Urinary Cadmium Concentrations Research Articles

Analysis of Whole Blood and Urine Trace Elements in Children with Autism Spectrum Disorders and Autistic Behaviors

The relationship between trace elements and neurological development is an emerging research focus. We performed a case–control study to explore (1) the differences of 13 trace elements chromium (Cr), manganese (Mn), cobalt (Co), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), stannum (Sn), stibium (Sb), mercury (Hg), titanium (TI), and plumbum (Pb) concentration in whole blood and urine between autism spectrum disorder (ASD) children and their typical development peers, and (2) the association between the 13 trace elements and core behaviors of ASD. Thirty ASD subjects (cases) and 30 age-sex-matched healthy subjects from Baise City, Guangxi Zhuang Autonomous Region, China, were recruited. Element analysis was carried out by inductively coupled plasma-optical emission spectrometry. Autistic behaviors were assessed using Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Children Neuropsychological and Behavior Scale (CNBS). The whole blood concentrations of Mo (p = 0.004), Cd (0.007), Sn (p = 0.003), and Pb (p = 0.037) were significantly higher in the ASD cases than in the controls. Moreover, Se (0.393), Hg (0.408), and Mn (− 0.373) concentrations were significantly correlated between whole blood and urine levels in ASD case subjects. There were significant correlations between whole blood Sb (0.406), Tl (0.365), Mo (− 0.4237), Mn (− 0.389), Zn (0.476), and Se (0.375) levels and core behaviors of ASD. Although the mechanism of trace element imbalance in ASD is unclear, these data demonstrate that core behaviors of ASD may be affected by certain trace elements. Further studies are recommended for exploring the mechanism of element imbalance and providing corresponding clinical treatment measures.

Urinary Metals as a Marker of Exposure in Men and Women in the Welding and Electrical Trades: A Canadian Cohort Study.

Men and women working in the welding trades undergo the same apprenticeship training but it is unknown whether, once in the trade, their exposures differ. Comparison of urinary metal concentrations, having adjusted for estimated airborne exposure, may provide an answer. Men and women were recruited to a cohort study of workers in the welding and electrical trades (the Workers Health in Apprenticeship Trades-Metal working and Electrical [WHAT-ME study]). They completed a recruitment questionnaire and further questionnaires every 6 months for up to 5 years. At each follow-up, they gave details on employment and, if welding, answered trade-specific questionnaires. Urine samples were collected by mail. Welding exposure matrices were developed to estimate metal exposures from welding process, base metal, and consumables. Urinary metal concentrations, determined by ICP-MS, were compared by trade (welding or electrical). Within welding, the relation of urinary concentrations to estimated airborne exposure was examined, with adjustment for potential confounders including sex, use of respiratory protective equipment (RPE), and time spent outdoors. Natural logarithms were taken of exposure estimates and urinary concentrations, to reduce skew. All regression analyses included creatinine concentration. Urinary metal concentrations were analysed for 12 metals in 794 samples. Antimony, arsenic, lead, and mercury had a high proportion of samples with no metal detected and were not considered further. The urinary concentrations of aluminum, cadmium, chromium, cobalt, copper, manganese, nickel, and zinc were compared for welders (434 samples) and electrical workers (360). After adjustment for potential confounders, welders had higher urinary concentrations for aluminum (β = 0.13 95%CI 0.03-0.24) and chromium (β = 0.66 95%CI 0.55-0.77). Of 434 welder urines, 334 could be matched securely to detailed information about the most recent day welding. For these, an estimate of airborne exposure was made for aluminum, chromium, manganese, and nickel. Male welders were estimated to have higher airborne exposure to chromium and nickel than women welders. No difference was seen in the estimated exposures for aluminum or manganese (or total dust). Regression analyses of the relation of urinary metals to estimated exposure showed a good concordance for aluminum (β = 0.09 95%CI 0.04-0.15 (P < 0.001) and chromium (β = 0.11 95%CI 0.05-0.17 P < 0.001). The concordance for manganese and nickel was positive, but much weaker. Urinary concentrations of aluminum and nickel were somewhat lower with increasing time wearing RPE and, for chromium and nickel, with time working outdoors. Having adjusted for estimated exposure, creatinine and other confounders, male welders had lower urine concentrations of aluminum (β = -0.35 95%CI -0.51 to -0.19 P < 0.001) chromium (β = -0.38 95%CI -0.57 to -0.19 P < 0.001) and manganese (β = -0.36 95%CI -0.49 to -0.23 P < 0.001) than female welders. Welders had higher urinary concentrations of aluminum and chromium than electrical workers. Exposure estimates of aluminum and chromium for welders were a valid representation of the airborne exposures to these metals. Although male welders were estimated to have higher exposures of chrome and nickel than female welders, the higher urinary metal concentrations in women welders is of concern, particularly for women who may conceive while in the trade.

Breast cancer and urinary metal mixtures in Mexican women

Humans are environmentally exposed to many metals throughout their lives. Simultaneous exposure to several metals could result in synergistic or antagonistic toxicological effects among them; however, the information on exposure to mixtures of metals and breast cancer (BC) is scarce. The objective of this report was to compare metals considered human carcinogens, individually and as mixtures, in women with and without BC.This is a secondary analysis of a population-based case-control study that was carried out from 2007 to 2011 in Northern Mexico. A total of 499 histologically confirmed BC cases and 499 controls were included. Information about sociodemographic, lifestyle and reproductive characteristics was obtained by in-person interviews. Urinary concentrations of aluminum (Al), cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb), antimony (Sb), cobalt (Co), molybdenum (Mo), tin (Sn), and vanadium (V) were determined by inductively coupled plasma triple quadrupole. Metal mixtures were identified by principal component analysis with creatinine-corrected metals.Over 90% of subjects had metal measurements above the detection limit except tin (86%) and antimony (78.4%). After adjusting by selected covariables, we observed that the individual urinary concentrations of V, Co, and Mo were lower among cases compared to controls; in contrast to Sn that had higher concentrations. We identified two principal component mixtures with opposite relationships with BC: Cr, Ni, Sb, Al, Pb and Sn (OR = 1.15; CI95% 1.06,1.25) and Mo and Co (OR = 0.56; CI95% 0.49,0.64).This is the first study that identified urinary metal mixtures that differed between women with and without BC. Our results warrant confirmation in further prospective epidemiological studies. In addition, the elucidation of underlying mechanisms of metal interactions on BC risk deserves further research.

The burden of coronary heart disease and stroke attributable to dietary cadmium exposure in Chinese adults, 2017

Cadmium (Cd) is a metal with a long biological half-life that could cause health issues, such as coronary heart disease (CHD), stroke, and other cardiovascular diseases (CVD). Recent studies showed an ascending trend in the dietary Cd intake in the Chinese population. The contribution of dietary Cd intake to CHD and stroke burden, on the other hand, remains to be established.To calculate the disease burden for CHD and stroke attributable to dietary Cd, we estimated dietary Cd intake by associating the Cd concentration in food with consumption frequency. The toxicokinetic (TK) model and dietary Cd consumption were used to simulate urinary cadmium (U-Cd) concentrations. The population attributable fraction (PAF) can be derived for the computation of the attributable disease burden expressed as Disability-Adjusted Life Years (DALYs) in provinces, genders, and age groups by combining the relative risk (RR) with the population distribution of U-Cd.The mean of dietary Cd consumption and the geometric mean of U-Cd in the Chinese adult population are 0.684 μg/kg bw/day and 0.88 μg/g creatinine. The CHD burden attributable to dietary Cd was 3.26 million DALYs, with a 9.69% proportion of the total CHD burden. The DALYs for stroke attributable to Cd in food was approximately 3.64 million, accounting for 8.22% of the overall stroke burden. Furthermore, the attributable disease burden of CHD and stroke are higher in the south, women, and middle-aged and older adults.Our study suggested that foodborne Cd exposure contributes a considerable proportion of the CHD and stroke burden. More attention is needed to control Cd in food in order to reduce the burden of CHD and stroke in the Chinese population.

Levels and determinants of urinary cadmium in general population in Spain: Metal-MCC-Spain study

BackgroundCadmium is a ubiquitous and persistent metal, associated with different harmful health effects and with increased morbidity and mortality. Understanding the main sources of exposure is essential to identify at risk populations and to design public health interventions. ObjectiveTo evaluate cadmium exposure in a random-sample of general adult population from three regions of Spain, assessed by the urinary cadmium (U–Cd) concentration, and to identify its potential determinants and sex-specific differences, including sociodemographic, lifestyle and dietary factors. Materials and methodsWe measured U–Cd (μg/g creatinine) in single urine spot samples from 1282 controls enrolled in the multicase-control study in common tumors in Spain (MCC-Spain) with inductively coupling plasma-mass spectrometry equipped with an octopole reaction systems (ICP-ORS-MS). The association between sociodemographic, lifestyle, and dietary characteristics and U–Cd concentrations was evaluated using geometric mean ratios (GMR) estimated by multiple log-linear regression models. ResultsOverall, geometric mean U–Cd concentration was 0.40 (95%CI: 0.38, 0.41) μg/g creatinine. Levels were higher in women than in men (GMR]: 1.19; 95%CI: 1.07, 1.32), and increased with age in males (ptrend< 0.001). Cigarette smoking was clearly associated to U–Cd levels (GMRformer vs non-smokers: 1.16; 95%CI: 1.05, 1.29; GMRcurrent vs non-smokers: 1.42; 95%CI: 1.26, 1.60); the relationship with secondhand tobacco exposure in non-smokers, was restricted to women (pinteraction = 0.02). Sampling season and region also seemed to influence U–Cd concentrations, with lower levels in summer (GMRsummer vs average: 0.79; 95%CI: 0.71, 0.88), and higher levels in North-Spain Asturias (GMRAsturias vs average: 1.13; 95%CI: 1.04, 1.23). Regarding diet, higher U–Cd concentration was associated with eggs consumption only in men (pinteraction = 0.04), just as rice intake was associated in women (pinteraction = 0.03). Conclusion: These results confirmed that tobacco exposure is the main modifiable predictor of U–Cd concentrations, and remark that the role of dietary/sociodemographic factors on U–Cd levels may differ by sex.

Associations of urinary and dietary cadmium with urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine and blood biochemical parameters

Cadmium is a heavy metal with established adverse effects on human health, namely on bone, liver and kidney function and the cardiovascular system. We assessed cadmium exposure and its correlation with biomarkers of toxicity. We recruited 137 non-smoking blood donors without a history of chronic disease or cancer who resided in the Northern Italy province of Reggio Emilia (mean age 47 years, range 30–60 years) in the 2017–2019 period. We used a semi-quantitative food frequency questionnaire to estimate dietary cadmium intake and urine samples to assess concentrations of urinary cadmium and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG). Median urinary cadmium and 8-oxodG concentrations were 0.21 μg/L (interquartile range (IQR): 0.11–0.34 μg/L) and 3.21 μg/g creatinine (IQR: 2.21–4.80 μg/g creatinine), respectively, while median dietary cadmium intake was 6.16 μg/day (IQR: 5.22–7.93 μg/day). We used multivariable linear and spline regression models to estimate mean differences exposure concentrations. Dietary and urinary cadmium were positively correlated, and both were positively and linearly correlated with 8-oxodG. We found a positive association of urinary cadmium with blood alanine aminotransferase (ALT), total cholesterol, low-density lipoprotein (LDL)-cholesterol and thyroid-stimulating hormone (TSH) concentrations. We also observed a positive association with triglycerides, in both linear (beta regression coefficient = 77.03, 95% confidence interval 32.27–121.78) and non-linear spline regression analyses. Despite the positive correlation between dietary and urinary cadmium estimates, dietary cadmium intake showed inconsistent results with the study endpoints and generally weaker associations, suggesting a decreased capacity to reflect actual cadmium exposure. Overall, these findings suggest that even low levels of cadmium exposure may adversely alter hematological and biochemical variables and induce oxidative stress.

Association between urinary cadmium concentrations and liver function in adolescents.

Evidence from previous studies has shown that exposure to cadmium (Cd) is associated with cardiovascular disease, kidney disease, and osteoporosis, but the effects of Cd on liver toxicity in adolescents are unclear. The data of 4411 adolescents who participated in the US The National Health and Nutrition Examination Survey (NHANES) during 1999-2016 was analyzed. Liver function was indicated by the levels of alanine aminotransferase (ALT) and aspartate amino transferase (AST). The associations between the levels of urinary Cd and liver function were evaluated using multivariate logistic regression models adjusted for covariates. The results showed that the odds ratios of ALT and AST in the highest quartiles of urinary Cd were 1.40 (95% confidence interval [CI], 1.07-1.82) and 1.64 (95% CI, 1.10-2.44), respectively, compared with the lowest quartiles, which were similar to using urinary creatinine as the covariate. We also found linear regression of associations of urinary Cd with elevated ALT and AST levels in boys. In addition, one augmented urinary Cd concentration unit (Log10) was associated with a 0.04-mg/dL increase in C-reactive protein and a 0.53-mg/dL decrease in HDL cholesterol in the fully adjusted model. Our results add novel evidence that exposure to Cd might be positively associated with indicators of liver injury, indicating the potential toxic effect of Cd exposure on the adolescent liver. Further confirmatory studies are needed.

Systematic Review and Meta-analysis of Environmental Toxic Metal Contaminants and the Risk of Ischemic Stroke.

Stroke is the second largest cause of mortality (WHO 2014) and long-lasting disability worldwide. Many risk factors are associated with stroke, such as age, gender, chronic illnesses, cardiovascular disease, lifestyle, and smoking. With global industrialization, the roles of environmental contaminants and their association with stroke are still unclear and have attracted much more attention. We conducted a systematic review on the environmental toxic metal contaminants and the risk of ischemic stroke. A comprehensive literature search was carried out till June 30, 2021 from databases such as PubMed, Science Direct, Embase, and Scopus. The quality of all the articles which met our inclusion criteria was assessed using Newcastle-Ottawa scaling, and four eligible studies were included for our systematic review. The serum and urine cadmium concentrations were positively associated with the risk of ischemic stroke. There was an inverse association of serum and urine concentrations of mercury (Hg), serum concentration of gold and cerium with ischemic stroke, and the serum and urine concentrations of lead (Pb) had no association with ischemic stroke risk. The study showed strong associations between heavy metals and ischemic stroke, but more studies are required to prove the associations.

Urinary Cadmium and Incident Heart Failure: A Case-Cohort Analysis Among Never-Smokers in Denmark.

Epidemiologic studies suggest cadmium exposure is associated with cardiovascular disease risk, including heart failure. However, prior findings may be influenced by tobacco smoking, a dominant source of cadmium exposure and risk factor for heart failure. The present study leverages up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to examine the relationship between urinary cadmium and incident heart failure among people who never smoked. Between 1993 and 1997, 19,394 never-smoking participants (ages 50-64 years) enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 men and 600 women and identified 958 incident heart failure cases occurring between baseline and 2015. Using a case-cohort approach, we estimated adjusted hazard ratios (aHR) for heart failure in Cox proportional hazards models with age as the time scale. Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median = 0.20; 25th, 75th = 0.13, 0.32 μg cadmium/g creatinine). In adjusted models, we found that higher urinary cadmium was associated with a higher rate of incident heart failure overall (aHR = 1.1 per interquartile range difference [95% CI = 1.0, 1.2). In sex-stratified analyses, the association seemed restricted to men (aHR = 1.5 [95% CI = 1.2, 1.9]). In this cohort of people who never smoked tobacco, environmental cadmium was positively associated with incident heart failure, especially among men.

Association Between Cadmium Exposure and Liver Function in Adults in the United States: A Cross-sectional Study.

ObjectivesCadmium is widely used, leading to extensive environmental and occupational exposure. Unlike other organs, for which the harmful and carcinogenic effects of cadmium have been established, the hepatotoxicity of cadmium remains unclear. Some studies detected correlations between cadmium exposure and hepatotoxicity, but others concluded that they were not associated. Thus, we investigated the relationship between cadmium and liver damage in the general population.MethodsIn total, 11 838 adult participants from National Health and Nutrition Examination Survey 1999-2015 were included. Urinary cadmium levels and the following liver function parameters were measured: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), total bilirubin (TB), and alkaline phosphatase (ALP). Linear and logistic regression analyses were performed to assess the associations between urinary cadmium concentrations and each liver function parameter after adjusting for age, sex, race/ethnicity, annual family income, smoking status, alcohol consumption status, physical activity, and body mass index.ResultsThe covariate-adjusted results of the linear regression analyses showed significant positive relationships between log-transformed urinary cadmium levels and each log-transformed liver function parameter, where beta±standard error of ALT, AST, GGT, TB, and ALP were 0.049±0.008 (p<0.001), 0.030±0.006 (p<0.001), 0.093±0.011 (p<0.001), 0.034±0.009 (p<0.001), and 0.040±0.005 (p<0.001), respectively. Logistic regression also revealed statistically significant results. The odds ratios (95% confidence intervals) of elevated ALT, AST, GGT, TB, and ALP per unit increase in log-transformed urinary cadmium concentration were 1.360 (1.210 to 1.528), 1.307 (1.149 to 1.486), 1.520 (1.357 to 1.704), 1.201 (1.003 to 1.438), and 1.568 (1.277 to 1.926), respectively.ConclusionsChronic exposure to cadmium showed positive associations with liver damage.

Metal(loid)s and human semen quality: The LIFE Study

Multiple studies have demonstrated a global population-wide decline in semen quality, with sperm concentrations having fallen 50 % over the past 50 years. Several metal and metalloid (“metal(loid)”) compounds are known to have testicular toxicity, raising concerns about their contribution to rising infertility. In the male reproductive tract, metal(loid)s can reduce semen quality and disturb function both directly, by inducing tissue damage, and indirectly, by disrupting hormone production and secretion. This study assessed associations between 15 creatinine-adjusted metal(loid)s and 7 measures of semen quality among 413 reproductive-aged men recruited from 16 U.S. counties between 2005–2009. Multi-metal(loid) multivariable linear regression models estimated associations between semen quality endpoints and urinary concentrations of chromium, cobalt, copper, molybdenum, selenium, zinc, antimony, arsenic, barium, cadmium, lead, thallium, tin, tungsten, and uranium. LASSO regression was employed to select model variables and account for multicollinearity of the metal(loid)s. A positive association was observed between tin and sperm morphology (β = 4.92 p = 0.045). Chromium (β = 1.87, p = 0.003) and copper (β= −1.30, p = 0.028) were positively and negatively associated with total sperm count, respectively. With respect to DNA fragmentation, cadmium (β = 12.73, p = 0.036) was positively associated and chromium was negatively associated (β = −5.08, p = 0.001). In this cohort of U.S. population-based men, there was evidence of both positive and negative associations between specific metal(loid)s and semen quality. Additional research is needed to determine interactions between metal(loid)s within a mixture, consistent with typical human exposure, and identify sperm effects resulting from cumulative metal(loid) exposures.

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

BackgroundPrevious 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).MethodsThis 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.ResultsThe 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.ConclusionsVariations in the urinary concentrations of lead and selenium were associated with blood pressure at low levels of exposure/intake.

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

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

Positive Association between Endothelium-Platelet Microparticles and Urinary Concentration of Lead and Cadmium in Adolescents and Young Adults.

(1) Background: In previous research, higher levels of urine heavy metals, especially lead and cadmium, have been associated with increased cardiovascular risk. However, there is no information linking exposure to heavy metal to endothelial and platelet microparticles (EMPs and PMPs), particularly in the younger population, which are novel biomarkers of endothelial dysfunction. (2) Methods: From a nationwide database, which was incepted in 1992–2000, screening for renal health among Taiwanese school children, a total of 789 subjects were recruited. Cross-sectional analysis was performed to evaluate the association between serum EMPs/PMPs and urine iron, nickel, copper, cadmium, lead, chromium, manganese, and zinc levels in the adolescent and young adult population. (3) Results: After we adjusted the conventional cardiovascular risk factors, CD31+/CD42a− and CD31+/CD42a+ counts, in subjects’ serum, respective markers of EMP and PMP displayed a significant positive dose-response relationship with urinary lead and cadmium levels. Higher quartiles of urine lead and cadmium levels were associated with an increased risk of higher EMPs/PMPs (≥75th percentile) in a multivariate logistic regression model. (4) Conclusion: Higher urinary lead and cadmium concentrations are strongly associated with endothelium–platelet microparticles in this adolescent and young adult population, which could help explain, in part, the mechanism through which heavy metal exposure results in cardiotoxicity.

Associations between blood lead and urinary cadmium levels and mortality, and effect modification by dietary inflammatory index

BACKGROUND AND AIM: Previous studies in the US reported a high mortality risk associated with higher blood lead (BPb) and urinary cadmium (UCd) concentrations. Although the mechanisms of these metals toxicity are not completely understood, increasing oxidative stress and inflammation are suspected major pathways. In parallel, diet with a high anti-inflammatory potential may prevent from chronic inflammation. We extended the follow-up of the previous analyses and evaluated the potential modifying effect of the dietary inflammatory index (DII) in the association between BPb and UCd concentrations and all-cause and specific causes of mortality. METHODS: We used data on 15,598 adults aged ≥20 years enrolled in the NHANES-III between 1988 and 1994 and followed up through Dec 31, 2015. The DII was computed from baseline dietary intake assessed using 24-hour dietary recalls. Mortality was determined from the National Death Index records. Associations between metals concentrations and mortality were assessed using Cox regression models while controlling for confounding. Interaction terms between metals concentrations and DII were included in the models and stratified analyses across the DII groups were presented. RESULTS:Over the follow-up, 1398 participants died (1398 from heart diseases, 399 from cerebrovascular diseases, 1247 from malignant neoplasms). Each increase in blood Pb level was associated with increased mortality from all-cause (HR: 1.50, 95%CI: 1.46-1.55), heart diseases (HR: 1.64, 95%CI: 1.55-1.74), cerebrovascular diseases (HR: 1.44, 95%CI: 1.30-1.60), and from malignant (1.46, 95%CI: 1.38-1.56). There was an interaction between BPb concentration and DII for all-cause and specific causes of mortality (p 0.033 for all). Participants with lower DII scores, corresponding to a higher anti-inflammatory potential of the diet, have lower risk of mortality compared to those with higher DII. The same patterns of associations were observed for UCd. CONCLUSIONS:Our findings suggest that a higher anti-inflammatory diet may help prevent BPb and UCd adverse effects in adult. KEYWORDS: Diet, Inflammation, Mortality, CVD, Cancer, Nhanes

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

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

Cadmium exposure and risk of prediabetes and diabetes: A systematic review and dose-response meta-analysis

BACKGROUND AND AIM: Elevated cadmium exposure has been associated with altered glucose metabolism, albeit the shape of such relation is still debated. We aimed at investigating the shape of the relation between cadmium exposure and type 2 diabetes and prediabetes. METHODS: We performed a systematic review with meta-analysis on the relation between biomarkers of cadmium exposure and disease risk. After performing an online literature search through March 15, 2021, we identified 34 eligible studies with cohort, cross-sectional and case-control design. RESULTS:In the meta-analysis comparing highest-versus-lowest cadmium exposure, there was an increased type 2 diabetes risk, with summary risk ratios (RRs) of 1.30 (95% confidence interval (CI): 1.00-1.69), 1.22 (95% CI 1.00-1.50), and 1.47 (95% CI 1.01-2.13) for blood, urine, and toenail cadmium concentrations, respectively. Similarly, we found a higher prediabetes risk in subjects with higher both urine and blood cadmium concentrations with RRs of 1.41 (95% CI 1.15-1.73) and 1.38 (95% CI 1.16-1.63), respectively. In the dose-response meta-analysis, compared with no exposure, prediabetes risk increased up to approximately 2 µg Cd/g creatinine, above which it reached a plateau with RR of 1.40 (95% CI 1.12-1.76) at 2 µg Cd/g creatinine. We also detected a substantial linear positive association between diabetes risk and urinary cadmium, with RR of 1.30 (95% CI 0.92-1.84) at 2.0 µg Cd/g creatinine. Diabetes risk also appeared to increase with higher blood cadmium concentrations but only above 1 µg/L, with RR of 3.25 (95% CI 1.13-9.37) at 2 µg/L. Despite limited data, there was little indication of differences in association by study design (cohort vs. case-control or cross-sectional), method of cadmium assessment, or sex (male vs. female). CONCLUSIONS:Overall, there was consistent evidence for a positive association between cadmium exposure and both prediabetes and diabetes risk. KEYWORDS: Heavy metals, Cardiovascular diseases, Endocrine disrupting chemicals, Environmental epidemiology, Toxicology

Diet quality (adequacy, variety, moderation) in relation to biomarkers of metal exposure in school-age children

BACKGROUND AND AIM: The relationship between dietary consumption and exposure to toxic metals/metalloids is complex. Foods may be a source of toxicant exposure, but they also provide many nutrients that compete with toxicants for intestinal absorption or contribute to lowering the toxicity of toxicants. Previous studies found associations between specific foods and blood or urinary lead (ex., diary), arsenic (rice) or cadmium (grains) biomarkers in children. Basing dietary recommendations on individual foods or single toxicants could result in contradictory or potentially harmful guidance. Our objective was to relate measures of overall diet quality with biomarkers of arsenic, lead and cadmium exposure in school-age children. METHODS: We constructed measures of dietary variety (servings of meats/eggs, dairy/beans, grains, fruits, vegetables), adequacy (intake of vegetables, fruit, grains, fiber, protein, iron, calcium and vitamin C) and moderation (intake of total fat, sugar sweetened beverages, pastries, sweets and chips) based on two non-consecutive 24-hr diet recalls conducted among parents of ~7 year old children in Montevideo Uruguay. Blood lead levels (BLL) were measured using atomic absorption spectrometry and total urinary arsenic (U-As) and cadmium (U-Cd) were measured via IC-PMS. Using linear regression models, we estimated the association between dietary quality and toxicant biomarkers, adjusting for child age, sex, and household socioeconomic status. RESULTS:U-As (median [5%, 95%]: 9.9 [4.1, 27.3] μg/L), U-Cd (0.06 [0.02, 0.15] μg/L) and BLL (3.8 [0.8, 7.8] μg/dL) indicated low-to-moderate exposure. Mean variety, adequacy and moderation scores were, respectively: 9.7±3.9 (out of 20), 25.0±4.7 (out of 40) and 12.3±4.8 (out of 30). Biomarkers of lead or arsenic were not associated with diet quality. Dietary variety and moderation were inversely associated with urinary cadmium concentrations. CONCLUSIONS:Diets that are varied and provide adequate levels of nutrients do not contribute to biomarkers of children’s exposure to arsenic, cadmium and lead. KEYWORDS: diet quality, lead, cadmium, arsenic, child

Genetic variation and urine cadmium levels: ABCC1 effects in the Strong Heart Family Study

BACKGROUND AND AIM: Genetic effects are suspected to influence cadmium internal dose. Our objective was to assess genetic determinants of urine cadmium in American Indian adults participating in the Strong Heart Family Study (SHFS). METHODS: Urine cadmium levels and genotyped short tandem repeat (STR) markers were available on 1936 SHFS participants. We investigated heritability, including gene-by-sex and smoking interactions, and STR-based quantitative trait locus (QTL) linkage, using a variance-component decomposition approach, which incorporates the genetic information contained in the pedigrees. We also used available single nucleotide polymorphisms (SNPs) from Illumina’s Metabochip and custom panel to assess whether promising QTLs associated regions could be attributed to statistically significant SNPs. RESULTS:Median urine cadmium levels were 0.44 μg/g creatinine. The heritability of urine cadmium concentrations was 28% in the SHFS, with no evidence of interaction by sex or by smoking. In QTL linkage analysis, we found strong statistical evidence for a genetic locus at chromosome 16 determining urine cadmium concentrations (Logarithm of odds score [LOD] = 3.8). Among the top 20 associated SNPs in this locus, 17 were annotated to ABCC1 (p-values from 0.0002 to 0.02), and attenuated the maximum linkage peak by a ~40%. For suggestive QTL signals (LOD 1.9) in chromosomes 2, 6, 11, 14, and 19, the top associated SNPs were in the genes NDUFA10, PDE10A, PLEKHA7, BAZ1A and CHAF1A, respectively. CONCLUSIONS:The findings support that urinary cadmium levels are heritable and influenced by a QTL on chromosome 16, which was explained by genetic variation in ABCC1 (potentially involved in glutathione transport and metabolism). Future studies with extended sets of genome-wide markers are needed to confirm these findings and to identify additional metabolism and toxicity pathways for cadmium. KEYWORDS: Exposure assessment, Heavy metals

Prenatal exposure to metal mixtures and lung function in children from the New Hampshire Birth Cohort Study

BACKGROUND AND AIM: Prenatal environmental exposure to metals and metalloids (referred to as “metals”) has been associated with childhood lung development, but limited data exist on metal mixtures. We aimed to investigate the association between gestational exposure to metal mixtures and childhood lung function among 267 maternal-child dyads from the New Hampshire Birth Cohort Study. METHODS: Maternal ~24-28-week gestational urinary arsenic speciation, aluminum, cadmium, cobalt, chromium, copper, iron, mercury, manganese, molybdenum, nickel, tin, lead, antimony, selenium, thallium, uranium, vanadium and zinc concentration were assessed using inductively coupled plasma mass spectroscopy (ICP-MS). Forced vital capacity (FVC), forced expiratory volume in the first second of exhalation (FEV1), and forced expiratory flow between 25% and 75% of FVC (FEF25-75) standardized z-scores were obtained at a median age of 7.4 years. We used quantile g-computation for each outcome and urinary metals adjusted for maternal smoking status, children’s age, sex and height. RESULTS:Urinary concentrations of cobalt, lead, nickel, cadmium, and chromium were inversely associated with lung function z-scores. Arsenic concentrations were inverse associated specifically with FVC and FEV1 z-scores. In contrast, lung function z-scores increased with vanadium, molybdenum, and thallium urine concentrations. CONCLUSIONS:Our findings suggest that prenatal exposure to metal mixtures impact lung function, with varying direction and magnitudes of effects. KEYWORDS: mixture, heavy metals, children’s environmental health, respiratory outcomes, biomarkers of exposure