Neurotoxicity produced by dibromoacetic acid in drinking water of rats.
Neurotoxicity produced by dibromoacetic acid in drinking water of rats.
复制标题
二溴乙酸在大鼠饮用水中产生的神经毒性。
DOI：
10.1093/toxsci/kfh081
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Butt,MT
中科院分区：
文献类型：
--
作者：
Moser,VC;Phillips,PM;Levine,AB;McDaniel,KL;Sills,RC;Jortner,BS;Butt,MT
要评估消毒副产物对人类健康的潜在不利影响，需要对癌症和非癌症终点进行研究；然而，还没有研究评估一种常见的卤代乙酸--二溴乙酸(DBA)的神经毒性潜力。本实验研究了DBA在大鼠饮水中暴露6个月的神经毒性。成年雄性和雌性Fischer 344大鼠分别以0、0.2、0.6和1.5g/L剂量染毒，按mg/kg/d剂量计算，平均摄入量分别为0、20、72和161 mg/kg/d。高浓度组体重增加受到抑制，并在暴露早期观察到与浓度相关的腹泻和脱发。在给药前以及给药后1、2、4和6个月，用功能性观察电池和运动活动进行测试。DBA产生浓度相关的神经肌肉毒性(中浓度和高浓度)，其特征是肢体无力、轻度步态异常和低张力，以及感觉运动抑制(所有浓度)，对尾巴挤压和咔嗒的反应降低。在最高浓度下的其他毒性迹象包括活动减少和紧握胸部。神经毒性早在一个月前就很明显，但随着持续暴露，神经毒性没有进展。主要神经病理改变为中、高浓度脊髓神经纤维变性。脊髓灰质(多数)和白质束(偶尔)的细胞空泡化也被观察到。脑、眼、外周神经或外周神经节未见与治疗相关的变化。对神经行为改变的最低可观察效应水平为20 mg/kg/d(由0.2g/L产生，测试的最低浓度)，而该剂量对神经病理改变则为无作用水平。这些研究表明，在卤代乙酸类的整体危害评估中应考虑神经毒性。
An evaluation of potential adverse human health effects of disinfection byproducts requires study of both cancer and noncancer endpoints; however, no studies have evaluated the neurotoxic potential of a common haloacetic acid, dibromoacetic acid (DBA). This study characterized the neurotoxicity of DBA during 6-month exposure in the drinking water of rats. Adolescent male and female Fischer 344 rats were administered DBA at 0, 0.2, 0.6, and 1.5 g/l. On a mg/kg/day basis, the consumed dosages decreased greatly over the exposure period, with average intakes of 0, 20, 72, and 161 mg/kg/day. Weight gain was depressed in the high-concentration group, and concentration-related diarrhea and hair loss were observed early in exposure. Testing with a functional observational battery and motor activity took place before dosing and at 1, 2, 4, and 6 months. DBA produced concentration-related neuromuscular toxicity (mid and high concentrations) characterized by limb weakness, mild gait abnormalities, and hypotonia, as well as sensorimotor depression (all concentrations), with decreased responses to a tail-pinch and click. Other signs of toxicity at the highest concentration included decreased activity and chest clasping. Neurotoxicity was evident as early as one month, but did not progress with continued exposure. The major neuropathological finding was degeneration of spinal cord nerve fibers (mid and high concentrations). Cellular vacuolization in spinal cord gray matter (mostly) and in white matter (occasionally) tracts was also observed. No treatment-related changes were seen in brain, eyes, peripheral nerves, or peripheral ganglia. The lowest-observable effect level for neurobehavioral changes was 20 mg/kg/day (produced by 0.2 g/l, lowest concentration tested), whereas this dosage was a no-effect level for neuropathological changes. These studies suggest that neurotoxicity should be considered in the overall hazard evaluation of haloacetic acids.