University of Ottawa, Ottawa, Canada.
Emeritus Professor, University of Surrey, Guildford, Surrey, UK.
Arch Toxicol. 2023 Apr;97(4):931-946. doi: 10.1007/s00204-023-03448-w. Epub 2023 Feb 17.
This review addresses the need for a framework to increase the consistency, objectivity and transparency in the regulatory assessment of respiratory sensitisers and associated uncertainties. Principal issues are considered and illustrated through a case study (with methyl methacrylate). In the absence of test methods validated for regulatory use, formal documentation of the weight-of-evidence for hazard classification both at the level of integration of individual studies within lines of evidence and across a broad range of data streams was agreed to be critical for such a framework. An integrated approach is proposed to include not only occupational studies and clinical evidence for the regulatory assessment of respiratory sensitisers, but also information on structure and physical and chemical factors, predictive approaches such as structure activity analysis and in vitro and in vivo mechanistic and toxicokinetic findings. A weight-of-evidence protocol, incorporating integration of these sources of data based on predefined considerations, would contribute to transparency and consistency in the outcome of the assessment. In those cases where a decision may need to be taken on the basis of occupational findings alone, conclusions should be based on transparent weighting of relevant data on the observed prevalence of occupational asthma in various studies taking into account all relevant information including the range and nature of workplace exposures to the substance of interest, co-exposure to other chemicals and study quality.
本综述旨在为呼吸致敏物的监管评估增加一致性、客观性和透明度提供一个框架，并考虑了相关的不确定性。主要问题通过案例研究（以甲基丙烯酸甲酯为例）进行了阐述和说明。在缺乏经监管使用验证的测试方法的情况下，对于这样的框架，在证据线内和跨广泛数据流的各个研究水平上，对危害分类的证据综合进行正式记录被认为至关重要。提出了一种综合方法，不仅包括呼吸致敏物监管评估的职业研究和临床证据，还包括关于结构和物理化学因素、预测方法（如结构活性分析）以及体外和体内机制和毒代动力学发现的信息。一个证据综合协议，根据预定义的考虑因素整合这些数据来源，将有助于评估结果的透明度和一致性。在某些情况下，可能需要仅根据职业研究结果做出决策，结论应基于对不同研究中观察到的职业性哮喘流行率的相关数据进行透明加权考虑，同时考虑到所有相关信息，包括接触物质的工作场所暴露范围和性质、与其他化学物质的共同暴露以及研究质量。
