Bhat H K, Kanz M F, Campbell G A, Ansari G A
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77550.
Fundam Appl Toxicol. 1991 Aug;17(2):240-53. doi: 10.1016/0272-0590(91)90216-q.
Chloroacetic acids are produced in drinking water as a result of disinfection processes. Chloroacetic acids are also metabolites of widely used and toxic halogenated hydrocarbons. Thus, chronic human exposure to these chemicals is likely to occur. The objective of the present study was to examine the toxic effects of monochloroacetic acid (MCA), dichloroacetic acid (DCA), and trichloroacetic acid (TCA) in a 90-day subchronic study in rats via oral exposure by drinking water. Chloroacetic acid solutions were prepared at concentrations which provided an approximate intake of 1/4 the LD50 dose per day: MCA, 1.9 mM; DCA, 80.5 mM; TCA, 45.8 mM. Control rats received distilled water only. After 90 days, major organs were removed, fixed, paraffin embedded, and stained. Light microscopic examination of the major organs revealed variable degrees of alterations in the lung and liver of all three treated groups. In the liver, morphological changes were predominantly localized to the portal triads, which were mildly to moderately enlarged with random bile duct proliferation, extension of portal veins, fibrosis, edema, and occasional foci of inflammation. In the lungs, minimal alterations were observed as foci of perivascular inflammation on small pulmonary veins. Morphological changes in the testes and brain were seen only in the DCA treated group. Testes were atrophic with few spermatocytes and no mature spermatozoa. Focal vacuolation and gliosis were present in the forebrain and brainstem. The results of these studies indicate that, relative to their respective LD50 values, DCA given at 80.5 mM is more toxic than TCA given at 45.8 mM and MCA at 1.9 mM is least toxic.
饮用水消毒过程会产生氯乙酸。氯乙酸也是广泛使用的有毒卤代烃的代谢产物。因此,人类很可能会长期接触这些化学物质。本研究的目的是通过饮用水经口暴露,对大鼠进行为期90天的亚慢性研究,以检测一氯乙酸(MCA)、二氯乙酸(DCA)和三氯乙酸(TCA)的毒性作用。制备的氯乙酸溶液浓度能提供大约每天1/4半数致死剂量的摄入量:MCA为1.9 mM;DCA为80.5 mM;TCA为45.8 mM。对照大鼠仅饮用蒸馏水。90天后,取出主要器官,固定、石蜡包埋并染色。对主要器官进行光学显微镜检查发现,所有三个处理组的肺和肝脏都有不同程度的改变。在肝脏中,形态学变化主要局限于门三联管,门三联管轻度至中度增大,伴有随机的胆管增生、门静脉延伸、纤维化、水肿以及偶尔的炎症灶。在肺中,观察到的最小改变是小肺静脉周围血管炎症灶。仅在DCA处理组的睾丸和大脑中观察到形态学变化。睾丸萎缩,精母细胞很少,没有成熟精子。前脑和脑干出现局灶性空泡化和胶质细胞增生。这些研究结果表明,相对于各自的半数致死剂量值,80.5 mM的DCA比45.8 mM的TCA毒性更大,而1.9 mM的MCA毒性最小。