Background

Toluene diisocyanate (TDI) is a highly reactive chemical that causes sensitization and has also been associated with increased lung cancer. A risk assessment was conducted based on occupational epidemiologic estimates for several health outcomes.

Methods

Exposure and outcome details were extracted from published studies and a NIOSH Health Hazard Evaluation for new onset asthma, pulmonary function measurements, symptom prevalence, and mortality from lung cancer and respiratory disease. Summary exposure–response estimates were calculated taking into account relative precision and possible survivor selection effects. Attributable incidence of sensitization was estimated as were annual proportional losses of pulmonary function. Excess lifetime risks and benchmark doses were calculated.

Results

Respiratory outcomes exhibited strong survivor bias. Asthma/sensitization exposure response decreased with increasing facility-average TDI air concentration as did TDI-associated pulmonary impairment. In a mortality cohort where mean employment duration was less than 1 year, survivor bias pre-empted estimation of lung cancer and respiratory disease exposure response.

Conclusion

Controlling for survivor bias and assuming a linear dose–response with facility-average TDI concentrations, excess lifetime risks exceeding one per thousand occurred at about 2 ppt TDI for sensitization and respiratory impairment. Under alternate assumptions regarding stationary and cumulative effects, one per thousand excess risks were estimated at TDI concentrations of 10 – 30 ppt. The unexplained reported excess mortality from lung cancer and other lung diseases, if attributable to TDI or associated emissions, could represent a lifetime risk comparable to that of sensitization.

中文翻译：

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甲苯二异氰酸酯和呼吸道疾病人体研究的风险评估

 背景

甲苯二异氰酸酯 (TDI) 是一种高反应性化学物质，会引起过敏，并且与肺癌增加有关。根据对几种健康结果的职业流行病学估计进行了风险评估。

 方法

暴露和结果详细信息是从已发表的研究和 NIOSH 健康危害评估中提取的，包括新发哮喘、肺功能测量、症状患病率以及肺癌和呼吸道疾病的死亡率。考虑到相对精度和可能的幸存者选择效应，计算了总结的暴露-反应估计值。估计致敏的归因发生率以及每年比例的肺功能损失。计算了超额终生风险和基准剂量。

 结果

呼吸系统结果表现出强烈的幸存者偏差。哮喘/过敏暴露反应随着设施平均 TDI 空气浓度的增加而降低，TDI 相关的肺损伤也是如此。在平均就业时间不到一年的死亡率队列中，幸存者偏差先于对肺癌和呼吸道疾病暴露反应的估计。

 结论

控制幸存者偏差并假设与设施平均 TDI 浓度呈线性剂量反应，在约 2 ppt TDI 时，致敏和呼吸损伤的超额终生风险超过千分之一。在关于固定效应和累积效应的替代假设下，TDI 浓度为 10 – 30 ppt 时估计存在千分之一的超额风险。无法解释的肺癌和其他肺部疾病导致的死亡率过高，如果归因于 TDI 或相关排放，可能会带来与致敏相当的终生风险。