Merrick B A, Robinson M, Condie L W
Toxicology and Microbiology Division, US Environmental Protection Agency, Cincinnati, OH 45268.
J Appl Toxicol. 1989 Feb;9(1):15-21. doi: 10.1002/jat.2550090105.
Subacute toxicity of trichloroethylene (TCE) was evaluated in male and female B6C3F1 mice using corn oil or aqueous gavage vehicles. Mice received oral doses of TCE five times a week for 4 weeks at 600, 1200 and 2400 mg/kg/day for males and 450, 900 and 1800 mg/kg/day for females. Vehicle control mice were dosed with either corn oil or a 20% aqueous solution of Emulphor. A dose-related increase in lethality occurred in male and female mice receiving TCE in Emulphor but not corn oil during the first week of treatment. Lethality was consistent with central nervous system depressant effects of TCE. After 4 weeks of exposure, body weights were not altered by TCE but liver/body weight ratios were uniformly increased by TCE administered in either vehicle in both sexes. Only male mice treated with TCE in corn oil, however, sustained elevations in serum enzyme levels, accompanied by liver histopathology. TCE in corn oil produced inflammation-associated focal necrosis in 30-40% of the male mice, with increasing severity from low to high dose. Lipid accumulation, as indicated by Oil-Red O staining, was most prevalent in male mice treated with TCE in corn oil but also occurred to a lesser degree in animals receiving either gavage vehicle alone. This study indicates that the type of oral gavage vehicle is an important factor in determining the nature of TCE toxicity.
使用玉米油或水性灌胃媒介物,对雄性和雌性B6C3F1小鼠进行了三氯乙烯(TCE)的亚急性毒性评估。小鼠每周口服TCE 5次,持续4周,雄性剂量为600、1200和2400 mg/kg/天,雌性剂量为450、900和1800 mg/kg/天。媒介物对照小鼠分别给予玉米油或20%的聚氧乙烯蓖麻油水溶液。在治疗的第一周,接受聚氧乙烯蓖麻油中TCE的雄性和雌性小鼠出现了与剂量相关的致死率增加,而接受玉米油中TCE的小鼠则未出现。致死率与TCE的中枢神经系统抑制作用一致。暴露4周后,TCE未改变体重,但两性中无论使用哪种媒介物给予TCE,肝/体重比均一致升高。然而,只有接受玉米油中TCE治疗的雄性小鼠血清酶水平持续升高,并伴有肝脏组织病理学变化。玉米油中的TCE在30-40%的雄性小鼠中产生了与炎症相关的局灶性坏死,从低剂量到高剂量严重程度增加。油红O染色显示的脂质积累在接受玉米油中TCE治疗的雄性小鼠中最为普遍,但在仅接受任一种灌胃媒介物的动物中也有较小程度的发生。这项研究表明,口服灌胃媒介物的类型是决定TCE毒性性质的一个重要因素。