CEC01-04 AOP and development of test methods to predict the respiratory sensitisation potential of substances

Abstract

Asthma is one of the most prevalent lung diseases in developed countries and is induced by exposure to sensitizing agents. Respiratory sensitization is a complex immunological process that is a result of continued or long-term expose to agents which can eventually lead to hypersensitivity. Although respiratory hypersensitivity has been known for decades, there are currently no validated approaches available for the identification of suspect agents. This is largely due to the different classifications for respiratory sensitizers, as well as complexity of the response and the late manifestation of symptoms. Additionally, it has been challenging to make a clear distinction between respiratory reactions triggered by sensitization of the respiratory tract and those triggered by other factors, including type and duration of exposure and concurrent exposure to other agents that may amplify the symptoms.

The causal linking of events at different levels of biological organization in adverse outcome pathway (AOP) concepts has evolved as important approach in chemical hazard and risk assessment. While this has been conducted for skin sensitizers, efforts to understand and assess the effect of respiratory sensitizers have been stagnant for over a decade, and no AOP has been established.

Due to the urgent need for accurate and reliable test methods for the identification of respiratory sensitizers, various testing methods are being explored. This presentation will discuss the most recent information on respiratory sensitization and key events potentially relevant in the AOP concept.