Chronic arsenic poisoning: A sinister cause of peripheral neuropathy in a young couple.

ABSTRACT: Arsenic compounds are colorless and odorless and toxicity can occur either acutely following ingestion of arsenicals with gastrointestinal disturbances or due to chronic exposure usually presenting with dermatologic lesions and peripheral neuropathy. We report a young couple who presented with signs and symptoms of painful sensorimotor peripheral neuropathy in a typical "stocking and glove" pattern. They had raised urinary arsenic levels with normal blood levels and thus, a diagnosis of chronic arsenic poisoning due to contaminated water intake was made after detecting elevated arsenic levels in their home water supply. Both patients underwent chelation therapy with dimercaprol for 14 days and reported subjective and objective improvement in symptoms with the reduction in urinary arsenic levels at the end of therapy.

Trace element levels: How Substance Use Disorder (SUD) contributes to the alteration of urinary essential and toxic element levels.

Increasing illicit drug use is one of the main problems in most countries or societies. Monitoring heavy metals and trace elements in this vulnerable group seems to be necessary. Therefore, we assessed the urinary trace element and toxic metals/metalloids concentrations (Zinc (Zn), Iron (Fe), Copper (Cu), Chromium (Cr), Lead (Pb), Cadmium (Cd), Arsenic (As), Nickel (Ni), and Mercury (Hg)) in opium, tramadol, and cannabis users compared to healthy subjects. In this cross-sectional study, patients with substance use disorder (SUD) (n = 74) were divided into four groups: cannabis, tramadol, opium, and mixed (simultaneous use of more than one of the three studied substances), along with a healthy group (n = 60). Urine samples were prepared by dispersive liquid-liquid microextraction method so that heavy metals/metalloids could be measured by ICP-MS. The mean urinary concentration of Cu (48.15 vs. 25.45; 89.2%, p<0.001), Hg (1.3 vs. 0.10; 1200%, p < 0.001), and Zn (301.95 vs. 210; 43.8%, p < 0.001) was markedly lower among patients with SUD. The mean urinary concentration of other elements including As (1.9 vs. 4.1; 115.8%), Cd (0.1 vs. 1.10; 1000%), Cr (6.80 vs. 11.65; 71.3%), Ni (2.95 vs. 4.95; 67.8%), and Pb (1.5 vs. 7.9; 426.6%) were significantly higher among patients with SUD compared to healthy subjects. When sub-groups were compared, no significant differences were observed between their trace element levels (Kruskal-Wallis test, p > 0.05). This can be an indication that regardless of the type of drug, the levels of trace elements are changed with respect to healthy individuals. Our results showed that illicit drug use causes changes in urinary trace element/heavy metal/metalloid levels and highlights the need for monitoring heavy metals and trace elements in individuals with substance use disorder. Assessment of different elements in biological samples of drug dependents may be useful for implementing new prevention and treatment protocols. In case of changes in their levels, complementary recommendations, attention to diet, and periodic assessment of toxic metal levels within treatment programs will be needed.

Method validation for (ultra)-trace element concentrations in urine for small sample volumes in large epidemiological studies: application to the population-based epidemiological multi-ethnic study of atherosclerosis (MESA).

Analysis of essential and non-essential trace elements in urine has emerged as a valuable tool for assessing occupational and environmental exposures, diagnosing nutritional status and guiding public health and health care intervention. Our study focused on the analysis of trace elements in urine samples from the Multi-Ethnic Study of Atherosclerosis (MESA), a precious resource for health research with limited sample volumes. Here we provide a comprehensive and sensitive method for the analysis of 18 elements using only 100 µL of urine. Method sensitivity, accuracy, and precision were assessed. The analysis by inductively coupled plasma mass spectrometry (ICP-MS) included the measurement of antimony (Sb), arsenic (As), barium (Ba), cadmium (Cd), cesium (Cs), cobalt (Co), copper (Cu), gadolinium (Gd), lead (Pb), manganese (Mn), molybdenum (Mo), nickel (Ni), selenium (Se), strontium (Sr), thallium (Tl), tungsten (W), uranium (U), and zinc (Zn). Further, we reported urinary trace element concentrations by covariates including gender, ethnicity/race, smoking and location. The results showed good accuracy and sensitivity of the ICP-MS method with the limit of detections rangings between 0.001 µg L-1 for U to 6.2 µg L-1 for Zn. Intra-day precision for MESA urine analysis varied between 1.4% for Mo and 26% for Mn (average 6.4% for all elements). The average inter-day precision for most elements was <8.5% except for Gd (20%), U (16%) and Mn (19%) due to very low urinary concentrations. Urinary mean concentrations of non-essential elements followed the order of Sr > As > Cs > Ni > Ba > Pb > Cd > Gd > Tl > W > U. The order of urinary mean concentrations for essential trace elements was Zn > Se > Mo > Cu > Co > Mn. Non-adjusted mean concentration of non-essential trace elements in urine from MESA participants follow the order Sr > As > Cs > Ni > Ba > Pb > Cd > Gd > Tl > W > U. The unadjusted urinary mean concentrations of essential trace elements decrease from Zn > Se > Mo > Cu > Co > Mn.

Association of urinary exposure to multiple metal(loid)s with kidney function from a national cross-sectional study.

BACKGROUND: Arsenic (As), cadmium (Cd) and copper (Cu) are hazardous for kidney function, while the effects of selenium (Se) and zinc (Zn) were unexplored for the narrow safe range of intake. Interactions exists between these multiple metal/metalloid exposures, but few studies have investigated the effects. METHODS: A cross-sectional survey was performed among 2210 adults across twelve provinces in China between 2020 and 2021. Urinary As, Cd, Cu, Se and Zn were measured using inductively coupled plasma-mass spectrometry (ICP-MS). Serum creatinine (Scr) and N-acetyl-beta-D glucosaminidases (urine NAG) were quantified in serum and urine, respectively. Kidney function was evaluated by the estimated glomerular filtration rate (eGFR). We employed logistic regression and Bayesian kernel machine regression (BKMR) models to explore the individual and joint effects of urinary metals/metalloids on the risk of impaired renal function (IRF) or chronic kidney disease (CKD), respectively. RESULTS: Association was found between As (OR = 1.24, 95 % CI: 1.03, 1.48), Cd (OR = 1.65, 95 % CI: 1.35, 2.02), Cu (OR = 1.90, 95 % CI: 1.59, 2.29), Se (OR = 1.51, 95 % CI: 1.24, 1.85) and Zn (OR = 1.33, 95 % CI: 1.09, 1.64) and the risk of CKD. Moreover, we observed association between As (OR = 1.18, 95 % CI: 1.07, 1.29), Cu (OR = 1.14, 95 % CI: 1.04, 1.25), Se (OR = 1.15, 95 % CI: 1.06, 1.26) and Zn (OR = 1.12, 95 % CI: 1.02, 1.22) and the risk of IRF. Additionally, it was found that Se exposure may strength the association of urinary As, Cd and Cu with IRF. Furthermore, it is worth noting that Se and Cu contributed greatest to the inverse association in IRF and CKD, respectively. CONCLUSION: Our findings suggested that metal/metalloid mixtures were associated with kidney dysfunction, Se and Cu were inverse factors. Additionally, interactions between them may affect the association. Further studies are needed to assess the potential risks for metal/metalloid exposures.

The Folic Acid and Creatine Trial: Treatment Effects of Supplementation on Arsenic Methylation Indices and Metabolite Concentrations in Blood in a Bangladeshi Population.

BACKGROUND: Chronic arsenic (As) exposure is a global environmental health issue. Inorganic As (InAs) undergoes methylation to monomethyl (MMAs) and dimethyl-arsenical species (DMAs); full methylation to DMAs facilitates urinary excretion and is associated with reduced risk for As-related health outcomes. Nutritional factors, including folate and creatine, influence one-carbon metabolism, the biochemical pathway that provides methyl groups for As methylation. OBJECTIVE: Our aim was to investigate the effects of supplementation with folic acid (FA), creatine, or the two combined on the concentrations of As metabolites and the primary methylation index (PMI: MMAs/InAs) and secondary methylation index (SMI: DMAs/MMAs) in blood in Bangladeshi adults having a wide range of folate status. METHODS: In a randomized, double-blinded, placebo (PBO)-controlled trial, 622 participants were recruited independent of folate status and assigned to one of five treatment arms: a) PBO (n=102), b) 400µg FA/d (400FA; n=153), c) 800µg FA/d (800FA; n=151), d) 3g creatine/d (creatine; n=101), or e) 3g creatine+400µg of FA/d (creatine+400FA; n=103) for 12 wk. For the following 12 wk, half of the FA participants were randomly switched to the PBO while the other half continued FA supplementation. All participants received As-removal water filters at baseline. Blood As (bAs) metabolites were measured at weeks 0, 1, 12, and 24. RESULTS: At baseline, 80.3% (n=489) of participants were folate sufficient (≥9 nmol/L in plasma). In all groups, bAs metabolite concentrations decreased, likely due to filter use; for example, in the PBO group, blood concentrations of MMAs (bMMAs) (geometric mean±geometric standard deviation) decreased from 3.55±1.89µg/L at baseline to 2.73±1.74 at week 1. After 1 wk, the mean within-person increase in SMI for the creatine+400FA group was greater than that of the PBO group (p=0.05). The mean percentage decrease in bMMAs between baseline and week 12 was greater for all treatment groups compared with the PBO group [400FA: -10.4 (95% CI: -11.9, -8.75), 800FA: -9.54 (95% CI: -11.1, -7.97), creatine: -5.85 (95% CI: -8.59, -3.03), creatine+400FA: -8.44 (95% CI: -9.95, -6.90), PBO: -2.02 (95% CI: -4.03, 0.04)], and the percentage increase in blood DMAs (bDMAs) concentrations for the FA-treated groups significantly exceeded that of PBO [400FA: 12.8 (95% CI: 10.5, 15.2), 800FA: 11.3 (95% CI: 8.95, 13.8), creatine+400FA: 7.45 (95% CI: 5.23, 9.71), PBO: -0.15 (95% CI: -2.85, 2.63)]. The mean decrease in PMI and increase in SMI in all FA groups significantly exceeded PBO (p<0.05). Data from week 24 showed evidence of a reversal of treatment effects on As metabolites from week 12 in those who switched from 800FA to PBO, with significant decreases in SMI [-9.0% (95% CI: -3.5, -14.8)] and bDMAs [-5.9% (95% CI: -1.8, -10.2)], whereas PMI and bMMAs concentrations continued to decline [-7.16% (95% CI: -0.48, -14.3) and -3.1% (95% CI: -0.1, -6.2), respectively] for those who remained on 800FA supplementation. CONCLUSIONS: FA supplementation lowered bMMAs and increased bDMAs in a sample of primarily folate-replete adults, whereas creatine supplementation lowered bMMAs. Evidence of the reversal of treatment effects on As metabolites following FA cessation suggests short-term benefits of supplementation and underscores the importance of long-term interventions, such as FA fortification. https://doi.org/10.1289/EHP11270.

Chronic Kidney Disease: Combined Effects of Gene Polymorphisms of Tissue Inhibitors of Metalloproteinase 3, Total Urinary Arsenic, and Blood Lead Concentration.

The tissue inhibitor of metalloproteinase 3 (TIMP3) is known to be an anti-fibrotic factor. Arsenic, lead, and cadmium exposure and selenium intake may affect TIMP3 expression. The downregulation of TIMP3 expression is related to kidney fibrosis. Genotypes of TIMP3 are related to hypertension and cardiovascular diseases. Therefore, this study explored whether TIMP3 polymorphism is associated with hypertension-related chronic kidney disease (CKD). In addition, the combined effects of TIMP3 polymorphism and total urinary arsenic, blood lead and cadmium, and plasma selenium concentrations on CKD, were investigated. This was a case-control study, with 213 CKD patients and 423 age- and sex-matched controls recruited. Polymerase chain reaction-restriction fragment length polymorphism was used to determine TIMP3 gene polymorphisms. The concentrations of urinary arsenic species, plasma selenium, and blood lead and cadmium were measured. The odds ratio (OR) of CKD in the TIMP3rs9609643 GA/AA genotype was higher than that of the GG genotype at high levels of total urinary arsenic and blood lead; the OR and 95% confidence interval (CI) were 0.57 (0.31-1.05) and 0.52 (0.30-0.93), respectively, after multivariate adjustment. High blood lead levels tended to interact with the TIMP3rs9609643 GG genotype to increase the OR of CKD, and gave the highest OR (95% CI) for CKD of 5.97 (2.60-13.67). Our study supports a possible role for the TIMP3rs9609643 risk genotype combined with high total urinary arsenic or with high blood lead concentration to increase the OR of CKD.

Determination of potential sources of heavy metals in patients with urothelial carcinoma in central Taiwan: a biomonitoring case-control study.

The clarification of possible exposure sources of multiple metals to identify associations between metal doses and urothelial carcinoma (UC) risk is currently limited in the literature. We sought to identify the exposure sources of 10 metals (Vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, cadmium, and lead) using principal component analysis (PCA) and then linked various principal component (PC) scores with environmental characteristics, including smoking-related indices, PM2.5, and distance to the nearest bus station. In addition, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and DNA hypomethylation markers (5-methyl-2'-deoxycytidine levels; %5-MedC) were investigated in combination with UC risks. We conducted this hospital-based case control study in 359 UC patients with histologically confirmed disease and 718 controls. All data were collected from face-to-face interviews and medical records. Approximately 6 mL blood was collected from participants for analysis of multiple heavy metal and DNA methylation in leukocyte DNA. Further, a 20 mL urine sample was collected to measure urinary cotinine and 8-OHdG levels. In addition, average values for PM2.5 for individual resident were calculated using the hybrid kriging/land-use regression model. In UC patients, significantly higher cobalt, nickel, copper, arsenic, and cadmium (µg/L) levels were observed in blood when compared with controls. Three PCs with eigenvalues > 1 accounted for 24.3, 15.8, and 10.7% of UC patients, and 26.9, 16.7, and 11.1% of controls, respectively. Environmental metal sources in major clusters were potentially associated with industrial activities and traffic emissions (PC1), smoking (PC2), and food consumption, including vitamin supplements (PC3). Multiple metal doses were linked with incremental urinary 8-OHdG and DNA hypomethylation biomarkers. For individuals with high PC1 and PC2 scores, both displayed an approximate 1.2-fold risk for UC with DNA hypomethylation.In conclusion, we provide a foundation for health education and risk communication strategies to limit metal exposure in environment, so that UC risks can be improved potentially.

Urine concentrations of selected trace metals in a cohort of Irish adults.

Human biomonitoring studies are of increasing importance in regulatory toxicology; however, there is a paucity of human biomonitoring data for the Irish population. In this study, we provide new data for urinary biomarker concentrations of aluminium, arsenic, cadmium, chromium, copper, mercury, manganese, lead and selenium. One hundred urine samples, collected between 2011 and 2014 from healthy participants of the EuroMOTOR project, were randomly selected. Metal concentrations were measured via ICPMS. Descriptive statistics for each of the metals stratified by gender were performed. There were 58 male and 42 female participants and metals were detectable for all samples. Geometric mean urinary concentrations for each metal in males were as follows: aluminium 8.5 µg/L, arsenic 8.1 µg/L, cadmium 0.3 µg/L, chromium 0.5 µg/L, copper 5.1 µg/L, mercury 0.4 µg/L, manganese 0.3 µg/L, lead 1.3 µg/L and selenium 10.8 µg/L; and in females: aluminium 8.5 µg/L, arsenic 10.2 µg/L, cadmium 0.4 µg/L, chromium 0.6 µg/L, copper 5.6 µg/L, mercury 0.3 µg/L, manganese 0.2 µg/L, lead 1.6 µg/L and selenium 13.7 µg/L. We observed higher geometric mean concentrations in women for arsenic, cadmium, chromium, copper, lead and selenium, with equal geometric mean concentrations for aluminium and manganese, leaving only mercury with lower geometric mean concentrations in women. Aluminium, cadmium, chromium, lead and urinary concentrations of metals were slightly elevated compared to European data, while for arsenic, copper, manganese and selenium, Irish levels were lower. Our findings highlight that there are differences in urinary metal concentrations between European populations.

The impact of essential and toxic elements on cardiometabolic risk factors in adults and older people.

BACKGROUND AND AIM: Evidence suggests an association between essential and toxic elements and the worsening of cardiometabolic risk factors. This study aimed to investigate the concentrations of zinc, copper, selenium, arsenic, cadmium, and mercury and their relationship with cardiometabolic risk factors in adults and older people. METHODS: This cross-sectional study was carried out with 112 adults with a mean age of 59 (sd 14) years old and a BMI of 29.30 (sd 5.11) Kg/m2. The subject's weight and height were measured for body mass index (BMI) calculation, classified according to the cut-off points recommended by the World Health Organization (WHO). We evaluated sociodemographic, clinical, lifestyle, waist circumference - WC, visceral adiposity index - VAI, glycemic lipid profile, blood pressure, and high-sensitive C-reactive protein (hs-CRP). Cardiovascular risk was defined by The Global Risk Score (GRS) score. Plasma zinc, selenium, copper levels, urinary arsenic, cadmium, and mercury levels were measured using the inductively coupled plasma mass spectrometry technique (ICP-MS). RESULTS: There was a negative association between urinary arsenic and VAI (ß - 0.03, p < 0.01), triglycerides (ß - 1.10, p < 0.01), and VLDL cholesterol (ß - 0.14, p = 0.02). Plasma copper and copper/zinc ratio were positively associated with fasting glucose and hs-CRP (ß 0.38, p < 0.01; ß 36.02, p = 0.01, ß 0.004, p < 0.01, ß 0.68, p < 0.001, respectively). Urinary arsenic (ß - 0.14, p = 0.04) and cadmium (ß - 36.42, p = 0.04) were negatively associated with systolic blood pressure. Also, urinary cadmium was negatively associated with diastolic blood pressure (ß - 21.55, p = 0.03), and urinary mercury showed an opposite behavior (ß 1.45, p = 0.03). CONCLUSION: Essential and toxic elements in urine and plasma could be potential biomarkers for cardiovascular risk factors. A healthy lifestyle should be adopted; in addition, government policies should be developed to guarantee sustainable production and a safe environment.

Gene-environment interaction analysis of redox-related metals and genetic variants with plasma metabolic patterns in a general population from Spain: The Hortega Study.

BACKGROUND: Limited studies have evaluated the joint influence of redox-related metals and genetic variation on metabolic pathways. We analyzed the association of 11 metals with metabolic patterns, and the interacting role of candidate genetic variants, in 1145 participants from the Hortega Study, a population-based sample from Spain. METHODS: Urine antimony (Sb), arsenic, barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), molybdenum (Mo) and vanadium (V), and plasma copper (Cu), selenium (Se) and zinc (Zn) were measured by ICP-MS and AAS, respectively. We summarized 54 plasma metabolites, measured with targeted NMR, by estimating metabolic principal components (mPC). Redox-related SNPs (N = 291) were measured by oligo-ligation assay. RESULTS: In our study, the association with metabolic principal component (mPC) 1 (reflecting non-essential and essential amino acids, including branched chain, and bacterial co-metabolism versus fatty acids and VLDL subclasses) was positive for Se and Zn, but inverse for Cu, arsenobetaine-corrected arsenic (As) and Sb. The association with mPC2 (reflecting essential amino acids, including aromatic, and bacterial co-metabolism) was inverse for Se, Zn and Cd. The association with mPC3 (reflecting LDL subclasses) was positive for Cu, Se and Zn, but inverse for Co. The association for mPC4 (reflecting HDL subclasses) was positive for Sb, but inverse for plasma Zn. These associations were mainly driven by Cu and Sb for mPC1; Se, Zn and Cd for mPC2; Co, Se and Zn for mPC3; and Zn for mPC4. The most SNP-metal interacting genes were NOX1, GSR, GCLC, AGT and REN. Co and Zn showed the highest number of interactions with genetic variants associated to enriched endocrine, cardiovascular and neurological pathways. CONCLUSIONS: Exposures to Co, Cu, Se, Zn, As, Cd and Sb were associated with several metabolic patterns involved in chronic disease. Carriers of redox-related variants may have differential susceptibility to metabolic alterations associated to excessive exposure to metals.

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

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

Associations between urinary heavy metal concentrations and blood pressure in residents of Asian countries.

BACKGROUND: Previous studies have suggested that exposures to heavy metals (arsenic, cadmium, lead, and selenium) may be associated with differences in blood pressure. However, the findings of these studies have been inconsistent. This study was performed to examine the associations between urinary heavy metal concentrations and blood pressure among residents of four Asian countries (Bangladesh, Indonesia, Nepal, and Vietnam). METHODS: This cross-sectional study examined 1899 adults in four Asian countries. Urinary concentrations of heavy metals were measured by inductively coupled plasma mass spectrometry. A questionnaire survey was administered regarding individual characteristics. Anthropometric measurements (height and weight) were performed. Systolic and diastolic blood pressures were measured after a short rest. Multiple linear regression models were applied to investigate associations between urinary heavy metal concentrations and blood pressure after adjustments for age, sex, and body mass index. RESULTS: The geometric means of the urinary concentrations of arsenic, cadmium, lead, and selenium were 84.6, 0.885, 2.09, and 16.5 µg/g creatinine, respectively. The urinary arsenic concentrations were slightly higher than those typically reported in non-polluted populations, while urinary cadmium, lead, and selenium concentrations were equivalent or slightly lower. The urinary lead concentrations were positively associated with both systolic and diastolic blood pressure, but urinary selenium concentrations were negatively associated with them. CONCLUSIONS: Variations in the urinary concentrations of lead and selenium were associated with blood pressure at low levels of exposure/intake.

Prenatal metal mixtures and child blood pressure in the Rhea mother-child cohort in Greece.

BACKGROUND: Child blood pressure (BP) is predictive of future cardiovascular risk. Prenatal exposure to metals has been associated with higher BP in childhood, but most studies have evaluated elements individually and measured BP at a single time point. We investigated impacts of prenatal metal mixture exposures on longitudinal changes in BP during childhood and elevated BP at 11 years of age. METHODS: The current study included 176 mother-child pairs from the Rhea Study in Heraklion, Greece and focused on eight elements (antimony, arsenic, cadmium, cobalt, lead, magnesium, molybdenum, selenium) measured in maternal urine samples collected during pregnancy (median gestational age at collection: 12 weeks). BP was measured at approximately 4, 6, and 11 years of age. Covariate-adjusted Bayesian Varying Coefficient Kernel Machine Regression and Bayesian Kernel Machine Regression (BKMR) were used to evaluate metal mixture impacts on baseline and longitudinal changes in BP (from ages 4 to 11) and the development of elevated BP at age 11, respectively. BKMR results were compared using static versus percentile-based cutoffs to define elevated BP. RESULTS: Molybdenum and lead were the mixture components most consistently associated with BP. J-shaped relationships were observed between molybdenum and both systolic and diastolic BP at age 4. Similar associations were identified for both molybdenum and lead in relation to elevated BP at age 11. For molybdenum concentrations above the inflection points (~ 40-80 µg/L), positive associations with BP at age 4 were stronger at high levels of lead. Lead was positively associated with BP measures at age 4, but only at high levels of molybdenum. Potential interactions between molybdenum and lead were also identified for BP at age 11, but were sensitive to the cutoffs used to define elevated BP. CONCLUSIONS: Prenatal exposure to high levels of molybdenum and lead, particularly in combination, may contribute to higher BP at age 4. These early effects appear to persist throughout childhood, contributing to elevated BP in adolescence. Future studies are needed to identify the major sources of molybdenum and lead in this population.

Associations between urinary heavy metal concentrations and blood pressure in residents of Asian countries

BACKGROUND@#Previous studies have suggested that exposures to heavy metals (arsenic, cadmium, lead, and selenium) may be associated with differences in blood pressure. However, the findings of these studies have been inconsistent. This study was performed to examine the associations between urinary heavy metal concentrations and blood pressure among residents of four Asian countries (Bangladesh, Indonesia, Nepal, and Vietnam).@*METHODS@#This cross-sectional study examined 1899 adults in four Asian countries. Urinary concentrations of heavy metals were measured by inductively coupled plasma mass spectrometry. A questionnaire survey was administered regarding individual characteristics. Anthropometric measurements (height and weight) were performed. Systolic and diastolic blood pressures were measured after a short rest. Multiple linear regression models were applied to investigate associations between urinary heavy metal concentrations and blood pressure after adjustments for age, sex, and body mass index.@*RESULTS@#The geometric means of the urinary concentrations of arsenic, cadmium, lead, and selenium were 84.6, 0.885, 2.09, and 16.5 μg/g creatinine, respectively. The urinary arsenic concentrations were slightly higher than those typically reported in non-polluted populations, while urinary cadmium, lead, and selenium concentrations were equivalent or slightly lower. The urinary lead concentrations were positively associated with both systolic and diastolic blood pressure, but urinary selenium concentrations were negatively associated with them.@*CONCLUSIONS@#Variations in the urinary concentrations of lead and selenium were associated with blood pressure at low levels of exposure/intake.

Association between exposure to arsenic, nickel, cadmium, selenium, and zinc and fasting blood glucose levels.

Associations between single metal and fasting blood glucose (FBG) levels have been reported in previous studies. However, the association between multi-metals exposure and FBG level are little known. To assess the joints of arsenic (As), nickel (Ni), cadmium (Cd), selenium (Se), and zinc (Zn) co-exposure on FBG levels, Bayesian kernel machine regression (BKMR) statistical method was used to estimate the potential joint associations between As, Ni, Cd, Se, and Zn co-exposure and FBG levels among 1478 community-based Chinese adults from two counties, Shimen (n = 696) and Huayuan (n = 782), with different exposure profiles in Hunan province of China. The metals levels were measured in spot urine (As, Ni, and Cd) and plasma (Se and Zn) using inductively coupled plasma-mass spectrometry, respectively. The exposure levels of all the five metals were significantly higher in Shimen area (median: As = 57.76 µg/L, Cd = 2.75 µg/L, Ni = 2.73 µg/L, Se = 112.67 µg/L, Zn = 905.68 µg/L) than those in Huayuan area (As = 41.14 µg/L, Cd = 2.22 µg/L, Ni = 1.88 µg/L, Se = 65.59 µg/L, Zn = 819.18 µg/L). The BKMR analyses showed a significantly positive over-all effect of the five metals on FBG levels when metals concentrations were all above the 50th percentile while a statistically negative over-all effect when metals concentrations were all under the 50th percentile in Shimen area. However, a totally opposite over-all effect of the mixture of the five metals on FBG levels was found in Huayuan area. BKMR also revealed a non-linear exposure-effect of Zn on FBG levels in Huayuan area. In addition, interaction effects of As and Se on FBG level were observed. The relationship between single or combined metals exposure and FBG was different against different exposure profiles. Potential interaction effects of As and Se on FBG levels may exist.

The association between plasma selenium and chronic kidney disease related to lead, cadmium and arsenic exposure in a Taiwanese population.

This study aimed to determine the interaction of red blood cell cadmium and lead, total urinary arsenic, and plasma selenium in chronic kidney disease (CKD). We recruited 220 CKD patients as well as 438 gender- and age-matched controls, and we defined CKD as <60 mL/min/1.73 m2 estimated glomerular filtration rate (eGFR) for three or more consecutive months. Plasma selenium and red blood cell cadmium and lead concentrations were measured by ICP-MS. Urinary arsenic species were determined via HPLC-HG-AAS and were summed to determine the total urinary arsenic concentration. Plasma selenium was positively correlated to eGFR, and subjects with high plasma selenium levels (>243.90 µg/L) had a significantly lower odds ratio (OR) and 95% confidence interval (CI) (0.23, 0.13-0.42) for CKD compared to those with low plasma selenium levels (≤ 196.70 µg/L). High plasma selenium and low red blood cell cadmium or lead concentrations interacted to decrease the OR and 95% CI for CKD (0.12, 0.06-0.26; 0.09, 0.04-0.19). High plasma selenium and low red blood cell lead levels also interacted to increase the eGFR (20.70, 15.56-26.01 mL/min/1.73 m2). This study is the first to suggest that selenium modifies the eGFR and OR in CKD induced by environmental toxicants.

Results of the first national human biomonitoring in Slovenia: Trace elements in men and lactating women, predictors of exposure and reference values.

The first national human biomonitoring in Slovenia surveyed cadmium (Cd), lead (Pb), mercury (Hg), arsenic (As), manganese (Mn), selenium (Se), copper (Cu) and zinc (Zn) in a childbearing population (18-49 years) selected from lactating primiparous women and men (N = 1084). The overall aim was to estimate trace elements' levels and geographical variations in order to identify sources of possible exposures and set the national reference values. The study population was selected evenly from 12 study areas across Slovenia, including rural, urban and known or potentially contaminated environments. Within 6-8 weeks after delivery, venous blood, spot urine, scalp hair and breast milk samples were collected to determine the selected elements. The data analysis included descriptive statistics and multiple linear regression using elemental concentrations in biological matrices, questionnaire data and environmental datasets. Essential elements showed no significant deficiencies or excessive levels in the study population and were largely determined by sex and/or the participating women's physiological status (postpartum, lactation), as well as by certain dietary sources. Toxic elements' levels were mainly below the levels considered to present increased health risk. Lifestyle and nutritional habits appeared as significant determinants of exposure to Cd (smoking and game meat consumption), Hg (seafood and amalgam fillings), As (seafood) and Pb (alcohol consumption, smoking, game meat consumption and type of water supply). A distinctive geographical pattern was confirmed, due to past mining activities combined with naturally elevated background levels in the cases of Pb (Mezica Valley), Hg (Idrija and Posocje) and As exposure (Zasavje). Increased seafood consumption in the coastal study area contributed to higher Hg and As (arsenobetaine) levels. Extensive sample size database accompanied with life-style and environmental data improved the prediction of exposure patterns, set the reference values for the childbearing population living in Slovenia, and provided a strong basis for evaluating spatial and temporal trends in exposure. To our best knowledge, this is the first study to establish reference values for lactating primiparous women.

Urinary concentrations of environmental metals and associating factors in pregnant women.

Pregnant women, a vulnerable population, can be exposed to a variety of environmental metals that may adversely affect their health at elevated concentrations. Moreover, environmental exposure and risk disparities are associated with several factors such as sociodemographic characteristics, pregnancy complications, and nutritional supplementation indicators. Our aim was to investigate whether and how the urinary metal concentrations vary according to these factors in a large pregnancy and birth cohort. Urinary levels of seven metals including manganese, zinc, selenium, arsenic, cadmium, thallium, and lead were assessed in 7359 participants across Wuhan City in China. In all, 7359 urine samples from the third trimester were analyzed and 15 sociodemographic characteristics, pregnancy complications, and nutritional supplementation indicators were assessed: maternal age, household income, multivitamin supplements during pregnancy, etc. Concentrations of Zn, As, and Cd were detected in all urine samples; Mn, Se, Tl, and Pb were detected in 95.3%, 99.8%, 99.8%, and 99.9% urine samples, respectively. The geometric mean (GM) of creatinine-adjusted urinary Mn, Zn, Se, As, Cd, Tl, and Pb concentrations were 1.42, 505.44, 18.24, 30.49, 0.64, 0.55, and 3.69 µg/g. Factors that associated with environmental metals concentration were as follows: (1) Urinary Zn and Cd concentrations increased with maternal age. (2) Pregnant women with higher education had lower Cd concentrations. (3) Pregnant women with folic acid supplementation had lower Mn and with multivitamin supplementation had higher Se and lower Tl. Our results demonstrated that the maternal age, education level, folic acid supplementation, and multivitamin supplementation were significantly associated with environmental metal concentrations. Furthermore, studies are recommended to explore the influence of diet on biological metals concentrations in more detail.

Effect of a Supplementation with Two Quelites on Urinary Excretion of Arsenic in Adolescents Exposed to Water Contaminated with the Metalloid in a Community in the State of Guanajuato, Mexico.

Quelites are Mexican wild plants, reported as excellent sources of nutritional compounds such as amino acids (serine, glycine, and cysteine), minerals (Mg, Fe, and Zn), and phytochemicals, as phenolic acids (chlorogenic acid) and flavonoids (phloridzin and naringenin); on the other hand, high biological activity has been shown in these compounds. This work aimed to evaluate the effect of a supplementation with two endemic quelites of Mexico (Chenopodium berlandieri L. and Portulaca Oleracea L.); in addition to supplementation, a nutritional intervention was performed; the biomarkers of hemoglobin (Hb), urinary malondialdehyde (UMDA), and urinary arsenic (UAs) were measured in adolescents exposed to arsenic. A clinical intervention study was conducted in 27 adolescents ages 11 to 12 years for 4 weeks. Weekly anthropometric and dietary evaluations were carried out, as well as the concentration of Hb; the UMDA and UAs were performed by plate-based colorimetric measurement and atomic absorption spectrophotometry with the hydrides generation system, respectively. The results showed that UMDA concentrations had a significant improvement in the supplemented group (SG) vs. control group (CG) (SG = 1.59 ± 0.89 µM/g creatinine vs. CG = 2.90 ± 0.56 µM/g creatinine) in the second week of intervention; on the other hand, the supplemented group showed an increase in Hb levels (15.12 ± 0.99 g/dL) in the same week; finally after the second week, an increase in UAs levels was observed significantly compared to the baseline value (Baseline: 56.85; Week 2: 2.02 µg/g creatinine). Therefore, the results show that the mixture of quelites (a rich source of phytochemicals and nutrients) improved hemoglobin and UMDA levels, and urinary arsenic excretion from the second week in the exposed population.