QUANTIFICATION OF SKIN ACRYLATE ADDUCTS

描述：（改编自研究者摘要）多功能 丙烯酸酯是有效的接触致敏剂， 接触性皮炎，并可能促进皮肤癌。 核心问题 了解由于暴露于 多功能丙烯酸酯是：什么是外部曝光，内部 接受的剂量（通过皮肤接触），以及由此产生的健康影响（例如， 过敏性接触性皮炎、皮肤癌）？ 主要局限于 这一研究领域的发展一直缺乏一种设备和/或 相关的方法来确定化学特异性皮肤沉积， 在职业接触条件下引起皮肤不良反应所需的剂量 暴露条件。 这项研究的最终目标是开发一种非侵入性的 收集表皮组织和检测沉积物的方法 以及MuFA渗透到角质层中， 丙烯酸酯-角蛋白加合物作为暴露的生物标志物。 定量 具有高通量的酶联免疫吸附测定（ELISA）方法 检测丙烯酸酯半抗原-角蛋白加合物的能力和效率 皮肤样本将被开发。 首先，制备了抗A 模型MuFA，三丙二醇二丙烯酸酯（TPGDA），和纯化的和 将产生溶解的人TPGDA-角蛋白半抗原复合物。 第二、 一个可靠的和可重复的磁带剥离程序的采样和 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，开发的ELISA 将对方法进行检测、评价和验证， 通过将志愿者暴露于精确的 非致敏浓度的模型MuFA的掌侧区域的 在受控的实验室条件下。 这项研究将有可能确定MuFA暴露于 在实验室和职业接触条件下的皮肤。 这些 结果将有助于进一步开发现有的和新的真皮 监测方法以及确定接触限值的依据 在职业环境下的皮肤接触， 出现可固化的丙烯酸酯制剂。 通过生物监测， 工人和暴露评估使用这些新的方法， 最大限度地减少接触，从而防止对健康的不利影响， 制定并实施。

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.