IMMUNOTOXICITY OF DERMAL PERMETHRIN & CIS UROCANIC ACID

描述 观察到免疫反应抑制后，职业， 无意中或治疗性地接触到外源物质。此外，反常的 免疫反应(例如，超敏反应、自身免疫)似乎 在人类中的增加，这一现象可能与环境有关 接触化学物质。新的研究计划正在确定这样的 暴露，以前通常被认为是无害的，实际上可能是 会损害人类的免疫健康。目前的建议 考虑联合皮肤暴露于普通皮肤造成的免疫毒性 拟除虫菊酯杀虫剂(二氯菊酯)和顺式熊果酸(CUCA，AN. 反式UCA和阳光的异构化产物)。初步数据显示 显示出全身性和区域性免疫毒性 低水平的局部使用的氯菊酯(以前不被认为是一种免疫毒剂)。 此前已经证明，CUCA还可以抑制皮肤和免疫 回应。拟议的研究将评估免疫毒性的风险。 由氯氰菊酯和皮内联合暴露，使用 国家毒理学计划批准的C57B1/6近交系测试程序 老鼠。这些免疫毒物也将在一定程度上联合使用 确定抑制小鼠的免疫反应，以研究 CUCA和/或氯氰菊酯可能引起的细胞因子依赖的机制 抑制豁免权。此外，在这方面：1)CUCA已经被证明是 抑制巨噬细胞的抗原提呈，2)新数据表明 表皮抗原提呈细胞(APC，朗格汉斯细胞[LC])可能是靶标 我们发现氯菊酯可以抑制皮肤接触。 超敏反应，单一和联合暴露的影响 这些通过LC呈递抗原的药物将作为一种机制进行检查。 与免疫毒性有关。提供新的数据以帮助估计 联合免疫毒物暴露的风险(CUCA和外用 在儿童中使用杀虫剂)是该提案的主要目标。

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.