Reactivity measurement in estimation of benzoquinone and benzoquinone derivatives’ allergenicity

Details

• Alternative Title:
  Toxicology
• Personal Author:
  Mbiya, Wilbes ; Chipinda, Itai ; Simoyi, Reuben H. ; Siegel, Paul D.
• Description:
  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.
• Subjects:
  Algorithms Allergens Allergic Contact Dermatitis Animals Animal Testing Alternatives Article Benzoquinone Benzoquinones Dermatitis, Allergic Contact Female Local Lymph Node Assay Methylation Mice Mice, Inbred BALB C Michael Addition Nucleophilic Vinylic Substitution Quantitative Structure-Activity Relationship Skin SNV Stimulation Index Structure-Activity Relationship Sulfhydryl Compounds Vinyl Compounds

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• Source:
  Toxicology. 339:34-39.
• Pubmed ID:
  26612505
• Pubmed Central ID:
  PMC4724239
• Document Type:
  Journal Article
• Funding:
  CC999999/Intramural CDC HHS/United States ; IAGY1-ES-0001-12/ES/NIEHS NIH HHS/United States
• Volume:
  339
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:72ed315e40d6778f806db31c09c195e2c5be888d51c6aa57e4275614c52fde20
• Download URL:
  https://stacks.cdc.gov/view/cdc/37621/cdc_37621_DS1.pdf
• File Type:
  [PDF - 567.24 KB ]