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1,1-二氯-1-氟乙烷(HCFC-141b)的吸入致畸学和两代繁殖研究

Inhalation teratology and two-generation reproduction studies with 1,1-dichloro-1-fluoroethane (HCFC-141b).

作者信息

Rusch G M, Millischer R J, de Rooij C, Brooker A J, Hughes E, Coombs D

机构信息

AlliedSignal Inc., Morristown, NJ 07962, USA.

出版信息

Food Chem Toxicol. 1995 Apr;33(4):285-300. doi: 10.1016/0278-6915(94)00144-d.

Abstract

HCFC-141b is one of the chemicals being considered as a replacement for CFC 11 in solvent and foam-blowing applications. Teratology studies were conducted in both rats and rabbits and a two-generation reproduction inhalation toxicity study was conducted in rats. The pregnant rabbits were exposed to levels of 0 (control), 1400, 4200 and 12,600 ppm HCFC-141b from day 7 to day 19 of gestation (6 hr/day). There was no evidence of developmental or teratogenic effects on the foetuses. The pregnant rats in the teratology study were exposed to levels of 0 (control), 3200, 8000 and 20,000 ppm from days 6 to 15 of gestation (6 hr/day). In the 20,000 ppm exposure group, there was an increase in implantation losses; furthermore, in this group, foetal weights tended to be lower than controls. As with the rabbits, there was no evidence of a teratogenic effect. The reproduction study was conducted at exposure levels of 0, 2000, 8000 and 20,000 ppm, 7 days/wk starting approximately 10 wk before the first pairing. Adult rats exposed at 20,000 ppm (and, to a lesser extent, those exposed to 8000 ppm) showed increases in water intake, slight increases in food consumption, and decreases in body weight. Following the mating of the F0 parents, there were fewer litters in the 20,000 ppm exposure level group than in controls. When these parents were then paired with different partners, again, the number of litters was lower in the 20,000 ppm group, although most of the animals that did not produce litters the first time mated successfully the second time. When the F1 animals were mated to produce the second generation, the number of litters was comparable for all groups. In the second F0 mating and the F1 mating, the number of pups per litter was lower at 20,000 ppm; although birth weights were comparable, body weight gain tended to be slower in the high-level exposure group. Survival was good in all groups. At 8000 ppm no significant effects were observed in the pups and only minimal signs in the adults. The 2000 ppm exposure level represented a clear no-observed-effect level for all indices.

摘要

HCFC - 141b是在溶剂和发泡应用中被考虑用作CFC - 11替代品的化学物质之一。在大鼠和兔子身上都进行了致畸学研究,并在大鼠身上进行了两代繁殖吸入毒性研究。怀孕的兔子在妊娠第7天至第19天(每天6小时)暴露于0(对照)、1400、4200和12,600 ppm的HCFC - 141b水平下。没有证据表明对胎儿有发育或致畸影响。致畸学研究中的怀孕大鼠在妊娠第6天至第15天(每天6小时)暴露于0(对照)、3200、8000和20,000 ppm的水平下。在20,000 ppm暴露组中,着床损失有所增加;此外,在该组中,胎儿体重往往低于对照组。与兔子一样,没有致畸作用的证据。繁殖研究在0、2000、8000和20,000 ppm的暴露水平下进行,每周7天,从首次配对前约10周开始。暴露于20,000 ppm的成年大鼠(以及在较小程度上,暴露于8000 ppm的大鼠)饮水量增加,食物摄入量略有增加,体重下降。F0代亲本交配后,20,000 ppm暴露水平组的窝数比对照组少。当这些亲本与不同的配偶再次配对时,同样,20,000 ppm组的窝数较低,尽管大多数第一次没有产仔的动物第二次交配成功。当F1代动物交配产生第二代时,所有组的窝数相当。在第二次F0代交配和F1代交配中,20,000 ppm时每窝幼崽数较少;尽管出生体重相当,但高暴露水平组的体重增加往往较慢。所有组的存活率都很高。在8000 ppm时,幼崽未观察到显著影响,成年动物仅有轻微迹象。2000 ppm的暴露水平对所有指标而言均代表明确的无观察到影响水平。

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