A comparative respiratory sensitization study of 2,4- and 2,6-toluene diisocyanate using guinea pigs

The potential exposure of workers to both 2,4-toluene diisocyanate (2,4-TDI) and 2,6-TDI led to an investigation of the comparative respiratory sensitization potential of these two isomers. Separate groups of guinea pigs were either sham exposed or exposed to one of the isomers 3 h/day for 5 consecutive days (sensitization phase). The mean concentration during the sensitization phase ranged from 1. 29 to 1.40 ppm. The animals were then conventionally housed for 2 wk and challenged for 1 h on 3 subsequent weeks with either the same isomer or the alternate isomer. The first 2 wk of the challenge phase involved exposure to TDI vapor (18 to 46 ppb), whereas the third challenge was to an aerosol of TDI-guinea pig serum albumin (GPSA) conjugate (18 to 32 mg/m(3)). The endpoint used to detect both immediate-onset and delayed-onset hypersensitivity responses was respiratory rate. Body weights and clinical signs were also recorded. There were clear decrements in weight gain in response to the wk 1 exposure to either isomer of TDI, but no isomer-specific differences were observed. Clinical signs revealed irritation to the respiratory tract only during the sensitization phase. A single animal challenged with TDI-GPSA may have experienced a severe anaphylactic response during the challenge phase. The incidence of immediate-onset hypersensitivity responses resulting from challenge with TDI vapor was less robust and less consistent than that resulting from challenge with the TDI-GPSA conjugate. All groups sensitized with either isomer showed an increased incidence of responders. There was no apparent difference between the two isomers. The delayed-onset phase produced more spontaneous variability in spontaneous respiratory rates and was not amenable to analysis for response to TDI challenge. Thus, no isomer-dependent differences were observed.