Sensory irritation, pulmonary irritation, and acute lethality of a polymeric isocyanate and sensory irritation of 2,6-toluene diisocyanate

Abstract

The use of monomeric and polymeric isocyanates in a wide variety of industries has been increasing. Little is known about the toxicity of polymeric isocyanates and the widely used 2,6-toluene diisocyanate (TDI) isomer. The pulmonary and sensory irritation of an aliphatic polyisocyanate (DES-N) based on hexamethylene diisocyanate (HDI) was studied in Swiss-Webster male mice during aerosol exposures in the range of 25 to 131 mg/m 3. The sensory irritation of 2,6-TDI vapor was studied in the range of 0.37 to 7.6 mg/m 3 (0.05 to 1.1 ppm). The aerodynamic equivalent diameter and geometric standard deviation for the DES-N aerosol were 0.6 μm and 2.4, respectively. High-speed liquid chromatography was used to determine both free HDI in DES-N and HDI in the exposure chamber. Each exposure was for 3 hr during which the tidal volume pattern and respiratory rate of groups of four mice were recorded. Unlike the monomeric isocyanates, DES-N acted predominantly as a pulmonary irritant, evoking little sensory irritation. The concentration needed to reduce the respiratory rate 50% due to pulmonary irritation was 57.1 mg/m 3. The LC50, determined by counting the number of deaths within the 24 hr period following a 4-hr exposure, was 91.2 mg/m 3. In groups of animals killed 2 hr after the 4-hr exposure, the concentration of DES-N needed to increase lung weight by 50% was 45 mg/m 3. Based on comparisons with another pulmonary irritant, nitrogen dioxide, the maximum concentration for DES-N permitted in industry should be 1 mg/m 3 with a time-weighted average for an 8-hr period of 0.5 mg/m 3. From the concentration-response relationship due to sensory irritation for 2,6-TDI, the RD50 was determined to be 1.8 mg/m 3 (0.26 ppm) which is close to the value of 1.4 mg/m 3 (0.20 ppm) determined previously for 2,4-TDI. No pulmonary irritation was observed. For industrial applications the exposure limit for 2,4-TDI of 0.04 mg/m 3 (0.006 ppm) is also suggested as appropriate for the 2,6-TDI isomer.