title: Mechanistic category formation for the prediction of respiratory sensitization.
abstract: This study investigates the ability of a set of previously published rules for protein binding, developed from skin sensitization data, to group chemicals into mechanistic domains and to develop knowledge on the chemical interactions relating to respiratory sensitization. The results of the analysis showed that 32 of 39 respiratory sensitizing chemicals could be assigned to a mechanistic domain based on the published rules. Analysis of the remaining six chemicals showed them to have electrophilic mechanisms that had not been explicitly covered by the skin sensitization protein binding rules. The study also highlighted the ability to develop subdomains within the mechanistic domains on the basis of simple chemistry principles. These subdomains were developed to allow a calculated electrophilic index to rationalize the differing respiratory sensitizing potentials of the chemicals assigned to them. The study clearly highlights how assigning the most likely mechanism of action for a chemical is useful in building chemical categories (domains) and subcategories (subdomains).
authors.affiliation: School of Pharmacy and Chemistry, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, England.
authors.forename: S J
authors.initials: SJ
authors.lastname: Enoch
authors.forename: D W
authors.initials: DW
authors.lastname: Roberts
authors.forename: M T D
authors.initials: MT
authors.lastname: Cronin
mesh_terms: D000215:Acylation; D004583:Electrons; D006873:Hydroquinones / Q000737:chemistry / Q000633:toxicity; D017953:Isocyanates / Q000737:chemistry / Q000633:toxicity; D009930:Organic Chemicals / Q000737:chemistry / Q000633:toxicity*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D012137:Respiratory System / Q000187:drug effects*; D012545:Schiff Bases / Q000737:chemistry
chemical_list: D006873:Hydroquinones; D017953:Isocyanates; D009930:Organic Chemicals; D011506:Proteins; D012545:Schiff Bases; C031927:hydroquinone