给药载体对溴二氯甲烷和四氯化碳大鼠发育毒性的影响

Michael G. Narotsky , Rex A. Pegram , Robert J. Kavlock
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引用次数: 29

摘要

几种卤代烃经玉米油口服后可引起fisher -344大鼠全凋落物吸收(FLR)。由于卤代烃经常作为饮用水的污染物出现,我们试图确定载体(含水与脂质)对其中两种物质的发育毒性的影响。在单独的实验中,在妊娠期(GD) 6-15天,将溴二氯甲烷(BDCM)和四氯化碳(CCl4)分别以0、25、50或75 mg/kg/天灌胃于玉米油或含有10%乳剂EL-620的水溶液中。允许母鼠分娩,并在出生后对幼崽进行检查。未分娩的母鼠子宫用10%硫化铵染色检测FLR。两种药物对母体体重增加的影响在较低剂量的水溶液中略显着,但在最高剂量时,ccl4在玉米油中对母体的毒性更大。在发育过程中,两种药物在50和75 mg/kg时均引起FLR。当玉米油浓度为75 mg/kg时,玉米油坝的FLR率(BDCM为83%,CCl4为67%)显著高于水车坝(BDCM为21%,CCl4为8%)。GD-6灌胃后BDCM的血药浓度显示,与油给药组(3.6 h)相比,水给药组(2.7 h)的消除半衰期较短。油给药组(18.9 mg/kg)和水给药组(14.0 mg/kg)的ccl4基准剂量相似。对于BDCM,玉米油培养液产生的保守值(39.3 mg/kg)低于水培养液(11.3 mg/kg),反映了在估计的5%效应剂量水平周围的不同置信区间。
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Effect of Dosing Vehicle on the Developmental Toxicity of Bromodichloromethane and Carbon Tetrachloride in Rats
Effect of Dosing Vehicle on the Developmental Toxicity of Bro- modichloromethane and Carbon Tetrachloride in Rats. Narotsky, M. G., Pegram, R. A., and Kavlock, R. J. (1997). Fundam. Appl. Toxicol. 40, 30-36.
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