Urinary Total Arsenic Levels Research Articles

Association between urinary arsenic levels and kidney damage in US adults: NHANES 2007–2018

BackgroundChronic arsenic exposure is known to be associated with various diseases by inducing multiple organ dysfunctions. Despite the high prevalence of kidney diseases in the US and globally, population-level research on the link between inorganic arsenic and kidney damage remains limited. In our study, we assessed the association between urinary arsenic levels and kidney damage among US adults using a multi-marker approach. MethodsWe analyzed data from the National Health and Nutrition Examination Survey (2007–2018). Multivariable logistic regression models were employed to estimate the odds ratios (ORs) for kidney damage based on total urinary arsenic levels and multiple kidney biomarkers, including albuminuria, low estimated glomerular filtration rate (eGFR), hyperuricemia, and elevated blood urea nitrogen (BUN), while adjusting for demographic, socioeconomic, and other risk factors. Total urinary arsenic levels were calculated by summing the levels of arsenous acid (As3), arsenic acid (As5), and their methylated metabolites, monomethylarsinic acid (MMA), and dimethylarsinic acid (DMA). Dimethylarsinic acid (DMA) was calibrated for arsenobetaine using a residual regression method to minimize the influence of seafood-related exposure. ResultsAfter adjusting for covariates, we observed 1.29-fold higher odds (95 % CI 1.01, 1.64) of kidney damage in the highest quartile of urinary arsenic compared to the lowest quartile. Specifically, the odds of albuminuria and hyperuricemia were 1.49-fold (95 % CI 1.09, 2.03) and 1.38-fold (95 % CI 1.01, 1.88) higher, respectively, in the highest quartile. Additionally, for every one-unit increase in the natural log of arsenic levels, significant associations were observed for overall kidney damage (OR 1.10, 95 % CI 1.01, 1.20), albuminuria (OR 1.15, 95 % CI 1.03, 1.29), and hyperuricemia (OR 1.12, 95 % CI 1.02, 1.24) when considering arsenic levels in drinking water as a continuous variable. ConclusionOur study concludes that higher urinary arsenic levels are positively associated with kidney damage. Further prospective studies are needed to confirm these findings.

Exposure to Arsenic and Subclinical Cardiovascular Disease in 9- to 11-Year-Old Children, Syracuse, New York

Studies in adults have demonstrated associations between arsenic exposure and clinical and subclinical cardiovascular disease (CVD). No studies to date have considered potential associations in children. To examine the association between total urinary arsenic levels in children and subclinical indicators of CVD. This cross-sectional study considered 245 children, a subset from the Environmental Exposures and Child Health Outcomes (EECHO) cohort. Children from the Syracuse, New York, metropolitan area were recruited from August 1, 2013, until November 30, 2017, with enrollment throughout the year. Statistical analysis was performed from January 1, 2022, to February 28, 2023. Total urinary arsenic was measured using inductively coupled plasma mass spectrometry. Creatinine concentration was used to adjust for urinary dilution. In addition, potential exposure routes (eg, diet) were measured. Three indicators of subclinical CVD were assessed: carotid-femoral pulse wave velocity, carotid intima media thickness, and echocardiographic measures of cardiac remodeling. The study sample included 245 children aged 9 to 11 years (mean [SD] age, 10.52 [0.93] years; 133 [54.3%] female). The geometric mean of the creatinine-adjusted total arsenic level in the population was 7.76 μg/g creatinine. After adjustment for covariates, elevated total arsenic levels were associated with significantly greater carotid intima media thickness (β = 0.21; 95% CI, 0.08-0.33; P = .001). In addition, echocardiography revealed that elevated total arsenic was significantly higher for children with concentric hypertrophy (indicated by greater left ventricular mass and greater relative wall thickness; geometric mean, 16.77 μg/g creatinine; 95% CI, 9.87-28.79 μg/g) relative to the reference group (geometric mean, 7.39 μg/g creatinine; 95% CI, 6.36-8.58 μg/g). With respect to exposure source, significant geographic clustering of total arsenic was found in 1 urban area of Syracuse, New York. These findings suggest a significant association between arsenic exposure and subclinical CVD in children. Elevated total arsenic levels were found in an area of Syracuse with known elevations of toxic metals from industrial waste, suggesting historical pollution as a possible source. Given the novelty and potential importance of this association, further research is needed to confirm our findings. Any potential effect of urinary arsenic exposure in childhood on actual clinical CVD outcomes in adulthood remains to be determined.

Dietary contribution to total urinary arsenic in Mexican women

Exposure to inorganic arsenic (iAs) damages health in many ways. The main routes of human exposure are consumption of contaminated water and diet, but evidence regarding the dietary contribution of iAs is limited. The objective of this work was to determine the foods and beverages that contribute to urinary total arsenic levels (TAs). This is a secondary analysis of an original study of breast cancer cases and population controls carried out in northern Mexico during the period 2007–2011, from which 1,462 women without a history of diabetes were selected. We estimated the consumption of the food and beverage groups with a frequency questionnaire. We measured the concentrations of urinary iAs metabolites by high performance liquid chromatography inductively coupled plasma mass spectrometry (HPLC-ICP-MS). Total arsenic ranged from 0.5 to 2,360 µg/g creatinine. After adjusting for covariates, we observed a positive association between TAs (with arsenobetaine) with non-bottled drinking water intake, as well as the consumption of root vegetables, vegetables and fruits rich in water, eggs, fish and shellfish. Our findings highlight the relevance of water consumption and some foods for TAs exposure. Food quality monitoring deserves attention in high-risk regions of arsenic contamination.

Associations between Plasma Folate and Vitamin B12, Blood Lead, and Bone Mineral Density among Adults and Elderly Who Received a Health Examination.

This study hypothesized that plasma folate and vitamin B12 levels modified the association between blood lead and cadmium and total urinary arsenic levels and bone loss. A total of 447 study subjects who received a physical examination at the Wanfang Hospital Medical Center were recruited. Bone loss was defined as a calcaneus bone mineral density T-score less than −1. Blood cadmium and lead concentrations were measured by ICP-MS. Urinary arsenic species were determined using HPLC-HG-AAS. A SimulTRAC-SNB radioassay was used to measure plasma folate, vitamin B12, and homocysteine levels. Total urinary arsenic and blood lead concentration were positively correlated with the odds ratio (OR) for bone loss in a dose–response manner. The OR and 95% confidence interval (CI) for bone loss in participants with blood lead concentrations > 56.14 versus ≤33.82 μg/dL were 1.82 and 1.10–3.01. No correlation between plasma folate and vitamin B12 levels alone and bone loss was observed. However, this study is the first observational study to find that blood lead concentrations tend to increase the OR of bone loss in a low plasma folate and plasma vitamin B12 group with multivariate ORs (95% CI) of 2.44 (0.85–6.96).

Alcohol Consumption Moderated the Association Between Levels of High Blood Lead or Total Urinary Arsenic and Bone Loss.

Metal exposure and lifestyle are important risk factors for osteoporosis. Our study aimed to investigate the association between red blood cell lead and cadmium, total urinary arsenic, and plasma selenium levels and bone mineral density (BMD). In addition, we explored whether alcohol and coffee consumption modified the association between BMD and metals and metalloids. In total, 437 participants who underwent adult or senile physical examinations were recruited. Bone loss was defined as a calcaneus BMD T-score of <-1. Blood cadmium and lead and plasma selenium levels were measured using inductively coupled plasma mass spectrometry. Levels of urinary arsenic species were determined using high-performance liquid chromatography–hydride generator–atomic absorption spectrometry. The total urinary arsenic level was defined as the sum of the levels of urinary arsenic species. The BMD T-scores decreased significantly with increasing blood lead levels. The BMD T-scores also showed a downward trend with increasing total urinary arsenic levels. The odds ratio (OR) and 95% confidence interval (CI) for bone loss in patients with blood lead levels >57.58 versus 35.74 μg/dL were 1.98 and 1.17–3.34. In addition, the greater the lead or arsenic exposure and alcohol intake was the higher the OR for bone loss with multivariate ORs of 2.57 (95% CI 1.45–4.56) and 2.96 (95% CI 1.67–5.22), respectively. To the best of our knowledge, this study is the first to demonstrate that high total urinary arsenic or blood lead levels and frequent or occasional alcohol consumption had a significant multiplicative interaction for increasing the OR for bone loss.

Plasma Vitamin B12 and Folate Alter the Association of Blood Lead and Cadmium and Total Urinary Arsenic Levels with Chronic Kidney Disease in a Taiwanese Population.

Heavy metals causing chronic nephrotoxicity may play a key role in the pathogenesis of chronic kidney disease (CKD). This study hypothesized that plasma folate and vitamin B12 would modify the association of CKD with total urinary arsenic and blood lead and cadmium levels. We recruited 220 patients with CKD who had an estimated glomerular filtration rate of <60 mL/min/1.73 m2 for ≥3 consecutive months and 438 sex- and age-matched controls. We performed inductively coupled plasma mass spectrometry to measure blood cadmium and lead levels. The urinary arsenic level was determined using a high-performance liquid chromatography–hydride generator–atomic absorption spectrometry. Plasma vitamin B12 and folate levels were measured through the SimulTRAC-SNB radioassay. Compared with patients with plasma vitamin B12 ≤ 6.27 pg/mL, the odds ratio (OR) and 95% confidence interval of CKD for patients with plasma vitamin B12 > 9.54 pg/mL was 2.02 (1.15–3.55). However, no association was observed between plasma folate concentration and CKD. A high level of plasma vitamin B12 combined with high levels of blood lead and cadmium level and total urinary arsenic tended to increase the OR of CKD in a dose-response manner, but the interactions were nonsignificant. This is the first study to demonstrate that patients with high plasma vitamin B12 level exhibit increased OR of CKD related to high levels of blood cadmium and lead and total urinary arsenic.

Abstract 857: Evaluating the relationship between arsenic exposure and cancer risk in Canada

Abstract Background: Arsenic is an established carcinogen for cancers of the skin, bladder and lungs; it is also the most prevalent environmental toxin, resulting in all Canadians being exposed to some extent. In a recent prospective study of a low-exposure population, our team found that women in the highest quartile of circulating arsenic had a significant 13-fold increased risk of developing breast cancer, compared to the lowest quartile. This suggests that even at low-doses, arsenic may be an important risk factor for breast, and potentially other cancers not previously recognized. To date, the sources of arsenic in Canada, a low-exposure population, are unclear. Objectives: To describe the status of arsenic exposure, identify the key predictors of arsenic status, and evaluate the relationship between arsenic exposure and cancer risk within the Canadian population. Methods: Using data from Cycles 1-5 (2007-2017) of the Canadian Health Measures Survey (CHMS), exposure data (e.g., diet, water), demographic information, and urinary arsenic biomarkers will be analyzed. The CHMS is an ongoing, nationally representative survey, collecting objective health measures and food intake information from participants in biennial cycles. Data will be described using weighted percentages or means, and arsenic levels (total and speciated urinary arsenic metabolite concentrations) will be reported by percentile. Weighted multivariate regression models will be used to identify predictors of total urinary arsenic. Linkage to the Canadian Cancer Registry will be performed to ascertain incident cancers, and Cox proportional hazards regression used to estimate the relationship between arsenic status and cancer risk (total and site-specific). Results: This analysis included 15,700 individuals, aged 18-80. The median total urinary arsenic level was 7.5 ug/g of creatinine. Significant predictors of total urinary arsenic levels were found to be weekly intake of fish and seafood (β= 0.3, 95%CI 0.27,0.33, P &amp;lt; 0.001), grains (β=-0.02, 95%CI -0.02, -0.01, P&amp;lt; 0.001) and consumption of well and/or cistern water (β = 0.13, 95%CI 0.04, 0.22, P=0.005). Linkage and data analysis are ongoing. Impact: This work is the first to ascertain national exposure estimates to an environmental carcinogen. Fish, seafood, grains, and consumption of well and/or cistern water represent significant predictors of total urinary arsenic levels in Canada. Ultimately, this information is needed to develop critical population-level intervention strategies to reduce the Canadian, and global burden of cancer. Citation Format: Katherine Pullella, Shelley A. Harris, John R. McLaughlin, Jan Lubinski, Steven A. Narod, Joanne Kotsopoulos. Evaluating the relationship between arsenic exposure and cancer risk in Canada [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 857.

Arsenic Exposure and Melanoma Among US Adults Aged 20 or Older, 2003-2016.

Chronic exposure to arsenic has been reported as a risk factor for nonmelanoma skin cancer, notably squamous cell carcinoma. However, current knowledge is limited about the association between arsenic exposure and melanoma. Our objectives were to (1) measure the association between total urinary arsenic levels and melanoma compared with nonmelanoma skin cancer and no cancer and (2) analyze the association between water source and melanoma and nonmelanoma skin cancer. We collected cross-sectional data from the 2003-2016 cycles of the National Health and Nutrition Examination Survey. We conducted univariate and multivariate logistic regressions. To evaluate the possible association of skin cancer with source of tap water, we calculated odds ratios for participants with melanoma and nonmelanoma skin cancer, compared with participants with no cancer. White race, higher education, higher socioeconomic status, and smoking history were associated with melanoma and nonmelanoma skin cancer in the full study population. After adjusting for age and race/ethnicity, the adjusted odds ratio of participants with >50 μg/L of total urinary arsenic for melanoma or nonmelanoma skin cancer was 1.87 (95% CI, 0.58-6.05) and 2.23 (95% CI, 1.12-4.45) times higher compared with no cancer, respectively. Participants with nonmelanoma skin cancer had 2.06 increased odds of reporting a nonmunicipal water source compared with participants without cancer. We did not find a relationship between the incidence of melanoma and exposure to arsenic among US adults. Nonmunicipal water sources were associated with nonmelanoma skin cancer and should be further investigated.

S1065 Arsenic Exposure and Risk of Liver Injury Among U.S. Adults: An Association Modified by Gender

INTRODUCTION: Arsenic has toxic effects on multiple organ systems; however, arsenic toxicity on the liver has not been well explored. Therefore, we examined the association between arsenic exposure and serum ALT, a marker for liver injury and effect modification by gender. METHODS: Individuals >19 years of age from 7 cycles of the National Nutrition and Health Examination Survey (NHANES 2003–16) were included. Associations between serum ALT and creatinine-standardized urinary concentrations of total and 7 arsenic forms were examined. Data were summarized with mean (standard deviation) or frequencies. Urinary arsenic and serum ALT were log-transformed due to right-skewed distributions. We used survey-weighted linear regression without and with adjustments for gender, age, diabetes, hypertension, race, smoking, alcohol use, estimated GFR, and body mass index(BMI). Effect-modification by gender was examined by with an interaction term between gender and arsenic forms. RESULTS: Of the 12,439 participants, 52% were females, 33% hypertensives, 9% were diabetics, 54% were non-smokers, and 68% were whites. The mean age was 48 years. BMI 29 Kg/m2, ALT 26 U/L, and total urinary arsenic 18.4 ug/L. As compared to females, males had significantly higher ALT (30.3 vs 21.9; P < 0.001) and total urinary arsenic levels (19.7 vs 17.3 P = 0.02). In adjusted models, each 10% increase in urinary total arsenic, dimethylarsonic acid, trimethylarsine oxide was associated with 0.1%, 0.4%, and 0.2% increase in serum ALT respectively (all P-values< 0.01); ALT increase with other urinary arsenic forms was not significant. Females had larger increases in ALT than males for 5 arsenic forms; for each 10% increase in arsenous acid, arsenic acid, arsenocholine, monomethylarsonic acid, and dimethylarsenic acid were associated with 0.3%, 0.6%, 0.4%, 0.6%, and 0.4% larger increase in ALT than males (all P < 0.05) (Figure). CONCLUSION: Urinary arsenic levels within an acceptable range (total urinary arsenic< 100ug/L) are associated with a small but significant risk of liver injury as measured by elevation in serum ALT. Females are particularly at a higher risk of liver injury than males. The clinical significance of this liver injury needs examination in longitudinal studies.Figure 1

Effect of plasma selenium, red blood cell cadmium, total urinary arsenic levels, and eGFR on renal cell carcinoma

High total urinary arsenic concentrations and low estimated glomerular filtration rate (eGFR) increase the risk of renal cell carcinoma (RCC). This study aimed to determine whether other metals or metalloids can affect RCC. A total of 401 patients with RCC and 774 age- and sex-matched controls were recruited between November 2006 and December 2012 in Taiwan. Surgical resection or image-guided biopsy of renal tumors was performed to pathologically verify RCC. High-performance liquid chromatography linked to a hydride generator and atomic absorption spectrometer were used to measure the urinary arsenic species concentrations. Inductively coupled plasma mass spectrometry was used to determine plasma selenium and red blood cell cadmium and lead concentration. Plasma selenium levels were inversely related to RCC, whereas red blood cell cadmium levels were directly related to RCC. The odds ratio (OR) and 95% confidence interval (CI) were 0.14 (95% CI, 0.10–0.20) and 1.33 (95% CI, 1.03–1.72), respectively. A low plasma selenium level tended to interact with high total urinary arsenic levels or with high red blood cell cadmium concentration to increase the OR of RCC. In particular, low eGFR multiplicatively interacted with high red blood cell cadmium concentration to increase the OR of RCC (Pinteraction=0.003). This study was the first to find a significant multiplicative interaction between eGFR and the red blood cell cadmium levels on the increased OR of RCC.

Polymorphism of nucleotide binding domain-like receptor protein 3 (NLRP3) increases susceptibility of total urinary arsenic to renal cell carcinoma

Our study showed that total urinary arsenic concentrations were positively correlated with renal cell carcinoma (RCC). Chronic inflammation is a key player in the development of RCC. This study explored the association between nucleotide-binding domain-like receptor protein 3 (NLRP3) genotypes and the development of RCC. We also investigated whether any of the NLRP3 genotypes modified the risk between arsenic and RCC. We recruited 350 RCC patients and 700 age-sex matched controls. RCC was confirmed by pathological assessment following surgical resection or image-guided biopsy of a renal tumor. Fifteen sites of NLRP3 gene polymorphisms were identified using the Agena Bioscience MassARRAY platform. The concentrations of the urinary arsenic species were determined by HPLC-HG-AAS. There was a significant dose-dependent association between arsenic and RCC. In addition, six of thirteen NLRP3 alleles, including rs12239046 C, rs10925025 G, rs1539019 C, rs10925026 A, rs10157379 T, and rs12143966 A, had increased odds ratios (ORs) for RCC than other NLRP3 alleles. Among these sites, we found the novel haplotype of five tag-SNPs (C-A-A-A-A) was significantly related to RCC, the OR and 95% confidence interval was 1.44 (1.08–1.92). Furthermore, participants with high total urinary arsenic levels and the NLRP3 rs1539019 C allele had significantly multiplicative and additive interactions for the risk of RCC (p interaction = 0.012). This study is the first to identify the modified effects of NLRP3 risk alleles involved in the association between arsenic and RCC risk in a population with low arsenic exposure.

Measurement of urinary arsenic profiles and DNA hypomethylation in a case-control study of urothelial carcinoma.

Environmental exposure to arsenic may be involved in the disturbance of DNA hypomethylation. The aim of this study is the first to explore the effect of interactions of urinary total arsenic levels, arsenic methylation capacity, 8-hydroxy-2'-deoxyguanosine (8-OHdG), plasma folate, and global 5-methyl-2'-deoxycytidine (5-MedC) levels on the risk of urothelial carcinoma (UC). A hospital-based case-control study was constructed. The research involved the histological recruitment and pathological verification of 178 UC patients and 356 age-/sex-matched controls without prior history of cancer. Arsenic species were determined by high-performance liquid chromatography (HPLC)-hydride generation and atomic absorption. 5-MedC levels were detected by HPLC and triple-quadrupole mass spectrometry (MS). 8-OHdG was processed by an online solid-phase extraction LC-MS/MS. Plasma folate levels were measured using the chemiluminescent technology. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multiple logistic regression analysis. Results indicate that the high levels of total urinary arsenic, inorganic arsenic percentage, and 8-OHdG and the low levels of DMA % and plasma folate were independent factors of UC. In addition, global 5-MedC levels in the first quartile versus fifth quartile significantly increased the twofold OR of UC after potential factors were adjusted (95% CI:1.10-4.03). The interaction of 5-MedC level and high total arsenic level, insufficient arsenic capacity, high 8-OHdG, and low folate levels was insignificant. Results of stepwise logistic regression analysis indicate that high total urinary arsenic levels (Q3 versus Q1), low plasma folate level, and low global 5-MedC (Q4 versus Q5) significantly increased the ORs of UC. The above results suggest that high total arsenic, low plasma folate, and 5-MedC levels affect the ORs of UC independently.

Adiponectin gene polymorphisms and obesity increase the susceptibility to arsenic-related renal cell carcinoma

Our recent study found that high urinary total arsenic levels were associated with renal cell carcinoma (RCC). Recent studies demonstrated that low circulating adiponectin was related to RCC. The aim of the present study was to explore the relationship between adiponectin gene (ADIPOQ) polymorphisms and RCC and investigate whether individuals with an ADIPOQ risk genotype, obesity, and high urinary total arsenic levels have a modified odds ratio (OR) of RCC. A total of 389 RCC patients and 389 age- and sex-matched controls were recruited between November 2006 and December 2012 in Taiwan. Image-guided biopsy or surgical resection of renal tumors was performed to pathologically verify RCC. Genomic DNA was used to examine the genotypes of the ADIPOQ rs182052, ADIPOQ rs2241766, ADIPOQ rs1501299, and ADIPOQ rs1063539 SNPs by PCR-RFLP. HPLC-HG-AAS was used to measure the concentrations of urinary arsenic species. Participants with the ADIPOQ rs182052 G/A+A/A genotype had a significantly higher OR of RCC compared with those with the ADIPOQ rs182052 G/G genotype. The OR (95% confidence interval [CI]) was 1.70 (1.23–2.36). The OR of RCC for the combined effect of high urinary total arsenic levels and obesity, which was dose-dependent, in individuals with the ADIPOQ rs182052 G/A+A/A genotype was 9.33 (3.85–22.62). The present study found significant combined effects of obesity and the ADIPOQ rs182052 G/A+A/A genotype on the arsenic-related risk of RCC in a population with low arsenic exposure. Arsenic exposure, obesity, and the ADIPOQ rs182052 polymorphism could be predictors of a higher OR of RCC.

Serum folate levels and urinary arsenic methylation profiles in the US population: NHANES, 2003-2012.

Arsenic is a prevalent environmental contaminant, and its folate-dependent methylation is important for detoxification in the body. In this study, we investigated the association between serum folate levels and methylation using data from the US National Health and Nutrition Examination Survey (NHANES) (2003-2012) (N = 11,016). Multivariate linear regression and penalized spline regression models were used to examine the association and possible upper limit of folate level regarding its impact on methylation in children (≤18 years) and adults (>18 years), respectively. Serum folate levels, methylation metabolites including urinary monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)), and demographic variables were extracted from NHANES. Results showed that urinary percentage of DMA(V) (%DMA(V)) was positively associated with log(serum folate levels) after adjustment in children (β = 1.93, p < 0.01); urinary percentage of MMA(V) (%MMA(V)) was positively associated with log (serum folate levels) after adjustment in adults (β = 0.40, p < 0.01). No upper limit of folate level regarding its impact on arsenic methylation was identified. More than 50% of Non-Hispanic black and smokers with high total urinary arsenic levels had low serum folate levels. Our results indicate that folate promotes arsenic methylation, but the patterns are different in children versus in adults. Future interventions may be needed for the population exposed to high level of arsenic but with low serum folate to protect against the potential adverse health effects of arsenic.

Associations between urinary total arsenic levels, fetal development, and neonatal birth outcomes: A cohort study in Taiwan

BackgroundArsenic exposure is a global health concern. Several studies have focused on chronic arsenic exposure in adults; however, limited data are available regarding the potential adverse effects of prenatal exposure on fetuses and neonates. ObjectivesTo assess which time point maternal arsenic exposure may influence the fetus during pregnancy and birth outcomes. MethodsIn this study, total arsenic concentrations were analyzed in urine samples collected from 130 women with singleton pregnancies (22–45years old) in Taiwan from March to December of 2010. All fetal biometric measurements in each trimester period and birth outcomes at delivery were obtained. We applied a generalized estimating equation model and multivariate regression models to evaluate the associations between maternal urinary total arsenic (UtAs) exposure during pregnancy, fetal biometric measurements, and neonatal birth outcomes. ResultsWe observed statistically significant correlations between maternal UtAs levels and the fetal biparietal diameter over all three trimesters (β=−1.046mm, p<0.05). Multiple regression analyses showed a negative association between maternal UtAs levels and chest circumference in the first trimester (β=−0.721cm, p<0.05), and second-trimester UtAs exposure was associated with decreases in birth weight (β=−173.26g, p<0.01), head circumference (β=−0.611cm, p<0.05), and chest circumference (β=−0.654cm, p<0.05). Dose-response relationships were also observed for maternal UtAs exposure and birth outcomes. ConclusionsWe identified a negative relationship between maternal UtAs levels during pregnancy, fetal development, and neonatal birth outcomes. These findings should be confirmed in future studies with large sample sizes.

Levels of plasma selenium and urinary total arsenic interact to affect the risk for prostate cancer

This study investigated whether plasma selenium levels modified the risk for prostate cancer (PC) related to arsenic exposure. We conducted a case-control study that included 318 PC patients and 318 age-matched, healthy control subjects. Urinary arsenic profiles were examined using HPLC-HG-AAS and plasma selenium levels were measured by ICP-MS. We found that plasma selenium levels displayed a significant dose-dependent inverse association with PC. The odds ratio (OR) and 95% confidence interval (CI) for PC was 0.07 (0.04–0.13) among participants with a plasma selenium level >28.06 μg/dL vs. ≤19.13 μg/dL. A multivariate analysis showed that participants with a urinary total arsenic concentration >29.28 μg/L had a significantly higher OR (1.75, 1.06–2.89) for PC than participants with ≤29.89 μg/L. The combined presence of a low plasma selenium level and a high urinary total arsenic concentration exponentially increased the OR for PC, and additively interacted with PSA at levels ≥20 ng/mL. This is the first epidemiological study to examine the combined effects of plasma selenium and urinary total arsenic levels on the OR for PC. Our data suggest a low plasma selenium level coupled with a high urinary total arsenic concentration creates a significant risk for aggressive PC.

Total arsenic concentrations in Chinese children's urine by different geographic locations, ages, and genders.

Little is known about the variation of Chinese children's exposure to arsenic by geography, age, gender, and other potential factors. The main objective of this study was to investigate the total arsenic concentration in Chinese children's urine by geographic locations, ages, and genders. In total, 259 24-h urine samples were collected from 210 2- to 12-year-old children in China and analyzed for total arsenic and creatinine concentrations. The results showed that the upper limit (upper limit of the 90% confidence interval for the 97.5 fractile) was 27.51µg/L or 55.88µg/g creatinine for Chinese children. The total urinary arsenic levels were significantly different for children in Guangdong, Hubei, and Gansu provinces (P<0.05), where the upper limits were 24.29, 58.70, and 44.29µg/g creatinine, respectively. In addition, the total urinary arsenic levels were higher for 2- to 7-year-old children than for 7- to 12-year-old children (P<0.05; the upper limits were 59.06 and 44.29µg/g creatinine, respectively) and higher for rural children than for urban children (P<0.05; the upper limits were 59.06 and 50.44µg/g creatinine, respectively). The total urinary arsenic levels for boys were not significantly different from those for girls (P>0.05), although the level for boys (the upper limit was 59.30µg/g) was slightly higher than that for girls (the upper limit was 58.64µg/g creatinine). Because the total urinary arsenic concentrations are significantly different for general populations of children in different locations and age groups, the reference level of total urinary arsenic might be dependent on the geographic site and the child's age.

Total and speciated urinary arsenic levels in the Spanish population

BackgroundVery few studies exist on urinary arsenic exposure in Spain. ObjectiveTo evaluate total and speciated urinary arsenic (As) levels in a Spanish population sample. MethodsDemographic, lifestyle and dietary data was collected for 124 volunteers (aged 20–76years; 88 women and 36 men), who were tested for total arsenic and five arsenic species using high-performance liquid chromatography-inductively coupled plasma mass spectrometry. ResultsArsenobetaine (AB) and dimethylarsinic acid (DMA) were detected in 96.8% of the study participants (limit of detection (LOD) 1.0μg/L for AB and 1.9μg/L for DMA). Monomethylarsonic acid (MMA) and arsenous acid (As(III)) were detected in 5.6% (LOD 1.8μg/L) and 1.6% (LOD 1.4μg/L) of the participants, respectively; arsenic acid (As(V)) was not detected (LOD 1.4μg/L). AB and DMA (geometric mean (GM) 29.1μg/L and 7.5μg/L, respectively) were the main contributors to total urinary arsenic levels. Urinary DMA was positively associated with AB. ConclusionTotal arsenic levels observed in the Spanish population sample were higher than those reported by other European studies. The most recurrent urinary arsenic species was AB, followed by DMA, probably attributable to the high Spanish consumption of seafood. We recommend using inorganic As+MMA as the two main urinary biomarkers for inorganic As exposure. Our results provide reference data for analysing arsenic speciation results and assessing human exposure.

Combined effects of DNA methyltransferase 1 and 3A polymorphisms and urinary total arsenic levels on the risk for clear cell renal cell carcinoma

Our previous study showed that high urinary total arsenic levels were associated with higher odds ratio (OR) for renal cell carcinoma (RCC). Single nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMTs) might influence DNMT enzyme activity associated with tumorigenesis. In this study, we investigated the association of five SNPs from DNMT1 (rs8101626 and rs2228611), DNMT3A (rs34048824 and rs1550117), and DNMT3B (rs1569686) with the risk of clear cell renal cell carcinoma (ccRCC). We also examined the combined effects of DNMT genotypes and urinary arsenic levels on ccRCC risk. We conducted a hospital-based case-control study, which included 293 subjects with ccRCC and 293 age- and gender-matched controls. The urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotypes were investigated using polymerase chain reaction and restriction fragment length polymorphism analyses. We observed that the DNMT1 rs8101626 G/G genotype was significantly associated with reduced odds ratio (OR) of ccRCC [OR=0.38, 95% confidence interval (CI) 0.14–0.99]. Subjects with concurrent DNMT1 rs8101626 A/A+A/G and DNMT3A rs34048824 T/T+T/C genotypes had significantly higher OR for ccRCC [OR=2.88, 95% CI 1.44–5.77]. Participants with the high-risk genotype of DNMT1 rs8101626 and DNMT3A rs34048824 with concurrently high urinary total arsenic levels had even higher OR of ccRCC in a dose-response manner. This is the first study to evaluate variant DNMT1 rs8101626 and DNMT3A rs34048824 genotypes that modify the arsenic-related ccRCC risk in a geographic area without significant arsenic exposure in Taiwan.

Consumption of Rice Products Containing Low Levels of Arsenic and Its Relationship to Health Outcomes Utilizing Blood Pressure Readings: An Initial Analysis of NHANES Data

Over the last several years, there has been an increasing concern regarding safety of food products which are reported to contain arsenic (As). Researchers has indicated that high levels of As in drinking water have been correlated with negative health outcomes. However, the dietary exposures from food items containing As levels well below the established water quality standards, have not been well investigated and have become a subject of increasing evaluation and priority.Rice is one widely consumed product, which contains As. The possible health ramifications of consuming a diet rich in rice, specifically regarding low‐level As exposure through rice ingestion, is not completely understood nor characterized. Considering the implication that low levels of As may be directly linked to a wide variety of adverse health effects including cancer, hypertension, and high blood sugar, this study will focus on evaluating the potential linkages between low‐level arsenic exposure (ingestion) due to consumption of rice and high blood pressure in a specified population.A sound starting point in this investigation is the National Health And Nutrition Examination Survey (NHANES). In the NHANES, over 5,000 individuals per year were sampled via a complex probability analysis between years 2003–2012. The objective of the current study is to explore the association between overall rice consumption by adults within the United States (18 years and older) with total urinary arsenic levels and hypertension as measured by Systolic Blood Pressure data. From the NHANES surveys and laboratory samples, our data analysis was completed utilizing linear regression models in order to test the associations between rice consumption, urinary arsenic levels, and high systolic blood pressure. Early stage evaluations support the research hypothesis, which indicates that arsenic containing rice products are likely contributing to high blood pressure, when specific demographics, as well the confounders of total water consumption, and water source are placed into the model.Support or Funding InformationLoma Linda University School of Public Health: Doctoral Research Allotted Funds