Ph.d.-vejledning: The lung surfactant bioasay for hazard identification of airborne compounds

Description

To protect workers and consumers, requirements for the hazard identification of inhaled chemicals and particles are set under a number of regulatory schemes, such as the regulation for the Registration, Evaluation, Authorisation and Restriction of Chemicals. While toxicity testing has traditionally been based on animal testing, there are scientific, ethical, and regulatory incentives to move away from in vivo methods. The development of alternative methods to replace experimental animals has been the focus of much investigation and it was stated in the European chemical strategy for 2020 that “safety testing and chemical risk assessment need to innovate in order to reduce dependency on animal testing but also to improve the quality, efficiency and speed of chem-ical hazard and risk assessments”. For hazard identification of airborne com-pounds, an alternative method to the existing test guidelines in animals has yet to be developed and accepted for regulatory use.
Unlike most studies focusing on in vitro cell models, the lung surfactant bio-assay presented in this thesis is a cell-free system. The method is based on the study of lung surfactant, a complex mixture of lipids and proteins. One of the lung surfactant’s critical roles is to ensure effortless breathing by decreasing the surface tension at the air-liquid interface in the alveoli. The layer of lung surfactant is the first entity which inhaled chemicals and particles will encoun-ter in the deepest part of the lungs. The lung surfactant coating the inside of the alveoli was identified as a toxicological target of inhaled compounds.
In this context, the overall objective of this thesis was to further develop and characterise the lung surfactant bioassay as well as to investigate its adequacy and regulatory readiness for hazard identification of airborne compounds. The specific aims were (i) to investigate the mechanism of toxicity of inhaled com-pounds for the lung surfactant at the molecular level, (ii) to characterise the lung surfactant bioassay, (iii) to evaluate the suitability of the method to predict adverse lung effects in humans and in rodents, and finally (iv) to discuss the intended purpose and the regulatory readiness of the lung surfactant bioassay.

Period	2017 → 2020
Held at	DTU Environment, Technical University of Denmark, Lyngby, Denmark., Denmark
Degree of Recognition	National