Determination of the “no-effect levels” of two pesticides, lindane and zineb, on the microsomal enzyme activities of rat liver

For 4 weeks young male Wistar rats were fed diets containing various doses of lindane, an inducer of liver microsomal mixed function oxidase, or of zineb, an inhibitor of this system. The dosages were: 0 (control), 0.2, 0.5, 2, 20, and 120 ppm, for lindane; and 0 (control), 6, 15, 60, 600, and 3600 ppm for zineb. The parameters assayed were liver microsomal aminopyrine-N-demethylase and aniline hydroxylase activities, and cytochrome P-450 concentration. Lindane had the same increasing effect on the three parameters assayed. The dose inducing the least significant difference at the p < 0.05 level was 4 ± 0.3 ppm, when results were relative to whole liver weight. Zineb did not have the same inhibiting effect, aniline hydroxylase being the most sensitive of the three parameters, with a computed dose of 74 ± 15 ppm, irrespective of the reference base. The no effect levels at the p < 0.95 confidence interval were 20 or 40 times lower than the preceding ones, being 0.16 ± 0.02 ppm for lindane and, in the case of aniline hydroxylase activity and zineb, 2 ± 0.3 ppm. From a probability point of view, the classical “no effect level” is a dose below which it can be said that the effect is truly zero, but with a confidence level only higher than 5%. The method presented here allows a reasonable downward extrapolation for a better confidence level of 95%.