Moving away from animal testing for acute inhalation toxicity testing

Emilie Da Silva*, Jorid Birkelund Sørli

*Corresponding author for this work

Research output: Contribution to conferenceConference abstract for conferenceResearchpeer-review

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Abstract

Testing for acute inhalation toxicity is required for chemicals manufactured or imported at tonnages ≥ 10 tons per year (Commission Regulation (EC) No 440/2008) and for biocides (Regulation (EU) No 528/2012) and plant protection products (Regulation (EU) No 283/2013) before they are allowed on the market. Currently, three OECD Test Guidelines are available (TG 403, TG 436, and TG 433), all based on the exposure of rodents to the substance of interest for up to 4 hours. The use of animals for toxicological evaluation does not come without challenges. Animal experiments are costly and time consuming. It is estimated that the turnaround time for carrying out an acute inhalation test is 3 to 4 months. Besides, using rodents in order to predict the toxicity of a compound in humans is arguable given the differences in the features of the respiratory tract. The development and the validation of alternative methods in chemico, in vitro and/or in silico are needed. To do so, the mechanistic understanding of the toxicity of inhaled chemicals is key.
An innovative in vitro method for acute inhalation toxicity will be presented. This cell-free method is based on the monitoring of lung surfactant function. Indeed, the lung surfactant layer in the alveoli is the first barrier that inhaled compounds will encounter when they reach the respiratory region in the lungs. Thus far, the method was successfully applied to a range of compounds, including excipients for drug formulation, pharmaceuticals and spray products and its correlation with in vivo endpoints was demonstrated. The next steps include further optimization of the method and the adoption of an integrated testing strategy combining several alternative methods rooted in the mechanism of acute inhalation toxicity to reduce, and ultimately, replace the use of animals in these tests.
Original languageEnglish
Publication date2019
Number of pages1
Publication statusPublished - 2019
EventLASA 3R'S Sectional Annual Conference - Birmingham, United Kingdom
Duration: 26 Nov 201926 Nov 2019

Conference

ConferenceLASA 3R'S Sectional Annual Conference
CountryUnited Kingdom
CityBirmingham
Period26/11/201926/11/2019

Cite this

Da Silva, E., & Sørli, J. B. (2019). Moving away from animal testing for acute inhalation toxicity testing. Abstract from LASA 3R'S Sectional Annual Conference, Birmingham, United Kingdom.