Metal Co-exposure Research Articles

Associations of Blood and Urinary Heavy Metals with Stress Urinary Incontinence Risk Among Adults in NHANES, 2003-2018.

People come into contact with heavy metals in various ways in their daily lives. Accumulating evidence shows that toxic metal exposure is hazardous to human health. However, limited information is available regarding the impact of metal mixtures on stress urinary incontinence (SUI). Therefore, we used data from 10,622 adults from the 2003-2018 National Health and Nutrition Examination Survey (NHANES) to investigate the independent and comprehensive association between heavy metal co-exposure and SUI. Among them, 2455 (23.1%) had been diagnosed with SUI, while the rest had no SUI. We evaluated the independent and combined associations of 3 blood metals and 10 urinary metals with SUI risk, along with subgroup analyses according to age and gender. In the single-exposure model, blood cadmium (Cd), lead (Pb), mercury (Hg), urinary Cd, Pb, and cesium (Cs) were found to be positively connected with SUI risk. Moreover, weighted quantile sum (WQS) regression, quantile-based g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) consistently demonstrated blood and urinary metal-mixed exposure were positively associated with the risk of SUI, and emphasized that blood Pb and Cd and urinary Cd and Cs were the main positive drivers, respectively. This association was more pronounced in the young and middle-aged group (20-59years old) and the female group. Nevertheless, further research is necessary to validate these significant findings.

Associations of mixed metal exposure with chronic kidney disease from NHANES 2011–2018

Metals have been proved to be one of risk factors for chronic kidney disease (CKD) and diabetes, but the effect of mixed metal co-exposure and potential interaction between metals are still unclear. We assessed the urine and whole blood levels of cadmium (Cd), manganese (Mn), lead (Pb), mercury (Hg), and renal function in 3080 adults from National Health and Nutrition Survey (NHANES) (2011–2018) to explore the effect of mixed metal exposure on CKD especially in people with type 2 diabetes mellitus (T2DM). Weighted quantile sum regression model and Bayesian Kernel Machine Regression model were used to evaluate the overall exposure impact of metal mixture and potential interaction between metals. The results showed that the exposure to mixed metals was significantly associated with an increased risk of CKD in blood glucose stratification, with the risk of CKD being 1.58 (1.26,1.99) times in urine and 1.67 (1.19,2.34) times in whole blood higher in individuals exposed to high concentrations of the metal mixture compared to those exposed to low concentrations. The effect of urine metal mixture was elevated magnitude in stratified analysis. There were interactions between urine Pb and Cd, Pb and Mn, Pb and Hg, Cd and Mn, Cd and Hg, and blood Pb and Hg, Mn and Cd, Mn and Pb, Mn and Hg on the risk of CKD in patients with T2DM and no significant interaction between metals was observed in non-diabetics. In summary, mixed metal exposure increased the risk of CKD in patients with T2DM, and there were complex interactions between metals. More in-depth studies are needed to explore the mechanism and demonstrate the causal relationship.

Association of individual and combined exposures of 10 metals with periodontitis: Results from a large population-based study.

To systematically investigate the association between individual and combined metal exposure and periodontitis. Data encompassing complete periodontal examinations and metal detection in blood and urine samples were procured from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Three statistical methods, namely weighted logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression, were used to evaluate the independent and combined associations between metals and periodontitis. Elevated concentrations of blood cadmium (odds ratio [OR]: 1.73, 95% confidence interval [CI]: 1.15-2.61) and blood lead (OR: 1.17, 95 %CI: 1.02-1.34) exhibited a positive association with periodontitis, even after adjusting for potential confounding factors. The BKMR and WQS regression suggested that the co-exposure of metals was also positively associated with periodontitis. Moreover, estradiol and albumin were identified as potential mediators in the relationship between the WQS index of the 10 metals in blood and periodontitis explaining 25.36% and 2.02% of the relationship, respectively. Furthermore, generally consistent patterns of associations between metals and periodontitis and mediating roles of estrogen and albumin were observed after a series of sensitivity analyses. This study provides evidence of positive associations between elevated levels of cadmium, lead or metal mixture and periodontitis, which may be partially mediated by sex hormones and oxidative stress indicators.

Effects of Heavy Metal Co-Exposure on the formation of DNA Adducts from Aristolochic Acid I: Implications for Balkan Endemic Nephropathy Development.

Accumulated evidence has shown that Balkan endemic nephropathy (BEN) is a multifactorial environmental disease, with exposure to aristolochic acids (AA), and the associated DNA adduct formation, as a key causative factor of BEN development. Here, we show that coexposure to arsenic, cadmium, and iron increases the DNA adduct formation of AA in cultured kidney cells, while exhibiting both an exposure concentration and duration dependence. In contrast, coexposure to calcium and copper showed a decreasing DNA adduct formation. Because DNA damage is responsible for both the nephrotoxicity and carcinogenicity of AA, these results shed greater light on the endemic nature of BEN.

Co-exposure of heavy metals in rice and corn reveals a probabilistic health risk in Guizhou Province, China

The adverse effects of heavy metals have arousing concern in the high geological background area, especially in southwestern Guizhou, China. However, the pollution status of heavy metals are still unclear when exposed to rice and corn in Guizhou province. Therefore, the concentration, pollution level, spatial distribution, and probabilistic health risks of Ni, Cr, Pb, Cu, and Zn are estimated in rice and corn. A total of 241 samples (117 for rice and 124 for corn) were collected from Guizhou province and measured by a method of inductively coupled plasma-mass spectrometry (ICP-MS). The results showed that rice and corn were contaminated with Ni and Cr. High concentrations of Ni were presented in the southeast of rice. It indicated that 22.0 % of rice samples were contaminated with Ni. HI values for children and adults exceeded 1.0 in rice and corn, suggesting that humans might be subject to probabilistic non-carcinogenic risks. FTCR demonstrated that rice and corn might cause probabilistic carcinogenic risks to children and adults, which were both greatly higher than 1.0 × 10−4. Moreover, the contributions of Ni to the HI and FTCR were the highest for adults and children. Therefore, more attention should be paid to the exposure of heavy metals in rice and corn, especially in Ni. The results would provide a novel prospective for pollution control and be helpful for environmental regulation.

Co-exposure of microplastics and heavy metals in the marine environment and remediation techniques: a comprehensive review.

Microplastics (MPs) and heavy metals are significant pollutants in the marine environment, necessitating effective remediation strategies to prevent their release into the sea through sewage and industrial effluent. This comprehensive review explores the current understanding of the co-exposure of MPs and heavy metal-enriched MPs, highlighting the need for effective remediation methods. Various mechanisms, including surface ion complexation, hydrogen bonding, and electrostatic forces, contribute to the adsorption of heavy metals onto MPs, with factors like surface area and environmental exposure duration playing crucial roles. Additionally, biofilm formation on MPs alters their chemical properties, influencing metal adsorption behaviors. Different thermodynamic models are used to explain the adsorption mechanisms of heavy metals on MPs. The adsorption process is influenced by various factors, including the morphological characteristics of MPs, their adsorption capacity, and environmental conditions. Additionally, the desorption of heavy metals from MPs has implications for their bioavailability and poses risks to marine organisms, emphasizing the importance of source reduction and remedial measures. Hybrid approaches that combine both conventional and modern technologies show promise for the efficient removal of MPs and heavy metals from marine environments. This review identifies critical gaps in existing research that should be addressed in future studies including standardized sampling methods to ensure accurate data, further investigation into the specific interactions between MPs and metals, and the development of hybrid technologies at an industrial scale. Overall, this review sheds light on the adsorption and desorption mechanisms of heavy metal-enriched MPs, underscoring the necessity of implementing effective remediation strategies.

Co-exposure of chromium or cadmium and a low concentration of amoxicillin are responsible to emerge amoxicillin resistant Staphylococcus aureus

Heavy metals and antimicrobials co-exist in many environmental settings. The co-exposure of heavy metals and antimicrobials can drive emergence of antimicrobial resistant (AMR) Enterobacteriaceae. We hypothesized that co-exposure to heavy metals and a low concentration of antibiotic might alter antimicrobial susceptibility patterns, which facilitate emergence of AMR Staphylococcus aureus. The growth kinetics of antimicrobial susceptibleS. aureuswas carried out in the presence of chromium or cadmium salt and a low concentration of antibiotics. Subsequently, the antimicrobial susceptibility pattern was determined by the Kirby-Bauer disc diffusion method.Moreover, the mRNA copy number was determined by reverse transcription polymerase chain reaction. The antimicrobial susceptibility profile revealed that the zone of inhibition (ZOI) for ampicillin, amoxicillin, ciprofloxacin and doxycycline was significantly decreased in chromium pre-exposed S. aureuscompared to unexposed bacteria, whereas cadmium pre-exposed bacteria only showed significant decreased in ZOI for amoxicillin. Moreover, the MIC of amoxicillin for S. aureus was increased by 8-fold in chromium and 32-fold in cadmium when bacteria were co-exposed with low concentrations of amoxicillin. The mRNA expression of femX, mepA and norA also significantly increased in S. aureus after exposure tochromium and a low concentration of amoxicillin. Cultivation of S. aureus at the minimum levels of chromium or cadmium and a low concentration of amoxicillin increased the inhibitory concentration of amoxicillin through inducing bacterial efflux pumps and antibiotic resistant genes. However, it is warranted to assess the whole transcriptome to find out all responsible factors behind this de novo amoxicillin resistant S. aureus.

Co-exposure to Fe, Zn, and Cu induced neuronal ferroptosis with associated lipid metabolism disorder via the ERK/cPLA2/AA pathway

Excessive amounts of iron (Fe), zinc (Zn), and copper (Cu) can be toxic to neuronal cells, even though these are essential trace elements for animals and humans. However, the precise mechanisms underlying the neurotoxicity of exposure to mixtures of Fe, Zn, and Cu are still mostly unclear. The research aimed to investigate the influence of co-exposure to iron, zinc and copper and the related mechanisms in HT22 murine hippocampal neuronal cells. Intracellular metal content, markers of oxidative damage, and biomarkers of ferroptosis were respectively detected. Afterward, metabolomic analyses were performed to obtain a comprehensive understanding of the metal mixtures on metabolism, and the functions of key enzymes on metabolic pathways were validated. The results showed that metal co-exposure resulted in cellular iron overload and increased lipid peroxidation, accompanied by significant pathological damage and mitochondrial abnormalities in HT22 cells. Meanwhile, it was found that GSH depletion, decreased GPX4, and increased expression of the lipid metabolism gene ACSL4 play important roles in ferroptosis induced by metal mixture. Further, metabolomic analysis revealed metal co-exposure induced significant alterations in metabolite levels, especially in the glycerophospholipid metabolism pathway and the arachidonic acid metabolism pathway. The levels of cPLA2 and its metabolite, arachidonic acid, were significantly increased after metal co-exposure. Then, inhibition of cPLA2 decreased the level of arachidonic acid and attenuated ferroptosis in neuronal cells. Collectively, our findings unveiled ferroptosis induced by metal co-exposure associated with crucial molecular changes in neuronal cells, providing a novel perspective on the comprehensive toxicity risk assessment of metal mixtures.

Essential metal mixtures exposure and NAFLD: A cohort-based case-control study in northern Chinese male adults

Epidemiologic evidence on metal mixtures and non-alcoholic fatty liver disease (NAFLD) is limited. We aimed to assess the relationship between multiple metal co-exposure and NAFLD among male adults in Northern China. We conducted a cohort-based case-control study with 648 NAFLD and 648 non-NAFLD males. Seven metal concentrations (calcium, copper, iron, magnesium, manganese, selenium, and zinc) were determined in the blood. We used logistic regression and restricted cubic splines (RCS) to estimate the associations between the single metal and NAFLD. The impact of metal mixtures was quantified by the environmental risk score (ERS) in the adaptive elastic-net regression, and the association with NAFLD was estimated by logistic regression. Age-adjusted RCS showed linear relationships between blood calcium, selenium, and NAFLD. Blood copper, iron, magnesium, and manganese were non-linearly associated with NAFLD. Single metal analysis observed significant relationships between calcium, copper, manganese, and NAFLD, with the adjusted odds ratio (95% confidence interval) for quartile 1 vs. quartile 4 of 1.99 (1.30, 3.05), 2.36 (1.52, 3.64), and 1.77 (1.22, 2.55), respectively. However, metal mixtures analysis revealed one squared term (copper [β = −0.146]) and five metal-metal interactions (calcium × copper [β = 0.200], copper × magnesium [β = 0.188], copper × selenium [β = 0.188], iron × magnesium [β = 0.143], magnesium × selenium [β = −0.297]) except the three main effects. Higher ERS indicated a higher risk for NAFLD when exposed to metal mixtures, with an adjusted odds ratio = 6.50 (95% confidence interval: 4.36–9.69) for quartile 4 vs. quartile 1. Mediation analysis suggested that 11.66% of the effect of ERS on NAFLD was suppressed by fasting blood glucose. Our results show that exposure to metal mixtures is associated with a higher risk for NAFLD than the single metal. Interactions between metals suggest the importance of balancing the various metals for health benefits. Prospective cohorts and mechanism studies need to confirm the findings.

Metal mixture and osteoporosis risk: Insights from plasma metabolite profiling

The pathophysiology of osteoporosis (OP) is influenced by exposure to nonessential harmful metals and insufficient or excessive intake of necessary metals. Investigating multiple plasma metals, metabolites, and OP risk among older adults may reveal novel clues of underlying mechanisms for metal toxicity on bone mass. A total of 294 adults ≥ 55 years from Wuhan communities were included. Plasma concentrations of 23 metals and metabolites were measured via inductively coupled plasma-mass spectrometry and global metabolite detection. To investigate the relationships between plasma metals, OP risk, and OP-related metabolites, three different statistical techniques were used: generalized linear regression model, two-way orthogonal partial least-squares analysis (O2PLS), and weighted quantile sum (WQS). The mean ages were 66.82 and 66.21 years in OP (n = 115) and non-OP (n = 179) groups, respectively. Of all 2999 metabolites detected, 111 differential between-group members were observed. The OP risk decreased by 58.5% (OR=0.415, 95% CI: 0.237, 0.727) per quartile increment in the WQS index indicative of metal mixture exposure. Consistency remained for bone mineral density (BMD) measurements. The O2PLS model identified the top five OP-related metabolites, namely, DG(18:2_22:6), 3-phenoxybenzoic acid, TG(16:1_16:1_22:6), TG(16:0_16:0_20:4), and TG(14:1_18:2_18:3), contributing most to the joint covariation between the metal mixture and metabolites. Significant correlations between each of them and the metal mixture were found using WQS regression. Furthermore, the five metabolites mediated the associations of the metal mixtures, BMD, and OP risk. Our findings shed additional light on the mediation functions of plasma metabolites in the connection between multiple metal co-exposure and OP pathogenesis and offer new insights into the probable mechanisms underpinning the bone effects of the metal mixture.

Associations of exposure to blood and urinary heavy metal mixtures with psoriasis risk among U.S. adults: A cross-sectional study

Accumulating evidence showed that environmental exposure to toxic metals was harmful to human health. However, information about the effects of exposure to metal mixtures on psoriasis was scarce. To investigate the independent and comprehensive associations between heavy metal co-exposure and psoriasis in adults, data of 6534 adults aged 20–80 years from the National Health and Nutrition Examination Survey (NHANES) were used. Among them, 187 (2.86 %) were diagnosed with psoriasis and the rest were participants without psoriasis. We examined the independent and combined associations of 3 blood metals and 11 urinary metals with psoriasis risk. In the single-metal analyses, urinary barium (Ba), cesium (Cs), antimony (Sb), uranium (Ur), and cadmium (Cd) were positively correlated with psoriasis risk, while urinary molybdenum (Mo) was identified as a protective factor for psoriasis. Moreover, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models consistently revealed the positive effect of urinary metal co-exposure on psoriasis risk. The associations were more evident in the young and middle-aged group than the elderly group. In the urinary mixtures, Ba was the highest weighted metal in the whole population and the young and middle-aged people, whereas Sb was the top weighted metal in the elderly group. Additionally, BKMR analysis revealed the potential interaction between certain components of urinary metal mixtures in psoriasis. The results of quantile-based g computation (qgcomp) model further proved the toxic effect of urinary metal mixtures on psoriasis, and the positive linear relationship between urinary Ba and psoriasis risk was identified by restricted cubic splines (RCS) regression. We concluded that co-exposure to multiple heavy metals was associated with psoriasis risk. Given the limitations of the NHANES study, further prospective designed studies are warranted.

Sex-specific associations of single metal and metal mixture with handgrip strength: a cross-sectional study among Chinese adults.

Metallic elements are ubiquitous in the natural environment and always collaborate to affect human health. The relationship of handgrip strength, a marker of functional ability or disability, with metal co-exposure remains vague. In this study, we aimed to investigate the effect of metal co-exposure on sex-specific handgrip strength. A total of 3594 participants (2296 men and 1298 women) aged 21 to 79years recruited from Tongji Hospital were included in the present study. Urinary concentrations of 21 metals were measured by inductively coupled plasma mass spectrometer (ICP-MS). We used linear regression, restricted cubic spline (RCS) model, and weighted quantile sum (WQS) regression to evaluate the association of single metal as well as metal mixture with handgrip strength. After adjusting for important confounding factors, the results of linear regression showed that vanadium (V), zinc (Zn), arsenic (As), rubidium (Rb), cadmium (Cd), thallium (Tl), and uranium (U) were adversely associated with handgrip strength in men. The results of RCS showed a non-linear association between selenium (Se), silver (Ag), and nickel (Ni) with handgrip strength in women. The results of WQS regression revealed that metal co-exposure was inversely related to handgrip strength for men (β = -0.65, 95% CI: -0.98, -0.32). Cd was the critical metal in men (weighted 0.33). In conclusion, co-exposure to a higher level of metals is associated with lower handgrip strength, especially among men, and Cd may contribute most to the conjunct risk.

Metabolomics and transcriptomics reveal the toxic mechanism of Cd and nano TiO2 coexposure on rice (Oryza sativa L.)

Engineered nanoparticles (ENPs) can resist heavy metal toxicity in plants, but their coexposure still exhibits toxicity to plants compared to plants without exposure to ENPs and heavy metals. There have been few studies on the toxic mechanism of nano TiO2-heavy metal coexposure and the effect mechanism of nano TiO2 in plants. Thus, transcriptomics and metabolomics were used to study the toxic mechanism of rutile nano TiO2 or TiO2-Cd (rutile nano TiO2 and CdCl2 mixture) on rice (Oryza sativa L.). After 40 days of exposure, the plant height and root dry weight of rice were significantly decreased in the nano TiO2-Cd group compared to the blank group (nano TiO2 and CdCl2 free). After Cd treatment, 423 differentially expressed genes (DEGs) and 16 differential metabolites were identified. Nano TiO2 exposure induced significant regulation of 299 DEGs and 6 metabolites. After nano TiO2-Cd coexposure, 1660 DEGs and 181 differential metabolites were identified. Notably, the EDGs (e.g., chalcone isomerase and hydroxycinnamoyl transferase) and differential metabolites (e.g., chrysin and galangin) demonstrated the disruption of flavonoid biosynthesis in Cd-treated rice. After rice was exposed to nano TiO2, the DEGs were related to ribosome, whereas the differential metabolites were associated with pyruvate metabolism and valine, leucine, and isoleucine biosynthesis. Furthermore, 14 DEGs (e.g., asparaginyl-tRNA synthetase and methionyl-tRNA formyltransferase) involved in aminoacyl-tRNA biosynthetic pathways were significantly upregulated in rice treated with nano TiO2-Cd, in line with the changes in related metabolites (e.g., L-asparagine and 10-formyltetrahydrofolate). Our results show that it is necessary to pay close attention to the toxicity of nano TiO2-Cd coexposure in paddy ecosystems and use ENPs with caution to combat the phytotoxicity of heavy metals.

Coexposure of heavy metals and piracetam destroys adaptive behaviour

In experiments on rats, it was found that lead, cadmium and cobalt salts inhibit the acquisition of an avoidance responses. Cases of increased neurotoxic effect of heavy metals on learning and memory in rats with their combined administration with piracetam have been noted. Ascorbic acid counteracts this neurotoxic impact of the heavy metals and piracetam cooexposure on the adaptive behaviour.

Differential behaviour of four genotypes of Andrographis paniculata (Burm.f.) Nees toward combined toxicity of As, Cd, and Pb: An ionomics and metabolic interpretation

The present study aims to evaluate differential ionomics and metabolic responses of genotypes (G1, G5, G6, and G11) of A. paniculata in mixed metal treatments. The experiment was performed in unary, binary, and ternary treatments of arsenic (As), cadmium (Cd), and lead (Pb) taking four genotypes of A. paniculata. The interactive effect of co-exposure of metals on their accumulation, growth parameters, ionomics, and metabolism in different genotypes was examined and compared. Results revealed that metal accumulation, ionomics, and metabolic in binary and ternary treatments were significantly different than unary treatments. The co-exposure of the mixture has an additive effect on As uptake, an antagonistic effect on Pb accumulation, and both antagonistic and synergistic effects on Cd. A differential ionomics network in plant tissues of genotypes well explained their differential responses toward the co-exposure of As, Cd, and Pb. Elements phosphorous (P), calcium (Ca), magnesium (Mg), and Manganese (Mn) played important roles in the differential uptake of metals. The oxidative stress and phytotoxicity were observed in G11 under co-exposure to metal. Among the four genotypes, G11 was separated according to its ionomics and metabolic profiling. Genotypes G1 were low accumulating G6 and G11 were tolerant and sensitive genotypes under co-metal stress.

Association of urinary heavy metals co-exposure and adult depression: Modification of physical activity

ObjectiveThis study aimed to evaluate the association between urinary heavy metal mixture exposure and depression, and the modifying role of physical activity in the effects of heavy metal mixture on depression risk was also considered. MethodsData of this study were derived from the National Health and Nutrition Examination Survey 2011–2016. Depression was measured by the Patient Health Questionnaire. We first selected 6 (cadmium, cobalt, tin, antimony, thallium, and mercury) from 14 heavy metals through elastic net regression for further analysis. Then binomial logistic regression, generalized additive model, environment risk score (ERS), and weighted quantile sum (WQS) regression were adopted to assess the effects of six metals individual and cumulative exposure on depression risk. Finally, we also examined whether physical activity could mitigate the effects of heavy metal co-exposure on depression risk. ResultsTotally, 4212 participants were included and 7.40% of subjects were with depression. We found urinary tin and antimony were separately associated with increased odds of depression (Sb: OR = 1.285, 95% CI: 1.064–1.553; Sn: OR = 1.281, 95% CI: 1.097–1.495), and a linear dose-response relationship between tin and depression was also noticed (P < 0.05). Meanwhile, urinary heavy metals co-exposure was positively related to depression risk (ERSQ4: OR = 2.691, 95% CI: 1.399–5.174; WQSpositive: OR = 1.465, 95% CI: 1.063–2.021), in which tin, antimony, and cadmium were identified with greater contributions to the overall mixture effect. In both ERS and WQS models, the significant positive association between the metal mixture and depression risk remained only in those who were inactive in physical activity. ConclusionOur study concluded the detrimental effect of heavy metals in combined exposure on the risk of depression, which might be attenuated by physical activity.

What adverse health effects will environmental heavy metal co-exposure bring us: based on a biological monitoring study of sanitation workers.

To investigate the relationship between health effect profile and co-exposure to heavy metal, 254 sanitation workers from Guangzhou, China, were recruited. Ten urinary metals were determined by inductively coupled plasma mass spectrometry. Parameters of physical examination, including blood lipid metabolism, renal function, blood pressure, and lung function, were tested for each participant. The hazard quotients (HQs) of eight heavy metals were evaluated. Cobalt, copper (Cu), molybdenum (Mo), nickel (Ni), and tin (Sn) demonstrated the top five associations with human health with the ∑19β as 2.220, 1.351, 1.234, 0.957, and 0.930, respectively. Most physical examination parameters of workers were under the normal ranges, except the levels of forced mid expiratory flow rate (MMEF75/25), the maximum expiratory flow rate at 25% vital capacity (MEF25) and apolipoprotein B in the first quartile, and the level of uric acid in the third quartile of sanitation works. Moreover, Cu was significantly associated with diastolic pressure, pulse, and high density lipid (p < 0.05). Each unit increase in Mo level was related to a 120% increase odd ratio (OR) of abnormal of systolic pressure, but was significantly and negatively correlated with high density lipoprotein and apolipoprotein A, suggesting that Mo exposure may be a risk factor of cardiovascular disease. Each unit increase in Ni and Sn levels was associated with an increased OR of abnormal rate of MMEF75/25 and MEF25 (p < 0.001), suggesting the increasing risks of respiratory diseases. Sanitation workers exposed to Ni and Pb alone had no carcinogenic risks (HQ < 1). However, 23.8%, 34.6%, and 87.3% of sanitation workers confronted non-carcinogenic risks when exposed to Cu, Mo alone (HQ > 1), or co-exposed to the four heavy metals (HI > 1). Our study preliminarily revealed the potential sensitive health indicators of heavy metal co-exposure, which will provide beneficial health protection suggestions for the occupational populations.

Associations between co-exposure of metals and the renal tubular damage of the residents in the metal contaminated smelter area

Background and aim: The effects of metals to renal tubular damage have been mostly reported for individual metals. We investigated non-linear effects of multiple metals for renal tubular damage and interactions among metals of the real population living near the metal contaminated smelter area. Methods: A total of 120 individuals were included for urine sampling and survey in the Forensic Research via Omics Markers(FROM) study. Nine metals(V, Cr, Mn, Ni, Mo, Cd, Sb, Pb, and Hg) in urine were analyzed by inductively coupled plasma-mass spectroscopy and mercury analyzer. Beta-2-microglobulin(β2-MG) and N-acetyl-β-D-glucosaminidase(NAG) were applied as renal tubular damage markers. We compared the difference between the single-metal models and the multiple-metal models. And Bayesian kernel machine regression(BKMR) was conducted to examine the joint effects of multiple metals on renal tubular damage, interactions among metals and non-linear dose-response effects. Results: V for β2-MG, and Hg and Cd for NAG were consistently significant in both simple and multiple linear regression, though Ni for β2-MG was significant only in the multiple linear regression model. Mn for NAG was significant only in the single linear regression model. The BKMR analysis showed that the co-exposure of metals was significantly increased only NAG and Hg contributed the most to the NAG(PIP, posterior inclusion probability=0.608). β2-MG was increased by co-exposure of metals but not statistically significant and V contributed the most to the β2-MG(PIP=0.704). Conclusions: This study suggests that co-exposure of metals was significantly associated with NAG. The interaction among metals for renal tubular damage was not shown but further study is needed. Keywords: Metals, Co-exposure, Kidney damage, BKMR, Metal exposure The Korea Environment Industry and Technology Institute through the Core Technology Development Project for Environmental Disease Prevention and Management, funded by the Korea Ministry of Environment (grant number 2021003320003).

The effects of metals and mixture exposure on lung function and the potential mediating effects of oxidative stress.

Exposure to metals is associated with lung function decline. However, limited data are available about effects of co-exposure of metals on lung function. Additionally, the mechanism of the association between metals and lung function remains unclear. We conducted a longitudinal panel study in 2017-2018 among 45 healthy college students. Urinary 15 metals, lung function, biomarkers of oxidative stress and inflammation of participants were measured. Linear mixed effect (LME) and Bayesian kernel machine regression (BKMR) models were applied to explore the associations of urinary metals and mixture with lung function. Furthermore, we analyzed the mediating effect of biomarkers in the association between urinary metals and lung function. LME models showed the negative associations of aluminum (Al), vanadium (V), manganese (Mn), cobalt (Co), nickel (Ni), cadmium (Cd) or antimony (Sb) with Forced vital capacity (FVC), and V, Co, Ni, and Sb with Forced expiratory volume in one second (FEV1). BKMR models indicated the overall effect of metals mixture was negatively associated with FEV1 and FVC; urinary Sb was identified as the major contributor to decreased FVC and FEV1. Urinary 8-hydroxydeoxyguanosine mediated the association of Al, Mn, or Sb with FVC and the relationship of V with FEV1. The results revealed the longitudinal dose-response relationships of urinary metals with pulmonary function among healthy adults. Oxidative stress may be the underlying mechanisms of metals exposure associated with decreased lung function. Due to the small sample size, the interpretation of the results of this study should be cautious, and more studies are needed to verify the findings of this study.

Occurrence, accumulation, and health risks of heavy metals in Chinese market baskets

Residual levels and accumulation characteristics of six hazardous heavy metal elements (As, Cd, Hg, Tl, Pb, and U) and seven essential heavy metal elements (Cr, Mn, Fe, Ni, Cu, Zn, and Se) were investigated in 17 kinds of frequently consumed foodstuffs collected from 33 cities distributed in five regions of China. The concentrations of the detected metals were lower than the maximum limits promulgated by the Chinese government except Pb and inorganic As (iAs). Foods of aquatic origin and terrestrial plant origin exhibited high potentials to accumulate heavy metals, especially algae and shellfish. The calculated hazard index (HI) of heavy metal exposure via consumption of foodstuffs were 2.93–5.01 for adults in the five surveyed region, implying the co-exposure of heavy metals via food consumption would lead to potential non-carcinogenic risks. iAs was the predominant contributor to HI values with the average contribution of 40.5% in all five regions. Consumption of terrestrial plant origin foods contributed 76.9% of HI values induced by heavy metal exposure. The calculated target cancer risks of iAs in the five regions were 5 × 10−4–1 × 10−3, all exceeding the acceptable level of 10−4, indicating it is necessary and urgent to reduce the contamination of iAs in foodstuffs on the Chinese markets.