title: Does the extreme skin sensitization potency of benzoquinone result from special chemistry?
abstract: BACKGROUND
  Benzoquinone is known to be an extreme skin sensitizer. Until now there has been no consideration of whether it owes its extreme skin sensitization potency to unique aspects of its chemistry or simply to its high reactivity as a Michael acceptor.
  
  
  OBJECTIVE
  To answer these questions, we have applied two mechanistic approaches to estimate a theoretical potency value for benzoquinone.
  
  
  METHODS
  A mechanistic read-across (MRA) approach, using known potency data for moderate sensitizers in the Michael acceptor domain, and a published quantitative mechanistic model (QMM) for skin sensitization potency of Michael acceptors, all in the moderate and weak range, were used.
  
  
  RESULTS
  The read-across approach gives a theoretical local lymph node assay (LLNA) EC3 value of 0.04%, and the QMM approach gives a theoretical value of 0.013%, compared with an experimental value of 0.010%.
  
  
  CONCLUSIONS
  The good agreement between the theoretical and experimental EC3 values supports the strength of the MRA and QMM approaches, and provides strong evidence that the extreme sensitization potency of benzoquinone can be attributed solely to its high reactivity as a Michael acceptor.
authors.affiliation: School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 3AF UK. d.w.roberts@ljmu.ac.uk
authors.forename: David W
authors.initials: DW
authors.lastname: Roberts
authors.forename: Aynur O
authors.initials: AO
authors.lastname: Aptula
mesh_terms: D000485:Allergens / Q000737:chemistry*; D016227:Benzoquinones / Q000737:chemistry*; D016208:Databases, Factual; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D023441:Local Lymph Node Assay; D008962:Models, Theoretical; D015394:Molecular Structure; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship; D012867:Skin / Q000187:drug effects*; D018675:Toxicity Tests
chemical_list: D000485:Allergens; D016227:Benzoquinones; C004532:quinone