Karol M H, Kramarik J A
Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, PA, USA.
Toxicol Lett. 1996 Dec 16;89(2):139-46. doi: 10.1016/s0378-4274(96)03798-8.
Diisocyanates, as a chemical class, are recognized for their ability to cause respiratory and dermal sensitization. By contrast, monofunctional isocyanates have not been associated with cases of clinical sensitization. We investigated the immunologic activity of phenyl isocyanate (PI), an aromatic monoisocyanate, which is a trace constituent in commercial 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 swelling 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 mumol/kg, compared with SD50 values of 0.5, 2.1, and 30.4 mumol/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-fold greater than those induced by TDI. The mean hapten-specific IgG antibody titer to PI was 1.4 x 10(4), compared with 1.3 x 10(3) for TDI. The anti-PI IgG1 anaphylactic antibody titer (1.2 x 10(4) was significantly greater than the anti-TDI IgG1 titer of 6.4 x 10(2). Hapten-specific IgE was not detected to either isocyanate. These results indicate that phenyl isocyanate is a potent inducer of both cellular and humoral immune responses. This activity may be a significant contribution to the sensitization potential of commercial products in which it is a trace contaminant.
二异氰酸酯作为一类化学物质,因其能够引起呼吸道和皮肤致敏而为人所知。相比之下,单官能异氰酸酯与临床致敏病例并无关联。我们研究了苯基异氰酸酯(PI)的免疫活性,PI是一种芳香族单异氰酸酯,是商用二苯基甲烷二异氰酸酯(MDI)产品中的一种痕量成分,因为据报道它会在大鼠中引发“哮喘样”综合征。使用小鼠耳部肿胀试验评估了PI作为接触致敏剂的效力。结果发现,PI是所测试的最有效的异氰酸酯,其半数致敏剂量(预计使50%的小鼠致敏的剂量)为0.04 μmol/kg,而二异氰酸酯致敏剂六亚甲基二异氰酸酯、MDI和甲苯二异氰酸酯(TDI)的半数致敏剂量分别为0.5、2.1和30.4 μmol/kg。在测试刺激体液免疫反应的能力时,针对PI的抗体滴度比TDI诱导的抗体滴度高十多倍。针对PI的平均半抗原特异性IgG抗体滴度为1.4×10⁴,而针对TDI的为1.3×10³。抗PI IgG1过敏抗体滴度(1.2×10⁴)显著高于抗TDI IgG1滴度6.4×10²。未检测到针对任何一种异氰酸酯的半抗原特异性IgE。这些结果表明,苯基异氰酸酯是细胞免疫和体液免疫反应的有效诱导剂。这种活性可能对含有该痕量污染物的商用产品的致敏潜力有重大影响。