Our previous research showed that endosulfan triggers the extrinsic coagulation pathway by damaging endothelial cells and causes hypercoagulation of blood. To identify the mechanism of endosulfan-impaired endothelial cells, we treated human umbilical vein endothelial cells (HUVECs) with different concentrations of endosulfan, with and without an inhibitor for Notch, N-[N-(3, 5-difluorophenacetyl)-1-alanyl]S-Phenylglycinet-butylester (DAPT, 20 μM), or a reactive oxygen species (ROS) scavenger, N-Acetyl-l-cysteine (NAC, 3 mM), for 24 h. The results showed that endosulfan could inhibit cell viability/proliferation by increasing the release of lactate dehydrogenase (LDH), arresting the cell cycle in both S and G2/M phases, and inducing apoptosis in HUVECs. We also found that endosulfan can damage microfilaments, microtubules, and nuclei; arrest mitosis; remarkably increase the expressions of Dll4, Notch1, Cleaved-Notch1, Jagged1, Notch4, Hes1, and p21; and significantly induce ROS and malondialdehyde production in HUVECs. The presence of DAPT antagonized the above changes of cycle arrest, proliferation inhibition, and expressions of Dll4, Notch1, Cleaved-Notch1, Hes1, and p21 caused by endosulfan; however, NAC could attenuate LDH release; ROS and malondialdehyde production; apoptosis; and the expression levels of Dll4, Notch1, Cleaved-Notch1, Notch4, and Hes1 induced by endosulfan. These results demonstrated that endosulfan inhibited proliferation through the Notch signaling pathway as a result of oxidative stress. In addition, endosulfan can damage the cytoskeleton and block mitosis, which may add another layer of toxic effects on endothelial cells.

Exposure to trihalomethanes (THMs) and haloacetic acids (HAAs) has been individually associated with adverse male reproductive effects; however, their joint male reproductive toxicity is largely unknown. This study aimed to explore the joint effects of THMs and trichloroacetic acid (TCAA) on semen quality in a Chinese population. A total of 337 men presenting to the Reproductive Center of Tongjing Hospital, in Wuhan, China to seek semen analysis were included this study. Baseline blood THMs [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and urinary TCAA were analyzed and dichotomized at their median levels. The joint effects of THMs and TCAA on below-reference semen quality parameters were evaluated by calculating the relative excess risk due to interaction (RERI). After adjusting for potential confounders, we found a suggestive synergistic effect between Br-THMs (sum of BDCM, DBCM, and TBM) and TCAA for below-reference sperm count (RERI = 2.14, 95% CI: −0.37, 4.91) (P = 0.076); men with high Br-THMs and TCAA levels (above the median) had 3.31 times (95% CI: 1.21, 9.07) elevated risk of having below-reference sperm count than men with low Br-THMs and TCAA levels (below the median). No apparent joint effects were observed between THMs and TCAA for other semen quality parameters. Our results suggest that co-exposure to Br-THMs and TCAA is associated with additive effects on decreased semen quality. However, further studies in a larger sample size and mechanistic studies are needed to confirm the findings.

We investigated mercury (Hg) concentrations in small fish (mainly yellow perch, Perca flavescens; ∼60% of fish collected) and in blood of common loons (Gavia immer) that prey upon them during the breeding season on lakes in 4 large, widely separated study areas in Canada (>13 lakes per study area; total number of lakes = 93). Although surface sediments from lakes near a base metal smelter in Flin Flon, Manitoba had the highest Hg concentrations, perch and other small fish and blood of common loon chicks sampled from these same lakes had low Hg concentrations similar to those from uncontaminated reference lakes. Multiple regression modeling with AIC analysis indicated that lake pH was by far the most important single factor influencing perch Hg concentrations in lakes across the four study areas (R2 = 0.29). The best model was a three-variable model (pH + alkalinity + sediment Se; Wi = 0.61, R2 = 0.85). A single-variable model (fish Hg) best explained among-lake variability in loon chick blood Hg (Wi = 0.17; R2 = 0.53). From a toxicological risk perspective, all lakes posing a potential Hg health risk for perch and possibly other small pelagic fish species (where mean fish muscle Hg concentrations exceeded 2.4 μg/g dry wt.), and for breeding common loons (where mean fish muscle Hg concentrations exceeded 0.8 μg/g dry wt., and loon chick blood Hg exceeded 1.4 μg/g dry wt.) had pH < 6.7 and were located in eastern Canada.

Stable Pb isotope ratios (Pb-IRs) have been recognized as an efficient tool for identifying sources. This study carried out at Kabwe mining area, Zambia, to elucidate the presence or absence of Pb isotope fractionation in goat and chicken, to evaluate the reliability of identifying Pb pollution sources via analysis of Pb-IRs, and to assess whether a threshold for blood Pb levels (Pb-B) for biological fractionation was present. The variation of Pb-IRs in goat decreased with an increase in Pb-B and were fixed at certain values close to those of the dominant source of Pb exposure at Pb-B > 5 μg/dL. However, chickens did not show a clear relationship for Pb-IRs against Pb-B, or a fractionation threshold. Given these, the biological fractionation of Pb isotopes should not occur in chickens but in goats, and the threshold for triggering biological fractionation is at around 5 μg/dL of Pb-B in goats.

Blood lead (Pb) level of children has widely been attracting public concern in China, particularly in the sites near mining or industrial areas. However, the policies about how to efficiently reduce the Pb intake of children are still under discussion. We collected six food types based on the local dietary habits and soils from Dexing, Leping, and Poyang Counties situated along the Le'an River Basin from upstream to downstream, and their Pb contents were analyzed. A Monte Carlo model was used to simulate the dietary chronic daily intake of Pb (CDIPb) from various foods and ingested soil by hand-to-mouth activities and its non-carcinogenic risk to children indicated by hazard quotient (HQ). Only in the rural area of Dexing, its soil and vegetables both had higher Pb content than the national tolerance limits of China, resulting its the highest CDIPb among all the areas. The Pb contents of the six food types and soils in other sites were overall below the limits. Vegetables and rice accounted for from 63% (Leping, urban) to 85% (Dexing, rural) of the total CDIPb and ingested soil overall took up ∼6%. In the rural area, Dexing had the highest proportion (82.8%) of children with HQ > 1, followed by Leping (36.1%) and Poyang (27.7%). Different order was found in the urban areas, i.e. Dexing (46.7%) > Poyang (41.0%) > Leping (26.4%). Vegetables and rice were overall the two major contributors to the total CDI of Pb, which should be focused on to control the Pb intake by the local children, especially for those living in the rural area of Dexing County.

Exposure to benzene is inevitable, and concerns regarding the adverse health effects of benzene have been raised. Most investigators found that benzene exposure induced hematotoxicity. In this regard, Our study aimed to explore a novel potential biomarker of adverse health effects following benzene exposure and the toxic mechanisms of benzene metabolites in vitro. This study consisted of 314 benzene-exposed workers and 288 control workers, an air benzene concentration of who were 2.64 ± 1.60 mg/m3 and 0.05 ± 0.01 mg/m3, respectively. In this population-based study, miR-34a expression was elevated in benzene-exposed workers. The correlation of miR-34a with the airborne benzene concentration, S-phenylmercapturic acid (S-PMA) and trans, trans-muconic acid (t, t-MA), all of which reflect benzene exposure, was found. Correlation analysis indicated that miR-34a was associated with peripheral blood count, alanine transaminase (ALT) and oxidative stress. Furthermore, multivariate analysis demonstrated that miR-34a expression was strongly associated with white blood cell count (structure loadings = 0.952). In population-based study, miR-34a had the largest contribution to altered peripheral blood counts, which reflect benzene-induced hematotoxicity. The role of miR-34a in benzene toxicity was assessed using lentiviral vector transfection. Results revealed that 1,4-benzoquinone induced abnormal cell apoptosis and simultaneously upregulated miR-34a accompanied with decreased Bcl-2. Finally, inhibition of miR-34a elevated Bcl-2 and decreased 1,4-benzoquinone-induced apoptosis. In conclusion, miR-34a was observed to be involved in benzene-induced hematotoxicity by targeting Bcl-2 and could be regarded as a potential novel biomarker for benzene toxicity.

Metals and metalloids are natural components of the biosphere, which are not produced per se by human beings, but whose form and distribution can be affected by human activities. Like all substances, they are a contaminant if present in excess compared to background levels and/or in a form that would not normally occur in the environment. Samples of liver, gills, gonads and muscle from European chub, Squalius cephalus, were analyzed for Al, As, B, Ba, Cr, Cu, Fe, Hg, Mn, Mo, Sr and Zn using inductively coupled plasma optical emission spectrometry (ICP-OES) to highlight the importance of tissue selection in monitoring research. The comet assay or single cell gel electrophoresis (SCGE) was selected as an in vivo genotoxicity assay, a rapid and sensitive method for measuring genotoxic effects in blood, liver and gills of the European chub. Microscopic images of comets were scored using Comet IV Computer Software (Perceptive Instruments, UK).The objective of our study was to investigate two reservoirs, Zlatar and Garasi, and one river, Pestan by: (i) determining and comparing metal and metalloid concentrations in sediment, water and tissues of European chub: liver, gills, muscle and gonads (ii) comparing these findings with genotoxicity of water expressed through DNA damage of fish tissues.A clear link between the level of metals in water, sediment and tissues and between metal and genotoxicity levels at examined sites was not found. This suggests that other xenobiotics (possibly the organic compounds), contribute to DNA damage.

Seabirds are ideal model organisms to track mercury (Hg) through marine food webs as they are long-lived, broadly distributed, and are susceptible to biomagnification due to foraging at relatively high trophic levels. However, using these species as biomonitors requires a solid understanding of the degree of species, sexual and age-specific variation in foraging behaviors which act to mediate their dietary exposure to Hg. We combined stomach content analysis along with Hg and stable isotope analyses of blood, feathers and common prey items to help explain inter and intra-specific patterns of dietary Hg exposure across three sympatric Pygoscelis penguin species commonly used as biomonitors of Hg availability in the Antarctic marine ecosystem. We found that penguin tissue Hg concentrations differed across species, between adults and juveniles, but not between sexes. While all three penguins species diets were dominated by Antarctic krill (Euphausia superba) and to a lesser extent fish, stable isotope based proxies of relative trophic level and krill consumption could not by itself sufficiently explain the observed patterns of inter and intra-specific variation in Hg. However, integrating isotopic approaches with stomach content analysis allowed us to identify the relatively higher risk of Hg exposure for penguins foraging on mesopelagic prey relative to congeners targeting epipelagic or benthic prey species. When possible, future seabird biomonitoring studies should seek to combine isotopic approaches with other, independent measures of foraging behavior to better account for the confounding effects of inter and intra-specific variation on dietary Hg exposure.

Lead poisoning, through the ingestion of spent lead gunshot, is an established cause of morbidity and mortality in waterbirds globally, but the thresholds at which blood levels begin to affect the physiology of birds in the wild are less well known. Here we determine the prevalence of lead exposure in whooper swans and, for the first time, identify the level of blood lead associated with initial reductions in body condition. Blood lead elevated above background levels (i.e. >20 μg dL⁻¹) was found in 41.7% (125/300) of swans tested. Blood lead was significantly negatively associated with winter body condition when levels were ≥44 μg dL⁻¹ (27/260 = 10%). Our findings indicating that sub-lethal impacts of lead on body condition occur at the lower end of previously established clinical thresholds and that a relatively high proportion of individuals in this population may be affected, reaffirm the importance of reducing contamination of the environment with lead shot.