Guinea pig pulmonary response to sensitization by five preformed monoisocyanate-ovalbumin conjugates.
The ability of 5 dissimilar monoisocyanates conjugated to ovalbumin (OA) as a carrier protein to induce pulmonary hypersensitivity towards the hapten specific component was assessed by using a previously described method based on the determination of a respiratory index (RI) in the guinea pig. The test chemicals included the commercially available p-tolyl and hexyl monoisocyanates (TMI and HMI), with 4-isocyanoto-4'-diphenylmethane (IDM), 4-isocyanoato-4'-methyldiphenylmethane (IMDM) and 1-isocyanato-methyl-1,3,3-trimethylcyclohexane (IMTC) as synthetized monoisocyanates. Guinea pigs were exposed daily to an aerosol of the OA conjugate of each monoisocyanate up to day 15. Increases in respiratory rate and/or respiratory collapse occurred in the guinea pigs exposed to TMI-OA and HMI-OA conjugates by days 9 and 15, with RI values of 155 and 177, respectively, being recorded. The greatest mean RI values in guinea pigs exposed to IDM-OA, IMDM-OA and IMTC-OA conjugates up to day 15 were 20, 25 and 22, respectively, and were not indicative of any pulmonary reaction. Guinea pigs exposed in parallel to each test conjugate did not exhibit any pulmonary reaction when they were exposed to OA on the challenge days. All these findings evidence pulmonary hypersensitivity as the result of exposure to TMI-OA and HMI-OA conjugates and suggest a high degree of conjugation and strong linkage of all the monoisocyanates with OA.(ABSTRACT TRUNCATED AT 250 WORDS)
D000336:Aerosols / Q000494:pharmacology; D000818:Animals; D003485:Cyanates / Q000494:pharmacology*; D004342:Drug Hypersensitivity / Q000503:physiopathology; D005260:Female; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D010047:Ovalbumin; D012119:Respiration / Q000187:drug effects; D013329:Structure-Activity Relationship; D013997:Time Factors
D000336:Aerosols; D003485:Cyanates; D010047:Ovalbumin