Nelson B K, Brightwell W S, Taylor B J, Khan A, Burg J R, Krieg E F, Massari V J
Division of Biomedical and Behavioral Science, National Institute for Occupational Safety and Health, Cincinnati, OH 45226.
Neurotoxicol Teratol. 1989 Mar-Apr;11(2):153-9. doi: 10.1016/0892-0362(89)90054-8.
Due to their structural similarity to ethanol, a human teratogen, and their widespread use in industry, a series of industrial alcohols are being investigated for developmental toxicity. This paper presents the results of exposures to 7000 ppm 1-propanol, which is minimally toxic to maternal animals and produces a low incidence of teratogenicity, and to 3500 ppm 1-propanol, which is not toxic to maternal rats and produces no teratogenicity. Propanol vapors or filtered air was administered for 7 hr/day to 15 pregnant Sprague-Dawley rats throughout gestation or to 18 male rats daily for 6 weeks. Tests of offspring were: a) ascent on a wire mesh screen b) rotorod, c) open field and optically monitored activity, d) running wheel, e) avoidance conditioning, and f) progressive fixed ratio schedule of reinforcement. Brains from 10 rats per group were dissected into cerebrum, cerebellum, brainstem, and midbrain, and were assayed for protein, acetylcholine, dopamine, norepinephrine, serotonin, beta-endorphin, Met-enkephalin, and substance P. Overall, the results indicate that exposure to high concentrations of 1-propanol can affect fertility in exposed males (only 2 of 17 produced litters), but there were no consistent effects seen in the behavioral or neurochemical tests measured. This lack of effects is surprising based on predictions from the structural similarity of 1-propanol to ethanol, and on long-standing observations that toxicity (to adult animals) increases with carbon chain length among the aliphatic alcohols.
由于一系列工业酒精在结构上与人类致畸剂乙醇相似,且在工业中广泛使用,因此正在对其发育毒性进行研究。本文介绍了对7000 ppm丙醇(对母本动物毒性极小且致畸发生率低)和3500 ppm丙醇(对母本大鼠无毒且无致畸性)暴露的结果。在整个妊娠期,每天7小时向15只怀孕的斯普拉格-道利大鼠给予丙醇蒸气或过滤空气,或每天向18只雄性大鼠给予6周。对后代的测试包括:a)在金属丝网筛上攀爬,b)转棒试验,c)旷场试验和光学监测活动,d)跑步轮试验,e)回避条件反射试验,以及f)渐进固定比率强化程序试验。每组10只大鼠的大脑被解剖成大脑、小脑、脑干和中脑,并对蛋白质、乙酰胆碱、多巴胺、去甲肾上腺素、血清素、β-内啡肽、甲硫氨酸脑啡肽和P物质进行检测。总体而言,结果表明,暴露于高浓度丙醇会影响暴露雄性的生育能力(17只中只有2只产仔),但在所测量的行为或神经化学测试中未发现一致的影响。基于丙醇与乙醇结构相似性的预测以及长期以来观察到的脂肪族醇类中(对成年动物的)毒性随碳链长度增加的现象,这种缺乏影响的情况令人惊讶。