CAVEATS REGARDING THE USE OF THE LABORATORY RAT AS A MODEL FOR ACUTE TOXICOLOGICAL STUDIES - MODULATION OF THE TOXIC RESPONSE VIA PHYSIOLOGICAL AND BEHAVIORAL MECHANISMS

The rodent, specifically the laboratory rat, is the primary experiment al animal used in toxicology testing. Despite its popularity, recent s tudies from our laboratory and others raise a number of questions conc erning the rat's appropriateness as an animal model for toxicological studies. While there may be additional areas in which the rat and othe r small rodents fail to adequately mimic the human response to xenobio tic agents, this article will focus on the area of temperature regulat ion. Thus, this article will review the thermoregulatory response of t he laboratory rat following acute exposure to toxic agents and examine the impact of this response on the extrapolation of toxicological dat a from experimental animals to humans. In general, the rat responds to acute intoxication by lowering its core temperature via both physiolo gical and behavioral mechanisms, thereby attenuating the induced toxic ity. Similar responses have not been reported in humans.