Urinary Cadmium Research Articles

Associations of Urinary Cadmium with Body Composition and Fat Distribution in US Adults: Findings from NHANES 2011-2018.

The effects of cadmium (Cd) on metabolic physiology remain controversial. Given the varying metabolic impacts associated with different body compositions, investigating the relationship between Cd exposure and body composition may facilitate further research. Here, the associations of body composition and fat distribution with urine Cd (UCd) were evaluated. This analysis included 2979 adult participants from the 2011-2018 National Health and Demographic Survey (NHANES). UCd was measured using inductively coupled plasma mass spectrometry and adjusted for urinary creatinine. Body composition and fat distribution were estimated using dual-energy x-ray absorptiometry (DXA). The study results show that UCd was negatively associated with fat mass index (FMI) and percent fat mass (p for trend < 0.001), and the negative correlation between UCd and FMI was stronger in males and smokers (all p for interaction < 0.05). In terms of abdominal fat distribution, UCd was negatively associated with abdominal subcutaneous adipose tissue (SAT) mass (p for trend < 0.001), but with abdominal visceral adipose tissue (VAT) mass only in those with low percent fat mass (< 32.3%) (p for trend = 0.026 and p for interaction < 0.05). UCd was positively related to percent VAT (p for trend < 0.001) and visceral-to-subcutaneous (VAT/SAT) ratio (p for trend = 0.003). And there was a significant negative association between UCd and android-to-gynoid (A/G) ratio (p for trend = 0.001). Meanwhile, UCd was negatively correlated with fat-free mass index (FFMI) (p for trend < 0.001). And the negative correlation between UCd and FFMI was stronger in males, smokers, and individuals with < 32.3 percent fat mass (all p for interaction < 0.05). We found the association of UCd with body composition and fat distribution, with distinct patterns observed in different demographic groups. These findings underscore the importance of considering UCd exposure in the context of body composition and fat distribution.

Impact of metals exposure on lung function and serum club cell secretory protein among schoolchildren: A mixture and mediation analysis

Particulate matter (PM) and its harmful components are significant contributors to respiratory diseases and impaired lung function, especially in children. Club cell secretory protein (CC16) is a maker of lung epithelium or club cell injuries. To date, the relationship between metals related with PM and CC16 and lung function impairment has been overlooked in children. We enrolled 603 schoolchildren exposed to different levels of PM in China. We found per doubling increase, urinary thallium, and iron was associated with a 3.42 % (95 % CI: 0.01, 6.72) and 3.09 % (95 % CI: 0.55, 5.56) decrease of serum CC16, respectively, whereas urinary cadmium was associated with a 4.74 % (95 % CI: 1.29, 8.31) increase of serum CC16. The Bayesian kernel machine regression (BKMR) model confirmed these associations and showed a potential synergistic interaction between thallium and cadmium. Urinary metal mixtures were associated with lower CC16 when they were below the 35th percentile compared with their median. Serum CC16 mediated 11.47 % (95 % CI: 0.06, 45.00) of the association between urinary thallium and FEV1/FVC decline. The inverted U-shaped association with CC16 and the mediation role of CC16 on associations with lung function provide insight into the mechanisms underlying lung injury induced by metals related with PM.

Urinary Metal Levels and Coronary Artery Calcification: Longitudinal Evidence in the Multi-Ethnic Study of Atherosclerosis

BackgroundExposure to metals, a newly recognized risk factor for cardiovascular disease (CVD), could be related to atherosclerosis progression. ObjectivesThe authors hypothesized that higher urinary levels of nonessential (cadmium, tungsten, uranium) and essential (cobalt, copper, zinc) metals previously associated with CVD would be associated with baseline and rate of change of coronary artery calcium (CAC) progression, a subclinical marker of CVD in MESA (Multi-Ethnic Study of Atherosclerosis). MethodsWe analyzed data from 6,418 MESA participants with spot urinary metal levels at baseline (2000-2002) and 1 to 4 repeated, continuous measures of CAC over a 10-year period. We used linear mixed-effect models to assess the association of baseline urinary metal levels with baseline CAC and cumulative change in CAC over a 10-year period. Urinary metals (μg/g creatinine) and CAC were log transformed. Models were adjusted for baseline sociodemographic factors, estimated glomerular filtration rate, lifestyle factors, and clinical factors. ResultsAt baseline, the median CAC was 6.3 (Q1-Q3: 0.7-58.2). Comparing the highest to lowest quartile of urinary cadmium, CAC levels were 51% (95% CI: 32%, 74%) higher at baseline and 75% (95% CI: 47%, 107%) higher over the 10-year period. For urinary tungsten, uranium, and cobalt, the corresponding CAC levels over the 10-year period were 45% (95% CI: 23%, 71%), 39% (95% CI: 17%, 64%), and 47% (95% CI: 25%, 74%) higher, respectively, with no difference for models with and without adjustment for clinical factors. For copper and zinc, the corresponding estimates dropped from 55% to 33% and from 85% to 57%, respectively, after adjustment for clinical factors. The associations of metals with CAC were comparable in magnitude to those for classical CVD risk factors. ConclusionsExposure to metals was generally associated with extent of coronary calcification at baseline and follow-up. These findings support that metals are associated with the progression of atherosclerosis, potentially providing a novel strategy for the prevention and treatment of atherosclerosis progression.

Association between heavy metal exposure and biomarkers for non-alcoholic fatty liver disease in Korean adolescents

ObjectivesThe global prevalence of non-alcoholic fatty liver disease (NAFLD) in adolescents has increased. In addition to childhood obesity, environmental risk factors, such as heavy metals that are known to be involved in hepatotoxicity, play role in NAFLD occurrence. However, their association with NAFLD remains unclear. This study aimed to investigate the association between heavy metal exposure and NAFLD biomarkers in adolescents. MethodsIn this cross-sectional study, we used the data of a total of 1505 adolescents aged 12–17 years who participated in the Korean National Environmental Health Survey III (2015–2017) and IV (2018–2020). The presence of blood lead (BPb), blood mercury (BHg), urinary mercury (UHg), and urinary cadmium (UCd) were measured. Liver enzymes including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were evaluated. For NAFLD biomarkers, the hepatic steatosis index (HSI) was calculated. Multivariate linear regression models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) model were used to investigate the association between heavy metals and NAFLD biomarkers. ResultsAmong heavy metals, mercury presence showed a significant association with NAFLD biomarkers. Two-fold increases in BHg and UHg were associated with 0.21 points (95 % confidence interval [CI]: 0.08–0.35) and 0.19 points (95 % CI: 0.09–0.30) higher HSI, respectively. In the WQS model, heavy metal mixture was significantly associated with increased HSI (β = 0.06, 95 % CI: 0.01–0.11). Similarly, in the BKMR model, heavy metal mixture was positively associated with NAFLD biomarkers, and BHg was the most important contributor in the association. ConclusionsBHg and UHg were significantly associated with NAFLD biomarkers in adolescents, indicating that organic and inorganic mercury exposure could potentially be a risk factor for NAFLD. To mitigate and address the risk of NAFLD associated with heavy metal exposure, it is imperative to take measure to reduce avoidable mercury exposure is necessary.

Cadmium (Third Edition) (Chemicals and Contaminants).

Exposure to cadmium tends to be higher in Japan than in other countries due to the wide spreading of ore deposits and many mines throughout Japan. The proximal tubule of the kidney is recognized as the most susceptible site to be affected by cadmium exposure. Food Safety Commission of Japan (FSCJ) considered it appropriate to investigate studies of the effects of cadmium intake on renal proximal tubular function using urinary β2-microglobulin concentration of 1,000 μg/g creatinine as a criterion for the dysfunction. Based on these epidemiological studies, FSCJ established a tolerable weekly intake (TWI) of 7 µg/kg bw per week for cadmium. This value is derived from the results of actual dietary surveys and urinary β2-microglobulin concentrations in Japan, and not from the results of application of blood or urinary cadmium levels to theoretical models. Therefore, no uncertainty factor is required. The estimated dietary intake of cadmium in 2022 was 2.03 µg/kg bw per week, approximately 30% of the TWI of 7 µg/kg bw per week. Therefore, it is unlikely that dietary cadmium intake in the general Japanese population would cause adverse health effects.

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

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

Serum and urinary cadmium and zinc profiles in breast cancer patients and their association with estrogen and HER-2 receptors, and redox status

BackgroundCadmium, a metal implicated in environmental toxicity, is linked to tumor growth and cancer. On the other hand, zinc plays an essential function in oxidative stress and can counteract cadmium toxicity and carcinogenicity. This research aims to evaluate the urine and serum values of cadmium and zinc in breast cancer (BC) patients and their association with estrogen (ER) and HER-2 receptors, and redox status. MethodsForty BC patients and thirty healthy subjects participated in this study. Cadmium and zinc levels were measured in serum and urine samples by atomic absorption spectrophotometer. Redox status markers were determined by colorimetric methods. ResultsThe amount of cadmium in the BC patients was substantially greater than in the healthy subjects. Zinc levels were significantly lower in patients with BC compared to controls. Breast cancer patients with ER-positive tumors had significantly higher urinary cadmium concentrations (U-Cd) compared to patients with ER-negative tumors. There was no significant difference between the parameters of redox status and the value of cadmium and zinc between patients with BC in the HER-2 subgroup. Malondialdehyde levels in the serum were substantially greater in BC patients than in healthy subjects. Total thiol level and catalase and superoxide dismutase activity in serum were considerably lower in BC patients than in healthy subjects. ConclusionsThe etiology of BC may be due to a disturbance in redox status and levels of elements. Increasing U-Cd and lowering zinc levels in the serum could be the risk factors for BC.

Impact of COVID-19 on temporal trends and health risks of urinary metal concentrations among residents of Guangzhou, China

Long-term biomonitoring of urinary metal ions is an essential tool for the epidemiological assessment of chronic exposure levels, enabling us to track changes in metal exposure over time and better understand its health implications. In this study, we evaluated the temporal trends of urinary metal ions among 1962 residents of Guangzhou, China, from 2018 to 2022. The total metal ion concentrations in the urine of the population did not change significantly between 2018 and 2019. With the onset of the COVID-19 pandemic in 2020, urinary total metal ion concentrations began to decline dramatically, reaching their lowest level in 2021. A rebound in concentrations was observed in 2022, which returned to the initial levels observed in 2018. Urine chromium and cadmium concentrations peaked in 2020, while urinary lead levels were the highest in 2021, and urinary nickel concentrations were the highest in 2022. Males consistently displayed higher urinary concentrations of lead and arsenic throughout each year of the study. Furthermore, minors consistently had higher urinary nickel levels than adults, whereas adults consistently had higher urinary cadmium concentrations than minors. Cluster analyses were conducted annually on urinary metal ions to examine the differences in their distribution and to evaluate changes in metal exposure patterns over time. The Monte Carlo simulations indicate that the whole population exhibits a high non-carcinogenic risk from arsenic exposure and significant carcinogenic risks associated with exposure to nickel, arsenic, chromium, and cadmium. The next two years were predicted by a gray prediction model, and the results are tested using mean absolute percentage error which demonstrating high accuracy.

Association between metal exposures and periodontitis among U.S. adults: the potential mediating role of biological aging

BackgroundThis study aimed to investigate the associations between metal exposures and periodontitis among U.S. adults, as well as the mediated effect of biological aging.MethodsUsing data from the National Health and Nutrition Examination Survey (NHANES) 2009–2014, we explored the single and mixed impacts of metal exposures on periodontitis through adjusted weighted logistic regression, robust Poisson regression, restricted cubic spline regression, and Bayesian kernel machine regression models. This study included 2,393 participants, with 46.9% experiencing periodontitis. Concentrations of nine urinary metals, including barium (Ba), cadmium (Cd), cobalt (Co), cesium (Cs), molybdenum (Mo), lead (Pb), thallium (Tl), tungsten (Tu), and uranium (Ur), were measured using inductively coupled plasma-mass spectrometry. In addition, we analyzed the association between metals and periodontitis, stratified by age, body mass index, gender, and smoking status. Mediation models were also applied to investigate the mediated effects of biological aging between metal exposures and periodontitis.ResultsWeighted logistic and robust Poisson regression identified positive associations between Cd, Pb and periodontitis (P < 0.05). BKMR analyses indicated that mixed metal exposures were significantly associated with periodontitis, particularly among smokers, second-hand smokers, and males, with Cd, Pb, Tl, and Ba contributing the most. Furthermore, subgroup analyses observed a modifying effect on the associations between urinary Cd, Pb and periodontitis in stratified gender and BMI subgroups in robust Poisson regression. Phenotype age was found to mediate the association between metals and periodontitis.ConclusionsThis study identified significant positive associations between metal exposures and periodontitis in the U.S. adults. In addition, the association between metal exposures and periodontitis could vary in different gender, BMI and smoking subgroups. These associations were likely partly mediated by biological aging, suggesting that metals may potentially increase the risk of periodontitis by promoting cell senescence and overall aging of the body.Graphical

Estimation of urinary cadmium benchmark dose thresholds for preschool children in a cadmium-polluted area based on Bayesian model averaging.

Urinary cadmium (U-Cd) values are indicators for determining chronic cadmium toxicity, and previous studies have calculated U-Cd indicators using renal injury biomarkers. However, most of these studies have been conducted in adult populations, and there is a lack of research on U-Cd thresholds in preschool children. We aimed to apply benchmark dose (BMD) analysis to estimate the U-Cd threshold level associated with renal impairment in preschool children in the cadmium-polluted area. 518 preschool children aged 3-5years were selected by systematic sampling (275 boys, 243 girls). Urinary cadmium and three biomarkers of early renal injury (urinary N-acetyl-β-D-glucosaminidase, UNAG; urinary β2-microglobulin, Uβ2-MG; urinary retinol-binding protein, URBP) were determined. Bayesian model averaging estimated the BMD and lower confidence interval limit (BMDL) of U-Cd. The medians U-Cd levels in both boys and girls exceeded the recommended national standard threshold (5μg/gcr) and U-Cd levels were higher in girls than in boys. Urinary N-acetyl-β-D-glucosaminidase (UNAG) was the most sensitive biomarker of renal effects in preschool children. The overall BMDL5 (BMDL at a benchmark response value of 5) was 2.76μg/gcr. In the gender analysis, the BMDL5 values were 1.92μg/gcr for boys and 4.12μg/gcr for girls. This study shows that the U-Cd threshold (BMDL5) is lower than the national standard (5μg/gcr) and boys' BMDL5 was lower than the limit set by the European Parliament and Council in 2019 (2μg/gcr), which provides a reference point for making U-Cd thresholds for preschool children.

Association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40-89 in selected areas of China

Objective: To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China. Methods: The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function. Results: The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M (Q1, Q3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95%CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion: Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Applying machine learning to construct an association model for lung cancer and environmental hormone high-risk factors and nursing assessment reconstruction.

To utilize machine learning techniques to develop an association model linking lung cancer and environmental hormones to enhance the understanding of potential lung cancer risk factors and refine current nursing assessments for lung cancer. This study is exploratory in nature. In Stage 1, data were sourced from a biological database, and machine learning methods, including logistic regression and neural-like networks, were employed to construct an association model. Results indicate significant associations between lung cancer and blood cadmium, urine cadmium, urine cadmium/creatinine, and di(2-ethylhexyl) phthalate. In Stage 2, 128 lung adenocarcinoma patients were recruited through convenience sampling, and the model was validated using a questionnaire assessing daily living habits and exposure to environmental hormones. Analysis reveals correlations between the living habits of patients with lung adenocarcinoma and exposure to blood cadmium, urine cadmium, urine cadmium/creatinine, polyaromatic hydrocarbons, diethyl phthalate, and di(2-ethylhexyl) phthalate. According to the World Health Organization's global statistics, lung cancer claims approximately 1.8 million lives annually, with more than 50% of patients having no history of smoking or non-traditional risk factors. Environmental hormones have garnered significant attention in recent years in pathogen exploration. However, current nursing assessments for lung cancer risk have not incorporated environmental hormone-related factors. This study proposes reconstructing existing lung cancer nursing assessments with a comprehensive evaluation of lung cancer risks. The findings underscore the importance of future studies advocating for public screening of environmental hormone toxins to increase the sample size and validate the model externally. The developed association model lays the groundwork for advancing cancer risk nursing assessments.

Association between urinary metals and prostate-specific antigen in aging population with depression: a cross-sectional study

ObjectiveThis study aims to investigate the impact of depression and urinary metals on Prostate-Specific Antigen (PSA).MethodsAnalysis was conducted on 1901 samples collected from the National Health and Nutrition Examination Survey (NHANES) database between 2001 and 2010. Analytical methods included stepwise multiple linear regression (MLR) analysis of the overall population’s urinary metals and PSA relationship, analysis of urinary metals and PSA relationship in older adults and BMI subgroups, analysis of urinary metals and PSA relationship in the depressed population, and restricted cubic spline (RCS) analysis. A significance level of p &amp;lt; 0.05 was considered statistically significant.ResultsIn the stepwise multiple linear regression, beryllium (Be) showed a dose–response association with PSA (third quartile: β = 0.05, 95%CI (0.02, 0.09); fourth quartile: β = 0.07, 95%CI (0.02, 0.12), p trend = 0.048). Subgroup analysis indicated that in individuals aged &amp;gt;60, Be at Q4 level [β = 0.09, 95%CI (0.05, 0.21)] exhibited a dose–response correlation with PSA. In the population with 25 ≤ BMI &amp;lt; 30, Be might more significantly elevate PSA, with Q4 level having a pronounced impact on PSA levels [β = 0.03, 95%CI (0.02, 1.27)]. In the depressed population, urinary cadmium (Cd) levels showed a significant positive dose–response relationship, with Q4 level of Cd having the maximum impact on PSA [β = 0.3, 95%CI (0.09, 0.49)].ConclusionIndividuals exposed to beryllium (Be), especially the older adults and overweight, should monitor their PSA levels. In depressed patients, cadmium (Cd) levels may further elevate PSA levels, necessitating increased monitoring of PSA levels among males.

Spatial - temporal mapping of urine cadmium levels in China during 1980 - 2040: Dietary improvements lower exposure amid rising pollution

Persistent cadmium exposure poses significant health risks to the Chinese population, underscored by its prevalence as an environmental contaminant. This study leverages a machine-learning model, fed with a comprehensive dataset of environmental and socio-economic factors, to delineate trends in cadmium exposure from 1980 to 2040. We uncovered that urinary cadmium levels peaked at 1.09 μg/g Cr in the mid-2000 s. Encouragingly, a decline is projected to 0.92 μg/g Cr by 2025, tapering further to 0.87 μg/g Cr by 2040. Despite this trend, regions heavily influenced by industrialization, such as Hunan and Guizhou, as well as industrial counties in Jilin, report stubbornly high levels of exposure. Our demographic analysis reveals a higher vulnerability among adults & adolescents over 14, with males displaying elevated cadmium concentrations. Alarmingly, the projected data suggests that by 2040, an estimated 41% of the population will endure exposure beyond the safety threshold set by the European Food Safety Authority. Our research indicates disproportionate cadmium exposure impacts, necessitating targeted interventions and policy reforms to protect vulnerable groups and public health in China.

Detection of Cadmium in Human Biospecimens by a Cadmium-Selective Whole-Cell Biosensor Based on Deoxyviolacein.

Cadmium poses a severe health risk, impacting various bodily systems. Monitoring human exposure is vital. Urine and blood cadmium serve as critical biomarkers. However, current urine and blood cadmium detection methods are expensive and complex. Being cost-effective, user-friendly, and efficient, visual biosensing offers a promising complement to existing techniques. Therefore, we constructed a cadmium whole-cell biosensor using CadR10 and deoxyviolacein pigment in this study. We assessed the sensor for time-dose response, specific response to cadmium, sensitivity response to cadmium, and stability response to cadmium. The results showed that (1) the sensor had a preferred signal-to-noise ratio when the incubation time was 4 h; (2) the sensor showed excellent specificity for cadmium compared to the group 12 metals and lead; (3) the sensor was responsive to cadmium down to 1.53 nM under experimental conditions and had good linearity over a wide range from 1.53 nM to 100 μM with good linearity (R2 = 0.979); and (4) the sensor had good stability. Based on the excellent results of the performance tests, we developed a cost-effective, high-throughput method for detecting urinary and blood cadmium. Specifically, this was realized by adding the blood or urine samples into the culture system in a particular proportion. Then, the whole-cell biosensor was subjected to culture, n-butanol extraction, and microplate reading. The results showed that (1) at 20% urine addition ratio, the sensor had an excellent curvilinear relationship (R2 = 0.986) in the range of 3.05 nM to 100 μM, and the detection limit could reach 3.05 nM. (2) At a 10% blood addition ratio, the sensor had an excellent nonlinear relationship (R2 = 0.978) in the range of 0.097-50 μM, and the detection limit reached 0.195 μM. Overall, we developed a sensitive and wide-range method based on a whole-cell biosensor for the detection of cadmium in blood and urine, which has the advantages of being cost-effective, ease of operation, fast response, and low dependence on instrumentation and has the potential to be applied in the monitoring of cadmium exposure in humans as a complementary to the mainstream detection techniques.

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

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

Cadmium Exposure was Associated with Sex-Specific Thyroid Dysfunction: Consistent Evidence from Two Independent Cross-Sectional Studies Based on Urinary and Blood Cadmium Measurements.

Population-based studies on the association between cadmium (Cd) exposure and thyroid function are limited and have shown conflicting results. Two independent cross-sectional studies using different Cd biomarkers were carried out in six rural areas with different soil Cd levels in China. Thyroid dysfunction was defined based on levels of thyroid stimulating hormone (TSH) and free thyroxine (FT4). Multivariable linear regression, multiple logistic regression, and restrictive cubic splines models were used to estimate the association between Cd and thyroid dysfunction. For both of the two independent studies, higher Cd levels were observed to be associated with lower TSH levels and higher risk of thyroid dysfunction. The negative relationship between urinary Cd and TSH was found in both total participants (β = - 0.072, p = 0.008) and males (β = - 0.119, p = 0.020) but not in females; however, the negative relationship between blood Cd and TSH was only found in females (β = - 0.104, p = 0.024). Higher urinary Cd was associated with higher risk of thyroid dysfunction (OR = 1.77, p = 0.031), while higher blood Cd was associated with higher risk of thyroid dysfunction (OR = 1.95, p = 0.011). Results from the two independent cross-sectional studies consistently suggested that higher Cd levels were associated with sex-specific thyroid dysfunction.

Baseline characteristics including blood and urine metal levels in the Trial to Assess Chelation Therapy 2 (TACT2)

BackgroundThe reduction in cardiovascular disease (CVD) events with edetate disodium (EDTA) in the Trial to Assess Chelation Therapy (TACT) suggested that chelation of toxic metals might provide novel opportunities to reduce CVD in patients with diabetes. Lead and cadmium are vasculotoxic metals chelated by EDTA. We present baseline characteristics for participants in TACT2, a randomized, double-masked, placebo-controlled trial designed as a replication of the TACT trial limited to patients with diabetes. MethodsTACT2 enrolled 1,000 participants with diabetes and prior myocardial infarction, age 50 years or older between September 2016 and December 2020. Among 959 participants with at least one infusion, 933 had blood and/or urine metals measured at the Centers for Diseases Control and Prevention using the same methodology as in the National Health and Nutrition Examination Survey (NHANES). We compared metal levels in TACT2 to a contemporaneous subset of NHANES participants with CVD, diabetes and other inclusion criteria similar to TACT2’s participants. ResultsAt baseline, the median (interquartile range, IQR) age was 67 (60, 72) years, 27% were women, 78% reported white race, mean (SD) BMI was 32.7 (6.6) kg/m2, 4% reported type 1 diabetes, 46.8% were treated with insulin, 22.3% with GLP1-receptor agonists or SGLT-2 inhibitors, 90.2% with aspirin, warfarin or P2Y12 inhibitors, and 86.5% with statins. Blood lead was detectable in all participants; median (IQR) was 9.19 (6.30, 13.9) µg/L. Blood and urine cadmium were detectable in 97% and median (IQR) levels were 0.28 (0.18, 0.43) µg/L and 0.30 (0.18, 0.51) µg/g creatinine, respectively. Metal levels were largely similar to those in the contemporaneous NHANES subset. ConclusionsTACT2 participants were characterized by high use of medication to treat CVD and diabetes and similar baseline metal levels as in the general US population. TACT2 will determine whether chelation therapy reduces the occurrence of subsequent CVD events in this high-risk population. Clinical Trials RegistrationClinicalTrials.gov. Identifier: NCT02733185. https://clinicaltrials.gov/study/NCT02733185

Urine cadmium and urolithiasis: A systematic review and meta-analysis

Exposure to cadmium may increase risk of urolithiasis, but the results remain inconclusive. This systematic review and meta-analysis aimed to access the association between cadmium exposure and urolithiasis. We searched Medline/PubMed, Embase, Web of Science Core Collection, and Cochrane Central for studies. The primary outcome was the incidence of urolithiasis compared to reference groups. We used relative risk as the summary effect measure. This meta-analysis included eight observational studies and divided into 39 study populations. Among 63,051 subjects, 5018 (7.96%) individuals had urolithiasis. The results indicated that people with an increment of 0.1 μg/g creatinine in urinary cadmium had a 2% increased risk of urolithiasis (pooled relative risk [RR], 1.02; 95% confidence interval [CI], 1.01–1.03) and there is no difference in the risk of urolithiasis in high and low cadmium exposure levels. Meanwhile, people with an increment of 0.1 μg/L in urinary cadmium had a 4% increased risk of urolithiasis (pooled RR, 1.04; 95% CI, 1.02–1.07). Our findings also showed similar associations in both sex, different region (Sweden, China, and Thailand), general and occupational population. The results indicate that cadmium exposure was significantly associated with an elevated risk of urolithiasis. Therefore, it is imperative to take steps to minimize cadmium exposure.

Abstract MP73: The Association of Urinary Metals With Cardiovascular Disease Incidence and All-Cause Mortality in the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Environmental exposure to metals is widespread yet preventable and has been associated with cardiovascular disease (CVD) endpoints, although evidence from prospective studies with racial and ethnic diversity is limited. Objective: We assessed the prospective association of urinary metals with incident coronary heart disease (CHD) and CVD and all-cause mortality in a diverse population of adults from the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: We included 6,638 MESA participants (mean (SD) age 62.1(10.2) years, 53% female, 39% non-Hispanic white, 27% non-Hispanic Black, 22% Hispanic/Latino, 12% Chinese). Urinary non-essential metals (cadmium, tungsten, and uranium), and essential metals (cobalt, copper, and zinc) were assessed at baseline (2000-2001). We used Cox proportional hazards regression to estimate adjusted (table footnote) hazard ratios (HR) for the association between urine metals with incident CHD, CVD, and all-cause mortality through 2019. Results: Over 17.7 years median follow up (IQR: 12.4, 18.5), 749 (11%) participants developed CHD, 1,162 (17%) developed CVD, and 1,844 (28%) died. In the models adjusted by sociodemographic and behavioral factors (Table 1, [Model 1]), one IQR increase in urinary cadmium, tungsten, cobalt, copper, and zinc at baseline was significantly associated with higher risk of incident CHD, incident CVD and all-cause mortality. Uranium levels were significantly associated with all-cause mortality and incident CVD, but not CHD. The magnitude of the association was attenuated when adjusting the models for clinical risk factors (Table 1, [Model 2]). A linear trend was identified for cadmium and copper and all endpoints. Conclusion: Our findings among a large and ethnically diverse US population support that metal exposure is associated with incident CVD and premature mortality. These findings can inform the development of novel preventive strategies to improve cardiovascular health.