Evaluation of liver weight changes following repeated administration of carbon tetrachloride in rats and body—liver weight relationship

Abstract The proper method of evaluating liver weight changes resulting from the primary toxic effect of a chemical was studied. We used a pair-feeding method with carbon tetrachloride (CCl 4 ), a chemical known to cause an increase in liver weight. Male rats were assigned to an untreated control group, CCl 4 -treated groups (daily dose of 10 μl or 50 μl of CCl 4 in olive oil/100 g body wt), olive oil-treated plus feed-restricted groups, and feed-restricted groups. In the 2 types of feed-restricted groups the body weight changes of the CCl 4 -treated groups were duplicated by imposing restrictions on feeding. Absolute and relative liver weights were compared among the 4 types of groups after treatment for 14 or 25 days. Either absolute or relative liver weight of the treated group when compared to that of the feed-restricted group was the most reliable and sensitive toxicity indicator. In comparing the treated group with the untreated control group, relative liver weight was a more sensitive toxicity indicator than absolute liver weight. However, when liver weight data for about 200 normal male rats were plotted against body weight, and the 95% confidence limits of the regression line ( γ = ax ) were estimated, most of the data for the feed-restricted rats were outside the lower confidence limit. This means that a comparison of the relative liver weights of the treated rats and untreated control rats is not strictly valid, because the body weight-liver weight relationships are not the same in the 2 groups.