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Air pollution is an example of a complex environmental mixture with different biological activities, making risk assessment challenging. Current cancer risk assessment strategies that focus on individual pollutants may overlook interactions among them, potentially underestimating health risks. Therefore, a shift towards the evaluation of whole mixtures is essential for accurate risk assessment. This study presents the application of an in vitro New Approach Methodology (NAM) to estimate relative cancer potency factors of whole mixtures, with a focus on organic pollutants associated with air particulate matter (PM). Using concentration-dependent activation of the DNA damage-signaling protein checkpoint kinase 1 (pChk1) as a readout, we compared two modeling approaches, the Hill equation and the benchmark dose (BMD) method, to derive Mixture Potency Factors (MPFs). MPFs were determined for five PM 2.5 samples covering sites with different land uses and our historical pChk1 data for PM 10 samples and Standard Reference Materials. Our results showed a concentration-dependent increase in pChk1 by all samples and a higher potency compared to the reference compound benzo[a]pyrene. The MPFs derived from the Hill equation ranged from 128 to 9793, while those from BMD modeling ranged from 70 to 303. Despite the differences in magnitude, a consistency in the relative order of potencies was observed. Notably, PM 2.5 samples from sites strongly impacted by biomass burning had the highest MPFs. Although discrepancies were observed between the two modeling approaches for whole mixture samples, relative potency factors for individual PAHs were more consistent. We conclude that differences in the shape of the concentration-response curves and how MPFs are derived explain the observed differences in model agreement for complex mixtures and individual PAHs. This research contributes to the advancement of predictive toxicology and highlights the feasibility of transitioning from assessing individual agents to whole mixture assessment for accurate cancer risk assessment and public health protection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In the context of a rising global temperature, biomass burning represents an increasing risk to human health, due to emissions of highly toxic substances such as polycyclic aromatic hydrocarbon (PAHs). Size-segregated particulate matter (PM) was collected in a region within the sugarcane belt of São Paulo state (Brazil), where biomass burning is still frequent, despite the phasing out of manual harvesting preceded by fire. The median of the total concentration of the 15 PAHs determined was 2.3 ± 1.8 ng m -3 (n = 19), where 63% of this content was in PM 1.0 . Concentrations of OPAHs and NPAHs were about an order of magnitude lower. PM 2.5 collected in the dry season, when most of the fires occur, presented PAHs and OPAHs total concentrations three times higher than in the wet season, showing positive correlations with fire foci number and levoglucosan (a biomass burning marker). These results, added to the fact that biomass burning explained 65% of the data variance (PCA analysis), evidenced the importance of this practice as a source of PAHs and OPAHs to the regional atmosphere. Conversely, NPAHs appeared to be mainly derived from diesel-powered vehicles. The B[a]P equivalent concentration was estimated to be 4 times higher in the dry season than in the wet season, and was greatly increased during a local fire event. Cytotoxicity and genotoxicity of PM 1.0 organic extracts were assessed using in vitro tests with human liver HepG2 cells. For both types of tests, significant toxicity was only observed for samples collected during the dry season. Persistent DNA damage that may have impaired the DNA repair system was also observed. The results indicated that there was a health risk associated with the air particulate mixture, mainly related to biomass burning, demonstrating the urgent need for better remediation actions to prevent the occurrence of burning events., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)