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Industrial growth has created the potential for environmental problems in Mexico, since attention to environmental controls and urban planning has lagged behind the pace of industrialization. The aim of this cross-sectional study was to assess lead exposure in children aged 6-9 yr attending 3 primary schools and living in the vicinity of the largest smelter complex in Mexico. One of the schools is located 650 m distant from a smelter complex that includes a lead smelter (close school); the second is located 1750 m away from the complex and at the side of a heavy traffic road (intermediate school) in Torreón, Coahuila. The third school is located in Gómez Palacio, Durango, 8100 m away from the smelter complex and distant from heavy vehicular traffic or industrial areas (remote school). Lead was measured in air, soil, dust, and well water. Lead in blood (PbB) was determined in 394 children attending the above mentioned schools. Determinations were performed by atomic absorption spectrometry. Diet, socioeconomic status, hygienic habits, and other variables were assessed by questionnaire. Median (range) PbB values were 7.8 µg/dl (3.54-29.61) in the remote school, 21.8 µg/dl (8.37-52.08) in the intermediate school and 27.6 µg/dl (7.37-58.53) in children attending the close school. The percentage of children with PbB >15 µg/dl was 6.8%, 84.9%, and 92.1% respectively. In this order, the geometric means (range) of Pb concentrations in air were 2.5 µg/m[sup 3] (1.1-7.5), 5.8 µg/m[sup 3] (4.3-8.5), and 6.1 µg/m[sup 3] (1.6-14.9). The Pb concentrations in dust from playgrounds areas in the intermediate and close school settings ranged from 1457 to 4162.5 mg/kg. Pb concentrations in drinking water were less than 5 µg/L. Soil and dust ingestion and inhalation appear to be the main routes of exposure. Our results indicate that environmental contamination has resulted in an increased body burden of Pb, suggesting that children living in the vicinity of the smelter complex are at high risk for adverse effects of lead. [ABSTRACT FROM AUTHOR]

Abstract Background To study the changes of children lead exposure in the city of Torreon during the last five years, after environmental and public health interventions, using the timeline of lead in blood concentration as the biomarker of exposure and its relation to lead in soil concentrations. Methods This follow-up study started in 2001 and consisted of 232 children living in nine neighborhoods in Torreon. Children were tested at 0, 6, 12 and 60 months. Lead in blood concentrations, Hemoglobin, Zinc-Protoporphyrin, anthropometric measures and socioeconomic status questionnaire was supplied to the parents. Results Median and range of lead in blood concentrations obtained at 0, 6, 12, 60 months were: 10.12 μg/dl (1.9 - 43.8), 8.75 μg/dl (1.85 - 41.45), 8.4 μg/dl (1.7 - 35.8) and 4.4 μg/dl (1.3 - 30.3), respectively. The decrease of lead in blood levels was significantly related to ages 0, 6, 12 and 60 months of the follow-up study. The timeline of B-Pb was associated with the timeline of lead in soil concentrations. Conclusions B-Pb levels have significantly decreased in the group of children studied. This could be explained by a) environmental interventions by authorities and the smelter companies, b) normal changes in hygienic habits as children age and c) lead redistribution from blood to hard tissues.

Background: Inorganic arsenic (iAs) is a ubiquitous metalloid and drinking water contaminant. Prenatal exposure is associated with birth outcomes across multiple studies. During metabolism, iAs is sequentially methylated to mono- and di-methylated arsenical species (MMAs and DMAs) to facilitate whole body clearance. Inefficient methylation (e.g., higher urinary % MMAs) is associated with increased risk of certain iAs-associated diseases. One-carbon metabolism factors influence iAs methylation, modifying toxicity in adults, and warrant further study during the prenatal period. The objective of this study was to evaluate folate, vitamin B12, and homocysteine as modifiers of the relationship between biomarkers of iAs methylation efficiency and birth outcomes., Methods: Data from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort (2011-2012)  with maternal urine and cord serum arsenic biomarkers and maternal serum folate, vitamin B12, and homocysteine concentrations were utilized. One-carbon metabolism factors were dichotomized using clinical cutoffs and median splits. Multivariable linear regression models were fit to evaluate associations between each biomarker and birth outcome overall and within levels of one-carbon metabolism factors. Likelihood ratio tests of full and reduced models were used to test the significance of statistical interactions on the additive scale (α = 0.10)., Results: Among urinary biomarkers, % U-MMAs was most strongly associated with birth weight (β = - 23.09, 95% CI: - 44.54, - 1.64). Larger, more negative mean differences in birth weight were observed among infants born to women who were B12 deficient (β = - 28.69, 95% CI: - 53.97, - 3.42) or experiencing hyperhomocysteinemia (β = - 63.29, 95% CI: - 154.77, 28.19). Generally, mean differences in birth weight were attenuated among infants born to mothers with higher serum concentrations of folate and vitamin B12 (or lower serum concentrations of homocysteine). Effect modification by vitamin B12 and homocysteine was significant on the additive scale for some associations. Results for gestational age were less compelling, with an approximate one-week mean difference associated with C-tAs (β = 0.87, 95% CI: 0, 1.74), but not meaningful otherwise., Conclusions: Tissue distributions of iAs and its metabolites (e.g., % MMAs) may vary according to serum concentrations of folate, vitamin B12 and homocysteine during pregnancy. This represents a potential mechanism through which maternal diet may modify the harms of prenatal exposure to iAs., (© 2022. The Author(s).)

The prenatal period represents a critical window of susceptibility to inorganic arsenic (iAs) exposure from contaminated drinking water. Ingested iAs undergoes hepatic methylation generating mono and di-methyl arsenicals (MMAs and DMAs, respectively), a process that facilitates urinary arsenic (As) elimination. Differences in pregnant women's metabolism of As as indicated by greater proportions of MMAs and smaller proportions of  DMAs in urine are a risk factor for adverse birth outcomes. One carbon metabolism (OCM), the nutritionally-regulated pathway essential for supplying methyl groups, plays a role in As metabolism and is understudied during the prenatal period. In this cross-sectional study from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico, we assessed the relationships among OCM indicators (e.g. maternal serum B12, folate, and homocysteine (Hcys)), and levels of iAs and its metabolites in maternal urine and in neonatal cord serum. The prevalence of folate sufficiency (folate levels > 9 nmol/L) in the cohort was high 99%, and hyperhomocysteinemia (Hcys levels > 10.4 μmol/L) was low (8%). However, 74% of the women displayed a deficiency in B12 (serum levels < 148 pmol/L). Association analyses identified that infants born to mothers in the lowest tertile of serum folate had significantly higher mean levels of %MMA in cord serum relative to folate replete women. In addition, elevated maternal Hcys was associated with total As in maternal urine and cord serum as well as cord serum %MMAs. The results from this study indicate that maternal OCM status may influence the distribution of As metabolites in cord serum.

Prenatal inorganic arsenic (iAs) exposure is associated with health effects evident at birth and later in life. An understanding of the relationship between prenatal iAs exposure and alterations in the neonatal metabolome could reveal critical molecular modifications, potentially underpinning disease etiologies. In this study, nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis was used to identify metabolites in neonate cord serum associated with prenatal iAs exposure in participants from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort, in Gómez Palacio, Mexico. Through multivariable linear regression, ten cord serum metabolites were identified as significantly associated with total urinary iAs and/or iAs metabolites, measured as %iAs, %monomethylated arsenicals (MMAs), and %dimethylated arsenicals (DMAs). A total of 17 metabolites were identified as significantly associated with total iAs and/or iAs metabolites in cord serum. These metabolites are indicative of changes in important biochemical pathways such as vitamin metabolism, the citric acid (TCA) cycle, and amino acid metabolism. These data highlight that maternal biotransformation of iAs and neonatal levels of iAs and its metabolites are associated with differences in neonate cord metabolomic profiles. The results demonstrate the potential utility of metabolites as biomarkers/indicators of in utero environmental exposure.

Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the metabolism of inorganic arsenic (iAs). Polymorphisms of AS3MT influence adverse health effects in adults, but little is known about their role in iAs metabolism in pregnant women and infants. The relationships between seven single nucleotide polymorphisms (SNPs) in AS3MT and urinary concentrations of iAs and its methylated metabolites were assessed in mother-infant pairs of the Biomarkers of Exposure to ARsenic (BEAR) cohort. Maternal alleles for five of the seven SNPs (rs7085104, rs3740400, rs3740393, rs3740390, and rs1046778) were associated with urinary concentrations of iAs metabolites, and alleles for one SNP (rs3740393) were associated with birth outcomes/measures. These associations were strongly dependent upon the male sex of the fetus but independent of fetal genotype for AS3MT. These data highlight a potential sex-dependence of the relationships among maternal genotype, iAs metabolism and infant health outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Dose-response functions used in regulatory risk assessment are based on studies of whole organisms and fail to incorporate genetic and metabolomic data. Bayesian belief networks (BBNs) could provide a powerful framework for incorporating such data, but no prior research has examined this possibility. To address this gap, we develop a BBN-based model predicting birthweight at gestational age from arsenic exposure via drinking water and maternal metabolic indicators using a cohort of 200 pregnant women from an arsenic-endemic region of Mexico. We compare BBN predictions to those of prevailing slope-factor and reference-dose approaches. The BBN outperforms prevailing approaches in balancing false-positive and false-negative rates. Whereas the slope-factor approach had 2% sensitivity and 99% specificity and the reference-dose approach had 100% sensitivity and 0% specificity, the BBN's sensitivity and specificity were 71% and 30%, respectively. BBNs offer a promising opportunity to advance health risk assessment by incorporating modern genetic and metabolomic data.

Background: Exposure to inorganic arsenic (iAs) from drinking water is a global public health problem, yet much remains unknown about the extent of exposure in susceptible populations., Objectives: We aimed to establish the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort in Gómez Palacio, Mexico, to better understand the effects of iAs exposure on pregnant women and their children., Methods: Two hundred pregnant women were recruited for this study. Concentrations of iAs in drinking water (DW-iAs) and maternal urinary concentrations of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) were determined. Birth outcomes were analyzed for their relationship to DW-iAs and to the concentrations and proportions of maternal urinary arsenicals., Results: DW-iAs for the study subjects ranged from < 0.5 to 236 μg As/L. More than half of the women (53%) had DW-iAs that exceeded the World Health Organization's recommended guideline of 10 μg As/L. DW-iAs was significantly associated with the sum of the urinary arsenicals (U-tAs). Maternal urinary concentrations of MMAs were negatively associated with newborn birth weight and gestational age. Maternal urinary concentrations of iAs were associated with lower mean gestational age and newborn length., Conclusions: Biomonitoring results demonstrate that pregnant women in Gómez Palacio are exposed to potentially harmful levels of DW-iAs. The data support a relationship between iAs metabolism in pregnant women and adverse birth outcomes. The results underscore the risks associated with iAs exposure in vulnerable populations.

Prenatal exposure to inorganic arsenic (iAs) is detrimental to the health of newborns and increases the risk of disease development later in life. Here we examined a subset of newborn cord blood leukocyte samples collected from subjects enrolled in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico, who were exposed to a range of drinking water arsenic concentrations (0.456-236 µg/l). Changes in iAs-associated DNA 5-methylcytosine methylation were assessed across 424,935 CpG sites representing 18,761 genes and compared with corresponding mRNA expression levels and birth outcomes. In the context of arsenic exposure, a total of 2919 genes were identified with iAs-associated differences in DNA methylation. Site-specific analyses identified DNA methylation changes that were most predictive of gene expression levels where CpG methylation within CpG islands positioned within the first exon, the 5' untranslated region and 200 bp upstream of the transcription start site yielded the most significant association with gene expression levels. A set of 16 genes was identified with correlated iAs-associated changes in DNA methylation and mRNA expression and all were highly enriched for binding sites of the early growth response (EGR) and CCCTC-binding factor (CTCF) transcription factors. Furthermore, DNA methylation levels of 7 of these genes were associated with differences in birth outcomes including gestational age and head circumference.These data highlight the complex interplay between DNA methylation, functional changes in gene expression and health outcomes and underscore the need for functional analyses coupled to epigenetic assessments., (© The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

High blood lead (BPb) levels in children and elevated soil and dust arsenic, cadmium, and lead were previously found in Torreón, northern Mexico, host to the world's fourth largest lead-zinc metal smelter. The objectives of this study were to determine spatial distributions of adolescents with higher BPb and creatinine-corrected urine total arsenic, cadmium, molybdenum, thallium, and uranium around the smelter. Cross-sectional study of 512 male and female subjects 12-15 years of age was conducted. We measured BPb by graphite furnace atomic absorption spectrometry and urine trace elements by inductively coupled plasma-mass spectrometry, with dynamic reaction cell mode for arsenic. We constructed multiple regression models including sociodemographic variables and adjusted for subject residence spatial correlation with spatial lag or error terms. We applied local indicators of spatial association statistics to model residuals to identify hot spots of significant spatial clusters of subjects with higher trace elements. We found spatial clusters of subjects with elevated BPb (range 3.6-14.7 μg/dl) and urine cadmium (0.18-1.14 μg/g creatinine) adjacent to and downwind of the smelter and elevated urine thallium (0.28-0.93 μg/g creatinine) and uranium (0.07-0.13 μg/g creatinine) near ore transport routes, former waste, and industrial discharge sites. The conclusion derived from this study was that spatial clustering of adolescents with high BPb and urine cadmium adjacent to and downwind of the smelter and residual waste pile, areas identified over a decade ago with high lead and cadmium in soil and dust, suggests that past and/or present plant operations continue to present health risks to children in those neighborhoods.

Positive associations between urine toxicant levels and measures of glomerular filtration rate (GFR) have been reported recently in a range of populations. The explanation for these associations, in a direction opposite that of traditional nephrotoxicity, is uncertain. Variation in associations by urine concentration adjustment approach has also been observed. Associations of urine cadmium, thallium and uranium in models of serum creatinine- and cystatin-C-based estimated GFR (eGFR) were examined using multiple linear regression in a cross-sectional study of adolescents residing near a lead smelter complex. Urine concentration adjustment approaches compared included urine creatinine, urine osmolality and no adjustment. Median age, blood lead and urine cadmium, thallium and uranium were 13.9 years, 4.0 μg/dL, 0.22, 0.27 and 0.04 g/g creatinine, respectively, in 512 adolescents. Urine cadmium and thallium were positively associated with serum creatinine-based eGFR only when urine creatinine was used to adjust for urine concentration (β coefficient=3.1 mL/min/1.73 m(2); 95% confidence interval=1.4, 4.8 per each doubling of urine cadmium). Weaker positive associations, also only with urine creatinine adjustment, were observed between these metals and serum cystatin-C-based eGFR and between urine uranium and serum creatinine-based eGFR. Additional research using non-creatinine-based methods of adjustment for urine concentration is necessary., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Exposure to inorganic arsenic (iAs) early in life is associated with adverse health effects in infants, children, and adults, and yet the biological mechanisms that underlie these effects are understudied. The objective of this research was to examine the proteomic shifts associated with prenatal iAs exposure using cord blood samples isolated from 50 newborns from Gómez Palacio, Mexico. Levels of iAs in maternal drinking water (DW-iAs) and the sum of iAs and iAs metabolites in maternal urine (U-tAs) were determined. Cord blood samples representing varying iAs exposure levels during the prenatal period (DW-iAs ranging from <1 to 236 μg As/l) were analyzed for altered expression of proteins associated with U-tAs using a high throughput, antibody-based method. A total of 111 proteins were identified that had a significant association between protein level in newborn cord blood and maternal U-tAs. Many of these proteins are regulated by tumor necrosis factor and are enriched in functionality related to immune/inflammatory response and cellular development/proliferation. Interindividual differences in proteomic response were observed in which 30 newborns were "activators," displaying a positive relationship between protein expression and maternal U-tAs. For 20 "repressor" newborns, a negative relationship between protein expression level and maternal U-tAs was observed. The activator/repressor status was significantly associated with maternal U-tAs and head circumference in newborn males. These results may provide a critical groundwork for understanding the diverse health effects associated with prenatal arsenic exposure and highlight interindividual responses to arsenic that likely influence differential susceptibility to adverse health outcomes.

The Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n = 40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 µg/L (mean = 51.7 µg/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 µg/L (mean = 64.5 µg/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: To study the changes of children lead exposure in the city of Torreon during the last five years, after environmental and public health interventions, using the timeline of lead in blood concentration as the biomarker of exposure and its relation to lead in soil concentrations., Methods: This follow-up study started in 2001 and consisted of 232 children living in nine neighborhoods in Torreon. Children were tested at 0, 6, 12 and 60 months. Lead in blood concentrations, Hemoglobin, Zinc-Protoporphyrin, anthropometric measures and socioeconomic status questionnaire was supplied to the parents., Results: Median and range of lead in blood concentrations obtained at 0, 6, 12, 60 months were: 10.12 μg/dl (1.9 - 43.8), 8.75 μg/dl (1.85 - 41.45), 8.4 μg/dl (1.7 - 35.8) and 4.4 μg/dl (1.3 - 30.3), respectively. The decrease of lead in blood levels was significantly related to ages 0, 6, 12 and 60 months of the follow-up study. The timeline of B-Pb was associated with the timeline of lead in soil concentrations., Conclusions: B-Pb levels have significantly decreased in the group of children studied. This could be explained by a) environmental interventions by authorities and the smelter companies, b) normal changes in hygienic habits as children age and c) lead redistribution from blood to hard tissues.

We evaluated environmental-lead (Pb) effects on semen quality and sperm chromatin, considering Pb in seminal fluid (PbSF), spermatozoa (PbSpz), and blood (PbB) as exposure biomarkers in urban men (9.3 microg/dL PbB). Several individuals (44%) showed decreases in sperm quality; sperm concentration, motility, morphology and viability associated negatively with PbSpz, whereas semen volume associated negatively with PbSF. Multiple linear regression estimated PbSF and PbSpz thresholds for alterations in semen quality. Forty-eight percent of samples showed high values of nuclear chromatin condensation (NCD) positively associated with PbSF and zinc in spermatozoa (ZnSpz). ZnSpz values were higher than in fertile men. These results suggest that Pb may affect sperm chromatin by altering sperm Zn availability. PbB was not associated with semen quality or NCD, suggesting that Pb in semen compartments assesses better the amount of Pb in the reproductive tract; therefore, these are better biomarkers to evaluate toxicity at low Pb-exposure levels.