ABSTRACT
The long-term bioassay for carcinogenic potential is a valuable tool for assessing human hazard, but suffers from severe limitations. Some of these follow directly from the use of animals as surrogates for man; others are created by study design and interpretations. It is recommended that much attention must be given to dose selection so as not to destroy the validity of the purported model and that emphasis must be placed upon elucidating the nature of the stimuli the test substance provides to the animal. Only after arriving at an understanding of the primary activity will it be possible to judge whether or not a similar response can be expected from man. The recently instituted change by the National Toxicology Program in expressing their interpretive conclusions promises a shift of the investigator's focus from the response of a test system to the action of the test substance.
Subject(s)
Biological Assay , Carcinogens/toxicity , Animals , Disease Models, Animal , Humans , Research Design , Species SpecificityABSTRACT
Testing of chemicals for carcinogenic potential usually involves studies in rats and mice. The approaches followed in recent years often were limited to assessing tumor incidences and rarely viewed such information from the perspective of other kinds of toxicity. This practice supports the notion that certain chemicals possess the inherent characteristic of carcinogenic activity, which once identified in one species must be regarded as potential oncogenic hazard to all, including man. As long as public policy is based upon that premise, the classification of chemicals depends upon the worst results obtained in any species. It is not obvious why substances must be tested in both rats and mice when confirmatory or contradictory responses have little impact. Recent experience was examined to build a basis for an alternate approach. Review of oncogenicity information obtained for 273 chemicals fed to rats and mice shows that both species responded similarly to the majority of the substances tested. This "redundancy" probably would be higher had modern protocols been used. In view of the high cost in scientific resources of chronic studies, tests in only one rodent would be more cost effective. Reasons are presented for favoring the rat as the species to be used. Some of the savings thus achieved should be expended to improve the design of the experiments to yield toxicology data more comprehensive than mere tumor counts, so that the proper perspective can be obtained on the results.