Serum matrix metalloproteinase-9 in children exposed to arsenic from playground dust at elementary schools in Hermosillo, Sonora, Mexico.

Arsenic exposure in adults has been associated with increased serum matrix metalloproteinase-9 (MMP-9), a biomarker which is associated with chronic respiratory disease, lung inflammation, cardiovascular disease and cancer. The objective of this study was to evaluate the association between serum MMP-9 levels in children, urinary arsenic, arsenic chronic daily intake (CDI) and arsenic exposure from playground dust. This cross-sectional study examined 127 children from five elementary schools, in Hermosillo, Sonora, Mexico. Arsenic was analyzed in the dust using a portable X-ray fluorescence (XRF) analyzer. Total urinary arsenic was determined by inductively coupled plasma/optical emission spectrometry. Serum was analyzed for MMP-9 using ELISA. Arsenic levels in playground dust averaged 16.9 ± 4.6 mg/kg. Urinary arsenic averaged 34.9 ± 17.1 µg/L. Arsenic concentration in playground dust was positively associated with serum MMP-9 levels in crude analyses and after adjustment (P < 0.01), MMP-9 and CDI were positively associated only after adjustment (P < 0.01), and no association was found between MMP-9 and urinary arsenic. In conclusion, our study showed an association in children between serum MMP-9 levels and playground dust arsenic concentrations. Therefore, exposure to arsenic in dust where children spend significant time may manifest toxic effects.

Exposure assessment of organochlorine pesticides, arsenic, and lead in children from the major agricultural areas in Sonora, Mexico.

There is a lack of information of exposure to organochlorine pesticides (OCP) and some metals, such as lead (Pb) and arsenic (As), both of which were used as arsenicals pesticides, in children living in the major agricultural areas of Mexico. The objective of this study was to assess the exposure of children to different OCP, As, and Pb in the Yaqui and Mayo valleys of Sonora to generate population baseline levels of these toxins. A cross-sectional study was undertaken in 165 children (age 6-12 years old) from 10 communities from both valleys during 2009. Blood samples were analyzed for OCP and Pb and first morning void urine for inorganic As (InAs). All of the blood samples had detectable levels of dichlorodiphenyltrichloroethylene (p,p'-DDE) ranging from 0.25 to 10.3 µg/L. However lindane, dichlorodiphenyltrichloroethane (p,p'-DDT), aldrin, and endosulfan were detected in far less of the population (36.4, 23.6, 9.1, and 3 %, respectively). Methoxychlor and endrin were not found in any sample. The average value of Pb in this population was 3.2 µg Pb/dL (range 0.17-9.0) with 8.5 % of the samples having levels <5.0 µg Pb/dL. Urinary As levels ranged from 5.4 to 199 µg As/L with an average value of 31.0 µg As/L. Levels > 50 µg/L were observed in 12.7 % of the samples. Our results show that is important to start a risk-reduction program to decrease exposure to these toxins in Mexican communities. In addition, the results can be used to establish the baseline levels of exposure to these toxins in this agricultural region and may be used as a reference point for regulatory agencies.

Indigenous American ancestry is associated with arsenic methylation efficiency in an admixed population of northwest Mexico.

Many studies provide evidence relating lower human arsenic (As) methylation efficiency, represented by high percent urinary monomethylarsonic acid (MMA(V)), with several As-induced diseases, possibly due to the fact that MMA(V) serves as a proxy for MMA(III), the most toxic As metabolite. Some epidemiological studies suggested that indigenous Americans (AME) methylate As more efficiently; however, data supporting this have been equivocal. The aim of this study was to characterize the association between AME ancestry and As methylation efficiency using a panel of ancestry informative genetic markers to determine individual ancestry proportions in an admixed population (composed of two or more isolated ancestral populations) of 746 individuals environmentally exposed to As in northwest Mexico. Total urinary As (TAs) mean and range were 170.4 and 2.3-1053.5 µg/L, while percent AME (%AME) mean and range were 72.4 and 23-100. Adjusted (gender, age, AS3MT 7388/M287T haplotypes, body mass index [BMI], and TAs) multiple regression model showed that higher AME ancestry is significantly associated with lower percentage of urinary As excreted as MMA(V) (%uMMA) in this population (p < .01). Data also demonstrated a significant interaction between BMI and gender, indicating negative association between BMI and %uMMA, stronger in women than men (p < .01). Moreover, age and the AS3MT variants 7388 (intronic) and M287T (nonsynonymous) were also significantly associated with As methylation efficiency (p < .01). This study highlights the importance of BMI and indigenous American ancestry in some of the observed variability in As methylation efficiency, underscoring the need to be considered in epidemiology studies, particularly those carried out in admixed populations.

Association between body mass index and arsenic methylation efficiency in adult women from southwest U.S. and northwest Mexico.

Human arsenic methylation efficiency has been consistently associated with arsenic-induced disease risk. Interindividual variation in arsenic methylation profiles is commonly observed in exposed populations, and great effort has been put into the study of potential determinants of this variability. Among the factors that have been evaluated, body mass index (BMI) has not been consistently associated with arsenic methylation efficiency; however, an underrepresentation of the upper BMI distribution was commonly observed in these studies. This study investigated potential factors contributing to variations in the metabolism of arsenic, with specific interest in the effect of BMI where more than half of the population was overweight or obese. We studied 624 adult women exposed to arsenic in drinking water from three independent populations. Multivariate regression models showed that higher BMI, arsenic (+3 oxidation state) methyltransferase (AS3MT) genetic variant 7388, and higher total urinary arsenic were significantly associated with low percentage of urinary arsenic excreted as monomethylarsonic acid (%uMMA) or high ratio between urinary dimethylarsinic acid and uMMA (uDMA/uMMA), while AS3MT genetic variant M287T was associated with high %uMMA and low uDMA/uMMA. The association between BMI and arsenic methylation efficiency was also evident in each of the three populations when studied separately. This strong association observed between high BMI and low %uMMA and high uDMA/uMMA underscores the importance of BMI as a potential arsenic-associated disease risk factor, and should be carefully considered in future studies associating human arsenic metabolism and toxicity.

Inflammation biomarkers associated with arsenic exposure by drinking water and respiratory outcomes in indigenous children from three Yaqui villages in southern Sonora, México.

Environmental arsenic exposure in adults and children has been associated with a reduction in the expression of club cell secretory protein (CC16) and an increase in the expression of matrix metalloproteinase-9 (MMP-9), both biomarkers of lung inflammation and negative respiratory outcomes. The objectives of this study were to determine if the levels of serum CC16 and MMP-9 and subsequent respiratory infections in children are associated with the ingestion of arsenic by drinking water. This cross-sectional study included 216 children from three Yaqui villages, Potam, Vicam, and Cocorit, with levels of arsenic in their ground water of 70.01 ± 21.85, 23.3 ± 9.99, and 11.8 ± 4.42 µg/L respectively. Total arsenic in water and urine samples was determined by inductively coupled plasma/optical emission spectrometry. Serum was analyzed for CC16 and MMP-9 using ELISA. The children had an average urinary arsenic of 79.39 µg/L and 46.8 % had levels above of the national concern value of 50 µg/L. Increased arsenic concentrations in drinking water and average daily arsenic intake by water were associated with decreased serum CC16 levels (ß = - 0.12, 95% CI - 0.20, - 0.04 and ß = - 0.10, 95% CI - 0.18, - 0.03), and increased serum MMP-9 levels (ß = 0.35, 95% CI 0.22, 0.48 and ß = 0.29, 95% CI 0.18, 0.40) at significant levels (P < 0.05). However, no association was found between levels of these serum biomarkers and urinary arsenic concentrations. In these children, reduced serum CC16 levels were significantly associated with increased risk of respiratory infections (OR = 0.34, 95% CI 0.13, 0.90). In conclusion, altered levels of serum CC16 and MMP-9 in the children may be due to the toxic effects of arsenic exposure through drinking water.

Genetic association between intronic variants in AS3MT and arsenic methylation efficiency is focused on a large linkage disequilibrium cluster in chromosome 10.

Differences in arsenic metabolism are known to play a role in individual variability in arsenic-induced disease susceptibility. Genetic variants in genes relevant to arsenic metabolism are considered to be partially responsible for the variation in arsenic metabolism. Specifically, variants in arsenic (3+ oxidation state) methyltransferase (AS3MT), the key gene in the metabolism of arsenic, have been associated with increased arsenic methylation efficiency. Of particular interest is the fact that different studies have reported that several of the AS3MT single nucleotide polymorphisms (SNPs) are in strong linkage-disequilibrium (LD), which also extends to a nearby gene, CYP17A1. In an effort to characterize the extent of the region in LD, we genotyped 46 SNPs in a 347,000 base region of chromosome 10 that included AS3MT in arsenic-exposed subjects from Mexico. Pairwise LD analysis showed strong LD for these polymorphisms, represented by a mean r(2) of 0.82, spanning a region that includes five genes. Genetic association analysis with arsenic metabolism confirmed the previously observed association between AS3MT variants, including this large cluster of linked polymorphisms, and arsenic methylation efficiency. The existence of a large genomic region sharing strong LD with polymorphisms associated with arsenic metabolism presents a predicament because the observed phenotype cannot be unequivocally assigned to a single SNP or even a single gene. The results reported here should be carefully considered for future genomic association studies involving AS3MT and arsenic metabolism.

Study of organochlorine pesticides and heavy metals in soils of the Juarez valley: an important agricultural region between Mexico and the USA.

The Juarez Valley is an important agricultural region in northern Mexico, conveniently organized into three modules (I to III). For decades, their soils have been exposed to organochlorine pesticides (OCPs) and also have been irrigated with wastewaters, which may contain heavy metals. Nowadays, there is very limited information regarding the presence of OCPs and heavy metals in these soils. Thus, the aim of this study was to diagnose these soils for OCPs and heavy metal content by using gas chromatography coupled with electron micro-capture detector and atomic absorption spectrometry, respectively. The results indicated that 4,4'-dichlorodiphenyldichloroethylene and 4,4'-dichlorodiphenyltrichloroethane were primarily disseminated across the three modules since they were found in 100% and 97% of the analyzed soils, respectively. According to international regulations, none of the determined OCP concentrations are out of the limits. Additionally, the Cu, Zn, Fe, Pb, and Mn were found in all sampled soils from the three modules. The highest concentration of Fe was found in module II (1902.7 ± 332.2 mg kg-1), followed by Mn in module III (392.43 ± 74.43 mg kg-1), Zn in module I (38.36 ± 26.57 mg kg-1), Pb in module II (23.48 ± 6.48 mg kg-1), and Cu in module I (11.04 ± 3.83 mg kg-1) (p ≤ 0.05). These values did not exceed the limits proposed by international standards. The Cd was detected in most of the analyzed soils and all their values, with an average of 2 mg kg-1, surpassed the Mexican standards (0.35 mg kg-1). This study has mapped the main OCPs and heavy metals in the Juarez Valley and can serve as a starting point to further monitor the behave of xenobiotics. Since these recalcitrant compounds might be bio-accumulated in biological systems, further analytical methods, as well as remediation techniques, should be developed.

Health Risk Assessment and Urinary Excretion of Children Exposed to Arsenic through Drinking Water and Soils in Sonora, Mexico.

Environmental arsenic exposure is associated with increased risk of non-cancerous chronic diseases and a variety of cancers in humans. The aims of this study were to carry out for the first time a health risk assessment for two common arsenic exposure routes (drinking water and soil ingestion) in children living in the most important agricultural areas in the Yaqui and Mayo valleys in Sonora, Mexico. Drinking water sampling was conducted in the wells of 57 towns. A cross-sectional study was done in 306 children from 13 villages in the valleys. First morning void urine samples were analyzed for inorganic arsenic (InAs) and monomethyl and dimethyl arsenic (MMA and DMA) by HPLC/ICP-MS. The results showed a wide range of arsenic levels in drinking water between 2.7 and 98.7 µg As/L. Arsenic levels in agricultural and backyard soils were in the range of < 10-27 mg As/kg. The hazard index (HI) = ∑hazard quotient (HQ) for drinking water, agricultural soil, and backyard soil showed values > 1 in 100% of the study towns, and the carcinogenic risk (CR) was greater than 1E-04 in 85%. The average of arsenic excreted in urine was 31.7 µg As/L, and DMA had the highest proportion in urine, with averages of 77.8%, followed by InAs and MMA with 11.4 and 10.9%, respectively, percentages similar to those reported in the literature. Additionally, positive correlations between urinary arsenic levels and HI values were found (r = 0.59, P = 0.000). These results indicated that this population is at high risk of developing chronic diseases including cancer.

Environmental arsenic exposure and microbiota in induced sputum.

Arsenic exposure from drinking water is associated with adverse respiratory outcomes, but it is unknown whether arsenic affects pulmonary microbiota. This exploratory study assessed the effect of exposure to arsenic in drinking water on bacterial diversity in the respiratory tract of non-smokers. Induced sputum was collected from 10 subjects with moderate mean household water arsenic concentration (21.1 ± 6.4 ppb) and 10 subjects with low household water arsenic (2.4 ± 0.8 ppb). To assess microbiota in sputum, the V6 hypervariable region amplicons of bacterial 16s rRNA genes were sequenced using the Ion Torrent Personal Genome Machine. Microbial community differences between arsenic exposure groups were evaluated using QIIME and Metastats. A total of 3,920,441 sequence reads, ranging from 37,935 to 508,787 per sample for 316 chips after QIIME quality filtering, were taxonomically classified into 142 individual genera and five phyla. Firmicutes (22%), Proteobacteria (17%) and Bacteriodetes (12%) were the main phyla in all samples, with Neisseriaceae (15%), Prevotellaceae (12%) and Veillonellacea (7%) being most common at the genus level. Some genera, including Gemella, Lactobacillales, Streptococcus, Neisseria and Pasteurellaceae were elevated in the moderate arsenic exposure group, while Rothia, Prevotella, Prevotellaceae Fusobacterium and Neisseriaceae were decreased, although none of these differences was statistically significant. Future studies with more participants and a greater range of arsenic exposure are needed to further elucidate the effects of drinking water arsenic consumption on respiratory microbiota.

Metals in residential soils and cumulative risk assessment in Yaqui and Mayo agricultural valleys, northern Mexico.

This investigation examines the extent of soil metal pollution associated with the Green Revolution, relative to agricultural activities and associated risks to health in the most important agricultural region of Mexico. Metal contents in bulk soil samples are commonly used to assess contamination, and metal accumulations in soils are usually assumed to increase with decreasing particle size. This study profiled the spatial distribution of metals (Ni, Cr, Pb, Cu, Fe, Cd, V, Hg, Co, P, Se, and Mn) in bulk soil and fine-grained fractions (soil-derived dust) from 22 towns and cities. The contamination of soil was assessed through the use of a geoaccumulation index (Igeo) and pollution index (PI). The results of this study indicated that a number of towns and cities are moderately to highly polluted by soil containing Be, Co, Hg, P, S, V, Zn, Se, Cr, and Pb in both size fractions (coarse and fine). Hazard index in fine fraction (HI(children)=2.1) shows that risk assessment based on Co, Mn, V, and Ni spatially related to power plants, have the potential to pose health risks to local residents, especially children. This study shows that risk assessment based on metal content in bulk soil could be overestimated when compared to fine-grained fraction. Our results provide important information that could be valuable in establishing risk assessment associated with residential soils within agricultural areas, where children can ingest and inhale dust.