)|
| 22.214.171.124 Simple Quantitative Method(s)|
| 126.96.36.199 Advanced Quantitative Method(s)|
| 8.2.2 Tests for biological specimens|
| 188.8.131.52 Simple Qualitative Test(s)|
| 184.108.40.206 Advanced Qualitative Confirmation Test(s)|
| 220.127.116.11 Simple Quantitative Method(s)|
| 18.104.22.168 Advanced Quantitative Method(s)|
| 22.214.171.124 Other Dedicated Method(s)|
| 8.2.3 Interpretation of toxicological analyses|
| 8.3 Biomedical investigations and their interpretation|
| 8.3.1 Biochemical analysis|
| 126.96.36.199 Blood, plasma or serum|
| 188.8.131.52 Urine|
| 184.108.40.206 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|
| 220.127.116.11 Central nervous system (CNS)|
| 18.104.22.168 Peripheral nervous system|
| 22.214.171.124 Autonomic nervous system|
| 126.96.36.199 Skeletal and smooth muscle|
| 9.4.4 Gastrointestinal|
| 9.4.5 Hepatic|
| 9.4.6 Urinary|
| 188.8.131.52 Renal|
| 184.108.40.206 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|
| 220.127.116.11 Acid-base disturbances|
| 18.104.22.168 Fluid and electrolyte disturbances|
| 22.214.171.124 Others|
| 9.4.13 Allergic reactions|
| 9.4.14 Other clinical effects|
| 9.4.15 Special risks|
| 9.5 Other|
| 9.6 Summary|
| 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|
|14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)|
International Programme on Chemical Safety
Poisons Information Monograph 574
Chlorinated "cyclodiene" insecticide
1.4 Identification numbers
1.4.1 CAS number
1.4.2 Other numbers
Standard Transportation Number 49 131 70
EPA Hazardous Waste Number UO36
DOT ID & Guide 2762 131
Transport Emergency Card: TEC(R)-61G41c
Chlordane [technical grade] CAS12789-03-6
trans-Chlordane CAS 5103-74-2
gamma-Chlordane CAS 5566-34-7
1.5 Main brand names, Main trade names
1.6 Main manufacturers, main importers
Velsicol Chemical Corp.
2.1 Main risks and target organs
Chlordane is a central nervous system stimulant. The
liver and the kidney are the other organs significantly
affected by chlordane.
2.2 Summary of clinical effects
Poisoning by the chlordane 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.
The diagnosis is based on the history of exposure
(dermal, inhalational or gastrointestinal) and signs of
central nervous system hyperexcitability including
Blood levels are not clinically useful, but could help to
confirm the exposure. Treatment will be determined by
Analysis is difficult because of the complex nature of
chlordane. 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
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
chlordane has been ingested not more than one 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 and 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
3. PHYSICOCHEMICAL PROPERTIES
3.1 Origin of the substance
A synthetic product (Budavari et al., 1996).
3.2 Chemical structure
Molecular formula C10H6Cl8
Molecular weight 409.8
3.3 Physical properties
Technical chlordane is a viscous, amber
It has a pungent, chlorine like odor (NIOSH, 1998)
Solubility: It is insoluble in water but soluble in
most organic solvents including acetone,
cyclohexanone, ethanol, deodorized kerosene,
isopropanol, trichloroethylene (Tomlin, 1994).
Boiling point at 0.27 kPa: 175 °C (IPCS/CEC,
Melting point: 103 to 105 °C (IPCS, 1988)
Relative density (water=1): 1.59-1.63 (Budavari et
Vapour pressure, Pa at 25 °C: 0.0013 (IPCS/CEC,
Octanol/water partition coefficient as log Pow: 2.78
Viscosity 69 Poises at 25 °C (Budavari et al.,
3.4 Hazardous characteristics
The substance decomposes on heating and/or on burning
and on contact with bases producing toxic fumes including
chlorine, hydrogen chloride, and phosgene. Attacks iron,
zinc, plastics, rubber and coatings (IPCS/CEC, 1999).
Above 56 °C explosive vapor/air mixtures may be formed.
Explosion hazard will depend on the solvent used or on the
characteristics of the dust.
Pesticide for use against invertebrate animals
Chlordane is a persistent, non-systemic,
contact and ingested insecticide with some fumigant
action. It is used on land against formicidae,
coleoptera, noctuidae larvae, saltatoria, subterranean
termites (including Coptotermes spp.) and many other
insect pests. It also controls household insects,
pests of man and domestic animals, is used as a wood
preservative, a protective treatment for underground
cables and to reduce earthworm populations in lawns.
It may be applied to soil, directly to foliage or as a
seed treatment (Tomlin, 1994).
All U.S registrations of chlordane have been cancelled
(Reigart & Roberts, 1999).
Chlordane is on 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 can occur in children by chlordane
stored in the home or garage.
Accidental exposure can occur among formulating plant
Exposure of the general population may occur in dwellings
treated with chlordane for termite control.
Individuals with a history of convulsive disorders would be
expected to be at increased risk from exposure (Mackison et
4.3 Occupationally exposed populations
Factory workers involved in syntheses of
chlordane,workers involved in formulating and dispensing
chlordane and public health workers involved in pest
5. ROUTES OF EXPOSURE
Ingestion occurs through accidental or deliberate
ingestion or accidental ingestion of contaminated
Chlordane vapor is absorbed by inhalation.
Chlordane is readily absorbed after dermal contact, and
the absorption is variable depending on the type on the type
of solvent used.
Exposure to vapors, dust and aerosols.
No data available.
No data available
6.1 Absorption by route of exposure
In studies on 4 male rabbits, a combination of
14C-alpha and gamma-chlordane (app. 1700 mg of each,
administered orally in 4 doses at 4-day intervals), was well
absorbed (Balba & Saha, 1978). Rats that breathed [14C]
chlordane vapor for 30 min retained 77% of the total inhaled
(Stubbfield & Dorough, 1979).
6.2 Distribution by route of exposure
Studies using radio-labelled chlordane showed that after
oral administration, the radioactivity was well distributed
in tissues of rats (Barnett & Dorough, 1974) and rabbits
(Balba & Saha, 1978). Rats, whether being treated with single
oral doses of chlordane or fed diets containing this
compound, retained the highest levels of residues in adipose
tissue, followed by the liver, kidney, brain and muscle. More
of the gamma-isomer was retained than of the alpha isomer.
The tissue distribution of chlordane in rabbits was found to
be similar to that in rats (Poonawalla & Korte, 1971; Balba &
Human milk samples obtained from 1436 women residing in
United States were analyzed by GLC . While chlordane was not
detected in any of the milk samples, its metabolite
oxychlordane was found above the detection limit (95.8 ppb)
in 74% of the samples (Savage et al., 1981).
6.3 Biological halflife by route of exposure
Serum half-life of 88 days was reported in one child
(Aldrich & Holmes, 1969). In another study, a half-life of 34
days for the elimination of chlordane was calculated from
kinetic studies of a patient who accidentally consumed a
chlordane-containing pesticide (Olanoff et al., 1983).
Chlordane is metabolized very slowly (Gosselin et al.,
1984). Most metabolites of chlordane are far less toxic than
the parent material, but oxychlordane is more toxic with a
LD50 in rats of 19.1 mg/kg (FAO/WHO, 1971).
In vivo and in vitro studies in rats have revealed two routes
of biotransformation of chlordane and shown that the
metabolites include trans-chlordane,
chlorohydrin, and 1,2-trans-dihydroxydihydrochlordene, as
well as metabolites of heptachlor (Tashiro & Matsumura, 1977;
Briemfield & Street 1979). In vitro studies showed that the
livers of rat and humans had almost identical ability to
degrade chlordane, except that human liver has little
capacity to convert trans-nonachlor to trans-chlordane. This
is consistent with the accumulation of trans-nonachlor in
people but not in rats (Tashiro & Matsumura, 1978).
6.5 Elimination and excretion
Chlordane is excreted primarily in the faeces
(Poonawalla & Korte, 1971).
Elimination of radiolabelled chlordane (3:1 alpha- and
gamma-chlordane) and the individual isomers was studied in
rats. Single oral doses of 0.05, 0.2 and 1 mg/kg body weight
in corn oil were almost completely eliminated after 7 days;
24 hours after administration, 70 % of alpha- chlordane and
60 % of the gamma-isomer were excreted. Female rats excreted
more of the dose in the urine than the males (Barnett &
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 (-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).
7.2.1 Human data
Chlordane has not been a common
substance causing poisoning. All established
cases have been associated with gross
exposure. In most instances, including those
with full recovery, convulsions appeared
within 0.5 to 3 hours after ingestion (Micks,
1954; Curley & Garretson, 1969; Aldrich &
Holmes, 1969) or after dermal exposure
During an acute episode, a man experienced a
brief episode of oliguria with proteinuria,
hematuria and mild hypertension, all of which
returned to normal (Stranger & Kerridge,
One 30-year-old woman was exposed to
chlordane through carelessness and overuse
over a 1 to 4 week period. Myoclonic jerks
occurred only after a delay of a month,
although the patient previously suffered from
circumoral numbness, anorexia, nausea and
fatigue (Garretson et al., 1985). Malaise and
anorexia became the dominant symptoms for 6
months before treatment. Dysfunctional
bleeding was attributed to hepatic enzyme
induction by the chlordane and increased
metabolism of contraceptive medication.
In an episode of contamination of a public
water supply by chlordane (probably
intentional) many people were affected and
the water level in a residence near the
point of intake was 6.600 ppm. Although
chlordane, its contaminants, or its
metabolites were not detected in residents, a
significant proportion reported
gastrointestinal symptoms, skin and eye
irritation and headaches (Morbidity and
Mortality Weekly Reports, 1981).
Two cases of chlordane poisoning were
reported in 1955. One was caused by
absorption of accidentally spilled chlordane,
40 minutes later the victim became confused
and suddenly began having convulsions. She
was dead on arrival to the physician's
office. The other was a suicide attempt where
the individual (female) swallowed 6 g of
chlordane (104 mg/kg body weight) and died 9´
days after the incident (Derbes et al.,
One man occupationally exposed to chlordane
developed episodes of paresthesia and later
twitching of the right hand and arm.
Additional episodes, beginning in the same
way, ended as grand mal convulsions followed
by unconsciousness. He has recovered without
treatment when he discontinued contact with
Topical skin application of about 30 g to an
adult resulted in death in 40 minutes (ACGIH,
The acute lethal dose for man is estimated to
be 25 to 50 mg/kg body weight (IPCS, 1984).
A 15-month-old girl ingested a
mouthful of chlordane suspension and after 3
hours, displayed tremors and incoordination
(Lensky & Evans, 1952). Repeated seizures
developed and she was treated with ethyl
chloride, amobarbital and gastric lavage with
magnesium sulfate. The child recovered
completely and ataxia and excitability
disappeared after 2 to 3 weeks. At 26 years
of age, she was in excellent health and
appeared not to suffer any consequences from
the childhood episode (Taylor et al.,
A 2-year-old child had drunk an unknown
amount of a 74% formulation of chlordane
(Curley & Garretson, 1969). Vomiting preceded
convulsions, which were controlled by
phenobarbital; the EEG pattern was normal
within 40 hours and the child recovered.
A similar poisoning incident was observed
with a 4-year-old child (Aldridge & Homes,
1969). Convulsions were treated with
phenobarbital and the individual recovered.
After a 21-month-old child who had typical
convulsions following ingestion of an unknown
number of chlordane pellets recovered; she
had albuminuria and a positive urine culture;
to what extent chlordane may have influenced
the renal tract infection was unclear
7.2.2 Relevant animal data
Acute oral LD50 for rats 460 mg/kg (IPCS, 1998)
Acute oral LD50 for mice 430 mg/kg
Acute oral LD50 for rabbits 300 mg/kg
Acute percutaneous LD50 for rabbits >200 but <2000
mg/kg (Tomlin, 1994), extremely irritating to their
eyes but produces only mild irritant to their
Inhalation LC50 (4 hour) (for exposure to an aerosol,
nominal concentration) >200 mg/L
NOEL for dogs 3 mg/kg diet.
7.2.3 Relevant in vitro data
Sufficient human data are available
7.2.4 Workplace standards
OSHA PEL TWA0.5 mg/m3 (skin)
TLV0.5 mg/m3 (as TWA) (ACGIH 1999)
NIOSH REL Ca TWA 0.5 mg/m3 skin
NIOSH IDLH Potential occupational carcinogen
7.2.5 Acceptable daily intake (ADI)
ADI 0.0005 mg/kg (IPCS, 1997)
Case reports of leukaemia and other blood dyscrasias
have been associated with exposure to chlordane/heptachlor,
primarily in domestic situations (Furie &
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 demonstrate 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.
Chlordane 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 chlordane and sufficient evidence in
experimental animals for the carcinogenicity of chlordane.
The overall evaluation of IARC on chlordane is Group 2B
(possibly carcinogenic to humans).
No evidence of teratogenicity was found in animal
studies (IPCS, 1984).
Alpha-chlordane, gamma chlordane and chlordene were
tested in the Ames Salmonella microsome assay and were not
mutagenic (Simon et al., 1977). Chlordane was not mutagenic
when tested using 5 different strains of Salmonella
typhimurium in the Ames assay (Ergovich & Rachid, 1977).
More studies on animal and human cells in culture have shown
that chlordane is not mutagenic or is only weakly mutagenic
(Williams, 1979; Maslansky & Williams, 1981; Tong et al.,
1981). Further work by Telang et al. (1982) showed that
chlordane, was not mutagenic to an adult rat liver cell line
but inhibited cell to cell communication in a rat liver
6-thioguanine resistant sensitive cell line.
Chlordane and heptachlor did not cause dominant lethal
effects in mice. Both compounds inhibited gap-junctional
intercellular communication and induced gene mutations in
rodent cells but did not induced unscheduled DNA synthesis.
Neither chlordane nor heptachlor was mutagenic to bacteria
and neither of these damaged bacterial or plasmid DNA (IARC,
Chlordane has been shown to exert a protective effect
against several organophosphorus and carbamate insecticides
(Williams, 1967; Street, 1969; Williams 1970).
Protein deficiency has been shown to double the acute
toxicity of chlordane in rats (Boyd, 1972). Chlordane has
also shown to increase the hepatotoxic effects of carbon
tetrachloride in the rat (Stenger et al., 1975;Mahon, 1977;
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
126.96.36.199 Toxicological analyses
188.8.131.52 Biomedical analyses
184.108.40.206 Arterial blood gas analysis
220.127.116.11 Haematological analyses
18.104.22.168 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
22.214.171.124 Toxicological analyses
126.96.36.199 Biomedical analyses
188.8.131.52 Arterial blood gas analysis
184.108.40.206 Haematological analyses
220.127.116.11 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
18.104.22.168 Toxicological analyses
22.214.171.124 Biomedical analyses
126.96.36.199 Arterial blood gas analysis
188.8.131.52 Haematological analyses
184.108.40.206 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
220.127.116.11 Simple Qualitative Test(s)
18.104.22.168 Advanced Qualitative Confirmation Test(s)
22.214.171.124 Simple Quantitative Method(s)
126.96.36.199 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
188.8.131.52 Simple Qualitative Test(s)
184.108.40.206 Advanced Qualitative Confirmation Test(s)
220.127.116.11 Simple Quantitative Method(s)
18.104.22.168 Advanced Quantitative Method(s)
22.214.171.124 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
126.96.36.199 Blood, plasma or serum
188.8.131.52 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
8.5 Overall interpretation of all toxicological analyses and
9. CLINICAL EFFECTS
9.1 Acute poisoning
Following ingestion of chlordane some patients
have experienced nausea and vomiting before signs of
central nervous system overactivity appeared. However
a convulsive fit could be the first clear indication
of illness. Convulsions often last about a minute and
may recur at intervals of about 5 minutes. Convulsions
usually are accompanied by confusion, incoordination,
excitability, or in some instances, coma. Respiratory
failure may also occur (Olanoff et al., 1983).
Chlordane may be absorbed by inhalation.
Symptoms are basically the same as by
9.1.3 Skin exposure
Skin is a significant route of exposure, and
may even result in death (ACGIH, 1986). Symptoms are
basically the same as by ingestion.
9.1.4 Eye contact
Contact with the eyes may cause ocular
irritation and pain (IPCS, CEC, 1999).
9.1.5 Parenteral exposure
No data available.
Symptoms were relatively mild in a poisoning by
rectally administered chlordane involving a dose of
0.53 to 1.9 mg/kg (Marquart, 1982).
9.2 Chronic poisoning
No data available.
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
Recent evidence indicates that neurotoxicity, a
known human endpoint in acute exposures may be a
relevant endpoint in chronic human exposures. No
chronic animal studies have examined neurotoxicity
(Kilburn & Thornton, 1995).
9.3 Course, prognosis, cause of death
Typical, serious poisoning by chlordane is characterized
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 chlordane 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 may occur
before signs of central nervous system activity have
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 (Olanoff
et al., 1983). Death may follow respiratory failure (IPCS,
9.4 Systematic description of clinical effects
Arrhythmias may occur owing to myocardial
sensitivity to catecholamines (Olson, 1999).
The effects of chlordane on the respiratory
system are secondary to the effects on the nervous
system (Hayes & Laws, 1991).
184.108.40.206 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.
220.127.116.11 Peripheral nervous system
Paraesthesia of the extremities has
been reported in a man accidentally exposed
to chlordane (Barnes, 1967).
18.104.22.168 Autonomic nervous system
No data available.
22.214.171.124 Skeletal and smooth muscle
Rhabdomyolysis may occur.
Nausea and vomit may occur.
Chlordane is a potent inducer of hepatic
microsomal enzymes (Hart et al., 1963).
After ingestion, renal injury may
develop (Olson, 1999).
No data available.
9.4.7 Endocrine and reproductive systems
Induction of hepatic microsomal enzymes may
result in hormonal disturbances because of accelerated
metabolism of endogenous steroids (Street et al.,
At concentrations above 30 mg per kg of fodder,
chlordane interferes with reproduction in rats and
mice (IPCS, 1988).
No multi-generational reproductive studies, by any
route, exist for technical chlordane. Several items
within the current chlordane database suggest that
reproductive effects could be a relevant endpoint for
chlordane. The study of Cassidy et al. (1994)
indicates alterations in reproductive-related
behaviour in male rats as a consequence of chlordane
Accumulation of a major component of a technical
chlordane (heptachlor) 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).
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
May cause redness and pain in the eyes
Case reports of leukaemia and other blood
dyscrasias have been associated exposure to chlordane.
The bone marrow showing evidence of dyserythropoiesis,
eosinophilia and megaloblastosis was reported after
extensive exposure with recovery after 4 months
Altered immune competence was reported in the
offspring off mice whose mothers had received
chlordane at a rate of 8.0 mg/kg/day throughout
gestation but not in young whose mothers received 0.16
mg/kg/day (Cranmer et. al., 1979, Spyker-Cranmer et
126.96.36.199 Acid-base disturbances
Metabolic acidosis may occur.
188.8.131.52 Fluid and electrolyte disturbances
No data available
No data available
9.4.13 Allergic reactions
No data available
9.4.14 Other clinical effects
9.4.15 Special risks
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)
Concentrations of chlordane 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 chlordane 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 chlordane was not found in any of the samples,
and its metabolite oxychlordane was found above the
detection limit (95.8 ppb) in 74% of the samples
(Savage et al., 1981).
No data available
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 chlordane
has been ingested less than one hour ago, gastric lavage
after endotracheal intubation may be indicated, 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
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
To control convulsions use clonazepam IV or diazepam IV or
per rectum. Intravenous barbituratesmay 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
If the patient has vomited spontaneously monitor respiratory
functions and watch for signs of pulmonary aspiration.
Remove and discard contaminated clothing. Wash exposed skin,
including hair and nails with (soap and) copious amounts of
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.
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 is seen within one
hour after ingestion.
In the case of ingestion of a solution, or an emulsifiable
concentrate, a risk of chemical pneumonitis following
10.4 Enhanced Elimination
Enhanced elimination is not indicated because of the
large volume of distribution of chlorinated hydrocarbon
10.5 Antidote treatment
There is no specific antidote
There is no specific antidote.
10.6 Management discussion
The use of activated charcoal in the treatment of an
acute chlordane intoxication is fully established. Repeated
dosing may be beneficial as it partially interrupts the
entero-hepatic circulation (Hayes & Laws, 1991).
Clonazepam or diazepam are the drugs of first choice, but
barbiturates also 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
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,
as required. (Shell Agriculture, 1990).
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
After a 21-month-old child who had a typical convulsion
following ingestion of an unknown number of chlordane
"pellet" was essentially recovered, she was found to have
albuminuria, and a positive urine culture; to what extend
chlordane may have influenced the renal tract infection was
unclear (Canada, 1962)
A woman working at a formulating plant who accidentally
spilled a solution of chlordane and DDT on her belly and
thighs became confused and suddenly began having convulsions
after 40 minutes. She was dead before she was taken to the
physician's office (Derbes, 1955).
One 30-year-old woman was exposed to chlordane by careless
handling and overuse over a 1 to 4 week period. Myoclonic
jerks occurred only after a delay of a month, although the
patient previously suffered from circumoral numbness,
anorexia, nausea and fatigue. Fatigue and anorexia became the
dominant symptoms for 6 months before treatment (Garretson et
12. Additional information
12.1 Specific preventive measures
Rescuers must take precautions not to contaminate
The manufacture of chlordane 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
Chlordane is persistent and rather immobile in soil,
this substance may be hazardous to the environment; special
attention should be given to fish in tropical areas. It is
strongly advised not to let the chemical enter into the
environment (IPCS, CEC, 1999)
ACGIH (1986) Document of the threshold limit values and
biological exposure indices. 5th ed. Cincinnati, OH: American
Conference of Governmental Industrial Hygienists. p. 114.
ACGIH (1999) Threshold limit values for chemical substances and
physical agents and biological exposure indices. Cincinnati, OH:
American Conference of Governmental Industrial Hygienists.
Aldrich FD and Holmes JH (1969) Acute chlordane intoxication in a
child. Case report with toxicological data. Arch Environ Health,
Balba HM and Saha JG (1978) Studies on the distribution,
excretion, and metabolism of alpha- and gamma-isomers of 14C
chlordane in rabbits. J Environ Sci Health, B13: 211-233.
Barnes R (1967) Poisoning by the insecticide chlordane. Med J Aus
Barnett RW and Dorough HW (1974) Metabolism of chlordane in rats.
J Agric Food Chem, 22: 612-619.
Boyd EM (1972) Chlordane. In: Protein deficiency and pesticide
toxicity, Springfield, Ill., Charles C. Thomas, 468 pp.
Briemfield AA and Street JC (1979) Mammalian biotransformation of
chlordane. In vivo and primary hepatic comparisons. Ann N.Y Acad
Sci 320, 247-256.
Budavari S ed. (1996) The Merck Index: an encyclopedia of
chemicals, drugs, and biologicals, 12th ed. Rahway, New Jersey,
Merck and Co., Inc.
Canada (1962) "Chlordane poisoning. Information release to poison
control centers". Release No.2. Reprinted in: World Health
Organization Information Circular on Toxicity of Pesticides to
Man. No11. P.10. World Health Organization, Geneva.
Cassidy RA, Vorhees CV, Minnema DJ, Hastings L (1994) The effects
of chlordane exposure during pre- and postnatal periods at
environmentally relevant levels on sex steroid-mediated behaviors
and functions in the rat. Toxicol Appl Pharmacol 126(2):
Cranmer JS, Avery DL, Barnett JB (1979) Altered immune competence
of offspring exposed during development to the chlorinated
hydrocarbon pesticide. Teratology 19, 23 A.
Curley A and Garretson LK (1969) Acute chlordane poisoning. Arch
Env Health 18, 211-215.
Derbes JV, Dent HJ, Forest WW, Johnson MF (1955) Fatal chlordane
poisoning. J Am Med Assoc, 158(15): 1367-1369.
Ercegovich CD and Rashid KA (1977) Mutagenesis induced in mutant
strains of Salmonella typhimurium by pesticides. Soc Abstr Pap,
Food and Agricultural Organization/World Health Organization
(1971). 1970 Evaluations of some pesticide residues in food.
WHO/Food Add./71.42. FAO/WHO Rome.
Furie B and Trubowitz S (1976) Insecticides and blood dyscrasias.
Chlordane exposure and self-limited refractory megaloblastic
anemia. J Am Med Assoc 235:1720 - 1722.
Garretson LK, Guzelian PS, Blanke RV (1985) Subacute chlordane
poisoning. J Toxicol Clin Toxicol 22, 565-571.
Gosselin ER, Smith PR, Hodge HC, Braddock JE (1984) Clinical
toxicology of Commercial Products. 5th ed. Williams and Wilkins.
Hart LG, Shultice RW, Fouts JR (1963) Stimulatory effects of
chlordane on hepatic microsomal drug metabolism in the rat.
Toxicol Appl Pharmacol 5: 371-386.
Hayes WJ (Jr) and Laws ER (Jr) (1991) Handbook of pesticide
toxicology. Academic Press Inc. pp. 816 - 822.
IARC (1991) IARC Monograph: Occupational Exposures in Insecticide
Application and Some Pesticides. Vol. 53 p. 115-179.
IARC (1987) IARC Monographs: An updating of IARC Monographs Vol. 2
to 42 Supplement 7 440 pp.
IPCS (1984) Environmental Health Criteria Monographs 34.
Chlordane. World Health Organization, Geneva.
IPCS (1988) Health and Safety Guide No.13: Chlordane. Health and
Safety Guide. International Programme on Chemical Safety, World
Health Organization, Geneva, Switzerland.
IPCS (1997) Inventory of IPCS and other WHO pesticide evaluations
and summary of toxicological evaluations performed by the Joint
Meeting on Pesticide Residues (JMPR). WHO/PCS/98.1. World Heath
IPCS (1998) The WHO Recommended classification of pesticides by
hazards and guidelines to classification 1998-1999.
WHO/PCS/98.21/Rev.1. World Health Organization, Geneva.
IPCS, CEC (1999) International Chemical Safety Cards: 0740
Chlordane (Technical Product).
Kilburn KH and Thornton JC (1995) Protracted neurotoxicity from
chlordane sprayed to kill termites. Environ Health Perspect
Klaassen CD & Watkins JB (1999) Casarett & Doull's toxicology: the
basic science of poisons. 5th ed. New York, MacGraw-Hill
Publishing Company 542-547.
KNMP (1996) Informatorium Medicamentorum 1996 deel 1, Koninklijke
Nederlandse Maatschappij ter bevordering der Pharmacie,
Lensky P and Evans HL (1952) Human poisoning by chlordane. Report
of a case. J Am Med Assoc, 121: 826-827.
Mackison FW, Stricoff RS, Partridge LJ (1981)
NIOSH/OSHA- Occupational Health Guidelines for Chemical Hazards.
DHHS (NIOSH) Publication No. 81-123 (3 vols.), Washington, DC:
U.S. Government Printing Office.
MacMahon B, Monson RR, Wang HH, Zengh TZ (1988) A second follow-up
of mortality in a cohort of pesticide applicators. J Occup Med, 30
Mahon DC (1977) Interactions, in rats, between carbon
tetrachloride-induced liver cirrhosis and chronic treatment with
the insecticide chlordane. Diss Abstr Int, 38: 4012B.
Mahon DC and Oloffs PC (1979) Effects of sub-chronic low-level
dietary intake of chlordane on rats with cirrhosis of the liver.
J Environ Sci Health, B14: 227-246.
Marquart ED (1982) Suicide attempt with rectally administered
chlordane. Drug Intell Clin Pharm, 16(3): 247-8.
Maslansky CJ and Williams GM (1981) Evidence for an epigenetic
mode of action in organochlorine pesticide hepatocarcinogenicity:
A lack of genotoxicity in rat, mouse and hamster hepatocytes. J
Toxicol Environ Health, 8: 121-130.
Micks DW (1954) Potential health hazards of organic insecticides.
Tex State J Med, 50, 148-153.
Morbidity and Mortality Weekly Reports (1981) Chlordane
contamination of a public water supply- Pittsburgh, Pennsylvania.
Morbid Mortal Wkly Rep 33, 687-693.
NIOSH (1998) Pocket Guide to Chemical Hazards. US Department of
Health and Human Services. Public Health Service. Centers for
Disease Control and Prevention. National Institute for
Occupational Safety and Health.
Olanoff LS, Bristow WJ, Colcolough J, Reigart JR (1983) Acute
chlordane intoxication. J Toxicol Clin Toxicol 20, 291-306.
Olson KR ed. (1999) Poisoning and drug overdose. Appleton and
Poonawalla NH and Korte F (1971) Metabolism of trans -Chlordane -
14C and isolation and identification of its metabolites from the
urine of rabbits. J Agric Food Chem, 19: 467.
Rani BE, Karanth NG, Krishnakumari MK (1992) Accumulation and
embriotoxicity of the insecticide heptachlor in the albino rat. J
Environ Biol 13(2) 95-100.
Reigart RJ, Roberts JR (1999) Recognition and Management of
Pesticide Poisonings. 5th ed. US Environment Protection Agency,
Savage EP, Keefe TJ, Tessari JD, Wheeler HW, Applehans FM, Goes
EA, Ford SA (1981) National study of chlorinated hydrocarbon
insecticide residues in human milk, USA. I. Geographic
distribution of dieldrin, heptachlor, heptachlor epoxide,
chlordane, oxychlordane and mirex. Am J Epidemiol: 113(4)
Shell agriculture (1990) Safety Guide. Shell International
Chemical Company Limited, Crop Protection Division, Shell Centre,
London, pp. 35-36, 71-75.
Simmon VF, Kauhanen K, Tardiff RG (1977) Mutagenic activity of
chemicals identified in drinking water. Dev Toxicol Environ Sci,
Spyker-Cranmer JM, Barnett JB, Avery DL, Cranmer MF (1982)
Immunoteratology of chlordane: Cell mediated and humoral immune
responses in adult mice exposed in utero. Toxicol Appl Pharmacol
Stenger RJ, Porway M, Johnson JEA, Datta RK (1975) Effects of
chlordane pretreatment on the hepatotoxicity of carbon
tetrachloride. Exp Mol Pathol, 23: 144-153.
Stevens MF, Ebell GF, Psaila-Savona P (1993) Organochlorine
pesticides in Western Australian nursing mothers. Med J Aust 1993,
Feb 15, 158(4): 238-241.
Stranger J & Kerridge G (1968) Multiple fractures of the dorsal
part of the spine following chlordane poisoning. Med J Aus 1,
Street JC, Mayer FL, Wagstaff J (1969) Ecological significance of
pesticide interactions. Ind Med Surg, 38: 409-414.
Stubblefield WA and Dorough HW (1979) Quantitative administration
of insecticide vapors to rats. Toxicol Appl Pharmacol 48,
Tashiro S and Matsumura F (1977) Metabolic routes of cis- and
trans chlordane in rats. J Agric Food Chem, 25, 872-880.
Tashiro S and Matsumura F (1978) Metabolism of trans-nonachlor and
related chlordane components in rat and man. Arch Environ Contam
Toxicol 7, 113-127.
Taylor JR, Calabrese VP, Blanke RV (1979) Organochlorine and other
insecticides. In: Vinken, P.J. & Bruyn, G.W., ed. Handbook of
clinical neurology, Vol. 36. Intoxications of the nervous system,
Amsterdam, New York, Elsevier/North-Holland Biomedical Press, Part
Telang S, Tong C, Williams GM (1982) Epigenetic membrane effects
of a possible tumour promoting type on cultured liver cells by the
non-genotoxic organochlorine pesticides chlordane and heptachlor.
Carcinogenesis, 3: 1175-1178.
Tomlin C ed. (1994) The Pesticide Manual. Incorporating the
Agrochemicals Handbook. The British Crop Protection Publications
Tong C, Fazio M, Williams GM (1981) Rat hepatocyte-mediated
mutagenesis of human cells by carcinogenic polycyclic aromatic
hydrocarbons but not organochlorine pesticides. Proc Soc Exp Biol
Med, 167: 572-575.
Williams GM (1979) Liver cell culture systems for the study of
hepatocarcinogenesis. In: Margison GP, ed. Advances in medical
oncology research and education, Oxford, Pergamon Press, Vol. 1,
Williams CH, Casterline JL, Jacobson KH (1967) Studies of toxicity
and enzyme activity from interaction between chlorinated
hydrocarbon and carbamate insecticides. Toxicol Appl Pharmacol,
Williams CH, Casterline JL (1970) Effects on toxicity and on
enzyme activity of the interactions between aldrin, chlordane,
piperonyl butoxide and banol in rats. Proc Soc Exp Biol Med, 135:
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
Author: Dr Nida Besbelli
World Health Organization
1211 Geneva 27
Tel: 41 22 791 4287
Fax: 41 22 791 4848
Prepared: June 2000
Reviewer: Janusz Szajewski, MD
Warsaw Poisons Centre
Tel/fax +48 (22) 839 06 77
Peer review: INTOX 12 Meeting, 7 - 11 November 2000
Drs J. Szajewski, C.Alonzo, R. Fernando.
Chlordane (EHC 34, 1984)