Toxic-induced hypothermia and hypometabolism: do they increase uncertainty in the extrapolation of toxicological data from experimental animals to humans?
Commonly used experimental mammals, such as the rat and mouse, exhibit hypothermia and hypometabolism when exposed acutely to many drugs and other chemical substances. This toxic-induced hypothermic/hypometabolic state may be an inherently protective response that can reduce the lethality of a toxic insult. However, as body mass increases, the ability to lower body temperature in response to toxic insult is diminished. Hence, the presence of a protective hypothermic/hypometabolic response in small laboratory mammals and apparent lack thereof in larger species, such as humans, may represent an additional physiological dissimilarity which may underestimate the risk assessment of acute toxicological data. It is proposed that acute toxicological studies in rodents be performed at relatively warm ambient temperatures (ca. 28 to 32 degrees C) to prevent toxic-induced hypothermia. This would assure a more uniform internal thermal environment between species, thus reducing a major physiological variable in species-to-species extrapolation.
Gordon
C J
CJ
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
D000818:Animals; D001835:Body Weight; D006801:Humans; D007035:Hypothermia / Q000139:chemically induced*; D008660:Metabolism / Q000187:drug effects*; D013045:Species Specificity