QUANTIFICATION OF SKIN ACRYLATE ADDUCTS

描述：(改编自《调查者摘要》)多功能 丙烯酸酯是有效的接触性敏感剂，因此可能会引起过敏。 接触性皮炎，可能会引发皮肤癌。核心问题 了解接触以下物质可能对健康造成的不利影响 多功能丙烯酸酯有：什么是外露，内露 接受的剂量(通过皮肤暴露)以及由此产生的健康影响(例如， 过敏性接触性皮炎、皮肤癌)？的主要限制是 这一研究领域的发展一直是缺乏设备和/或 相关方法学，以确定化学比皮肤沉积和 职业性皮肤不良反应所需剂量 曝光条件。 这项拟议研究的最终目标是开发一种非侵入性的 收集表皮组织并检测沉积的程序 和多不饱和脂肪酸进入角质层并形成 丙烯酸酯-角蛋白加合物作为暴露的生物标记物。数量上的 一种高通量的酶联免疫吸附试验方法 检测丙烯酸酯半抗原-角蛋白加合物的能力和效率 将从皮肤样本中开发出。首先，制备抗A细胞的多克隆抗血清 型号MUFA，三丙二醇二丙烯酸酯(TPGDA)，并提纯和 将产生可溶解的人TPGDA-角蛋白半抗原复合体。第二, 一种可靠且可重复的磁带剥离程序，用于采样和 从角质层中分离TPGDA-角蛋白加合物(抗原) 将制定明确的实验室条件。第三，研制的酶联免疫吸附试验 方法将针对检测和验证进行测试、评估和验证 通过让志愿者接触精确的MUFA来量化MUFA暴露 模型多不饱和脂肪酸对大脑皮层掌侧区的非敏化浓度 前臂在受控的实验室条件下。 这项研究将使定义MUFA暴露于 实验室和职业暴露条件下的皮肤。这些 研究结果将有助于进一步开发现有的和新的真皮 监测方法以及确定暴露限值的依据 适用于暴露于辐射的职业环境下的皮肤暴露 出现了可固化的丙烯酸酯配方。通过生物监测 使用这些新方法的工人和暴露评估，战略 最大限度地减少暴露，从而防止对健康的不利影响 制定并实施了。

DESCRIPTION: (Adapted from Investigator's Abstract) Multifunctional acrylate are potent contact sensitizers and, thus, may cause allergic contact dermatitis and may promote skin cancer. Questions central to understanding the potential adverse health effects due to exposure to multifunctional acrylate are: what is the external exposure, the internal dose (via dermal exposure) received, and the resulting health effect(e.g., allergic contact dermatitis, skin cancer)? The major limitation to the development of this area of research has been the absence of a device and/or associated methodology to determine chemical specific skin deposition and the dose required to induce adverse dermal effects under occupational exposure conditions. The ultimate goal of this proposed research is to develop a noninvasive procedure for collection of epidermal tissue and to detect the deposition and penetration of a MuFA into the stratum corneum and the formation of acrylate-keratin protein adducts as a biomarker of exposure. A quantitative enzyme-linked immunosorbent assay (ELISA) method with a high throughput capacity and efficiency to detect acrylate hapten-keratin protein adducts from skin samples will be developed. First, a polyclonal antisera to a model MuFA, tripropylene glycol diacrylate (TPGDA), and purified and solubilized human TPGDA-keratin haptenic complex will be produced. Second, a reliable and reproducible tape-stripping procedure for sampling and isolation of TPGDA-keratin adducts (antigen) from the stratum corneum under defined laboratory conditions will be developed. Third, the developed ELISA method will be tested, evaluated, and validated for the detection and quantification of MuFA exposure by exposing volunteers to precise nonsensitizing concentrations of the model MuFA to the volar region of the forearm under controlled laboratory conditions. This research will make it possible to define the exposure of a MuFA to the skin under both laboratory and occupational exposure conditions. These results will be useful for developing further the existing and new dermal monitoring methods as well as a basis for establishing the exposure limits for dermal exposure under occupational settings where exposure to radiation curable acrylate formulations occurs. Through biological monitoring of workers and exposure assessment using these new methods, strategies for minimizing exposure and, thus, preventing adverse health effects can be developed and implemented.