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化学物质暴露引起的小鼠和大鼠肝脏重量变化与组织病理效应之间的关联:对毒性参考数据库 (ToxRefDB) 的数据进行分析
Roman Mezencev1, Madison Feshuk2, Lori Kolaczkowski2,3
1Center for Public Health and Environmental Assessment, Office of Research and Development, US EPA, Washington, District of Columbia, USA.
概括
动物的肝脏体重变化可以预测化学诱导的肝脏损伤. 分析肝脏体重变化和组织病理学有助于确定有毒性评估的生物学相关影响.
科学领域:
- 毒理学 毒理学 毒理学
- 药理学 药理学是指药理学的学科.
- 生物统计学 生物统计学
背景情况:
- 绝对 (ALW) 和相对 (RLW) 肝脏体重变化是动物毒性研究中的关键指标.
- 这些变化经常用于基准剂量反应建模 (BMD),用于对肝毒化学品进行定量健康风险评估.
研究的目的:
- 为了确定生物相关的肝脏体重变化对化学物质暴露的反应.
- 为了将肝脏体重变化与动物毒性研究中的组织病理学发现相关联.
主要方法:
- 从毒性参考数据库 (ToxRefDB) 分析了389个小鼠和老鼠的亚慢性研究.
- 对273种化学物质的肝脏组织病理学与肝脏体重变化 (ALW和RLW) 相关的数据的评估.
主要成果:
- 在剂量组之间观察到ALW和RLW的显著差异,有和没有肝脏病理学变化.
- 化学诱导的ALW和RLW变化有效预测了基因病理发现的存在.
结论:
- 肝脏体重的变化是化学诱导肝脏组织病理学的可靠预测因素.
- ALW和RLW数据可以为BMD建模和毒性值推导提供生物学相关终点的选择信息.
相关概念视频
Toxic Reactions: Overview
When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
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