Moving away from animal experimentation for acute inhalation toxicity testing

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.

The correlation between the inhibition of the lung surfactant function and the decrease in tidal volume in mice was shown with a variety of compounds including excipients for drug formulation, and impregnation spray products. During this webinar, the method will be introduced and explained, and case studies using different chemical groups will be presented.