PESTICIDE PERCUTANEOUS ABSORPTION, METABOLISM AND CUTANEOUS TOXICITY

农药经皮吸收、代谢和皮肤毒性

• 批准号: 3754916
• 负责人: FRANK E GUTHRIE
• 金额: --
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 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/3754916
• 关键词: biological models; chemical structure function; chlorohydrocarbon insecticide; dosage; environmental toxicology; herbicides; isolation perfusion; mathematical model; mirex /kepone; model design /development; pesticide biological effect; pesticide interaction; pesticides; pharmacokinetics; phenylamide; pyrethroid; skin; skin absorption; skin circulation; swine; toxin metabolism

Topical exposure to pesticides is a primary route of entry for systemic toxicity in humans. The purpose of this proposal is to continue to employ the isolated perfused porcine skin flap (IPPSF) as a biologically relevant in vitro model to quantitate pesticide absorption and cutaneous distribution after topical application. This model system is ideally suited to study these phenomenon because it is an isolated perfused tissue model which has an intact and viable epidermis in association with a functional microcirculation. Previous studies have shown its ability to estimate in vivo absorption in humans for a variety of compounds and to detect the direct cutaneous toxicity of these same compounds. By utilizing a physiologically-relevant pharmacokinetic model, the relationships of pesticide penetration through the skin, distribution within the skin and absorption into the circulation can be quantitatively studied. The effects of cutaneous biotransformation can also be integrated into this model. In order to correlate IPPSF model parameters with physical and chemical properties of topical pesticides, additional compounds from different chemical classes are required. This will allow for the definition of structure-activity relationships to be made which govern penetration and absorption in a biologically complex in vitro system. The objective of the present project is to model the penetration, distribution, absorption, and direct cutaneous toxicity of ten pesticides from three chemical classes which are being studied in other program projects. Three doses of each compound will be modelled as will the effects of occlusive and nonocclusive applications. By the end of this project, these data should improve the basis upon which rational toxicologic assessments can be made for topically applied pesticides.

局部接触农药是全身性接触农药的主要途径 对人体的毒性。 该提案的目的是继续 采用分离的灌注猪皮瓣（IPPSF）作为生物学 相关的体外模型来定量农药吸收和皮肤 局部应用后分布。 该模型系统非常理想 适合研究这些现象，因为它是一种孤立的灌注 具有完整且有活力的表皮的组织模型 功能性微循环。 之前的研究已经证明了它的能力 估计多种化合物在人体中的吸收 检测这些相同化合物的直接皮肤毒性。 经过 利用生理相关的药代动力学模型， 农药经皮渗透、分布的关系 可以定量地在皮肤内和吸收到循环中 研究过。 皮肤生物转化的影响也可以是 集成到这个模型中。 为了关联 IPPSF 模型参数 具有外用杀虫剂的物理和化学特性，另外 需要来自不同化学类别的化合物。 这将允许 结构-活性关系的定义 控制体外生物复合物的渗透和吸收 系统。 本项目的目标是模拟 渗透、分布、吸收和直接皮肤毒性 正在研究的来自三个化学类别的十种农药 其他计划项目。 将模拟每种化合物的三个剂量 闭塞和非闭塞应用的效果也是如此。 由 在该项目结束时，这些数据应改进的基础 可以对局部应用进行合理的毒理学评估 杀虫剂。