Hypothermic effects of a homologous series of short-chain alcohols in rats.
The purpose of this study was to assess the utility of the thermoregulatory system as an end point in predicting the toxicity of various short-chain alcohols. Male Fischer rats developed significant hypothermia following acute administration (ip) of methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, or 2-butanol. The hypothermic responses to the six alcohols all showed similar segmented responses characterized by a threshold dose below which no change in body temperature occurred, and a suprathreshold regression with increasing dose causing greater hypothermia. Relative potency of the alcohols was assessed using both the threshold dose to cause hypothermia and the dose that would cause body temperature to decrease by 1 degree C. Both measures gave the progression of toxicity from least to most potent of methanol less than ethanol less than 2-propanol less than 1-propanol less than 2-butanol less than 1-butanol. The effective dose of each alcohol was compared to its membrane/buffer partition coefficient (Pm/b), and there was a high inverse correlation between the hypothermic dose of an alcohol and its lipid solubility. That the potency of an alcohol was strongly correlated with its Pm/b suggests that the membrane disordering theory of narcosis may also be used to explain the hypothermic action of alcohols.
Mohler
F S
FS
U.S. Environmental Protection Agency, Neurotoxicology Division, Research Triangle Park, NC 27711.
Gordon
C J
CJ
D000438:Alcohols / Q000633:toxicity*; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007035:Hypothermia / Q000139:chemically induced*; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship
D000438:Alcohols