Classification of chemicals as respiratory allergens based on human data: Requirements and practical considerations.

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.