Toxicological effects of PM_2.5-derived and PM_2.5-relevant mixture of chlorinated paraffins on A549/THP-1 co-culture...

Chlorinated paraffins (CPs) are complex mixture of chlorinated straight-chain hydrocarbons, including short-, medium-, and long-chain CPs (SCCPs, MCCPs, and LCCPs), to which humans are exposed environmentally. Although PM_2.5-bound CPs were positively associated with asthma and related symptoms, the toxicological effects of CPs on the respiratory system remain limitedly understood. CPs were extracted from PM_2.5 samples collected in three cities in southern China, representing distinct SCCPs, MCCPs, and LCCPs profiles. The A549/THP-1 co-culture cells, an in vitro respiratory model, were exposed to PM_2.5-derived extracts containing CPs (CP extract). The gradient was established according to the extract dosage calibrated based on its quantified SCCP content with environmentally relevant concentrations. Cell viability, oxidative stress, inflammatory factors, cell cycle distribution, and genotoxicity were assessed. CP extracts reduced cell viability, increased pro-inflammatory factors concentrations, induced cell cycle arrest and DNA damage. Furthermore, CP mixtures were prepared using standards to simulate PM_2.5-relevant compositions. But the results showed weak toxicological effects of CP mixtures, suggesting CPs play a relatively weak role or CPs exhibit toxicological effects through alternative pathways. Interesting, varying compositional ratios of SCCPs, MCCPs, and LCCPs may induce different cytotoxic effects. These findings provide in vitro evidence for explaining adverse effects of PM_2.5-bound CPs on A549/THP-1 cells. More research is needed to clarify the respiratory toxicological effects of CPs.