Sponsor
This work was supported by an Interagency Agreement with the NIEHS (IAG#Y1-ES-0001-12) and Grant Number CHE 1056311 from the National Science Foundation.
Published In
Toxicology
Document Type
Article
Publication Date
1-2-2016
Subjects
Benzoquinones -- Allergenicity, Alternative toxicity testing
Abstract
Benzoquinone (BQ) and benzoquinone derivatives (BQD) are used in the production of dyes and cosmetics. While BQ, an extreme skin sensitizer, is an electrophile known to covalently modify proteins via Michael Addition (MA) reaction whilst halogen substituted BQD undergo nucleophilic vinylic substitution (SNV) mechanism onto amine and thiol moieties on proteins, the allergenic effects of adding substituents on BQ have not been reported. The effects of inserting substituents on the BQ ring has not been studied in animal assays. However, mandated reduction/elimination of animals used in cosmetics testing in Europe has led to an increased need for alternatives for the prediction of skin sensitization potential. Electron withdrawing and electron donating substituents on BQ were assessed for effects on BQ reactivity toward nitrobenzene thiol (NBT). The NBT binding studies demonstrated that addition of EWG to BQ as exemplified by the chlorine substituted BQDs increased reactivity while addition of EDG as in the methyl substituted BQDs reduced reactivity. BQ and BQD skin allerginicity was evaluated in the murine local lymph node assay (LLNA). BQD with electron withdrawing groups had the highest chemical potency followed by unsubstituted BQ and the least potent were the BQD with electron donating groups. The BQD results demonstrate the impact of inductive effects on both BQ reactivity and allergenicity, and suggest the potential utility of chemical reactivity data for electrophilic allergen identification and potency ranking.
DOI
10.1016/j.tox.2015.11.002
Persistent Identifier
http://archives.pdx.edu/ds/psu/18887
Citation Details
Mbiya, W., Chipinda, I., Simoyi, R. H., & Siegel, P. D. (2016). Reactivity measurement in estimation of benzoquinone and benzoquinone derivatives’ allergenicity. Toxicology, 339, 34-39.
Description
To the best of our knowledge, this work was authored as part of the Contributor's official duties as an Employee of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.