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Inductive effects on reactivity of the contact allergen benzoquinone and its derivatives to proteins.
Mbiya-W; Chipinda-I; Seigel-P; Simoyi-R
Toxicologist 2013 Mar; 132(1):225
Benzoquinone (BQ) and substituted benzoquinones (SB) are used for dye and cosmetics production. BQ is an electrophile known to covalently modify proteins via Michael Addition (MA) but the reactivity, reaction mechanistic domains and allergenicity of SB are unknown. Electron withdrawing and electron donating substituents on BQ were assessed for effects on BQ reactivity and allergenicity. Alternative potential protein binding mechanisms were explored. BQ binding to Cys34 on human serum albumin (HSA) was studied and for BQ and SB reactivity studies, nitrobenzenethiol (NBT) was used as a model nucleophile. Hammett and Taft (HT) constants were used to evaluate the influence of these substituents on chemical reactivity. Both NBT binding studies and HT values demonstrated chlorine SB to be more reactive than methyl and t-butyl SB. Production of semiquinone radicals from SB and characterization of SB-NBT adducts demonstrated that haptenation may also occur via free radical mechanism which is pH dependent, and vinylic substitution mechanisms, in addition to the predominant MA. BQ and SB dermal allergenicity as evaluated in the murine local lymph node assay (LLNA) was consistent with that predicted by reactivity and HT data. These results demonstrate the effect of substituents on BQ reactivity and allergenicity while suggesting potential utility of chemical reactivity data and HT values for electrophilic allergen identification and potency ranking.
Toxicology; Immune-reaction; Biological-agents; Quinones; Cosmetics; Dyes; Proteins; Allergens; Allergic-reactions; Chemical-binding; Chemical-reactions; Protein-biochemistry; Nitro-compounds; Benzenes; Thiols; Chlorine-compounds; Methyl-compounds; Free-radical-generation; Free-radicals; Bioassays; Lymph-nodes
Issue of Publication
Healthcare and Social Assistance
The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas
OR; WV; TX
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division