Exposure to volatile organic compounds (VOCs) such as benzene, styrene, toluene and formaldehyde is associated with genotoxicity and increased risk of cancer. In this systematic review and meta-analysis, we have assessed the effects of VOCs exposure on levels of DNA strand breaks in leukocytes, measured by the comet assay, in human biomonitoring studies. The literature search led to 57 studies included in the review. Of these, 50 studies met the criteria to be used in the meta-analysis. Using standardized mean difference and 95% confidence interval (CI), the meta-analyses show increased levels of DNA strand breaks in subjects exposed to benzene (1.59, 95% CI: 0.94, 2.24), styrene (0.87, 95% CI: 0.23, 1.51), formaldehyde (0.39, 95% CI: -0.15, 0.92) and other organic solvents (2.14, 95% CI: 1.48, 2.81). Results originate mainly from studies on workers, with only a few studies on environmental benzene exposure. Subgroup analysis indicates that all studies combined from middle-income countries have a higher effect size (1.81, 95% CI: 1.26, 2.36, n = 28) than studies from high-income countries (0.87, 95% CI: 0.49, 1.24, n = 22). This difference between middle- and high-income countries may be due to differences in exposure levels or exposure assessment. However, this might not be the only reason, as sensitivity analysis indicates that effect sizes are at risk of comet assay measurement bias, as 78% (39 out of 50 studies) and 60% (30 studies) have not reported the use of assay controls and blinded analysis of samples, respectively. Relatively few studies have a high risk of bias due to an inadequate comet assay procedure description (14%, 7 studies) and exposure misclassification (16%, 8 studies). Limitations of the study were the differences in protocols, comet descriptors, exposure assessment and control for confounding factors among the studies. In conclusion, this systematic review and meta-analysis shows that exposure to VOCs - benzene, styrene, formaldehyde and others - is associated with increased levels of DNA strand breaks in human leukocytes.

Humans are exposed to environmental or occupational air pollution from combustion emissions in outdoor and indoor environments. Irrespective of the sources, combustion emissions are characterized by being a complex mixture of particles, volatile compounds and gases. The present systematic review summarizes results on DNA strand breaks measured by the comet assay in leukocytes, from studies on human exposure to traffic-related vehicle exhaust, biomass combustion and coke oven work environments. These exposures have in common the combustion of fuel, which generates particles and polycyclic aromatic hydrocarbons. Standardized mean differences (SMDs) have been calculated by random effects models. Meta-analyses show increased levels of DNA strand breaks in studies on traffic-related exhausts (SMD = 0.62, 95% CI: 0.36, 0.89, n = 21), biomass combustion (1.73, 95% CI: 0.72, 2.74, n = 10) and coke oven emission (0.84, 95% CI: 0.30, 1.37, n = 10). Studies from high-income countries have reported much smaller differences in DNA strand break levels than have studies from middle-income countries. These differences may be attributed to higher exposures related to less strict emission control, and more susceptible populations in middle-income populations; unrecognized confounding despite efforts to match subjects on traditional confounders; or higher risk of comet assay measurement bias and exposure misclassification. In conclusion, this systematic review and meta-analysis show that exposure to combustion-derived air pollution, with clear exposure gradients in terms of particulate matter or polycyclic aromatic hydrocarbons, is associated with increased levels of DNA strand breaks in human leukocytes.

Anaesthetic gases are agents used to induce and maintain general anaesthesia during surgical procedures. Common examples include sevoflurane, isoflurane, and desflurane, which act by depressing the central nervous system to produce unconsciousness and analgesia. These gases are administered through a vaporiser and inhaled via a mask or endotracheal tube. While effective, they can contribute to environmental pollution and increase the risk of occupational exposure. Medical personnel working in operating or post-operating facilities are unavoidably exposed to anaesthetic gases. Several adverse health effects have been associated with anaesthetic gas exposure; therefore, this review aims to summarise findings on DNA strand breaks, assessed by the comet assay in leucocytes of exposed medical workers. Standardised mean differences (SMDs) have been calculated by random effects models. The meta-analysis included 16 studies. Of these, 11 showed statistically significant increased levels of DNA strand breaks, whereas another five studies showed no significant effect. Overall, there is an increased level of DNA strand breaks in exposed subjects in unadjusted analysis (SMD = 1.17, 95 % confidence interval: 0.71, 1.62) as well as analysis adjusted for missing studies by the trim-and-fill method (SMD = 0.53, 95 % confidence interval: -0.14, 1.21). In conclusion, this systematic review and meta-analysis demonstrate that exposure to anaesthetic gases in an occupational setting induces primary DNA damage in human leucocytes, warranting further research to minimise any adverse effects on exposed medical personnel. Besides, the relevance of the use of the comet assay in assessing DNA damage in human biomonitoring studies is proven.

The comet assay is widely used in human biomonitoring studies of environmental and occupational exposures. However, it is clear from multiple studies that various types of confounding factors might affect the direct relationship between exposure and DNA damage in the comet assay. In addition to common confounders such as age, sex, and smoking, other factors considered to be important determinants for background levels of DNA damage in the comet assay include exhaustive physical exercise, chronic diseases, medical treatment, and diet. These are typically controlled in biomonitoring studies by restriction or matching of subjects. Period effects (or seasonal variation) have been observed in a relatively large number of studies. There are various putative factors, which may cause period effects, including temporal variation in solar radiation, temperature, and air pollution. The present review describes the effects of these confounding factors in measurements of DNA strand breaks by the comet assay. In general, the literature does not indicate that any confounding factor is consistently associated with an increased level of DNA damage, measured by the comet assay. In this respect, it is important to balance the need to control for confounding with the risk of introducing in the statistical analysis a variable, which is influenced by exposure and outcome (i.e. collider bias). In addition, it is important that investigators describe procedures for controlling the effect of confounding factors in the selection of subjects and statistical analysis. Care should be taken in study design and statistical analysis to avoid unwanted effects of confounding factors.

Exposure to pesticides, most usually in occupational settings, is associated with different adverse health effects. In this systematic review and meta-analysis, we have assessed the effects of pesticide exposure on the level of DNA strand breaks in human peripheral blood cells, measured by the comet assay, in human biomonitoring studies. The literature search led to 80 studies included in the review. Of these, 66 studies met the criteria to be used in the meta-analysis. Using standardized mean difference and 95 % confidence interval (CI), the meta-analyses show an increased level of DNA strand breaks in subjects exposed to pesticides (2.02, 95 % CI: 1.69, 2.35). Results originate mainly from studies on workers, with only a few studies on environmental pesticide exposure. Subgroup analysis indicates that all studies combined from middle-income countries have a higher effect size (2.22, CI: 1.84, 2.59, n = 55) than studies from high-income countries (1.09, CI: 0.41, 1.76, n = 11). This difference between middle- and high-income countries may be mostly due to legislative, economic, and socio-cultural aspects. It has to be pointed out that only 9 % of the studies were classified as having an overall low risk of bias, while 12 % of studies used exposure biomarkers. In conclusion, this systematic review and meta-analysis shows that exposure to pesticides is associated with increased levels of DNA strand breaks in human peripheral blood cells.

Exposure to heavy metals such as lead, arsenic and chromium is associated with genotoxicity and increased risk of cancer. In this systematic review and meta-analysis, we have assessed effects of heavy metal exposure on levels of DNA strand breaks in leukocytes, measured by the comet assay, in human biomonitoring studies. We distinguish between traditional toxic metals (lead), semi-metals/metalloids (arsenic), transition metals (chromium), and other heavy metals. The literature search led to 66 studies, which were assessed by meta-analysis. Using standardized mean difference and 95 % confidence interval (CI), the meta-analyses show increased levels of DNA strand breaks in subjects exposed to lead (1.99, 95 % CI: 1.47, 2.51), arsenic (1.36, 95 % CI: 0.94, 1.77), chromium/welding fume (2.03, 95 % CI: 1.48, 2.57), and other heavy metals (0.81, 95 % CI: 0.45, 1.18). Subgroup analysis indicates that all studies combined from middle-income countries have higher effect size (1.99, 95 % CI: 1.63, 2.35) than have studies from high-income countries (0.81, 95 % CI: 0.37, 1.26). The lower effect size in high-income countries may be due to differences in exposure levels, related to stricter regulation of emissions or more awareness/use of personal protective equipment in the working environment. Sensitivity analysis does not unequivocally link effect size to comet assay measurement bias, inferred by insufficient information on comet assay procedures, missing assay controls, non-blinded analysis of samples, or exposure misclassification. In conclusion, this systematic review and meta-analysis shows that exposure to heavy metals - lead, arsenic and chromium - is associated with increased levels of DNA strand breaks in human leukocytes.