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To establish further a practical quantitative in chemico reactivity assay for screening contact allergens, lysine peptide was incorporated into a liquid chromatography and tandem mass spectrometry-based assay for reactivity assessments of hapten and pre-/pro-hapten chemical sensitizers. Loss of peptide was determined following 24 h coincubation with test(More)
Skin protein reactivity is a well established key step in the development of skin sensitization. Understanding the relationship between a chemical's ability to react with or modify skin protein and skin sensitization has led to the development of the Direct Peptide Reactivity Assay (DPRA) in our laboratory. A current limitation of the DPRA is that it cannot(More)
The strong sensitizing potencies of the most important primary intermediates of oxidative hair dyes, p-phenylenediamine (PPD) and p-toluylenediamine (PTD, i.e. 2-methyl-PPD) are well established. They are considered as the key sensitizers in hair dye allergic contact dermatitis. While modification of their molecular structure is expected to alter their(More)
Approaches to assess the role of absorption, metabolism and excretion of cosmetic ingredients that are based on the integration of different in vitro data are important for their safety assessment, specifically as it offers an opportunity to refine that safety assessment. In order to estimate systemic exposure (AUC) to aromatic amine hair dyes following(More)
1. To develop a framework for exposure calculation via the dermal route to meet the needs of 21st century toxicity testing and refine current approaches; 2. To demonstrate the impact of exposure scenario and application conditions on the plasma concentration following dermal exposure. A workflow connecting a dynamic skin penetration model with a generic(More)
2-Phenoxyethanol (PhE) has been shown to induce hepatotoxicity, renal toxicity, and hemolysis at dosages ≥ 400 mg/kg/day in subchronic and chronic studies in multiple species. To reduce uncertainty associated with interspecies extrapolations and to evaluate the margin of exposure (MOE) for use of PhE in cosmetics and baby products, a physiologically-based(More)
We present a quantitative in vitro-in vivo extrapolation framework enabling the estimation of the external dermal exposure dose from in vitro experimental data relevant to a toxicity pathway of interest. The framework adapts elements of the biological pathway altering dose (BPAD) method [Judson et al. Chem Res Toxicol 2011;24:451] to the case of dermal(More)
Sensitizing chemicals are commonly associated primarily with either skin or respiratory sensitization. In the Direct Peptide Reactivity Assay (DPRA), when compared with skin sensitizers, respiratory allergens have been demonstrated to selectively react with lysine rather than cysteine. The Peroxidase Peptide Reactivity Assay (PPRA) has been developed as a(More)
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