Pemberton Mark A, Kimber Ian
Systox Ltd, UK.
Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Regul Toxicol Pharmacol. 2021 Jul;123:104925. doi: 10.1016/j.yrtph.2021.104925. Epub 2021 Apr 5.
Occupational asthma is an important health problem that can include exacerbation of existing asthma, or induce new asthma either through allergic sensitisation, or non-immunological mechanisms. While allergic sensitisation of the respiratory tract can be acquired to proteins, or to low molecular weight chemicals (chemical respiratory allergens) this article is on the latter exclusively. Chemical respiratory allergy resulting in occupational asthma is associated with high levels of morbidity and there is a need, therefore, that chemicals which can cause sensitisation of the respiratory tract are identified accurately. However, there are available no validated, or even widely accepted, predictive test methods (in vivo, in vitro or in silico) that have achieved regulatory acceptance for identifying respiratory sensitising hazards. For this reason there is an important reliance on human data for the identification of chemical respiratory allergens, and for distinguishing these from chemicals that cause occupational asthma through non-immunological mechanisms. In this article the reasons why it is important that care is taken in designating chemicals as respiratory allergens are reviewed. The value and limitations of human data that can aid the accurate identification of chemical respiratory allergens are explored, including exposure conditions, response characteristics in specific inhalation challenge tests, and immunological investigations.
职业性哮喘是一个重要的健康问题，它可能包括使现有的哮喘病情加重，或者通过过敏致敏或非免疫机制诱发新的哮喘。虽然呼吸道的过敏致敏可能是由蛋白质或低分子量化学物质（化学性呼吸道变应原）引起的，但本文仅关注后者。导致职业性哮喘的化学性呼吸道过敏与高发病率相关，因此，需要准确识别能够引起呼吸道致敏的化学物质。然而，目前尚无经过验证的、甚至未被广泛接受的预测性测试方法（体内、体外或计算机模拟）能够获得监管部门认可用于识别呼吸道致敏危害。因此，在识别化学性呼吸道变应原以及将它们与通过非免疫机制导致职业性哮喘的化学物质区分开来方面，很大程度上依赖于人体数据。本文回顾了在将化学物质指定为呼吸道变应原时谨慎行事的重要原因。探讨了有助于准确识别化学性呼吸道变应原的人体数据的价值和局限性，包括接触条件、特定吸入激发试验中的反应特征以及免疫学研究。
