Updating Reaction Mechanistic Domains for Skin Sensitization: 1. Nucleophilic Skin Sensitizers.

ABSTRACT: It has long been recognized that skin sensitizers either are electrophilic or can be activated to electrophilic species. Several nonanimal assays for skin sensitization are based on this premise. In the course of a project to update dermal sensitization thresholds (DST), we found a substantial number of sensitizers, with no electrophilic or pro-electrophilic alerts, that could be simply explained in terms of the sensitizer acting as a nucleophile. In some cases, the nucleophilic center is a sulfur or phosphorus atom, while in others, it is an aromatic carbon atom. For carbon-centered nucleophiles, a quantitative mechanistic model based on a combination of Hammett σ⁺ and logP values has been derived. This has been applied to rationalize several groups of known sensitizers with no

SUBMITTER: Roberts DW 

PROVIDER: S-EPMC11577424 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature