An in vitro method to predict acute lung toxicity due to pulmonary surfactant inhibition

Contact: Jorid Birkelund Sørli, Søren Thor Larsen

The overall aim of the project is to reduce the number of animal experiments related to consumer product safety assessment. This aim will be reached by developing an in vitro model based on pulmonary surfactant inhibition, allowing a broad range of chemicals and consumer products to be investigated for toxic effects on the pulmonary surfactant system and thereby their potential to induce acute lung toxicity. To validate the quality and reliability of the in vitro model (based on sensitivity,specificity, precision and negative predictive value), a limited number of mouse inhalation studies must be carried out.

Project status at january 2017

Aerosol products for weatherproofing shoes, textiles, furniture and construction materials are used both by private individuals and in professional settings. During application of the products, small droplets of fluid will form in the air (aerosols) that can be inhaled. Some products have caused acute toxic poisoning of persons during the spraying process. The typical symptoms are coughing and shortness of breath but the effects can be more serious, including reduced pulmonary function. The current standard method involves the use of laboratory animals and is associated with discomfort and some suffering for the animals.

We have shown that proofing sprays are toxic, primarily because they inhibit the function of a pulmonary surfactant which is vital for the function of the lungs. When the pulmonary surfactant is functioning, breathing is effortless. When toxic proofing aerosols are deeply inhaled into the lungs and react with the pulmonary surfactant layer, the surfactant’s function is destroyed. As a result, the pulmonary alveoli begin to collapse. The opening and collapse of the alveoli explains the intoxication symptoms experienced by users shortly after application of toxic products. In this project, we have tested 22 products in a dynamic model of the pulmonary surfactant function – an artificial alveolus. The surface of the pulmonary surfactant is increased and reduced with the same frequency and extent as in the lungs, and at the same time the surfactant is exposed to the proofing spray product. The products were divided into two groups – toxic and non-toxic – based on whetherthe surfactant function was inhibited or not. To test the usefulness of the in vitro method, the same products were tested with a modified in vivo model. The modified method minimizes the discomfort and suffering of the animals, for instance by stopping the exposure before the mice become very affected by the products. There is a good correlation between the in vitro and in vivo methods. In 77% of the cases, the in vitro model predicts the result of toxicity for the mice. Using the in vitro method can reduce the necessity of using laboratory animals to test the toxicity of proofing spray products, even before marketing, and thus prevent

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