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 experimental animal used in toxicology testing. Despite its popularity, recent studies from our laboratory and others raise a number of questions concerning the rat's appropriateness as an animal model for toxicological studies. While there may be additional areas in which the rat and other small rodents fail to adequately mimic the human response to xenobiotic agents, this article will focus on the area of temperature regulation. Thus, this article will review the thermoregulatory response of the laboratory rat following acute exposure to toxic agents and examine the impact of this response on the extrapolation of toxicological data from experimental animals to humans. In general, the rat responds to acute intoxication by lowering its core temperature via both physiological and behavioral mechanisms, thereby attenuating the induced toxicity. Similar responses have not been reported in humans.
Watkinson
W P
WP
Environmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Gordon
C J
CJ
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000633:toxicity; D000818:Animals; D000830:Animals, Laboratory / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001833:Body Temperature Regulation / Q000187:drug effects* / Q000502:physiology; D002742:Chlorphenamidine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009532:Nickel / Q000633:toxicity; D010126:Ozone / Q000633:toxicity; D051381:Rats / Q000378:metabolism*; D013686:Telemetry
D015104:3,4-Methylenedioxyamphetamine; D010126:Ozone; C022838:nickel chloride; D009532:Nickel; D002742:Chlorphenamidine; D018817:N-Methyl-3,4-methylenedioxyamphetamine