Beyond dermal exposure: The respiratory tract as a target organ in hazard assessments of cosmetic ingredients.

Abstract Dermal contact is the main route of exposure for most cosmetics; however, inhalation exposure could be significant for some formulations (e.g., aerosols, powders). Current cosmetic regulations do not require specific tests addressing respiratory irritation and sensitisation, and despite the prohibition of animal testing for cosmetics, no alternative methods have been validated to assess these endpoints to date. Inhalation hazard is mainly determined based on existing human and animal evidence, read-across, and extrapolation of data from different target organs or tissues, such as the skin. However, because of mechanistic differences, effects on the skin cannot predict effects on the respiratory tract, which indicates a substantial need for the development of new approach methodologies addressing respiratory endpoints for inhalable chemicals in general. Cosmetics might present a particularly significant need for risk assessments of inhalation exposure to provide a more accurate toxicological evaluation and ensure consumer safety. This review describes the differences in the mechanisms of irritation and sensitisation between the skin and the respiratory tract, the progress that has already been made, and what still needs to be done to fill the gap in the inhalation risk assessment of cosmetic ingredients.