Guinea pig respiratory response to isocyanates

Area of Science:

• Immunology
• Toxicology
• Occupational Health

Background:

• Isocyanates, such as toluene diisocyanate, are known respiratory sensitizers.
• Protein conjugates of isocyanates can induce hypersensitivity reactions.

Purpose of the Study:

• To evaluate the respiratory response of guinea pigs to protein conjugates of isocyanatoethyl methacrylate (IEM) and isocyanatoethyl propionate (IEP).
• To investigate the role of the isocyanate moiety versus the protein carrier in inducing sensitization.

Main Methods:

• Guinea pigs were exposed to aerosols of bovine serum albumin (BSA) or BSA conjugated with IEM or IEP.
• Dose-response studies with IEM vapor and polymer aerosols were conducted.
• Skin sensitization tests were performed with IEP conjugates and monomer.
• Cross-reactivity studies were performed with different isocyanate conjugates.

Main Results:

• Exposure to IEM and IEP protein conjugates induced significant increases in respiratory rate in guinea pigs.
• The response was dependent on the degree of isocyanate conjugation to the protein.
• A dose threshold for IEM monomer-induced responses was observed.
• Cross-reactivity was noted between IEM and IEP conjugates, but not with hexyl isocyanate conjugates.
• Skin application of IEP conjugates caused immediate wheal and flare responses.

Conclusions:

• The findings suggest the induction of Type I hypersensitivity (asthmatic responses) directed towards the isocyanate portion of the conjugate.
• These results highlight the potential of IEM and IEP as respiratory sensitizers.