Several in vivo and in vitro assays have been developed to test for mutagens which are chemicals having the ability to cause gene mutation. The in vitro assay that has received the widest attention and acceptance is the Ames test (Slide 11). The relatively high correlation between mutagens and carcinogens has lent considerable support to the implication that a genotoxic action would eventually induce an oncogenic effect, as asserted by the somatic mutation theory (Vanparys et al., 1996). Genetic toxicology involves not only point mutation at the DNA level, but also genome mutation which usually deals with chromosome aberrations. Tests for genetic toxicity are numerous, many of which have been summarized by Hoffmann (1996). A newly accepted mutagenicity test appears to be that with transgenic mice, which are rodents that possess a small part of foreign DNA in their genome.

Tests on general fertility and reproductive performance are usually performed in rats. The teratogenic potential for chemicals is determined in rabbits, rats, or mice, with doses typically administered during the first trimester which is usually the most vulnerable stage for organogenesis. The perinatal and postnatal toxicities also are examined. In addition, a multigeneration study is often conducted in rats mating over two or three generations to determine the effects on the reproduction system.

Tests for toxic responses of other organs (nervous system, kidney, lung, liver, blood, skin, heart, eye, etc.) in general require the conduct of acute, subchronic, and chronic studies which are discussed in the next slide.