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二氯乙酸和三氯乙酸对大鼠的亚慢性90天毒性

Subchronic 90 day toxicity of dichloroacetic and trichloroacetic acid in rats.

作者信息

Mather G G, Exon J H, Koller L D

机构信息

University of Idaho, WOI School of Veterinary Medicine and Pharmacology/Toxicology Graduate Program, Moscow 83843.

出版信息

Toxicology. 1990 Oct;64(1):71-80. doi: 10.1016/0300-483x(90)90100-u.

Abstract

Male Sprague-Dawley rats were treated with either dichloroacetic acid (DCA) or trichloroacetic acid (TCA) in the drinking water at levels of 0, 50, 500 and 5000 ppm for a period of 90 days to determine the toxicities associated with subchronic exposure. All animals were sacrificed and examined for gross and histopathologic lesions, serochemical changes, immune dysfunction, hepatic peroxisomal and mixed function oxidase enzyme induction and organ-body weight changes. Animals treated with DCA had decreased body weight gains (500 and 5000 ppm) and decreased total serum protein (all doses). Rats given either TCA (5000 ppm) or DCA (500 or 5000 ppm) had increased liver and kidney organ to body weight ratios. Rats offered DCA had significantly elevated alkaline phosphatase (500 and 5000 ppm) and alanine-amino transferase (5000 ppm). No consistent immunotoxicity was observed in animals exposed to either compound. Rats treated with 5000 ppm TCA or DCA had significantly increased hepatic peroxisomal beta-oxidation activity. These data, along with histopathologic changes, suggest that TCA and DCA produce substantial systemic organ toxicity to the liver and kidney during a 90-day subchronic exposure, although only at doses greater than those expected to occur in the environment.

摘要

将雄性斯普拉格-道利大鼠置于饮用水中分别含有0、50、500和5000 ppm的二氯乙酸(DCA)或三氯乙酸(TCA)的环境中,持续90天,以确定与亚慢性暴露相关的毒性。所有动物均处死后进行大体和组织病理学损伤检查、血清化学变化检测、免疫功能障碍评估、肝脏过氧化物酶体和混合功能氧化酶诱导情况以及器官与体重变化的测定。接受DCA处理的动物体重增加减少(500和5000 ppm组),血清总蛋白降低(所有剂量组)。给予TCA(5000 ppm)或DCA(500或5000 ppm)的大鼠肝脏和肾脏器官与体重的比值增加。给予DCA的大鼠碱性磷酸酶(500和5000 ppm组)和丙氨酸氨基转移酶(5000 ppm组)显著升高。在接触这两种化合物的动物中均未观察到一致的免疫毒性。用5000 ppm TCA或DCA处理的大鼠肝脏过氧化物酶体β-氧化活性显著增加。这些数据以及组织病理学变化表明,在90天的亚慢性暴露期间,TCA和DCA对肝脏和肾脏产生了实质性的全身器官毒性,尽管仅在高于预期环境中出现的剂量时才会如此。

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