Overview of inhalation exposure techniques: strengths and weaknesses

Abstract

The vast majority of toxicity studies and risk evaluations deal with single chemicals. Due to the growing interest in potential human health risks originating from exposure to environmental pollutants or lifestyle-related complex chemical mixtures, well thought-out tailor-made mechanistic inhalation toxicity studies have been performed. In contrast to the complex mixtures potentially encountered from hazardous waste sites, drinking water disinfection by-products, natural flavoring complexes or the cumulative intake of food additives and pesticide residues, the scientific evaluation of complex airborne mixtures, such as acid aerosols, atmospheres produced by combustion or thermolysis, e.g. residual oil fly ash (ROFA), diesel and gasoline exhaust, and tobacco smoke, or volatile organic chemicals (VOCs) in residential areas, to mention but a few, is a daunting challenge for experimental toxicologists. These challenges include the controlled in situ generation of exposure atmospheres, the compositions of which are often process-determined and metastable. This means that volatile agents may partition with liquid aerosols or be adsorbed onto surfaces of solid aerosols. Similarly, the nature and composition of test atmospheres might change continuously through oxidation and aging of constituents or coagulation of particles. This, in turn, poses additional challenges to the analytical characterization of such complex test atmospheres, including the identification of potential experimental artifacts. Accordingly, highly standardized and controlled inhalation studies are required for hazard identification of complex mixtures and the results of inhalation studies have to be analyzed judiciously due to the great number of experimental variables. These variables may be related to technical issues or to the specific features of the animal model. Although inhalation exposure of animals mimics human exposure best, not all results obtained under such rigorous test conditions might necessarily also occur under real-life exposure conditions. In addition, to simulate experimentally specific use or exposure patterns may impose a particular challenge to traditional approaches in terms of relevant exposure metrics and the analytes chosen to characterize exposure atmospheres. This paper addresses major developments in the discipline of inhalation toxicology with particular emphasis on the state-of-the-art testing of complex mixtures.