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Factores Inmunológicos , Pénfigo , Rituximab , Pénfigo/tratamiento farmacológico , Pénfigo/patología , Humanos , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Resultado del Tratamiento , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , AdultoRESUMEN
Kidney dysfunction is increasing worldwide and is exacerbated by exposure to toxic metals. Also, pregnancy poses an overload on kidney function. We investigated how blood lead (PbB) and cadmium (CdB) levels were associated with kidney function in pregnant women from Recôncavo Baiano, Brazil, during their second trimester. In this cross-sectional study, the estimated glomerular filtration rate (eGFR) was calculated from serum creatinine and whole blood metal levels were measured by graphite furnace atomic absorption spectrophotometry in 136 volunteers. Sociodemographic data were collected using semi-structured questionnaires. The medians (IQR) of PbB, CdB, and eGFR were 0.85 µg/dL (0.45-1.75), 0.55 µg/L (0.08-0.91), and 121.8 mL/min/1.73 m2 (106.0-127.9), respectively. PbB medians were significantly higher in the eGFR < 90 group at 2.00 µg/dL (0.83, 3.10). After age-adjusted logistic regression, pregnant women with elevated PbB levels had decreased eGFR (OR = 1.82; 95%-CI, 1.14-3.14). However, the participants with elevated PbB levels who reported consuming alcohol during pregnancy or had CdB in the highest tertile had higher odds of reduced eGFR (OR = 2.44; 95%-CI, 1.30-5.47) and (OR = 11.22; 95% CI, 2.53-103.51), respectively. These results suggest that low Pb exposure may affect kidney function in pregnant women and calls for further investigation into toxic metal co-exposures on kidney function during pregnancy in at-risk communities.
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Prenatal exposure to potentially toxic metals (PTM) may impair fetal growth (FG). We investigated the relationship between maternal exposure to lead (Pb), cadmium (Cd) and manganese (Mn) and birth weight (BW) of 74 newborns. Blood was collected during the second trimester of pregnancy to determine Pb (PbB) and Cd (CdB), while hair (MnH) and toenails (MnTn) were used for Mn. Samples were analyzed by graphite furnace atomic absorption spectrophotometry (GFAAS). Sociodemographic and BW data were collected from questionnaires and maternity records, respectively. The medians (P25th-P75th) of PbB, CdB, MnH, and MnTn were, respectively, 0.9 (0.5-1.8) µg/dL; 0.54 (0.1-0.8) µg/L; 0.18 (0.1-0.4) µg/g; and 0.65 (0.37-1.22) µg/g. The means (standard deviation) of birth weight according to sex were 3067 (426.3) and 3442 (431) grams, respectively, for girls and boys. MnTn presented an inverse correlation with the BW/gestational age ratio for girls (rho = -0.478; p = 0.018), suggesting the effect of sex modification. Although BW correlation with CdB was not statistically significant, hierarchical linear regression (beta = -2.08; 95% CI-4.58 to 0.41) suggested a fetotoxic effect. These results confirmed the threat PTMs may represent and the need for more extensive research to elucidate their role in inadequate FG in developing countries.
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Exposición a Riesgos Ambientales , Exposición Materna , Masculino , Humanos , Recién Nacido , Femenino , Embarazo , Exposición Materna/efectos adversos , Exposición a Riesgos Ambientales/análisis , Peso al Nacer , Plomo/toxicidad , Cohorte de Nacimiento , Brasil/epidemiología , Cadmio/toxicidad , Manganeso , Intoxicación por Metales PesadosRESUMEN
Exposure to potentially toxic metals (PTM) threatens maternal and child health. We investigated the determinants of exposure to lead (Pb), cadmium (Cd), arsenic (As), and manganese (Mn) in 163 pregnant women from the Recôncavo Baiano, Brazil, enrolled in the DSAN-12M cohort. We measured these metals in biological samples (blood, toenails, and hair) and the Pb dust loading rates (RtPb) at their homes by graphite furnace atomic absorption spectrophotometry (GFAAS). Questionnaires were applied to collect sociodemographic and general habits data. Only 2.91% (n = 4) of the pregnant women had As levels above the detection limit. Few participants had levels above the recommended reference values for blood Pb (5.1; 95% CI: 2.1-10.1%), and Mn in hair or toenails (4.3; 95% CI: 2.3-10.1%). On the other hand, 61.1 (95% CI: 52.4-69.3%) had elevated blood Cd levels. After binary logistic regression, low socioeconomic status, domestic waste burning, being a passive smoker, multiparity, and renovating the house significantly increased the chances of having high levels of Mn, Pb, and Cd. We detected a worrying situation related to exposure to Cd, showing the urgency of implementing human biomonitoring in the general population, especially in situations of social vulnerability.
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Arsénico , Metales Pesados , Niño , Humanos , Femenino , Embarazo , Cadmio , Plomo , Mujeres Embarazadas , Brasil , Manganeso , Intoxicación por Metales Pesados , Metales Pesados/toxicidadRESUMEN
Neuropsychological alterations have been identified in populations heavily exposed to metals with neurotoxic potential, such as manganese (Mn). This study examined the associations between Mn environmental exposure in school-aged children and executive functions, using structural equation modeling. Children, aged between 7 and 12 years (N = 181), were recruited from four elementary schools located in a region that is under the influence of atmospheric emissions from a ferro-manganese alloy plant in the municipality of Simões Filho, Bahia, Brazil. The following cognitive functions were evaluated: Intelligence, Inhibitory Control, Cognitive Flexibility, Verbal and Design Fluency, Verbal and Visual Working Memory and Attention. We performed structural equation modeling to identify the following executive functions latent variables: working memory, inhibitory control and cognitive flexibility. We further analyzed the relations between executive functions and Mn measured in hair (MnH) and toenails (MnTn) with linear mixed models, after controlling for co-variables. A positive effect at the individual level on working memory, inhibition control and cognitive flexibility was observed with MnTn after controlling for co-variables, but no association was found with MnH levels. However, children attending school most environmentally exposed to Mn emissions, which had the highest rate of Mn dust deposition, had the poorest scores on working memory. These findings suggest both benefits and risk of Mn on children's cognitive development.
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Función Ejecutiva , Manganeso , Niño , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Humanos , Iones/análisis , Iones/farmacología , Manganeso/análisis , Manganeso/toxicidad , Memoria a Corto Plazo , Análisis MultinivelRESUMEN
Delta-aminolevulinic acid dehydratase (ALAD) enzyme catalyzes the second phase of the heme biosynthesis and is involved in lead toxicokinetics. This research aimed to evaluate its influence on the relationship between blood lead (PbB) levels and intellectual performance in Afro-Brazilian children. PbB, hemoglobin concentration, ALAD activity, and polymorphism were determined in whole blood. Anthropometric, socioeconomic, and family environment stimuli data were collected with appropriate instruments. The non-verbal intelligence of children and their mothers or guardians was assessed using the correspondent Raven's Progressive Matrix versions. The medians (range) of PbB levels and ALAD activity were 1.0 µg/dL (0.1-21.3) and, 71 U/L (31-113), respectively. ALAD G177C was distributed as follows: 97.9% for ALAD1/1 and 2.1% for ALAD1/2 genotypes. The mean of Raven raw score was 19.3 (± 5.6) points and there were no differences according to sex or environmental Pb exposure. No statistically significant association was observed between PbB level and children's IQ. However, ALAD activity presented an inverse significant association with PbB levels, children's percentile IQ, and children's IQ/Age ratio, suggesting a neuroprotective role of ALAD1 genotype in those with low PbB level.
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Inteligencia , Plomo , Porfobilinógeno Sintasa , Factores Sociales , Brasil , Niño , Exposición a Riesgos Ambientales , Etnicidad , Genotipo , Humanos , Plomo/sangre , Porfobilinógeno Sintasa/genéticaRESUMEN
OBJECTIVE: Assess cadmium (Cd) exposure of adults living in two estuarine communities in Aratu bay, Bahia, Brazil and its association with effects on renal function. METHODS: This cross-sectional study included 88 volunteers aged 17-55 years, living in the following two communities: Santa Luzia (SL) located more intimately in the bay and Cotegipe (CT), a bit further and closer to a ferro-manganese alloy plant. Cd in blood (CdB) and urine (CdU), along with blood lead (PbB) levels were determined by graphite furnace atomic absorption spectrometry. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) and tubular cell biomarkers: retinol binding protein (RBP), ß2-microglobulin (ß2M), and N-acetyl-ß-D-glucosaminidase (NAG). RESULTS: The median CdU levels in villagers of the two communities were 0.20 and 0.44 µg/g creat. and SL vs CT, respectively. Age range (> 35 years), cigarette smoking and lower family income were significantly associated with more elevated CdU levels. Multiple linear regression analysis demonstrated a significant association between LnCdU and LnRBP levels (ß = 0.200, 95%CI 0.074-0.365) after adjusted for sex, urinary creatinine and blood lead levels. CONCLUSION: These data show consistent evidences of association between Cd exposure and elevated tubular cell biomarker excretion in estuarine villagers living close to an industrial site.
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Cadmio , Plomo , Acetilglucosaminidasa/metabolismo , Adolescente , Adulto , Biomarcadores/orina , Cadmio/efectos adversos , Cadmio/sangre , Cadmio/orina , Intoxicación por Cadmio , Estudios Transversales , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Femenino , Humanos , Riñón/química , Riñón/metabolismo , Plomo/análisis , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Lead (Pb) is used as a flux in the glazing process of pottery utensils in several regions of the world. It can affect the nervous and hematopoietic systems; in addition, it is classified as a probable human carcinogen. This work aims to evaluate Pb exposure of potters and describe the main determinants of elevated blood Pb (PbB) levels in this group of workers. METHODS: This is a cross-sectional study with potters of Maragogipinho Village, Bahia, Brazil, of both sexes, aged 16-72 years (n = 85). Non-exposed workers of the same age range residing in the urban area of Aratuípe town were also recruited (n = 50). We evaluated Pb dust deposition rates (PbDrt) in pottery workshops and PbB levels. All Pb measurements were performed by Graphite Furnace Atomic Absorption Spectrometry. RESULTS: The median of PbB (min-max) and geometric mean (SD) PbDrt for the exposed group were 7.9 (0.9-49.8) µg/dL and 1463 (± 290,000) µg/m2/30 days, respectively. For the control group, levels were 1.5 (0.1-19.8) µg/dL and 82 (46) µg/m2 30 days, respectively. CONCLUSION: The data found showed an excessive exposure among artisans, exceeding occupationally safe levels and those reported in the literature. It is important to implement occupational hygiene measures and improvements of the working conditions of these labors, especially the replacement of lead oxide in the pottery-glazing process.
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Cerámica , Polvo/análisis , Plomo/análisis , Exposición Profesional/análisis , Adolescente , Adulto , Anciano , Brasil , Estudios Transversales , Monitoreo del Ambiente , Femenino , Humanos , Plomo/sangre , Masculino , Persona de Mediana Edad , Factores de Riesgo , Adulto JovenRESUMEN
Lead (Pb) exposure compromises heme synthesis by inhibiting ferrochelatase, forming zinc-protoporphyrin (ZnPP). This study aims to validate a method for the determination of ZnPP by HPLC with fluorescence detection and apply this method to evaluate the extent of Pb exposure of artisanal pottery workers. Extraction procedures were tested using both nonacid and acid liquid-liquid extraction. The former presented a better chromatogram and recovery results. The validated method yielded a good resolution of ZnPP and its free form peaks with acceptable precision and accuracy. Total run time was 15 min and ZnPP peak retention time was 5.6 min. We applied this method to evaluate 39 potters (90% male), mean age 40 years (9-80). The medians (ranges) of blood lead, ZnPP and hemoglobin were 16.0 µg/dl (2.2-71.5), 12.6 µg/dl (4.6-279.8) and 15.1 g/dl (11.0-17.8), respectively. Significant differences were observed for blood lead according to gender, age range (>40 years), direct handling of lead oxide and years of occupation. Significantly higher levels of ZnPP were observed in male potters involved with lead glazing activity. The validated method was shown to be simple with one-step nonacid extraction, good sensitivity, reproducibility and accuracy. Our data shows that these laborers are dangerously exposed to Pb, reflecting the effect on the heme synthesis.
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Cromatografía Líquida de Alta Presión/métodos , Plomo/sangre , Exposición Profesional/análisis , Protoporfirinas/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Niño , Femenino , Hemoglobinas/análisis , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Fluorescencia , Adulto JovenRESUMEN
Brazilian raw propolis samples (brown, green, red, and yellow) were investigated to evaluate the content of three elements of nutritional value (Cu, K, and Se) and three toxic metals (As, Cd, and Pb). The propolis samples (n = 19) were obtained from different regions of Brazil and analysed by atomic absorption spectrometry after microwave-assisted digestion. A descriptive analysis of the variables was carried out, and nonparametric tests (Kruskal-Wallis or Mann-Whitney) were performed to verify the differences in metal contents. The elemental concentrations of the Brazilian propolis were in the following ranges: As < 0.048-8.47 µg·g-1, Pb < 0.006-0.72 µg·g-1, Cu 0.57-11.60 µg·g-1, Se < 0.041-0.54 µg·g-1, and K 0.23-7.94 mg·g-1; Cd was below LOD (0.008 µg·g-1) in all samples, except one. Seven samples exceeded the limits defined for As or Pb by the Brazilian regulation.
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Metales Pesados/análisis , Evaluación Nutricional , Própolis/análisis , Própolis/química , Brasil , Análisis de los Alimentos , Contaminación de AlimentosRESUMEN
This study aimed to evaluate the exposure to environmental lead (Pb) of children from a traditional community of African descent in Brazil and the effects on hematological parameters. Children (n = 75) aged 5.5-13 years from the exposed areas classified as low (LEx) and moderately (MEx) exposed were compared with children (n = 75) of a control group (CG). Dust Pb loading rates (RtPbs) at children's homes were measured. Peripheral venous blood samples were collected to assess Pb biomarkers of exposure and effects. All Pb determinations were performed by graphite furnace atomic absorption spectrometry. The median (IQR) of RtPb, PbB level, and ALA-D activity were 65 (25-137) µgPb/m2/30 days, 1.0 (0.1-2.8) µg/dL, and 71 (55-86) U/L, respectively. Spearman correlation evidenced the relationship of PbB with RtPb (rho = 0.368, P < 0.001) and ALA-D activity (rho = -0.587; P Ë 0.001). After adjusting for exposure degree and child's age, a decline of 7.4 U/L in ALA-D activity was associated with a 10-fold increase in PbB. The prevalence ratio of elevated PbB (>5 µg/dL) in LEx and MEx areas were 1.5 and 3.7, respectively. Indoor dust exposure, living near pottery workshops and the secondary exposure were the main determinants of elevated PbB levels, which were associated with hematological effects.
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Población Negra , Industria Química , Polvo/análisis , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/sangre , Plomo/sangre , Adolescente , Biomarcadores/sangre , Brasil , Cerámica , Niño , Preescolar , Estudios Transversales , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Humanos , Hierro/metabolismo , Masculino , Prevalencia , Factores Socioeconómicos , Espectrofotometría AtómicaRESUMEN
This report describes a severe outbreak of the gill fluke Centrocestus formosanus in farm-raised platies Xiphophorus maculatus in Brazil, with mortality rate approaching 95%. Typical clinical signs of infection were observed, with microscopic examinations of fresh gills revealing multiple cysts containing a once-folded metacercaria with an X-shaped excretory bladder. The 18S subunit of the metacercariae (BR1) was amplified by PCR, sequenced and analyzed by BLAST. Subsequent phylogenetic analyses revealed that the BR1 isolate was closely related to C. formosanus from Thailand. This is the first report of C. formosanus in ornamental fish in Brazil. Our observations suggest that platies are highly sensitive to this digenetic parasite. Controlling population densities of the parasite's intermediate host, the snail Melanoides tuberculata, would help to reduce outbreaks.
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Ciprinodontiformes , Enfermedades de los Peces , Heterophyidae , Trematodos , Infecciones por Trematodos , Animales , Brasil , Brotes de Enfermedades , Granjas , Filogenia , Tailandia , Infecciones por Trematodos/veterinariaRESUMEN
It has been suggested that manganese (Mn) plays a fundamental role in the reproductive system through interference with the regulation of the secretion of hormones related to puberty. The objective of this study was to evaluate the environmental exposure to Mn and its effects on the endocrine regulation of hormones related to puberty in school-aged children living near a ferro-manganese alloy plant. Toenails, occipital hair, and blood samples were collected from 225 children, between 7 and 12 years of age, in four elementary schools in Simões Filho, Bahia, Brazil, who were exposed to different Mn levels owing to different Mn dust deposition rates. The Mn content was determined in the toenails (MnTn), hair (MnH), and blood (MnB), in addition to blood lead levels (PbB), by using graphite furnace atomic absorption spectrometry. Luteinizing hormone (LH), prolactin (PRL), estradiol (E2), testosterone (T), and thyroid stimulating hormone (TSH) levels were determined by using a chemiluminescence method. Of the total participants, 50.2% were boys, with an average age of 9 years. PRL values were higher in children attending the school with a higher Mn deposition rate (pâ¯<â¯0.004). We observed that MnTn was positively correlated with PRL levels and exhibited a non-linear association with LH levels. None of the tested Mn biomarkers were associated with E2, T, or TSH levels. To date, despite several animal studies that have focused on the correlation between Mn exposure and the endocrine regulation of hormones and pubertal development, very few studies have reported a similar relationship between environmental Mn effects and the human endocrine system. Our findings support the hypothesis that elevated exposure to Mn in children may be associated with hormonal imbalances that might trigger the early onset of puberty.
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Sistema Endocrino , Exposición a Riesgos Ambientales , Contaminantes Ambientales , Hierro , Manganeso , Brasil , Niño , Sistema Endocrino/efectos de los fármacos , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/toxicidad , Femenino , Hormonas Esteroides Gonadales/análisis , Hormonas Esteroides Gonadales/sangre , Cabello/química , Humanos , Hierro/toxicidad , Plomo/sangre , Plomo/toxicidad , Masculino , Manganeso/análisis , Manganeso/sangre , Manganeso/toxicidad , Uñas/química , Pubertad , Maduración Sexual/efectos de los fármacosRESUMEN
Studies have demonstrated that, for urban children, dust represents the main exposure to sources of metals like lead (Pb) and manganese (Mn). We aimed to investigate the exposure to these metals and their association with intellectual deficit in children living in an industrial region. This cross-sectional study recruited volunteers from four elementary schools in the town of Simões Filho, Brazil. We evaluated 225 school-aged children (7â»12 years) for blood lead (PbB) and manganese hair (MnH) and toenails (MnTn) by graphite furnace atomic absorption spectrometry. Child and maternal IQs were estimated using the Wechsler Abbreviated Scale for Intelligence (WASI). Median and range PbB were 1.2 (0.3â»15.6) µg/dL. MnH and MnTn medians (ranges) were 0.74 (0.16â»8.79) µg/g and 0.85 (0.15â»13.30) µg/g, respectively. After adjusting for maternal IQ, age and Mn exposure, child IQ drops by 8.6 points for a 10-fold increase in PbB levels. Moreover, an effect modification of Mn co-exposure was observed. In children with low MnTn, association between Pb and child IQ was not significant (ß = -6.780, p = 0.172). However, in those with high MnTn, the association was increased by 27.9% (ß = -8.70, p = 0.036). Low Pb exposure is associated with intellectual deficit in children, especially in those with high MnTn.
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Polvo/análisis , Exposición a Riesgos Ambientales/efectos adversos , Inteligencia/fisiología , Plomo/efectos adversos , Manganeso/efectos adversos , Estudiantes/estadística & datos numéricos , Encefalopatías , Brasil , Niño , Estudios Transversales , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente , Femenino , Cabello/química , Humanos , Pruebas de Inteligencia , Plomo/sangre , Masculino , Manganeso/sangre , Intoxicación por Manganeso/epidemiología , Instalaciones Industriales y de Fabricación , Uñas/química , Instituciones Académicas , Población Urbana/estadística & datos numéricosRESUMEN
Excessive exposure to Mn can lead to its accumulation in the brain with neurotoxic consequences. In children, elevated Mn has been associated with deficits in certain neuropsychological domains such as cognition, motor function, memory and attention, and in some instances, hyperactivity and behavioral problems. The aim of this study was to evaluate behavioral effects in school-aged children living near a ferro-manganese alloy plant and examine their association with Mn exposure. Occipital hair, toenails and blood samples were collected from 225 children (7-12 years old) enrolled in four elementary schools with different levels of exposure to Mn, based on dust Mn deposition rates. Full data set collection was completed and run from 165 children. Mn in hair (MnH), toenails (MnTn), blood (MnB) and blood lead levels (PbB) were determined by graphite furnace atomic absorption spectrometry. Children's behavior was assessed with the Child Behavior Check List (CBCL) reported by parents. Median levels and range of MnH, MnT and MnB were, respectively, 0.73⯵g/g (0.16-8.79), 0.84⯵g/g (0.15-9.29) and 8.98⯵g/L (1.51-40.43). Median and range of PbB were 1.2⯵g/dL (0.2-15.6). MnH and MnB were not associated with any scale of the CBCL behavior scores. We found a positive association between logMnTn and raw total CBCL score (ßâ¯=â¯10.17, pâ¯=â¯0.034), adjusting for sex, age, maternal IQ and logPbB. Analyses using Generalized Additive Model showed non-linear associations between MnTn and externalizing behavior (pâ¯=â¯0.035), as well as with the related subscales: aggressive behavior (pâ¯=â¯0.045) and rule-breaking behavior (pâ¯=â¯0.024). Further positive associations were observed between MnTn and thought problems (pâ¯=â¯0.031) and social problems (pâ¯=â¯0.027). These findings corroborate previous studies showing an association between Mn exposures and externalizing behavior. Our results suggest that toenail Mn, as a biomarker of environmental exposure, is associated with disruptive behavior in children living near a ferro-manganese alloy plant.
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Agresión , Contaminantes Atmosféricos , Manganeso , Problema de Conducta , Contaminantes Atmosféricos/toxicidad , Niño , Exposición a Riesgos Ambientales , Femenino , Humanos , Hierro , Plomo , Masculino , Manganeso/toxicidadRESUMEN
Previously, we showed that manganese (Mn) levels in settled dust in elementary schools increased at a rate of 34.1% per km closer to a ferro-manganese alloy plant in the rainy season. In this study, we investigated how this environmental pollution indicator varied in the dry season and if there was an association with Mn biomarker levels in school-aged children. Dust samples were collected with passive samplers (disposable Petri dishes) placed in interior and exterior environments of 14 elementary schools. Occipital hair, toenails and blood samples were collected from 173 students aged 7-12 years from three of these schools, with varying distance from the industrial plant. Mn and lead (Pb) levels were measured by graphite furnace atomic absorption spectrometry. Mn concentration geometric means (GM) in dust fall accumulation in interior environments of schools located at 2, 4, 6 and > 6 km-radii from the plant were 2212, 584, 625 and 224 µg Mn/m2/30 days, respectively. The modelled rate of change of dust Mn levels decreases by 59.8% for each km further from the plant. Pb levels in settled dust varied between 18 and 81 µg/m2/30 days with no association with distance from the plant. Blood lead levels median (range) were 1.2 µg/dL (0.2-15.6), of which 97.8% were <5 µg/dL. Mn in hair and toenails were 0.66 µg/g (0.16-8.79) and 0.86 µg/g (0.15-13.30), respectively. Mn loading rates were positively associated with log MnH (ß = 1.42 × 10-5, p < 0.001) after adjusting for children's age; and also with log MnTn (ß = 2.31 × 10-5, p < 0.001) independent of age. Mn loading rates explained 18.5% and 28.5% of the variance in MnH and MnTn levels, respectively. School-aged children exposure to Mn, independently of age, increases significantly with school proximity to the ferro-manganese alloy plant.