IMMUNOTOXICITY OF DERMAL PERMETHRIN & CIS UROCANIC ACID

皮肤氯菊酯的免疫毒性

• 批准号: 6043524
• 负责人: Steven D Holladay
• 金额: $ 19.24万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-15 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6043524
• 关键词: antigen presentation; antigen presenting cell; cytokine; environmental toxicology; immunosuppression; immunotoxicity; laboratory mouse; light adverse effect; pesticide biological effect; pyrethroid; skin hypersensitivity; toxicant interaction; ultraviolet radiation; urocanate

DESCRIPTION Inhibited immune responses have been observed following occupational, inadvertent, or therapeutic exposure to xenobiotics. Further, aberrant immune responses (e.g., hypersensitivity, autoimmunity) appear to be increasing in humans, a phenomenon which may be related to environmental chemical exposure. New research initiatives are determining that such exposures, often previously considered to be innocuous, may in fact be contributing to impaired human immune health. The present proposal considers immunotoxicity resulting from combined dermal exposure to a common pyrethroid insecticide (permethrin) and to cis-urcanic acid (cUCA, an isomerization product of trans-UCA and sunlight). Preliminary data have been generated showing both systemic and regional immunotoxicity from low-level topical permethrin (formerly not considered an immunotoxicant). It has previously been demonstrated that cUCA also inhibits skin and immune responses. The proposed studies will estimate the risk of immunotoxicity from combined topical permethrin and intradermal cUCA exposure, using National Toxicology Program-approved testing procedures in C57B1/6 inbred mice. These immunotoxicants will also be co-administered at levels determined to inhibit immune responses in mice, to investigate cytokine-dependent mechanisms by which cUCA and/or permethrin may cause suppression of immunity. Further, in that: 1) cUCA has been shown to inhibit antigen presentation by macrophages, 2) new data suggest the epidermal antien presenting cell (APC, Langerhans cell [LC]) may be a target of cUCA, and 3) permethrin was shown by us to inhibit skin contact hypersensitivity responses, the effect of single and combined exposure to these agents on antigen presentation by LC will be examined as a mechanism related to immunotoxicity. Providing new data to assist the estimation of risk from the combined immunotoxicant exposure (cUCA and topical insecticide) in children is a primary goal of the proposal.

描述 在职业性， 无意或治疗性接触外源性物质。 此外，异常 免疫应答（例如，超敏反应、自身免疫）似乎是 在人类中增加，这一现象可能与环境有关 化学暴露 新的研究计划正在确定， 暴露，以前通常被认为是无害的，实际上可能是 导致人体免疫健康受损。 现时的建议 认为皮肤接触常见的 拟除虫菊酯杀虫剂（氯菊酯）和顺式-urcanic酸（cUCA， 反式-UCA和阳光异构化产物）。 初步数据 显示全身和局部免疫毒性， 低水平的局部二氯苯醚菊酯（以前不被认为是免疫毒素）。 先前已经证明，cUCA还抑制皮肤和免疫系统。 应答 拟议的研究将估计免疫毒性的风险 联合局部氯菊酯和皮内cUCA暴露，使用 国家毒理学计划批准的C57 B1/6近交系动物检测程序 小鼠 这些免疫毒素也将以 确定抑制小鼠的免疫反应，以研究 cUCA和/或氯菊酯可能导致的尼古丁依赖性机制 抑制免疫力。 此外，因为：1）cUCA已被证明 抑制巨噬细胞的抗原呈递，2）新的数据表明， 表皮抗原呈递细胞（APC，Langerhans细胞[LC]）可能是一个靶点 氯菊酯对皮肤接触有抑制作用 超敏反应，单次和联合暴露的影响， 这些药物对LC抗原递呈的作用将作为一种机制进行研究 与免疫毒性有关。 提供新的数据，以协助估计 联合免疫毒物暴露（cUCA和局部）的风险 杀虫剂）是该提案的主要目标。