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Table 1. Tumor incidence in yellow mice exposed to γ-HCH (lindane) (Wolff et al., 1987)
Dietary Concentration of
Tumor Type and Incidence
γ-HCH (ppm) Lung Carcinomas Liver Adenomas
0 4/95 8/93
160 18/95 33/94
Thorpe and Walker (1973) showed an increase in liver tumors of male CF1 mice fed 400 ppm lindane
for 110 weeks, compared with controls. The time-weighted dose was estimated as 52 mg/kg/day by
US EPA (1988). In this experiment, control mice exhibited an incidence of 11/45 for liver tumors,
compared to 27/29 for the 52 mg/kg/day group.
A study by Goto et al. (1972) showed a positive effect of lindane on cancer in mice. However, this
experiment used only 10 animals per treatment group and was of a short duration. The NCI (1977)
study on male mice showed a significant increase in cancer incidence in mice exposed to 80, but not
160 ppm γ-HCH. The absence of a clear dose-response precluded this data from use in determining
the cancer potency for lindane.
IV.
DERIVATION OF CANCER POTENCY
Basis for Cancer Potency
The US EPA (1988) selected the study by Thorpe and Walker (1973) as the basis for the cancer
potency for lindane. This was considered to be the best study for development of a cancer potency
factor for lindane because of the large sample size of mice surviving for a full lifespan, and the large
numbers of tumors in the treatment group. Thorpe and Walker (1973) showed an increase in liver
tumors in male CF1 mice fed 400 ppm lindane in the diet for 110 weeks, compared with controls.
Control mice exhibited an incidence of 11/45 for liver tumors, compared to 27/29 for the lindanetreated
group (p < 0.01). Some lung metastases were also reported in the male and female mice
treated with lindane.
Methodology
A linearized multistage procedure was used to estimate the cancer potency of lindane from the Thorpe
and Walker (1973) data in male CF1 mice (Crump et al., 1982). The concentrations of lindane given
in the feed were 0 or 160 ppm. The 95% upper confidence bound on the dose-response slope was
used to derive the human cancer potency value for lindane.
The animal cancer potency, q animal , was calculated from the linear slope using the lifetime scaling factor
q animal = q 1 * × (T/T e ) 3 , where T/T e is the ratio of the experimental duration to the lifetime of the animal.
An estimated value for the human cancer potency was determined using the relationship q human = q animal
× (bw h /bw a ) 1/3 , where bw is the default body weight of human or animal (mouse).
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