Risk assessment of consumer spray products using in vitro lung surfactant function inhibition, exposure modelling and chemical analysis.

Consumer spray products release aerosols that can potentially be inhaled and reach the deep parts of the lungs. A thin layer of liquid, containing a mixture of proteins and lipids known as lung surfactant, coats the alveoli. Inhibition of lung surfactant function can lead to acute loss of lung function. We focused on two groups of spray products; 8 cleaning and 13 impregnation products, and in the context of risk assessment, used an in vitro method for assessing inhibition of lung surfactant function. Original spray-cans were used to generate aerosols to measure aerodynamic particle size distribution. We recreated a real-life exposure scenario to estimate the alveolar deposited dose. Most impregnation products inhibited lung surfactant function at the lowest aerosolization rate, whereas only two cleaning products inhibited function at the highest rates. We used inhibitory dose and estimated alveolar deposition to calculate the margin of safety (MoS). The MoS for the inhibitory products was ≤1 for the impregnation products, while much larger for the cleaning products (>880). This risk assessment focused on the risk of lung surfactant function disruption and provides knowledge on an endpoint of lung toxicity that is not investigated by the currently available OECD test guidelines.

In vitro prediction of clinical signs of respiratory toxicity in rats following inhalation exposure.

To date there are no OECD validated alternative approaches to study toxicity following inhalation exposure to airborne chemicals. The available OECD test guidelines for acute inhalation toxicity aim to estimate a value of the lethal air concentration of the test chemical leading to the death of 50% of the exposed animals (LC50), to satisfy hazard classification and labelling requirements. This paper explores the view that alternative approaches must compare to outcomes of existing guideline methods to become accepted and implemented in a regulatory context. This case study describes the initiatives taken to validate the lung surfactant bioassay, an in vitro cell-free method, and discusses the challenges faced. While the lung surfactant bioassay could not predict the GHS classification for acute inhalation toxicity of 26 chemicals, the assay successfully predicted the clinical signs of respiratory toxicity observed during or shortly after exposure in vivo as reported in registration dossiers. The lung surfactant bioassay is a promising alternative approach to assess the potential of chemicals to cause changes to respiration remaining after exposure (indicating decreased lung function), and can be combined with other test methods in an integrated approach to testing and assessment of inhaled substances.

Pulmonary toxicity following exposure to a tile coating product containing alkylsiloxanes. A clinical and toxicological evaluation.

CONTEXT: Coating products are widely used for making surfaces water and dirt repellent. However, on several occasions the use of these products has been associated with lung toxicity. OBJECTIVE: In the present study, we evaluated the toxic effects of an aerosolized tile-coating product. METHODS: Thirty-nine persons, who reported respiratory and systemic symptoms following exposure to the tile-coating product, were clinically examined. The product was analysed chemically and furthermore, the exposure scenario was reconstructed using a climate chamber and the toxicological properties of the product were studied using in vivo and by in vitro surfactometry. RESULTS: The symptoms developed within few hours and included coughing, tachypnoea, chest pain, general malaise and fever. The physical examination revealed perihilar lung infiltrates on chest radiograph and reduced blood oxygen saturation. The acute symptoms resolved gradually within 1-3 days and no delayed symptoms were observed. By means of mass spectrometry and X-ray spectroscopy, it was shown that the product contained non-fluorinated alkylsiloxanes. The exposure conditions in the supermarket were reconstructed under controlled conditions in a climate chamber and particle and gas exposure levels were monitored over time allowing estimation of human exposure levels. Mice exposed to the product developed symptoms of acute pulmonary toxicity in a concentration-and time-dependent manner. The symptoms of acute pulmonary toxicity likely resulted from inhibition of the pulmonary surfactant function as demonstrated by in vitro surfactometry. Among these patients only a partial association between the level of exposure and the degree of respiratory symptoms was observed, which could be because of a high inter-individual difference in sensitivity and time-dependent changes in the chemical composition of the aerosol. CONCLUSION: Workers need to cautiously apply surface coating products because the contents can be highly toxic through inhalation, and the aerosols can disperse to locations remote from the worksite and affect bystanders.