Toxicology of 2-butyne-1,4-diol
A review of the literature
Metabolically, 2-butyne-1,4-diol appears to be activated to a toxic metabolite in vivo by liver alcohol dehydrogenase (ADH). In Wistar rats, 2- butyne-1,4-diol hen administered i.p. induced mortality in a dose-dependent manner, while pretreatment with pyrazole (an inhibitor of liver ADH) prevented death. Pretreatment with pyrazole prevented also the induction of marked behavioral effects. Using rat liver extract, it was shown that 2-butyne-1,4-diol was a substrate for ADH, and that pyrazole competitively inhibited the oxidation and, therefore, the metabolism of 2-butyne-1,4-diol. It was proposed that inactivation of alcohol oxidase by 2-butyne-1,4-diol was due to the enzymatic production of 4-hydroxy-2-butynal, a potent electrophile which could function as an affinity label for the enzyme.
2-Butyne-1,4-diol has been extensively evaluated for acute and subchronic toxicity in different species (mouse, rat, rabbit, guinea pig, cat) using different routes of exposure (dermal, oral, i.p., ocular, inhalation). The 7-day acute oral LD50 for mice, rats, rabbits, and guinea pigs were between 100 and 200 mg/kg bw (1200 to 2400 :mol/kg bw). For i.p. administration, the 7-day acute LD50 in mice was also about 100 mg/kg bw (1200 :mol/kg bw), while the 24-hour acute LD50 in rats was approximately 50 mg/kg bw (609 to 635 :mol/kg bw). The 2-hour inhalation LCLo (lowest lethal concentration) for mice and rats exposed to 2- butyne-1,4-diol was 150 mg/m3 (1700 :mol/m3). Treatment with 2-butyne-1,4- diol acutely or subchronically resulted in irritation and/or systemic toxicity, the latter primarily involving damage to the liver and kidneys and, depending on the route of exposure, to the skin and lungs. Administration of 2-butyne-1,4-diol i.p. to rats also induced hypothermia.
