STRAIN AS A DETERMINANT FACTOR IN THE DIFFERENTIAL RESPONSIVENESS OF RATS TO CHEMICALS

The beneficial effects derived from the use of chemicals in agricultur e, energy production, transportation, pharmaceuticals, and other produ cts that improve the quality of life are clearly established. However, continued exposure to these chemicals is only advantageous in conditi ons where the benefit far outweighs toxic manifestations. By law, dete rmination of risk of toxicity necessitates the use of laboratory anima ls to establish whether chemical exposure is safe for humans. To simul ate the human condition, it is incumbent upon investigators to choose a species in which pharmacokinetic and toxicokinetic principles are es tablished and resemble those of humans. Some of the advantages to the use of rat in chemical toxicity testing include (a) similarities in me tabolism, anatomy, and physiological parameters to humans; (b) the sho rt life span, especially for carcinogenesis study; (c) the availabilit y, ease of breeding, and maintenance at a relatively low cost; and (d) the existence of a large database to enable comparison of present to reported literature findings. However, the choice of rat can be compli cated by several factors such as sex, age, and nutrition, but especial ly strain, where currently there are over 200 different strains of rat known to exist. The aim of this review is to demonstrate that there a re differences in the responsiveness of rat strains to chemicals and t hat the susceptibility observed is dependent on the tissue examined. I t is evident that the genotype differs among strains, and this may be responsible for differences in sensitivities to chemicals. Awareness o f strain as a factor in susceptibility to toxicant action needs to be taken into account in interpretation of relevance of risk of toxicity for humans.