Hellwig J, Jäckh R
Department of Toxicology, BASF Aktiengesellschaft, Ludwigshafen, Germany.
Food Chem Toxicol. 1997 May;35(5):489-500. doi: 10.1016/s0278-6915(97)00007-0.
One straight-chain alcohol (n-octanol) and five branched-chain alcohols [2-ethylhexanol (2-EH), isodecanol, two types of isononanol and a C7-9-11 alcohol] were investigated for developmental effects in Wistar rats at equimolar dose levels (0, 1, 5 and 10 mmol/kg by gavage from gestation day 6 to 15; 10 animals per group). n-Octanol and both isononanols were also investigated in a supplementary experiment at 7.5 mmol/kg/day. Pronounced maternal but no developmental toxicity was achieved with n-octanol. C7-9-11 alcohol, which is a mixture of isomers mostly of a low degree of branching (alpha-methyl), showed no adverse effects at any dose levels. The two types of isononanols (typical mixtures of two different sets of isomers originating from two different production routes) exhibited a marked degree of maternal and foetal toxicity at 7.5 and 10 mmol/kg and slight foetal effects at 5 mmol/kg. Because of maternal toxicity in the top dose, a statistically significant increase in malformations was obtained only in the dose window of 7.5 mmol/kg in the supplementary experiment. Isodecanol (a mixture of different isomers) elicited maternal toxicity at 10 mmol/kg and caused a low incidence of retardations and rare malformations at that dose level. Some maternal signs but no foetal effects were observed at 5 mmol/kg. 2-EH showed strong maternal and also foetal toxicity at 10 mmol/kg and slight maternal and foetal toxicity at 5 mmol/kg. The differential responses to the test materials indicate that, at present, within this chemical class of alcohols, the potential for developmental toxicity has to be investigated case by case for each individual structure.
研究了一种直链醇（正辛醇）和五种支链醇[2-乙基己醇（2-EH）、异癸醇、两种异壬醇和一种C7-9-11醇]对Wistar大鼠的发育影响，剂量水平为等摩尔（从妊娠第6天至15天经口灌胃给予0、1、5和10 mmol/kg；每组10只动物）。正辛醇和两种异壬醇还在补充实验中以7.5 mmol/kg/天的剂量进行了研究。正辛醇对母体有明显影响，但未产生发育毒性。C7-9-11醇是一种异构体混合物，大多为低支化度（α-甲基），在任何剂量水平下均未显示出不良反应。两种异壬醇（分别源自两条不同生产路线的两种不同异构体混合物）在7.5和10 mmol/kg时表现出明显的母体和胎儿毒性，在5 mmol/kg时对胎儿有轻微影响。由于高剂量组存在母体毒性，在补充实验中仅在7.5 mmol/kg的剂量范围内畸形率有统计学意义的增加。异癸醇（不同异构体的混合物）在10 mmol/kg时引起母体毒性，并在该剂量水平导致低发生率的发育迟缓及罕见畸形。在5 mmol/kg时观察到一些母体体征，但对胎儿无影响。2-EH在10 mmol/kg时表现出强烈的母体和胎儿毒性，在5 mmol/kg时表现出轻微的母体和胎儿毒性。对受试物质的不同反应表明，目前在这类醇类化合物中，每种个体结构的发育毒性潜力都必须逐例研究。
