Associations of ambient exposure to benzene, toluene, ethylbenzene, and xylene with daily mortality: a multicountry time-series study in 757 global locations

Background: The presence of benzene, toluene, ethylbenzene, and xylene isomers (BTEX) in the environment is of increasing concern due to their toxicity and ubiquity. Although the adverse health effects of BTEX exposure have been documented, robust epidemiological evidence from large-scale, multicountry studies using advanced exposure assessment methodologies remains scarce. We aimed to assess the association of short-term ambient exposure to individual BTEX components and their mixture with daily total, cardiovascular, and respiratory mortality on a global scale. Methods: Daily data on mortality, meteorological factors, and air pollution were collected from 757 locations across 46 countries or regions. Data on individual chemicals (ie, benzene, toluene, xylenes [summation of ethylbenzene, m-xylene, p-xylene, and o-xylene]) and the aggregate mixture (ie, BTEX) were estimated using a chemistry-climate model. We examined the short-term associations of each individual chemical as well as the BTEX mixture with daily total, cardiovascular, and respiratory mortality in a multicountry framework. Using a two-stage time-series design, we first applied generalised additive models with a quasi-Poisson distribution to obtain location-specific associations, which were subsequently pooled using random-effects meta-analysis. Two-pollutant models were used to assess the independent effects of BTEX after adjusting for co-pollutants (PM2·5, PM10, nitrogen dioxide, sulphur dioxide, ozone, and carbon monoxide). Additionally, we assessed the overall exposure-response curves with spline terms. Findings: An IQR increment of BTEX concentration on lag 0-2 days (3-day moving average of the present day and the previous 2 days) was associated with increases of 0·57% (95% CI 0·49-0·65), 0·42% (0·30-0·54), and 0·68% (0·50-0·86) in total, cardiovascular, and respiratory mortality, respectively. The corresponding effect estimates for an IQR increment in individual chemicals (benzene, toluene, and xylenes) were 0·38-0·61%, 0·44-0·70%, and 0·41-0·65%, respectively. The associations remained significant after adjusting for co-pollutants, with a general decline in magnitude, except for a slight increase after adjustment for ozone. The shape of the exposure-response curves for all pollutants and causes of death was almost linear, with steeper slopes at low concentrations and no discernible thresholds. Interpretation: This global study provides novel evidence linking short-term exposure to ambient BTEX, both individually and as a mixture, with increased daily total, cardiovascular, and respiratory mortality. Our findings underscore the need for comprehensive air pollution mitigation policies, including stringent controls on BTEX emissions, to protect public health. Funding: Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, Shanghai Municipal Science and Technology Major Project, Shanghai B&R Joint Laboratory Project, and Shanghai International Science and Technology Partnership Project.