Mohler F S, Gordon C J
U.S. Environmental Protection Agency, Neurotoxicology Division, Research Triangle Park, NC 27711.
J Toxicol Environ Health. 1991 Feb;32(2):129-39. doi: 10.1080/15287399109531473.
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.
本研究的目的是评估体温调节系统作为预测各种短链醇毒性终点的效用。雄性Fischer大鼠在急性腹腔注射甲醇、乙醇、1-丙醇、2-丙醇、1-丁醇或2-丁醇后出现显著体温过低。对这六种醇的体温过低反应均表现出相似的分段反应，其特征为存在一个阈值剂量，低于该剂量体温无变化，以及随着剂量增加导致体温过低程度加重的超阈值回归。使用引起体温过低的阈值剂量和使体温降低1摄氏度的剂量来评估醇的相对效力。两种测量方法均得出毒性从低到高的顺序为甲醇＜乙醇＜2-丙醇＜1-丙醇＜2-丁醇＜1-丁醇。将每种醇的有效剂量与其膜/缓冲液分配系数（Pm/b）进行比较，发现醇的体温过低剂量与其脂溶性之间存在高度负相关。醇的效力与其Pm/b密切相关，这表明麻醉的膜紊乱理论也可用于解释醇的体温过低作用。
