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Occupational manganese (Mn) exposure has been associated with cognitive and olfactory dysfunction; however, few studies have incorporated cumulative biomarkers of Mn exposure such as bone Mn (BnMn). Our goal was to assess the cross-sectional association between BnMn, blood Mn (BMn), and fingernail Mn (FMn) with cognitive and olfactory function among Mn-exposed workers. A transportable in vivo neutron activation analysis (IVNAA) system was designed and utilized to assess BnMn among 60 Chinese workers. BMn and FMn were measured using inductively coupled plasma mass spectrometry. Cognitive and olfactory function was assessed using Animal and Fruit Naming tests, World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test (AVLT) and the University of Pennsylvania Smell Identification Test (UPSIT). Additional data were obtained via questionnaire. Regression models adjusted for age, education, factory of employment, and smoking status (UPSIT only), were used to assess the relationship between Mn biomarkers and test scores. In adjusted models, increasing BnMn was significantly associated with decreased performance on average AVLT scores [β (95% confidence interval (CI)) = -0.65 (-1.21, -0.09)] and Animal Naming scores [β (95% CI) = -1.54 (-3.00, -0.07)]. Increasing FMn was significantly associated with reduced performance measured by the average AVLT [β (95% CI) = -0.35 (-0.70, -0.006)] and the difference in AVLT scores [β (95% CI) = -0.40 (-0.77, -0.03)]. BMn was not significantly associated with any test scores; no significant associations were observed with Fruit Naming or UPSIT tests. BnMn and FMn, but not BMn, are associated with cognitive function in Mn-exposed workers. None of the biomarkers were significantly associated with olfactory function., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Airborne exposure to manganese (Mn) can result in neurologic effects. Stationary air sampling is the traditional technique to assess Mn exposure for communities, yet may not accurately reflect children's personal exposure. The goal of the study was to characterize personal exposure to Mn and PM(2.5) in a cohort of children ages 7-9 years residing near a ferromanganese refinery. A subset of children living in non-smoking households ages 7-9 enrolled in the Marietta Community Actively Researching Exposure Study during March-June 2009 and 2010 were invited to participate. Blood and hair were collected and analyzed for Mn. Participants wore a PM(2.5) sampler (Personal Modular Impactor) for 48 h. TWD was based on time spent at home and school and the distance of each from the refinery. Stationary outdoor air sampling was conducted 8 km from the refinery using a Harvard-type PM(2.5) impactor. The relationship between personal Mn exposure and TWD was examined by multiple regression adjusting for stationary air Mn concentration, wind speed and direction, and precipitation. Complete personal air sampling data were collected on 38 children. TWD ranged from 4.7 km to 28.5 km with a mean distance of 11.1 (4.7 sd) km. Mn concentration in personal air samples ranged from 1.5 ng/m3 to 54.5 ng/m3 (geometric mean, 8.1 ng/m3). TWD was a significant predictor of natural log personal air Mn concentration (lnMn) with an associated decrease of 0.075 lnMn for each km TWD (p<0.05, 95% CI -0.13 to -0.01). Personal Mn exposures were positively associated with stationary air Mn levels and inversely associated with wind speed. A child's location (home and school) relative to the refinery is a significant predictor of personal Mn exposure. Wind speed is also an important contributor to personal Mn exposure., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The International Commission on Radiological Protection (ICRP) is updating its biokinetic models used to derive dose coefficients and assess bioassay data for intake of radionuclides. This paper reviews biokinetic data for manganese and proposes a biokinetic model for systemic manganese in adult humans. The proposed model provides a more detailed and physiologically meaningful description of the behavior of absorbed manganese in the body than the current ICRP model. The proposed model and current ICRP model yield broadly similar estimates of dose per unit activity of inhaled or ingested radio-manganese but differ substantially with regard to interpretation of bioassay data. The model is intended primarily for use in radiation protection but can also serve as a baseline model for evaluation of potentially excessive intakes of stable manganese in occupational settings., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Despite the toxicity and widespread use of manganese (Mn) and lead (Pb) as additives to motor fuels and for other purposes, information regarding human exposure in Africa is very limited. This study investigates the environmental exposures of Mn and Pb in Durban, South Africa, a region that has utilized both metals in gasoline. Airborne metals were sampled as PM(2.5) and PM(10) at three sites, and blood samples were obtained from a population-based sample of 408 school children attending seven schools. In PM(2.5), Mn and Pb concentrations averaged 17±27 ng m(-3) and 77±91 ng m(-3), respectively; Mn concentrations in PM(10) were higher (49±44 ng m(-3)). In blood, Mn concentrations averaged 10.1±3.4 μg L(-1) and 8% of children exceeded 15 μg L(-1), the normal range. Mn concentrations fit a lognormal distribution. Heavier and Indian children had elevated levels. Pb in blood averaged 5.3±2.1 μg dL(-1), and 3.4% of children exceeded 10 μg dL(-1), the guideline level. Pb levels were best fit by a mixed (extreme value) distribution, and boys and children living in industrialized areas of Durban had elevated levels. Although airborne Mn and Pb concentrations were correlated, blood levels were not. A trend analysis shows dramatic decreases of Pb levels in air and children's blood in South Africa, although a sizable fraction of children still exceeds guideline levels. The study's findings suggest that while vehicle exhaust may contribute to exposures of both metals, other sources currently dominate Pb exposures., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Heavy metal contamination from occupational origin is a cause for concern because of its potential accumulation in the environment and in living organisms leading to long term toxic effects. This study was aimed to assess Cd, Cr, Mn, Ni and Pb levels in whole blood, urine, axillary hair and saliva from 178 individuals with occupational exposure to heavy metals. Levels of metal compounds were determined by atomic absorption spectrometry. We collected information on occupation, lifestyle habits and food intake by questionnaire. Multiple linear regression analyses for metal ion concentration in whole blood, urine, axillary hair and saliva were adjusted for age, gender, smoking and alcohol consumption, lifetime workplace exposure, residence area and food habits. Overall, blood and urine median concentrations found for the five metals analyzed do not exceed biological exposure indexes, so that they are very similar to a non-occupationally exposed population. Toxicokinetic differences may account for the lack of correlations found for metal levels in hair and saliva with those in blood or urine. For those heavy metals showing higher median levels in blood with respect to hair (Cd, Mn and Pb) indicating lesser hair incorporation from blood, the lifetime working experience was inversely correlated with their hair levels. The longer the lifetime working experience in industrial environments, the higher the Mn and Ni concentration in saliva. Axillary hair and saliva may be used as additional and/or alternative samples to blood or urine for biomonitoring hair Mn, and saliva Ni in subjects with occupational exposure., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The extent of children's exposure to multiple toxic metals is not well described in many developing countries. We examined metal exposures in young children (6-37 months) from Montevideo, Uruguay and their mothers (15-47 years) participating in a community-based study. Hair samples collected from 180 children and their mothers were analyzed for: lead (Pb), cadmium (Cd), manganese (Mn), and arsenic (As) concentration using inductively coupled plasma-mass spectrometry (ICP-MS). Median metal levels (microg/g) were: Pb 13.69, Mn 1.45, Cd 0.17, and As 0.09 for children and Pb 4.27, Mn 1.42, Cd 0.08, and As 0.02 for mothers. Of the child and maternal samples, 1.7% and 2.9% were below the limit of detection (LOD) for Cd, and 21.3% and 38.5% were below the LOD for As, respectively. Correlations between maternal and child levels ranged 0.38-0.55 (p<0.01). Maternal hair metal levels were the strongest predictors of metal concentrations in children's hair. Girls had significantly lower As levels than boys (p<0.01) but did not differ on other metals. In addition, in bivariate logistic regressions predicting the likelihood that the child would be exposed to multiple metals, hemoglobin <10.5 g/dL (OR=2.12, p<0.05), blood lead (OR=1.17, p<0.01), and the mother being exposed to two or more metals (OR=3.34, p<0.01) were identified as significant predictors of increased likelihood of multiple metal exposure. Older child age (OR=0.96, p<0.05), higher maternal education (OR=0.35, p<0.01), and higher number of household possessions (OR=0.83, p<0.01) were significantly associated with decreased likelihood of multiple metal exposure. Preschool children in Uruguay are exposed to multiple metals at levels that in other studies have been associated with cognitive and behavioral deficits. Sources of exposure, as well as cognitive and behavioral consequences of multiple metal exposure, should be investigated in this population., (Copyright 2010 Elsevier B.V. All rights reserved.)

Copper, manganese and selenium are elements involved in protecting the body against oxidative stress. Determining their plasma level may contribute to assessing the health and nutritional status of populations. The aim of this study was to assess factors influencing copper, manganese and selenium plasma levels in an adult Mediterranean population and to identify groups at risk of deficiency. A cross-sectional survey was carried out in Andalusia, a region in southern Spain. Blood samples were obtained in a random subsample of 340 subjects. Food consumption was assessed by 48-h recall. Height, weight, skinfolds, waist and hip circumferences were measured. Copper, manganese and selenium were measured in plasma. Information about physical exercise, educational level, alcohol and smoking habits was obtained with a structured questionnaire. Plasma copper was found to be higher in women than among men. Hypocupraemia was found in 4.4% of the population, while 9.7% presented hypomanganesemia. Moreover, 86.5% presented plasma selenium values below 125microg/L (cutoff for optimal glutathione peroxidase activity). No association was found between plasma elements, anthropometric indices and lifestyle factors; there were tendencies, no more. Copper tended to decrease in obese and increase in sedentary, while selenium tended to decrease among smokers. Plasma Cu was positively correlated with the consumption of monounsaturated and polyunsaturated fats. Plasma Mn was directly correlated with the consumption of dairy products. Levels of Se were positively correlated with age, the consumption of fruit, vegetables, energy obtained from carbohydrates, and the consumption of fibre, and inversely correlated with the consumption of meat and sweets. Our results provide an estimate of the copper, manganese and selenium status in the adult population of southern Spain. The correlations found for Se suggest that there is a tendency for Se levels to be better maintained among the population that shows a stronger preference for the traditional diet., (Copyright 2009 Elsevier B.V. All rights reserved.)

Monitoring the nutritional status of essential elements and assessing exposure of individuals to toxic elements is of great importance for human health. Thus, the appropriate selection and measurement of biomarkers of internal dose is of critical importance. Due to their many advantages, hair samples have been widely used to assess human exposure to different contaminants. However, the validity of this biomarker in evaluating the level of trace elements in the human body is debatable. In the present study, we evaluated the relationship between levels of trace elements in hair and whole blood or plasma in a Brazilian population. Hair, blood and plasma were collected from 280 adult volunteers for metal determination. An ICP-MS was used for sample analysis. Manganese, copper, lead and strontium levels in blood varied from 5.1 to 14.7, from 494.8 to 2383.8, from 5.9 to 330.1 and from 11.6 to 87.3 microg/L, respectively. Corresponding levels in hair varied from 0.05 to 6.71, from 0.02 to 37.59, from 0.02 to 30.63 and from 0.9 to 12.6 microg/g. Trace element levels in plasma varied from 0.07 to 8.62, from 118.2 to 1577.7 and from 2.31 to 34.2 microg/L for Mn, Cu and Sr, respectively. There was a weak correlation (r=0.22, p<0.001) between lead levels in hair and blood. Moreover, copper and strontium levels in blood correlate with those levels in plasma (r=0.64 , p<0.001 for Cu) and (r=0.22, p<0.05 for Sr). However, for Cu, Mn and Sr there was no correlation between levels in hair and blood. Our findings suggest that while the idea of measuring trace elements in hair is attractive, hair is not an appropriate biomarker for evaluating Cu, Mn and Sr deficiency or Pb exposure.

Previous research has suggested that heavy metals may be ototoxic in humans, and further, that a reversal of this toxicity may occur when the trace element selenium is present, through formation of metals selenide complexes. This study investigates the relationship between hearing thresholds and blood concentrations of four elements (selenium, lead, manganese, and arsenic) in factory workers, Taiwan. We conducted a hospital-based case-control study with 294 individuals who received the periodic occupational health examination in the Kaohsiung Medical University Hospital. All control subjects (n=173) had normal hearing. Case subjects (n=121) had average hearing threshold over 25 decibels (dB). In all individuals, blood concentrations of lead (Pb), manganese (Mn), arsenic (As), and selenium (Se) were determined by an ICP-MS and standard methods. Possible confounding factors were collected by a questionnaire and medical history reviews. Relationships were analyzed by multiple linear regressions and mixed model. Geometric means of Pb, Mn, As, and Se were determined for case subjects (107.2, 5.5, 17.8, and 229.1 microg/L) and controls (38.9, 5.4, 15.5, and 234.4 microg/L). In our regression models, age, lead and selenium concentrations (logarithmic transformed) were associated significantly with hearing thresholds. In addition, we found that the selenium was inversely associated with hearing thresholds, and may be an antagonist to lead ototoxicty. The present study demonstrated a dose-response relationship between blood lead and hearing thresholds, after adjusting other potential confounders in multiple regressions. In addition, we found that selenium may be a protection element on auditory function. However, additional studies will be needed to clarify the mechanisms of lead toxicity and selenium on the hearing function in molecular and genetic levels.

Overexposure to manganese (Mn) causes neurotoxicity (a Parkinson-like syndrome) or psychiatric damage ("manganese madness"). Several studies have shown alterations to motor and neural behavior associated with exposure to Mn in the workplace. However, there are few studies on the effects of environmental exposure of whole populations. We studied the risk of motor alterations in people living in a mining district in Mexico. We studied 288 individual people (168 women and 120 men) from eight communities at various distances from manganese extraction or processing facilities in the district of Molango. We measured manganese concentrations in airborne particles, water, soil and crops and evaluated the possible routes of Mn exposure. We also took samples of people's blood and determined their concentrations of Mn and lead (Pb). We used "Esquema de Diagnóstico Neuropsicológico" Ardila and Ostrosky-Solís's neuropsychological battery to evaluate motor functions. Concentrations of Mn in drinking water and maize grain were less than detection limits at most sampling sites. Manganese extractable by DTPA in soils ranged between 6 and 280 mg kg(-1) and means were largest close to Mn extraction or processing facilities. Air Mn concentration ranged between 0.003 and 5.86 microg/m(3); the mean value was 0.42 microg/m(3) and median was 0.10 microg/m(3), the average value (geometric mean) resulted to be 0.13 microg/m(3). Mean blood manganese concentration was 10.16 microg/l, and geometric mean 9.44 microg/l, ranged between 5.0 and 31.0 mcrog/l. We found no association between concentrations of Mn in blood and motor tests. There was a statistically significant association between Mn concentrations in air and motor tests that assessed the coordination of two movements (OR 3.69; 95% CI 0.9, 15.13) and position changes in hand movements (OR 3.09; CI 95% 1.07, 8.92). An association with tests evaluating conflictive reactions (task that explores verbal regulations of movements) was also found (OR 2.30; CI 95% 1.00, 5.28). It seems from our results that people living close to the manganese mines and processing plants suffer from an incipient motor deficit, as a result of their inhaling manganese-rich dust.

Unlabelled: Manganese (Mn) is widely distributed in the biosphere but occurs in only trace amounts in animal tissues. Although Mn deficiency and toxicity both have pathological consequences, the underlying biochemical lesions have not been well defined. In vitro studies suggest that transport proteins are affected by Mn, lead (Pb), and selenium (Se). Among these transport proteins, the calmodulin-regulated calcium pump (Ca(2+)Mg(2+)ATPase) could be inhibited by Mn. In order to understand Mn biochemical pathways, we examined the relationships between Mn blood levels and red blood cell Ca-pump activity among 248 mothers and newborns, environmentally exposed to Mn, Pb, and Se., Population and Methods: 248 mother-newborn pairs were recruited at Robert Debré University Hospital (Paris). Blood Mn and Pb concentrations were measured by absorption spectrophotometry. Se was measured by fluorometric method. Red blood cell membrane suspensions were obtained for Ca-pump activity measurements. Linear and quadratic regression models and Pearson correlation were performed., Results: A non-linear parabolic relationship between maternal Mn blood levels and newborn Ca-pump activity was discovered from the analysis of the observed data. The peak level of maternal Mn that corresponded to a maximal activity of the newborn Ca-pump was estimated at 23.9 microg/l with a 95% confidence interval of 17.6 to 32.4 microg/l. An inhibition of this enzyme was observed at low and high levels of maternal Mn. The relationships between the newborn Ca-pump activity and maternal Se and Pb levels became non-significant after adjustment on all the co-factors included in the final model., Conclusion: Maternal environmental exposure to Mn, as reflected by maternal blood levels of this metal, is associated with a reduced activity of newborn erythrocyte Ca-pump in a non-linear pattern. Mn levels between 17.6 and 32.4 microg/l in maternal blood probably correspond to the optimal physiological concentration for the metabolism of this enzyme in newborns.

Manganese (Mn) and lead (Pb) are two neurotoxic chemicals and experimental evidence suggests that they can cross the placental barrier. Tetraethyl lead was still in use as an antiknock agent in Paris during the sampling period of the study, while it has been replaced by methylcyclopentadienyl manganese tricarbonyl (MMT) in Canada since 1977. By 1990, MMT was in 100% of gasoline in Canada. In a study of 160 pairs of mothers-neonates in Montreal and 206 pairs in Paris, we compared levels of Mn and Pb in the umbilical cord and in maternal blood. Neonates and mothers had significantly higher Pb levels in Paris where lead additives were still used in gasoline. Geometric mean maternal blood Pb levels were 5.4 microg/dl compared to 2.1 microg/dl in Montreal and cord blood Pb levels were 3.2 microg/dl in Parisian mothers compared to 1.7 microg/dl in Montreal. The prevalence of Paris Pb values superior to the 95th percentile of the Montreal distribution was highly elevated in all media studied. The prevalence of high Mn levels in umbilical cord blood was also significantly higher in Montreal. Surveillance programs are important to limit Pb overexposure and associated neurological effects in neonates where tetraethyl Pb is still in use as a gasoline additive. Since Mn is an essential element and dietary Mn intake may differ between Montreal and Paris, the difference observed with regard to high Mn values between Montreal and Paris cannot, at this time, be attributed to MMT in Montreal's gasoline. Further studies are needed to infer an association between Mn emissions from MMT and prenatal exposure to Mn.

Serum manganese levels were determined in 250 healthy subjects (122 men and 128 women) living in Barcelona in northeastern Spain. The study was designed to assess the reference levels for serum manganese and to investigate its relationship to age and sex. The age distribution ranged from 15 to 90 years. The assays were performed by means of a graphite furnace atomic absorption spectrometry. The geometric mean of serum manganese concentration was 1.1 microg/l, ranging from 0.3 microg/l to 2.5 microg/l. In almost every case, the 95th upper percentiles of this element were < 1.8 microg/l. No correlation between the concentration of manganese and sex could be established, but in the younger population the manganese levels were nearly three times higher than the results obtained in the older population.

This study is part of the EURO-TERVIHT project (Trace Element Reference Values in Human Tissues) which aims at establishing reference intervals for trace elements in blood, urine and other human tissues. In this study reference intervals (0.05-0.95 fractiles) were estimated for lead in blood (105-529 nmol/l for men, 80-340 nmol/l for women), manganese in blood (100-271 nmol/l) and arsenic in urine (36-541 nmol/l for men, 21-475 nmol/l for women). Upper reference limits (0.95 fractile) were established for chromium in urine (13 nmol/l), nickel in urine (52 nmol/l) and cobalt in urine (23 nmol/l for men, 31 nmol/l for women). The reference group was a Danish subpopulation (n = 189), age 40-70 years. The influence of gender, age, health status parameters, nutrition and various lifestyle factors was investigated. Urinary arsenic and blood lead levels were found to be higher for men than for women. Arsenic levels also increased with age up to 60 years, and then decreased. Alcohol intake lead to increased arsenic levels in urine as well as blood lead levels. Urinary nickel levels were higher in persons frequently eating porridge and porridge oats.

The results of the present epidemiological study among 141 workers (mean age: 34 years) from a Mn salts and oxides producing plant in Belgium suggest that preclinical perturbations (lung function, CNS, biological parameters) may occur in subjects exposed to airborne Mn levels (7 years on the average) usually lower (total dust, geometric mean about 1 mg/m3, 95th percentile 3.3 mg/m3) than the levels actually (5 mg/m3) tolerated.

The use of scalp hair to monitor manganese was studied as part of an investigation of manganese intoxication amongst a group of Aborigines living on manganese-rich soil on Groote Eylandt, in the Northern Territory of Australia. High scalp-hair manganese values were due largely to manganese from exogenous sources. Manganese (IV) dioxide in dust, trapped in hair, was reduced by the components of sweat, leading to the diffusion of manganese (II) into the hair shaft. At least 15 micrograms Mn g-1 hair could be incorporated into hair via this exogenous route. To overcome the problems of manganese contamination, the ability of a number of leaching agents to remove exogenous manganese selectively from hair was tested. Measurements of manganese along the length of hair strands were extrapolated back to zero length to estimate the amount of manganese in the hair as it emerged from the scalp. Using this extrapolation technique, Aborigines on Groote Eylandt had a mean scalp-hair manganese of 16 ppm. Aborigines in non-manganese areas had 2 ppm manganese in hair. Caucasians living in the same manganese-rich area had 2.5 ppm manganese in hair, compared to 0.5 ppm manganese in non-manganese areas. Measurements of manganese in hair and blood of Groote Eylandt Aborigines showed that the population had a high exposure to manganese, but did not distinguish between those individuals affected/unaffected by the neurological condition, Groote Eylandt Syndrome.