Reactivity measurement in estimation of benzoquinone and benzoquinone derivatives’ allergenicity

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• 作者：Wilbes Mbiya^a ; ^{wilbesm@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; ^{mbiya@ohsu.edu" class="auth_mail" title="E-mail the corresponding author} ; Itai Chipinda^b ; Reuben H. Simoyi^a ; Paul D. Siegel^b
• 关键词：ACD ; Allergic contact dermatitis ; BQ ; p- benzoquinone ; BQD ; benzoquinone derivatives ; CBQ ; chlorobenzoquinone ; 2 ; 5-DCBQ ; 2 ; 5-dichlorobenzoquinone ; EDG ; electron donating groups ; EWG ; electron withdrawing groups ; ICD ; irritant contact dermatitis ; LLNA ; local lymph node assay ; EC3 ; estimated concentration that produces a 3 fold increase in lymph node cell proliferation over the vehicle control ; 2-MBQ ; 2 methyl- benzoquinone ; MA ; Michael addition ; NBT ; nitrobenzenethiol ; SI ; stimulation index ; 2-t
• 刊名：Toxicology
• 出版年：2016
• 出版时间：2 January 2016
• 年：2016
• 卷：339
• 期：Complete
• 页码：34-39
• 全文大小：928 K

文摘

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.