Urinary Arsenic 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.

Association of chronic arsenic exposure with cellular immune profile in MINIMat adolescents: A birth cohort in Bangladesh

Chronic arsenic exposure is known to affect the immune system. We aimed to evaluate the association between arsenic exposure and immune cell profile in 15 years old adolescents (n=389) in rural Bangladesh, with chronic exposure to groundwater arsenic. Single blood and urine were collected. Urinary arsenic (U-As) concentration was measured using atomic absorption spectrometry. Peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometry. Non-linear association was found between U-As (median, 24.9 µg/L) and immune cells with a cut-off at U-As 20 µg/L. U-As (<20 µg/L) were significantly associated with increases in CD8+T (21 %), naïve CD8+T (42 %) and early B cells (40 %), and classical monocytes (55 %), but reduction in CD3+T cells (37%) and intermediate-monocytes (56 %). U-As (>20 µg/L) were associated with a 3 % reduction in memory B cells. Arsenic exposure was associated with altered immune cell profile in adolescents likely rendering them vulnerable to adverse health effects in later life.

Long-term effects of arsenic on glucose-insulin homeostasis: A gene-environment interaction study

Abstract Background Arsenic exposure and genetic factors are associated with an increased risk of type 2 diabetes, yet study of environment-gene interaction on glucose-insulin homeostasis remains scarce. We aimed to investigate the associations and interactions of urinary total arsenic (UTAs) and genetic susceptibility with glucose-insulin homeostasis through a longitudinal epidemiological study. Methods A total of 6136 observations (3063 participants) from the baseline, 3-year follow-up, and 6-year follow-up of the Wuhan-Zhuhai cohort were included in this study. In each study period, we repeatedly measured UTAs, fasting plasma glucose (FPG), fasting plasma insulin (FPI), and homeostasis model-assessed insulin resistance (HOMA-IR) and β-cell function (HOMA-β). Polygenic risk scores (PRSs) specific for all traits were constructed by corresponding genome-wide association summary statistics. Linear mixed models were used to assess associations and interactions of UTAs and PRSs with four indicators of glucose-insulin homeostasis. Results After adjustment for all covariates, the βs (95% CIs) for the annual growth rates of FPG, FPI, and HOMA-IR were 0.020 (0.008, 0.032), 0.007 (0.002, 0.013), and 0.011 (0.004, 0.017), respectively, associated with each ln-unit increase in UTAs. Compared to subjects with the first-quartile PRS and low UTAs, participants with the fourth-quartile PRS and high UTAs had a 0.029 (0.012, 0.047) or 0.032 (0.012, 0.051) ln-unit increase in the annual growth rate of FPI or HOMA-IR, respectively. UTAs and PRS had significant interactions on the longitudinal progressive increases of FPI and HOMA-IR (P interaction &amp;lt; 0.05). Conclusions Arsenic exposure and genetic variants are significantly synergistic risk factors for dysregulation and progressive deterioration of glucose-insulin homeostasis. Our findings emphasize the importance of reducing arsenic exposure to maintain normal glucose-insulin metabolism, especially for those at higher genetic risk. Key messages • Arsenic exposure was associated with annual increased rates of FPG, FPI, and HOMA-IR. • Arsenic exposure and trait-specific PRSs are synergistic risk factors for glucose-insulin homeostasis impairment.

Current exposure to environmental pollutants in the general adult population of Kinshasa, Democratic Republic of Congo (DRC): A cross-sectional study

BackgroundEnvironmental pollution is a serious public health problem because of its adverse effects on both human health and biodiversity. In Western countries, many human biomonitoring (HBM) studies are conducted to assess population exposure to pollutants. In contrast, the number of HBM studies in Africa is very low. ObjectiveTo measure contamination by arsenic, lead, 4,4′-dichlorodiphenyldichloroethylene (4,4′-DDE) and polychlorobiphenyls (PCBs) in the adult population of Kinshasa and to identify the susceptible population. MethodsIn the present work, we measured the contamination by arsenic in urine and lead in blood and by 4,4′-DDE and polychlorobiphenyls (PCBs) in serum in samples collected from 151 volunteers recruited in Kinshasa, the capital of the Democratic Republic of Congo (DRC). ResultsThe PCBs 180, -153 and −138 were detected in most samples with median concentrations of 0.04, 0.05 and 0.04 ng/ml, respectively. The median concentration of 4,4′-DDE was 0.83 ng/ml and 12.7% of our population showed contamination above the threshold of 3.675 ng/ml, which is associated with a significantly higher risk of cancer. Arsenic concentrations were also high (median: 48.1 μg/L in urine). Finally, exposure to lead is problematic: the median blood concentration was 54.9 μg/L, which is above the thresholds proposed by the WHO and the US CDC (50 μg/L and 35 μg/L respectively) to initiate clinical intervention, and 12.6% of the population had a lead level above 100 μg/L, which is associated with several health outcomes. ConclusionsOur results highlight the need for further HBM studies in Africa and should encourage the authorities of the DRC to implement laws and regulations to reduce pollution and population exposure.

The role of age and sex in non-linear dilution adjustment of spot urine arsenic

BackgroundPrevious research introduced V-PFCRC as an effective spot urinary dilution adjustment method for various metal analytes, including the major environmental toxin arsenic. V-PFCRC normalizes analytes to 1 g/L creatinine (CRN) by adopting more advanced power-functional corrective equations accounting for variation in exposure level. This study expands on previous work by examining the impacts of age and sex on corrective functions.MethodsLiterature review of the effects of sex and age on urinary dilution and the excretion of CRN and arsenic. Data analysis included a Data Set 1 of 5,752 urine samples and a partly overlapping Data Set 2 of 1,154 combined EDTA blood and urine samples. Both sets were classified into age bands, and the means, medians, and interquartile ranges for CRN and TWuAs in uncorrected (UC), conventionally CRN-corrected (CCRC), simple power-functional (S-PFCRC), sex-aggregated (V-PFCRC SA), and sex-differentiated V-PFCRC SD modes were compared. Correlation analyses assessed residual relationships between CRN, TWuAs, and age. V-PFCRC functions were compared across three numerically similar age groups and both sexes. The efficacy of systemic dilution adjustment error compensation was evaluated through power-functional regression analysis of residual CRN and the association between arsenic in blood and all tested urinary result modes.ResultsSignificant sex differences in UC and blood were neutralized by CCRC and reduced by V-PFCRC. Age showed a positive association with blood arsenic and TWuAs in all result modes, indicating factual increments in exposure. Sex-differentiated V-PFCRC best matched the sex-age kinetics of blood arsenic. V-PFCRC formulas varied by sex and age and appeared to reflect urinary osmolality sex-age-kinetics reported in previous research.V-PFCRC minimized residual biases of CRN on TWuAs across all age groups and sexes, demonstrating improved standardization efficacy compared to UC and CCRC arsenic.InterpretationSex differences in UC and CCRC arsenic are primarily attributable to urinary dilution and are effectively compensated by V-PFCRC. While the sex and age influence on V-PFCRC formulas align with sex- and age-specific urinary osmolality and assumed baseline vasopressor activities, their impact on correction validity for entire collectives is minimal.ConclusionThe V-PFCRC method offers a robust correction for urinary arsenic dilution, significantly reducing systemic dilution adjustment errors. Its application in various demographic contexts enhances the accuracy of urinary biomarker assessments, benefiting clinical and epidemiological research. V-PFCRC effectively compensates for sex differences in urinary arsenic. Age-related increases in TWuAs are exposure-related and should be additionally accounted for by algebraic normalization, covariate models, or standard range adjustments.

Effect of Adopting a Gluten-Free Diet on Exposure to Arsenic and Other Heavy Metals in Children With Celiac Disease: A Prospective Cohort Study.

Lifelong adherence to a gluten-free diet (GFD) is the primary treatment of celiac disease (CeD), a gluten-driven enteropathy. Concerns have been raised about increased exposure to arsenic from a GFD because rice, which naturally bioaccumulates arsenic, is commonly used as a substitute for gluten-containing grains such as wheat. We hypothesize that arsenic exposure increases in newly diagnosed children with CeD after they adopt a GFD. This is a single-center prospective longitudinal cohort study of children (age 2-18 years) with elevated celiac serology who underwent a diagnostic endoscopy before initiation of a GFD between January and May 2022. The primary outcome was change in urinary arsenic concentration between endoscopy and after 6 months on a GFD. Of the 67 recruited participants, 50 had a biopsy diagnostic of CeD and were invited to continue the study. Thirty-five participants completed sample collection. Participants were from a middle-class, well-educated population that was predominantly White with presenting symptoms of abdominal pain (51%) and diarrhea (29%). After 6 months on a GFD, there was a significant increase in the median urinary arsenic concentration (3.3 µg/L vs 13.6 µg/L, P = 0.000004). In regression models, family history of CeD and Hispanic ethnicity were associated with having a higher urinary arsenic concentration after 6 months on a GFD. Children with newly diagnosed CeD have increased arsenic exposure shortly after transitioning to a GFD. While the arsenic levels were well below acutely toxic concentrations, the clinical impact of chronic exposure to mildly elevated arsenic levels is unknown.

Early postnatal and concurrent exposure to metals and neurobehavioral outcomes at 5 years: Associations with individual environmental exposures and mixtures

BackgroundLittle is known about the effect of postnatal exposure to heavy metals on children’s behavior problems. This study aimed to investigate the association between metal exposure during different stages of postnatal life and neurobehavioral outcomes in preschool children. MethodsUrinary concentrations of six metals (arsenic, cadmium, chromium, lead, manganese, and vanadium) were measured using inductively coupled plasma mass spectrometry in 220 participants at two time points: before 1 year and at 5 years of age. Mothers completed the Child Behavior Checklist when the children were 5 years old. Multivariable linear and logistic regression analyses were used to evaluate the association between metal concentrations and behavioral outcomes. We employed Bayesian kernel machine regression (BKMR) to assess possible joint effects and potential interactions between metal mixtures and behavioral outcomes. ResultsConcentrations of urinary arsenic (As) in infants were associated with higher scores for anxious/shy behavior problems (β ranging from 0.03 to 0.23). Further analyses showed that As exposure increased the odds of scores falling into the borderline or clinical range on anxious/depressed, affective, and pervasive developmental problems (ORs: 2.45–3.40). Stratification by sex indicated significance in girls but not in boys. BKMR analysis showed that, among the metal mixtures, As displayed a major effect on behavior scores. Concentrations of urinary cadmium in infants were also associated with higher behavioral scores but did not increase the risk of clinical problems. A cross-sectional survey in 5-year-olds did not show a significant association between concurrent metal exposure and behavioral outcome. ConclusionOur results showed that exposure to As and Cd during infancy was associated with emotional problems in children. The effect of arsenic exposure was more pronounced among female infants. We suggest reducing exposure to toxic metals during early postnatal life to prevent behavioral problems in children."

Arsenic speciation analysis in human urine for long term epidemiological studies: The Multi-Ethnic Study of Atherosclerosis (MESA)

Arsenic is a ubiquitous toxic metalloid causing serious health problems. Speciation analysis of arsenic in human urine provides valuable insights for large-scale epidemiological studies and informs on sources of exposure as well as human metabolism. The Multi-Ethnic Study of Atherosclerosis (MESA) is a valuable cohort for assessing chronic low-moderate arsenic exposure and health effects in an ethnically diverse US population. We present a state-of-the-art arsenic speciation analysis methodology and its application to 7677 MESA spot urine samples based on high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry. This method is fast, robust and detects a total of 11 individual As species at method detection limits of 0.02–0.03 μg arsenic/L urine for each individual species. Our analytical approach features excellent mean method accuracy (98%) and precision (5%) for the main arsenic species in urine (arsenobetaine, methylarsonic acid, dimethylarsinic acid, and total inorganic As); intra- (3–6%) and inter-day coefficients of variability (5–6%); column recovery (96 ± 7%); and spike recovery (97 ± 6%). The main arsenic species were detectable in ≥95% of urine samples due to the implementation of an oxidation step. Each individual minor arsenic species was detectable in ≤25% of all urines, although at least one of them was detected in almost half the participants. We identified two minor urinary arsenic species as dimethylarsinoylacetic acid and dimethylarsinoylpropionic acid, potential metabolites of seafood-related arsenicals. We observed differences in individual As species excretion by race/ethnicity, with Asian-American participants featuring 3–4 times higher concentrations compared to other participants. We also found differences by site, body mass index, smoking status, rice intake, and water arsenic levels, potentially indicating different exposures or related to individual bio-metabolism. The proposed approach is suitable for epidemiological studies and the collected data will constitute the base for future research on potential health effects of chronic low-level arsenic exposure.

Associations between Non-Essential Trace Elements in Women's Biofluids and IVF Outcomes in Euploid Single-Embryo Transfer Cycles.

Previous studies have found inconsistent associations between heavy metals and metalloids (cadmium, lead, mercury, and arsenic), and reproductive outcomes. The biofluid concentrations of ten non-essential trace elements (Hg, Pb, As, Ba, Sr, Rb, Cs, Sn, Ni, and Co) were evaluated in 51 Spanish women undergoing ICSI, PGT-A, and SET/FET. Nine out of ten non-essential elements were detectable in follicular fluid, whole blood, and urine collected the day of vaginal oocyte retrieval (VOR) and the day of embryo transfer and then analyzed by ICP-MS or Tricell DMA-80 for mercury. Elevated mercury and strontium concentrations in follicular fluid were associated with poor ovarian response and preimplantation outcomes. Worst preimplantation outcomes were also identified in women with elevated whole-blood strontium or mercury, urinary arsenic, barium, and tin the day of VOR. High concentrations of urinary rubidium on VOR day were linked with enhanced fertilization and blastocyst development. Excessive titanium in whole blood was associated with lower odds of implantation, clinical pregnancy, and achieving a live birth in a given IVF cycle. Excessive urinary arsenic on the day of embryo transfer was associated with lower odds of live birth. Although these preliminary results need to be confirmed in larger populations, distinguishing organic and inorganic element forms, our findings show that some non-essential elements have a detrimental impact on human IVF outcomes.

Determination of toxicological relevant arsenic species in urine by hydride generation microwave-induced plasma optical emission spectrometry

An analytical method for the determination of toxicological relevant species of arsenic in urine was developed and validated using hydride generation microwave-induced emission spectrometry (HG-MP-AES). This strategy can be used as an alternative to HG-HPLC-ICP-MS considered as a reference technique for arsenic speciation. This procedure is notably less expensive than other techniques and sample preparation and requires only a few steps.•Hydride generation with MP-AES detection has proven to be an effective technique for measuring arsenic metabolites in urine, which is relevant for occupational monitoring and health risk assessment purposes.•This method offers simplicity and cost-effectiveness, serving as an alternative to classical analytical procedures typically used for arsenic analysis in urine.•The methodology has been successfully applied for the purpose of workers' health surveillance.

Organochlorine pesticide residues and urinary arsenic and fluoride levels in mothers and their newborns who are residents of rural areas in Durango State, Mexico

ABSTRACT Maternal and prenatal exposure to organochlorine pesticides (OCP), arsenic (As), and fluoride (F−) is a critical public health concern. The present study assessed serum OCP residues and urinary As and F− levels in mother and newborn pairs who are residents of rural areas of Durango State, Mexico, from August 2018 to February 2019. Levels of OCP, As, and F− were measured in serum and urine samples by Gas chromatography – Tandem mass spectrometry (GC – MS/MS), Hydride generation – Atomic fluorescent spectrometry (HG-AFS, and ion-selective electron analysis (ISE), respectively, in 60 binomial mothers – newborns. Dieldrin, endrin aldehyde, and endosulfan-II were significantly higher in newborns than in mothers (p ˂0.05). Meanwhile, no significant differences were observed for As and F− concentrations between mother – newborn pairs. Differences were observed in ∑Dienes and ∑DDTs comparing newborns with normal and low birth weights and a positive relationship in ƩDienes, ƩChlordanes, and ƩDDTs between mother and newborn pairs (p ˂ 0.05). These findings highlight the importance of extensive research regarding the influence of pollution.

Exposure assessment of metal(loids) in indoor air and biomonitoring in six urban residential areas in Iran

Exposure to metal(loid)s can cause adverse health effects. This study evaluated the concentrations of aluminum, arsenic, cadmium, chromium, mercury, nickel, and lead in particulate matter <10 μm (PM10) and in the urine of 100 participants from urban residential areas in Iran. A total of 100 residential buildings (one adult from each household) in six cities across Iran were recruited for this study. The levels of metal(loid)s in PM10 and the urine of participants were measured using acid digestion followed by inductively coupled plasma mass spectrometry (ICP-MS). The average (±SE) PM10 concentration in the buildings was 51.7 ± 3.46 μg/m3. Aluminum and cadmium had the highest and lowest concentrations among the metal(loid)s, averaging 3.74 ± 1.26 μg/m3 and 0.01 ± 0.001 μg/m3, respectively. In 85 % of the samples, the concentration of metal(loid)s in indoor air exceeded WHO air quality standards. Cadmium and lead had the highest and lowest numbers of indoor air samples exceeding the recommended standards, respectively. A significant correlation was found between the concentration of metal(loid)s in urine samples and indoor PM10 levels, as well as the wealth index of participants. There was also a significant direct relationship between the concentrations of nickel, arsenic, lead, and mercury in urine and the age of participants. Factors such as building location, type of cooling systems, use of printers at home, and natural ventilation influenced the concentration and types of metal(loid)s in the indoor air.

Evaluation of oxidative damage and genotoxicity in populations exposed to arsenic in drinking water from Santa Fe province, Argentina

The presence of arsenic in the environment is a public health problem. Groundwater of certain regions of Argentina contains arsenic of natural origin in concentrations that exceed the guide level recommended by World Health Organization (WHO, 10 µg/L). Pathologies derived from chronic arsenic consumption justify the planning of human biomonitoring. Hence, the aim of this study was to evaluate oxidative damage and genotoxicity and its relationship with nutritional variables in populations exposed to arsenic through drinking water in Santa Fe province, Argentina. A total of 322 participants were analyzed for arsenic in urine together with biomarkers of genotoxicity (Comet assay in blood and frequency of Micronuclei and other Nuclear Abnormalities in exfoliated buccal cells) and oxidative stress (modified Comet assay with Endonuclease III, Lipid peroxidation and antioxidant enzyme activity), as well as nutritional and biochemical variables. Results showed that 45 % of participants excreted arsenic in the urine. Consumption of water with arsenic, whether currently or previously, was associated with statistically significant increase of oxidative DNA damage and lipid peroxidation. MN in exfoliated buccal cells serve as an early biomarker of genotoxicity and showed significant differences in the current exposed group. Biochemical results indicate dyslipidemias potentially linked to dietary choices, and insufficient intake of fruits and vegetables rich in antioxidants, was also noted. This study advocates risk communication to the population, educators, and health authorities, emphasizing the need for preventive health strategies and improved food education.

Associations among global long interspersed nuclear element-1 DNA methylation, metal exposure, and chronic kidney disease.

Long interspersed nuclear element-1 (LINE-1) methylation serves as an indicator of global DNA methylation. This study explored the correlation between LINE-1 methylation and chronic kidney disease (CKD). We also evaluated whether LINE-1 methylation could modify the association between CKD and metal exposure. A total of 213 patients with clinically defined CKD, without hemodialysis and 416 age and sex matched controls were recruited. Levels of LINE-1 methylation, total urinary arsenic, blood lead, blood cadmium, and plasma selenium were assessed. The results reveal a positive association between LINE-1 methylation and CKD, with an odds ratio (OR) of 5.30 (95% confidence interval: 2.81 to 9.99). Total urinary arsenic and blood cadmium concentrations were positively related with LINE-1 methylation. This study was the first to observe that low plasma selenium, high blood cadmium, and high blood lead levels significantly and additively interact with increased LINE-1 methylation to increase the OR of CKD. Additionally, high LINE-1 methylation interacted multiplicatively with low plasma selenium to increase the OR of CKD (p < 0.001). This study highlighted the significant association between LINE-1 hypermethylation and CKD. Furthermore, the results demonstrate that LINE-1 methylation can interact with high blood cadmium or low plasma selenium to affect CKD risk.

Abstract PO4-09-03: Environmental Metal Exposures and Breast Cancer Risk: A Prospective Study of Nationally Representative Canadian Data

Abstract Introduction: The impact of metal exposure on breast cancer risk remains unclear. Studies have explored metals independently with limited investigation into chronic exposures and mixture analyses. This project describes exposure to eight heavy and essential metals and evaluates the association between metals and breast cancer risk, independently and in a mixture, among Canadian women. Methods: Demographic information and concentrations of urinary or blood metal biomarkers from 2007-2017 of the Canadian Health Measures Survey (CHMS) were analyzed. Incident breast cancers were ascertained through linkage to the Canadian Cancer Registry. Metal exposure was described using weighted percentiles and categorized by tertiles. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for metal exposure and breast cancer risk. Quantile g-computation was used to estimate the joint association between metal exposure and breast cancer risk. Results: This analysis included 5,100 women (mean age 44.6 years) with an average follow-up of 6.6 years. Higher urinary arsenic (&amp;gt; 13.0 µg/L) and cadmium (&amp;gt; 10.0 µg/L) had a significant increased risk of breast cancer (HR Arsenic T3 vs. T1 = 2.05; 95%CI 1.05-3.94; HR Cadmium T3 vs. T1 = 1.71; 95%CI 1.01 – 5.87). Analyses into the joint association between the metal exposure mixture and breast cancer risk are ongoing, and matrix results will be presented. Conclusion: This represents the first evaluation of metal exposure and breast cancer risk in a nationally representative cohort. Our findings suggest that arsenic and cadmium, even at low levels, may be associated with an increased risk of breast cancer. These findings can inform population-level interventions to reduce the burden of cancer in Canada. Citation Format: Katherine Pullella, Jan Lubinski, Anthony Hanley, Shelley Harris, Steven Narod, Joanne Kotsopoulos. Environmental Metal Exposures and Breast Cancer Risk: A Prospective Study of Nationally Representative Canadian Data [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-09-03.

Influence of folic acid and vitamin B12 supplementation on arsenic methylation: A double-blinded, placebo-controlled trial in Bangladeshi children

BackgroundInorganic arsenic is metabolized to monomethyl- (MMAs) and dimethyl- (DMAs) species via one-carbon metabolism (OCM); this facilitates urinary arsenic elimination. OCM is influenced by folate and vitamin B12 and previous randomized control trials (RCTs) showed that folic acid (FA) supplementation increases arsenic methylation in adults. This RCT investigated the effects of FA + B12 supplementation on arsenic methylation in children, a key developmental stage where OCM supports growth. MethodsA total of 240 participants (8–11 years, 53 % female) drinking from wells with arsenic concentrations > 50 μg/L, were encouraged to switch to low arsenic wells and were randomized to receive 400 μg FA + 5 μg B12 or placebo daily for 12-weeks. Urine and blood samples were collected at baseline, week 1 (only urine) and week 12. Generalized estimated equation (GEE) models were used to assess treatment effects on arsenic species in blood and urine. ResultsAt baseline, the mean ± SD total blood and urinary arsenic were 5.3 ± 2.9 μg/L and 91.2 ± 89.5 μg/L. Overall, total blood and urine arsenic decreased by 11.7% and 17.6%, respectively, at the end of follow up. Compared to placebo, the supplementation group experienced a significant increase in the concentration of blood DMAs by 14.0% (95% CI 5.0, 25.0) and blood secondary methylation index (DMAs/MMAs) by 0.19 (95% CI: 0.09, 0.35) at 12 weeks. Similarly, there was a 1.62% (95% CI: 0.43, 20.83) significantly higher urinary %DMAs and −1.10% (95% CI: −1.73, −0.48) significantly lower urinary %MMAs in the supplementatio group compared to the placebo group after 1 week. The direction of the changes in the urinary %iAs, %MMAs, and %DMAs at week 12 were consistent with those at week 1, though estimates were not significant. Treatment effects were stronger among participants with higher baseline blood arsenic concentrations. Results were consistent across males and females, and participants with higher and lower folate and B12 status at baseline. ConclusionThis RCT confirms that FA + B12 supplementation increases arsenic methylation in children as reflected by decreased MMAs and increased DMAs in blood and urine. Nutritional interventions may improve arsenic methylation and elimination in children, potentially reducing arsenic toxicity while also improving nutritional status.

Interplay of arsenic exposure and cigarette smoking on oxidative DNA damage in healthy males

BackgroundLong-term exposure to inorganic arsenic (As) and cigarette smoking has been associated with adverse health effects such as cancer, cardiovascular disease, and respiratory disease. Oxidative stress is one of the most well-known damage mechanisms for both. However, studies on the association with induced 8-hydroxy-2-deoxyguanosine (8-OHdG) in Iran are scarce, with no study on the interactive effect of As exposure and smoking in the literature.ObjectiveThis stratified cross-sectional study aimed to assess urinary and serum 8-OHdG levels in the relation to As exposure from drinking water, smoking and their interaction effect.MethodsThis study was based on 132 healthy male subjects living in villages of Hashtroud County, Iran (2021). All participants were categorized into four groups: (i) non-As exposed, never smokers (n = 33); (ii) non-As exposed, active smokers (n = 33); (iii) As exposed, never smokers (n = 33); and (iv) As exposed, active smokers (n = 33). Data on demographic and lifestyle factors were collected, and urinary and serum levels of 8-OHdG were determined by enzyme-linked immunosorbent assay (ELISA). The smoker's daily cigarette consumption and the duration of smoking were self-reported data.ResultsParticipants consuming drinking water with an As concentration > 10 µg/L had significantly higher urinary total arsenic (U-tAs) concentrations (median 26.96, IQR 21.35–37.17) µg/g Cr compared to the reference group (median 19.33, IQR 17.29–23.26) µg/g Cr. There was a significant difference in the serum concentration of 8-OHdG between groups (i) and (iii), (iv) and also between groups (ii) and (iv). We did not find a significant interaction effect of As exposure and smoking on the both urinary and serum 8-OHdG levels (P > 0.05). Serum 8-OHdG (S-8OHdG) was associated with average daily intake of As (As-ADI) (β = 0.32; 95% CI 0.01, 0.04, P-value = 0.001) and cigarettes smoked per day (β = 0.3; 95% CI 0.00, 0.043, P-value = 0.046). While As-ADI (β = 0.16; 95% CI 0.001, 0.004, P-value = 0.01) and U-tAs (β = 0.6; 95% CI 0.006, 0.009, P-value < 0.001) were associated with increased urinary 8-OHdG (U-8OHdG), moderate physical activity (β = − 0.15; 95% CI − 0.07, − 0.008, P-value < 0.015) inversely decreased biomarker levels.ConclusionOur findings suggest that As exposure and smoking are potential risk factors for oxidative DNA damage, and it is strongly recommended to pay more attention to the role of lifestyle factors in future studies.

Associations of Urinary Total Arsenic and Arsenic Species and Periodontitis

AimsArsenic exposure is a significant global public health concern and has been implicated in endocrine disruption and increased oxidative stress, both of which are crucial pathogenic mechanisms of periodontitis. This study aimed to investigate the association of urinary total arsenic and arsenic species with periodontitis and to further explore the potential mediating roles of sex hormones and oxidative stress indicators. MethodsData used in this study were derived from the 2013–2014 National Health and Nutrition Examination Survey (NHANES) in the US population. In all, 1063 participants with complete data were included in this study. Weighted logistic regression analyses were used to evaluate the relationship between urinary arsenic and periodontitis. Mediation analyses were used to explore the effects of potential mediators on these associations. ResultsHigh concentrations of urinary dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), 2 types of toxic urinary arsenic (TUA2), and 4 types of toxic urinary arsenic (TUA4) were positively related to periodontitis (P < .05). After adjusting for potential confounders, the positive association remained significant (odds ratio, 1.32; 95% confidence interval, 1.01–1.71). Testosterone may partially mediate the relationship between MMA and periodontitis, with mediating effects of 21.78% and 39.73% of the total effect. No significant mediation effect of oxidative stress indicators was found for this relationship. ConclusionsThis study reports a positive association between urinary MMA and periodontitis, and testosterone may mediate this relationship. Our findings serve as a call for action to avoid the deployment of arsenic-containing therapeutic agents as treatment modalities for oral afflictions.

Genotoxicity in humans exposed to arsenic, lithium, and boron in drinking water in the Bolivian Andes-A cross sectional study.

Elevated concentrations of arsenic, lithium and boron in drinking water have already been reported in Bolivia. Arsenic is known to cause genotoxicity but that caused by lithium and boron is less well known. The aim of the present cross-sectional study was to evaluate potential genotoxic effects of exposure to arsenic, while considering exposure to lithium and boron and genetic susceptibility. Women (n = 230) were recruited in villages located around Lake Poopó. Exposure to arsenic was determined as the sum of concentrations of arsenic metabolites inorganic arsenic, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in urine. Exposure to lithium and boron was determined based on their concentrations in urine. Genetic susceptibility was determined by GSTM1 (glutathione S-transferase-mu-1) and GSTT1 (glutathione S-transferase-theta-1) null genotypes and AS3MT (Arsenite Methyltransferase) rs3740393. Genotoxicity was measured in peripheral blood leukocytes using the comet assay. The geometric means of arsenic, lithium, and boron concentrations were 68, 897, and 3972 μg/L, respectively. GSTM1 and GSTT1 null carriers had more DNA strand breaks than gene carriers (p = .008, p = .005). We found no correlation between urinary arsenic and DNA strand breaks (rS = .03, p = .64), and only a weak non-significant positive association in the adjusted multivariate analysis (β = .09 [-.03; .22], p = .14). Surprisingly, increasing concentrations of lithium in urine were negatively correlated with DNA strand breaks (rS = -.24, p = .0006), and the association persisted in multivariate analysis after adjusting for arsenic (β = -.22 [-.36; -.08], p = .003). We found no association between boron and DNA strand breaks. The apparent protective effect of lithium merits further investigation.

Correlation analysis of urinary arsenic species and health effect indicators of occupational arsenic exposure workers

Objective: To explore the correlation between urinary arsenic and health effects through the determination and analysis of urinary arsenic levels in occupational arsenic exposed workers. Methods: In November 2021, 95 workers exposed to arsenic and its inorganic compounds and 31 administrative personnel from a non-ferrous metal smelter in Yunnan Province were selected as the contact group and control group, respectively. Urine forms of arsenic, blood tumor markers, liver function were detected, and micronucleus test was used to analyze the chromosome damage. The correlation between urine forms of arsenic and health effects were analyzed. Results: Compared with the control group, the concentrations of urinary trivalent inorganic arsenic (iAs(3+)) , pentavalent inorganic arsenic (iAs(5+)) , inorganic arsenic (iAs=ΣiAs(3+)+iAs(5+)) , monomethyl arsenic (MMA) , dimethyl arsenic (DMA) and urinary arsenic (ΣiAs+MMA+DMA) at the end of class in contact group were higher (P<0.05) . There was no statistically significant difference in blood tumor markers and liver function indicators between the two groups (P>0.05) . Compared with the control group, the peripheral blood micronucleus rate and cell micronucleus rate in the contact group were significantly increased (P<0.05) . The urinary arsenic, iAs(5+), inorganic arsenic and DMA were positively correlated with peripheral blood micronucleus rate in contact group (r(s)=0.48, 0.34, 0.37, 0.23, P<0.05) , and the urinary arsenic, iAs(5+), DMA were positively correlated with peripheral blood micronucleus rate (r(s)=0.48, 0.34, 0.26, P<0.05) . Conclusion: There is a significant correlation between different valence states of arsenic in the urine and abnormal health effects of occupational arsenic exposed workers. It is necessary to strengthen the detection of arsenic species in the urine of occupational arsenic exposed workers to better protect their health.