Abstract  Appalachian Kentucky (App KY) leads the nation in lung cancer incidence and mortality. Trace elements, such as As, have been associated with lung cancers in other regions of the country and we hypothesized that a population-based study would reveal higher trace element concentrations in App KY individuals with cancer compared to controls. Using toenail and drinking water trace element concentrations, this study investigated a possible association between lung cancer incidence and trace-element exposure in residents of this region. This population-based case-control study had 520 subjects, and 367 subjects provided toenail samples. Additionally, we explored the relationship between toenail and fingernail trace-element concentrations to determine if fingernails could be used as a surrogate for toenails when patients are unable to provide toenail samples. We found that, contrary to our initial hypothesis, trace element concentrations (Al, As, Cr, Mn, Co, Fe, Ni, Cu, Se, and Pb) were not higher in cancer cases than controls with the exception of Zn where concentrations were slightly higher in cases. In fact, univariate logistic regression models showed that individuals with lower concentrations of several elements (Al, Mn, Cr, and Se) were more likely to have lung cancer, although only Mn was significant in multivariate models which controlled for confounding factors. While drinking water concentrations of Al, Cr and Co were positively related to cancer incidence in univariate models, only Co remained significant in multivariate models. However, since the drinking water concentrations were extremely low and not reflected in the toenail concentrations, the significance of this finding is unclear. We also found that fingernail concentrations were not consistently predictive of toenail concentrations, indicating that fingernails should not be used as surrogates for toenails in future studies.

Abstract  The occurrence and mobility of different elements in oral smokeless tobacco products (STPs) were determined because the effects on human health must take into account their availability. In this research, the elemental analysis of 15 oral STPs of different brands purchased in local specialty stores in Europe, and the determination of % extraction of the different elements into an artificial salivary juice during the sucking or chewing operations were performed. In all samples analyzed, cobalt (Co) and chromium (Cr) (total) levels were <0.326 mg/kg. As far as non-essential or toxic elements, U was always <1.0 mg/kg, Th and Ti <0.1 mg/kg, Cd was <0.5. Pb was detectable in 60% of the samples, As in 33.3% and Ce in 20% of the samples; La was <1 mg/kg in 13 samples; Sb was <5 mg/kg in all sample with exception of sample 13; Al, Ni, Sr, Rb, Ba, Sn, Te, Ti and Hg were detectable in all samples. Using artificial saliva, the data of extractable levels show that the toxic elements, although poorly extracted, are not totally retained within the STPs, with a consequent potential health hazard associated with oral use of these products.

Abstract  The neurological prognoses of very low birth weight preterm (VLBWP) children during the first 2 years of life will influence their neurodevelopment during subsequent childhood years and adolescence. The objective of this study was to systemic investigate relationships of urinary arsenic (As) concentrations, the As methylation capability, and toenail As concentrations on cognitive, language, and motor development in VLBWP children under 24 months of corrected age.Participants (n = 60) in our study were recruited from October 2010 to April 2013. Urine and toenail samples were collected for evaluation to assess As exposure. The Bayley scales of infant development III were used to evaluate neurodevelopment at 2 years of corrected age. Concentrations of As species in urine and the As concentration in toenails were, respectively, analyzed using HPLC-HG-AAS and ICP-MS.The mean concentration of total As was 28.6 μg/g creatinine, and inorganic As was 1.01 μg/L in urine. The urine contained an average of 3% inorganic As, 2% monomethylarsonic acid, and 95% dimethylarsinic acid (DMA). The mean concentration of As in toenails was 225 ng/g. Children with a longer gestational age (≥28 weeks) and higher DMA % levels appeared to have the highest unadjusted cognitive and fine motor scores.Our study results suggest that gestational age is associated with neurodevelopment in VLBWP children. We recommend that further study simultaneously analyze multiple environmental contaminants that may have adverse effects on neurodevelopment, use biomarkers for the mother-child pair, and determine whether prenatal or postnatal As exposure has a greater influence on the neurological development of VLBWP children.

Abstract  Arsenic (As) contamination in groundwater has become a geo-environmental as well as a toxicological problem across the globe affecting more than 100-million people in nearly 21 countries with its associated disease "arsenicosis." Arsenic poisoning may lead to fatal skin and internal cancers. In present review, an attempt has been made to generate awareness among the readers about various sources of occurrence of arsenic, its geochemistry and speciation, mobilization, metabolism, genotoxicity, and toxicological exposure on humans. The article also emphasizes the possible remedies for combating the problem. The knowledge of these facts may help to work on some workable remedial measure.

Abstract  The constant interplay between environment (including both exogenous and endogenous factors) and epigenome (defined as the combination of chromatin, its covalent modifications and noncoding RNAs) triggers epigenetic events that, by modulating gene expression, capture information about changes in the environment. In this mini review, we will focus on the neurodevelopmental implications of exposure to adverse prenatal milieu with emphasis on mechanistic and functional aspects. Several neurotoxic insults have been shown to affect epigenetics with negative consequences on the development of the nervous system; among them are methylmercury, lead, arsenic and cadmium, as well as excess of glucocorticoids. Further investigations on the individual susceptibility to epigenetic changes are needed to propose and validate such modifications as possible biomarkers for early identification of neurological/neurodevelopmental disorders and for predicting/monitoring response to treatment.

Abstract  The occurrence of a large number of diverse arsenic species in the environment and in biological systems makes it important to compare their relative toxicity. The toxicity of arsenic species has been examined in various cell lines using different assays, making comparison difficult. We report real-time cell sensing of two human cell lines to examine the cytotoxicity of fourteen arsenic species: arsenite (AsIII), monomethylarsonous acid (MMAIII) originating from the oxide and iodide forms, dimethylarsinous acid (DMAIII), dimethylarsinic glutathione (DMAGIII), phenylarsine oxide (PAOIII), arsenate (AsV), monomethylarsonic acid (MMAV), dimethylarsinic acid (DMAV), monomethyltrithioarsonate (MMTTAV), dimethylmonothioarsinate (DMMTAV), dimethyldithioarsinate (DMDTAV), 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone, Rox), and 4-aminobenzenearsenic acid (p-arsanilic acid, p-ASA). Cellular responses were measured in real time for 72hr in human lung (A549) and bladder (T24) cells. IC50values for the arsenicals were determined continuously over the exposure time, giving rise to IC50histograms and unique cell response profiles. Arsenic accumulation and speciation were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS). On the basis of the 24-hr IC50values, the relative cytotoxicity of the tested arsenicals was in the following decreasing order: PAOIII≫MMAIII≥DMAIII≥DMAGIII≈DMMTAV≥AsIII≫MMTTAV>AsV>DMDTAV>DMAV>MMAV≥Rox≥p-ASA. Stepwise shapes of cell response profiles for DMAIII, DMAGIII, and DMMTAVcoincided with the conversion of these arsenicals to the less toxic pentavalent DMAV. Dynamic monitoring of real-time cellular responses to fourteen arsenicals provided useful information for comparison of their relative cytotoxicity.

Abstract  BACKGROUND AND PURPOSE: The purpose of this case-cohort study was to examine urinary arsenic levels in relation to incident ischemic stroke in the United States.

METHODS: We performed a case-cohort study nested within the REGARDS (REasons for Geographic and Racial Differences in Stroke) cohort. A subcohort (n=2486) of controls was randomly sampled within region-race-sex strata while all incident ischemic stroke cases from the full REGARDS cohort (n=671) were included. Baseline urinary arsenic was measured by inductively coupled plasma-mass spectrometry. Arsenic species, including urinary inorganic arsenic and its metabolites monomethylarsonic acid and dimethylarsinic acid, were measured in a random subset (n=199). Weighted Cox's proportional hazards models were used to calculate hazard ratios and 95% confidence intervals of ischemic stroke by arsenic and its species.

RESULTS: The average follow-up was 6.7 years. Although incident ischemic stroke showed no association with total arsenic or total inorganic arsenic, for each unit higher level of urinary monomethylarsonic acid on a log-scale, after adjustment for potential confounders, ischemic stroke risk increased ≈2-fold (hazard ratio=1.98; 95% confidence interval: 1.12-3.50). Effect modification by age, race, sex, or geographic region was not evident.

CONCLUSIONS: A metabolite of arsenic was positively associated with incident ischemic stroke in this case-cohort study of the US general population, a low-to-moderate exposure area. Overall, these findings suggest a potential role for arsenic methylation in the pathogenesis of stroke, having important implications for future cerebrovascular research.

Abstract  This study was conducted in rural Pakistan to assess the dose-response relationship between skin lesions and arsenic exposure and their variation by demographic characteristics. The study included 398 participants (66 participants with skin lesions and 332 without) residing in six previously unstudied villages exposed to ground water arsenic in the range of <1 to 3090μgL-1. The skin lesions identification process involved interview and physical examinations of participants followed by confirmation by a physician according to UNICEF criteria. Urinary inorganic arsenic (iAs), total arsenic (tAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were analysed to determine methylation capacity, methylation efficiency and the dose-response relationship with skin lesions. Study participants with skin lesions were found to be exposed to arsenic >10μgL-1with a daily arsenic intake of 3.23±3.75mgday-1from household ground water sources for an exposure duration of 10-20years. The participants with skin lesions compared to those without skin lesions showed higher levels of urinary iAs (133.40±242.48 vs. 44.24±86.48μgg-1Cr), MMA (106.38±135.04 vs. 35.43±39.97μgg-1Cr), MMA% (15.26±6.31 vs.12.11±4.68) and lower levels of DMA% (66.99±13.59 vs. 73.39±10.44) and secondary methylation index (SMI) (0.81±0.11 vs. 0.86±0.07). Study participants carrying a lower methylation capacity characterized by higher MMA% (OR 5.06, 95% CI: 2.09-12.27), lower DMA% (OR 0.64, 95% CI: 0.33-1.26), primary methylation index (PMI) (OR 0.56, 95% CI: 0.28-1.12) and SMI (OR 0.43, 95% CI: 0.21-0.88) had a significantly higher risk of skin lesions compared to their corresponding references after adjusting for occupation categories. The findings confirmed that inefficient arsenic methylation capacity was significantly associated with increased skin lesion risks and the effect might be modified by labour intensive occupations.

Abstract  Arsenic and its compounds are well-established, potent, environmentally widespread and persistent toxicants with metabolic, genotoxic, mutagenic, teratogenic, epigenetic and carcinogenic effects. Arsenic occurs naturally in the Earth's crust, but anthropogenic arsenic emissions have surmounted the emissions from important natural sources such as volcanism. Inorganic arsenicals exhibit acute and chronic toxicities in virtually all cell types and tissues, and hence arsenic intoxication affects multiple systems. Whereas acute arsenic intoxication is rare and relatively easy to diagnose, chronic arsenic intoxication (CAsI) is common but goes often misdiagnosed. Based on a review of the literature as well as our own clinical experience, we propose a chronic arsenic intoxication diagnostic score (CAsIDS). A distinctive feature of CAsIDS is the use of bone arsenic load as an essential criterion for the individual risk assessment of chronic arsenic intoxication, combined with a systemic clinical assessment. We present clinical examples where CAsIDS is applied for the diagnosis of CAsI, review the main topics of the toxicity of arsenic in different cell and organ systems and discuss the therapy and prevention of disease caused or aggravated by chronic arsenic intoxication. CAsIDS can help physicians establish the diagnosis of CAsI and associated conditions.

Abstract  Inorganic arsenic (iAs) is a known toxicant and carcinogen. Worldwide arsenic exposure has become a threat to human health. The severity of arsenic toxicity is strongly correlated with the speed of arsenic metabolism (methylation) and clearance. Furthermore, oxidative stress is recognized as a major mechanism for arsenic-induced toxicity. Nuclear factor-E2-related factor 2 (Nrf2), a key regulator in cellular adaptive antioxidant response, is clearly involved in alleviation of arsenic-induced oxidative damage. Multiple studies demonstrate that Nrf2 deficiency mice are more vulnerable to arsenic-induced intoxication. However, what effect Nrf2 deficiency might have on arsenic metabolism in mice is still unknown. In the present study, we measured the key enzymes involved in arsenic metabolism in Nrf2-WT and Nrf2-KO mice. Our results showed that basal transcript levels of glutathione S-transferase omega 2 (Gsto2) were significantly higher and GST mu 1 (Gstm1) lower in Nrf2-KO mice compared to Nrf2-WT control. Arsenic speciation and methylation rate in liver and urine was then studied in mice treated with 5mg/kg sodium arsenite for 12h. Although there were some alterations in arsenic metabolism enzymes between Nrf2-WT and Nrf2-KO mice, the Nrf2 deficiency had no significant effect on arsenic methylation. These results suggest that the Nrf2-KO mice are more sensitive to arsenic than Nrf2-WT mainly because of differences in adaptive antioxidant detoxification capacity rather than arsenic methylation capacity.

Abstract  Arsenic contamination of drinking water is a great concern for public health throughout the world. This alarming situation led to many independent research studies but there are only a few studies till date which collectively articulated all studies together with a multidisciplinary approach for better understanding. The present article is an effort towards collating the advances made in understanding the impacts of arsenic toxicity on human beings. It discusses the sources, mobility, sensing and metabolism patterns of arsenic. It also deals with understanding the impact of arsenic toxicity over clinical health, nutritional status, carcinogenicity, genomics, and social and economic status of human beings. Though many evaluative studies have been conducted, there are no easy and effective measures of sensing and remediation available till date. Hence, we conclude that more collective, multidisciplinary, advanced and target-specific studies are essential, the outcome of which can contribute in developing better prevention strategies and technological mitigation programmes for the betterment of human kind.

Abstract  Rice accumulates 10-fold higher inorganic arsenic (i-As), an established human carcinogen, than other grains. This review summarizes epidemiologic studies that examined the association between rice consumption and biomarkers of arsenic exposure. After reviewing the literature we identified 20 studies, among them included 18 observational and 2 human experimental studies that reported on associations between rice consumption and an arsenic biomarker. Among individuals not exposed to contaminated water, rice is a source of i-As exposure - rice consumption has been consistently related to arsenic biomarkers, and the relationship has been clearly demonstrated in experimental studies. Early-life i-As exposure is of particular concern due to its association with lifelong adverse health outcomes. Maternal rice consumption during pregnancy also has been associated with infant toenail total arsenic concentrations indicating that dietary exposure during pregnancy results in fetal exposure. Thus, the collective evidence indicates that rice is an independent source of arsenic exposure in populations around the world and highlights the importance of investigating its affect on health.

Abstract  Inter-individual differences in arsenic metabolism have been linked to arsenic-related disease risks. Arsenic (+3) methyltransferase (AS3MT) is the primary enzyme involved in arsenic metabolism, and we previously demonstrated in vitro that N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) also methylates the toxic inorganic arsenic (iAs) metabolite, monomethylarsonous acid (MMA), to the less toxic dimethylarsonic acid (DMA). Here, we evaluated whether AS3MT and N6AMT1 gene polymorphisms alter arsenic methylation and impact iAs-related cancer risks. We assessed AS3MT and N6AMT1 polymorphisms and urinary arsenic metabolites (%iAs, %MMA, %DMA) in 722 subjects from an arsenic-cancer case-control study in a uniquely exposed area in northern Chile. Polymorphisms were genotyped using a custom designed multiplex, ligation-dependent probe amplification (MLPA) assay for 6 AS3MT SNPs and 14 tag SNPs in the N6AMT1 gene. We found several AS3MT polymorphisms associated with both urinary arsenic metabolite profiles and cancer risk. For example, compared to wildtypes, individuals carrying minor alleles in AS3MT rs3740393 had lower %MMA (mean difference = -1.9%, 95% CI: -3.3, -0.4), higher %DMA (mean difference = 4.0%, 95% CI: 1.5, 6.5), and lower odds ratios for bladder (OR = 0.3; 95% CI: 0.1-0.6) and lung cancer (OR = 0.6; 95% CI: 0.2-1.1). Evidence of interaction was also observed for both lung and bladder cancer between these polymorphisms and elevated historical arsenic exposures. Clear associations were not seen for N6AMT1. These results are the first to demonstrate a direct association between AS3MT polymorphisms and arsenic-related internal cancer risk. This research could help identify subpopulations that are particularly vulnerable to arsenic-related disease. Environ. Mol. Mutagen. 58:411-422, 2017. © 2017 Wiley Periodicals, Inc.

Abstract  Chronic arsenic exposure can result in adverse development effects including decreased intellectual function, reduced birth weight, and altered locomotor activity. Previous in vitro studies have shown that arsenic inhibits stem cell differentiation. MicroRNAs (miRNAs) are small non-coding RNAs that regulate multiple cellular processes including embryonic development and cell differentiation. The purpose of this study was to examine whether altered miRNA expression was a mechanism by which arsenic inhibited cellular differentiation. The pluripotent P19 mouse embryonal carcinoma cells were exposed to 0 or 0.5 μM sodium arsenite for 9 days during cell differentiation, and changes in miRNA expression was analyzed using microarrays. We found that the expression of several miRNAs important in cellular differentiation, such as miR-9 and miR-199 were decreased by 1.9- and 1.6-fold respectively following arsenic exposure, while miR-92a, miR-291a, and miR-709 were increased by 3-, 3.7- and 1.6-fold, respectively. The members of the miR-466-669 cluster and its host gene, Scm-Like with four Mbt domains 2 (Sfmbt2), were significantly induced by arsenic from 1.5- to 4-fold in a time-dependent manner. Multiple miRNA target prediction programs revealed that several neurogenic transcription factors appear to be targets of the cluster. When consensus anti-miRNAs targeting the miR-466-669 cluster were transfected into P19 cells, arsenic-exposed cells were able to more effectively differentiate. The consensus anti-miRNAs appeared to rescue the inhibitory effects of arsenic on cell differentiation due to an increased expression of NeuroD1. Taken together, we conclude that arsenic induces the miR-466-669 cluster, and that this induction acts to inhibit cellular differentiation in part due to a repression of NeuroD1.

Abstract  Pollution by trace elements and its possible effect on organisms has become a worldwide concern due to the increasing presence of trace elements in the environment and especially in the food chain. Exposure to chemicals has traditionally been measured using environmental samples, however, human biomonitoring brings a different perspective, in which all sources and exposure pathways are integrated. The objective of this paper is to discern the possible relationship between children's diet and the metals found in children urine. With this aim in mind, a total of 120 voluntaries participated in a diet survey carried out in a school-aged population (age 6-11) from the Valencian region. In addition, twenty trace elements were analysed in children urine (arsenic, antimony, barium, beryllium, caesium, cadmium, cobalt, copper, lead, manganese, mercury, molybdenum, nickel, platinum, selenium, thallium, thorium, uranium, vanadium and zinc). Results permitted to compare metal levels in urine with metal levels of other biomonitoring studies to conclude that values, including ours, were similar in most studies. On the other hand, children who ate more vegetables had the highest values in cadmium, copper, molybdenum, antimony, thallium, vanadium, and zinc, while those who ate more fish reached higher values in mercury. Finally, children who ate more cereals and baked products had higher values in total arsenic.

Abstract  Consumption of contaminated food is a major route of exposure to toxic contaminants for humans. To protect against potential negative health effects from rice consumption, As and Cd concentrations in rice sold in Bangkok were determined, and non-carcinogenic and carcinogenic risk assessments were conducted. Four types of rice (n = 97), namely, white jasmine, white, glutinous, and brown jasmine, were collected. Samples were acid-digested and analyzed for total concentrations of As and Cd by ICP-MS. The average concentrations of As and Cd were 0.205 ± 0.008 and 0.019 ± 0.001 mg kg-1, respectively. Approximately 22.8, 62.5, and 57.1% of white, white jasmine, and brown jasmine rice, respectively, contained As concentrations exceeding the Codex inorganic As standards for polished and unpolished rice. Brown jasmine rice contained significantly higher As concentrations than the other types of rice. However, Cd concentrations in all rice samples were significantly lower than the Codex standard of 0.4 mg kg-1. Children are exposed to the highest amounts of both elements. Concerning As exposure through the consumption of different types of rice in the same age group, the consumption of brown jasmine rice caused approximately 1.7 to 2.3 times higher As exposure rates compared to the consumption of other types of rice. Non-carcinogenic risks (hazard quotient (HQ)) of As exposure from all types of rice were higher than the threshold limit of 1. HQ in children ranging from 2.1 to 4.9 was significantly higher than HQ in the other age groups. The cancer risks from As exposure were negligible in all groups.

Abstract  Human studies suggest that in utero exposure to arsenic results in adverse pregnancy outcomes. The use of dietary supplements, such as sodium selenite (SS) or α-tocopherol succinate (α-TOS), is a reasonable approach to ameliorate such health effects. Sodium arsenite at 100ppm was administered via drinking water to female hamsters from gestational days 1 or 8 to the time of delivery. Viable fetuses, fetal resorptions and non-viable fetuses were recorded during and after pregnancy and total arsenic and its metabolites were characterized in pregnant animals, placentas and fetuses. Arsenic was found to accumulate in the placenta and fetus, increasing fetal mortality, non-viable fetuses and resorptions. Co-administration of SS and α-TOS significantly reduced the observed teratogenic effects. SS influenced arsenic biotransformation by reducing the MMA/InAs index and increasing the DMA/MMA, whereas α-TOS more likely exerts its protective effect through its potent antioxidant activity.

Abstract  BACKGROUND: Rice contains arsenic, a known skin carcinogen. Rice intake has been associated with arsenic-related skin lesions in South Asia, but its association with skin cancers is as yet unknown.

OBJECTIVES: We aimed to investigate whether rice intake contributes to urinary arsenic concentration and risk of squamous cell carcinoma (SCC) of the skin in a U.S. population.

METHODS: Rice consumption was assessed using a food frequency questionnaire administered as part of a population-based case-control study of 487 SCC cases and 462 age- and gender-matched controls. Arsenic concentration in household tap water and urine samples were measured using inductively coupled mass spectrometry (ICP-MS) and high-resolution ICP-MS, respectively. Odds ratios (OR) for SCC associated with the frequency of rice consumption were estimated using logistic regression, with adjustment for age, gender, and caloric intake.

RESULTS: Those who reported any rice consumption had higher urinary arsenic concentrations than those who did not consume rice, and the association was most pronounced among those with <1μg/L arsenic in their household water (19.2% increase in total urinary arsenic, 95% CI: 5.0, 35.3%). Any rice consumption was associated with a 1.5-fold (95% CI: 1.1, 2.0) higher odds of SCC compared with those who reported no rice consumption, and the relation appeared to be largely among those with <1μg/L water arsenic.

CONCLUSION: Rice consumption may be related to the occurrence of SCC in the United States, especially among those with relatively low drinking water arsenic exposure. https://doi.org/10.1289/EHP1065.

Abstract  Our group previously reported that arsenic (As) exposure induced apoptosis in hippocampus neurons. The aim of the present study was to clarify the protective capacity of taurine (Tau) on As-induced neuronal apoptosis and the related mechanism in mouse hippocampus. Mice were divided into: control group, Tau control group, As exposure group and Tau protective group, randomly. The apoptotic rate of mouse hippocampus was determined by TUNEL staining. The levels of Bcl-2 and Bax gene and protein were analyzed by real time RT-PCR and WB, respectively. Furthermore, cytochrome c (Cyt C) release, and the activity of caspase-8 and caspase-3 were also determined. The results showed that Tau treatment induced the decrease of TUNEL-positive cells, prohibited the disturbance of Bcl-2 and Bax expression, and inhibited Cyt C release and caspase-8 and caspase-3 activation significantly. The results indicated that Tau supplement markedly ameliorates As-induced apoptosis by mitochondria-related pathway in mouse hippocampus.

Abstract  BACKGROUND: Arsenic 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.

OBJECTIVES: To assess which time point maternal arsenic exposure may influence the fetus during pregnancy and birth outcomes.

METHODS: In 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.

RESULTS: We 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.

CONCLUSIONS: We 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.

Abstract  A slurry sampling procedure for arsenic speciation analysis in baby food by arsane generation, cryogenic trapping and detection with atomic absorption spectrometry is presented. Several procedures were tested for slurry preparation, including different reagents (HNO3, HCl and tetramethylammonium hydroxide - TMAH) and their concentrations, water bath heating and ultrasound-assisted agitation. The best results for inorganic arsenic (iAs) and dimethylarsinate (DMA) were reached when using 3molL-1HCl under heating and ultrasound-assisted agitation. The developed method was applied for the analysis of five porridge powder and six baby meal samples. The trueness of the method was checked with a certified reference material (CRM) of total arsenic (tAs), iAs and DMA in rice (ERM-BC211). Arsenic recoveries (mass balance) for all samples and CRM were performed by the determination of the tAs by inductively coupled plasma mass spectrometry (ICP-MS) after microwave-assisted digestion and its comparison against the sum of the results from the speciation analysis. The relative limits of detection were 0.44, 0.24 and 0.16µgkg-1for iAs, methylarsonate and DMA, respectively. The concentrations of the most toxic arsenic species (iAs) in the analyzed baby food samples ranged between 4.2 and 99µgkg-1which were below the limits of 300, 200 and 100µgkg-1set by the Brazilian, Chinese and European legislation, respectively.

Abstract  BACKGROUND: Chronic exposure to inorganic arsenic is an important public health problem and leads to hyperpigmentation, hyperkeratosis, Bowen's disease and non-melanoma skin cancers in humans. Arsenic keratosis is the most common skin change that is associated with arsenic exposure. It may be an indicator of arsenic induced health hazards.

OBJECTIVE: To determine the needs of patients with arsenic keratosis by evaluating the impact of disease on the quality of life with respect to treatment and provide rehabilitation services.

METHODS: A total of 47 subjects with arsenic hyperkeratosis, were enrolled in this crossover study. The demographics, smoking status and the presence of chronic diseases diagnosed by the physician were recorded. Weight and height of the subjects were measured and BMI was calculated. The patients were asked to respond the visual analogue scale and EuroQoL-5D scales for assessing the pain and quality of life impairment associated with arsenic hyperkeratosis.

RESULTS: In the study group, moderate to severe problems were reported in 78.7% of patients for pain/uncomfortable condition domains and in 91.5% in anxiety/depression domains. Lower quality of life was reported in those with associated chronic disorders, at an advanced age, in thin patients and in those with severe lesions.

CONCLUSION: According to our knowledge, our study is the first one measuring the quality of life in patients with arsenic keratosis in the literature. By this study, we tried to underline the guidance of health services to be developed towards the needs of patients and the need for the development of new health policies by determining the requirements of these patients.

Abstract  BACKGROUND: Shortening of gestation and intrauterine growth restriction (IUGR) are the two main determinants of birthweight. Low birthweight has been linked with prenatal arsenic exposure, but the causal relation between arsenic and birthweight is not well understood.

OBJECTIVES: We applied a quantile causal mediation analysis approach to determine the association between prenatal arsenic exposure and birthweight in relation to shortening of gestation and IUGR, and whether the susceptibility of arsenic exposure varies by infant birth sizes.

METHODS: In a longitudinal birth cohort in Bangladesh, we measured arsenic in drinking water (n=1182) collected at enrollment and maternal toenails (n=1104) collected ≤1-month postpartum using inductively coupled plasma mass spectrometry. Gestational age was determined using ultrasound at ≤16weeks' gestation. Demographic information was collected using a structured questionnaire.

RESULTS: Of 1184 singleton livebirths, 16.4% (n=194) were low birthweight (<2500g), 21.9% (n=259) preterm (<37weeks' gestation), and 9.2% (n=109) both low birthweight and preterm. The median concentrations of arsenic in drinking water and maternal toenails were 2.2μg/L (range: below the level of detection [LOD]-1400) and 1.2μg/g (range: <LOD-46.6), respectively. Prenatal arsenic exposure was negatively associated with birthweight, where the magnitude of the association varied across birthweight percentiles. The effect of arsenic on birthweight mediated via shortening of gestation affected all infants irrespective of birth sizes (β range: 10th percentile=-19.7g [95% CI: -26.7, -13.3] to 90th percentile=-10.9g [95% CI: -18.5, -5.9] per natural log water arsenic increase), whereas the effect via pathways independent of gestational age affected only the smaller infants (β range: 10th percentile=-28.0g [95% CI: -43.8, -9.9] to 20th percentile=-14.9g [95% CI: -30.3, -1.7] per natural log water arsenic increase). Similar pattern was observed for maternal toenail arsenic.

CONCLUSIONS: The susceptibility of prenatal arsenic exposure varied by infant birth sizes, placing smaller infants at greater risk of lower birthweight by shortening of gestation and possibly growth restriction. It is important to mitigate prenatal arsenic exposure to improve perinatal outcomes in Bangladesh.

Abstract  Exposure to arsenic leads to inhibition of the anti-oxidant defense mechanism of the body. Reactive oxygen species generated in response to arsenic causes reproductive failures in exposed females and also acts as an inducer of apoptosis. As a prospective remedial agent, all-trans retinoic acid (ATRA) was assessed for reversing arsenic-induced oxidative stress and apoptosis. Rats exposed to arsenic for 28 days were allowed to recover naturally or were treated simultaneously with ATRA for 28 days or up to 56 days. Production of H2O2was detected using 2',7'-dichlorfluorescein diacetate (DCFCA) by flow cytometry. Catalase, superoxide dismutase, glutathione, ALT, and AST were estimated by biochemical assays and Western blot analyses. Detection of apoptosis was performed using annexin V-FITC/propidium iodide. Expressions of p53, p21, cleaved caspase 3, JNK/pJNK, and ERK/pERK levels were estimated using Western blot analysis. Elemental arsenic deposition in the rat uterus and liver was estimated by atomic absorption spectrophotometry. Our results confirmed that ATRA ameliorated sodium arsenite-induced ROS generation, restored redox balance, and prevented apoptosis. Concomitant recovery was observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Tissue arsenic deposition was significantly reduced in the uterus upon continuous ATRA treatment. The results revealed that ATRA reversed arsenic-induced free radical generation, activated the anti-oxidant defence system, and subsequently repressed p53-dependent apoptosis through inhibition of the MAPK signaling components.

Abstract  The environmental obesogen model proposes that in addition to a high-calorie diet and diminished physical activity, other factors such as environmental pollutants and chemicals are involved in the development of obesity. Although arsenic has been recognized as a risk factor for Type 2 Diabetes with a specific mechanism, it is still uncertain whether arsenic is also an obesogen. The impairment of white adipose tissue (WAT) metabolism is crucial in the onset of obesity, and distinct studies have evaluated the effects of arsenic on it, however only in some of them for obesity-related purposes. Thus, the known effects of arsenic on WAT/adipocytes were integrated based on the diverse metabolic and physiological processes that occur in WAT and are altered in obesity, specifically: adipocyte growth, adipokine secretion, lipid metabolism, and glucose metabolism. The currently available information suggests that arsenic can negatively affect WAT metabolism, resulting in arsenic being a potential obesogen.