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.