Although it is a probable human carcinogen, propylene oxide is widely applied in industry and daily life. However, data on neurodevelopmental effects of propylene oxide exposure among children are extremely limited. We aimed to determine the urinary concentrations of propylene oxide metabolite among school-aged children and evaluate the potential association of propylene oxide exposure with risk of dyslexia. A total of 355 dyslexic children and 390 controls were recruited from three cities (Jining, Wuhan, and Hangzhou) in China, between 2017 and 2020. Urinary N-acetyl-S-(2-hydroxypropyl)-L-cysteine (i.e., 2-hydroxypropyl mercapturic acid; 2-HPMA) was measured as the biomarker of propylene oxide exposure. The detection frequency of 2-HPMA was 100%. After adjusting for potential confounders, the odds ratio (OR) for dyslexia per 2-fold increase in urinary 2-HPMA was 1.19 [95% confidence interval (95% CI): 1.01, 1.40, P = 0.042]. Compared with the lowest quartile of urinary 2-HPMA concentrations, children with the highest quartile of 2-HPMA had a 1.63-fold (95% CI: 1.03, 2.56, P = 0.036) significantly increased risk of dyslexia, with a dose-response relationship (P-trend = 0.047). This study provides epidemiological data on the potential association between propylene oxide exposure and the risk of dyslexia in children. Further studies are warranted to confirm the findings and reveal the underlying biological mechanisms.

The exposure of benzo [a]pyrene (BaP) in recent times is rather unavoidable than ever before. BaP emissions are sourced majorly from anthropogenic rather than natural provenance from wildfires and volcanic eruptions. A major under-looked source is via the consumption of foods that are deep-fried, grilled, and charcoal smoked foods (meats in particular). BaP being a component of poly aromatic hydrocarbons has been classified as a Group I carcinogenic agent, which has been shown to cause both systemic and localized effects in animal models as well as in humans; has been known to cause various forms of cancer, accelerate neurological disorders, invoke DNA and cellular damage due to the generation of reactive oxygen species and involve in multi-generational phenotypic and genotypic defects. BaP's short and accumulated exposure has been shown in disrupting the fertility of gamete cells. In this review, we have discussed an in-depth and capacious run-through of the various origins of BaP, its economic distribution and its impact as well as toxicological effects on the environment and human health. It also deals with a mechanism as a single compound and its ability to synergize with other chemicals/materials, novel sensitive detection methods, and remediation approaches held in the environment.

Arsenic, a class I human carcinogen, is ubiquitously found throughout the environment and around the globe, posing a great public health concern. Notably, Bangladesh and regions of West Bengal have been found to have high levels (0.5–4600 μg/L) of arsenic drinking water contamination, and approximately 50 million of the world’s 200 million people chronically exposed to arsenic in Bangladesh alone. This study was carried out to examine genome-wide gene expression changes in individuals chronically exposed to arsenic-contaminated drinking water. Our study population includes twenty-nine Bangladeshi female participants with urinary arsenic levels ranging from 22.32 to 1828.12 μg/g creatinine. RNA extracted from peripheral blood mononuclear cells (PBMCs) were evaluated using RNA-Sequencing analysis. Our results indicate that a total of 1,054 genes were significantly associated with increasing urinary arsenic levels (FDR p < 0.05), which include 418 down-regulated and 636 up-regulated genes. Further Ingenuity Pathway Analysis revealed potential target genes (DAPK1, EGR2, APP), microRNAs (miR-155, -338, −210) and pathways (NOTCH signaling pathway) related to arsenic carcinogenesis. The selection of female-only participants provides a homogenous study population since arsenic has significant sex dependent effects, and the wide exposure range provides new insight for key gene expression changes that correlate with increasing urinary arsenic levels.

Rice intake is a major route of oral exposure to inorganic arsenic (iAs), a known human carcinogen. The recent risk assessment on iAs in rice conducted by the US Food & Drug Administration (FDA) didn’t propose an action level for iAs in rice mainly because of the relatively low consumption rate in the general US population. However, this decision may not be applicable to high rice-intake populations, such as the Chinese population.The objective of this study was to probabilistically characterize the exposure of iAs via rice intake in Chinese population with a focus on the urban population.With the consideration of bioaccessibility of iAs in rice, iAs exposure is mainly determined by rice intake rate and iAs concentration in rice. To estimate the daily rice consumption, a dietary survey consisting of 1873 subjects was conducted in three major Chinese cities (Beijing, Guangzhou, and Hangzhou). Speciated As concentration in rice was measured using 480 rice samples collected from markets in these three cities. Monte Carlo simulation approach was applied to distributionally estimate the average daily dose (ADD) of iAs through rice intake.The estimated distribution of daily iAs exposure of the study population has a mean of 10.5 μg/day with a 95th percentile interval from 0.1 to 75.3 μg/day. The estimated distribution of ADD has a mean of 0.179 μg/kg/day with a 95th percentile interval from 0.001 to 1.224 μg/kg/day. Greater level of iAs exposure (due to higher rice intake) was observed in males than females, and in summer than other seasons with lower temperature. Geographically, the ADD of iAs exposure from rice intake reduces from south to north.About 13% of the Chinese urban population are exposed to iAs via rice intake higher than the Reference Dose (RfD) level.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants and hazardous to human health. Aflatoxin B1 (AFB1) is a strong carcinogen dependent on activation by cytochrome P450 (CYP) 1A2 and 3A4. Humans in some regions may be exposed to both PCBs and AFB1. Since PCBs are CYP inducers, we were interested in their combined genotoxicity. In this study, the effects of non-coplanar 2,3,3′-tri- (PCB 20), 2,2′5,5′-tetra- (PCB 52), 2,3,3′,4′-tetrachlorobiphenyl (PCB 56), and coplanar 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) on protein levels of CYP1A1, 1A2, and 3A4, and nuclear receptors AhR, CAR and PXR in a human hepatocyte (L-02) line were investigated. Moreover, the combined effects of each PCB and AFB1 for induction of micronuclei and double-strand DNA breaks (indicated by an elevation of γ-H2AX) were analyzed. The results indicated that PCBs 20, 52 and 56 reduced the expression of AhR, while elevated that of CAR and PXR, with thresholds at low micromolar concentrations. However, they were less potent than PCB 126, which was active at sub-nanomolar levels. Overexpression of human splice variant CAR 3 in the cells increased CYP1A2 and 3A4 levels, which were further enhanced by each non-coplanar PCB, suggesting a role of CAR in modulating CYPs. Pretreatment of cells with each test PCB potentiated both micronuclei formation and DNA damage induced by AFB1. This study suggests that both non-coplanar and coplanar PCBs may enhance the genotoxicity of AFB1, through acting on various nuclear receptors; the potentiation of AFB1 genotoxicity by PCBs and the potential health implications may deserve concerns and further investigation.

1,4-Dioxane is a probable human carcinogen and an emerging contaminant that has been detected in surface water and groundwater resources. Many conventional water treatment technologies are not effective for the removal of 1,4-dioxane due to its high water solubility and chemical stability. Biological degradation is a potentially low-cost, energy-efficient approach to treat 1,4-dioxane-contaminated waters. Two bacterial strains, Pseudonocardia dioxanivorans CB1190 (CB1190) and Mycobacterium austroafricanum JOB5 (JOB5), have been previously demonstrated to break down 1,4-dioxane through metabolic and co-metabolic pathways, respectively. However, both CB1190 and JOB5 have been primarily studied in laboratory planktonic cultures, while most environmental microbes grow in biofilms on surfaces. Another treatment technology, adsorption, has not historically been considered an effective means of removing 1,4-dioxane due to the contaminant's low Koc and Kow values. We report that the granular activated carbon (GAC), Norit 1240, is an adsorbent with high affinity for 1,4-dioxane as well as physical dimensions conducive to attached bacterial growth. In abiotic batch reactor studies, 1,4-dioxane adsorption was reversible to a large extent. By bioaugmenting GAC with 1,4-dioxane-degrading microbes, the adsorption reversibility was minimized while achieving greater 1,4-dioxane removal when compared with abiotic GAC (95–98% reduction of initial 1,4-dioxane as compared to an 85–89% reduction of initial 1,4-dioxane, respectively). Bacterial attachment and viability was visualized using fluorescence microscopy and confirmed by amplification of taxonomic genes by quantitative polymerase chain reaction (qPCR) and an ATP assay. Filtered samples of industrial wastewater and contaminated groundwater were also tested in the bioaugmented GAC reactors. Both CB1190 and JOB5 demonstrated 1,4-dioxane removal greater than that of the abiotic adsorbent controls. This study suggests that bioaugmented adsorbents could be an effective technology for 1,4-dioxane removal from contaminated water resources.

Activation of the aryl hydrocarbon receptor (AhR)-mediated activity is one of key events in toxicity of polycyclic aromatic hydrocarbons (PAHs). Although various classes of AhR ligands may differentially activate human and rodent AhR, there is presently a lack of data on the human AhR-inducing relative potencies (REPs) of PAHs. Here, we focused on estimation of the AhR-mediated activities of a large set of environmental PAHs in human gene reporter AZ-AhR cell line, with an aim to develop the human AhR-based REP values with potential implications for risk assessment of PAHs. The previously identified weakly active PAHs mostly failed to activate the AhR in human cells. The order for REPs of individual PAHs in human cells largely corresponded with the available data from rodent-based experimental systems; nevertheless, we identified differences up to one order of magnitude in REP values of PAHs between human and rodent cells. Higher REP values were found in human cells for some important environmental contaminants or suspected carcinogens, such as indeno[1,2,3-cd]pyrene, benz[a]anthracene or benzo[b]fluoranthene, while lower REP values were determined for methyl-substituted PAHs. Our results also indicate that a different rate of metabolism for individual PAHs in human vs. rodent cells may affect estimation of REP values in human cell-based assay, and potentially alter toxicity of some compounds, such as benzofluoranthenes, in humans. We applied the AZ-AhR assay to evaluation of the AhR-mediated activity of complex mixtures of organic compounds associated with diesel exhaust particles, and we identified the polar compounds present in these mixtures as being particularly highly active in human cells, as compared with rodent cells. The present data suggest that differences may exist between the AhR-mediated potencies of PAHs in human and rodent cells, and that the AhR-mediated effects of polar PAH derivatives and metabolites in human cell models deserve further attention.

The environmental dioxin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a Group 1 human carcinogen and teratogenic agent. We hypothesize that TCDD-induced oxidative stress may also interfere with mitochondrial ATP-sensitive potassium channels (mitoKATP), which are known to regulate and to be regulated by mitochondrial redox state. We investigated the effects of an acute treatment of male Wistar rats with TCDD (50 μg/kg i.p.) and measured the regulation of cardiac mitoKATP. While the function of cardiac mitochondria was slightly depressed, mitoKATP activity was 52% higher in animals treated with TCDD. The same effects were not observed in liver mitochondria isolated from the same animals. Our data also shows that regulation of mitochondrial ROS production by mitoKATP activity is different in both groups. To our knowledge, this is the first report to show that TCDD increases mitoKATP activity in the heart, which may counteract the increased oxidative stress caused by the dioxin during acute exposure.

The oral bioaccessibility and the human health risks of As, Hg and other metals (Cu, Pb, Zn, Ni, Co, Cd, Cr, Mn, V and Fe) in urban street dusts from different land use districts in Nanjing (a mega-city), China were investigated. Both the total contents and the oral bioaccessibility estimated by the Simple Bioaccessibility Extraction Test (SBET) of the studied elements varied with street dusts from different land use districts. Cd, Zn, Mn, Pb, Hg and As showed high bioaccessibility. SBET-extractable contents of elements were significantly correlated with their total contents and the dust properties (pH, organic matter contents). The carcinogenic risk probability for As and Cr to children and adults were under the acceptable level (<1 × 10⁻⁴). Hazard Quotient values for single elements and Hazard Index values for all studied elements suggested potential non-carcinogenic health risk to children, but not to adults.