TOXICITY STUDIES OF STYRENE AND RELATED CHEMICALS

苯乙烯及相关化学品的毒性研究

• 批准号: 3777469
• 负责人: D L MORGAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3777469
• 关键词: 5 bromouracil; DNA damage; chemical carcinogenesis; cytochrome P450; dosage; environmental toxicology; genetic crossing over; genetic strain; glutathione; hepatotoxin; inhalation drug administration; laboratory mouse; laboratory rat; liver metabolism; lymphocyte proliferation; pharmacokinetics; polystyrenes; species difference; tissue /cell culture; toxin metabolism

Pharmacokinetic studies were conducted to evaluate and compare the uptake and metabolism of styrene in B6C3F1 mice and F344 rats during nose-only inhalation exposure. Blood, liver, and fat samples were collected from rats and mice during and after exposure to 125, 250, or 500 ppm styrene. Samples are being analyzed for styrene and styrene oxide content. In addition, hepatic glutathione levels are being determined in rats and mice at the different time points. A subsequent study was conducted to investigate the effects hepatic P450 induction and inhibition on the in vivo metabolism and pharmacokinetics of styrene and styrene oxide in mice. These data will be used in a physiologically-based pharmacokinetic model to evaluate species and mouse strain differences in styrene toxicity. Clastogenicity and sister chromatid exchange (SCE) were evaluated in female mice and rats exposed to 125, 250, or 500 ppm styrene 6h/day for 14 days. In mice, there was a significant dose related elevation of SCE frequency in lymphocytes from the spleen, and the peripheral blood as well as in cells from the lung. No changes were detected in the frequency of chromosome aberrations in cultured splenocytes or lung cells. Rat samples are still being evaluated. Studies were conducted to evaluate the effects of styrene inhalation on cell proliferation in the liver, and to investigate the role of cell proliferation in the progression of hepatoxicity in the mouse. Evaluations of BrdU-labeled cells are in progress.

进行了药代动力学研究，以评估和比较 B6C3F1小鼠和F344大鼠的苯乙烯的摄取和代谢 仅鼻子吸入暴露。 血液，肝脏和脂肪样本是 在暴露于125、250或之后从大鼠和小鼠收集 500 ppm苯乙烯。 样本正在分析苯乙烯和苯乙烯 氧化物含量。 此外，肝谷胱甘肽水平正在 在不同时间点在大鼠和小鼠中确定。 随后的 进行了研究以研究肝P450诱导的影响 并抑制体内代谢和药代动力学的抑制作用 小鼠的苯乙烯和苯乙烯。 这些数据将用于 基于生理的药代动力学模型，以评估物种和 苯乙烯毒性中的小鼠应变差异。 那层和姐妹 在雌性小鼠和大鼠中评估染色单体交换（SCE） 暴露于125、250或500 ppm苯乙烯/天苯乙烯/天14天。 在老鼠中， SCE频率的显着剂量相关升高 来自脾脏的淋巴细胞，外周血以及 来自肺部的细胞。 未检测到的频率 培养的脾细胞或肺细胞中的染色体畸变。 鼠 样本仍在评估。 进行了研究以评估 苯乙烯吸入对肝脏细胞增殖的影响， 研究细胞增殖在进展中的作用 小鼠中的肝毒性。 BRDU标记的细胞的评估在 进步。