MECHANISMS OF ARSINE GAS AND GALLIUM ARSENIDE TOXICITY

砷气和砷化镓的毒性机制

• 批准号: 3855825
• 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/3855825
• 关键词: animal mortality; arsenic; biotransformation; cytotoxicity; dosage; environmental toxicology; gallium; gas; hamsters; heme; laboratory mouse; laboratory rat; occupational hazard; porphyrin biosynthesis; porphyrins; pulmonary respiration; toxin metabolism; urinalysis

Studies have been conducted to evaluate the acute and short-term toxicity of arsine gas. Fischer 344 rats, B6C3Fl and C57BL/6 mice and Syrian golden hamsters have been exposed to arsine gas at concentrations of 10 ppb to 50 ppm for periods ranging from .5 hr to 90 days. All groups exposed to a single 6 hr exposure of 25 ppm experienced 100% mortality, while those exposed to 5 ppm for 4 weeks or 2.5 ppm for 13 weeks, showed no overt signs of toxicity. Urine samples from these studies showed increased levels of coproporphyrin and 7- and 8- carboxyl uroporphyrin. These data suggest that alterations in the heme biosynthetic pathway as reflected in increases of specific species of urinary porphyrins may be used as early biological indicators of ongoing arsine toxicity. A method has been developed to improve the measurement of specific porphyrin species in rodent urine to further refine this model. Tissues from these exposures are being analyzed for arsenic content to provide a measure of the tissue dose for specific exposure regimens.

已进行研究评估急性和短期毒性 砷化氢气体。 Fischer 344 大鼠、B6C3Fl 和 C57BL/6 小鼠以及叙利亚小鼠 金仓鼠曾接触过浓度为 10 ppb 的砷化氢气体 至 50 ppm，持续 0.5 小时至 90 天。 所有暴露于 单次暴露于 25 ppm 的浓度 6 小时，死亡率为 100%，而那些 暴露于 5 ppm 4 周或 2.5 ppm 13 周，没有表现出明显迹象 的毒性。 这些研究的尿液样本显示， 粪卟啉以及7-和8-羧基尿卟啉。 这些数据表明 血红素生物合成途径的改变反映在增加 特定种类的尿卟啉可用作早期生物学 持续砷化氢毒性的指标。 已经开发出一种方法 改进啮齿动物尿液中特定卟啉种类的测量 进一步完善这个模型。 正在分析这些暴露的组织 砷含量以提供特定组织剂量的测量 暴露方案。