FOXE1 polymorphisms and chronic exposure to nitrates in drinking water cause metabolic dysfunction, thyroid abnormalities, and genotoxic damage in women.

Nitrates in drinking water has been associated to adverse health effects, including changes in glucose and lipid levels, thyroid hormone imbalance and adverse reproductive effects. We analyzed metabolic and thyroid hormone alterations and genotoxic damage in women with chronic exposure to nitrates in drinking water. The concentration of nitrates in drinking water was quantified and according to this parameter, participants were divided into three exposure scenarios. Blood and urine samples were collected from 420 women living in Durango, Mexico and biomarkers were determined. We found nitrates concentrations in drinking water above the permissible limit (>50 mg/L), and an increase in the percentage of methemoglobin (p=0.0001), nitrite in blood plasma and urine (p=0.0001), glucose (p=0.0001), total cholesterol (p=0.001), LDL (p=0.001) and triglycerides (p=0.0001). We also found alterations in TSH (p=0.01), fT3 (p=0.0003), T4T (p=0.01) and fT4 (p=0.0004) hormones. Frequency of subclinical hypothyroidism was 8.33%; differences in FOXE1 (rs965513, rs1867277) genotypes distribution were found and both polymorphisms were associated with a decrease in TSH. A high percentage of micronucleus in binucleate lymphocyte cells was found (35%, p=0.0001). In conclusion, the chronic exposure to nitrates in water for human consumption caused metabolic and hormonal alterations and genotoxic damage in women.

Impact of urine concentration adjustment method on associations between urine metals and estimated glomerular filtration rates (eGFR) in adolescents.

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 (ß 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.

Association between arsenic exposure and behavior among first-graders from Torreón, Mexico.

Previous studies suggest adverse effects of arsenic exposure on children's cognitive function. In this study, we examined the potential association between arsenic exposure and children's behavior. Five hundred and twenty-six children, 6-7 years old, living near a metal foundry in Torreón, Mexico, participated in the study. Arsenic exposure was measured as total urinary arsenic (UAs) and arsenic metabolites-monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) concentrations. Children's behavior was assessed by Conners Behavior Rating Scales for parents and teachers. The median (interquartile range) concentrations of UAs, MMA and DMA were 55.2 (39.7), 6.7 (5.9) and 39.3 (28.5) µg/L, respectively. The mean behavior scores from parent and teacher ratings were within the clinically normal range (T<65). The relationship between behavior and urinary arsenic was modeled in linear and logistic regression models, with UAs, MMA and DMA tested in separate models and entered as quartiles. No significant association was found between any measure of urinary arsenic and parent ratings of behavior. However, higher UAs was modestly associated with higher scores on the Oppositional, Cognitive Problems and ADHD sub-scales of the teacher ratings; a dose-response relationship was not established between UAs quartiles and behavior. Higher urinary DMA was associated with higher ratings on the Oppositional, Cognitive Problems and ADHD Index by teachers. The associations between UAs and behavior became statistically non-significant after adjustment for the Peabody Picture Vocabulary Test scores, suggesting that the harmful effects of arsenic on behavior may be secondary to arsenic-induced cognitive deficits. These data suggest a potential adverse association between arsenic and children's behavior and indicate a need to further study the effects of arsenic and arsenic metabolites on neurobehavioral outcomes in children.

The association between lead and micronutrient status, and children's sleep, classroom behavior, and activity.

The role of lead exposure or micronutrient deficiencies in children's sleep problems is unknown. Although elevated blood lead concentrations (BPb) are clearly related to behavior problems in children, few researchers have used objective observations. The authors investigated relationships between lead, micronutrient status, sleep, classroom behavior, and activity in Mexican children aged 6-8 years living close to a metal foundry. Mean BPb was 11.5 +/- 6.1 microg/dL; 50% had levels >or= 10 microg/dL. Ten percent of children had hemoglobin < 12.4 g/dL. Parents reported on children's sleep and fatigue (n 550). The authors also observed classroom behavior (n = 157) and measured physical activity (n = 168). BPb >or= 10 microg/dL was associated with later waking time and shorter duration of sleep. Anemia was linked to more off-task behaviors, lower physical activity, earlier bedtime, and shorter sleep onset. Researchers should investigate these relationships further, using more sensitive measures.

Efficacy of iron and/or zinc supplementation on cognitive performance of lead-exposed Mexican schoolchildren: a randomized, placebo-controlled trial.

OBJECTIVE: Lead exposure in children has been associated with both global and specific cognitive deficits. Although chelation therapy is advised for children with blood lead concentrations of >44 microg/dL, treatment options for children with lower blood lead values are limited. Because lead absorption is related to children's nutritional status, micronutrient supplements may be 1 strategy for combating low-level, chronic lead exposure. This study was designed to test the efficacy of iron and zinc supplementation for lowering blood lead concentrations and improving cognitive performance in schoolchildren who live in a lead-contaminated city. METHODS: This randomized, double-blind, placebo-controlled field trial was conducted in public elementary schools in Torreón, an industrialized city in northern Mexico. A metal foundry, located close to the city center and within 3.5 km of 9 schools, was the main source of lead exposure. A total of 602 children who were aged 6 to 8 years and regularly attending first grade in the study schools were enrolled. Children were given 30 mg of iron, 30 mg of zinc, both, or a placebo daily for 6 months. A total of 527 completed the treatment, and 515 were available for long-term follow-up, after another 6 months without supplementation. Eleven cognitive tests of memory, attention, visual-spatial abilities, and learning were administered at baseline and each follow-up. RESULTS: There were no consistent or lasting differences in cognitive performance among treatment groups. CONCLUSIONS: Daily supplementation with iron and/or zinc may be of limited usefulness for improving cognition in lead-exposed schoolchildren. However, these treatments may be effective in settings with higher prevalence of nutritional deficiencies or in younger children.

Deficits in cognitive function and achievement in Mexican first-graders with low blood lead concentrations.

Elevated blood lead levels in children are associated with lower scores on tests of cognitive functioning. Recent studies have reported inverse relations between lifetime exposure and intellectual functioning at blood lead concentrations below 10 microg/dL, the Centers for Disease Control and Prevention's (CDC) level of concern. We report associations between blood lead and cognitive performance for first-grade Mexican children living near a metal foundry. Using a cross-sectional design, we examined the relation between children's concurrent blood lead concentrations (mean (SD) 11.4 microg/dL (6.1)) and their performance on 14 tests of global or specific cognitive functions. The blood lead-cognition relations were modeled using both linear and nonlinear methods. After adjustment for covariates, a higher blood lead level was associated with poorer cognitive performance on several cognitive tests. Segmented linear regressions revealed significant effects of lead but only for the segments defined by a concurrent blood lead concentration below 10-14 microg/dL. One implication of these findings is that at the age of 7 years, even in the absence of information on lead exposure in infancy and early childhood, a test result with blood lead < 10 microg/dL should not be considered safe. Together with other recent findings, these results add to the empirical base of support available for evaluating the adequacy of current screening guidelines and for motivating efforts at primary prevention of childhood lead exposure.