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) or though nucleophilic vinylic substitution (SNV) reaction mechanism. Electron withdrawing and electron donating substituents on BQ were assessed for effects on BQ reactivity and allergenicity. 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. For SB with electron donating groups chemicals potency was dependent on the hydrophobicity of the test chemicals whilst for SB with electron withdrawing groups chemical potency was dependent on the reactivity of the test chemical. 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.

Determination of allergenicity of benzoquinone derivatives using rate constants and the LLNA assay and quantitative mechanistic modeling for the MA and SVN domains

248th National Meeting (2014)

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