Weight and survival depression in rodent bioassays with and without tumor decreases

It has been suggested that the decreased tumor rates (anticarcinogenicity) commonly observed in the National Toxicology Program (NTP) rodent bioassays may be caused by compound-induced decreases in body weight or decreases in survival of treated animals. In this study, weight decrement and survival depression following chemical treatment was studied for those chemicals which induce site specific decreases in tumor rates (anticarcinogens) and those which do not (non-anticarcinogens) in a database of 312 chemicals tested in the NTP bioassay program prior to 1983. There is an evident difference in weight depression and animal survival between anticarcinogens and non-anticarcinogens but it is small relative to the variability between chemicals in the two groups. We argue that weight or survival depression cannot, in a simple way, explain the difference between anticarcinogenic and non-anticarcinogenic chemicals. In fact, there are a number of chemicals that are anticarcinogenic with no evidence of weight or survival depression and many chemicals that cause significant weight or survival decreases with no apparent anticarcinogenic effects. There is a small but statistically insignificant relationship between the degree of weight depression and the number of tumor sites found to have lower tumor rates in treated animals. These analyses suggest that biological factors other than weight and survival depression are involved in decreased tumor rates in rodent bioassays. These results, and those of the companion paper (I. Linkov et al., this issue), suggest that the anticarcinogenic responses observed in rodent cancer bioassays should be carefully considered in evaluations of the overall carcinogenic potential of chemicals.