Single Metal Exposure Research Articles

Association between multiple metal exposure and bone mineral density among Chinese adults.

Previous studies about metal exposures and bone mineral density (BMD) have mainly focused on individual metals. The objective of this study was to explore the association of single and multiple metal exposures with BMD among Chinese adults. We recruited 2922 participants from Tongji Hospital in Wuhan, China. The urinary concentrations of 21 metals were measured by the inductively coupled plasma mass spectrometer. BMD was measured using dual-energy X-ray absorptiometry. We applied linear regression and Bayesian kernel machine regression (BKMR) to examine the association of single and multiple metal exposure with BMD, respectively. The linear regression model showed that cadmium (Cd) and strontium (Sr) were associated with lower BMD (all P-trend < 0.05). Compared with the lowest quantiles, the β (95% CI) of BMD in the highest quartile of Cd and Sr was - 0.032 (- 0.049, - 0.016) and - 0.033 (- 0.049, - 0.018), respectively. The BKMR results showed that co-exposure to 21 metals was negatively associated with BMD among the total participants and males. Our study suggested that exposure to multiple metals was negatively associated with BMD, particularly among males. More prospective studies are needed to identify these associations and reveal the underlying mechanisms.

Associations of urinary heavy metals with age at menarche, age at menopause, and reproductive lifespan: A cross-sectional study in U.S. women

Female reproductive timing and lifespan, with a close relation to long-term health outcomes, have been altered in U.S. women over the past decades. However, epidemiologic evidence of the potential causes was lacking. On the basis of 1981 naturally postmenopausal women from the National Health and Nutrition Examination Survey 1999–2020, this study aimed to investigate the associations of urinary heavy metals with age at menarche, age at menopause, and reproductive lifespan. Multivariate generalized linear regression and addictive models were used for single metal exposure analysis, and weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were employed for mixed exposures. In the fully adjusted model, higher urinary antimony concentration was associated with earlier age at menarche of 0.137 years, while higher concentrations of cadmium, cesium, lead, antimony, and thallium were associated with delayed age at menopause of 0.396–0.687 years. Additionally, urinary barium, cesium, lead, antimony, and thallium levels were associated with longer reproductive lifespan ranging between 0.277 and 0.713 years. Both WQS and BKMR models showed significantly positive associations of metal mixtures with age at menopause (β: 0.667, 95 % CI: 0.120–1.213) and reproductive lifespan (β: 0.686, 95 % CI: 0.092–1.280), with cadmium and lead identified as principal contributors. In conclusion, heavy metal exposures were associated with reproductive timing and lifespan of U.S. women, highlighting the need for further prevention and intervention strategies.

Vitamin D deficiency may exacerbate the role of metal exposure in depression: A cross-sectional analysis of NHANES data from 2007 to 2018

People are paying more and more attention to the effects of environmental factors such as heavy metals on depression, and heavy metals may destroy the homeostasis of vitamin D in the body by affecting human metabolism, and the lack of vitamin D will increase the risk of depression. There are few studies on vitamin D deficiency in depression caused by heavy metals, and it is not deep enough. Therefore, this study used logistic regression, restricted cubic spline curve, weighted quantile and Quantile g-computation model to analyze the effects of heavy metal exposure alone and in combination on vitamin D and depression, as well as the potential role of vitamin D deficiency in the process of heavy metal-induced depression. The results showed that cadmium exposure alone or in combination increased the risk of depression (P < 0.05). When Cd increased by 1 unit, the risk of depressive symptoms increased by 1.178 units. Arsenic and its compounds and lead affected vitamin D levels in the body and contributed the second highest or highest weight in the mixture (P < 0.05). It is worth noting that after grouping according to vitamin D deficiency, compared with the normal group, the mixed exposure of heavy metals in the vitamin D deficiency group had more types of metals related to depression and contributed more weight (P < 0.05). This study found that single metal or multi-metal mixed exposure is associated with depression. Vitamin D deficiency may increase the risk of depression. Vitamin D may be a potential factor in the treatment of depression caused by metal, and the specific mechanism of action needs further study.

The Relationship Between Metal Exposure and HPV Infection: Evidence from Explainable Machine Learning Methods.

HPV is a ubiquitous pathogen implicated in cervical and other cancers. Although vaccines are available, they do not encompass all subtypes. Meanwhile, metal exposure may elevate the risk of HPV infection and amplify its carcinogenic potential, but studies to further elucidate this relationship are insufficient.This study entailed a cross-sectional analysis utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. The study sample comprised 2765 women. Multivariate logistic regression was employed to examine the association between single metal exposure and HPV infection, weighted quantile sum (WQS) regression was utilized for assessing the mixed metal exposure effect, and the XGBoost + SHapley Additive exPlanations (SHAP) to evaluate the contribution of metal exposure in HPV infection.Multivariate logistic regression analysis indicated that elevated Co concentration was inversely associated with HPV infection (OR 0.891; 95% CI 0.814-0.975), while elevated Pb concentration correlated with an increased HPV infection (OR 1.176; 95% CI 1.074-1.287). Regression analysis of the WQS for mixed metal exposure suggested that the WQS index was potentially linked to an increased likelihood of HPV infection in the positive direction (OR 1.249; 95% CI 1.052-1.482), with no significant association observed in the negative direction (OR 0.852; 95% CI 0.713-1.017). SHAP analysis prioritized the importance of characteristics: number of sexual partners, marital status, poverty-to-income ratio (PIR), Co, Pb, and alcohol consumption.Exposure to Pb was associated with an increase in the incidence of HPV infection, whereas Co exposure demonstrated an inverse relationship. The composite exposure to multiple metals showed a positive association with the prevalence of HPV infection. These findings indicate that exposure to metals could potentially escalate the prevalence of HPV infection.

Uric acid mediates the relationship between mixed heavy metal exposure and renal function in older adult people.

Population aging is a pivotal trend observed globally, and the exposure to heavy metals can exacerbate the aging process and lead to kidney damage. However, the impact of combined heavy metal exposure on renal function among older individuals remains elusive. Our study employs machine learning techniques to delve into the effects and underlying mechanisms of mixed exposure to heavy metals on the renal function of the aging population. This study extracted comprehensive data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2015 and 2020. A total of 3,175 participants aged 60 years and above, with complete information on six metals - lead, cadmium, manganese, cobalt, mercury, and selenium, along with relevant covariates, were included in the study. To assess the impact of single or mixed metal exposure on the renal function of older adult individuals, various statistical techniques were employed: multiple logistic regression, weighted quantitative sum (WQS) regression, Bayesian kernel machine regression (BKMR), and mediation effects analysis. Multiple logistic regression revealed that selenium and manganese were protective factors for chronic kidney disease (CKD). Cobalt was a risk factor for CKD. High concentrations of lead, cadmium, and cobalt were risk factors for urinary albumin creatinine ratio (ACR). WQS analyses revealed that mixed metal exposure was positively correlated with estimated glomerular filtration rate (eGFR) but negatively correlated with CKD. Selenium and manganese can neutralize the effects of other metals on eGFR. Mixed metal exposure was positively correlated with ACR, with lead and cadmium having a substantial effect. Mediation analysis showed that uric acid (UA) had a mediating effect of 9.7% and -19.7% in the association between mixed metals exposure and proteinuria and CKD, respectively. The impact of heavy metals on renal function in the older adult differs from that of adolescents and adults. This study suggests that elevated levels of mixed metals exposure are linked to proteinuria and CKD, with UA serving as a mediating factor.

Co-exposure to Aluminium and Cadmium Mediates Postpartum Maternal Variation in Brain Architecture and Behaviour of Mice; Involvement of Oxido-nitrergic and Cholinergic Mechanisms : Postpartum effects of Aluminium and Cadmium co-exposure in pregnancy.

Most research has not been done on the possible relationship between pregnant women's cross-metal exposures and postpartum neuroendocrine functions. The purpose of this study was to look into how co-exposure to aluminium chloride (AlCl3) and cadmium chloride (CdCl2) affected the neuroendocrine and neurometabolic changes in postpartum mice. A total of 24 adult pregnant female mice were used for the study. Group 1 served as control and received neither AlCl3nor CdCl2 (n=6), group 2 comprised pregnant mice treated with AlCl3 (10mg/kg), group 3 with CdCl2 (1.5mg/kg), group 4 with a combination of AlCl3(10 mg/kg) and CdCl2 (1.5 mg/kg).Oral treatment of animals was done daily from gestation day 7 to gestation day 20. Upon delivery and weaning on postnatal day 21 (PND 21), behavioural assessment was done on the postpartum mice and immediately followed by sacrifice for assessment of histological and neuroendocrine markers. Our findings revealed that the brain-to-body weight ratio was affected and brain oxidative stress was elevated in mice exposed to AlCl3 and CdCl2 during pregnancy. Given the strong association between postpartum hyperactivity, social interaction index, brain catalase and acetylcholinesterase activity, and the brain/body weight ratio, it is plausible that these effects have played a role in the adverse behavioural abnormalities observed in the postpartum maternal mice. Moreover, it was noted that in certain situations, co-exposures to the metals tended to have opposite effects to single metal exposures.

Effect of Toxicity of Chromium (VI) Stressors Alone and Combined to High Temperature on the Histopathological, Antioxidation, Immunity, and Energy Metabolism in Fish Phoxinus lagowskii

Fish in aquatic ecosystems are often impacted by environmental stressors like temperature fluctuations and exposure to heavy metals. Chromium (Cr6+) is a known environmental pollutant that poses a threat to aquatic life. Various environmental factors, such as water temperature, have been found to affect the toxicity of dissolved chemicals in aquatic ecosystems. We investigated the toxicity of combinations of different concentrations of hexavalent chromium (Cr6+) with high temperatures in fish. Hematological indices demonstrated changes in white blood cells (WBCs), hematocrit (HCT), red blood cells (RBCs), and hemoglobin (Hb) levels during the exposure. The qualitative and semi-quantitative analyses of different tissues confirmed that higher concentrations of Cr6+ caused more significant damage than lower concentrations, with evident alterations observed in circulatory and regressive aspects. Furthermore, brain acetylcholinesterase levels decreased in both single heavy metal exposure and combined exposure at a high temperature. The activity of antioxidant oxidase and immunological parameters increased in all treatment groups compared with the control group following long-term exposure. A significant and increased effect of Cr6+ in the high-temperature groups was observed on the evaluated biomarkers, suggesting a possible synergistic effect between Cr6+ and increased temperature. The integrated biomarker response (IBR) reported the highest level of stress at 10 mg/L Cr6+ combined with high temperature. The IBR analysis revealed that the highest activity of response enzymes, such as acid phosphatase (ACP), superoxide dismutase (SOD), and glutathione S-transferases (GST), was observed in the liver, whereas the gills displayed alkaline phosphatase (ALP), GST, and SOD activity, and the kidneys demonstrated SOD, ACP, and aspartate aminotransferase (AST) to be most active. Through histopathology, antioxidant enzymes, and metabolism- and immunity-related enzymes, we determined that high temperatures enhance the potential toxicity of Cr6+ in fish. We recommend conducting a thorough assessment of the impact of climate change, particularly temperature fluctuations, when studying the toxic effects of metal pollution, like chromium, in aquatic ecosystems.

Metal mixture exposures and serum lipid levels in childhood: the Rhea mother-child cohort in Greece.

Growing evidence suggests that cardiovascular disease develops over the lifetime, often beginning in childhood. Metal exposures have been associated with cardiovascular disease and important risk factors, including dyslipidemia, but prior studies have largely focused on adult populations and single metal exposures. To investigate the individual and joint impacts of multiple metal exposures on lipid levels during childhood. This cross-sectional study included 291 4-year-old children from the Rhea Cohort Study in Heraklion, Greece. Seven metals (manganese, cobalt, selenium, molybdenum, cadmium, mercury, and lead) were measured in whole blood using inductively coupled plasma mass spectrometry. Serum lipid levels included total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. To determine the joint and individual impacts of child metal exposures (log2-transformed) on lipid levels, Bayesian kernel machine regression (BKMR) was employed as the primary multi-pollutant approach. Potential effect modification by child sex and childhood environmental tobacco smoke exposure was also evaluated. BKMR identified a positive association between the metal mixture and both total and LDL cholesterol. Of the seven metals examined, selenium (median 90.6 [IQR = 83.6, 96.5] µg/L) was assigned the highest posterior inclusion probability for both total and LDL cholesterol. A difference in LDL cholesterol of 8.22 mg/dL (95% CI = 1.85, 14.59) was observed when blood selenium was set to its 75th versus 25th percentile, holding all other metals at their median values. In stratified analyses, the positive association between selenium and LDL cholesterol was only observed among boys or among children exposed to environmental tobacco smoke during childhood. Growing evidence indicates that cardiovascular events in adulthood are the consequence of the lifelong atherosclerotic process that begins in childhood. Therefore, public health interventions targeting childhood cardiovascular risk factors may have a particularly profound impact on reducing the burden of cardiovascular disease. Although growing evidence supports that both essential and nonessential metals contribute to cardiovascular disease and risk factors, such as dyslipidemia, prior studies have mainly focused on single metal exposures in adult populations. To address this research gap, the current study investigated the joint impacts of multiple metal exposures on lipid concentrations in early childhood.

Metal (loid) Exposure and Overweight and Obesity in 6–12-Year-Old Spanish Children

AbstractEpidemiological studies focusing on metal(oid) exposure and excess body weight among children show inconsistent results and the influence of metal(loid) mixtures has been little studied. We aimed to explore the effect of 10 metal(loid)s, individually and in combinations, on overweight and obesity among children aged 6–12. Urinary levels of these metal(oid)s from 92 controls and 51 cases with overweight and obesity were analyzed. Metal(loid) levels were log-transformed and categorized into tertiles according to the control group cutoff points. Two logistic regression models and weighted quantile sum regressions (WQS) were run: model 1 adjusting for age, sex, creatinine, energy intake and physical activity and model 2 additionally adjusting for maternal education, rice and fish consumption. In the single metal(oid) exposure model, there was a trend of significant negative association for urinary cobalt (Co), where children in the third tertile had lower odds of present overweight and obesity than those in the first (Odds Ratio, OR = 0.43; 95% Confidence Interval, CI = 0.20–0.93). Urinary chromium (Cr) levels were borderline-significant negatively associated with overweight and obesity (ORa = 1.70; 95% CI = 0.97–2.98). Molybdemun, Cr and Co had a major contribution to the inverse association between metal(loid) mixture and overweight and obesity as well as lead, cadmium and total arsenic in the positive relationship. Our findings in this explorative study suggested an inverse association of high urinary Co levels with overweight and obesity. Moreover, metal(loid) mixture exposure may have influence on overweight and obesity with an important contribution of Co in the potential negative effect.

Association and mediation analyses among multiple metal exposure, mineralocorticoid levels, and serum ion balance in residents of northwest China

Toxic metals are vital risk factors affecting serum ion balance; however, the effect of their co-exposure on serum ions and the underlying mechanism remain unclear. We assessed the correlations of single metal and mixed metals with serum ion levels, and the mediating effects of mineralocorticoids by investigating toxic metal concentrations in the blood, as well as the levels of representative mineralocorticoids, such as deoxycorticosterone (DOC), and serum ions in 471 participants from the Dongdagou–Xinglong cohort. In the single-exposure model, sodium and chloride levels were positively correlated with arsenic, selenium, cadmium, and lead levels and negatively correlated with zinc levels, whereas potassium and iron levels and the anion gap were positively correlated with zinc levels and negatively correlated with selenium, cadmium and lead levels (all P < 0.05). Similar results were obtained in the mixed exposure models considering all metals, and the major contributions of cadmium, lead, arsenic, and selenium were highlighted. Significant dose–response relationships were detected between levels of serum DOC and toxic metals and serum ions. Mediation analysis showed that serum DOC partially mediated the relationship of metals (especially mixed metals) with serum iron and anion gap by 8.3% and 8.6%, respectively. These findings suggest that single and mixed metal exposure interferes with the homeostasis of serum mineralocorticoids, which is also related to altered serum ion levels. Furthermore, serum DOC may remarkably affect toxic metal-related serum ion disturbances, providing clues for further study of health risks associated with these toxic metals.

Association between exposure to multiple metals and stress urinary incontinence in women: a mixture approach.

There is limited evidence linking exposure to heavy metals, especially mixed metals, to stress urinary incontinence (SUI). This study aimed to explore the relationship between multiple metals exposure and SUI in women. The data were derived from the National Health and Nutrition Examination Survey (NHANES), 2007-2020. In the study, a total of 13 metals were analyzed in blood and urine. In addition, 5155 adult women were included, of whom 2123 (41.2%) suffered from SUI. The logistic regression model and restricted cubic spline (RCS) were conducted to assess the association of single metal exposure with SUI risk. The Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) were used to estimate the combined effect of multiple metals exposure on SUI. First, we observed that blood Pb, Hg and urinary Pb, Cd were positively related to SUI risk, whereas urinary W was inversely related by multivariate logistic regression (all p-FDR < 0.05). Additionally, a significant non-linear relationship between blood Hg and SUI risk was observed by RCS analysis. In the co-exposure models, WQS model showed that exposure to metal mixtures in blood [OR (95%CI) = 1.18 (1.06, 1.31)] and urine [OR (95%CI) = 1.18 (1.03, 1.34)] was positively associated with SUI risk, which was consistent with the results of BKMR model. A potential interaction was identified between Hg and Cd in urine. Hg and Cd were the main contributors to the combined effects. In summary, our study indicates that exposure to heavy metal mixtures may increase SUI risk in women.

Association between blood metals mixture and chronic kidney disease in adults: NHANES 2013-2016

BackgroundThe association between single metal exposure and chronic kidney disease (CKD) has been established. However, there is limited research on the effects of multi-metal mixtures and their potential age-specific associations with kidney injury. This study aimed to examine the relationship between metal mixtures and kidney function in adults, while also exploring the modifying effects of age. MethodsWe included a subset (n = 4250) of a nationally representative adult population in the National Health and Nutrition Examination Survey (NHANES) 2013–2016. Kidney function was assessed using the glomerular filtration rate (eGFR) and creatinine albumin ratio (ACR). The individual and combined effects of lead (Pb), cadmium (Cd), mercury, and manganese on kidney injury and the risk of CKD were evaluated. ResultsPb and Cd were found to be positively associated with decreased kidney function. For a one Ln-unit increase in lead and cadmium, the adjusted ORs of CKD were 1.60 (95% CI: 1.35, 1.90) and 1.41 (95% CI:1.12, 1.77), respectively. We also observed an interaction between lead and cadmium for ACR. We also observed the joint effect between Pb and Cd on eGFR, ACR and CKD. Stratified analysis found a higher risk of decreased kidney function among older individuals. The quantile-g calculation model further showed that metal mixture was associated with decreased kidney function and the risk of CKD (OR = 1.53, 95% CI: 1.22, 1.90). And lead and cadmium were the main contributors. And Pb and Cd were the major components that increased the risk of CKD. ConclusionCo-exposure to metal mixture were associated with reduced kidney function in adults, especially in older. Our findings support co-exposure to lead and cadmium as risk factors of CKD in adults.

Associations of multiple plasma metals with osteoporosis: findings from the Dongfeng-Tongji cohort.

With the aging population, osteoporosis has become a more prevalent public health issue. Existing researches have indicated significant relations of single metal exposure with osteoporosis (e.g., lead, copper, and zinc), whereas the evidence regarding the joint association of metal mixtures with osteoporosis remain limited and inconclusive. A total of 4924 participants from the Dongfeng-Tongji cohort were included in the present study. Plasma levels of 23 metals were determined by inductively coupled plasma mass spectrometry, and the presence of osteoporosis was defined as a bone mineral density T-score ≤ - 2.5. We applied stepwise regression, plasma metal score, and quantile g-computation model to evaluate the association between plasma metal mixtures and osteoporosis risk. Of the 4924 participants, the prevalence of osteoporosis was 10.9% (N = 265) in males and 27.5% (N = 684) in females. In the multiple-metals model, arsenic was positively associated with osteoporosis in males, while zinc was positively associated with osteoporosis in females. Comparing extreme quartiles, the multivariate-adjusted ORs of osteoporosis were 2.20 (95% CI, 1.29, 3.79; P-trend = 0.006) for arsenic in males and 2.16 (95% CI, 1.44, 3.23; P-trend < 0.001) for zinc in females. The plasma metal score was significantly and positively associated with a higher risk of osteoporosis, with ORs (95% CI) comparing extreme quartiles were 5.00 (95% CI, 3.36, 7.65; P-trend < 0.001) in males and 1.76 (95% CI, 1.35, 2.29; P-trend < 0.001) in females. Furthermore, the results of quantile g-computation revealed a consistent positive trend of metal mixtures with risk of osteoporosis and suggested the dominant role of arsenic in males and zinc in females, respectively. Our findings highlighted the importance of controlling metal mixtures exposure for the prevention of osteoporosis in the middle-aged and elder population. Further prospective studies in larger populations are warranted to confirm our findings.

Co-exposure to lead, mercury, and cadmium induces neurobehavioral impairments in mice by interfering with dopaminergic and serotonergic neurotransmission in the striatum.

Humans are exposed to lead (Pb), mercury (Hg), and cadmium (Cd) through various routes, including drinking water, and such exposure can lead to a range of toxicological effects. However, few studies have investigated the toxic effects of exposure to mixtures of metals, particularly in relation to neurotoxicity. In this study, 7-week-old male mice were exposed to Pb, Hg, and Cd individually or in combination through their drinking water for 28 days. The mice exposed to the metal mixture exhibited significantly reduced motor coordination and impaired learning and memory abilities compared to the control group and each of the single metal exposure groups, indicating a higher level of neurotoxicity of the metal mixture. The dopamine content in the striatum was significantly lower in the metal mixture exposure group than in the single metal exposure groups and the control group. Furthermore, compared to the control group, the metal mixture exposure group showed a significantly lower expression level of tyrosine hydroxylase (TH) and significantly higher expression levels of dopamine transporter (DAT), tryptophan hydroxylase 1 (TPH1), and serotonin reuptake transporter (SERT). Notably, there were no significant differences in SERT expression between the single metal exposure groups and the control group, but SERT expression was significantly higher in the metal mixture exposure group than in the single metal and control groups. These findings suggest that the key proteins involved in the synthesis and reuptake of dopamine (TH and DAT, respectively), as well as in the synthesis and reuptake of serotonin (TPH1 and SERT, respectively), play crucial roles in the neurotoxic effects associated with exposure to metal mixtures. In conclusion, this study demonstrates that simultaneous exposure to different metals can impact key enzymes involved in dopaminergic and serotonergic neurotransmission processes, leading to disruptions in dopamine and serotonin homeostasis and consequently a range of detrimental neurobehavioral effects.

Using Multiple Metal Mixture Models to Predict Toxicity of Riverine Sediment Porewater to the Benthic Life Stage of Juvenile White Sturgeon (Acipenser transmontanus).

Five metal mixture dose-response models were used to predict the toxicity of porewater to young sturgeon at areas of interest in the Upper Columbia River (WA, USA/BC, Canada) and to evaluate these models as tools for risk assessments. Dose components of metal mixture models included exposure to free metal ion activities or metal accumulation by biotic ligands or humic acid, and links of dose to response used logistic equations, independent joint action equations, or additive toxicity functions. Laboratory bioassay studies of single metal exposures to juvenile sturgeon, porewater collected in situ in the fast-flowing Upper Columbia River, and metal mixture models were used to evaluate toxicity. The five metal mixture models were very similar in their predictions of adverse response of juvenile sturgeon and in identifying copper (Cu) as the metal responsible for the most toxic conditions. Although the modes of toxic action and the 20% effective concentration values were different among the dose models, predictions of adverse response were consistent among models because all doses were tied to the same biological responses. All models indicated that 56% ± 5% of 122 porewater samples were predicted to have <20% adverse response, 25% ± 5% of samples were predicted to have 20% to 80% adverse response, and 20% ± 4% were predicted to have >80% adverse response in juvenile sturgeon. The approach of combining bioassay toxicity data, compositions of field porewater, and metal mixture models to predict lack of growth and survival of aquatic organisms due to metal toxicity is an important tool that can be integrated with other information (e.g., survey studies of organism populations, life cycle and behavior characteristics, sediment geochemistry, and food sources) to assess risks to aquatic organisms in metal-enriched ecosystems. Environ Toxicol Chem 2024;43:62-73. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

Association of Exposure to Heavy Metal Mixtures with Systemic Immune-Inflammation Index Among US Adults in NHANES 2011-2016.

In reality, people are often co-exposed to multiple heavy metals; however, current research has focused on the association between individual heavy metals and inflammation. Therefore, it is more relevant to explore the combined effects of multiple heavy metal exposure on inflammation. The study included data from the National Health and Nutrition Examination Survey (NHANES), 2011-2016. The systemic immune-inflammation index (SII) was used to reflect systemic immune-inflammation status. In this study, single variable models were used to assess the linear and non-linear relationships between single heavy metal exposures and SII. To analyze the combined effect of mixed heavy metals exposure on SII, we constructed three statistical models, including weighted quantile sum (WQS) regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR). The single-exposure analysis found positive associations between multiple heavy metals and SII, while mercury in blood was negatively associated with SII, and U-shaped correlations were observed between blood lead, urine barium and strontium, and SII. In the WQS model, SII increased significantly with increasing concentrations of mixed heavy metals, while consistent results in the qgcomp model, but not statistically significant. In the BKMR model, exposure to heavy metal mixtures was positively associated with SII, with mercury, cadmium, and cobalt in urine contributing the most to the mixed exposure. In addition, synergistic and antagonistic effects between heavy metals on increasing SII were found in our study. In summary, our results reveal that combined exposure to multiple heavy metals is positively associated with SII in the US adults.

Trimester-specific effects of maternal exposure to single and mixed metals on cord serum inflammatory cytokines levels: A prospective birth cohort study

BackgroundCord blood inflammatory cytokines are vital in early-life programming. An increasing number of studies concern the effect of maternal exposure to different metal elements during pregnancy on inflammatory cytokines, but limited studies have explored the association between maternal exposure to mixed metals and cord blood inflammatory cytokine levels. MethodsWe measured serum concentrations of vanadium (V), copper (Cu), arsenic (As), cadmium (Cd), and barium (Ba) in the first, second, and third trimesters and eight cord serum inflammatory cytokines (IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and TNF-α) in 1436 mother-child dyads from the Ma'anshan Birth Cohort. Generalized linear models and Bayesian kernel machine regression (BKMR) were performed to assess the association of single and mixed metal exposure during each trimester with cord serum inflammatory cytokine levels, respectively. ResultsRegarding metal exposure in the first trimester, V was positively associated with TNF-α (β = 0.33, 95 % CI: 0.13, 0.53); Cu was positively associated with IL-8 (β = 0.23, 95 % CI: 0.07, 0.39); Ba was positively associated with IFN-γ and IL-6; As was negatively associated with IFN-γ and IL-17A; and Cd was negatively associated with IFN-γ, IL-1β, IL-12p70, IL-17A, and TNF-α. BKMR revealed that exposure to metal mixtures in the first trimester was positively associated with IL-8 and TNF-α but negatively associated with IL-17A. Moreover, V contributed the most to these associations. Interaction effects were observed between Cd and As and between Cd and Cu with IL-8, and between Cd and V with IL-17A. Among males, As decreased inflammatory cytokines; among females, Cu increased inflammatory cytokine levels, whereas Cd decreased inflammatory cytokine concentrations. ConclusionsMaternal exposure to metal mixtures in the first trimester interfered with cord serum inflammatory cytokine levels. The associations of maternal exposure to As, Cu and Cd with inflammatory cytokines showed sex differences. Further studies are warranted to support the findings and explore the mechanism of the susceptibility window and sex-specific disparity.

High Sensitivity of the Antarctic Rotifer Adineta editae to Metals and Ecological Relevance in Contaminated Site Risk Assessments.

Anthropogenic activities in Antarctica have led to contamination of terrestrial sites, and soils in ice-free areas have elevated concentrations of metals, particularly around current and historic research stations. Effective management of Antarctic contaminated sites depends on the assessment of risks to a representative range of native terrestrial species. Bdelloid rotifers are an abundant and biodiverse component of Antarctic limnoterrestrial communities and play a key role in nutrient cycling in Antarctic ecosystems. The present study investigates the toxicity of five metals (cadmium, copper, nickel, lead, and zinc) to the endemic bdelloid rotifer Adineta editae, both singly and in metal mixtures. Based on the concentrations tested, zinc was the most toxic metal to survival with a 7-day median lethal concentration (LC50) of 344 µg Zn/L, followed by cadmium with a 7-day LC50 of 1542 µg Cd/L. Rotifers showed high sensitivity using cryptobiosis (chemobiosis) as a sublethal behavioral endpoint. Chemobiosis was triggered in A. editae at low metal concentrations (e.g., 6 µg/L Pb) and is likely a protective mechanism and survival strategy to minimize exposure to stressful conditions. Lead and copper were most toxic to rotifer behavior, with 4-day median effect concentrations (EC50s) of 18 and 27 µg/L, respectively, followed by zinc and cadmium (4-day EC50 values of 52 and 245 µg/L, respectively). The response of rotifers to the metal mixtures was antagonistic, with less toxicity observed than was predicted by the model developed from the single-metal exposure data. The present study provides evidence that this bdelloid rotifer represents a relatively sensitive microinvertebrate species to metals and is recommended for use in contaminant risk assessments in Antarctica. Environ Toxicol Chem 2023;42:1409-1419. © 2023 SETAC.

The association between multi-heavy metals exposure and lung function in a typical rural population of Northwest China

Heavy metal exposure is acknowledged to be associated with decrease oflung function, but the relationship between metals co-exposure and lung function in rural areas of Northwest China remains unclear, particularly in an area famous for heavy metal pollution and solid fuel use. Therefore, the purpose of this study is to explore the effects of heavy metal exposure on lung function and the potential impacts of living habit in a rural cohort of Northwest China. The study area included five villages of two regions in Northwestern China-Gansu province. All participants were recruited from the Dongdagou-Xinglong (DDG-XL) rural cohort in the study area. Urine levels of 10 common and representative heavy metals were detected by ICP-MS, including Cobalt (Co), Nickel (Ni), Molybdenum (Mo), Cadmium (Cd), Stibium (Sb), Copper (Cu), Zinc (Zn), Mercury (Hg), Lead (Pb), and Manganese (Mn). The lung function was detected by measuring percentages of predicted forced vital capacity (FVC%) and predictedforced expiratory volume in one second (FEV1%) as well as the ratio of FEV1/FVC. We also analyzed the association between heavy metals and pulmonary ventilation dysfunction (PVD). Restricted cubic spline, logistic regression, linear regression, and bayesian kernel machine regression (BKMR) model were used to analyze the relationship between heavy metal exposure and lung function. Finally, a total of 382 participants were included in this study with an average age of 56.69 ± 7.32years, and 82.46% of them used solid fuels for heating and cooking. Single metal exposure analysis showed that the higher concentration of Hg, Mn, Sb, and lower Mo may be risk factors for PVD. We also found that FEV1% and FVC% were negatively correlated with Sb, Hg, and Mn, but positively correlated with Mo. The effect of mixed heavy metals exposure could be observed through BKMR model, through which we found the lung function decreased with the increase of heavy metal concentration. Furthermore, the males, BMI ≥ 24kg/m2 and who used solid fuels showed a higher risk of PVD when exposed to Co, Zn, and Hg. Our results suggested that heavy metal exposure was associated with decrease of lung function regardless of single exposure or mixed exposure, particularly for Sb, Hg, Mn and those who use solid fuels.

Association of metal exposure with arterial stiffness in Chinese adults

BackgroundArterial stiffness is an important indicator of cardiovascular aging. However, studies assessing the association between metal exposure and arterial stiffness are limited. ObjectiveThe aim of this study was to investigate the independent and joint associations of metal exposure with arterial stiffness. MethodsThis cross-sectional study recruited 2982 Chinese adults from August 2018 to March 2019 in Wuhan, China. The concentrations of 20 urinary metals were determined using inductively coupled plasma mass spectrometer. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). We used generalized linear model (GLM) to estimate the association of single metal exposure with baPWV. We used weighted quantile sum (WQS) regression to estimate the association of metal mixture with baPWV. ResultsIn GLM regression analysis, each doubling of urinary copper (Cu) and chromium (Cr) concentrations were associated with 6.48 (95 % CI: 2.51–10.45) cm/s and 3.78 (95 % CI: 0.42–7.14) cm/s increase in baPWV, respectively. In WQS regression analysis, each unit increase in WQS index of the metal mixture was associated with a 9.10 (95 % CI: 2.39–15.82) cm/s increase in baPWV. Cu, Zn, and Cr were the dominant urinary metals associated with baPWV. ConclusionMetal exposure, both individually and in mixture, was associated with an increased risk of arterial stiffness. Our findings may provide a target for preventative strategies against cardiovascular aging.