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.

本次审查解决了对框架的需求，以提高呼吸致敏剂和相关不确定性监管评估的一致性、客观性和透明度。通过案例研究（甲基丙烯酸甲酯）来考虑和说明主要问题。在缺乏经过验证可用于监管用途的测试方法的情况下，危险分类的证据权重的正式文件，无论是在证据线内的个别研究整合水平上，还是在广泛的数据流中，都被认为是至关重要的这样一个框架。提出了一种综合方法，不仅包括用于呼吸致敏剂监管评估的职业研究和临床证据，还包括结构和物理和化学因素的信息、结构活性分析等预测方法以及体外和体内机制和毒代动力学发现。证据权重协议根据预先确定的考虑因素整合这些数据源，将有助于提高评估结果的透明度和一致性。在可能需要仅根据职业调查结果做出决定的情况下，结论应基于各种研究中观察到的职业性哮喘患病率的相关数据的透明加权，并考虑所有相关信息，包括范围和性质工作场所接触感兴趣物质、同时接触其他化学品和研究质量的情况。