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对通过饮食给予斯普拉格-道利大鼠一年的多氯联苯1016、1242、1254和1260的神经毒性评估。

An assessment of neurotoxicity of aroclors 1016, 1242, 1254, and 1260 administered in diet to Sprague-Dawley rats for one year.

作者信息

Freeman G B, Lordo R A, Singer A W, Peters A C, Neal B H, McConnell E E, Mayes B A

机构信息

Battelle, Columbus, Ohio 43201, USA.

出版信息

Toxicol Sci. 2000 Feb;53(2):377-91. doi: 10.1093/toxsci/53.2.377.

Abstract

As part of a comparative chronic toxicity/oncogenicity study of different Aroclors (1016, 1242, 1254, and 1260), neurotoxicity was assessed in male and female Sprague-Dawley rats using functional observational battery (FOB) and motor activity tests, and histopathologic evaluation of selected nervous system tissues. Doses varied by Aroclor and ranged from 25 to 200 ppm in the diet. Animals were evaluated prior to initiation of dosing and at 13, 26, 39, and 52 weeks of exposure. Clinical signs, body weights, and feed consumption were evaluated weekly. Data analysis of FOB and motor activity results revealed several instances where Aroclor-treated groups were different from control. However, these were considered incidental, as they lacked any consistent dose- or time-related pattern that would suggest Aroclor-induced neurotoxicity. The nonremarkable findings during each of the four assessments were supported by the absence of any treatment-related clinical signs or mortality. Decreased body weight gain was evident in the male 100 ppm Aroclor 1254 dose group and in all female Aroclor 1254 dose groups late in the study (when a linear relationship was assumed between body weight and time), correlating with decreased feed consumption. Although a variety of incidental, spontaneous, degenerative changes were found in nervous tissue evaluated histopathologically, these changes were seen with similar incidence and severity in treated and control groups. No lesions were found that could be attributed to Aroclor-related neurotoxicity. In summary, 52 weeks of exposure to Aroclors 1016, 1242, 1254, or 1260 mixed in the diet did not yield any functional or morphologic changes indicative of PCB-induced neurotoxicity.

摘要

作为不同多氯联苯混合物(1016、1242、1254和1260)比较性慢性毒性/致癌性研究的一部分,使用功能性观察组合(FOB)和运动活性测试对雄性和雌性斯普拉格-道利大鼠的神经毒性进行了评估,并对选定的神经系统组织进行了组织病理学评估。剂量因多氯联苯混合物而异,在饮食中的范围为25至200 ppm。在给药开始前以及暴露13、26、39和52周时对动物进行评估。每周评估临床症状、体重和饲料消耗量。对FOB和运动活性结果的数据分析显示,多氯联苯混合物处理组在几个方面与对照组不同。然而,这些被认为是偶然的,因为它们缺乏任何一致的剂量或时间相关模式,表明多氯联苯混合物诱导的神经毒性。四次评估中的每一次的无显著发现都得到了没有任何与治疗相关的临床症状或死亡率的支持。在研究后期,雄性100 ppm多氯联苯混合物1254剂量组和所有雌性多氯联苯混合物1254剂量组的体重增加明显减少(当假设体重与时间之间存在线性关系时),这与饲料消耗量减少相关。尽管在组织病理学评估的神经组织中发现了各种偶然的、自发的、退行性变化,但在处理组和对照组中这些变化的发生率和严重程度相似。未发现可归因于多氯联苯混合物相关神经毒性的病变。总之,在饮食中混合暴露于多氯联苯混合物1016、1242、1254或1260 52周未产生任何表明多氯联苯诱导神经毒性的功能或形态变化。

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