Lee J C, Shin I S, Ahn T H, Kim K H, Moon C, Kim S H, Shin D H, Park S C, Kim Y B, Kim J C
Animal Medical Center, College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea.
Regul Toxicol Pharmacol. 2009 Feb;53(1):63-9. doi: 10.1016/j.yrtph.2008.11.001. Epub 2008 Nov 20.
This study investigated the potential adverse effects of 1,3-dichloro-2-propanol (1,3-DCP) on pregnant dams and the embryo-fetal development after maternal exposure on gestational days (GD) 6 through 19 in Sprague-Dawley rats. The test chemical was administered to pregnant rats by gavage at dose levels of 0, 10, 30, and 90mg/kg per day (n=10 for each group). All dams underwent Caesarean sections on GD 20, and their fetuses were examined for morphological abnormalities. Maternal toxicity was noted at 90mg/kg/day. Manifestations of toxicity included clinical signs of illness, lower body weight gain, decreased food intake, and increases in the weight of the adrenal glands and the liver. Developmental toxic effects including decreases in fetal body weight and increases in visceral and skeletal variations also occurred at the highest dose. At 30mg/kg, only a minimal maternal toxicity, including a decrease in maternal food intake and an increase in the liver weight, was observed. No adverse maternal or developmental effects were observed at 10mg/kg/day. These results revealed that a 14-day repeated oral dose of 1,3-DCP was minimally embryotoxic but not teratogenic at a maternal toxic dose (90mg/kg/day), and was not embryotoxic at a minimally maternal toxic dose (30mg/kg/day) in rats. Because the developmental toxicity of 1,3-DCP was observed only in the presence of maternal toxicity, it is concluded that the developmental findings observed in the present study are secondary effects to maternal toxicity. Under these experimental conditions, the no-observed-adverse-effect level of 1,3-DCP is considered to be 10mg/kg/day for dams and 30mg/kg/day for embryo-fetal development.
本研究调查了1,3 - 二氯 - 2 - 丙醇（1,3 - DCP）对妊娠母鼠的潜在不良影响，以及在妊娠第6天至第19天母体暴露后对胚胎 - 胎儿发育的影响。将受试化学物质以每天0、10、30和90mg/kg的剂量水平通过灌胃给予妊娠大鼠（每组n = 10）。所有母鼠在妊娠第20天进行剖腹产，并检查其胎儿的形态异常。在90mg/kg/天的剂量下观察到母体毒性。毒性表现包括疾病的临床体征、体重增加减少、食物摄入量减少以及肾上腺和肝脏重量增加。在最高剂量下也出现了发育毒性作用，包括胎儿体重下降以及内脏和骨骼变异增加。在30mg/kg时，仅观察到最小的母体毒性，包括母体食物摄入量减少和肝脏重量增加。在10mg/kg/天的剂量下未观察到母体或发育方面的不良影响。这些结果表明，在大鼠中，14天重复口服1,3 - DCP在母体毒性剂量（90mg/kg/天）下具有最小的胚胎毒性但无致畸性，在最小母体毒性剂量（30mg/kg/天）下无胚胎毒性。由于仅在存在母体毒性的情况下观察到1,3 - DCP的发育毒性，因此得出结论，本研究中观察到的发育结果是母体毒性的继发效应。在这些实验条件下，1,3 - DCP对母鼠的未观察到不良影响水平被认为是10mg/kg/天，对胚胎 - 胎儿发育的未观察到不良影响水平是30mg/kg/天。
