Quantification of skin acrylate adducts.
NIOSH 2001 Dec; :1-7
This project aimed to develop a noninvasive procedure for collection of an epidermal tissue sample and to detect the deposition and penetration of a multifunctional acrylates into the stratum corneum and the formation of acrylate-keratin protein adducts as a biomarker of exposure. Although a reliable and reproducible tape-stripping procedure was developed for tripropylene glycol diacrylate (TPGDA) exposed human skin, synthesis of a TPGDA-protein haptenic complex failed to produce epitope specific antisera for quantification. Two different methods to produce antisera failed, most likely, due to cross-linking of difunctional acrylate to multiple nonspecific sites. Therefore, an alternative procedure was adopted in order to accomplish the principal goals of this project. The alternative procedure focused on the preparation of a conjugated haptenic-peptide synthesized from benzene and naphthalene. Conjugated haptenicpeptides synthesized from benzene or naphthalene (adduction to form S-phenylcysteine) substituted cysteines complexed to keyhole limpet hemocyanin (KLH) were synthesized and the antibodies produced using New Zealand white rabbits. This successful demonstration of an antigenic epitope using this method provides a model for synthesis of an acrylated cysteine for synthesis of an antigenic keratin-lor keratin-lO peptide for preparation of an immunogenic complex. In addition, a reliable and reproducible tape-stripping procedure for sampling and isolation of naphthalene-keratin adducts (antigen) from the stratum corneum under defined laboratory conditions was developed and tested on human volunteers exposed to jet fuel instead of TPGDA. Keratin concentration as well as naphthalene concentration (as a marker for jet fuel exposure) from the adhesive tape strips were determined. This method can be used for isolation of keratin protein for identification and quantification of adducts by an enzyme-linked immunoabsorbent assay (ELISA). We will continue the project by validating the developed methods under occupational exposure settings. This research can be extended to make it possible to define the dermal exposure to any hazardous chemical that reacts with keratin-rich epidermis, in either occupational or environmental exposure conditions. The results increase our knowledge of the correlation of dermal exposure with both the dermal dose and the potential dermal and systemic effects.
Dermatitis; Skin; Skin-absorption; Skin-diseases; Skin-tests; Sampling; Sampling-methods; Biological-monitoring; Acrylates; Adhesives; Proteins; Peptides; Antigens; Immunological-tests
University of North Carolina, School of Public Health, Department of Environmental Sciences and Engineering, CB#7431, Rosenau Hall, Chapel Hill, NC 27599-7400
Final Grant Report
Disease and Injury; Allergic and Irritant Dermatitis
National Institute for Occupational Safety and Health
University of North Carolina, School of Public Health, Department of Environmental Sciences and Engineering, Chapel Hill, North Carolina