PHENYL ISOCYANATE IS A POTENT CHEMICAL SENSITIZER

Diisocyanates, as a chemical class, are recognized for their ability t o cause respiratory and dermal sensitization. By contrast, monofunctio nal isocyanates have not been associated with cases of clinical sensit ization. We investigated the immunologic activity of phenyl isocyanate (PI), an aromatic monoisocyanate, which is a trace constituent in com mercial diphenyl methane diisocyanate (MDI) products, since it is has been reported to cause an 'asthma-like' syndrome in rats. The potency of PI as a contact sensitizer was assessed using the mouse ear swellin g test. PI was found to be the most potent isocyanate tested yielding an SD50 (dose predicted to sensitize 50% of the mice) of 0.04 mu mol/k g, compared with SD50 values of 0.5, 2.1, and 30.4 mu mol/kg, for the diisocyanate sensitizers hexamethylene diisocyanate, MDI, and toluene diisocyanate (TDI), respectively. When tested for ability to stimulate humoral immune responses, antibody titers to PI were more than ten-fo ld greater than those induced by TDI. The mean hapten-specific IgG ant ibody titer to PI was 1.4 x 10(4), compared with 1.3 x 10(3) for TDI. The anti-PI IgG(1) anaphylactic antibody titer (1.2 x 10(4)) was signi ficantly greater than the anti-TDI IgG(1) titer of 6.4 x 10(2). Hapten -specific IgE was not detected to either isocyanate. These results ind icate that phenyl isocyanate is a potent inducer of both cellular and humoral immune responses. This activity may be a significant contribut ion to the sensitization potential of commercial products in which it is a trace contaminant.