PESTICIDE PERCUTANEOUS ABSORPTION, METABOLISM AND CUTANEOUS TOXICITY

农药经皮吸收、代谢和皮肤毒性

• 批准号: 3777005
• 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/3777005
• 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.

局部暴露于农药是系统性的主要进入途径 人类的毒性。 该提议的目的是继续 在生物学上使用孤立的灌注猪皮皮瓣（IPPSF） 相关的体外模型，以量化农药吸收和皮肤 局部应用后分发。 理想情况下，此模型系统是 适合研究这些现象，因为它是一种孤立的灌注 组织模型，具有完整且可行的表皮 功能性微循环。 先前的研究表明了它的能力 估计人体中各种化合物的体内吸收和 检测这些相同化合物的直接皮肤毒性。 经过 利用与生理相关的药代动力学模型， 农药穿透穿过皮肤的关系，分布 在皮肤内并吸收进入循环系统 研究。 皮肤生物转化的影响也可以是 集成到该模型中。 为了关联IPPSF模型参数 具有局部农药的物理和化学特性，额外 需要来自不同化学类别的化合物。 这将允许 为了定义结构活动关系 控制生物学上复杂的体外渗透和吸收 系统。 本项目的目的是建模 穿透，分布，吸收和直接皮肤毒性 从三个化学类中研究的十种农药 其他程序项目。 每种化合物的三剂将建模 以及闭塞和非限制应用的影响。 由 该项目的结尾，这些数据应改善 可以局部应用理性毒理学评估 农药。