A review on potential approach for in silico toxicity analysis of respirable fraction of ambient particulate matter.

Abstract

Epidemiological and toxicological studies have shown the adverse effect of ambient particulate matter (PM) on respiratory and cardiovascular systems inside the human body. Various cellular and acellular assays in literature use indicators like ROS generation, cell inflammation, mutagenicity, etc., to assess PM toxicity and associated health effects. The presence of toxic compounds in respirable PM needs detailed studies for proper understanding of absorption, distribution, metabolism, and excretion mechanisms inside the body as it is difficult to accurately imitate or simulate these mechanisms in lab or animal models. The leaching kinetics of the lung fluid, PM composition, retention time, body temperature, etc., are hard to mimic in an artificial experimental setup. Moreover, the PM size fraction also plays an important role. For example, the ultrafine particles may directly enter systemic circulations while coarser PM10 may be trapped and deposited in the tracheo-bronchial region. Hence, interpretation of these results in toxicity models should be done judiciously. Computational models predicting PM toxicity are rare in the literature. The variable composition of PM and lack of proper understanding for their synergistic role inside the body are prime reasons behind it. This review explores different possibilities of in silico modeling and suggests possible approaches for the risk assessment of PM particles. The toxicity testing approach for engineered nanomaterials, drugs, food industries, etc., have also been investigated for application in computing PM toxicity.