CHLORDANE JMPR 1977
Explanation
Chlordane was evaluated by the Joint Meetings of 1965, 1967, 1969,
1970 and 1974 (FAO/WHO 1965, 1968, 1970, 1971, 1973 and 1975).
A carcinogenicity study with rats and mice has become available and is
evaluated below.
The 1974 Meeting of the Codex Committee on Pesticide Residues (CCPR)
returned a number of recommended maximum residue limits at levels of
0.3 and 0.2 mg/kg to the Joint Meeting with the request to investigate
whether these limits could be reduced when only alpha (cis)-chlordane
and gamma (trans)-chlordane were to be measured. The 1974 Joint
Meeting concluded that, although the recommended maximum residue
levels were slightly higher than the residues reported, insufficient
latitude was available to reduce the recommended figures.
The 1977 CCPR meeting, unable to reach agreement on the proposed
figures, again returned them (see ALINORM 78/24, items 12.16-12.31) to
the Joint Meeting with the request for new proposals in view of the
reduction in the use of chlordane in recent years. It was also agreed
that in most cases a "practical residue limit" i.e. an extraneous
residue limit, would be more realistic than a maximum residue limit as
proposed.
EVALUATION FOR ACCEPTABLE DAILY INTAKE
TOXICOLOGICAL STUDIES
Special studies on carcinogenicity
Mice
The groups receiving high and low doses of chlordane consisted of 50
male and 50 female mice, the control group of 10 males and 10 females.
In the final evaluation pooled control groups were formed by combining
controls from other experiments. The doses which were used decreased
during the study because of toxicity. For the males the time-weighted
average doses were 30 ppm in the low and 56 ppm in the high dose
group. For the females these were respectively 30 and 64 ppm. The mice
were administered chlordane for 80 weeks, then observed for 10 weeks.
Hepatocellular carcinoma was induced at a highly significant rate of
incidence in mice given chlordane, particularly at the high dose
(National Cancer Institute, 1977).
Rats
The groups receiving high and low doses of chlordane consisted of 50
male and 50 female rats, the control groups of 10 males and 10
females. The rats were administered chlordane for 80 weeks, then
observed for 29 weeks. In the final evaluation pooled control groups
were formed by combining controls from other experiments. The doses
which were used were decreased during the study because of toxicity.
For the males the time-weighted average doses were 204 ppm in the low
and 407 ppm in the high dose group. For the females these were
respectively 121 and 242 ppm. The body weights in the high dose group
were lower in both males and females. The incidence of hepatocellular
adenoma was extremely low. There was no statistically significant
increase in the number of neoplastic nodules. A dose-related trend in
follicular cell lesions of the thyroid was found, which was
significant for females. In the males a significant dose-related trend
in malignant fibrous histiocytoma was found. However, the nature,
incidence and severity of the thyroid lesions and the histiocytomas
were not sufficient to indicate a clearly carcinogenic effect of
chlordane in rats.
The sample of chlordane used in both carcinogenicity studies contained
94.8% chlordane (71.7% cis-chlordane and 23.1% trans-chlordane)
(National Cancer Institute, 1977).
Short-term studies
Rat
Various experiments were carried out with doses of 2, 5, 10, 20 and 50
ppm in the diet during two weeks. At the end of this period the
microsomal liver enzymes hexobarbital oxidase, aminopyrine demethylase
and aniline hydroxylase were determined. Many experiments were done to
establish the no-effect level in this respect as accurately as
possible. In this comparative study, in which about 15 pesticides were
studies, a no-effect level of 5 ppm was found for chlordane. (Den
Tonkelaar and Van Esch, 1974).
COMMENTS
Chlordane is a member of the group of organochlorine insecticides
which have the common effect of inducing liver microsomal enzymes.
(See Report of 1977 Meeting, FAO/WHO, 1978, Sections 3.1 and 3.2)
In long-term studies, chlordane caused hepatocellular carcinoma in
mice at a dose of 60 ppm in the diet, but not in rats at doses as high
as 400 ppm for males and 240 ppm for females. Both male and female
rats were found to have an increase in proliferative lesions of
follicular cells of the thyroid. Male rats only showed an increase of
malignant fibrous histiocytomas, but these observations were
discounted because of their low incidence and the high variability of
the number of tumours in earlier experiments at the same research
center.
In a short-term test with liver enzyme induction as the most sensitive
criterion, a no-effect level in rats was established which is lower
than the one of 20 ppm established earlier.
TOXICOLOGICAL EVALUATION
Level causing no toxicological effect
Rat: 5 mg/kg in the diet, equivalent to 0.25 mg/kg bw
Dog: 3 mg/kg in the diet, equivalent to 0.075 mg/kg bw
ESTIMATE OF ACCEPTABLE DAILY INTAKE FOR HUMANS
0-0.001 mg/kg bw
RESIDUES IN FOOD AND THEIR EVALUATION
The only new data made available to the 1977 Joint Meeting were
figures from the USA from their 1975 and 1976 Food Surveys. They are
contained in Tables 1 and 2.
It would seem that the considerations of the 1974 Joint Meeting with
regard to the latitude of the residues to be expected are confirmed by
the data from the Food Survey.
As most of the residues result from registered uses, it does not seem
justified to consider the proposed MRLs specified by the CCPR other
than as maximum residue limits.
APPRAISAL
The 1977 CCPR asked for a reduction of the proposed maximum residue
limits for the items contained in ALINORM 78/24, 12.16-12.31. No data
being available to the 1977 Joint Meeting to justify such a reduction,
the existing recommendations are not changed.
There is no reason to consider the proposed limits as extraneous
residue limits as they can result from registered uses.
FURTHER WORK OR INFORMATION
Desirable
1. Further studies to elucidate the long-term effects.
2. Further information relating to the occurrence of residues in
various commodities as listed by the Codex Committee on Pesticide
Residues at its Ninth Session (1977, ALINORM 78/24, p. 10).
TABLE 1. Residues of chlordane found in USA Foood Survey 1975
Beans Carrots Cucumbers Onions Potatoes Rutabagas Snap beans Strawberries Sweet potatoes Catfish
Range,
mg/kg
Trace 2 13 1 2 2
0.01 - 0.02
>0.02 - 0.03
>0.03 - 0.05 1
>0.05 - 0.1 1 1 1
>0.1 - 0.2 1 29 2 1
>0.2 - 0.3 1 16 1 1
>0.3 - 0.5 17 1
>0.5 - 1.0 14
>1.0 1
Total 1 3 1 1 91 3 1 3 4 1
Individual
residues
exceeding
1 mg/kg 2.0
TABLE 1A. Residues of chlordane found in USA Foood Survey 1975
Other fish Bone meal Fish meal Fish oil
Trace 1
0.01 -0.02
>0.02 - 0.03 1
>0.03 - 0.05
>0.05 - 0.1
>0.1 - 0.2 1 2
>0.2 - 0.3
>0.3 - 0.5
>0.5 -1.0 2
>1.0 2
Total 1 1 6 1
Individual
residues
exceeding 6.68
1 mg/kg 9.6
TABLE 2A. Residues of chlordane found in USA Food Survey, 1976
Beans Cantaloupes Carrots Cherries Coriander Corn Cucumbers Lettuce Oranges Parsley Peanuts
Range, mg/kg
Trace 3 3 1
0.01 - 0.02 2 1 1
>0.02 - 0.03
>0.03 - 0.05 1
>0.05 - 0.1 1 1
>0.1 - 0.2 1 4 1 2 1
>0.2 - 0.3 1 1
>0.3 - 0.5 1 1 1
>0.5 - 1.0 2
1.0
Total 1 5 7 1 1 1 9 1 1 1 2
Individual
residues
exceeding
1 mg/kg
TABLE 2B. Residues of chlordane found in USA Food Survey, 1976
Potatoes Pumpkins Rice Rice bran Squash Strawberries Tomatoes Yams Eggs Bluefish Carp Catfish
Range, mg/kg
Trace 18 3 3 2
0.01 - 0.02 1 1
>0.02 - 0.03 3
>0.03 - 0.05 1 2 1 4
>0.05 - 0.1 6 2 1 3 1 1 1
>0.1 - 0.2 22 1 2 2
>0.2 - 0.3 12 2 1 1
>0.3 - 0.5 8 1 4
>0.5 - 1.0 1 1 4
1.0 5
Total 67 3 2 2 10 3 5 3 3 1 2 20
Individual residues exceeding
1 mg/kg 1.12
1.12
1.24
1.45
1.59
4.83
TABLE 2C. Residues of chlordane found in USA Food Survey, 1976
Turbot Other fish Fish products Dairy feed Fish meal
Range, mg/kg
Trace 2 3 1 3
0.01 - 0.02 1 2 2
>0.02 - 0.02 1 1
>0.03 - 0.05
>0.05 - 0.1
>0.1 - 0.2 1 3 3
>0.2 - 0.3 1 2 2
>0.3 - 0.5 1
>0.5 - 1.0 1
1.0 1
Total 2 6 11 1 11
Individual
residues
exceeding
1 mg/kg 3.57
REFERENCES
Den Tonkelaar, E.M. and Van Esch, G.J. (1974) No-effect levels of
organochlorine pesticides based on induction of microsomal liver
enzymes in short-term toxicity experiments. Toxicology 2 371-380
National Cancer Institute. (1977) Bioassay of chlordane for possible
carcinogenicity. Carcinogenesis Technical Report Series no. 8.
(Unpublished report)
FAO/WHO (1965) Evaluation of the toxicity of pesticide residues in
food. FAO Meeting Report, No. PL:1965/10/1; WHO/Food Add./27.65.
FAO/WHO (1968) 1967 evaluation of some pesticide residues in food.
FAO/PL:1967/M/11/1; WHO/Food Add./68.30.
FAO/WHO (1970) 1969 evaluations of some pesticide residues in food.
FAO/PL:1969/M/17/1; WHO/Food Add./70.38
FAO/WHO (1971) 1970 evaluations of some pesticide residues in food.
AGP:1970/M/12/1; WHO/Food Add./71.42.
FAO/WHO (1973) 1972 evaluations of some pesticide residues in food.
AGP:1972/M/9/1; WHO Pesticide Residues Series, No. 2.
FAO/WHO (1975) 1974 evaluations of some pesticide residues in food.
AGP:1974/M/11; WHO Pesticide Residues Series, No. 4.
FAO/WHO (1978) Pesticide residues in food. Report 1977. FAO Plant
Production and Protection Paper No. 10.
See Also:
Toxicological Abbreviations
Chlordane (EHC 34, 1984)
Chlordane (HSG 13, 1988)
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: 1982 evaluations)
Chlordane (Pesticide residues in food: 1984 evaluations)
Chlordane (Pesticide residues in food: 1986 evaluations Part II Toxicology)