QUANTIFICATION OF SKIN ACRYLATE ADDUCTS

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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.