Shiotsuka R N, Warren D L, Halliburton A T, Sturdivant D W
Toxicolgy, Agriculture Division, Bayer Corporation, Stillwell, Kansas, USA.
Inhal Toxicol. 2000 Jul;12(7):605-15. doi: 10.1080/08958370050030976.
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.
工人有可能同时接触2,4 - 甲苯二异氰酸酯（2,4 - TDI）和2,6 - TDI，这引发了对这两种异构体相对呼吸道致敏潜力的研究。将豚鼠分成不同组，分别进行假暴露，或连续5天每天暴露于其中一种异构体3小时（致敏阶段）。致敏阶段的平均浓度范围为1.29至1.40 ppm。然后将动物常规饲养2周，并在随后的3周中，每周用相同异构体或另一种异构体进行1小时激发。激发阶段的前2周涉及暴露于TDI蒸气（18至46 ppb），而第三次激发是暴露于TDI - 豚鼠血清白蛋白（GPSA）偶联物的气雾剂（18至32 mg/m³）。用于检测速发型和迟发型超敏反应的终点指标是呼吸频率。还记录了体重和临床症状。暴露于TDI的任何一种异构体后，第1周体重增加明显减少，但未观察到异构体特异性差异。临床症状仅在致敏阶段显示出呼吸道刺激。一只用TDI - GPSA激发的动物在激发阶段可能经历了严重的过敏反应。由TDI蒸气激发引起的速发型超敏反应的发生率不如由TDI - GPSA偶联物激发引起的那样强烈和一致。用任何一种异构体致敏的所有组中，反应者的发生率均增加。两种异构体之间没有明显差异。迟发型阶段在自发呼吸频率上产生了更多的自发变异性，并且不适合分析对TDI激发的反应。因此，未观察到异构体依赖性差异。
