Maternal inorganic mercury exposure and renal effects in the Wanshan mercury mining area, southwest China.

This study evaluated the relationship between urine mercury (UHg) concentrations and renal function (serum creatinine (SCr) and blood urea nitrogen (BUN)) in delivery women in the Wanshan mercury (Hg) mining area. Leishan County was selected as the control area. 165 and 65 maternal samples were collected from the Wanshan and Leishan area, respectively. The geometric means of UHg concentrations were 1.09 and 0.29 µg/L in Wanshan and Leishan subjects, respectively. Significant differences (p < 0.01) of UHg were observed between the two populations, indicating the potential risks of inorganic Hg exposure in the Wanshan population. The median (interquartile range) values of SCr were 69.1 (12.5) µmol/L and 46.0 (11.0) µmol/L for the Wanshan and Leishan populations, respectively, indicating significant differences (p < 0.01) between the two groups. However, no significant differences among BUN values for the two groups were observed. A significant positive correlation (r = 0.385, p < 0.001) was observed between UHg concentration and SCr in the study population. The odds ratio (OR) value of UHg in Wanshan area was 9.29 times higher than that in Leishan area (95% confidence interval (CI): 3.58-24.1). The OR value of SCr decrease in patients with low UHg was 0.32 times higher than that in patients with high UHg (95% CI: 0.19-0.55). The OR value of SCr decrease in the population with fish consumption was 0.71 times higher than that of the population without fish consumption (95% CI: 0.58-0.88). In conclusion, maternal IHg exposure caused impaired renal function and fish consumption may play a role in preventing Hg-induced nephrotoxicity.

Oxidative stress index is increased in children exposed to industrial discharges and is inversely correlated with metabolite excretion of voc.

Although the Atoyac River has been classified as highly polluted by environmental authorities, several communities are settled on its banks, affecting around 1.5 million persons, as well as farmland, due to an environmental distribution of toxics in the area. Our aim was to demonstrate that this environment affects important physiological processes that have an impact in health, so we conducted a study of schoolchildren from small communities on the banks of the river and in another similar town located far from it. 91 and 93 students, boys and girls, were studied from each site for oxidative stress index (OSI), calculated from the total antioxidant capacity and the total oxidative status, BTEX metabolite excretion and relevant metabolic polymorphisms participating in the bioactivation-detoxification of most VOC: CYP2E1 RsaI, NQO1 C609T, and null polymorphisms of GSTT1 and GSTM1. Results showed that OSI was significantly higher in children living by the river (5.23 ± 3.4 vs 2.59 ± 1.46, 95% C.I.). At this site, OSI was correlated with diminished metabolite excretion and a diminished antioxidant capacity; an association with genotypes CYP2E1RsaI (c2c2), GSTT1 present and NQO1*2 (CC) was also observed. Furthermore, boys at this site exhibited a diminished BMI compared to boys from the other community who were younger. IN CONCLUSION: children living at polluted sites like this, show early biological effects that might lead to health problems in their adult life. Environmental protection should be enforced to protect people's health in these sites where not even environmental monitoring is done. Environ. Mol. Mutagen. 59:639-652, 2018. © 2018 Wiley Periodicals, Inc.

A competitive immunoassay for ultrasensitive detection of Hg(2+) in water, human serum and urine samples using immunochromatographic test based on surface-enhanced Raman scattering.

An immunochromatographic test (ICT) strip was developed for ultrasensitive competitive immunoassay of Hg(2+). This strategy was achieved by combining the easy-operation and rapidity of ICT with the high sensitivity of surface-enhanced Raman scattering (SERS). Monoclonal antibody (mAb) against Hg(2+) and Raman active substance 4-mercaptobenzoic acid (MBA) dual labelled gold nanoparticles (GNPs) were prepared as an immunoprobe. The Raman scattering intensity of MBA on the test line of the ICT strip was measured for quantitative determination of Hg(2+). The ICT was able to directly detect Hg(2+) without complexing due to the specific recognition of the mAb with Hg(2+). The IC50 and limit of detection (LOD) of the assay for Hg(2+) detection were 0.12 ng mL(-1) and 0.45 pg mL(-1), respectively. There was no cross-reactivity (CR) of the assay with other nineteen ions and the ICT strips could be kept for 5 weeks without loss of activity. The recoveries of the assay for water, human serum and urine samples spiked with Hg(2+) were in range of 88.3-107.3% with the relative standard deviations (RSD) of 1.5-9.5% (n = 3). The proposed ICT was used for the detection of Hg(2+) in urine samples collected from Occupational Disease Hospital and the results were confirmed by cold-vapor atomic fluorescence spectroscopy (CV-AFS). The assay exhibited high sensitivity, selectivity, stability, precision and accuracy, demonstrating a promising method for the detection of trace amount of Hg(2+) in environmental water samples and biological serum and urine samples.

Lung inflammation biomarkers and lung function in children chronically exposed to arsenic.

Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases.

Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile.

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g., <200µg/L). In this study, urinary arsenic metabolites were measured in 94 lung and 117 bladder cancer cases and 347 population-based controls from areas in northern Chile with a wide range of drinking water arsenic concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.99-3.67), and 3.26 (1.76-6.04) (p-trend <0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.06-3.11), and 2.02 (1.15-3.54) (p-trend <0.001). In analyses confined to subjects only with arsenic water concentrations <200µg/L (median=60µg/L), lung and bladder cancer odds ratios for subjects in the upper tertile of %MMA compared to subjects in the lower two tertiles were 2.48 (1.08-5.68) and 2.37 (1.01-5.57), respectively. Overall, these findings provide evidence that inter-individual differences in arsenic metabolism may be an important risk factor for arsenic-related lung cancer, and may play a role in cancer risks among people exposed to relatively low arsenic water concentrations.

Application of electrolysis for detoxification of an antineoplastic in urine.

Antineoplastics in excreta from patients have been considered to be one of the origins of cytotoxic, carcinogenic, teratogenic, and mutagenic contaminants in surface water. Recent studies have demonstrated that antineoplastics in clinical wastewater can be detoxified by electrolysis. In this study, to develop a method for the detoxification of antineoplastics in excreta, methotrexate solution in the presence of human urine was electrolyzed and evaluated. We found that urine inhibits detoxification by electrolysis; however, this inhibition decreased by diluting urine. In urine samples, the concentrations of active chlorine generated by anodic oxidation from 0.9% NaCl solution for inactivation of antineoplastics increased in dilution-dependent and time-dependent manner. These results indicate that electrolysis with platinum-based iridium oxide composite electrode is a possible method for the detoxification of a certain antineoplastic in urine.

Prevalence of nickel sensitization and urinary nickel content of children are increased by nickel in ambient air.

In a cross-sectional study performed in 2000, an unexpected positive association between nickel (Ni) in ambient air, urinary Ni content and the prevalence of Ni sensitization in a subgroup of 6-yr-old children living near a steel mill was observed. Between 2005 and 2006, in a different and larger study population, we examined if Ni from ambient air or urinary Ni concentration was related to Ni sensitization in children living next to Ni-emitting steel mills. We studied 749 school beginners living in four Ni-polluted industrial areas of North Rhine-Westphalia, Germany. We assessed Ni in ambient air, Ni in urine from children and mothers, and Ni in tap water, conducted patch tests in children (including the NiSO(4)-dilution test) and collected questionnaire data. Statistics were done by linear and logistic regression analyses, adjusted for covariates. At increased Ni concentration in ambient air (unit of increase: 10 ng/m(3)), urinary Ni concentrations rose in both mothers (9.1%; 95% CI: 6.8-11.4%) and children (2.4%; 95% CI: 0.4-4.4%). The prevalence of Ni sensitization in children was associated with increased Ni from ambient air (unit of increase: 18 ng/m(3); odds ratio 1.28; 95% CI: 1.25-1.32) and urinary Ni concentration (unit of increase: 7.1 µg/L; odds ratio 2.4; 95% CI: 1.20-4.48). Ni in ambient air of areas with Ni-emitting factories contributes to internal Ni exposure in residents via inhalation and, furthermore, is a risk factor for the development of Ni sensitization in children.

Association of genetic variation in cystathionine-beta-synthase and arsenic metabolism.

Variation in individual susceptibility to arsenic-induced disease may be partially explained by genetic differences in arsenic metabolism. Mounting epidemiological evidence and in vitro studies suggest that methylated arsenic metabolites, particularly monomethylarsonic (MMA3), are more acutely toxic than inorganic arsenic; thus, MMA3 may be the primary toxic arsenic species. To test the role of genetic variation in arsenic metabolism, polymorphisms in genes involved in one-carbon metabolism [methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), cystathionine-beta-synthase (CBS), thymidylate synthase (TYMS), dihydrofolate reductase (DHFR), serine hydroxymethyltransferase 1 (SHMT1)] and glutathione biosynthesis [glutathione-S-transferase omega 1 (GSTO1)] were examined in an arsenic-exposed population to determine their influence in urinary arsenic metabolite patterns. In 142 subjects in Cordoba Province, Argentina, variant genotypes for CBS rs234709 and rs4920037 SNPs compared with wild-type homozygotes were associated with 24% and 26% increases, respectively, in the mean proportion of arsenic excreted as monomethylarsonic acid (%MMA). This difference is within the range of differences in %MMA seen between people with arsenic-related disease and those without such disease in other studies. Small inverse associations with CBS rs234709 and rs4920037 variants were also found for the mean levels of the proportion of arsenic excreted as dimethylarsinous acid (%DMA). No other genetic associations were found. These findings are the first to suggest that CBS polymorphisms may influence arsenic metabolism in humans and susceptibility to arsenic-related disease.

Cadmium dietary intake and biomarker data in French high seafood consumers.

Seafood and especially mollusks are known to be a rich source of cadmium (Cd), but little data are available concerning French seafood contamination and Cd exposure of French populations. The objective was then to assess food intake and biological level of Cd in high consumers of seafood, and to determine the impact of the consumption of self-fished mollusks on urinary Cd. Seafood consumption levels of 80 products were assessed for 1011 high consumers aged 18 and over in four French coastal areas, thanks to a validated food frequency questionnaire (FFQ). According to a total diet study approach, seafood samples were collected taking into account preservation methods and supply habits. Food samples were analyzed for Cd. Exposure was assessed by crossing consumption data with contamination data. Total blood and urine samples were collected from 380 subjects of the cohort and analyzed for Cd. The impact of the self-collected mollusks consumption on the Cd biological level adjusted for creatinine was assessed by a multivariate linear regression model. The mean dietary intake of Cd is 2.44+/-3.34 microg/kg bw/wk and the mean urinary Cd (U-Cd) level is 0.65+/-0.45 microg/g creatinine, and is significantly higher in women than in men (P<0.05). The consumption of self-fished mollusks is significantly negatively associated with U-Cd (r=-0.11 [-0.185, -0.009], P=0.03). The results of this study indicate that the biological Cd levels remain below the standards, and also suggest a protective effect of self-fishing, which inspires confidence about the high consumer health safety in terms of Cd exposure.

Speciation of key arsenic metabolic intermediates in human urine.

Biomethylation is the major human metabolic pathway for inorganic arsenic, and the speciation of arsenic metabolites is essential to a better understanding of arsenic metabolism and health effects. Here we describe a technique for the speciation of arsenic in human urine and demonstrate its application to the discovery of key arsenic metabolic intermediates, monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII), in human urine. The study provides a direct evidence in support of the proposed arsenic methylation pathway in the human. The finding of MMAIII and DMAIII in human urine, along with recent studies showing the high toxicity of these arsenicals, suggests that the usual belief of arsenic detoxification by methylation needs to be reconsidered. The arsenic speciation technique is based on ion pair chromatographic separation of arsenic species on a 3-micron particle size column at 50 degrees C followed by hydride generation atomic fluorescence detection. Speciation of MMAIII, DMAIII, arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) in urine samples is complete in 6 min with detection limits of 0.5-2 micrograms/L. There is no need for any sample pretreatment. The capability of rapid analysis of trace levels of arsenic species, which resulted in the findings of the key metabolic intermediates, makes the technique useful for routine arsenic speciation analysis required for toxicological and epidemiological studies.