The exposure–response associations of ambient heavy metals and persistent organic pollutants (POPs) with mortality in the general population remain unclear. This cohort study aimed to explore the long-term effect of exposure to four air pollutants, including lead (Pb), cadmium (Cd), mercury (Hg), and benzo(a)pyrene [B(a)P] on all-cause and cause-specific mortality. This study involved 497,056 participants from the UK Biobank cohort. We used the Cox proportional hazards model to calculate associations. Effects of joint exposure to heavy metals were estimated using quantile g-computation. Shape of the exposure–response association was examined by fitting penalty splines, in both the total population and subpopulations stratified by age, sex, smoking status, and genetic factors. Modifying effects of age, sex, smoking status, and genetic factors were also examined. Over a median follow-up of 13.7 years, we identified 39,530 (8.0%) deaths. Exposure to mixtures of Pb, Cd, and Hg was associated with 1.040–1.154 times increased risk of all-cause cancer, cardiovascular disease (CVD), stroke, and respiratory disease mortality. Of the specific causes of mortality, Pb and Cd were most strongly associated with respiratory diseases, including chronic obstructive pulmonary disease, followed by ischemic heart disease, CVD, and cancer. Hg and B(a)P seemed to exhibit lower toxicity compared with Pb and Cd. Exposure–response curves demonstrated monotonically increased risk for most mortality outcomes, though Hg was found to be nonlinearly associated with all-cause and stroke mortality. Age, smoking status, and genetic factors were found to modify the susceptibility to heavy metals. Our findings suggested that long-term exposure to heavy metals and B(a)P was monotonically associated with elevated risk of multiple mortality outcomes, indicating there may be no safe threshold for these chemicals. Substantial benefits to public health could be achieved through stringent environmental regulations and clean air initiatives.

In this study we compared cancer risks from organic hazardous air pollutants (HAPs) based on total personal exposure summed across different microenvironments and exposure pathways.We developed distributions of personal exposure concentrations using field monitoring and modeling data for inhalation and, where relevant, ingestion pathways. We calculated risks for a nonoccupationally exposed and nonsmoking population using U.S. Environmental Protection Agency (EPA) and California Office of Environmental Health and Hazard Assessment (OEHHA) unit risks. We determined the contribution to risk from indoor versus outdoor sources using indoor/outdoor ratios for gaseous compounds and the infiltration factor for particle-bound compounds.With OEHHA's unit risks, the highest ranking compounds based on the population median are 1,3-butadiene, formaldehyde, benzene, and dioxin, with risks on the order of 10(-4)-10(-5). The highest risk compounds with the U.S. EPA unit risks were dioxin, benzene, formaldehyde, and chloroform, with risks on a similar order of magnitude. Although indoor exposures are responsible for nearly 70% of risk using OEHHA's unit risks, when infiltration is accounted for, inhalation of outdoor sources contributed 50% to total risk, on average. Additionally, 15% of risk resulted from exposures through food, mainly due to dioxin.Most of the polycyclic aromatic hydrocarbon, benzene, acetaldehyde, and 1,3-butadiene risk came from outdoor sources, whereas indoor sources wer

Air quality monitoring currently relies mostly on a combination of epidemiological data and classic experimental data. Our objective was to design an alternative approach for assessing air pollutant risk potential using a specialized platform capable of detecting the cumulative and indirect effects of exposure via the inhaled route. We used a bronchial airways-on-chip (BOC) that captures key physiological features of the human lung. The platform integrates our previously developed device with in vitro differentiated bronchial epithelium derived from induced pluripotent stem cells (iPSCs). This setup is capable of replicating bronchial epithelial exposure to irritants at the air-liquid interface under controlled and reproducible conditions. It comprises the first proof-of-concept design combining a BOC with iPSC-derived bronchial epithelium as an alternative approach toward potential risk assessment of inhaled pollutants. As a representative pollutant, we use benzene, a volatile organic compound (VOC). At low concentrations and short-term exposure, it is not considered acutely harmful, but long-term exposure can result in mutagenic and carcinogenic effects. As air pollutant toxicity is known to be mediated by the respiratory epithelial lining and secretion of cytokines, we demonstrate our system to be sufficiently sensitive to capture increased cytokine secretion corresponding to increasing concentrations of benzene. Of utmost relevance is our finding that a cumulative effect could be detected, only caused by prolonged exposure at low concentrations of benzene, previously shown to be nontoxic in classic short-term in vitro studies. Finally, the cumulative effect could be reversed using a commonly used asthma medication (Montelukast), further supporting the relevance of the setup.

This study aimed to quantitatively evaluate the potential health effects of exposure to major air pollutants inside newly manufactured automobiles and to develop a grading system for automobile indoor air quality based on this assessment. To achieve this, the concentrations of 28 air pollutants were measured in five different automobile models. Among these, 18 substances were selected for health risk assessment based on the availability of acute and chronic toxicity data and the requirement that each substance had been detected at least once under one or more of the automobile test modes (AM, PM, and DM). Acute hazard quotients (HQ_acute), chronic non-carcinogenic hazard quotients (HQ), and excess lifetime cancer risks (ECR) were subsequently calculated. The results of acute and chronic health risk assessments showed significant variation depending on the automobile test mode, and some automobiles exceeded health-based reference values for certain pollutants. Based on these findings, this study developed a 10-level grading system for automobile indoor air quality by comprehensively integrating pollutant-specific health risk levels and exceedances of the recommended limits outlined in Ministry of Land, Infrastructure, and Transport's "Indoor Air Quality Guidelines for Newly Manufactured Automobiles." The grading scale ranges from Grade 1 (Excellent) to Grade 10 (Hazardous), reflecting both acute and chronic health risks as well as legal standards, thereby improving upon conventional concentration-based management approaches. The proposed grading system enables a quantitative interpretation of automobile indoor air quality from a health-based perspective and is expected to be applicable in various fields, including automobile manufacturers' air quality control, consumer information disclosure, and policy development.