Toxicological evaluation of airborne particulate matter. Are cell culture technologies ready to replace animal testing?

Exposure to atmospheric particulate matter (PM) can affect human health, causing asthma, atherosclerosis, renal disease and cancer. In the last few years, outdoor air pollution has increased globally, leading to a public health emergency. Epidemiological studies have reported a correlation between the development of severe respiratory and systemic diseases and exposure to PM. To evaluate the toxic effect of PM of different origins, conventional experimental toxicological investigations have been conducted in animals; however, animal experimentation poses major ethical issues and usually differs from human conditions. As an alternative, human cell cultures are increasingly being used to investigate cellular and molecular mechanisms of PM toxicity. Although 2D cell cultures have been proven helpful, they are far from being a valid alternative to animal tests. Recently, 3D cell culture and organ-on-chip technology have provided systems that are more complex and that can be more informative for toxicity studies. In this review, the results of the 2D systems that are most frequently used for PM toxicity evaluations are summarized with a special focus on their limitations. We also examined to which extent 3D cell culture and particularly the organ-on-chip technology may overcome these limitations and represent effective tools to improve airborne PM toxicity evaluations.