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通过连续繁殖方案评估二甘醇和二甘醇单乙醚对瑞士CD-1小鼠的生殖影响。

Reproductive effects of diethylene glycol and diethylene glycol monoethyl ether in Swiss CD-1 mice assessed by a continuous breeding protocol.

作者信息

Williams J, Reel J R, George J D, Lamb J C

机构信息

Developmental and Reproductive Toxicology Group, National Toxicology Program, NIEHS, Research Triangle Park, North Carolina 27709.

出版信息

Fundam Appl Toxicol. 1990 Apr;14(3):622-35. doi: 10.1016/0272-0590(90)90266-m.

DOI:10.1016/0272-0590(90)90266-m
PMID:2340988
Abstract

Diethylene glycol (DEG) and diethylene glycol monoethyl ether (DEGEE) were evaluated for reproductive toxicity in CD-1 mice using a continuous breeding protocol. Compounds were administered in the drinking water at 0, 0.35, 1.75, and 3.5% w/v (DEG) or 0, 0.25 1.25, and 2.5% w/v (DEGEE). Exposure of the breeding pairs to 3.5% DEG for 14 weeks produced statistically significant decreases in the number of litters per pair, live pups per litter, proportion of pups born alive, and live pup weight. There was also a significant increase in the cumulative days to litter and a significant decrease in the number of pairs producing the third, fourth, and fifth litters for the 3.5% DEG-exposed mice. A crossover mating trial of the F0 mice to determine the affected sex was inconclusive, but suggested that offspring development was compromised in females exposed to 3.5% DEG. Slight maternal (F0) toxicity was noted for the 3.5 DEG group (7% decrease in body weight). The F1 generation, at 3.5% DEG, had decreased body weights at birth and exhibited poor postnatal survival. At the intermediate dose of DEG, body weights of both sexes were depressed at weaning, at onset of mating, and at necropsy. However, no adverse effects on reproduction were observed. DEGEE had no effect on reproduction in the F0 or F1 generation mice despite a 34% decrease in cauda epididymal sperm motility in the F1 males at 2.5% DEGEE. Other signs of toxicity observed in these F1 mice included increased relative liver weights. These data indicate that DEG is a reproductive toxicant in Swiss mice affecting fertility and reproductive performance, albeit at high doses (equivalent to 6.1 g/kg/day). However, its monoethyl derivative, DEGEE, is without adverse effects on fertility and reproductive performance.

摘要

采用连续繁殖方案,对CD - 1小鼠评估了二甘醇(DEG)和二甘醇单乙醚(DEGEE)的生殖毒性。化合物以0、0.35、1.75和3.5% w/v(DEG)或0、0.25、1.25和2.5% w/v(DEGEE)的浓度添加到饮用水中。繁殖对暴露于3.5% DEG 14周后,每对产仔数、每窝活仔数、活产仔比例和活仔体重均出现统计学上的显著下降。暴露于3.5% DEG的小鼠,产仔累计天数也显著增加,产第三、第四和第五窝的配对数量显著减少。对F0小鼠进行交叉交配试验以确定受影响的性别,但结果尚无定论,但表明暴露于3.5% DEG的雌性小鼠后代发育受到损害。3.5% DEG组出现轻微的母体(F0)毒性(体重下降7%)。在3.5% DEG剂量下,F1代出生时体重下降,出生后存活率低。在DEG的中间剂量下,两性在断奶、开始交配和尸检时体重均下降。然而,未观察到对生殖的不利影响。尽管在2.5% DEGEE剂量下F1雄性小鼠附睾尾精子活力下降了34%,但DEGEE对F0或F1代小鼠的生殖没有影响。在这些F1小鼠中观察到的其他毒性迹象包括相对肝脏重量增加。这些数据表明,DEG是瑞士小鼠中的一种生殖毒物,尽管在高剂量(相当于6.1 g/kg/天)下会影响生育力和生殖性能。然而,其单乙醚衍生物DEGEE对生育力和生殖性能没有不利影响。

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