Volatile organic compounds exposure and all health outcomes: An umbrella review and evidence map

초록

Volatile organic compounds (VOCs) are common environmental and occupational pollutants, yet evidence on their health impacts remains fragmented. This umbrella review aimed to integrate and evaluate the credibility of associations between exposures to major VOCs and adverse health outcomes. We conducted an umbrella review of meta-analyses, systematically searching PubMed/MEDLINE, Embase, CINAHL, and Google Scholar from inception to May 30, 2025. Eligible studies were meta-analyses of observational studies (cohort, case-control, and cross-sectional) that investigated exposure to VOCs and health outcomes. For each association, effect sizes were recalculated using random-effects models and expressed as equivalent odds ratios (eORs) with 95% confidence intervals (CIs). Methodological quality was assessed using AMSTAR 2, and the class of evidence (CE) for each association was graded using predefined criteria for observational evidence (Classes I-IV). A total of 27 meta-analyses met the inclusion criteria, covering 50 exposure-outcome associations across 35 countries. Methodological quality was varied substantially (6 high, 6 moderate, 6 low, and 9 critically low). For occupational exposure, benzene was associated with a range of outcomes, including micronucleus frequency (eOR, 2.31 [95% CI, 1.04-5.13]; CE=IV), nervous system cancers (1.21 [1.05-1.38]; CE=IV), and several solid tumors. Styrene was associated with dyschromatopsia (2.79 [1.81-4.31]; CE=IV), and formaldehyde was linked to sinonasal cancer (1.79 [1.23-2.60]; CE=IV). In environmental exposure settings, benzene was associated with childhood hematologic malignancies, asthma, and low birth weight. Xylene showed a modest association with asthma (1.04 [1.01-1.07]; CE=IV), while formaldehyde was associated with childhood asthma (1.27 [1.05-1.53]; CE=IV). Styrene exposure was also associated with autism spectrum disorder (1.37 [1.12-1.68]; CE=III). Exposure to VOCs is associated with multiple health outcomes, although the overall credibility of evidence remains limited by low methodological quality. Strengthened emission control, improved exposure assessment, and well-designed prospective biomonitoring studies are needed to clarify causal relationships. Study Registration: CRD420251240414.

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