title: A two-centre study for the evaluation and validation of an animal model for the assessment of the potential of small molecular weight chemicals to cause respiratory allergy.
abstract: This study evaluated a single intradermal injection model in the guinea pig with subsequent inhalation challenge and serological analysis as a method to predict the potential of chemicals to induce respiratory allergy. Four known respiratory allergens (trimellitic anhydride, diphenyl methane diisocyanate, phthalic anhydride and toluene diisocyanate (TDI)) were screened by two industrial research laboratories using this protocol. Dinitrochlorobenzene, a potent contact allergen, was included as a negative control material. In both laboratories, the respiratory allergens, but not the contact allergen, induced high titre antigen-specific antibodies in treated animals. The inhalation challenge results were similar in both laboratories but were less conclusive in that exposure to free TDI failed to induce pulmonary responses, probably because it fails to penetrate to the deep lung in sufficient concentration. Although the assay shows promise as a means of identifying chemical respiratory sensitisers, its use as a routine screen for the prediction of the ability of materials to induce respiratory allergy in man is probably questionable.
authors.affiliation: Zeneca Central Toxicological Laboratory, Macclesfield, Cheshire, UK.
authors.forename: L
authors.initials: L
authors.lastname: Blaikie
authors.forename: T
authors.initials: T
authors.lastname: Morrow
authors.forename: A P
authors.initials: AP
authors.lastname: Wilson
authors.forename: P
authors.initials: P
authors.lastname: Hext
authors.forename: P J
authors.initials: PJ
authors.lastname: Hartop
authors.forename: N J
authors.initials: NJ
authors.lastname: Rattray
authors.forename: D
authors.initials: D
authors.lastname: Woodcock
authors.forename: P A
authors.initials: PA
authors.lastname: Botham
mesh_terms: D000280:Administration, Inhalation; D000485:Allergens / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex; D004137:Dinitrochlorobenzene / Q000008:administration & dosage / Q000633:toxicity; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006168:Guinea Pigs; D006241:Haptens / Q000276:immunology / Q000378:metabolism / Q000633:toxicity; D007271:Injections, Intradermal; D017953:Isocyanates / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D008970:Molecular Weight; D010796:Phthalic Anhydrides / Q000008:administration & dosage / Q000633:toxicity; D012119:Respiration / Q000187:drug effects; D012130:Respiratory Hypersensitivity / Q000139:chemically induced*; D012709:Serum Albumin / Q000378:metabolism; D014051:Toluene 2,4-Diisocyanate / Q000008:administration & dosage / Q000633:toxicity; D001559:Benzhydryl Compounds
chemical_list: D000485:Allergens; D000936:Antigen-Antibody Complex; D004137:Dinitrochlorobenzene; D006241:Haptens; D017953:Isocyanates; D010796:Phthalic Anhydrides; D012709:Serum Albumin; D014051:Toluene 2,4-Diisocyanate; C015559:trimellitic anhydride; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds; C043103:phthalic anhydride