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评估大鼠吸入三氯乙烯和氯乙烯后潜在的免疫毒性。

Assessment of the immunotoxic potential of trichloroethylene and perchloroethylene in rats following inhalation exposure.

机构信息

Toxicology and Environmental Research and Consulting, Dow Chemical Company, Midland, MI 48674, USA.

出版信息

J Immunotoxicol. 2013 Jul-Sep;10(3):311-20. doi: 10.3109/1547691X.2012.735275. Epub 2012 Nov 20.

Abstract

The immunotoxic potential of trichloroethylene (TCE) and perchloroethylene (PERC) was assessed after inhalation exposure through the evaluation of the antibody forming cell (AFC) response to sheep red blood cells (SRBC). Female Sprague-Dawley rats were exposed to TCE or PERC vapor at 0, 100, 300, or 1000 ppm for 6 h/day, 5 days/week for 4 weeks (20 exposure days). Additional 0 ppm control groups were included and were dosed with cyclophosphamide via intraperitoneal injection to serve as positive immunosuppressive controls in the SRBC assay. Additional end-points evaluated included liver, kidney, spleen, and thymus weights, hematology, cellular differentials in bronchoalveolar lavage fluid, histopathology of select tissues, and assessment of the phagocytic activity of pulmonary alveolar macrophage (PERC only). Exposure to the high concentration of TCE (1000 ppm) resulted in increases in relative liver and kidney weights and suppression of AFC responses (AFC/spleen and AFC/10(6) spleen cells) by ≈ 70%, while no treatment-related effects were noted at 100 and 300 ppm. Animals exposed to PERC at levels of 300 or 1000 ppm had statistically significant increases in relative liver weights that were accompanied by very slight hypertrophy of the centrilobular hepatocytes. Animals exposed to PERC did not demonstrate a treatment-related effect on the AFC response and no effect was noted on the phagocytic activity of pulmonary alveolar macrophages. The results of these studies indicate that TCE had immunotoxic potential only at high exposure concentrations (1000 ppm), while PERC, at similar exposure concentrations, did not display any evidence of immunotoxicity.

摘要

三氯乙烯(TCE)和四氯乙烯(PERC)的免疫毒性潜力是通过评估对绵羊红细胞(SRBC)的抗体形成细胞(AFC)反应来评估的。雌性 Sprague-Dawley 大鼠在 0、100、300 或 1000 ppm 的 TCE 或 PERC 蒸气中暴露,每天 6 小时,每周 5 天,共 4 周(20 次暴露)。还包括了额外的 0 ppm 对照组,并通过腹腔注射环磷酰胺作为 SRBC 测定中的阳性免疫抑制对照。评估的其他终点包括肝、肾、脾和胸腺重量、血液学、支气管肺泡灌洗液中的细胞差异、选定组织的组织病理学以及肺泡巨噬细胞吞噬活性的评估(仅 PERC)。暴露于高浓度的 TCE(1000 ppm)导致相对肝和肾重量增加,AFC 反应(AFC/脾和 AFC/106 脾细胞)受到约 70%的抑制,而在 100 和 300 ppm 时未观察到与处理相关的影响。暴露于 300 或 1000 ppm PERC 的动物肝相对重量呈统计学显著增加,伴有中央小叶肝细胞的轻微肥大。暴露于 PERC 的动物的 AFC 反应没有表现出与处理相关的影响,也没有注意到对肺泡巨噬细胞吞噬活性的影响。这些研究的结果表明,TCE 仅在高暴露浓度(1000 ppm)下具有免疫毒性潜力,而 PERC 在类似的暴露浓度下没有显示出任何免疫毒性的证据。

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