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.

Manganese accumulation in red blood cells as a biomarker of manganese exposure and neurotoxicity.

Although overexposure to manganese (Mn) is known to cause neurotoxic damage, effective exposure markers for assessing Mn loading in Mn-exposed workers are lacking. Here, we construct a Mn-exposed rat model to perform correlation analysis between Mn-induced neurological damage and Mn levels in various biological samples. We combine this analysis with epidemiological investigation to assess whether Mn concentrations in red blood cells (MnRBCs) and urine (MnU) can be used as valid exposure markers. The results show that Mn exposure resulted in neurotoxic damage in rats and that MnRBCs correlated well with neurological damage, showing potential as a novel Mn exposure biomarker. These findings provide a basis for health monitoring of Mn-exposed workers and the development of more appropriate biological exposure limits.

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

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

The effect of mask fit test on the association between the concentration of metals in biological samples and the results of time-weighted average personal exposure: A study on Japanese male welders.

OBJECTIVES: The mask fit test confirms whether the wearing condition of the wearer's face and the facepiece of the respirators are used appropriately. This study aimed to examine whether the results of the mask fit test affect the association between the concentration of metals related to welding fumes in biological samples and the results of time-weighted average (TWA) personal exposures. METHODS: A total of 94 male welders were recruited. Blood and urine samples were obtained from all participants to measure the metal exposure levels. Using personal exposure measurements, the 8-h TWA (8 h-TWA) of respirable dust, TWA of respirable Mn, and 8-h TWA of respirable Mn were calculated. The mask fit test was performed using the quantitative method specified in the Japanese Industrial Standard T8150:2021. RESULTS: Fifty-four participants (57%) passed the mask fit test. Only in the Fail group of the mask fit test, it was observed that blood Mn concentrations be positively associated with the results of TWA personal exposure after adjusting for multivariate factors (8-h TWA of respirable dust; coefficient, 0.066; standard error (SE), 0.028; P = 0.018, TWA of respirable Mn: coefficient, 0.048; SE, 0.020; P = 0.019, 8 h-TWA of respirable Mn: coefficient, 0.041; SE, 0.020; P = 0.041). CONCLUSIONS: The results clarify that welders with high concentrations of welding fumes in their breathing air zone are exposed to dust and Mn if there is leaking air owing to the lack of fitness between respirators and the wearer's face when using human samples in Japan.

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

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

Multibiomarker approach to assess the magnitude of occupational exposure and effects induced by a mixture of metals.

Metals and metalloids including lead (Pb), arsenic (As) and manganese (Mn) can occur as mixtures in occupational contexts, such as mines. These chemicals are all known to be neurotoxic and provoke changes in heme metabolism also known to induce neurotoxicity. The objective of this work was to propose a multi-biomarker (BM) methodology to screen subjects exposed to the mixture of Pb, As and Mn and assess the severity of their exposure/effects, in an individual basis. The urinary levels of the metals, dela-aminolevulinic acid (ALA) and porphyrins were determined in Portuguese miners and in a control group. The combination of Pb and As urinary levels had the highest capability to identify subjects occupationally exposed to this mixture in mines, as evaluated through Receiver Operating Characteristic (ROC) (A = 98.2%; p < 0.05), allowing that 94.2% of 86 studied subjects were properly identified and the generation of an equation indicating the odd of a subject be considered as exposed to the metal mixture. The combination of urinary ALA and porphyrins revealed to be best one to be applied in the assessment of subjects with high, intermediate, and low magnitudes of exposure/effects, with 95.7% of 46 miners classified correctly according to their severity sub-group and allowing to generate equations, which can be applied in new subjects. The proposed methodology showed a satisfactory performance, evaluating in an integrated manner the magnitude of exposure/effects of the exposed workers, may contributing to improve the control of their health.

Association of Heavy Metals with Overall Mortality in a Taiwanese Population.

Previous studies have shown links between heavy metals and many health issues. However, data on the association between heavy metals and mortality in the general population are still limited. Therefore, the aim of this study was to investigate the relationship between heavy metals and overall mortality in the general population. We enrolled 2497 participants (1001 males and 1496 females) living in southern Taiwan, and measured levels of seven heavy metals: lead (Pb) in blood and cadmium (Cd), nickel (Ni), copper (Cu), chromium (Cr), manganese (Mn) and arsenic (As) in urine. The median follow-up period was 41.8 (4-50) months, during which 40 (1.6%) patients died. Compared to the participants who survived, those who died had higher urine Cd, higher urine Cu and lower urine Mn levels. Multivariate analysis showed that high urine Cd (per 1 µg/L; hazard ratio [HR], 1.352; 95% confidence interval [CI], 1.089-1.680; p = 0.006), high urine Cu (per 1 µg/dL; HR, 1.350; 95% CI, 1.151-1.583; p < 0.001), and low urine Mn (per 1 µg/L; HR, 0.717; 95% CI, 0.557-0.923; p = 0.010) were associated with increased overall mortality. In conclusion, our results demonstrated that high levels of urine Cd and Cu and low urine Mn level were associated with increased overall mortality in the general population.

Association between maternal urinary manganese concentrations and newborn telomere length: Results from a birth cohort study.

OBJECTIVE: Telomere length (TL) is a biomarker for biological aging, and the initial setting of TL at birth is a determinant factor of TL in later life. Newborn TL is sensitive to maternal metals concentrations, while study about the association between maternal manganese (Mn) concentrations and newborn TL was not found. Our study aimed to investigate whether newborn TL is related to maternal Mn concentrations. METHODS: Data were collected from a birth cohort study of 762 mother-newborn pairs conducted from November 2013 to March 2015 in Wuhan, China. We measured the Mn concentrations in spot urine samples collected during three trimesters by inductively coupled plasma mass spectrometry (ICP-MS) and relative cord blood TL by quantitative real-time polymerase chain reaction (qPCR). We applied multiple informant models to investigate the associations between maternal Mn concentrations and cord blood TL. RESULTS: The geometric mean of creatinine-corrected urinary Mn concentrations were 1.58 µg/g creatinine, 2.53 µg/g creatinine, and 2.62 µg/g creatinine in the first, second, and third trimester, respectively. After adjusting for potential confounders, a doubling of maternal urinary Mn concentration during the second trimester was related to a 2.10% (95% CI: 0.25%, 3.99%) increase in cord blood TL. Mothers with the highest tertile of urinary Mn concentrations during the second trimester had a 9.67% (95% CI: 2.13%, 17.78%) longer cord blood TL than those with the lowest tertile. This association was more evident in male infants. No relationship was found between maternal urinary Mn concentrations and cord blood TL during the first and third trimesters in our study. CONCLUSIONS: Our findings suggested that maternal Mn concentration during the second trimester was positively associated with newborn TL. These results might provide an epidemiology evidence on the protective role of maternal Mn for newborn TL and offer clues for the early prevention of telomere shortening related diseases.

Associations of Heavy Metals with Metabolic Syndrome and Anthropometric Indices.

Previous studies have revealed associations between heavy metals and extensive health problems. However, the association between heavy metals and metabolic problems remains poorly defined. This study aims to investigate relationships between heavy metals and metabolic syndrome (MetS), lipid accumulation product (LAP), visceral adiposity index (VAI), and anthropometric indices, including body roundness index (BRI), conicity index (CI), body adiposity index (BAI), and abdominal volume index (AVI). We conducted a health survey of people living in southern Taiwan. Six heavy metals were measured: lead (Pb) in blood and nickel (Ni), chromium (Cr), manganese (Mn), arsenic (As), and copper (Cu) in urine. A total of 2444 participants (976 men and 1468 women) were enrolled. MetS was defined according to the Adult Treatment Panel III for Asians. Multivariable analysis showed that participants with high urine Ni (log per 1 µg/L; odds ratio (OR): 1.193; 95% confidence interval (CI): 1.019 to 1.397; p = 0.028) and high urine Cu (log per 1 µg/dL; OR: 3.317; 95% CI: 2.254 to 4.883; p < 0.001) concentrations were significantly associated with MetS. There was a significant trend of a stepwise increase in blood Pb and urine Ni, As, and Cu according to the number of MetS components (from 0 to 5, a linear p ≤ 0.002 for trend). For the determinants of indices, urine Cu was positively correlated with LAP, BRI, CI, and VAI; blood Pb was positively correlated with BRI, BAI, and AVI; urine Ni was positively correlated with LAP. High urine Cu and urine Ni levels were significantly associated with MetS, and there was a significant trend for stepwise increases in blood Pb and urine Ni, As, and Cu, accompanied by an increasing number of MetS components. Furthermore, several indices were positively correlated with urine Cu, urine Ni, and blood Pb.

Sex-specific associations of blood and urinary manganese levels with glucose levels, insulin resistance and kidney function in US adults: National health and nutrition examination survey 2011-2016.

Exposures to heavy metals play a role in the etiopathogenesis of diabetes. Epidemiological studies investigating a potential sex-specific linkage between manganese (Mn) exposures and glucose homeostasis are rare. We comprehensively estimated the associations of blood and urinary Mn levels with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), insulin, and estimated glomerular filtration rate (eGFR) among 1417 adults in the US National Health and Nutrition Examination Survey (NHANES) 2011-2016. We further examined the potential heterogeneities by sex and joint-effects of multiple metal exposures by the Bayesian kernel machine regression (BKMR). Among women, we found positive linear relationships between urinary Mn with FPG (Poverall = 0.003, Pnonlinear = 0.817) and HbA1c (Poverall = 0.023, Pnonlinear = 0.854). Among men, J-shaped relationships were observed between blood Mn with HOMA-IR (Pnonlinear = 0.042) and insulin (Pnonlinear = 0.014). For eGFR, positive linear relationships were obserned among women for blood Mn (Pnonlinear = 0.549) and among both men and women for urinary Mn levels. The joint-effects of urinary Mn with molybdenum (Mo) on FPG and HbA1c, urinary Mn with cadmium (Cd) and cesium (Cs) on eGFR, and blood Mn with Cd and lead (Pb) on eGFR were detected. In summary, blood and urinary Mn levels were independently associated with glucose levels, insulin resistance and kidney function with potential sex-dependent heterogeneities. These findings emphasize the probable role of Mn in the regulation of glucose metabolism and kidney function, and confirm the need for more studies on sex-specific risk of diabetes.

[Determination of manganese in human urine by dispersive ionic liquid-liquid microextraction-graphite furnace atomic absorption spectrometry].

Objective: To establish a method for the determination of manganese in urine with graphite furnace atomic absorption spectrometry (GFAAS) by using ionic liquid microextraction. Methods: The ethanol, 8-hydroxyquinoline and ionic liquid 1-octyl-3-methyl-imidazolium hexafluorophosphate were used as dispersive solvent, chelating agent and extraction solvent respectively, for the preconcentration of manganese. After the optimal extraction conditions were optimized by single factor rotations, evaluate the performance indicators such as methodological precision, accuracy, and detection limit. Results: The linear range of urine manganese was 0.0-1.6 µg/L, and the correlation coefficient of standard curve line was 0.992, the detection limit was 0.03 µg/L, the recovery of sample spiked was 84.90%-96.50%, and the relative standard deviation was 0.36%-1.84%. Conclusion: The method has the advantages of low detection limit, high recovery rate and high sensitivity. It is suitable for the determination of manganese in urine samples from occupational exposure populations and the general population.

Ambulatory Blood Pressure in Relation to Plasma and Urinary Manganese.

The association of blood pressure (BP) with manganese-an essential trace element required for human health-remains poorly studied. In 734 randomly recruited Swiss participants (mean age, 47.5 years; 51.4% women), we related ambulatory BP to 2 biomarkers, plasma manganese (pMn) and the urinary manganese (uMn) excretion. To allow for diurnal variation, we assessed BP and uMn over 24 hours and during wakefulness and sleep, using split urine samples. Twenty-four-hour, daytime, and nighttime systolic/diastolic BPs averaged 119.8/78.1, 123.8/81.2, and 107.0/68.3 mm Hg; the corresponding median uMn were 199.5, 83.0, and 51.5 µmol and median pMn, 0.52 µg/L. In analyses dichotomized by the median of the biomarkers, greater pMn was associated with higher 24-hour systolic/diastolic BP (+4.1/+2.3 mm Hg; P≤0.0003), greater daytime uMn with lower daytime BP (-3.5/-1.9 mm Hg; P≤0.0067), and greater nighttime uMn with higher nighttime BP (+2.9/+1.2 mm Hg; P≤0.046). In multivariable-adjusted analyses, significance (P≤0.030) was retained for the positive association of 24-hour and daytime diastolic BP with pMn and for systolic BP in relation to uMn at night. The association sizes for a 2-fold increment in the biomarkers amounting to 0.77 mm Hg (95% CI, 0.08-1.47 mm Hg), 0.97 (CI, 0.20-1.76) and 1.33 (CI, 0.20-2.50 mm Hg), respectively. In conclusion, there were positive associations between diastolic BP and pMn over 24 hours and during daytime and between systolic BP and uMn at night.

Assessment of copper, iron, zinc and manganese status and speciation in patients with Parkinson's disease: A pilot study.

BACKGROUND: The objective of this pilot study was to assess iron (Fe), copper (Cu), zinc (Zn), and manganese (Mn) status (hair, serum, and urine) and speciation (serum) in Parkinson's disease (PD) patients. METHODS: A pilot study involving a total of 27 subjects (13 PD patients, 14 controls) was performed. Serum, urine, and hair metal content was assessed using ICP-MS. Speciation analysis of Cu, Zn, Fe, and Mn was performed using a hybrid HPLC-ICP-MS system. RESULTS: Group comparisons did not reveal any significant group difference in serum Cu, Zn, Fe, and Mn total metal level between PD patients and controls. Speciation analysis revealed a significant decrease in Cu/ceruloplasmin copper in association with elevation of low-molecular weight species (amino acids)-bound copper. It is proposed that in PD, binding of Cu(II) ions to ceruloplasmin is reduced and free copper ions coordinate with low molecular weight ligands. The level of Mn-albumin complexes in PD patients was more than 4-fold higher as compared to the respective value in the control group. The observed difference may be considered as a marker of redistribution between high and low molecular weight ligands. CONCLUSIONS: Metal speciation is significantly affected in serum of PD-patients. These findings are indicative of the potential role of metal metabolism and PD pathogenesis, although the exact mechanisms of such associations require further detailed studies.

Dietary Intake and Urinary Excretion of Manganese in Korean Healthy Adults.

Manganese (Mn) is an essential element for the body's composition and is required for various functions, including nutrient metabolism, immune system function, and antioxidant ability. However, there are insufficient data on the nutritional status of Mn. In this study, we aimed to analyze the relationship between Mn intake and urinary excretion in Korean adults. A twice dietary intake survey using a 24-h recall method was conducted on 640 adults (320 men and 320 women), aged 20 to 69 years. Eighty 24-h urine samples were also twice collected and urinary Mn excretions were analyzed. Results indicated that total Mn intake per day was 4.1 mg for men and 3.9 mg for women (p < 0.05). Mn intake per 1000 kcal of energy consumption was significantly higher in women than in men (2.0 mg/1,000 kcal vs. 2.2 mg/1000 kcal, p < 0.01). Additionally, Mn intake as a percentage of Adequate Intake was 103.0% for men and 110.3% for women (p < 0.05). Mn was mostly consumed from cereals (1.78 mg/day for men and 1.53 mg/day for women), followed by vegetables, seasonings, fruits, and pulses. The main food sources of Mn were rice (27.8% for men, 22.0% for women), kimchi (3.5% for men, 1.4% for women), and tofu (2.8% for men, 2.3% for women); the percentage of Mn consumed from 20 types of foods was 55.6% (women) to 60.4% (men). Urinary Mn excretion was negatively correlated with Mn intake from cereals and positively with mushrooms only for women after adjusting for confounding factors (p < 0.05). In conclusion, dietary Mn intake by Korean adults was adequate to meet the Dietary Reference Intake, but the relationship between Mn intake and urinary excretion was not clear.

Reproducibility of essential elements chromium, manganese, iron, zinc and selenium in spot samples, first-morning voids and 24-h collections from healthy adult men.

Evaluation of Cr, Mn, Fe, Zn and Se in humans is challenged by the potentially high within-individual variability of these elements in biological specimens, which are poorly characterised. This study aimed to evaluate their within-day, between-day and between-month variability in spot samples, first-morning voids and 24-h collections. A total of 529 spot urine samples (including eighty-eight first-morning voids and 24-h collections) were collected from eleven Chinese adult men on days 0, 1, 2, 3, 4, 30, 60 and 90 and analysed for these five elements using inductively coupled plasma-MS. Intraclass correlation coefficients (ICC) were utilised to characterise the reproducibility, and their sensitivity and specificity were analysed to assess how well a single measurement classified individuals' 3-month average exposures. Serial measurements of Zn in spot samples exhibited fair to good reproducibility (creatinine-adjusted ICC = 0·47) over five consecutive days, which became poor when the samples were gathered months apart (creatinine-adjusted ICC = 0·33). The reproducibility of Cr, Mn, Fe and Se in spot samples was poor over periods ranging from days to months (creatinine-adjusted ICC = 0·01-0·12). Two spot samples were sufficient for classifying 60 % of the men who truly had the highest (top 33 %) 3-month average Zn concentrations; for Cr, Mn, Fe and Se, however, at least three specimens were required to achieve similar sensitivities. In conclusion, urinary Cr, Mn, Fe, Zn and Se concentrations showed a strong within-individual variability, and a single measurement is not enough to efficiently characterise individuals' long-term exposures.

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

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

Effect of an Acute Exercise Until Exhaustion on the Serum and Urinary Concentrations of Cobalt, Copper, and Manganese Among Well-Trained Athletes.

The current information about the effect of physical exercise on the body concentrations of several minerals is still limited, both in the acute (short-term) and adaptive (long-term) responses. So, this manuscript aims, on the one hand, to assess the possible differences on basal levels of cobalt (Co), copper (Cu), and manganese (Mn) concentrations in serum and urine between athletes and sedentary participants and, on the other hand, to evaluate the effect of an acute progressive physical exercise until voluntary exhaustion on the serum and urinary concentrations of Co, Cu, and Mn. Two groups participated in this survey, one was formed by untrained, sedentary males (CG; n = 26), and the other group was constituted by national endurance (long and middle distances) athletes (AG; n = 21). All participants were from the same region of Spain. Participants of both groups performed a physical test on a treadmill, reaching voluntary exhaustion. Blood and urine samples of each participant were collected before and at after the tests. Once obtained and processed, the concentrations of Co, Cu, and Mn elements were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). The differences in the studied variables were evaluated using a mixed model by means of an ANOVA and Bonferroni post hoc tests. In the comparison of the pre-test values between groups, the results showed that serum concentrations of Mn were significantly lower in CG than in AG (p < 0.01). In urine, Co and Mn levels were significantly higher among CG participants (p < 0.01) than among AG ones, while in the case of Cu, the values were lower (p < 0.01) in the CG than in the AG. Regarding the effects of the effort tests, no significant changes were found among the participants of the CG. It was observed that the serum concentrations of Co (p < 0.05) and Cu (p < 0.01) decreased after the test among the AG participants. Also, the results showed that there were no statistical differences in Co and Mn values (expressed in µg/g creatinine). However, the urinary post-test Cu concentrations were lower (p < 0.05) among AG participants. In basal conditions, serum concentrations of Mn were significantly lower in CG than in AG. In urine, Co and Mn levels were significantly higher among CG participants and Cu level was significantly lower in CG, a fact which may reflect adaptive responses to exercise. An incremental exercise to exhaustion in AG produces a decrease in Co and Cu serum concentrations, as well as in urinary excretion of Cu.

The reproducibility of urinary ions in manganese exposed workers.

PURPOSE: Manganese (Mn) is found in environmental and occupational settings, and can cause cognitive and motor impairment. Existing Mn exposure studies have not reached consensus on a valid and reproducible biomarker for Mn exposure. METHODS: Previously, global metabolomics data was generated from urine collected in October 2014 using mass spectrometry (MS). Nine ions were found to be different between persons exposed and unexposed to Mn occupationally, though their identity was not able to be determined. Here, we investigated these nine ions in a follow-up set of urine samples taken from the same cohort in January 2015, and in urine samples from a separate Mn-exposed cohort from Wisconsin. We fit an elastic net model fit using the nine ions found in the October 2014 data. RESULTS: The elastic net correctly predicted exposure status in 72% of the follow-up samples collected in January 2015, and the area under the curve of the receiver operating characteristic (ROC) curve was 0.8. In the Wisconsin samples, the elastic net performed no better than chance in predicting exposure, possibly due to differences in Mn exposure levels, or unmeasured occupational or environmental co-exposures. CONCLUSIONS: This work underscores the importance of taking repeat samples for replication studies when investigating the human urine metabolome, as both within- and between-person variances were observed. Validating and identifying promising results remains a challenge in harnessing global metabolomics for biomarker discovery in occupational cohorts.

Occupational manganese exposure, reproductive hormones, and semen quality in male workers: A cross-sectional study.

It has been found that exposure to manganese (Mn) could induce reproductive dysfunction, but its occupational risk in male workers is unclear. This study aims to assess the association of occupational Mn exposure with reproductive hormones and semen quality in a cross-sectional study. Urinary Mn, semen quality, and reproductive hormones were explored in 84 male workers occupationally exposed to Mn and 92 referents. Multiple linear regression analyses were used to assess the relationship. Urinary Mn levels in Mn-exposed workers ranged from 0.56 to 34.25 µg/L, and the average level was 15.92 ± 8.49 µg/L. Compared with the control group, gonadotropin-releasing hormone (GnRH) levels and luteinizing hormone (LH) levels increased significantly and the levels of testosterone (TSTO) decreased significantly in the Mn-exposed group. There was a significant positive linear association between urinary Mn and GnRH and LH, while the linear association between urinary Mn and TSTO was negative. Sperm progressive motility and total motility decreased significantly in the Mn-exposed group. There was a significantly negative linear association between urinary Mn and sperm progressive motility and total motility. In conclusion, occupational Mn exposure was inversely associated with reproductive health of male workers, resulting in the abnormality of hormones secretion and decrease of sperm motility.