Toxicology and applied pharmacology

Guinea pig respiratory response to isocyanates.

PMID 6195771


Exposure to some isocyanates (e.g., toluene diisocyanate) has been associated with development of respiratory sensitization. In this study, guinea pig respiratory response to protein conjugates of isocyanatoethyl methacrylate (IEM) and isocyanatoethyl propionate (IEP) was evaluated. Guinea pigs were exposed to daily induction exposures with an aerosol of bovine serum albumin (BSA) or BSA conjugated with IEM or IEP. After approximately 2 weeks significant increases in respiratory rate occurred in the guinea pigs exposed to the isocyanate conjugates. The number of animals responding was related to the degree of conjugation of isocyanate to protein. No response to unconjugated BSA was observed. The isocyanates conjugated to another carrier, guinea pig serum albumin (GSA), elicited responses. In guinea pigs responding to BSA-IEM, 0.01 ppm IEM monomer did not elicit responses; 0.1 to 0.4 ppm IEM vapor elicited responses similar to conjugates but which were delayed; 0.5 and 0.6 ppm induced irritation responses. An IEM polymer aerosol that contained less than 0.004% monomer did not elicit a response. These data suggest a response threshold. Guinea pig developing responses to either of the isocyanate conjugates displayed cross-reactions to challenge with the other. A conjugate of BSA with hexyl isocyanate (HI) did not induce cross-responses in guinea pigs reactive to BSA-IEM. Application of BSA-IEP or IEP monomer to the scratched skin of guinea pigs that responded by inhalation to BSA-IEP resulted in immediate wheal and flare responses not seen in unexposed animals. All of these findings suggest induction of Type I hypersensitivity (asthmatic) directed toward the isocyanate portion of the conjugate and not the protein.

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2-Isocyanatoethyl methacrylate, contains ≤0.1% BHT as inhibitor, 98%