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 sensit ization potential of these two isomer. Separate groups of guinea pigs were either sham exposed or exposed to one of the isomers 3 h/day for 5 consecut ive days (sensitization phase). The mean concentration during the sensitiza tion phase ranged from 1.29 to 1.40 ppm. The animals were then conventional ly 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 p hase involved exposure to TDI vapor (18 to 46 ppb), whereas the third chall enge 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 delay ed-onset hypersensitivity responses was respiratory rare. Body weights and clinical signs were also recorded. There were clear decrements in iz eight gain in response to the wk I exposure to either isomer of TDI. bur no isome r-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 respon se during the challenge phase. The incidence of immediate-onset hypersensit ivity responses resulting from challenge with TDI vapor was less robust and less consistent than that resulting from challenge with the TDI-GPSA conju gate. All groups sensitized with either isomer showed an increased incidenc e of responders. Tl,ere was no apparent difference between the two isomers. The delayed-onset phase produced more spontaneous variability in spontaneo us respiratory rates and was not amenable to analysis for response to TDI c hallenge. Thus, no isomer dependent differences were observed.