Urinary Arsenic Concentrations Research Articles

Excretion of Heavy Metals and Glyphosate in Urine and Hair Before and After Long-Term Fasting in Humans.

Background: Dietary exposure to environmental pollutants in humans is an important public health concern. While long-term fasting interrupts the dietary exposure to these substances, fat mobilization as an energy source may also release bioaccumulated substances. This was, to our knowledge, only investigated in obese people decades ago. This study explored the effects of 10-days fasting on the excretion of heavy metals and glyphosate.Methods: Urinary levels of arsenic, chromium, cobalt, lead, nickel, mercury and glyphosate were measured before and after 10 fasting days in 109 healthy subjects. Additionally, hair analysis was done before and ten weeks after fasting in 22 subjects.Results: Fasting caused a decrease in body weight, and in urinary arsenic (by 72%) and nickel (by 15%) concentrations. A decrease in lead hair concentrations (by 30%) was documented. Urinary mercury levels were unchanged for chromium, cobalt and glyphosate, which were undetectable in most of the subjects. Additionally, fatigue, sleep disorders, headache and hunger were reduced. Body discomfort symptoms diminished four weeks after food reintroduction.Conclusions: The results of this study provide the first insights into the changes in heavy metal excretion caused by long-term fasting. Further studies focusing on the kinetics of efflux between different compartments of the body are needed.Clinical Trial Registration: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016657, identifier: DRKS00016657.

Impact of modernization on urinary concentrations of arsenic, cadmium, lead, and selenium in rural residents of Northern Laos.

The impacts of modernization on toxic heavy metal exposure and essential trace element intake in indigenous populations of subsistence societies are unknown. We assessed urinary trace element concentrations in rural residents of Northern Laos and examined associations with levels of modernization. A cross-sectional study was conducted comprising 380 residents of three villages in Northern Laos with different levels of modernization. We surveyed general characteristics and measured the weight and height of 341 participants. Arsenic, cadmium, lead, and selenium concentrations were measured in spot urine samples by inductively coupled plasma mass spectrometry. We examined associations between urinary trace element concentrations and variables related to modernization (village, roofing material, possessions index [total number of possessions], and body mass index [BMI]) using multilevel analyses with household as a random effect, after adjusting for sex, age, and smoking status. Urinary concentrations of arsenic and cadmium were high, while those of lead and selenium were low in comparison to previous reports of populations in non-contaminated regions or without excess/deficiency. We observed associations between urinary trace element concentrations and village-level modernization: lead and selenium concentrations were higher in more modernized villages and cadmium concentration was highest in the least modernized village. Urinary arsenic concentration was not predicted by the modernization level of a village, although we observed significant differences among villages. In addition, urinary selenium concentration was higher in participants inhabiting more modernized houses. Modernization of villages may impact toxic heavy metal exposure and selenium intake in rural residents of Northern Laos.

The combined effects of nucleotide-binding domain-like receptor protein 3 polymorphisms and levels of blood lead on developmental delays in preschool children

Nucleotide-binding domain-like receptors protein 3 (NLRP3) inflammasomes are associated with neuroinflammation and multiple NLRP3 genes regulate NLRP3 expression. Our study aimed to investigate the association of NLRP3 polymorphisms with developmental delay in preschool children. We also explored whether NLRP3 polymorphisms modified the effects of total urinary arsenic and blood cadmium and lead to developmental delays. A total of 178 children with developmental delays and 88 healthy children were analyzed for urinary arsenic concentrations and red blood cell lead and cadmium concentrations. We examined the genotypes of fifteen common single-nucleotide polymorphisms in NLRP3. We observed that levels of total urinary arsenic and blood lead were significantly associated with developmental delay. The NLRP3rs10754555 CG versus CC/GG, NLRP3rs12048215 AG versus AA/GG, and NLRP3rs12137901 TC/TT versus CC genotype showed a lower odds of developmental delay, with the odds ratio (OR) and 95% confidence interval (CI) = 0.38 (0.19–0.75), 0.52 (0.27–0.99), and 0.33 (0.12–0.90), respectively. Children with the NLRP3rs10754555 CC/GG genotype and high blood lead levels had a significant multiplicative interaction with developmental delay [OR (95% CI) = 9.74 (3.59–26.45)]. This study found evidence that suggested the joint effects of NLRP3rs10754555 CC/GG genotype and high blood lead levels on developmental delays.

Arsenic Secondary Methylation Capacity Is Inversely Associated with Arsenic Exposure-Related Muscle Mass Reduction.

Skeletal muscle mass reduction has been implicated in insulin resistance (IR) that promotes cardiometabolic diseases. We have previously reported that arsenic exposure increases IR concomitantly with the reduction of skeletal muscle mass among individuals exposed to arsenic. The arsenic methylation capacity is linked to the susceptibility to some arsenic exposure-related diseases. However, it remains unknown whether the arsenic methylation capacity affects the arsenic-induced reduction of muscle mass and elevation of IR. Therefore, this study examined the associations between the arsenic methylation status and skeletal muscle mass measures with regard to IR by recruiting 437 participants from low- and high-arsenic exposure areas in Bangladesh. The subjects’ skeletal muscle mass was estimated by their lean body mass (LBM) and serum creatinine levels. Subjects’ drinking water arsenic concentrations were positively associated with total urinary arsenic concentrations and the percentages of MMA, as well as inversely associated with the percentages of DMA and the secondary methylation index (SMI). Subjects’ LBM and serum creatinine levels were positively associated with the percentage of DMA and SMI, as well as inversely associated with the percentage of MMA. HOMA-IR showed an inverse association with SMI, with a confounding effect of sex. Our results suggest that reduced secondary methylation capacity is involved in the arsenic-induced skeletal muscle loss that may be implicated in arsenic-induced IR and cardiometabolic diseases.

Associations between arsenic, cadmium, and selenium exposure and oxidative stress in rural residents of northern Laos

BACKGROUND AND AIM: Oxidative stress is an important consequence of exposure to arsenic and cadmium, but it is unclear to what extent low-level exposures contribute to oxidative stress. Additionally, previous studies suggested that selenium suppresses the toxicity of arsenic and cadmium. This study aimed to examine associations between arsenic and cadmium exposure and oxidative damage to DNA and lipid in rural residents of northern Laos, considering selenium interactions with the two toxic elements. METHODS: We collected data on general characteristics (village, sex, age, smoking, drinking, height, and weight) and a single spot urine sample from the participants (n = 341). Urinary concentrations of arsenic, cadmium, and selenium were measured by inductively coupled plasma mass spectrometry to estimate their exposure/intake levels. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane concentrations were measured by liquid chromatography-tandem mass spectrometry (oxidative stress biomarkers of DNA and lipid, respectively). Multiple linear regression analyses examined associations of urinary concentrations of arsenic and cadmium with those of oxidative stress markers, adjusted for covariates. We performed additional analyses to include interaction terms between urinary concentrations of arsenic/cadmium and selenium. RESULTS:Geometric means of specific gravity-adjusted urinary concentrations of arsenic, cadmium, selenium, 8-OHdG, and 8-isoprostane were 40.0, 1.38, 11.7, 3.89, and 0.934 µg/L, respectively. Urinary concentration of arsenic and cadmium showed positive associations with that of 8-isoprostane. We also observed that there were significant interactions between arsenic and selenium in the association with 8-OHdG (Coefficient (95% CI) = -0.21 (-0.37, -0.05)) and between cadmium and selenium in the association with 8-isoprostane (Coefficient (95% CI) = -0.14 (-0.25, -0.03)). CONCLUSIONS:Our findings suggested that arsenic and cadmium exposure were positively associated with oxidative stress in rural residents of northern Laos. Additionally, selenium might have protective effects on arsenic-/cadmium-induced oxidative stress. KEYWORDS: Heavy metals, Chemical exposures, Environmental epidemiology

Urinary Metal Mixtures and Incident Metabolic Syndrome in Midlife Women: the Study of Women’s Health Across the Nation (SWAN)

BACKGROUND AND AIM: Exposure to metals may contribute to the development of metabolic syndrome (MetS); however, evidence from midlife women who are at greater risk of cardiometabolic disease is limited. We prospectively examined the associations of 15 urinary metal concentrations with incident MetS in the Study of Women’s Health Across the Nation Multi-Pollutant Study. METHODS: The sample included 947 White, Black, Chinese and Japanese women from 5 study sites in the United States, aged 45-56 years and free of MetS at baseline (1999-2000), followed through 2017. Urinary concentrations of 15 metals, including arsenic, barium, cadmium, cobalt, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, and zinc, were quantified at baseline. Incident MetS was identified annually as the presence of at least 3 of the following 5 components: high blood pressure, impaired fasting glucose, abdominal obesity, high triglycerides, and low high-density lipoprotein cholesterol. RESULTS:After adjustment for potential confounders, the hazard ratios (HR) (95% confidence interval (CI)) for MetS associated with each doubling of urinary metal concentration was 1.14 (1.08, 1.23) for arsenic, 1.14 (1.01, 1.29) for cobalt, and 1.20 (1.06, 1.37) for zinc, in Cox proportional hazards models. Positive associations of urinary arsenic with high blood pressure and impaired fasting glucose, positive associations of urinary cobalt with high blood pressure and abdominal obesity, and positive associations of urinary zinc with high blood pressure, impaired fasting glucose, abdominal obesity, and high triglyceride were observed. In the quantile-based g-computation assessing the joint effect of metal mixtures, increasing urinary arsenic, cobalt, and zinc concentrations by one quartile was associated with a higher incidence of MetS (HR=1.73, 95% CI: 1.21, 2.48). CONCLUSIONS:Higher urinary arsenic, cobalt, and zinc concentrations were associated with an elevated incidence of MetS in midlife women. Future studies should confirm these findings and further investigate the underlying mechanisms. KEYWORDS: Metals, mixtures, metabolic syndrome, women, cohort study.

Water as a relevant source of inorganic arsenic exposure in U.S. cities

BACKGROUND AND AIM: Water arsenic represents a health concern for US residents served by community water systems (CWS) exceeding the Environmental Protection Agency (EPA) Maximum Contaminant Level (MCL) of 10 µg/L, and for residents reliant on unregulated private wells. Little is known on the contribution of CWS arsenic exposures below the MCL, particularly in urban areas. We evaluated whether water arsenic is a relevant source of urinary arsenic in urban settings in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: We examined the association of CWS arsenic with urinary arsenic concentrations (µg/L) for 910 MESA participants from Baltimore, Chicago, Los Angeles, New York City, St. Paul, MN, and Winston-Salem, NC. We assigned three-year population weighted averages of CWS arsenic concentrations using 2006-2008 EPA data (before MCL implementation) to participants by zip code. Dietary information and urinary samples were collected in 2000-2002. Urinary arsenic species were measured using HPLC-ICPMS. We accounted for seafood intake using a residual based method. Linear models adjusted for race/ethnicity, income, smoking status, diet (rice) and urinary creatinine to account for urine dilution. RESULTS:CWS arsenic levels ranged from 0.5 µg/L (LOD) in several cities to 3.05 µg/L in Chicago (median 0.44 µg/L). CWS arsenic was positively correlated (p 0.05) with urinary inorganic arsenic (Spearman’s rho 0.11), dimethylarsinate (DMA) (0.09), monomethylarsonate (MMA) (0.16) and their sum (0.10). In adjusted models, a 1 µg/L change in CWS arsenic was associated with 1.29 (95%CI 1.01, 1.64) higher inorganic arsenic and 1.19 (1.03, 1.38) higher MMA. The association with DMA, sum of inorganic and methylated species was not statistically significant. CONCLUSIONS:Drinking water arsenic is a relevant source of exposure and internal dose in US urban areas, determined by urinary arsenic biomarkers. Research is needed to determine health implications of chronic exposure to water arsenic below the MCL, including vulnerable subpopulations. KEYWORDS: arsenic, drinking water, exposure assessment, environmental epidemiology

Urinary Heavy Metals and Longitudinal Changes in Blood Pressure in Midlife Women: the Study of Women’s Health Across the Nation

BACKGROUND AND AIM: Environmental exposure to heavy metals may contribute to increased blood pressure, however, evidence from midlife women who are at greater risk of cardio-metabolic disease, is limited. We evaluated the associations of urinary concentrations of arsenic, cadmium, mercury, and lead with longitudinal changes in blood pressure in the Study of Women’s Health Across the Nation Multi-Pollutant Study. METHODS: The sample included 1,317 White, Black, Chinese and Japanese women, aged 45-56 years at baseline (1999-2000), whose systolic and diastolic blood pressure (SBP and DBP) were measured annually or biannually through 2017. Urinary metal concentrations were determined at baseline. Longitudinal changes in SBP and DBP were modeled using linear mixed effects models by tertiles of metal concentrations. RESULTS:After multivariable adjustment, estimated annualized increases (95% CI) in SBP in the highest and lowest tertiles were 0.93 (0.85, 1.01) mmHg and 0.74 (0.66, 0.82) mmHg for arsenic, 0.82 (0.75, 0.90) mmHg and 0.72 (0.65, 0.80) mmHg for mercury, and 0.86 (0.78, 0.93) mmHg and 0.72 (0.64, 0.79) mmHg for lead, respectively. Similar results were observed for associations of arsenic, mercury, lead with DBP. Urinary cadmium was associated with a greater rate of increase in SBP only among never smokers. Women with higher concentrations of all four metals had greater annualized increases in SBP and DBP than those with lower concentrations. CONCLUSIONS:Our findings suggest that exposure to heavy metals may accelerate the increase in blood pressure in midlife women, supporting the need for continued efforts to reduce these environmental exposures. KEYWORDS: Metals, blood pressure, women, cohort study

Association of urinary arsenic and sleep disorder in the US population: NHANES 2015-2016.

Arsenic is a known carcinogen and neurotoxin and is found in the natural earth crust. Arsenic exposure can develop depression, memory dysfunction, and neurodegenerative disorder. The mechanism of arsenic toxicity on the nervous system is not known. There is a lack of research on the association between arsenic exposure and sleep disturbance in humans. This study aims to investigate the relationship between six types of urinary speciated arsenic exposure and sleep disturbance in adults from the general population using the National Health and Nutrition Examination Survey (NHANES) 2015-2016 dataset. Sleep disturbance was measured using self-reported questionnaires, asking participants if they had ever told a doctor they had trouble sleeping. We utilized multivariate logistic regression analysis using complex survey procedures to examine the association between six types of urinary arsenic concentration and trouble sleeping. The total sample included 1,611 adults who were 20 years and older. Of the study participants, 30.0% had trouble sleeping. Compared to individuals with urinary arsenous acid below the lower level of detection (LLOD), those with urinary arsenous acid at or above the detection limit had lower odds of trouble sleeping [odds ratio: 0.72 (95% confidence interval 0.51-1.00, p-value: 0.05)]. The other five types of urinary speciated arsenic studied (arsenic acid, arsenobetaine, arsenocholine, dimethylarsinic acid, monomethylarsonic acid) were not associated with a sleep disorder. More studies are required to confirm or refute these findings.

Associations between rice consumption, arsenic metabolism, and insulin resistance in adults without diabetes.

Rice consumption is an important source of arsenic exposure. Little has known about the impact of rice consumption on arsenic metabolism, which is related to insulin resistance. In this study, we examined the associations between rice consumption and arsenic metabolism, and between arsenic metabolism and insulin resistance in non-diabetic U.S adults who participated in the National Health and Nutrition Examination Survey (NHANES) 2003-2016. Rice consumer was defined as ≥0.25 cups of cooked rice/day. HOMA2-IR was calculated using HOMA2 Calculator software based on participant's fasting glucose and insulin values. Urinary arsenic concentrations below limits of detection were imputed first, and then arsenic metabolism (the proportions of inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) to their sum) were calculated (expressed as iAs%, MMA%, and DMA%). Using the leave-one-out approach, rice consumers compared with non-consumers had a 1.71% (95% CI: 1.12%, 2.29%) higher DMA% and lower MMA% when iAs% fixed; a 1.55% (95% CI: 0.45%, 2.66%) higher DMA% and lower iAs% when MMA% fixed; and a 1.62% (95% CI: 0.95%, 2.28%) higher iAs% and lower MMA% when DMA% fixed, in multivariable adjustment models. With every 10% decrease in MMA%, the geometric mean ratio of HOMA2-IR was 1.06 (95% CI:1.03,1.08) and 1.05 (95% CI:1.02, 1.09) when DMA% and iAs% was fixed, respectively; however, the associations were attenuated after adjusting for body mass index. In stratified analysis, we found that lower MMA% was associated with higher HOMA2-IR in participants with obesity: a 10% increase in iAs% with a 10% decrease in MMA% was associated with higher HOMA2-IR with the geometric mean ratio of 1.05 (95% CI: 1.01, 1.09). Our findings suggest that rice consumption may contribute to lower MMA% that was further associated with higher insulin resistance, especially in individuals with obesity. Future prospective studies are needed to confirm our results in different populations.

Clinimetallomics: Arsenic Speciation in Urine from Patients With Arsenism by HPLC-ICP-MS

Clinimetallomics is proposed as a branch of metallomics that focuses on the study of the metallome in clinical samples of urine, blood, and tissues. As the clinical diagnosis of arsenic poisoning is mainly based on the concentration of total arsenic in urine, the toxicity of arsenic varies greatly in different speciation. Analysis of arsenic speciation with excessive total arsenic in urine can provide a basis for precise treatment. It can also be used to understand the fate of arsenic in the body of patients with arsenic poisoning after treatment with sodium dimercaptopropane sulfonate. In this study, a HPLC-ICP-MS method was established for the determination of arsenic species in urine samples from patients diagnosed with arsenism. Use the established method to detect urine samples, which can be directly assayed after simple sample dilution with 20 mmol/L EDTA-2Na. With the concentration of arsenic speciation in the range of 1.0~100.0 ng/mL, the linear correlation coefficient was higher than 0.99996. The recoveries were between 92.4% and 109.0%. The precision of the concentration and retention time (n = 3) were less than 3.0% and 0.3%, respectively, and the detection limit was between 1.42 ng/mL and 1.86 ng/mL. This method can be applied to arsenic speciation in the urine of healthy people, in patients treated for arsenic poisoning, and in patients diagnosed with arsenism.

Environmental exposure to metals and the risk of high blood pressure: a cross-sectional study from NHANES 2015-2016.

Exposure to metal pollution can be caused from inhalation, ingestion, or absorption from air, water, or food. Chronic exposure to trace amounts of metals can lead to high blood pressure, or hypertension, and other chronic diseases. The rationale of our study was to determine if there was a correlation between nineteen forms of urinary metal concentrations and high blood pressure, defined as ≥ 130 mm Hg systolic or ≥ 80 mm Hg diastolic, in the adult US population, to understand the possible impacts of metal exposure on humans. Five types of urinary arsenic species and fourteen types of urinary metals were studied to examine their correlation with high blood pressure. We used the dataset from the 2015-2016 National Health and Nutrition Examination Survey (NHANES) for the study. A specialized complex survey design analysis package was used in analyzing the NHANES data. We used pairwise t tests and the logit regression models to study the correlation between urinary arsenic (five types) and urinary metal (fourteen types) concentrations and high blood pressure. The total study population analyzed included 4037 adults aged 20 years and older, of whom 57.9% of males and 51.7% of females had high blood pressure. Urinary arsenous acid (OR: 2.053, 95% CI: 1.045, 4.035), tin (OR: 1.983, 95% CI: 1.169, 3.364), and cesium (OR: 2.176, 95% CI: 1.013, 4.675) were associated with increased odds of high blood pressure. The other four types of urinary arsenic and twelve types of urinary metals were not associated with high blood pressure. Our results determined that exposure to environmental metals such as arsenous acid, tin, and cesium can be associated with high blood pressure. Further investigation is suggested to support our findings.

The relatively higher concentrations of trace elements to arsenic may have influenced on methylation process of inorg- As in humans

The relatively higher concentrations of trace elements to arsenic may have influenced on methylation process of inorg- As in humans

Prenatal heavy metal exposure, total immunoglobulin E, trajectory, and atopic diseases: A 15-year follow-up study of a Taiwanese birth cohort.

Prenatal exposure to heavy metals may cause atopic diseases. Little association between cord blood total immunoglobulin E (CB-tIgE) levels and the occurrence of atopic diseases has been found. This study investigated the atopic status and tIgE trajectory trend in a Taiwanese birth cohort over 15years. We also assessed the effect of maternal heavy metal exposure on maternal serum cytokine and CB-tIgE levels. We recruited 430 pregnant women during their third trimester in 2000-2001. Maternal urinary heavy metal concentrations and serum cytokine levels were measured. The CB-tIgE and serum tIgE levels of the women's children when they were aged 5, 8, 11, and 14years were measured. The upper quartile of the maternal urinary arsenic concentration was associated with an increased risk of a CB-tIgE level higher than 1IU/mL (odds ratio, 1.845; 95% confidence interval, 1.003-3.395). Serum tIgE trajectory levels were the highest in children with asthma, followed by those with atopic dermatitis and allergic rhinitis at the age of 5-14years. Serum tIgE levels tended to peak at the age of 11years in the atopic children but were stable from the age of 8years in the non-atopic children. We first demonstrated that serum tIgE levels reached a trajectory peak in the atopic children aged 11years. Prenatal exposure to arsenic may increase the risk of elevated CB-tIgE levels. Further investigation is warranted to elucidate the mechanism through which maternal serum cytokines affect the occurrence of atopic diseases in children.

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 < 0.001), grains (β=-0.02, 95%CI -0.02, -0.01, P< 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.

Urinary Heavy Metals and Longitudinal Changes in Blood Pressure in Midlife Women: The Study of Women's Health Across the Nation.

[Figure: see text].

Urinary arsenic and heart disease mortality in NHANES 2003–2014

BackgroundEvidence evaluating the prospective association between low-to moderate-inorganic arsenic (iAs) exposure and cardiovascular disease in the general US population is limited. We evaluated the association between urinary arsenic concentrations in National Health and Nutrition Examination Survey (NHANES) 2003–2014 and heart disease mortality linked from the National Death Index through 2015. MethodsWe modeled iAs exposure as urinary total arsenic and dimethylarsinate among participants with low seafood intake, based on low arsenobetaine levels (N = 4990). We estimated multivariable adjusted hazard ratios (HRs) for heart disease mortality per interquartile range (IQR) increase in urinary arsenic levels using survey-weighted, Cox proportional hazards models, and evaluated flexible dose-response analyses using restricted quadratic spline models. We updated a previously published relative risk of coronary heart disease mortality from a dose-response meta-analysis per a doubling of water iAs (e.g., from 10 to 20 μg/L) with our results from NHANES 2003–2014, assuming all iAs exposure came from drinking water. ResultsA total of 77 fatal heart disease events occurred (median follow-up time 75 months). The adjusted HRs (95% CI) of heart disease mortality for an increase in urinary total arsenic and DMA corresponding to the interquartile range were 1.20 (0.83, 1.74) and 1.18 (0.68, 2.05), respectively. Restricted quadratic splines indicate a significant association between increasing urinary total arsenic and the HR of fatal heart disease for all participants at the lowest exposure levels <4.5 μg/L. The updated pooled relative risk of coronary heart disease mortality per doubling of water iAs (μg/L) was 1.16 (95% CI 1.07, 1.25). ConclusionsDespite a small number of events, relatively short follow-up time, and high analytical limits of detection for urinary arsenic species, iAs exposure at low-to moderate-levels is consistent with increased heart disease mortality in NHANES 2003–2014 although the associations were only significant in flexible dose-response models.

Invited Perspective: Metal Mixtures and Child Health: The Complex Interplay of Essential and Toxic Elements.

Invited Perspective: Metal Mixtures and Child Health: The Complex Interplay of Essential and Toxic Elements.

Essential hypertension in patients exposed to high-arsenic exposed areas in western China: Genetic susceptibility and urinary arsenic metabolism characteristics

ObjectiveTo clarify the urinary arsenic metabolism characteristics in individuals with essential hypertension and to analyze the relationship between lipid metabolism gene polymorphisms and susceptibility to essential hypertension in individuals in high-arsenic areas in western China. MethodsA case-control study was conducted and involved individuals exposed to high arsenic levels (in this study, the arsenic content in the pressurized well water was 0–510.2 μg/L, and that in the mechanical well water was 167 μg/L) in two adjacent high-arsenic areas in Shanxi Province and the Inner Mongolia Autonomous Region, China. A total of 699 samples were collected, including 192 case samples (patients with hypertension) and 507 control samples (no hypertension). Blood pressure measurement data obtained from an epidemiological survey were used to determine whether the subjects had hypertension, and a logistic regression model was used to analyze the association between lipid metabolism gene polymorphisms and hypertension susceptibility. Blood and urine samples were collected based on epidemiological methods, single nucleotide polymorphisms (SNPs) were genotyped using a SNPscan™ multiple SNP typing kit, and urinary arsenic concentrations were determined using the hydride generation atomic fluorescence method (HG-AFS). ResultsADIPOQ/rs266729 was the dominant genetic model [(GC + GG) vs CC = 0.686:1, 95 % CI = 0.478−0.983], and FABP2/rs1799883 was the recessive genetic model [TT vs (CC + TC) = 1.690:1, 95 % CI = 1.014–2.816]. The distribution of the urinary arsenic secondary methylation ratio (SMR) [dimethylated arsenic (DMA)/monomethylated arsenic (MMA)] was different between hypertensive patients and controls. ConclusionADIPOQ/rs266729 and FABP2/rs1799883 polymorphisms affect susceptibility to essential hypertension in individuals exposed to high levels of arsenic; there was a clear difference in the urinary arsenic metabolism pattern between hypertensive patients and controls.

The effects of the exposure to neurotoxic elements on Italian schoolchildren behavior

Neurodevelopmental disorders are constantly increasing on a global scale. Some elements like heavy metals are known to be neurotoxic. In this cross-sectional study we assessed the neurobehavioral effect of the exposure to trace elements including lead, mercury, cadmium, manganese, arsenic and selenium and their interactions among 299 schoolchildren residing in the heavily polluted Taranto area in Italy. Whole blood, urine and hair were collected for metal analyses, while the Child Behavior Checklist and the Social Responsiveness Scale, administered to the main teacher and the mothers were considered to identify behavioral problems in children. Blood lead mainly influenced social problems, aggressive behavior, externalizing and total problems. Urinary arsenic showed an impact on anxiety and depression, somatic problems, attention problems and rule breaking behavior. A significant interaction between lead and arsenic was observed, with a synergistic effect of the two metals increasing the risk of attention problems, aggressive behavior, externalizing problems and total problems. Overall, we were able to test that higher blood lead, urinary arsenic concentrations and their interaction increase the risk of neurobehavioral problems. This is in line with the U.S. Environmental Protection Agency’s priority list of hazardous substances where arsenic and lead are ranked as first and second respectively.