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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY


    ENVIRONMENTAL HEALTH CRITERIA 34






    CHLORDANE








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

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

    World Health Orgnization
    Geneva, 1984


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CONTENTS

ENVIRONMENTAL HEALTH CRITERIA FOR CHLORDANE

1. SUMMARY AND RECOMMENDATIONS

    1.1. Summary
         1.1.1. Identity and analytical methods
         1.1.2. Use and sources of exposure
         1.1.3. Environmental concentrations, exposures,
                and effects
         1.1.4. Kinetics and metabolism
         1.1.5. Studies on experimental animals
         1.1.6. Effects on man
    1.2. Recommendations

2. IDENTITY, PROPERTIES AND ANALYTICAL METHODS

    2.1. Identity
    2.2. Properties and analytical methods
         2.2.1. Physical and chemical properties
         2.2.2. Analytical methods

3. SOURCES OF ENVIRONMENTAL POLLUTION, ENVIRONMENTAL
    TRANSPORT AND DISTRIBUTION

    3.1. Sources of environmental pollution
         3.1.1. Industrial production and uses
    3.2. Environmental transport and distribution
         3.2.1. Air
         3.2.2. Water
         3.2.3. Soil
         3.2.4. Abiotic degradation
         3.2.5. Biodegradation

4. ENVIRONMENTAL LEVELS AND EXPOSURES

    4.1. Environmental levels
         4.1.1. Air
         4.1.2. Water
         4.1.3. Soil
         4.1.4. Crops and wildlife
         4.1.5. Food
         4.1.6. Human milk
    4.2. General population exposure
    4.3. Occupational exposure

5. KINETICS AND METABOLISM

    5.1. Absorption
    5.2. Distribution and storage
    5.3. Biotransformation
    5.4. Elimination and excretion

6. STUDIES ON EXPERIMENTAL ANIMALS

    6.1. Short-term exposures
         6.1.1. Oral exposure
         6.1.2. Dermal exposure
         6.1.3. Parenteral exposure
    6.2. Long-term exposures
         6.2.1. Oral exposure
         6.2.2. Dermal exposure
    6.3. Reproduction studies and teratogenicity
    6.4. Mutagenicity
    6.5. Carcinogenicity
    6.6. Behavioural studies
    6.7. Other studies
    6.8. Factors influencing toxicity

7. EFFECTS ON MAN:  EPIDEMIOLOGICAL AND CLINICAL STUDIES

    7.1. Poisoning incidents
    7.2. Occupational and epidemiological studies
    7.3. Treatment of poisoning

8. EFFECTS ON THE ENVIRONMENT

    8.1. Toxicity for aquatic organisms
    8.2. Toxicity for terrestrial organisms
    8.3. Toxicity for microorganisms
    8.4. Bioaccumulation and biomagnification
    8.5. Population and community effects
    8.6. Effects on the abiotic environment
    8.7. Appraisal

9. PREVIOUS EVALUATIONS OF CHLORDANE BY INTERNATIONAL BODIES

10. EVALUATION OF HEALTH RISKS FOR MAN AND EFFECTS ON THE ENVIRONMENT

    10.1. Chlordane toxicity
    10.2. Exposure to chlordane
    10.3. Evaluation of overall environmental effects
    10.4. Evaluation of risks for human health
          and the environment

REFERENCES


TASK GROUP MEETING ON ENVIRONMENTAL HEALTH CRITERIA FOR
ORGANOCHLORINE PESTICIDES OTHER THAN DDT (CHLORDANE,
HEPTACHLOR, MIREX, CHLORDECONE, KELEVAN, CAMPHECHLOR)


 Members

Dr Z. Adamis, National Institute of Occupational Health,
   Budapest, Hungary

Dr D.A. Akintonwa, Department of Biochemistry, Faculty of
   Medicine, University of Calabar, Calabar, Nigeriaa

Dr R. Goulding, Chairman of the Scientific Sub-committee, UK
   Pesticides Safety Precautions Scheme, Ministry of
   Agriculture, Fisheries & Food, London, England  (Chairman)

Dr S.K. Kashyap, National Institute of Occupational Health
   (Indian Council of Medical Research), Meghaninager,
   Ahmedabad, India

Dr D.C. Villeneuve, Environmental Contaminants Section,
   Environmental Health Centre, Tunney's Pasture, Ottawa,
   Ontario, Canada  (Rapporteur)

Dr D. Wassermann, Department of Occupational Health, The
   Hebrew University, Haddassah Medical School, Jerusalem,
   Israel  (Vice-Chairman)

 Representatives of Other Organizations

Dr C.J. Calo, European Chemical Industry Ecology and
   Toxicology Centre (ECETOC)

Mme van der Venne, Commission of the European Communities (CEC),
   Health and Safety Directorate, Luxembourg

Dr D.M. Whitacre, International Group of National Associations
   of Agrochemical Manufacturers (GIFAP)

 Secretariat

Dr M. Gilbert, International Register for Potentially Toxic
    Chemicals, United Nations Environment Programme, Geneva,
    Switzerland

Mme B. Goelzer, Division of Noncommunicable Diseases, Office
   of Occupational Health, World Health Organization, Geneva,
   Switzerland

-------------------------------------------------------------------
a  Unable to attend.

 Secretariat (contd.)                                             

Dr Y. Hasegawa, Division of Environmental Health,
   Environmental Hazards and Food Protection, World Health
   Organization, Geneva, Switzerland

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

Mr B. Labarthe, International Register for Potentially Toxic
   Chemicals, United Nations Environment Programme, Geneva,
   Switzerland

Dr I.M. Lindquist, International Labour Organization, Geneva,
   Switzerland

Dr M. Vandekar, Division of Vector Biology and Control,
   Pesticides Development and Safe Use Unit, World Health
   Organization, Geneva, Switzerland

Mr J.D. Wilbourn, Unit of Carcinogen Identification and
   Evaluation, International Agency for Research on Cancer,
   Lyons, France

NOTE TO READERS OF THE CRITERIA DOCUMENTS


    While every effort has been made to present information in the 
criteria documents as accurately as possible without unduly 
delaying their publication, mistakes might have occurred and are 
likely to occur in the future.  In the interest of all users of the 
environmental health criteria documents, readers are kindly 
requested to communicate any errors found to the Manager of the 
International Programme on Chemical Safety, World Health 
Organization, Geneva, Switzerland, in order that they may be 
included in corrigenda, which will appear in subsequent volumes. 

    In addition, experts in any particular field dealt with in the 
criteria documents are kindly requested to make available to the 
WHO Secretariat any important published information that may have 
inadvertently been omitted and which may change the evaluation of 
health risks from exposure to the environmental agent under 
examination, so that the information may be considered in the event 
of updating and re-evaluation of the conlcusions contained in the 
criteria documents. 

                          *  *  *


     A detailed data profile and a legal file can be obtained from 
the International Register of Pontentially Toxic Chemicals, Palais
des Nations, 1211 Geneva 10, Switzerland ( Telephone no. 988400 -
985850)

ENVIRONMENTAL HEALTH CRITERIA FOR CHLORDANE


    Following the recommendations of the United Nations Conference 
on the Human Environment held in Stockholm in 1972, and in response 
to a number of World Health Resolutions (WHA23.60, WHA24.47, 
WHA25.58, WHA26.68), and the recommendation of the Governing 
Council of the United Nations Environment Programme, (UNEP/GC/10, 
3 July 1973), a programme on the integrated assessment of the 
health effects of environmental pollution was initiated in 1973.  
The programme, known as the WHO Environmental Health Criteria 
Programme, has been implemented with the support of the Environment 
Fund of the United Nations Environment Programme.  In 1980, the 
Environmental Health Criteria Programme was incorporated into the 
International Programme on Chemical Safety (IPCS).  The result of 
the Environmental Health Criteria Programme is a series of criteria 
documents. 

    A WHO Task Group on Environmental Health Criteria for 
organochlorine pesticides other than DDT met in Geneva from 
28 November - 2 December, 1984.  Dr K.W. Jager opened the meeting 
on behalf of the Director-General.  The Task Group reviewed and 
revised the draft criteria document on chlordane and made an 
evaluation of the health risks of exposure to chlordane. 

    The first drafts of the document were prepared by 
Dr D.C. Villeneuve of Canada, and Dr S. Dobson of the United 
Kingdom. 

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


                             * * *


    Partial financial support for the publication of this criteria 
document was kindly provided by the United States Department of 
Health and Human Services, through a contract from the National 
Institute of Environmental Health Sciences, Research Triangle Park, 
North Carolina, USA - a WHO Collaborating Centre for Environmental 
Health Effects. 


1.  SUMMARY AND RECOMMENDATIONS

1.1.  Summary 

1.1.1.  Identity and analytical methods

    Chlordane is a viscous, light yellow to amber-coloured liquid.  
Technical chlordane is a mixture of at least 26 different 
components and up to 14 distinct chromatographic components have 
been described.  Its main components are alpha- and gamma-
chlordane. 

    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. 

1.1.2.  Use and sources of exposure

    Chlordane has been used for more than 35 years as a broad-
spectrum contact insecticide, mainly on non-agricultural crops and 
on animals.  In its country of origin, the USA, its use is now 
restricted to underground termite control.  In several other 
countries, approved uses have been gradually withdrawn. 

    The main source of exposure of the general population is 
through residues in food.  This is not a significant problem since 
chlordane is not normally used on food crops, and residues in food 
of animal origin are usually below accepted residue levels in 
various countries.  Under normal circumstances, chlordane intake 
from air and water is insignificant.  Chlordane has, however, been 
detected in the air of buildings where the compound has been used 
for termite and other insect control. 

    Under occupational exposure conditions, both inhalation and 
skin contact are relevant, if adequate preventive and protection 
measures are lacking. 


1.1.3.  Environmental concentrations, exposures, and effects

    Chlordane is stable to light under normal conditions.  It is 
readily adsorbed on soil particles and therefore there is no 
significant migration through the soil profile or leaching into 
ground water.  Some volatilisation into air from treated soils, and 
some run-off into surface waters can take place. 

    Chlordane is fairly persistent in soil and sediments, 
especially in the form of its alpha- and gamma-isomers, which are, 
to a certain extent, translocated into crops grown on the soil. 

    Limited bioaccumulation in the adipose tissue of terrestrial 
and aquatic organisms can take place.  In general, concentration 
factors in mammals are less than 1. 

    Chlordane is highly toxic to earthworms, which may present its 
greatest long-term hazard for the environment. 

1.1.4.  Kinetics and metabolism

    In experimental animals, chlordane is readily absorbed via the 
skin and through oral ingestion, and probably also following 
inhalation.  It is readily distributed in the body, the highest 
levels being found in adipose tissue, followed by the liver.  The 
distribution was found to be similar in the rat and the rabbit.  
The metabolism of chlordane, which is a complex mixture, has been 
largely elucidated.  Several metabolites have been identified and 
species differences have been found.  Oxychlordane is the most 
relevant animal metabolite, being more persistant and toxic than 
the parent compound. 

    Following a single, oral dose, elimination of chlordane was 
almost complete after 7 days in the rat.  After long-term exposure, 
elimination from the body was slower. 

1.1.5.  Studies on experimental animals

    Chlordane is moderately toxic according to the scale of Hodge & 
Sterner (1956) (acute oral LD50 for rat:  200 - 590 mg/kg body 
weight).  WHO (1984) classified the technical product as moderately 
hazardous.  Most of its metabolites are slightly to moderately 
toxic, with the exception of oxychlordane, which is highly toxic 
(acute oral LD50 for rat:  19.1 mg/kg body weight). 

    Signs of poisoning in various animal species are neurotoxic 
manifestations such as disorientation, tremors, and convulsions.  
Death may follow respiratory failure.  On continuous exposure, a 
certain degree of accumulation may occur in the body, mainly in 
adipose tissue and to a lesser extent in the liver.  The induction 
of hepatic microsomal enzyme activity is one of the most sensitive 
parameters for long-term, low-level chlordane exposure.  At higher 
levels, liver hypertrophy with histopathological and functional 
changes may occur. 

    At high dosages (50 - 320 mg/kg diet), chlordane decreased the 
fertility of rats and mice and the viability of the offspring. 

    There were no indications for teratogenicity. 

    Chlordane is not generally active in short-term tests for 
genetic activity. 

    It induces hepatocellular carcinomas in mice.

1.1.6.  Effects on man

    Cases of accidental and suicidal poisoning with chlordane have 
been reported.  With the exception of suicide cases, recovery was 
generally complete.  The acute lethal dose for man is estimated to 
be 25 - 50 mg/kg body weight.  No adverse effects have been 

reported in occupationally-exposed workers.  Epidemiological data 
are insufficient to judge the potential carcinogenicity of 
chlordane for man. 

1.2.  Recommendations 

    (a) Figures relating to the current production and use of 
        chlordane should be made available;

    (b) More information on human exposure from sources other
        than food, such as its used in termite control, are
        required;

    (c) Further research is required in order to better
        assess the significance for man of the carcinogenic
        findings in mice;

    (d) Epidemiological studies on workers who, in the past,
        have been exposed to chlordane, should continue.

2.  IDENTITY, PROPERTIES AND ANALYTICAL METHODS

2.1.  Identity 

Chemical Structure

Molecular formula:         C10H6C18

CAS chemical name:         1,2,4,5,6,7,8,8-octachloro-2,3,3a,4,
                           7,7a-hexahydro-4,7-methano-1H-indene

Common trade names:        Aspon, Belt, CD 68, Chlorindan,
                           Chlorkil, Chlordane, Corodan,
                           Cortilan-neu, Dowchlor, HCS 3260,
                           Kypchlor, M140, Niran, Octachlor,
                           Octaterr, Ortho-Klor, Synklor, Tat
                           Chlor 4, Topichlor, Toxichlor,
                           Velsicol-1068

CAS registry number:       57-47-9

Relative molecular mass:   409.8

2.2.  Properties and Analytical Methods

2.2.1.  Physical and chemical properties

    Chlordane is a viscous, light yellow to amber-coloured liquid 
(IARC, 1979) with a melting point of 106 - 107 C for the alpha-
isomer and 104 - 105 C for the gamma-isomer.  It has a density of 
1.59 - 1.63 g/ml and a vapour pressure of 1 x 10-5 mm Hg at 25 C.  
It is insoluble in water but soluble in most organic solvents. 

    The major isomers of chlordane have the endo-endo-configuration 
on the carbon skeleton (US EPA, 1976a,b).  However, the term 
chlordane actually refers to a complex mixture of chlordane 
isomers, other chlorinated hydrocarbons and by-products.  According 
to the Canada National Research Council (1974), the technical 
product is described as follows: 

        "Technical chlordane is a mixture of insecticidal
    components, including chlorinated addition and substitution
    derivatives of 4,7-methano-3a,4,7,7a-tetrahydro-indane.
    The chlorine content is 64-67%.  The principal components
    are alpha- and gamma-chlordane (C10H6 x Cl8), heptachlor 

    (C10H5Cl7) and non-achlor (C10H5Cl9).  Technical chlordane 
    conforms to the biological, chemical and physical properties 
    of reference technical chlordane".

    The production of technical chlordane is strictly controlled 
and its composition varies within narrow limits (Canada, National 
Research Council, 1974).  Technical chlordane is a mixture of at 
least 26 different components, mainly however alpha- and gamma-
chlordane.  Up to 14 distinct chromatographic components have been 
described (Cochrane et al., 1975; Cochrane & Greenhalgh, 1976; US 
EPA, 1976a,b; Gaeb et al., 1977; Sovocool et al., 1977; Kadam et 
al., 1978; Parlar et al., 1979).  The composition has been 
essentially, but not completely, worked out.  Chlordane is 
available in the USA in five basic formulations (von Rumker et al., 
1974, IARC, 1979), including 5% granules, oil solutions containing 
chlordane at 2 - 200 g/litre, and emulsifiable concentrates 
containing chlordane at 400 - 800 g/litre. 

2.2.2.  Analytical methods

    Determination of chlordane residues is difficult because 
of the complex nature of the components and the fact that each 
component degrades independently.  Resulting residues may bear 
little relation to the proportions in the technical product 
(Council for Agriculture Science and Technology, 1975).  
Separation from interfering materials can be carried out by thin-
layer chromatography or other partition and clean-up methods (US 
EPA, 1976a,b).  Extraction from crops, other plant products, dairy 
products, plants, and oils was achieved with an 80 - 110% 
efficiency using acetonitrile for extraction, petroleum ether for 
partitioning, and clean-up on a Florisil column (Canada, National 
Research Council, 1974).  Gel-permeation chromatography can also be 
used for clean-up, particularly with human adipose tissue (Wright 
et al., 1978). 

    The principal method for the qualitative and quantitative 
estimation of chlordane isomers is gas-liquid chromatography with 
electron capture detection (US EPA, 1976a,b).  This method has a 
high sensitivity and specificity (Canada, National Research 
Council, 1974; Cochrane et al., 1975).  According to Atallah et al. 
(1977), the highly sensitive electron capture detector can, 
however, lead to the incorrect identification of residues of 
chlordane and its metabolites.  Confirmation of gas-chromatographic 
analysis can be carried out with GLC-Mass spectrometry, a method 
that can also give a better determination of some of the components 
such as heptachlorepoxide (US EPA, 1976a,b).  Other methods of 
detection include bioassay, carbon-skeleton chromatography, 
colorimetric, and total chlorine methods (US EPA, 1976a,b). 

    Analysis for total organically-bound chlorine (Canada, National 
Research Council, 1974) remains the preferred method for the 
determination of technical chlordane and the active ingredient 
(chlordane) in formulations. 

3.  SOURCES OF ENVIRONMENTAL POLLUTION, ENVIRONMENTAL
TRANSPORT AND DISTRIBUTION

3.1.  Sources of Environmental Pollution 

3.1.1.  Industrial production and uses

    Chlordane was first prepared in the 1940s by exhaustive 
chlorination of the cyclopentadiene-hexachlorocyclopentadiene 
adduct (IARC, 1979).  It was first described as an insecticide in 
1945 by Kearns (Spencer, 1973). 

    Chlordane is produced commercially by reacting hexachloro-
cyclopentadiene with cyclopentadiene to form chlordene, which is 
then chlorinated to produce chlordane (IARC, 1979).  Chlordane was 
first produced commercially in the USA in 1947 (IARC, 1979).  
Production in the USA, in 1974, amounted to 9.5 million kg (IARC, 
1979).  Chlordane is not produced in Europe nor has it ever been 
manufactured in Japan (IARC, 1979).  In Japan, the only permitted 
use of the compound is for the control of termites.  It is also 
used against wood-boring beetles and in ant baits.  Both the 
amounts of chlordane produced and used have decreased considerably 
in recent years (WHO, 1982). 

    Chlordane has been used as an insecticide for more than 35 
years.  It is a versatile, broad spectrum, contact insecticide and 
is used mainly for non-agricultural purposes (primarily for the 
protection of structures, but also on lawn and turf, ornamental 
trees, and drainage ditches) (von Rumker et al., 1974).  Further- 
more, it is used on corn, potatoes, and livestock.  In 1978, a US 
EPA cancellation proceeding led to a settlement on contested uses.  
This settlement allowed for limited usage by crop, location, amount 
allowed, and maximum time interval for use. 

    Since 1 July 1983, the only use of chlordane approved in the 
USA is for the control of underground termites (IARC, 1979).  In 
Canada, the use of chlordane is controlled under the Pest Control 
Products Act and it is used for the protection of structures, 
ornamental plants, lawns, and various crops.  Accepted uses vary 
from province to provide (Canada, National Research Council, 1974). 

3.2.  Environmental Transport and Distribution 

3.2.1.  Air

    Entry into the atmosphere occurs mainly through aerial 
applications of dusts and sprays, soil erosion by the wind, and 
volatilization from soil and water (Canada, National Research 
Council, 1974). 

3.2.2.  Water

    Few data are available on the routes of entry or the behaviour 
and fate of chlordane in aquatic systems.  It can be assumed that 
not much originates from ground water since there is little 
leaching of chlordane.  One possible source is surface run-off, but 
no studies have tested the extent of this assumption.  Another 
source is rain; however, in two studies, chlordane levels did not 
exceed 2 - 3 ng/litre rain water (Bevenue et al., 1972a; US EPA, 
1976a,b). 

    One important aspect of chlordane residues is that they 
accumulate in sediment.  The fate and behaviour of chlordane was 
investigated in an isolated fresh water lake, previously free from 
pesticide residues (Oloffs et al., 1978).  The lake was treated 
with technical chlordane at 10 g/litre, and sediment samples were 
analysed for chlordane residues 7, 24, 52, 279, and 421 days after 
treatment.  It was found that water residue concentrations declined 
rapidly.  After 7 days, only 46.1% of the chlordane residue 
remained.  After 421 days, residues were still detectable, but all 
levels were below 0.01% of the initial concentration.  It was 
observed that chlordane residues moved quickly to the bottom 
sediment and persisted there.  Mean residue levels in sediment were 
35.29 g/kg wet weight after 7 days and 10.31 g/kg after 421 days. 

3.2.3.  Soil

    Chlordane is used almost exclusively as a soil insecticide to 
control soil pests such as termites (Canada, National Research 
Council, 1974).  Thus, residues of chlordane are mainly present in 
this environmental compartment.  In most temperate climates, only 
the two chlordane isomers generally persist (Canada, National 
Research Council, 1974).  For example, in Nova Scotia, chlordane 
was applied at 5 kg/ha per year to sandy loam soil for 3 years.  
Fifteen years later, approximately 15% of the residues remained, 
the alpha and gammma isomers being the major components (US EPA, 
1976a,b). 

    The components of technical chlordane are relatively insoluble 
in water and are readily adsorbed onto soil particles.  As a 
result, one of the characteristics of soil residues is that they do 
not migrate readily through the soil profile (Canada, National 
Research Council, 1974; von Rumker et al., 1974).  In general, not 
more than 15% of the residues migrate below the cultivated layer 
(Canada, National Research Council, 1974).  As a result, residues 
are not likely to become a serious contaminant of the lower soil 
strata or deep water sources (Canada, National Research Council, 
1974).  The organic matter and moisture contents of the soil can 
affect the volatilization of chlordane components (Stauffer, 1977). 
The organic matter causes greater adsorption and thus reduces 
volatilization while soil moisture increases volatilization 
(Stauffer, 1977).  Also, liquid formulations are more volatile than 
granular (Atallah et al., 1979). 

3.2.4.  Abiotic degradation

    Chlordane is stable to light under normal conditions.  When it 
is exposed to photosensitizers such as rotenone or benzophenone and 
short irradiation exposure at wavelengths above 300 nm, some 
components will isomerize (Canada, National Research Council, 
1974).  No detectable degradation products were formed on plant 
foliage in the absence of a photosensitizer (Ivie et al., 1972). 

3.2.5.  Biodegradation

    Three conversion products of gamma-chlordane were found in 
white cabbage and carrots, 4 weeks after application.  One of the 
two metabolites isolated from white cabbage (35% of the total), was 
given the chlordene chlorohydrin structure.  The other isolated 
metabolite (15% of the total) was assigned the dihydroxy-beta-
dihydroheptachlor structure.  The third metabolite was not 
identified.  1,2-Dichlorochlordene, oxychlordane, and photo-alpha-
chlordane, as well as the parent chlordane compounds, were found in 
alfalfa after treatment of the soil with chlordane (Canada, 
National Research Council, 1974). 

    Oxychlordane (or 1,2-dichlorochlordene epoxide) is the common 
metabolite derived from both alpha- and gamma-chlordane.  It has 
been found in the fat of pigs fed either of the isomers and in the 
milk and cheese from cows fed alfalfa treated with technical 
chlordane.  According to some authors, alpha- and gamma-chlordane 
give rise to oxychlordane via the intermediate 1,2-dichloro-
chlordene (Canada, National Research Council, 1974). 

4.  ENVIRONMENTAL LEVELS AND EXPOSURES

4.1.  Environmental Levels 

4.1.1.  Air

    Generally, atmospheric concentrations of chlordane appear to be 
insignificant.  However, chlordane has been detected in the air of 
buildings where the compound has been used for termite or other 
insect control (US EPA, 1976a,b).  Insufficient information is 
available on this. 

4.1.2.  Water

    Data from several studies indicate that contamination of water 
with chlordane is not a widespread problem (US EPA, 1976a,b), and 
that, generally, water residue levels are non-measureable or very 
low (Canada, National Research Council, 1974). 

    In a study of the bottom material of 26 tributary streams in 
San Fransisco Bay, chlordane was found to be ubiquitous at 
concentrations ranging from a trace to 800 g/kg (Oloffs et al., 
1978). 

    No chlordane was detected in 188 samples of surface water from 
southern Florida but it was detected in 30% of 214 sediment samples 
(Mattraw, 1975).  In a study in Hawaii in 1970-71 (Bevenue et 
al., 1972b), chlordane was found in drinking-water in 9% of samples 
at a mean level of 1.0 ng/litre.  Chlordane was detected in non-
potable waters from canals at levels ranging from 3.7 - 9.1 
ng/litre.  Again, sediments showed much higher levels of 190 - 378 
g/kg.  Chlordane was found to occur in the lower Mississippi river 
almost continuously throughout 1974 at values ranging from 1.3 to 
2.9 ng/litre (Brodtmann, 1976).  In a study in the lower 
Mississippi (Barthel et al., 1969), during 1964-67, chlordane 
residues ranged from 0.80 to 2.80 mg/kg in river bed material 
samples.  In tributaries of the river, values ranged from 0.56 - 
6.44 mg/kg, in 13 out of 348 samples.  No chlordane was detected in 
any water or sediment samples taken from the upper Great Lakes in 
1974 (Glooschenko et al., 1976).  In one study in 1976 (Harrington 
et al., 1978), chlordane contamination of a municipal water system 
was reported, concentrations of chlordane accidently rising to 1.2 
g/litre. 

4.1.3.  Soil

    One study has shown that the alpha- and gamma-isomers of 
chlordane are less persistent in mineral sand soil than in organic 
mucky soil (Harris & Sans, 1976).  Data from the National Soils 
Monitoring Program in 1970 showed that chlordane occurred in 0.07% 
of 1346 sites in 35 States.  The range of residues was 0.01 - 13.34 
mg/kg dry weight with a mean of 0.08 mg/kg (Crockett et al., 1974).  
Monitoring of the corn belt region in the USA (12 States) in 1970 
showed chlordane to be one of the most commonly detected 
insecticides with values of ND - 0.20 mg/kg (Carey et al., 1973).  

Data from 9 States in 1971 detected chlordane in one soil sample at 
0.04 mg/kg dry weight (Gowen et al., 1976).  Monitoring in 1973 
showed residues ranging from 0.001 - 0.020 mg/kg with generally 
higher values in urban areas.  When urban soils were tested in 14 
cities in the USA in 1970, values ranged from 0.01 - 1.27 mg/kg.  
In the Atlantic provinces of Canada, chlordane was detected in less 
than 10% of agricultural lands at concentrations below 1 mg/kg dry 
weight (Duffy & Wong, 1967).  In another study on chlordane in 
Saskatchewan soils (Saha & Sumner, 1971), 7 out of 41 samples 
contained chlordane with residue values ranging from 0.01 to 3.91 
mg/kg dry weight.  The duration of soil contamination has been 
studied by several investigators.  Using bioassay techniques, it 
was found in one study that 15% of active ingredients remained in 
turf soils in Wisconsin after 12 years (Lichtenstein & Poliuka, 
1959).  In a study in 1970 (Lichtenstein, 1970), it was found that 
10 years after application of chlordane at 8.5 kg /ha, 
approximately 18 - 20% remained. 

4.1.4.  Crops and wildlife

    Since chlordane residues are present predominantly in the soil, 
translocation into plants is an important factor.  In most 
temperate climates, alpha- and gamma-chlordane are the principal 
plant residues.  In the Canadian climate, the composition of plant 
residues resembles that of technical chlordane (Canada, National 
Research Council, 1974).  In a field study on soil/plant 
relationships, it was found that the relationship between residues 
in soil and those in crops was not consistent and consequently not 
predictable (Boyd, 1971). 

    In a three-year study, Onsager et al. (1970) monitored 
chlordane residues in sugar beets cultivated on loam soil treated 
once at 6 different application rates ranging from 1.4 - 22.4 
kg/ha.  In the first growing season, only sugar beets treated at 
the two lowest rates (1.4 and 2.8 mg/kg) showed residues below 0.3 
mg/kg dry weight.  In the last two seasons, beets from soil treated 
at all rates contained residues below this value.  In another 
study, uptake by root crops was shown to be related to the soil 
type (Stewart, 1975).  When chlordane was applied to sandy loam 
soil with 12% clay at 15 kg/ha, residues in beets, carrots, 
parsnips, potatoes, and rutabagas were 0.03, 0.26, 0.24, 0.04, and 
0.01 mg/kg, respectively.  In sandy loam containing 28% clay, 
values were 0.01, 0.07, 0.12, 0.15, and 0.01 mg/kg, respectively.  
A study of residues in alfalfa following applications of high 
purity chlordane showed that during the first 4 months following 
treatment, oxychlordane and photo-alpha-chlordane accounted for 16% 
and 17% of the residues, respectively (Wilson & Oloffs, 1973a). 

    Generally, no detectable residues of chlordane were found in 
wildlife such as birds (Canada, National Research Council, 1974; 
Fitzhugh & Fairchild, 1976; Clark & Krynitsky, 1978).  However, 
in one study (Clark & Prouty, 1976), mean total residues of 
oxychlordane ranging from 0.11 to 6.63 g found in the carcasses 
of bats from Maryland and Virginia were attributed to chlordane 
use. 

    In extensive surveys, residues in fish have generally been low.  
In 1976, residues in several species from Lake Erie and Lake Saint 
Claire in Canada were found to range from non-detectable to 0.046 
mg/kg fresh weight (Frank et al., 1978a,b).  Residues in Canadian 
commercially caught fish in 1970 were not detectable (Reinke et 
al., 1972).  The National Pesticide Monitoring Program from 1967-68 
found chlordane residues in 128 out of 590 fish samples at levels 
generally less than 0.5 mg/kg (Wilson & Oloffs, 1973b).  From 
1972-76, chlordane residues were found in only 3% of the samples of 
estuarine fish in the USA (Butler & Schutzmann, 1978).  Chlordane 
residues were also not detectable in fish and fishery products from 
the Northwestern Atlantic (Meith-Avcin et al., 1973; Sims et al., 
1977). 

4.1.5.  Food

    There have been many studies in Canada, Great Britain, the USA, 
and other countries on the occurrence of pesticide residues in 
food.  Generally, the results of these studies showed that residues 
of chlordane seldom occur and uptake by man is negligible (Canada, 
National Research Council, 1974).  Residue tolerances for chlordane 
have been established at the following levels:  Belgium, Luxembourg, 
and the Netherlands, 0.1 mg/kg, Canada, 0.3 mg/kg, European 
Economic Community, 0.2 mg/kg and the USA, 0.3 mg/kg.  These levels 
are for a wide variety of foods (US EPA, 1976a,b).  A temporary 
acceptable daily intake (ADI) for human beings for the sum of the 
alpha- and gamma-isomers of chlordane and oxychlordane of 0 - 0.001 
mg/kg body weight was advised by the Joint Meeting on Pesticide 
Residues (FAO/WHO, 1983).  Chlordane is rarely present in market 
basket surveys, and then only at low levels.  It is not among the 
top 10 chlorinated pesticides usually found as residues in food (US 
EPA, 1976a,b).  For example, in a survey in the USA from 1963 to 
1969, chlordane residues were found in less than 1% of the samples 
and ranged from 1 - 5 g/kg. 

    It has already been shown that crops will translocate chlordane 
residues from the soil.  Generally, the amounts in crops are low.  
Residues tend to accumulate in the crude oils of oil-seed crops at 
levels higher than those in the original seed and in the oil-seed 
meal.  However, these levels are reduced by refining processes.  
Chlordane residues were found in meat, milk, and eggs.  Residues in 
feed crops or from direct applications to cattle and poultry were 
shown to result in significant residues in milk, meat, and eggs (US 
EPA, 1976a,b).  In a study on eggs in Canada, gamma-chlordane was 
found in 78% of the samples with a mean value of 2 g/kg fresh 
weight and alpha-chlordane in 81% of the eggs with a mean value of 
1 g/kg (Mes et al., 1974).  In another study (Herrick et al., 
1969), no residues were found in the eggs of chickens fed chlordane 
in their diet at 0.08 mg/kg for a week. 

    In a study on samples of cow's milk analysed in the USA, 87% 
were positive for chlordane with levels ranging from 0.02 to 0.06 
mg/litre (IARC, 1979).  In another study (US EPA, 1976a,b), the 
milk of cows grazing on pastures with chlordane applied at 0.55 
kg/ha contained an average chlordane concentration of 0.03 

mg/litre.  No residues were found at lower treatment levels.  
Chlordane was also found in Canadian meat samples at levels ranging 
from 0 to 106 g/kg in beef, 0 to 32 g/kg in pork, and 0 to 70 
g/kg in fowl (Saschenbrecker, 1976). 

4.1.6.  Human milk

    Several studies on pesticide residues in human breast milk did 
not reveal any residues of chlordane, but oxychlordane, trans-
nonachlor, and heptachlor epoxide were found, which may be related 
to chlordane exposure.  In a study on 54 women in Arkansas and 
Mississippi from 1973-74, breast milk contained oxychlordane at 
0.005 mg/litre, heptachlor epoxide at 0.004 mg/litre, and trans-
nonachlor at 0.001 mg/litre (Strassman & Kutz, 1977).  In another 
study on 34 samples of breast milk in Northern Mississippi from 
1973-75, oxychlordane levels were found of 0.005 mg/litre in high-
pesticide-usage areas and 0.002 mg/litre in low-usage areas 
(Barnett et al., 1979).  In a survey involving 1436 lactating 
mothers in the USA, the mean levels of oxychlordane in the milk 
ranged from 75.4 - 116 g/litre on an adjusted fat basis (Savage, 
1976).  In a study of Canadian human milk samples in 1974, 
oxychlordane was found in 77% of the samples, trans-nonachlor in 
68%, and heptachlor epoxide in 69%, each at a mean level of 1 
mg/litre whole milk (Mes & Davies, 1978). 

    Jensen (1983) recently reviewed the levels of chlordane
and oxychlordane in human milk, and his data, including the
above-mentioned studies as well as more recent data, are
reproduced in Table 1.

4.2.  General Population Exposure 

    Oxychlordane was found together with other organochlorine
pesticides in human fat samples at levels ranging from 0.03 to
0.4 mg/kg wet weight (mean 0.14 mg/kg) in residents of the USA
(Biros & Enos, 1973).  Sovocool & Lewis (1975) also reported
the identification of oxychlordane in human fat.  As indicated
by Biros & Enos (1973), the occurrence of oxychlordane
residues in human adipose tissue in the general population may
reflect previous exposure to chlordane and/or oxychlordane.
This organochlorine compound is included in the human tissue
residue monitoring program (Kutz et al., 1976).

4.3.  Occupational Exposure 

    Permissible levels of exposure to chlordane in the workplace 
air have been adopted in different countries (ILO, 1980).  Examples 
include:  0.5 mg/m3 as a time-weighted average concentration in 
Belgium, Finland, Japan, the Netherlands, and the USA (both OSHA 
and ACGIH), 0.3 mg/m3 as a time-weighted average and 0.6 mg/m3 
as a ceiling concentration in Romania, and 0.01 mg/m3 as maximum 
allowable concentration in the USSR. 

    People primarily exposed are those employed in the application 
of chlordane for the control of insects and pests (IARC, 1979).  
Chlordane has been found in household dust in the homes of farmers 
(mean level 5.79 mg/kg air-dried dust) and pesticide formulators 
(mean level 23.11 mg/kg) (Starr et al., 1974). 


Table 1.  Chlordane and oxychlordane in human milka
------------------------------------------------------------------------------------------------------
                                                 Oxychlordane and 
                                                 chlordane content inb       
                                                 ---------------------
                        No. of samples  Fat      Whole milk   Milk fat
Area, year              (% positive)    % (mean) (mg/litre)   (mg/kg)        References
------------------------------------------------------------------------------------------------------
Canada (1975)           100             2.2      1            -              Mes & Davies (1978)
                                                 (< 2)

Japan
  Tokyo (1978)          11              -        0.5          -              Miyazaki et al. (1980)
                                                 (0.1 - 1.0)
  Tokyo (1979)          12              -        0.5          -              Miyazaki et al. (1980)
                                                 (0.3 - 1.1)

Mexico (1976)           620             -        -            0.40 (median)  FAO/WHO (1981)

Spain (1979)            45 (17.8%)      -        0.3c         0.026c         Lora et al. (1979)
                                                              (0 - 0.72)
USA
  Arkansas/Mississippi  57 (46%)        3.0      12/10        -              Strassman & Kutz (1977);
  (1973-4)                                       (0 - 20)                    FAO/WHO (1981)
------------------------------------------------------------------------------------------------------
Table 1.  (contd.)                                    
------------------------------------------------------------------------------------------------------
                                                 Oxychlordane and 
                                                 chlordane content inb       
                                                 ---------------------
                        No. of samples  Fat      Whole milk   Milk fat
Area, year              (% positive)    % (mean) (mg/litre)   (mg/kg)        References
------------------------------------------------------------------------------------------------------
  Hawaii (1979-80)      50 (100%)       3.2      -            0.059          Takahashi et al. (1981)
                                                              (0.01 - 0.16)
  Mississippi (1973-5)  34 (100%)       -        5            0.13           Barnett et al. (1979)
  (pesticide area)                               (1 - 22)     (0.03 - 0.70)
  Mississippi (1973-5)  6 (68%)         -        2            0.05           Barnett et al. (1979)
  (non-pesticide area)                           (0 - 4)      (0 - 0.12)

  USA-NE (1975)         233             -        -            0.08  0.05    Savage (1976);
                                                                             Savage et al. (1981)
  USA-SE (1975)         288             -        -            0.12  0.15    Savage (1976);
                                                                             Savage et al. (1981)
  USA-MW (1975)         378             -        -            0.08  0.05    Savage (1976);
                                                                             Savage et al. (1981)
  USA-SW (1975)         388             -        -            0.11  0.35    Savage (1976);
                                                                             Savage et al. (1981)
  USA-NW (1975)         149             -        -            0.08  0.05    Savage (1976);
                                                                             Savage et al. (1981)
  USA (total) (1975)    1 436 (74%)     -        2 (median)   0.096  0.195  Savage (1976);
                                                              (0.013 - 0.57) Savage et al. (1981)
                                                                             FAO/WHO (1981)
------------------------------------------------------------------------------------------------------
a  From:  Jensen (1983).
b  Results are expressed as means  S.D. Ranges are listed in parentheses below.
c  Chlordane.

5.  KINETICS AND METABOLISM

5.1.  Absorption 

    In studies on 4 male rabbits, a combination of 14C-alpha and 
gamma-chlordane (approximately 1700 mg of each, administered orally 
in 4 doses at 4-day intervals), was well absorbed (Balba & Saha, 
1978).  Brief exposure of dogs to topically applied chlordane 
solutions (3.2 g/litre) resulted in a significant and long-lasting 
decrease in the biological half-life of orally-administered 
warfarin (Bachmann & Burkman, 1974). 

5.2.  Distribution and Storage 

    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-isomers was retained than of the 
alpha-isomer.  Residues in the fat of rats fed radiolabelled 
chlordane (3:1 alpha- and gamma-chlordane) at 1, 5, and 25 mg/kg 
diet for 56 days were approximately 3 times higher than those in 
the diets.  Oxychlordane was the most persistent residue in the 
tissues of these rats after chlordane was removed from the diet 
(Barnett & Dorough, 1974).  The tissue distribution of chlordane in 
rabbits was found to be similar to that in rats (Poonawalla & 
Korte, 1971; Balba & Saha, 1978). 

5.3.  Biotransformation 

    Poonawalla & Korte (1971) showed that 70% of gamma-chlordane
fed to rabbits was excreted in the urine in the form of
metabolities, a.o., gamma-1-hydroxy-2-chlorodihydrochlordene and
1,2-dihydroxydichlordene.

    Oxychlordane has been isolated from the fat of dogs, rats 
(Polen et al., 1971), pigs (Schwemmer et al., 1970), and cattle 
(Lawrence et al., 1970).  It has also been isolated from human fat 
(Biros & Enos, 1973).  Barnett & Dorough (1974) indicated that the 
faecal extracts of rats fed 14C-chlordane showed the presence of 
eight radioactive areas on the TLC plate.  Although the structures 
of the metabolites were not fully elucidated, they were tentatively 
identified as mono-, di-, and tri-hydroxylated products of 
chlordane. 

    The major route of metabolism for both alpha- and gamma-
chlordane was via dichlorochlordene and oxychlordane (Tashiro & 
Matsumura, 1977).  The results of these studies were in general 
agreement with the proposal of Street & Blau (1972) and the results 
of  in vitro metabolism studies of Brimfield et al. (1978).  
Tashiro & Matsumura (1977) were able to isolate 1-exo-hydroxy-2-
endo-chloro-2,3-exoepoxychlordene, and found another major 

metabolic route for alpha-chlordane that involved a more direct 
hydroxylation reaction to form 1-exo-hydroxy-dihydrochlordenes and 
1,2-gamma-dihydroxydihydrochlordene.  Both Brimfield et al. (1978) 
and Tashiro & Matsumura (1977) indicated that oxychlordane and, to 
a lesser extent, heptachlor were metabolites of chlordane.  
However, they did not agree as to whether these two metabolites 
would be terminal residues or intermediates in the metabolic 
pathways of chlordane.  Recent investigations have indicated that 
other metabolites were present in the urine of rabbits fed 
chlordane.  Thus, alpha-chlordane gave rise to 1-hydroxy-2-
chlorochlordene, 1-hydroxychlordene, and gamma-chlordene 
chlorhydrin.  Administration of the gamma-isomer resulted in 
excretion in the urine of the rabbits of 1,2-dichlorochlordene, 
1-hydroxy-2-chlorochlordene, gamma-chlordene chlorhydrin, and 
3-hydroxychlordane (Balba & Saha, 1978). 

     In vitro metabolism studies have been summarized by Brimfield 
& Street (1979).  By incubation of alpha- and gamma-chlordane with 
rat liver postmitochondrial supernatant, dichlorchlordene and 
oxychlordane were isolated, a result that was similar to those from 
 in vivo studies.  Hart et al. (1963) and Hart & Fouts (1965) 
reported that chlordane induced non-specific microsomal enzyme 
activity in the rat, resembling, from this point of view, 
phenobarbital. 

5.4.  Elimination and Excretion 

    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 h after administra-
tion, 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 & Dorough, 1974). 

6.  STUDIES ON EXPERIMENTAL ANIMALS

    The toxicity and the residue data on chlordane including some 
unpublished studies have been reviewed several times by 
international bodies such as FAO/WHO (1968, 1973, 1978, 1981, 
1983), CEC (1981), and IARC (1979).  For their conclusions, refer 
to section 9. 

6.1.  Short-term Exposures 

6.1.1.  Oral exposure

    The acute toxicity of chlordane in several animal species is 
shown in Table 2. 

    The signs associated with acute chlordane poisoning include 
ataxia, convulsions, respiratory failure, and cyanosis followed by 
death (US EPA, 1976a,b).  Correlation between respiratory 
difficulty and EEG patterns suggest that respiratory failure is a 
contributing factor in chlordane-induced mortality (Hyde & 
Falkenberg, 1976).  Pathological manifestations include haemorrhage 
in the gastrointestinal tract, kidneys, lung, and heart as well as 
pulmonary congestion and oedema, and degenerative changes in the 
central nervous system (US EPA, 1976a,b). 

    Seven dogs were given chlordane in single oral doses ranging 
from 200 - 700 mg/kg body weight.  Convulsions were seen in one dog 
at 200 mg/kg (lowest dose) but 700 mg/kg (highest dose) did not 
induce any effects (Batte & Turk, 1948).  Four groups of 2 - 4 dogs 
were given chlordane orally in doses of 5 - 200 mg/kg body weight.  
All of the dogs died within 25 days to 93 weeks (Lehman, 1952b). 

    Chlordane administered by stomach-tube to sheep at 500 mg/kg 
body weight induced toxic symptoms (incoordination, partial 
blindness).  Full recovery occurred in 5 - 6 days.  A dose of 1000 
mg/kg body weight induced severe respiratory and nervous symptoms 
16 h after treatment and death after 48 h (Welch, 1948). 

    When a diet containing 1000 mg chlordane/kg was fed to 12 male 
rats, all of them died within 10 days (Stohlman et al., 1950).  At 
500 mg/kg all 12 died within 70 days and, at 300 mg/kg, 9 animals 
out of 12 were alive after 100 days.  Daily oral doses of 6.25 - 25 
mg/kg body weight administered to 5 rats for 15 days did not induce 
tremors or convulsions, but daily doses of 50 mg/kg body weight 
induced toxic symptoms, and 2 of the animals died (Ambrose et al., 
1953).  Cytoplasmic bodies in the liver cells were observed in all 
groups and were dose-related. 


Table 2.  Acute toxicity of chlordane in experimental animals
---------------------------------------------------------------------------
Species  Sex  Route   Vehicle         LD50         Reference
                                      (mg/kg)
---------------------------------------------------------------------------
Rat      F    dermal  xylene          530          Gaines (1969)

Rat      M    dermal  xylene          205          Gaines (1969a)

Rabbit   NS   dermal  "early"         < 780        Ingle (1965b)
                      chlordane

Rabbit   NS   dermal  "later"         1100 - 1200  Ingle (1965b)
                      chlordane
                      (more purified)

Rat      M    oral    peanut oil      335          Gaines (1969)

Rat      F    oral    peanut oil      430          Gaines (1969)

Rat      NS   oral    variety         200 - 590a   Ambrose et al. (1953);
                                                   Ingle (1965a)

Rat      NS   oral    NS              283          Buck et al. (1973)

Rat      NS   oral    NS              350          Truhaut et al. (1974)

Rabbit   NS   oral    NS              100 - 300a   Stohlman et al. (1950)

Rabbit   NS   oral    NS              20 - 40a     Ingle (unpublished
                                                   data, 1955)

Hamster  NS   oral    NS              1720         Truhaut et al. (1974)

Goat     NS   oral    NS              180          Welch (1948)

Sheep    NS   oral    NS              500 - 1000   Welch (1948)

Chicken  NS   oral    NS              220 - 230    FAO/WHO (1968)

Mallard  NS   oral    NS              1200         Buck et al. (1973)

Cow      NS   oral    NS              25 - 90      Buck et al. (1973)
---------------------------------------------------------------------------
a  The wide range is explained by the use of different solvents and the
   fact that chlordane produced before 1950 contained a considerable
   amount of hexachlorocyclopentadiene.

NS - Not specified.
6.1.2.  Dermal exposure

    The single-dose dermal LD50 of "early" chlordane in rabbits 
was reported to be less than 780 mg/kg body weight (Ingle, 1965b), 
and it was noted that this concentration caused severe skin 
irritation, tremors, and convulsions (Lehman, 1952a).  The dermal 
LD50 of the later, more purified chlordane was 1100 - 1200 mg/kg 
(Ingle, 1965b). 

6.1.3.  Parenteral exposure

    Male gerbils were dosed intramuscularly with chlordane at 2.5 
mg/kg body weight every 3 days for 45 days.  Treatment induced 
hyperproteinemia, hyperglycemia, and enhanced serum alkaline and 
acid phosphatase activities (Karel & Saxena, 1976). 

6.2.  Long-term Exposures 

6.2.1.  Oral exposure

    Groups of 4 - 7 male and 4 - 7 female dogs were fed dietary 
levels of 0, 0.3, 3, 15, or 30 mg chlordane/kg for 2 years.  
Abnormalities in the results of clinical liver function tests were 
seen in the 15 and 30 mg/kg groups.  In animals selected for 
necropsy at the end of the first year, increased relative liver 
weights and associated hepatocellular changes were found at 30 
mg/kg; at the end of two years, dose-related increases in relative 
liver weights were found at 15 and 30 mg/kg, with non-dose-related 
hepatocellular changes.  There was no difference between the 
severity of the liver lesions of the 30 mg/kg animals and those of 
four animals withdrawn from 30 mg/kg treatment for eight months 
prior to sacrifice.  Liver biopsies on two animals of the 30 mg/kg 
group at 1, 3, and 6 months showed hepatocellular changes at 6 
months but not at 1 or 3 months.  No adverse effects were seen on 
behaviour, appearance, survival, weight gain, blood picture, or the 
results of periodic physical examinations, at any level (Wazeter, 
1967). 

    Twenty-four rats, 12 of each sex, were fed dietary levels of 
2.5, 25, or 75 mg chlordane/kg for 2 years (Lehman, 1952b).  The 
two higher levels caused moderate to severe signs of toxicity.  The 
lowest level caused histological liver changes.  Rats were fed 
technical chlordane (early production) for two years at levels in 
the diet of 0, 5, 10, 30, 150 or 300 mg/kg (Ingle, 1952; 1965a).  
Convulsions and tremors were observed in animals receiving 150 
mg/kg or more.  Hepatocellular alterations consisting of 
hypertrophy, cytoplasmic oxyphilia and hyalinization, karyorrhexis, 
karyolysis, and cell necrosis were obvious at 150 and 300 mg/kg, 
slight at 30 mg/kg, minimal at 10 mg/kg and absent at 5 mg/kg.  
Growth was retarded and liver weight and mortality rate increased 
at 150 and 300 mg/kg.  In a subsequent study on rats (Ingle, 
1965a), technical chlordane of later production containing fewer 
by-products was administered at levels of 2.5 - 300 mg/kg diet for 
2 years.  Changes in food consumption, growth, and mortality rate 
were seen only at the highest dose.  Cellular alterations were seen 
at 50 mg/kg and higher. 

    Rats were fed chlordane at levels ranging from 10 to 1280 mg/kg 
diet for 407 days (Ambrose et al., 1953).  The animals in the two 
highest dose groups died early; liver weight was increased at 320 
mg/kg; fatty infiltration and cytoplasmic margination were seen in 
the liver parenchymatous cells in males at 40 mg/kg and above, and 
in females at 80 mg/kg and above. 

    Groups, each comprising 20 male and 20 female rats, were fed 
dietary levels of 0, 5, 15, 25, or 35 mg/kg of alpha-chlordane, 15, 
25, 35, or 75 mg/kg of gamma-chlordane or 5, 15, 25, 35 or 50 mg/kg 
of a 1:1 mixture of alpha- and gamma-chlordane (Ingle, 1969).  In 
the group fed alpha-chlordane, growth retardation became apparent 
in the rats fed 35 mg/kg after 4 months in males and after 5 months 
in females; with gamma-chlordane, the 75 mg/kg group of males only 
displayed growth retardation after 8 months.  With the mixture, 
growth retardation was evident in both sexes fed 50 mg/kg, 
beginning earlier in males than in females.  Growth retardation was 
not evident in any group fed lower doses of either isomer.  Food 
consumption bore a relationship to growth.  Increased mortality 
rates for both sexes became significant in the groups fed alpha-
chlordane at 35 mg/kg, gamma-chlordane at 75 mg/kg, or the alpha- 
gamma mixture at 50 mg/kg.  Haematocrit was normal for all test 
groups.  Autopsy did not reveal any gross pathological lesions.  
There was no evidence of tumours.  Histological examination did not 
show any changes from feeding chlordane in any organ except the 
liver.  Compression of sinusoids due to slight hepatic cell 
hypertrophy in the centrolobular region and minimal bile duct 
proliferation were evident with administration of alpha-chlordane 
at 35 mg/kg.  The same changes were noted, but were minimal with 
the same isomer at 25 mg/kg.  Slight to moderate cytoplasmic 
homogeneity of the hepatic cells in the centrolobular region, 
minimal cytoplasmic margination, and minimal cell hypertrophy with 
compressed sinusoids were noted with administration of gamma-
chlordane at 75 mg/kg.  Slight cytoplasmic homogeneity of hepatic 
cells in the centrolobular region and occasional cytoplasmic 
margination were observed with the alpha-gamma mixture at 50 mg/kg.  
The above alterations were minimal with the same mixture at 35 
mg/kg.  No liver changes were evident after feeding lower levels of 
the chlordane isomers. 

    Groups of 6 female and 6 male rats were fed 2.5 mg or 25 mg of 
a sample of technical chlordane containing 60 - 75% chlordane and 
25 - 40% unrelated products per kg diet for up to 9 months (Ortega 
et al., 1957).  Centrolobular cell hypertrophy, cytoplasmic 
margination, and cytoplasmic bodies were observed in the liver in 1 
male fed 2.5 mg/kg and in 5 males fed 25 mg/kg.  No changes were 
seen in females. 

    In a two-year feeding study, pure-bred male and female beagle 
dogs were fed chlordane at levels of 0, 0.3, 3.0, 15, or 30 mg/kg 
diet.  No adverse treatment-related alterations were observed in 
behaviour, appearance, eye examination, body weight, food 
consumption, haematology, or plasma biochemistry.  Some liver 
enzyme activities were altered throughout the study at the 15 and 
30 mg/kg levels.  Relative liver weights were slightly increased 

after two years in the two highest groups.  Treatment-related 
microscopic changes, observed in dogs fed the two highest levels, 
consisted of enlargement of centrolobular hepatocytes with 
margination of coarse cytoplasmic granules (IRDC, 1967). 

    The Joint Meeting on Pesticide Residues (JMPR) reviewed the 
toxicity data on chlordane at its 1977 meeting (FAO/WHO 1978) and 
decided on the following "no-observed-adverse-effect levels": 

    -   rat:    5 mg/kg in the diet, equivalent to 0.25 mg/kg
                body weight; and

    -   dog:    3 mg/kg in the diet, equivalent to 0.075 mg/kg
                body weight.

    These "no-observed-adverse-effect levels" were confirmed by the 
1982 JMPR (FAO/WHO, 1983). 

6.2.2.  Dermal exposure

    When male guinea-pigs were exposed to chlordane at 67 mg/kg 
body weight/day, through dermal painting for 90 days, mild 
degenerative changes in the skin and testis were evident (Datta et 
al., 1975). 

    The ninety-day repeated daily dose LD50 for rabbits was 
reported in the paper by Lehman (1952a) (section 6.1.2) to be from 
20 - 40 mg/kg body weight.  Ingle (1965b) reviewed the dermal 
toxicity of chlordane and attributed the toxicity of early 
technical chlordane to the significant content of hexachloro-
cyclopentadiene (HCPD).  A more pure product, which did not contain 
significant quantities of HCPD, was only half as toxic to rabbits 
as the earlier chlordane and did not cause any skin irritation or 
damage to mucous membranes. 

6.3.  Reproduction Studies and Teratogenicity 

    Rats, maintained from weaning on a diet containing a chlordane 
level of 320 mg/kg, showed reduced rates of mating, of viable 
litters, and an increased rate of death of progeny prior to 
weaning.  It was concluded that, at this dosage, chlordane 
interfered with both fertility and litter survival (Ambrose et al., 
1953).  Groups of 10 male and 20 female rats were used in a 3-
generation study at dietary levels of technical chlordane of 0, 
0.3, 3, 15, 30, and 60 mg/kg (Ingle, unpublished data, 1967).  Two 
litters in each filial generation were studied.  Levels up to and 
including 30 mg/kg did not have any effect on fertility, number of 
offspring, or weight, growth, or mortality rate of the young 
animals to weaning age.  Autopsy of animals after weaning did not 
reveal any gross or microscopic differences between the groups.  At 
60 mg/kg, there was a high (10.6%) mortality rate in the second F3 
generation litters during the latter part of the nursing period; 
these animals showed gross and microscopic pathological changes, 
comparable with those characteristic for chlordane intoxication.  
However, survivors of this generation did not show any tissue 

changes at all.  A third set of F3 litters at 60 mg/kg suffered 17% 
mortality during the nursing period, with symptomatology and gross 
and microscopic tissue changes characteristic of chlordane 
intoxication.  Third F3 generation litters from dams removed from 
the 60 mg/kg group and placed on chlordane-free diets for 30 days 
prior to remating showed no differences in any respect from control 
litters.  No evidence of teratogenicity was found in this study. 

    Hens and cocks fed up to 0.3 mg chlordane/kg diet did not show 
any toxic symptoms or any adverse effects on egg weight, 
hatchability, or growth of chicks (Biotox, unpublished data, 1969). 

    Mice fed diets containing chlordane at 25 - 100 mg/kg for 6 
generations showed decreased viability in the first and second 
generations at 100 mg/kg; in the third generation at this level, no 
offspring were produced (Keplinger et al., 1968).  At 50 mg/kg, 
viability was reduced in the fourth and fifth generations, and at 
25 mg/kg no statistically significant effects were observed, even 
after 6 generations. 

    Chlordane was administered to rabbits orally at levels of 1.0, 
5.0, and 15 mg/kg body weight per day on the 6th - 18th days of 
gestation.  A control group and a positive control group were used.  
No changes were seen in behaviour, appearance, or body weight.  
Miscarriages were seen in 3 rabbits at the 1.0 mg/kg level and one 
rabbit at 15 mg/kg dose level.  No effects on any of the maternal 
or fetal parameters were noted.  No teratogenic effects were noted 
(IRDC, 1972). 

6.4.  Mutagenicity 

    Alpha-Chlordane, gamma-chlordane, and chlordene were tested in 
the Ames  Salmonella microsome assay and were not mutagenic (Simmon 
et al., 1977).  Chlordane was not mutagenic when tested using 5 
different strains of  Salmonella typhimurium in the Ames assay 
(Ercegovich & Rashid, 1977).  Chlordane was shown to enhance the 
number of ouabain-resistant mutants in Chinese hamster V79 cells 
and was considered weakly mutagenic (Ahmed et al., 1977b). 

    Chlordane induced unscheduled DNA synthesis in SV-40 human 
cells in culture without activation (Ahmed et al., 1977a).  It was 
established that chlordane-treated cells did not (for the most 
part) re-enter mitosis.  They were, instead, arrested somewhere 
between the G1 and G2 phases of the cell cycle.  Studies involving 
DNA synthesis were undertaken to determine more precisely at which 
phase (G1, S, G2) the cells are blocked.  The data showed that the 
treated cells were as competant in DNA replication as the control 
cells.  In both control and treated cultures, 25 - 30% of total DNA 
persisted as light-density material indicating that some of the 
pre-existing DNA never engaged in DNA synthesis.  Either a large 
fraction of cells failed to complete DNA synthesis or 25 - 30% of 
the cells did not enter phase S.  In any case, treated and control 
cells behaved the same in terms of DNA synthesis, indicating that 
treatment of the cells with chlordane blocked the cells at the G2 
stage of the cell cycle (Brubaker et al., 1970). 

    Chlordane induced gene conversions in  Saccharomyces cerevisiae  
strain D4 (Chambers & Dutta, 1976). 

    Neither alpha-chlordane (42, 58, and 290 mg/kg body weight 
single ip doses or 5 daily oral doses of 75 mg/kg body weight) nor 
the gamma-isomer (5 daily oral doses of 50 mg/kg body weight) had a 
significant effect in a dominant lethal assay on mice (Epstein et 
al., 1972).  Technical chlordane at dose levels of 50 or 100 mg/kg 
body weight in a dominant lethal study using mice failed to induce 
any dominant lethal changes (Arnold et al., 1977). 

    More recent 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.  Telang et al. proposed that chlordane was exhibiting 
properties exerted by many promoting agents. 

6.5.  Carcinogenicity 

    Epstein (1976) reported a previously unpublished study by the 
International Research and Development Corporation, carried out in 
1973, in which groups of 100 male and 100 female Charles River CD-1 
mice, 6 weeks of age, were fed technical-grade chlordane (purity 
not given) at 5, 25, and 50 mg/kg diet, for 18 months.  Excluding 
10 animals sacrificed from each group for interim study at 6 
months, mortality rates at 18 months ranged from 27 - 49%, except 
in males and females receiving the 50 mg/kg diet, in which the 
mortality rates were 86 and 75%, respectively.  A relatively large 
number of the deceased animals was lost due to autolysis.  A dose-
related increased incidence of liver hyperplastic nodules was 
reported in the 25 and 50 mg/kg diet test groups and a dose-related 
increased incidence of liver cell hypertrophy was found in all test 
groups.  A significant incidence of hepatocellular carcinomas 
compared with controls was also reported.  In the males receiving 
chlordane at 0, 5, 25, or 50 mg/kg diet, hepatocellular carcinomas 
were found in 3/33, 5/55, 41/52, and 32/39 animals, respectively; 
in females, the respective incidences were 0/45, 0/61, 32/50, and 
26/37. 

    Groups of 50 male and 50 female B6C3F1 hybrid mice, 5 weeks of 
age, were fed analytical-grade chlordane, consisting of 94.8% 
chlordane (71.7% alpha-chlordane and 23.1% gamma-chlordane), 0.3% 
heptachlor, 0.6% nonachlor, 1.1% hexachlorocyclopentadiene, 0.25% 
chlordene isomers, and other chlorinated compounds for 80 weeks 
(NCI, 1977).  Males received initial levels of 20 or 40 mg/kg diet, 
and females 40 and 80 mg/kg diet; time-weighted average dietary 
concentrations were 30 and 56 mg/kg for males and 30 and 64 mg/kg 
diet for females.  There were 20 male and 10 female matched 
controls and 100 male and 80 female pooled controls. Survival in 
all groups was relatively high, i.e., over 60% in treated males, 
over 80% in treated females, and over 90% in male and female 
controls.  A dose-related increase in the incidence of 

hepatocellular carcinomas was found in males and females.  The 
incidences were 43/49 and 34/49 in high-dose males and females, 
respectively, and 16/48 and 3/47 in low-dose males and females, 
respectively, compared with 2/18 and 0/19 in male and female 
matched controls, respectively. 

    Groups of 50 male and 50 female, 5-week-old Osborne-Mendel rats 
were given analytical-grade chlordane in the diet for 80 weeks, at 
initial levels of 400 and 800 mg/kg for males and 200 and 400 mg/kg 
for females (NCI, 1977).  The levels had to be reduced during the 
study because of adverse toxic effects; the time-weighted average 
dietary concentrations were 407 and 203 mg/kg for males and 241 and 
121 mg/kg for females.  There were 10 male and 10 female matched 
controls and 60 male and 60 female pooled controls.  Survivors were 
killed at 80 weeks, at which time approximately 50% of treated and 
control males and 60% of treated females and 90% of control females 
were still alive.  In all treated animals combined, there was an 
excess incidence of follicular-cell thyroid neoplasms (10/75 in 
treated females and 7/65 in treated males versus 0/10, 3/58, 0/6, 
and 4/51 in matched and pooled female and male controls); there was 
an excess of malignant fibrous histiocytomas in the treated male 
groups (8/88 versus 0/8 and 2/58 in matched and pooled male 
controls). 

    A committee of the National Academy of Sciences (NAS) in the 
USA was asked to review all available carcinogenicity data on 
chlordane as part of the cancellation hearings.  Chlordane was not 
found to be carcinogenic in rats and the only target organ site for 
carcinogenic response in certain strains of mice was the liver.  
The committee concluded that "there are no adequate data to show 
that these compounds are carcinogenic in humans, but because of 
their carcinogenicity in certain mouse strains and the extensive 
similarity of the carcinogenic action of chemicals in animals and 
in humans, the committee concluded that chlordane, heptachlor 
and/or their metabolites may be carcinogenic in humans.  Although 
the magnitude of risk is greater than if no carcinogenicity had 
been found in certain mouse strains, in the opinion of the 
committee the magnitude of risk cannot be reliably estimated 
because of the uncertainties in the available data and in the 
extrapolation of carcinogenicity data from laboratory animals to 
humans" (US NAS, 1977). 

    IARC (1979), in its evaluation of the carcinogenic risk of 
chlordane, concluded:  "There is sufficient evidence that chlordane 
is carcinogenic in mice."  In 1982, another IARC Working Group 
reviewed existing data on chlordane and concluded that there was 
limited evidence for the carcinogenicity of chlordane for 
experimental animals (IARC, 1982).  The group of Williams (Telang 
et al., 1982) suggested that chlordane had the properties of many 
promoting agents. 

6.6.  Behavioural Studies 

    Offspring of chlordane-treated mice (1 or 2.5 mg/kg body weight 
for 7 consecutive days) made fewer conditioned avoidance responses 

than controls (Al-Hachim & Al-Baker, 1973).  In addition, progeny 
of mothers receiving the higher dose were more active than the 
controls. 

6.7.  Other Studies 

    Chlordane induces hepatic mixed-function oxidase enzymes in 
rats (Fouts, 1963; Hart et al., 1963; Hart & Fouts, 1965; 
Villeneuve et al., 1972; den Tonkelaar et al., 1974; Madhukar & 
Matsumura, 1979) and enhances estrone metabolism in rats and mice 
(Welch et al., 1971).  Chlordane has been shown to inhibit skin 7-
ethoxycoumarin de-ethylase activity (7-EC) (EC 1.14.13) in mice at 
doses which induced hepatic 7-EC activity (Pohl & Fouts, 1977).  
Several studies were carried out in which rats were fed chlordane 
at levels of 2, 5, 10, 20, or 50 mg/kg diet during two weeks (den 
Tonkelaar et al., 1974).  At the end of this period, the liver 
microsomal enzymes hexobarbital oxidase (EC 1.1), aminopyrine 
demethylase (EC 1.5.3), and aniline hydroxylase (EC 1.14.14) were 
determined.  A no-observed-adverse-effect level of 5 mg/kg was 
found for chlordane.  Chlordane inhibition of rat brain ATPase 
activity (Folmar, 1978) and bovine carbonic anhydrase (EC 4.2.1.1) 
(Maguire & Watkin, 1975) has been demonstrated in  in vitro  
systems.  The  in vivo inhibition of rat brain ATPase has also 
been reported (Drummond et al., 1980). 

    Three female and 3 male baboons were fed atherogenic diets to 
which chlordane was added at 0.1 or 1 mg/kg body weight per day for 
two years.  At the higher dose level, chlordane increased 
cytochrome P-450 activity significantly, otherwise no adverse 
effects on general health or on any major organ systems were found 
(McGill, 1979). 

    Acute intramuscular doses (50 mg/kg body weight) of chlordane 
have been shown to increase the alkaline phosphatase (EC 3.1.3.1) 
activity in gerbils temporarily (Karel, 1976) and stimulate 
gluconeogenetic enzymes in the liver and kidney cortex of rats 
(Kacew & Singhal, 1973a).  Oral administration of 200 mg alpha-
chlordane/kg body weight to mature Wistar rats also induced 
elevated serum levels of glucose and urea with a concomitant 
decrease in liver glycogen at sacrifice, 1 h later (Kacew & 
Singhal, 1973b).  The chlordane-induced alterations have been 
attributed to the enhanced ability of these organs to synthesize 
cyclic AMP (Kacew & Singhal, 1973b, 1974; Singhal & Kacew, 1973, 
1976; Kraybill, 1977). 

    Rats were administered chlordane ip daily for 42 days at levels 
of 0.15, 1.75, or 25.0 mg/kg body weight.  Results revealed "dose-
dependent alterations of brain potentials without behavioural signs 
of chronic toxicity" (Hyde & Falkenberg, 1976, Hyde et al., 1978).  
Chlordane has also been shown to influence brain biogenic amines 
including acetylcholine (Hrdina et al., 1973). 

    Prenatal exposure to 0.16 mg chlordane/kg body weight, in 
peanut butter, on each day of gestation, resulted in increased 
plasma corticosterone levels in adult male mice (Cranmer et al., 

1978).  When neonatal mice were treated with 0.075 mg alpha- or 
gamma-chlordane on days 2 - 4 after birth, growth rates were 
depressed and eye and vaginal opening were delayed (Talamantes & 
Jang, 1977). 

    Female Balb C mice were mated and treated with chlordane at 
0.16 or 8 mg/kg body weight throughout gestation. Decreased cell-
mediated immune competence was found in offspring of high-dose-
treated females, at 101 days of age, challenged with oxazolone 
(Spyker-Cranmer et al., 1982). 

    Chlordane added to the medium at a concentration of
1 mg/kg inhibited the growth of  Streptococcus viridans in
 vitro by more than 50%.  Total growth inhibition occurred at a
chlordane concentration of 3 mg/kg (Goes et al., 1978).

6.8.  Factors Influencing Toxicity

    Metabolites

    The acute oral toxicity of chlordane isomers and their 
metabolites is summarized in Table 3. 

Table 3.  Toxicity of chlordane isomers and metabolites
-----------------------------------------------------------------------
Compound                Species    LD50 (mg/kg   Reference
                        (sex)      body weight)
-----------------------------------------------------------------------
alpha-chlordane         rat (M)    392           Wazeter et al. (1968)

gamma-chlordane         rat (M)    327           Wazeter et al. (1968)

alpha + gamma-          rat (M)    371           Wazeter et al. (1968)
chlordane (1:1 ratio)

oxychlordane            rat (M,F)  19.1          Mastri et al. (1969a)

chlordene               rat (M,F)  over 4600     Mastri et al. (1969b)
                                                 
3-chlorchlordene        rat (M,F)  over 4600     Mastri et al. (1969b)

1-hydroxychlordene      rat (M,F)  over 4600     Mastri et al. (1969b)

chlordene epoxide       rat (M,F)  over 4600     Mastri et al. (1969c)

1-hydroxy, 2,3-epoxy    rat (F)    over 4600     Mastri et al. (1969c)
chlordene

2-chlorchlordene        rat (F)    over 10 200   Mastri et al. (1969c)
-----------------------------------------------------------------------

    Only oxychlordane was more toxic than the parent compounds.  
Two male and 2 female rats were given the chlordane metabolite 
oxychlordane in their diet, at a level of 2.0 mg/kg body weight 
(Plank et al., 1970).  Following 90 days feeding, the surviving 
animals were sacrificed.  Body-weight gain, food consumption, 
behaviour, mortality rate, organ weights and organ to body weight 
ratios, and the results of haematological and blood chemistry tests 
and urological studies were considered to be within the normal 
range for the strain of rat used.  No gross pathological 
abnormalities were evident, and no histopathological lesions could 
be attributed to oxychlordane. 

    Groups of 25 male and 25 female rats were fed dietary levels of 
1-hydroxychlordene of 0, 100, 250, 500, 1000, and 2000 mg/kg for up 
to 224 days (Ingle, 1965a).  After 110 days, 3 females from each 
feeding level were mated with males at all levels.  The mortality 
rate in all groups was low, and no statistically significant 
differences existed.  No gross abnormalities were revealed at 
autopsy after 224 days.  The histopathological study of the 
visceral organs did not show any pathological effects.  Slight to 
moderate hyperplasia of the smooth endoplasmatic reticulum and 
cytoplasmic margination of a few liver cells were noted at the 1000 
and 2000 mg/kg levels. 

    Interactions

    Chlordane has been shown to exert a protective effect against 
several organophosphorous and carbamate insecticides (Williams et 
al., 1967; Street et al., 1969; Williams & Casterline, 1970; US 
EPA, 1976a,b). 

    Protein deficiency has been shown to double the acute toxicity 
of chlordane in rats (Boyd, 1972). 

    Chlordane has also been shown to increase the hepatotoxic 
effects of carbon tetrachloride in the rat (Stenger et al., 1975; 
Mahon, 1977; Mahon & Oloffs, 1979; Mahon et al., 1979). 

7.  EFFECTS ON MAN: EPIDEMIOLOGICAL AND CLINICAL STUDIES

7.1.  Poisoning Incidents 

    A 15-month-old girl ingested a mouthful of chlordane suspension 
and, after 3 h, 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 - 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., 1979). 

    A 2-year-old child had drunk an unknown amount of a 74% 
formulation of chlordane (Curley & Garrettson, 1969).  Vomiting 
preceeded convulsions, which were controlled by phenobarbital; the 
EEG pattern was normal within 40 h and the child recovered. 

    A similar poisoning incident was observed with a 4-year-old 
child (Aldrich & Holmes, 1969).  Convulsions were treated with 
phenobarbital.  As with the previous case, the individual 
recovered. 

    Two other cases of chlordane poisoning were reported in 1955 
(Derbes et al., 1955).  One was caused by the absorption of 
accidentally-spilled chlordane and the other was a suicide attempt 
where the individual (female) swallowed 6 g of chlordane (104 mg/kg 
body weight) and died 9 1/2 days after the incident (Derbes et al., 
1955). 

    When a section of a municipal water system in Chattanooga, 
Tennessee, USA was contaminated with chlordane in concentrations of 
up to 1.2 g/litre in 1976, 13 persons showed gastrointestinal 
and/or neurological symptoms (Harrington et al., 1978). 

7.2.  Occupational and Epidemiological Studies 

    No deleterious effects associated with occupational exposure to 
chlordane have been reported.  Twenty-two men, who had been 
occupationally exposed to chlordane during its manufacture for 
periods of 1 - 3 years, did not show any evidence of intoxication 
(Princi & Spurbeck, 1951).  Other clinical studies have been 
reported on men engaged in the manufacture of chlordane (Alvarez & 
Hyman, 1953; Fishbein et al., 1964; Morgan & Roan, 1969). 

    Infante et al. (1978) reviewed 25 previously reported cases of 
blood dyscrasia together with a small number of newly identified 
cases of aplastic anaemia, leukaemia, or neuroblastoma in children 
in relation to their possible association with pre- and post-natal 
chlordane or heptachlor exposure and reported an anecdotal 
relationship.  However, in a case-control study, no association was 
found between blood dyscrasias and occupational exposure to a 
number of pesticides including chlordane (Wang & Gruffenman, 1981). 

    Wang & MacMahon (1979 a,b) studied a cohort of workers engaged 
in the manufacture of chlordane, heptachlor, and endrin and another 
cohort of 16 000 pesticide-spraying personnel, including termite-
control workers.  Both studies showed a deficit of deaths from all 
cancers and slight excesses of lung, skin, or bladder cancer that 
were not statistically significant. 

    In 1982, an IARC Working Group concluded that the above studies 
were inadequate to evaluate the carcinogenicity of chlordane for 
human beings (IARC, 1982). 

    Shindell & Associates (1981) studied the mortality experience 
of 783 workers engaged in the manufacture of chlordane and 
heptachlor.  Workers had been employed for a minimum of 3 months 5, 
10, 15, or 20 years ago.  SMRs for cancer were not increased among 
124 deaths. 

    In a retrospective cohort study of workers involved in the 
production of chlorinated hydrocarbon pesticides, Ditraglia et al. 
(1981) studied the workers in a chlordane-manufacturing plant; the 
same workers were also studied by Wang & MacMahon (1979a).  SMRs 
for all cancer deaths were lower than expected; a slight excess of 
stomach cancer (3 vs 0.99 expected), which was observed, was not 
statistically significant.  The number of workers studied was small 
and further follow-up of the cohort was recommended by the authors. 

    MacMahon & Wang (1982) carried out a second follow-up study of 
mortality rates in a cohort of workers employed in spraying 
pesticides, including termite-control workers.  Among 540 deaths 
for which the cause was ascertainable, small excesses of bladder 
cancer in termite-control operators and of skin and lung cancer in 
other operators were observed, but these were not statistically 
significant. 

7.3.  Treatment of Poisoning 

    In case of overexposure, medical advice should be sought 
immediately. 

    Treatment before person is seen by a physician

    The person should stop work immediately, remove contaminated 
clothing and wash the affected skin with soap and water, if 
available, flushing the area with large quantities of water.  If 
swallowed, vomiting should be induced, if the person is conscious 
(FAO/WHO, 1978). 

    Medical Treatment

    If the pesticide has been ingested, gastric lavage should be 
Performed with 2 - 4 litres of water, followed by saline 
purgatives.  Barbiturates (preferably phenobarbitone or 
pentobarbitone) or diazepam should be given intramuscularly or 
intravenously in sufficient dosage to control restlessness or 
convulsions.  Mechanical respiratory assistance with oxygen may be 

required.  Calcium gluconate, 10% in 10 ml, injected 
intramuscularly at 4-h intervals, may be helpful.  Contraindicated 
are oily purgatives, epinephrine, and other adrenergic drugs and 
central stimulants of all types (FAO/WHO, 1978). 

8.  EFFECTS ON THE ENVIRONMENT

8.1.  Toxicity for Aquatic Organisms 

    Data on the toxicity of chlordane for aquatic organisms are 
given in Table 4.  A more comprehensive table, listing different 
conditions and exposure times is available on request from IRPTC, 
Geneva, Switzerland.  It is of importance for the interpretation of 
these data to note that a change in the purity of technical of 
chlordane occurred in the early 1950s. 

    Studies of the effects of chlordane on fish began with the 
application of the original material to rainbow trout by Cope et 
al. (1947).  They determined minimum disabling 24-h doses of 
chlordane in a xylene emulsion, an acetone solution, a fuel oil 
solution, and a Velsicol AR-50 solution, and found this to be 
higher than 6 mg chlordane/litre.  An application of 1.12 kg/ha of 
a field formulation of chlordane to a small pond killed 87% of 
bluegills present (Surber, 1948), application of 0.56 kg/ha killed 
some bluegills whilst at 0.28 kg/ha all fish survived (Linduska & 
Surber, 1948).  In a study by Lawrence (1950) on bluegill 
fingerlings, large-mouth black bass fingerlings, and juvenile 
goldfish in aquaria, no deaths occurred at 100 g chlordane/litre 
(original formulation), whilst at 200 g/litre, a 30-h exposure 
killed bass, and an 87-h exposure killed bluegills; goldfish were 
not affected.  In earthen ponds, large-mouth black bass fingerlings 
were killed by a concentration of 200 g/litre, but bluegills and 
fingerlings and juvenile goldfish survived. 

    Studies using the current formulation of chlordane are 
summarised in Table 4.  A definite temperature effect demonstrated 
by Macek et al. (1969) during acute exposures, i.e., fish showed a 
greater susceptibility at higher temperatures, was not present in 
96-h exposure studies.  Temperature effects were also noted in 
toxicity tests on tubificid worms,  Branchuria sowerbyi (Naqvi, 
1973).  In static tests, 500 g chlordane/litre caused 100% 
mortality at 4.4 and 32 C, but no mortality at 21 C.  Nutrition 
has been shown to affect chlordane toxicity in rainbow trout, with 
96-h LC50s ranging from 8.2 to 47 g/litre, depending on the 
composition of the diet given to the fish (Merhle et al., 1974). 

    Recent  in vitro studies on bluegills (Koch et al., 1971)
and on rainbow trout (Davis et al., 1972) have shown that chlordane 
acts as an inhibitor of ATPase systems. 

8.2.  Toxicity for Terrestrial Organisms 

    Studies of the effects of chlordane on soil microfauna have 
been limited to work on nematodes.  Populations of plant-feeding 
nematodes were reduced by an insecticide mixture containing 
chlordane (as well as DDT, diazinon, and zinophos) in July, 
following application in March, but at no other time during the 
study period (Corbett & Webb, 1968).  Nematodes are generally 
unaffected by most soil insecticides (Edwards, 1965a). 


Table 4.  Toxicity of chlordane for aquatic organisms
---------------------------------------------------------------------------------------------------------
Organism          Age/   Temp  pH   Flow/ Grade  Hard- alk   sal   End        Para- Concen- Reference
                  size   ( C)      stat         ness  (mg/  o/oo  point      meter tration   
                                                 (mg/  litre)                       (g/
                                                 litre)                             litre)
---------------------------------------------------------------------------------------------------------
Eastern oyster    29-53  31.6       flow  tech               27.3  % reduc-   96-h  6.2     Parrish et
 (Crassostrea      mm                                               tion shell EC50          al. (1976)
 virginica)                                                         deposition

Annelid                             stat                     sea              288-h 220     McLeese et
 (Nereis virens)                                              water            LC50          al. (1982)

Scud              5 mm   16.7  7.9  flow  tech   148   152         immobili-  168-h 97.1    Cardwell et
 (Hyalella         juv.                                             sation     EC50          al. (1977)
 azteca) 

Cladoceran        1st    15.5  7.4- stat                           immobili-  48-h  29      Sanders &
( Daphnia pulex)   instar       7.8                                 sation     EC50          Cope (1966)

Pink shrimp       50-65  28.4       flow  tech               21.8             96-h  0.4     Parrish et
 (Penaeus          mm                                                          LC50          al. (1976)
 duorarum)

Dungeness crab    adult  13         stat  tech               25               96-h  220     Caldwell
 (Cancer                                                                       LC50          (1977)
 magister)         zoeal  13         stat  tech               25    immobili-  96-h  1.3 
                                                                   sation     EC50      

Backswimmer       5-6 mm 18-24      stat  25% EM                              168-h 0.79    Konar (1968)
 (Notonecta) sp                                                                LC50 

Water scorpion    24-28  18-24      stat  25% EM                              168-h 182     Konar (1968)
 (Nepa) sp         mm                                                          LC50 

Bluegill          38-84  25    7.1  flow  100%   20    18                     96-h  22      Henderson et
 (Lepomis          mm                                                          LC50          al. (1959)
 macrochirus) 
---------------------------------------------------------------------------------------------------------


    Table 4.  (contd.)
---------------------------------------------------------------------------------------------------------
Organism          Age/   Temp  pH   Flow/ Grade  Hard- alk   sal   End        Para- Concen- Reference
                  size   ( C)      stat         ness  (mg/  o/oo  point      meter tration   
                                                 (mg/  litre)                       (g/
                                                 litre)                             litre)
---------------------------------------------------------------------------------------------------------
Fathead minnow    1 day  21/25 7.7  flow  tech   156   166         major      11-mo         Cardwell et.
 (Pimephales                                                        chronic    lowest        al. (1977)
 promelas)                                                          effects    dose        
                                                                              life 
                                                                              cycle
                                                                              tests

                  38-84  25    7.1  flow  100%   20    18                     96-h  52      Henderson et
                  mm                                                          LC50          al. (1959)

                  38-84  25    7.1  flow  75%    20    18                     96-h  170     Henderson et
                  mm                      EM                                  LC50          al. (1959)

Rainbow trout     0.9 g  13               tech                                96-h  7.8     Cope (1965)
 (Salmo gairdneri)                                                             LC50 

Murrel            24-26  18-24      stat  25% EM                              168-h 0.51    Konar (1968)
 (Channa           mm                                                          LC50 
 punctatus) 
                  48-50  18-24      stat  25% EM                              168-h 3       Konar (1968)
                  mm                                                          LC50 

                  100-   18-24      stat  25% EM                              168-h 25.5    Konar (1968)
                  105 mm                                                      LC50 

Tropical fish     juv.   18-24      stat  25% EM                              168-h 0.7-    Konar (1968)
                                                                              LC50  3.7

Channel catfish   finger 25         stat  tech                                96-h  500     Clemens &
 (Ictalurus        ling                                                        LC50          Sneed (1959)
 punctatus)

Common toad       tad-   18-20      stat                                      48-h  2000    Ludemann &
 (Bufo bufo)       pole                                                        LC50          Neumann
                                                                                            (1962)
---------------------------------------------------------------------------------------------------------
    Soil fauna populations (mainly arthropods with a small 
percentage of earthworms and nematodes) were reduced to very low 
levels by the normal application rate (112 kg/ha per year) of a 
commercial formulation of chlordane (Gould & Hampstead, 1951).  
However, Long et al. (1967) did not find any significant reductions 
in most soil arthropod populations following application of 
technical chlordane to sugar cane at 2.24 kg/ha, although numbers 
of Diplura and Pauropoda were reduced.  In a summary of the effects 
of pesticides on soil invertebrates, Edwards (1965b) stated that 
chlordane caused a large reduction in the numbers of Coleoptera, 
Diptera, hemiedaphic Collembola, and non-predatory mites, but 
little reduction in the numbers of edaphic Collembola or predatory 
mites at application rates of 1.12 - 2.24 kg/ha.  He also stated 
that chlordane was lethal for fly and beetle larvae. Fox (1958) 
produced a few data indicating that carabid and staphylinid beetle 
populations returned to normal 3 years after a field application 
of chlordane (as a 40% wettable powder) at 8.96 or 11.2 kg/ha. 

    Chlordane is toxic both to earthworms and to enchytraeid worms 
at application rates well within the range of normal usage (Hopkins 
& Kirk, 1957; Doane, 1962).  The toxicity of chlordane for earth-
worms is given in Table 5.  Legg (1968) made a single application 
of 25% EC chlordane at 9.0, 13.4, or 20.2 kg/ha on closely-mown 
turf and counted worm casts for up to 13 months.  After 19 days, 
there were reductions of 52, 72, and 98%, respectively, for the 3 
doses compared with control plots; after 13 months, the reductions 
were 89, 95, and 97%, respectively.  Long et al. (1967) reported a 
significant reduction in earthworm populations, 6 - 11 months after 
an application of chlordane at 2.2 kg/ha.  A reduction in worm 
casts to zero, 1 year after an application of chlordane at 11.2 
kg/ha, either as granules or in spray formulation was shown by 
Doane (1962).  Lidgate (1966) applied chlordane, either as 20% 
granules or 75% EC diluted with water, at rates between 13.4 and 
35.2 kg/ha, to a putting green and measured worm activity by the 
number of worm casts.  The first count of casts, 18 days after 
treatment, showed that worm activity was significantly depressed by 
granular applications of 17.6 and 35.2 kg/ha but not by spray 
formulations of 13.4 or 26.4 kg/ha.  Activity became depressed on 
sprayed plots about 8 weeks after treatment.  There were still 
significantly fewer worm casts on treated plots, 5 years later. 


Table 5.  Toxicity of chlordane for earthworms
-----------------------------------------------------------------------------------------
Organism     Grade    Application Concen-  Effect                 Reference
                      method      tration
                                  (kg/ha)
-----------------------------------------------------------------------------------------
Earthworm    25% EC   spray       9        52% reduction in worm  Legg (1968)
 (Lumbricus                                 casts at 19 days
 terrestris)
             25% EC   spray       13.4     72% reduction in worm  Legg (1968)
                                           casts at 19 days

             25% EC   spray       20.2     98% reduction in worm  Legg (1968)
                                           casts at 19 days

             25% EC   spray       9        89% reduction in worm  Legg (1968)
                                           casts at 1 year

             25% EC   spray       13.4     95% reduction in worm  Legg (1968)
                                           casts at 1 year

             25% EC   spray       20.2     97% reduction in worm  Legg (1968)
                                           casts at 1 year

Red earth-   5% dust  soil        35       0% mortality in        Hopkins & Kirk (1957)
worm                  incorpor-            4 days
 (Eisenia              ation  
sp)
             5% dust  soil        70       46% mortality in       Hopkins & Kirk (1957)
                      incorpor-            4 days
                      ation
            
             5% dust  soil        141      40% mortality in       Hopkins & Kirk (1957)
                      incorpor-            4 days
                      ation

             5% dust  soil        282      79% mortality in       Hopkins & Kirk (1957)
                      incorpor-            4 days
                      ation

             5% dust  soil        100      96-h LC50              Hopkins & Kirk (1957)
                      incorpor-    
                      ation
-----------------------------------------------------------------------------------------
    The toxicity of chlordane for birds, when given in the diet, is 
summarised in Table 6.  LC50 values as mg/kg diet ranged from 170 
to 858 in studies where chlordane was given for between 5 days and 
100 weeks.  When chlordane was applied to marshland at 1.12 kg/ha, 
the fecundity of marsh birds was affected (Hanson, 1952); blue-
winged teal and shovelers did not produce any young, and coot and 
redwinged-blackbirds produced 60% fewer young.  It was postulated 
that chlordane had caused disruption in food cycles in the marsh 
and that this was the probable cause of reproductive failure in the 
birds. 

8.3.  Toxicity for Microorganisms 

    Some effects of chlordane on microorganisms are summarised in 
Table 7.  Its effects may be due, at least in part, to inhibition 
of enzyme activity (Nakas, 1977).  Some work has been reported on 
the effects of chlordane on soil microorganisms.  Gram-positive 
bacteria appear to be more sensitive to chlordane than gram-
negative bacteria, since the growth of gram-positives was inhibited 
whilst that of gram-negatives was unaffected (Trudgill et al., 
1971).  When  Bacillus subtilis cultures were treated with technical 
chlordane at 20 mg/litre, they ceased to grow.  Viable count and 
respiration rate fell to zero after about 3 h of exposure.  The 
actual concentration experienced by the bacteria is not known, but 
it is likely to be less than the 20 mg/litre added because of the 
poor solubility of chlordane in aqueous solution.  Langlois & Sides 
(1972) investigated the effects of constituents of technical 
chlordane on the growth of  Staphylococcus aureus.  The viability 
of the culture, the length of the lag-phase, and the generation 
time were affected by the amount of chlordane and gamma-chlordane 
applied. 

8.4.  Bioaccumulation and Biomagnification 

    Grimes & Morrison (1975) examined the uptake of chlordane by 13 
types of bacteria and found that although the uptake of alpha- and 
beta-isomers of chlordane was the same for any one species, the 
concentration factors (CF) differed greatly between species.  The 
CFs ranged from a few hundred to several thousand, with 3 species 
giving much higher values.  The highest CF was 53 000 for 
 Caulobacter vibrioides.  Caulobacter cells were found to contain 4 
distinct lipid-containing materials, and this was offered as an 
explanation of the high CF.  Sanborn et al. (1976) used unlabelled 
chlordane and labelled 14C-chlordane on filamentous  Oedogonium  
alga and obtained CFs of 49 500 and 98 386.  The lower figure may 
be due to uncertainties in determining chlordane in solution and in 
the alga.  Moore et al. (1977), using the planktonic alga 
 Ankistrodesmus amalloides, obtained a very much lower CF of 5560, 
but even this species shows accumulation potential. 


Table 6.  Toxicity of chlordane for birds
--------------------------------------------------------------------------------
Species      Age       Route  Parameter     Concen-    Reference
                                            trationa 
                                            (mg/kg)
--------------------------------------------------------------------------------
Mallard      4 - 5 mo  oral   acute LD50    1200       Tucker & Crabtree (1970)
             10 days   diet   5-day LC50b   858        Hill et al. (1975)

Bobwhite     14 weeks  diet   10-week LC0   10         Ludke (1976)
quail        17 days   diet   5-day LC50b   331        Hill et al. (1975)
             young     diet   100-day LC50  100        DeWitt et al. (1963)
             young     diet   10-day LC50   250        DeWitt et al. (1963)
             adult     diet   100-day LC50  250        DeWitt et al. (1963)

Japanese     7 days    diet   5-day LC50b   350        Hill et al. (1975)
quail

Ring-necked  15 days   diet   5-day LC50b   430        Hill et al. (1975)
pheasant     young     diet   10-day LC50   500        DeWitt et al. (1963)
             young     diet   100-day LC50  50         DeWitt et al. (1963)
             adult     diet   100-day LC50  200        DeWitt et al. (1963)

Cowbird      adult     diet   30-week LC50  500        DeWitt et al. (1963)
--------------------------------------------------------------------------------
a  Concentration in mg/kg body weight for oral dosing; concentration in mg/kg 
   diet for dietary dosing.
b  5 days of treated diet followed by 3 days of clean diet.  Mortality rate 
   determined on day 8.

Table 7.  Toxicity of chlordane for microorganisms
----------------------------------------------------------------------------------------
Organism       F/M/ Temp  Grade Solvent  Endpoint        Time    Concen-  Reference     
               S    ( C)                                        tration                
                                                                 (g/                   
                                                                 litre)a               
----------------------------------------------------------------------------------------
 Scenedesmus    F    23    tech  acetone  stimulation of  5 - 7   0.1-     Glooschenko & 
 quadricauda                              cell division   days    100      Lott (1977)   
                                                                                       
               F    23    tech  acetone  inhibition of   1 - 5   50 &     Glooschenko & 
                                         photosynthesis  days    100      Lott (1977)   
                                                                                       
 Chlamydomonas  S    23    tech  acetone  stimulation of  7 - 11  0.1-     Glooschenko & 
sp                                       cell division   days    50       Lott (1977)   
                                                                                        
               S    23    tech  acetone  stimulation of  3 - 4   0.1-     Glooschenko & 
                                         respiration     h       100      Lott (1977)   
                                                                                        
               S    23    tech  acetone  inhibition of   7 - 11  100      Glooschenko & 
                                         cell division   days             Lott (1977)   
                                                                                        
               F    23-   60%   acetone  50% reduction   3 days  100 000  Clegg &       
                    25                   ATPase                           Koevenig      
                                         activity;                        (1974)        
                                         no effect on                                   
                                         cell density                                   
                                                                                        
 Volvox sp      F    18-   20%   none     100% mortality  7 days  1        Konar (1968)  
 Pandorina sp        24    EM                                                            
 Closterium sp                                                                           
                                                                                        
 Chlorella      F    23-   60%   acetone  reduced ATPase  3 days  100 000  Clegg &
 ellipsoidea         25                   levels;                          Koevenig
 Euglena                                  no effect on                     (1974)    
 elastica                                 cell density                                   

 Exuviella      M          60%   methanol virtual cessa-  7 days  50       Magnani et 
 baltica                                  tion of growth                   al. (1978)

Natural        M          60%   acetone  94% decrease    4 h     1000     Butler (1963)
estuarine                                in product-    
phytoplankton                            ivity

Estuarine      M    7-14  60%   methanol no effect       5 days  5        Biggs et al.
phytoplankton  M    7-14  60%   methanol growth and 14C  5 days  10       (1978)
                                         uptake reduced 
                                         in laboratory

 Bacillus       S          tech  acetone  growth ceased;  3 h     20 000   Trudgill et
 subtilis                                 decline in                       al. (1971)
                                         viable count;     
                                         respiration
                                         to zero
----------------------------------------------------------------------------------------
a  Solubility of chlordane: 6 - 9 g/litre.  F = freshwater; M = marine; S = soil.
    Accumulation of alpha- and and gamma-isomers of chlordane and 
nonachlor, and chlordenes was studied by Cardwell et al. (1977) in 
3 species of freshwater invertebrates.   Chironomus larvae did not 
show any detectable accumulation.  After one week's exposure to 1.7 -
21.6 g/litre,  Daphnia magna gave CFs ranging from 15 000 to 
175 000.  After 65 days of exposure to 1.4 - 11.5 /litre,  Hyallela
 azteca showed CFs ranging from 41 000 to 144 000.  After a 24-h 
exposure to 0.5 g alpha- and gamma-chlordane/litre,  Daphnia pulex  
gave a CF of 24 000 (Moore et al., 1977).  Sanborn et al. (1976) 
found a CF of 6132 for insect larvae.  A fresh-water gastropod 
 Physa sp., concentrated chlordane 132 613 times (Sanborn et al., 
1976). Little bioaccumulation has been observed in the marine 
invertebrate species studied.  Wilson (1965) exposed oysters to 
0.01 mg chlordane/litre and determined a CF of 7300, which is 
considerably lower than that for fresh-water gastropods. Water and 
oyster samples from Galveston Bay, Texas were analysed following an 
extensive mosquito-control programme (Casper, 1967).  Oysters 
sampled did not contain any detectable chlordane and only 2 out of 
9 water samples gave a positive result of less than 0.001 g/litre.  
Chlordane was detected by Bugg et al. (1967) in 20 out of 133 
oyster samples taken from the South Atlantic and the Gulf of 
Mexico, but 19 of these gave values of less than 0.01 mg/kg drained 
weight.  Clams, which were living in water containing chlordane at 
0.01 g/litre for 106 days, showed CFs of 1000 or less (Godsil & 
Johnson, 1968).  Parrish et al. (1976) reported that chlordane was 
concentrated in the tissues of the estuarine pink and grass shrimps 
at 1000 - 2300 times levels measured in water. 

    Few data are available on soil invertebrates.  One report on 
earthworms has been published by Gish (1970), who measured the 
levels of gamma-chlordane in the soil and earthworms.  CFs of 0.37, 
7.1, 10.6, and 152 were obtained for 4 worms in agricultural soils. 

    Several studies are available on fresh-water fish. Henderson et 
al. (1969) found that fish from Atlantic-coast streams, which gave 
positive samples, contained between 0.1 and 7.29 mg chlordane/kg 
(whole fish wet weight), fish from the Great Lake drainage areas 
contained between 0.01 and 0.39 mg/kg, and fish from the 
Mississippi River system contained between 0.01 and 0.72 mg/kg.  
Fish from other systems (Hudson Bay, Colorado River, Interior 
basins, Californian streams, Columbia River, Pacific coast and 
Alaskan streams) contained less than 0.01 mg/kg.  A further study 
by Henderson et al. (1971) yielded 16 positive samples out of 666 
fish taken from 50 sites, giving chlordane levels of between 0.09 
and 13.5 mg/kg (whole fish wet weight).  Working on chlordane 
accumulation in sucker-fish, Roberts et al. (1977) showed that 
accumulation from food was directly proportional to the lipid 
levels of the fish.  Chlordane was given to the northern redhorse 
sucker,  Moxostoma macrolepidotum, in the feed at 45 g/kg dry 
feed for 5 consecutive days and to the white sucker,  Catostomus 
 commersoni, directly to the stomach in a single dose of 340 mg 
in corn oil.  Both tests gave CF values of less than, or equal, to 
0.52.  CF values obtained in fish by uptake from the food were 
lower than those obtained by uptake from water (goldfish at a CF of 
162 with chlordane in diet (Moore et al., 1977); mosquito fish at a 

CF of 8258 with chlordane in diet and in water (Sanborn et al., 
1976)).  This suggests that chlordane is taken up directly from 
water (bioaccumulated) more than it is from ingested food 
(biomagnified). 

    Schimmel et al. (1976a,b) reported that CFs for two species of 
marine fish were similar to those found in fresh-water species.  
Spot and sheepshead minnow concentrated gamma-chlordane 3700 - 14 
800 and 9000 - 16 800 times, respectively, in 4 days, and 3300 - 
5100 and 10 300 times, respectively, in 24 days.  Veith et al. 
(1979) exposed fathead minnows to 5.9 g chlordane/litre for 32 
days and obtained a CF of 37 800 for the whole body.  Parrish et 
al. (1978) similarly reported 16 000 for whole body in the 
sheepshead minnow after exposure for 189 days.  They also 
determined the CF after only 28 days exposure and found a 
comparable whole-body value of 15 300.  A range of CFs between 9000 
and 16 786 was reported by Schimmel et al. (1976a) when sheepshead 
minnows were exposed to gamma-chlordane (in technical heptachlor) 
at 1.1 - 2.8 g/litre for 96 h.  In a field study, long-term 
exposure (209 days or less) of large-mouth bass to between 0.01 and 
0.1 g/litre chlordane gave concentration factors of between 157 
and 3308 (Godsil & Johnson, 1968). 

    Food chain magnification is unlikely in terrestrial organisms.  
Species of birds and mammals studied show little bioaccumulation, 
probably because chlordane is rapidly broken down in homoiotherms.  
There are very few data on birds.  One report (Foster et al., 1972) 
refers to a study on the accumulation of chlordane in laying hens 
fed 0.1 mg/kg diet.  CF values were maximal after 7 - 9 weeks, diet 
to fat was between 0.01 and 3.3, and diet to eggs was between 0.01 
and 2.  After 3 weeks on an untreated diet, chlordane was not 
detectable.  McCaskey et al. (1968) dosed hens with the equivalent 
of a diet containing 10 - 15 mg 60% technical chlordane/kg for 5 
days and obtained a maximum CF value in eggs of 0.38 on day 6. 

8.5.  Population and Community Effects 

    The fate of 14C-chlordane was investigated in a terrestrial-
aquatic model ecosystem composed of an alga  (Oedogonium), snails 
 (Physa), mosquito larvae  (Culex), and fish  (Gambusia)  
(Sanborn et al., 1976).  Accumulation of chlordane residues was 
evident in all organisms in the ecosystem, but no toxic effects 
were reported. 

    Exposure of a natural phytoplankton population to 5 and 10 g 
chlordane/litre for 5 days had virtually no effect on its species 
composition (Biggs et al., 1978). 

8.6.  Effects on the Abiotic Environment 

    No data are available on abiotic effects. 

8.7.  Appraisal 

    Data on aquatic toxicity require interpretation.  Although the 
solubility of chlordane in water has been measured at between 6 
and 9 g/litre, in many studies on its aquatic toxicity, chlordane 
has been applied at much higher nominal concentrations.  Either the 
chlordane has not been in solution or was added with a solvent.  
Actual levels of chlordane in natural waters rarely exceed 250 
ng/litre with most levels below 20 ng/litre.  Test levels are 
therefore unrealistically high.  The data should thus be critically 
examined unless the actual concentrations experienced by the test 
organisms were measured. 

    Few long-term studies of the chronic effects of chlordane are 
available.  Data do not define threshold levels, although they 
suggest levels at which effects might be expected.  Data seldom 
provide quantitative dose-response relationships. 

    Effects of chlordane on primary producers in the aquatic food 
chain are largely unknown because studies have used unrealistically 
high concentrations.  Some data on lethal doses for aquatic 
organisms are available, but data on sub-lethal effects on 
reproduction or behaviour are not.  There are data on the acute 
toxicity of chlordane for fish at concentrations approaching the 
water solubility, but few on long-term exposure at lower doses. 

    Most terrestrial studies have been on soil organisms. Effects 
here might be due to the heptachlor in technical chlordane or to a 
combination of heptachlor and chlordane.  Only very high 
application rates of chlordane affected arthropods.  Field studies 
do not indicate direct toxicity but a combination of toxicity and 
avoidance of the compound. 

    Of major importance is the clear toxicity of chlordane for 
earthworms with implications for soil fertility.  Molluscs also 
appear to be particularly sensitive to chlordane. 

9.  PREVIOUS EVALUATIONS OF CHLORDANE BY INTERNATIONAL BODIES

    An IARC Working Group (IARC, 1982) concluded that the available 
epidemiological studies on chlordane were inadequate for the 
evaluation of the cancer risk for man and that there was limited 
evidence of the carcinogenicity of chlordane for experimental 
animals. 

    WHO has recommended a guideline value of 0.3 g/litre for 
chlordane (total isomers) in drinking-water (WHO, 1982). 

    The Joint Meeting on Pesticide Residues (JMPR) reviewed 
residues and toxicity data on chlordane on several occasions in the 
past (1965, 1967, 1970).  In November 1972, it re-established 
residue tolerences ranging from 0.02 - 0.5 mg/kg for the sum of 
alpha- and gamma-isomers of chlordane and oxychlordane (FAO/WHO, 
1973).  The acceptable daily intake (ADI) for human beings of 
0 - 0.001 mg/kg body weight was confirmed in December 1977 
(FAO/WHO, 1978).  This was based on no-observed-adverse-effect-
levels of: 

    -   5 mg/kg in the diet, equivalent to 0.25 mg/kg body
        weight in the rat; and

    -   3 mg/kg in the diet, equivalent to 0.075 mg/kg body
        weight in the dog.

    Both "no-observed-adverse-effect-levels" and the ADI were 
reviewed by the 1982 JMPR (FAO/WHO, 1983).  The ADI was given 
"temporary" status pending the results of toxicology studies still 
in progress. 

    WHO (1984), in its "Guidelines to the Use of the WHO 
Recommended Classification of Pesticides by Hazard", classified 
technical chlordane as moderately hazardous. 

    The WHO/FAO (1978) has issued practical advice in its "Data 
Sheet on Pesticides" including one on Chlordane (No. 36) dealing 
with labelling, safe-handling, transport, storage, disposal, 
decontamination, training and medical supervision of workers, first 
aid and medical treatment. 

    Regulatory standards established by national bodies in 12 
different countries (Argentina, Brazil, Czechoslovakia, the Federal 
Republic of Germany, India, Japan, Kenya, Mexico, Sweden, the 
United Kingdom, the USA, and the USSR) and the EEC is available 
from the IRPTC (International Register of Potentially Toxic 
Chemicals) Legal file (IRPTC, 1983). 

    The CEC reviewed the data available on chlordane in 1981.

10.  EVALUATION OF HEALTH RISKS FOR MAN AND EFFECTS ON THE 
ENVIRONMENT

10.1.  Chlordane Toxicity 

    Chlordane is readily absorbed in both animals and man via the 
skin, via ingestion, and probably also by inhalation.  Some 
accumulation occurs in the body on repeated exposure - mainly in 
adipose tissue.  Elimination from the body is fairly slow.  The 
half-life in various species, including man, is of the order of a 
few weeks. 

    The oral LD50 values of chlordane in the rat range from
200 - 590 mg/kg body weight.  Thus, chlordane is moderately toxic 
in acute exposures. 

    Acute poisoning in man and animals is characterized by 
manifestations of central nervous system stimulation such as 
disorientation, tremors, and convulsions.  Death may follow 
respiratory failure. 

    In experimental animals (rats and dogs), prolonged exposure 
to levels in the diet exceeding 3 - 5 mg/kg resulted in the 
induction of hepatic microsomal enzymes and, at a later stage, 
liver hypertrophy with histological changes.  At higher levels 
(i.e., > 15 mg/kg body weight per day), chlordane is hepatotoxic.  
For no-observed-adverse-effect levels see section 6.1.1. 

    At dosages above 30 mg/kg diet, chlordane interferes with 
reproduction in rats and mice, but this was reversible after 
exposure ceased.  There are no indications for teratogenicity in 
the rabbit at 15 mg/kg body weight per day. 

    Chlordane produces hepatocellular carcinomas in mice.  It
is not generally active in short-term tests designed to measure 
genetic activity.  Chlordane can interfere with cell to cell 
communication  in vitro, a characteristic of many promoting agents. 

10.2.  Exposure to Chlordane 

    Food is the major source of exposure of the general population 
to chlordane, but the use of chlordane on food crops has decreased 
and residues in food from animal origin are low.  Some chlordane 
exposure can occur in buildings where chlordane has been used for 
termite or other insect control. 

    No adverse health effects have been reported in workers engaged 
in the manufacture of chlordane or in pest-control operations, 
where exposure could be quite high.  However, several cases of 
accidental and suicidal poisoning in man have been reported 
resulting in the symptoms described in section 7.1. 

10.3.  Evaluation of Overall Environmental Effects 

    Chlordane is used primarily to control soil pests.  Technical 
chlordane is a mixture of chlorinated hydrocarbons and contains 
heptachlor, which might contribute significantly to the 
insecticidal properties of the technical formulation. 

    About half of the chlordane applied to soil disappears in the 
first season, presumably by volatalisation or by "run-off" into 
surface waters.  Remaining residues persist for several seasons.  
If chlordane is applied annually for several successive seasons, 
residues accumulate in the soil.  Most chlordane persists in the 
cultivated levels, since there is little leaching into subsoil. 

    The high rate of metabolism of chlordane in warm-blooded 
animals means that there is little possibility of accumulation in 
these animals or magnification in food chains at this level.  
Concentration factors are generally modest in aquatic organisms; 
this combined with its low solubility in water means that chlordane 
presents a limited hazard for aquatic vertebrates.  Long-term 
effects are not sufficiently well-documented to say that there is 
not a potential hazard for fish, but this seems unlikely from the 
information available, as far as temperate areas are concerned.  
The compound shows a higher toxicity at higher temperatures. 
Significant mortality in tropical species of fish at concentrations 
well within the solubility of the compound, suggest that chlordane 
may be a greater aquatic hazard at lower latitudes. 

    The high toxicity of chlordane for earthworms may constitute 
its greatest potential hazard.  The long-term effects of reduced 
numbers of earthworms in the soil cannot be readily assessed 
because the ecology of the animal is still poorly understood. 

10.4.  Evaluation of Risks for Human Health and the Environment 

    Although there is no evidence that incriminates chlordane as a 
human carcinogen, the suspicion principally arising from the mouse 
carcinogenicity studies cannot be entirely put aside.  Further 
research is required to elucidate this problem.  Nevertheless, in 
the present state of knowledge, it is concluded that: 

    1.  As long as occupational hygiene procedures are maintained 
        to keep exposure levels to a minimum, whether or not by the 
        imposition of maximum allowable concentrations, there is 
        little reason to believe that workers will be at risk from 
        their handling, or contacts, with chlordane.

    2.  For the general population, consumers should suffer no 
        adverse effects from chlordane as food residues, provided 
        that the intake is kept within the temporary ADI set by the 
        Joint FAO/WHO Meeting.
 
        In certain regions of the world, the exposure of the
        general population to chlordane may be augmented by its
        use as a termiticide in buildings.

    3.  Apart from the possible long-term adverse effects on
        aquatic organisms in tropical areas and the depleted soil
        fertility that may arise, in time, from the suppression of
        the earthworm population, chlordane seems to cause little
        environmental concern in its normal use as a termiticide
        and in other non-agricultural applications.

REFERENCES

AHMED, F.E., HART, R.W., & LEWIS, N.J.  (1977a)  Pesticide 
induced DNA damage and its repair in cultured human cells.  
 Mutat. Res.,  42: 161-174.

AHMED, F.E., LEWIS, N.J., & HART, R.W.  (1977b)  Pesticide 
induced ouabain resistant mutants in Chinese hamster.   Chem. 
 Biol. Interactions,  19: 369-374.

ALDRICH, F.D. & HOLMES, J.H.  (1969)  Acute chlordane 
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    See Also:
       Toxicological Abbreviations
       Chlordane (HSG 13, 1988)
       Chlordane (PDS)
       Chlordane (PIM 574)
       Chlordane (FAO Meeting Report PL/1965/10/1)
       Chlordane (FAO/PL:1967/M/11/1)
       Chlordane (FAO/PL:1969/M/17/1)
       Chlordane (AGP:1970/M/12/1)
       Chlordane (WHO Pesticide Residues Series 2)
       Chlordane (WHO Pesticide Residues Series 4)
       Chlordane (Pesticide residues in food: 1977 evaluations)
       Chlordane (Pesticide residues in food: 1982 evaluations)
       Chlordane (Pesticide residues in food: 1984 evaluations)
       Chlordane (Pesticide residues in food: 1986 evaluations Part II Toxicology)