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 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.

[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.

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.

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.

Autosomal-Recessive Intellectual Disability with Cerebellar Atrophy Syndrome Caused by Mutation of the Manganese and Zinc Transporter Gene SLC39A8.

Manganese (Mn) and zinc (Zn) are essential divalent cations used by cells as protein cofactors; various human studies and animal models have demonstrated the importance of Mn and Zn for development. Here we describe an autosomal-recessive disorder in six individuals from the Hutterite community and in an unrelated Egyptian sibpair; the disorder is characterized by intellectual disability, developmental delay, hypotonia, strabismus, cerebellar atrophy, and variable short stature. Exome sequencing in one affected Hutterite individual and the Egyptian family identified the same homozygous variant, c.112G>C (p.Gly38Arg), affecting a conserved residue of SLC39A8. The affected Hutterite and Egyptian individuals did not share an extended common haplotype, suggesting that the mutation arose independently. SLC39A8 is a member of the solute carrier gene family known to import Mn, Zn, and other divalent cations across the plasma membrane. Evaluation of these two metal ions in the affected individuals revealed variably low levels of Mn and Zn in blood and elevated levels in urine, indicating renal wasting. Our findings identify a human Mn and Zn transporter deficiency syndrome linked to SLC39A8, providing insight into the roles of Mn and Zn homeostasis in human health and development.

Manganese in toenails is associated with hearing loss at high frequencies in humans.

PURPOSE: Elevated hearing thresholds from high frequencies are known to be one of the hallmarks of age-related hearing loss. Our recent study showed accumulation of manganese (Mn) in inner ears resulting in acceleration of age-related hearing loss in mice orally exposed to Mn. However, there is no evidence showing an association between Mn in non-invasive biological samples and hearing loss in humans evaluated by pure tone audiometry (PTA). In this study, we evaluated Mn in non-invasive biological samples as a possible biomarker for hearing loss in humans. MATERIALS AND METHODS: We determined hearing levels by PTA and Mn levels in toenails, hair and urine with an inductively coupled plasma mass spectrometer (ICP-MS) in 145 healthy subjects in Bangladesh. RESULTS: Multivariable analyses showed that Mn levels in toenails, but not in hair and urine samples, were significantly associated with hearing loss at 8 kHz and 12 kHz. Moreover, our experimental study showed a significant correlation between Mn levels in inner ears and nails, but not hair, in mice orally exposed to Mn. CONCLUSIONS: The results provide novel evidence that Mn in toenails is a possible biomarker for hearing loss at high frequencies in humans.

Biomarkers of exposure and effect in a working population exposed to lead, manganese and arsenic.

Lead (Pb), manganese (Mn) and arsenic (As) are among the major toxicants in mining environments. Miners are commonly and repeatedly exposed to this toxic mixture. Some adverse effects may appear at concentrations below environmental quality guidelines for individual mixture components. Further, Pb, Mn, and As induce common adverse outcomes, such as interferences in the cholinergic system and heme synthesis. It is thus vital to monitor miners through biomarkers (BM), such that subclinical effects may be identified at an early stage. The main objectives of this study were to evaluate the exposure of a mining population to these three metals and determine alterations in cholinergic and heme synthesis parameters. Blood and urine samples of workers (n = 60) were obtained from a Portuguese mining industry and compared with a control population (n = 80). The levels of the metals were determined in biological samples, as well as urinary heme precursor levels, delta aminolevulinic acid (ALA) and porphyrins, and blood acetylcholinesterase (AChE) activity. The miners exhibited significantly higher values of Pb and As in blood and urine compared to control. In the case of Mn near or slightly higher than limit values were found. Our data show that heme precursors may be used simultaneously with metal levels as BMs for multiple metal exposures on an individual basis, resulting in 94.3% and 95.7% accuracy, respectively, in blood and urine, for subjects correctly identified with respect to occupation. This study also revealed that biological monitoring of this working population regarding metal body burden and heme precursor accumulation is advisable.

[Direct determination of manganese in urine by Graphite Furnace Atomic Absorption Spectrometry].

Objective: To establish a method for the determination of manganese in urine by graphite furnace atomic absorption spectrometry (AAS) without the use of matrix modifier. Methods: The urine samples were 5 times diluted with 1% nitric acid then directly determined by AAS. Zeeman was used for background correction. Results: The linear range for determination of manganese in urine was 5~60 µg/L (urine) . The correlation coefficient was greater than 0.995 with the detection limit of 1.5 µg/L and with the lower limit of quantification of 5.0 µg/L. The relative standard deviations (RSDs) of within-run precision was between 1.1%~4.3%, the RSDs of between-run precision was between 3.3%~7.0%. The average recovery was 102.6%. The samples can be stored for 14 days at room temperature, 4℃, -8 ℃ and -35 ℃. Conclusion: The method is feasible for determination of manganese in urine.

Application of linear mixed-effects model with LASSO to identify metal components associated with cardiac autonomic responses among welders: a repeated measures study.

BACKGROUND: Environmental and occupational exposure to metals is ubiquitous worldwide, and understanding the hazardous metal components in this complex mixture is essential for environmental and occupational regulations. OBJECTIVE: To identify hazardous components from metal mixtures that are associated with alterations in cardiac autonomic responses. METHODS: Urinary concentrations of 16 types of metals were examined and 'acceleration capacity' (AC) and 'deceleration capacity' (DC), indicators of cardiac autonomic effects, were quantified from ECG recordings among 54 welders. We fitted linear mixed-effects models with least absolute shrinkage and selection operator (LASSO) to identify metal components that are associated with AC and DC. The Bayesian Information Criterion was used as the criterion for model selection procedures. RESULTS: Mercury and chromium were selected for DC analysis, whereas mercury, chromium and manganese were selected for AC analysis through the LASSO approach. When we fitted the linear mixed-effects models with 'selected' metal components only, the effect of mercury remained significant. Every 1 µg/L increase in urinary mercury was associated with -0.58 ms (-1.03, -0.13) changes in DC and 0.67 ms (0.25, 1.10) changes in AC. CONCLUSION: Our study suggests that exposure to several metals is associated with impaired cardiac autonomic functions. Our findings should be replicated in future studies with larger sample sizes.

Associations between IVF outcomes and essential trace elements measured in follicular fluid and urine: a pilot study.

PURPOSE: A hypothesis-generating pilot study exploring associations between essential trace elements measured in follicular fluid (FF) and urine and in vitro fertilization (IVF) endpoints. METHODS: We recruited 58 women undergoing IVF between 2007 and 2008, and measured cobalt, chromium, copper, manganese, molybdenum, and zinc in FF (n = 46) and urine (n = 45) by inductively coupled plasma mass spectrometry (ICP-MS). We used multivariable regression models to assess the impact of FF and urine trace elements on IVF outcomes, adjusted for age, body mass index, race, and cigarette smoking. RESULTS: Trace elements were mostly present at lower concentrations in FF than in urine. The average number of oocytes retrieved was positively associated with higher urine cobalt, chromium, copper, and molybdenum concentrations. FF chromium and manganese were negatively associated with the proportion of mature oocytes, yet urine manganese had a positive association. FF zinc was inversely associated with average oocyte fertilization. Urine trace elements were significant positive predictors for the total number of embryos generated. FF copper predicted lower embryo fragmentation while urine copper was associated with higher embryo cell number and urine manganese with higher embryo fragmentation. No associations were detected for implantation, pregnancy, or live birth. CONCLUSIONS: Our results suggest the importance of trace elements in both FF and urine for intermediate, although not necessarily clinical, IVF endpoints. The results differed using FF or urine biomarkers of exposure, which may have implications for the design of clinical and epidemiologic investigations. These initial findings will form the basis of a more definitive future study.

[An investigation of normal urinary manganese value in healthy adults in different places in Guangxi, China].

Objective: To investigate the normal urinary manganese value in healthy adults in Guangxi, China and its distribution characteristics. Methods: From 2015 to 2016, stratified random sampling based on age and sex was performed to select 1533 healthy adults aged 18-60 years in Nanning,Liuzhou,Guilin,Hezhou,Wuzhou,Yulin,Guigang,Beihai,Qinzhou,Laibin,Hechi Nandan,Bose Jingxi,Chongzuo Daxin,and Fangchenggang.All of them had no history of occupational manganese exposure or acute or chronic liver/renal diseases and had lived in the local area for more than one year. A total of 1417 urine samples with normal specific gravity and complete data were obtained, and graphite furnace atomic absorption spectrometry was used to measure urinary manganese.The distribution characteristics of urinary manganese level were analyzed among adults with different ages,sexes,or presence or absence of smoking habits or among those who lived or did not live in the mining area. Results: The geometric mean of urinary manganese among healthy adults in Guangxi was 0.52 µg/L,and the upper limit of normal was 5.68µg/L. There was no significant difference in urinary manganese level between the healthy adults with different ages, sexes,or presence or absence of smoking habits (P>0.05).The healthy adults who lived in the mining area of nonferrous metal mines had a significantly higher geometric mean of urinary manganese than those who did not live in such areas(1.65µg/Lvs0.34µg/L,P<0.01). Conclusion: The upper limit of normal of urinary manganese is 5.68 µg/L among healthy adults in Guangxi,and the healthy adults who live in the mining area of manganese mine or nonferrous metal mines have a significantly higher urinary manganese level than those who do not live in such areas.

An assessment of clinical laboratory performance for the determination of manganese in blood and urine.

BACKGROUND: Proficiency testing or external quality assessment schemes (PT/EQASs) are an important method of assessing laboratory performance. As each scheme establishes assigned values and acceptable ranges for the analyte according to its own criteria, monitoring of participant performance varies according to the scheme and can lead to conflicting conclusions. METHODS: Standard deviations (SDs) for PT were derived from Thompson's and biological variation models applied to blood and urine manganese (Mn) robust data from four EQASs from North America and Europe. The fitness for purpose was verified by applying these SDs to individual results. RESULTS: Using Thompson characteristic function the relationship between SD and Mn concentration, expressed in nmol/L was the square root of [19.72+(0.07712×Mn concentration2)] for blood and the square root of [6.772+(0.09852×Mn concentration2)] for urine. While the biological variation model was not suitable for urine, it produced an acceptable range for blood as ±54.4 nmol/L (assigned value ≤320 nmol/L) or 17% (assigned value >320 nmol/L). For blood, individual performance evaluated by the two approaches led to similar conclusions. CONCLUSIONS: The biological variation model can be used to propose quality specifications for blood, however it could not be applied to urine. The Thompson characteristic function model could be applied to derive quality specifications for Mn in urine and, to a lesser extent in blood. The more lenient quality specifications for blood highlight the difficulty of determining Mn in this matrix. Further work is needed to harmonize PT, such as using assigned ranges for the specimens.

Maternal urinary manganese and risk of low birth weight: a case-control study.

BACKGROUND: Manganese (Mn) is an essential element for humans, but exposure to high levels has been associated with adverse developmental outcomes. Early epidemiological studies evaluating the effect of Mn on fetal growth are inconsistent. METHODS: We investigated the association between maternal urinary Mn during pregnancy and the risk of low birth weight (LBW). Mn concentrations in maternal urine samples collected before delivery were measured in 816 subjects (204 LBW cases and 612 matched controls) recruited between 2012 and 2014 in Hubei Province, China. RESULTS: The median Mn concentration in maternal urine was 0.69 µg/g creatinine. Compared to the medium tertile of Mn levels, an increased risk of LBW was observed for the lowest tertile (≤0.30 µg/g creatinine) [adjusted odds ratio (OR) = 1.28; 95 % confidence interval (CI) = 0.67, 2.45], and a significantly increased risk of LBW was observed for the highest tertile (≥1.16 µg/g creatinine) [adjusted OR = 2.04; 95 % CI = 1.12, 3.72]. A curvilinear relationship between maternal urinary Mn and risk of LBW was observed, showing that the concentration at 0.43 µg/g creatinine was the point of inflection. Similar associations were observed among the mothers with female infants and among the younger mothers < 28 years old. However, among the mothers with male infants or the older mothers ≥ 28 years old, only higher levels of Mn were positively associated with LBW. CONCLUSIONS: Lower or higher levels of maternal urinary Mn are associated with LBW, though only the association of LBW risk and higher levels of Mn was statistically significant. The findings also show that the associations may vary by maternal age and infant sex, but require confirmation in other populations.

[Association between personal exposure to metals in fine particulate matter and urinary metals: baseline results from a panel study].

OBJECTIVE: To investigate the associations between 21 metals in fine particulate matter (PM2.5) and their corresponding concentrations in urine in the general population. METHODS: Between April and May 2011, this panel study enrolled 120 residents using random sampling approach in Wuhan communities which contained 3 035 subjects. Participants were aged 18 to 80 years and had lived in the sampling buildings for at least 5 years. Data from basic questionnaires, physical examinations, and morning blood and urine samples under fasting conditions were collected. Participants with missing data were excluded. Finally, 83 particpants included. Participants were instructed to use personal air samplers to continuously monitor PM2.5 for 24 h. The following 21 metals were measured in PM2.5 and urine by inductively coupled plasma mass spectrometry: aluminum, titanium, vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, selenium, rubidium, strontium, molybdenum, cadmium, tin, antimony, barium, tungsten, thallium and lead. The associations between PM2.5 metals and urinary metals were investigated using generalized linear regression models. RESULTS: The age of the study population was (51.5±6.3)years. After adjusting for age, sex, smoking status, BMI, education and income, elevated urinary chromium was significantly associated with increased chromium concentrations in personal PM2.5. The least square means (standard deviation) of urinary chromium in participants classified as having low exposure (<12.491 ng/m(3)), intermediate exposure (12.491-32.388 ng/m(3)) and high exposure (>32.388 ng/m(3)) were (-1.334±0.756), (-1.114±0.813) and (-0.718±0.645) µg/mmol creatinine, respectively (P=0.009). However, the association between urinary and personal PM chromium was not observed after additionally adjusting for false discovery rate (P>0.05). Furthermore, the results demonstrated that other metals in PM2.5 were not related to their corresponding concentrations in urine of subjects. CONCLUSION: Urinary concentrations of metals did not reflect human exposure to metals in air, and may not be appropriate as an index to assess personal exposure to metals in particulate matter.

Urinary metal concentrations among female welders.

As part of a Canada-wide study of women entering non-traditional trades [Women's Health in Apprenticeship Trades-Metalworkers and Electricians (WHAT-ME)], we examined spot urine samples from women welders in Alberta to determine whether urinary metal concentrations exceeded those of the general population, to compare levels to previously published urinary concentrations in male welders and to examine the relationship with welding tasks. Women mailed-in urine samples collected close to the time of completing a detailed exposure questionnaire, including welding tasks on their most recent day welding at work. Of 53 welders working in their trade, 45 had urinary creatinine >0.3-≤3.0g l(-1) and were included in analyses. Seven metals were examined for which both population and male welder urinary concentrations were available: cadmium, chromium, cobalt, copper, manganese, nickel, and zinc. Principal component analysis was used to extract three components from natural log transformed creatinine-corrected metal concentrations. Of the 45 women, 17 reported more than one main task. Overall two thirds worked in fabrication, a third on pipe welding, and smaller numbers on repair, in construction or other tasks: manual metal arc welding was reported by 62%, semi-automatic arc welding by 47%, and arc welding with a tungsten electrode by 15%. In multiple regression analyses, little relation was found between urinary metals and task or type of welding, except for cadmium where lower levels were seen in those reporting semi-automatic manual welding (after adjustment for age and smoking). The proportion of women welders exceeding the selected general population 95th percentile was high for manganese (96%) and chromium (29%). Urinary metal concentrations were similar to those reported for male welders with only manganese, with a geometric mean in women of 1.91 µg g(-1) creatinine, and perhaps copper (11.8 µg g(-1) creatinine), consistently lower in male welders. Although not evident from the task analysis reported here, differences in exposure by sex may be explained by type of welding or by other work practices. A closely comparable cohort of male welders would be necessary to examine this hypothesis more fully.

Biomarkers of manganese exposure in pregnant women and children living in an agricultural community in California.

Manganese (Mn) is an essential nutrient but at high exposure levels is a neurotoxicant. There is no well-validated biomarker to assess perinatal Mn exposure. A total of 75 mother-child pairs provided blood, urine, and/or deciduous tooth samples. We analyzed Mn in dentin and enamel of shed teeth; maternal, cord, and child blood; and maternal and child urine and examined the interrelationships of Mn levels in all matrices. We observed higher Mn levels in prenatal than postnatal dentin (geometric mean (GM) = 0.51 vs 0.16 Mn:Ca, p < 0.001), maternal blood at delivery than 26 weeks gestation (GM = 20.7 vs. 14.6 µg/L, p = 0.001), and cord blood than child blood at 24 months of age (39.9 vs 25.0 µg/L, p = 0.005). There were no significant correlations between Mn in dentin and Mn concentrations in maternal blood or maternal or child urine. Levels of Mn in prenatal dentin, prenatal maternal blood, and 24 month urine were higher (p < 0.05) among mothers and children living with a farm worker. Prenatal Mn levels in dentin were correlated with Mn loadings and concentrations in prenatal house dust. Levels of Mn measured in tooth dentin constitute a promising biomarker of perinatal exposure.

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.

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.

Urine manganese, cadmium, lead, arsenic, and selenium among autism spectrum disorder children in Kuala Lumpur.

Background: The development of autism spectrum disorder (ASD) may stem from exposure to environmental pollutants such as heavy metals. The primary objective of this study is to determine the role of heavy metals of concern such as manganese (Mn), cadmium (Cd), lead (Pb), arsenic (As), and essential trace element selenium (Se) among ASD children in Kuala Lumpur, Malaysia. Method: A total of 155 preschoolers in Kuala Lumpur between the ages 3 to 6 participated in an unmatched case-control study, comprising ASD children (n = 81) recruited from an early intervention program for autism, and 74 children without autism who were recruited from public preschools. Urine samples were collected at home, delivered to the study site, and transported to the environmental lab within 24 hours. Inductively coupled plasma mass spectrometry (ICP-MS) was applied to measure the concentration of heavy metals in the samples. Data were analysed using bivariate statistical tests (Chi-square and T-test) and logistic regression models. Result: This study demonstrated that Cd, Pb, and As urine levels were significantly greater in children without autism relative to those affected with ASD (p < 0.05). No significant difference was in the levels of Se (p = 0.659) and Mn (p = 0.875) between children with ASD and the control group. The majority of children in both groups have urine As, Pb, and Cd values lower than 15.1 µg/dL, 1.0 µg/dL, and 1.0 µg/dL, respectively which are the minimal risk values for noncarcinogenic detrimental human health effect due to the heavy metal's exposure . Factors associated with having an ASD child included being a firstborn, male, and higher parental education levels (adjusted odds ratios (aOR) > 1, p < 0.05). Conclusion: Preschoolers in this study demonstrated low levels of heavy metals in their urine samples, which was relatively lower in ASD children compared to the healthy matched controls. These findings may arise from the diminished capacity to excrete heavy metals, especially among ASD children, thereby causing further accumulation of heavy metals in the body. These findings, including the factors associated with having an ASD child, may be considered by healthcare professionals involved in child development care, for early ASD detection. Further assessment of heavy metals among ASD children in the country and interventional studies to develop effective methods of addressing exposure to heavy metals will be beneficial for future reference.