Life-long arsenic exposure damages the microstructure of the rat hippocampus.

Epidemiological studies demonstrate that arsenic exposure is associated with cognitive dysfunction. Experimental arsenic exposure models showed learning and memory deficits and molecular changes resembling the functional and pathologic neurodegeneration features. The present work focuses on hippocampal pathological changes in Wistar rats induced by continuous arsenic exposure from in utero up to 12 months of age, evaluated by magnetic resonance imaging along with immunohistochemistry. Diffusion-weighted images revealed age-related lower fractional anisotropy and higher radial-axial and mean diffusivity at 6 and 12 months, indicating that arsenic exposure leads to hippocampal demyelination. These structural alterations were paralleled by immunohistochemical changes that showed a significant loss of myelin basic protein in CA1 and CA3 regions accompanied by increased glial fibrillary acidic protein expression at all time-points studied. Concomitantly, arsenic exposure induced an altered morphology of astrocytes at all studied ages, whereas increased synaptogenesis was only observed at two months of age. These results suggest that environmental arsenic exposure is linked to impaired hippocampal connectivity and perhaps early glial senescence, which together might resemble a premature aging phenomenon leading to cognitive deficits.

Arsenic Exposure Contributes to the Bioenergetic Damage in an Alzheimer's Disease Model.

Worldwide, every year there is an increase in the number of people exposed to inorganic arsenic (iAs) via drinking water. Human populations present impaired cognitive function as a result of prenatal and childhood iAs exposure, while studies in animal models demonstrate neurobehavioral deficits accompanied by neurotransmitter, protein, and enzyme alterations. Similar impairments have been observed in close association with Alzheimer's disease (AD). In order to determine whether iAs promotes the pathophysiological progress of AD, we used the 3xTgAD mouse model. Mice were exposed to iAs in drinking water from gestation until 6 months (As-3xTgAD group) and compared with control animals without arsenic (3xTgAD group). We investigated the behavior phenotype on a test battery (circadian rhythm, locomotor behavior, Morris water maze, and contextual fear conditioning). Adenosine triphosphate (ATP), reactive oxygen species, lipid peroxidation, and respiration rates of mitochondria were evaluated, antioxidant components were detected by immunoblots, and immunohistochemical studies were performed to reveal AD markers. As-3xTgAD displayed alterations in their circadian rhythm and exhibited longer freezing time and escape latencies compared to the control group. The bioenergetic profile revealed decreased ATP levels accompanied by the decline of complex I, and an oxidant state in the hippocampus. On the other hand, the cortex showed no changes of oxidant stress and complex I; however, the antioxidant response was increased. Higher immunopositivity to amyloid isoforms and to phosphorylated tau was observed in frontal cortex and hippocampus of exposed animals. In conclusion, mitochondrial dysfunction may be one of the triggering factors through which chronic iAs exposure exacerbates brain AD-like pathology.

Mercury Mining in Mexico: I. Community Engagement to Improve Health Outcomes from Artisanal Mining.

BACKGROUND: Mercury is an element that cannot be destroyed and is a global threat to human and environmental health. In Latin America and the Caribbean, artisanal and small-scale gold mining represents the main source of mercury emissions, releases, and consumption. However, another source of concern is the primary production of mercury. In the case of Mexico, in the past 2 years the informal production of mercury mining has increased 10-fold. Considering this scenario, an intervention program was initiated to reduce health risks in the mining communities. The program's final goal is to introduce different alternatives in line to stop the mining of mercury, but introducing at the same time, a community-based development program. OBJECTIVE: The aim of this study was to present results from a preliminary study in the community of Plazuela, located in the municipality of Peñamiller in the State of Queretaro, Mexico. METHODS: Total mercury was measured in urine and environmental samples using atomic absorption spectrometry by cold vapor technique. Urine samples were collected from children aged 6-14 years and who had lived in the selected area from birth. Urine samples were also collected from miners who were currently working in the mine. To confirm the presence of mercury in the community, mining waste, water, soil, and sediment samples were collected from those high-risk areas identified by members of the community. FINDINGS: Children, women, and miners were heavily exposed to mercury (urine samples); and in agreement, we registered high concentrations of mercury in soils and sediments. CONCLUSION: Considering these results and taking into account that the risk perception toward mercury toxicity is very low in the community (mining is the only economic activity), an integral intervention program has started.

The "CHILD" framework for the study of artisanal mercury mining communities.

In this paper, our group reports the use of a new framework in sites contaminated with mercury. This is significant because under the Minamata Convention on Mercury each Party shall endeavor to develop appropriate strategies for identifying and assessing sites contaminated by mercury or mercury compounds. This new approach, the "CHILD" framework has five steps: i) Community-based risk characterization; ii) Habilitation; iii) Intervention; iv) Laws and Regulation; and v) Development. We are using this framework in three mercury artisanal mining sites, and preliminary results are depicted in this report.

Exposición infantil al plomo en sitios contaminados / Children exposure to lead in contaminated sites

OBJETIVO: Determinar el grado de la exposición infantil al plomo en diversos tipos de sitios contaminados. MATERIAL Y MÉTODOS: El estudio se realizó de junio 2008 a diciembre 2009 en cuatro sitios de México: metalúrgica de Ávalos, Chihuahua.; metalúrgica de Morales, San Luis Potosí (SLP); zona alfarera en La Trinidad, Tlaxcala, y sitio minero en Cedral, SLP. Se cuantificó plomo en polvo y se realizó un biomonitoreo humano en niños de la comunidad. RESULTADOS: Los valores obtenidos de plomo en polvo exterior superaron el límite establecido de 400 mg/kg para suelos residenciales en un intervalo de valores para los cuatro sitios de 62 a 5 187 mg/kg. En cuanto al monitoreo biológico, todas las poblaciones presentaron valores extremos, desde los 22 µg/dL en Cedral, 31 µg/dL en Morales, y 32 µg/dL en Ávalos, hasta los 52 µg/dL en La Trinidad. Es importante señalar que encontramos una correlación positiva y significativa entre los valores de plomo en polvo y plomo en sangre en todos los sitios de estudio (p<0.001). CONCLUSIÓN: Estos sitios son un ejemplo de los riesgos en salud relacionados con la exposición a plomo en México; por consiguiente, se requiere de un programa nacional de salud pública dirigido a reducir la exposición a este metal en poblaciones vulnerables.

OBJECTIVE: To assess the exposure to lead in children living in various types of contaminated sites. MATERIALS AND METHODS: The study was conducted from June 2008 to December 2009 at four sites in Mexico: Avalos metallurgical, Chihuahua; Morales metallurgical, San Luis Potosí (SLP); Trinidad pottery area, Tlaxcala and Cedral mine site, SLP. These sites contain different sources of lead. The metal levels were quantified in outdoor dust and in peripheral blood of children. RESULTS: Lead dust concentrations exceed the National Guidelines for residential soils (400 mg/kg) in a range of values for the four sites from 62 to 5 187 mg/kg. Regarding biological monitoring, the studied children showed maximum lead blood levels of 22 µg/dL in Cedral, 31 µg/dL in Morales, 32 µg/dL in Avalos, and 52 µg/dL in Trinidad. It is important to mention that in all the studied sites, a significative positive correlation was found between blood lead levels and the lead concentrations in dust. CONCLUSION: These sites are an example of the health risks related to lead exposure in Mexico; therefore, there is an urgent need for a national public health program aimed at reducing lead exposure in vulnerable populations.

[Children exposure to lead in contaminated sites]. / Exposición infantil al plomo en sitios contaminados.

OBJECTIVE: To assess the exposure to lead in children living in various types of contaminated sites. MATERIALS AND METHODS: The study was conducted from June 2008 to December 2009 at four sites in Mexico: Avalos metallurgical, Chihuahua; Morales metallurgical, San Luis Potosí (SLP); Trinidad pottery area, Tlaxcala and Cedral mine site, SLP. These sites contain different sources of lead. The metal levels were quantified in outdoor dust and in peripheral blood of children. RESULTS: Lead dust concentrations exceed the National Guidelines for residential soils (400 mg/kg) in a range of values for the four sites from 62 to 5 187 mg/kg. Regarding biological monitoring, the studied children showed maximum lead blood levels of 22 µg/dL in Cedral, 31 µg/dL in Morales, 32 µg/dL in Avalos, and 52 µg/dL in Trinidad. It is important to mention that in all the studied sites, a significative positive correlation was found between blood lead levels and the lead concentrations in dust. CONCLUSION: These sites are an example of the health risks related to lead exposure in Mexico; therefore, there is an urgent need for a national public health program aimed at reducing lead exposure in vulnerable populations.

DNA damage and decreased DNA repair in peripheral blood mononuclear cells in individuals exposed to arsenic and lead in a mining site.

The aim of this study was to evaluate DNA damage and the capacity for DNA repair in children exposed to arsenic and lead. During 2006, we studied a total of 85 healthy children (aged 4-11 years) who were residents of Villa de la Paz (community A), Matehuala (community B), and Soledad de Graciano Sanchez (community C) in San Luis Potosi, Mexico. The quantification of arsenic in urine (AsU) and lead in blood (PbB) was performed by atomic absorption spectrophotometry. The alkaline comet assay was used to evaluate DNA damage and DNA repair. The highest levels of AsU and PbB in children were found in community A (44.5 µg/g creatinine for arsenic and 11.4 µg/dL for lead), followed by community B (16.8 µg/g creatinine for arsenic and 7.3 µg/dL for lead) and finally by children living in community C (12.8 µg/g creatinine for arsenic and 5.3 µg/dL for lead). When DNA damage was assessed, children living in community A had the highest DNA damage. Analysis of these same cells 1 h after a challenge with H(2)O(2) 10 µM showed a dramatic increase in DNA damage in the cells of children living in community B and community C, but not in the cells of children living in community A. Moreover, significantly higher levels of DNA damage were observed 3 h after the challenge ended (repair period) in cells from individuals living in community A. Our results show that children exposed to metals might be more susceptible to DNA alterations.

Apoptosis of peripheral blood mononuclear cells in children exposed to arsenic and fluoride.

In this study, we evaluated apoptosis induction in human immune cells in children exposed to arsenic (As) and fluoride (F). Children living in two areas in Mexico (Soledad de Graciano Sanchez (SGS) in San Luis Potosí and Colonia 5 de Febrero in Durango) were studied. Water, urine and blood samples were collected. Approximately 90% of the water samples in 5 de Febrero had As and F levels above the World Health Organization intervention guideline (10 µg/L and 1.5mg/L, respectively). In SGS, 0% of the water samples exceeded Mexican guidelines. Urinary As and F levels in children living in 5 de Febrero were significantly higher than the levels found in children living in SGS. In addition, the level of apoptosis was higher in children from the 5 de Febrero community when compared with the level of apoptosis in children living in SGS. Thus, in a worldwide context, our study demonstrates the health risks to children living in these regions.

Chronic exposure to low levels of inorganic arsenic causes alterations in locomotor activity and in the expression of dopaminergic and antioxidant systems in the albino rat.

Several studies have associated chronic arsenicism with decreases in IQ and sensory and motor alterations in humans. Likewise, studies of rodents exposed to inorganic arsenic ((i)As) have found changes in locomotor activity, brain neurochemistry, behavioral tasks, oxidative stress, and in sensory and motor nerves. In the current study, male Sprague-Dawley rats were exposed to environmentally relevant doses of (i)As (0.05, 0.5 mg (i)As/L) and to a high dose (50 mg (i)As/L) in drinking water for one year. Hypoactivity and increases in the striatal dopamine content were found in the group treated with 50 mg (i)As/L. Exposure to 0.5 and 50 mg (i)As/L increased the total brain content of As. Furthermore, (i)As exposure produced a dose-dependent up-regulation of mRNA for Mn-SOD and Trx-1 and a down-regulation of DAR-D2 mRNA levels in the nucleus accumbens. DAR-D1 and Nrf2 mRNA expression were down-regulated in nucleus accumbens in the group exposed to 50 mg (i)As/L. Trx-1 mRNA levels were up-regulated in the cortex in an (i)As dose-dependent manner, while DAR-D1 mRNA expression was increased in striatum in the 0.5 mg (i)As/L group. These results show that chronic exposure to low levels of arsenic causes subtle but region-specific changes in the nervous system, especially in antioxidant systems and dopaminergic elements. These changes became behaviorally evident only in the group exposed to 50 mg (i)As/L.

Exposure assessment of persistent organic pollutants and metals in Mexican children.

Environmental policies in Mexico have contributed to the reduction in the production or use of some persistent organic pollutants (POPs) and metals. However, monitoring of POPs concentrations in humans living in hot spots is lacking. Therefore, the objective of this study was to conduct a screening for POPs and metals first in Mexican children living in high-risk areas. During the year 2004, we analyzed a total of 229 healthy children (aged 6-12 years old) who resided in communities located in nine Mexican states. Organochlorine insecticides, PCBs and metals were quantified in plasma and urine samples. We detected p'p-DDE in all the children; moreover, p'p-DDT, lindane and hexachlorobenzene were detected respectively in 14%, 85% and 10% of the children studied. Measurable levels of PCBs were recorded in only one community, where six of 14 PCB congeners assayed were detected (numbers 52, 118, 138, 153, 170 and 180). All the children had detectable levels of lead in their blood (mean level, 4.6 microg dL(-1)); furthermore, 57% of the children studied had levels higher than 5.0 microg/dL. The mean level of urinary arsenic (UAs) for all the children was 22.35 microg g(-1) creatinine and 15% of those children had concentrations of UAs above 50 microg g(-1) creatinine. For cadmium, the mean urinary level was 0.78 microg g(-1) creatinine, and only one percent of the children had values above 2.0 microg g(-1) creatinine. The results cannot be generalized since the communities selected are not representative of the Mexican population; however, they indicate that Mexican children are exposed to chemicals and some at risk levels.

Attempted breastfeeding before hospital discharge on both sides of the US-Mexico border, 2005: the Brownsville-Matamoros Sister City Project for Women's Health.

INTRODUCTION: The US-Mexico border region has a growing population and limited health care infrastructure. Preventive health behaviors such as breastfeeding ease the burden on this region's health care system by reducing morbidity and health care costs. We examined correlates of attempted breastfeeding before hospital discharge on each side of the US-Mexico border and within the border region. METHODS: The cross-sectional study included women who delivered a live infant in Matamoros, Tamaulipas, Mexico (n = 489), and Cameron County, Texas (n = 457), which includes Brownsville, Texas. We interviewed women before hospital discharge from August 21 through November 9, 2005. We used multivariate logistic regression to estimate the odds of attempted breastfeeding before hospital discharge in Cameron County, Texas, the municipality of Matamoros, Mexico, and the 2 communities combined. RESULTS: Prevalence of attempted breastfeeding before hospital discharge was 81.9% in Matamoros compared with 63.7% in Cameron County. After adjusting for potential confounders, the odds of attempted breastfeeding before hospital discharge were 90% higher in Matamoros than in Cameron County (adjusted odds ratio [AOR], 1.93; 95% confidence interval [CI], 1.31-2.84 for the combined model). In the 2 communities combined, odds of attempted breastfeeding before hospital discharge were higher among women who had a vaginal delivery than among women who had a cesarean delivery (AOR, 1.98; 95% CI, 1.43-2.75) and were lower among women who delivered infants with a low birth weight than among women who delivered infants with a normal birth weight (AOR, 0.26; 95% CI, 0.15-0.44). CONCLUSION: The rate of attempted breastfeeding in Matamoros was significantly higher than in Cameron County. Additional breastfeeding support and messages on the US side of the US-Mexico border are needed.

Decreased intelligence in children and exposure to fluoride and arsenic in drinking water.

Recent evidence suggests that fluoride (F) and arsenic (As) may adversely affect intelligence quotient (IQ) scores. We explore the association between exposure to F and As in drinking water and intelligence in children. Three rural communities in Mexico with contrasting levels of F and As in drinking water were studied: Moctezuma (F 0.8+/-1.4 mg/L; As 5.8+/-1.3 microg/L); Salitral (F 5.3+/-0.9 mg/L; As 169+/-0.9 microg/L) and 5 de Febrero (F 9.4+/-0.9 mg/L; As 194+/-1.3 microg/L). The final study sample consisted of 132 children from 6 to 10 years old. After controlling for confounders, an inverse association was observed between F in urine and Performance, Verbal, and Full IQ scores (beta values = -13, -15.6, -16.9, respectively). Similar results were observed for F in drinking water (beta values = -6.7, -11.2, -10.2, respectively) and As in drinking water (beta values= -4.30, -6.40, -6.15, respectively). The p-values for all cases were < 0.001. A significant association was observed between As in urine and Full IQ scores (beta = -5.72, p = 0.003). These data suggest that children exposed to either F or As have increased risks of reduced IQ scores.

An integrated health risk assessment approach to the study of mining sites contaminated with arsenic and lead.

In order to test the value of an integrated approach for the analysis of health risks at contaminated sites, an integrated health risk assessment in a mining area was performed following 3 steps: 1) Environmental monitoring of surface soil, 2) assessment of exposure to metals in children and native rodents, and 3) DNA damage evaluation (comet assay) in children and rodents. These aspects also were studied in less exposed populations. Our results in humans showed that children living in the most polluted area (Villa de la Paz, Mexico) had higher lead blood concentrations (geometric mean of 13.8 microg/dL) and urinary arsenic levels (geometric mean of 52.1 microg/g creatinine) compared to children living in a control area (Matehuala, Mexico; blood lead of 7.3 microg/dL; urinary arsenic of 16.8 microg/g creatinine). Furthermore, the exposed children also had increased DNA damage (tail moment mean in Villa de la Paz of 4.8 vs 3.9 in Matehuala; p < 0.05). Results in rodents were identical. Animals captured in the polluted area had higher levels of arsenic (geometric mean of 1.3 microg/g in liver and 1.8 microg/g in kidney), lead (0.2 microg/g in liver and 0.9 microg/g in kidney), and cadmium (0.8 microg/g in liver and 2.2 microg/g in kidney), and increased DNA damage (tail moment mean of 18.2) when compared to control animals (arsenic in liver of 0.08 microg/g and kidney of 0.1 microg/g; lead in liver of 0.06 microg/g and kidney of 0.3 microg/g; cadmium in liver of 0.06 microg/g and kidney of 0.6 microg/g; and tail moment of 14.2). With the data in children and rodents, the weight-of-evidence for health risks (in this case DNA damage) associated with metal exposure in Villa de la Paz was strengthened. Therefore, a remediation program was easier to justify, and a feasibility study at this site is under way.

Decreased intelligence in children and exposure to fluoride and arsenic in drinking water

Recent evidence suggests that fluoride (F) and arsenic (As) may adversely affect intelligence quotient (IQ) scores. We explore the association between exposure to F and As in drinking water and intelligence in children. Three rural communities in Mexico with contrasting levels of F and As in drinking water were studied: Moctezuma (F 0.8±1.4mg/L; As 5.8±1.3µg/L); Salitral (F 5.3±0.9mg/L; As 169±0.9µg/L) and 5 de Febrero (F 9.4±0.9mg/L; As 194±1.3µg/L). The final study sample consisted of 132 children from 6 to 10 years old. After controlling for confounders, an inverse association was observed between F in urine and Performance, Verbal, and Full IQ scores (beta values = -13, -15.6, -16.9, respectively). Similar results were observed for F in drinking water (beta values = -6.7, -11.2, -10.2, respectively) and As in drinking water (beta values= -4.30, -6.40, -6.15, respectively). The p-values for all cases were < 0.001. A significant association was observed between As in urine and Full IQ scores (beta = -5.72, p = 0.003). These data suggest that children exposed to either F or As have increased risks of reduced IQ scores.

Estudios recientes sugieren que el flúor (F) y el arsénico (As) pueden tener efectos adversos sobre el coeficiente intelectual (CI). En este estudio exploramos la asociación entre el F y el As y la inteligencia en niños expuestos a estas sustancias a través del agua. Tres comunidades rurales de México con diferentes niveles de F y As fueron estudiadas: Moctezuma (F 0,8±1,4mg/L; As 5,8±1,3µg/L); Salitral (F 5,3±0,9mg/L; As 169±0,9µg/L) y 5 de Febrero (F 9,4±0,9mg/L; As 194±1,3µg/L). La muestra final fue de 132 niños de 6 a 10 años de edad. Después de controlar por confusores, se obtuvieron asociaciones inversas entre F en orina y las puntuaciones de los CI (Desempeño, Verbal y Total) (valores beta = -13, -15,6, -16,9, respectivamente) p < 0,001 en todos los casos. Resultados similares se obtuvieron con F en agua (valores beta = -6,7, -11,2, -10,2, respectivamente) y con As en agua (valores beta = -4,30, -6,40, -6,15, respectivamente). En todos los casos p < 0,001. Para As en orina, se obtuvo una asociación inversa con las puntuaciones del CI total (beta= -5,72; p = 0,003). Estos datos sugieren que los niños expuestos al F o al As tienen mayor riesgo de tener disminución en las puntuaciones del CI.

Genotoxicidad en niños que viven en una zona metalúrgica del estado de San Luis Potosí, México / Genotoxicity in children living in a smelter area in San Luis Potosí, Mexico

Al poniente de la Ciudad de San Luis Potosí, México, se encuentra ubicadauna metalúrgica alrededor de la cual se ha encontrado contaminación por arsénico y plomo tanto en aire como en suelo/polvo. Varios estudios han mostrado que los niños que habitan cerca de este lugar están expuestos a dichos metales. Considerando lo anterior y tomando en cuenta reportes de genotoxicidad asociada al arsénico y al plomo, en este trabajo se evaluó el daño al ADN en los niños expuestos empleando el ensayo cometa. Los resultados indican que casi la mitad de los niños que viven en este lugar presentan valores por encima de los límites de acción que marca CDC para arsénico (50 ug/g de creatinina) y paraplomo (10 ug/dL de sangre). En cuanto al daño al ADN el 35% de los niños sobrepasa el máximo valor de daño encontrado en la población control.

A smelter area where arsenic and lead have been found in air and soil/dust is located in San Luis Potosi, México. Some studies have reported that children living in this area are exposed to those metals. Therefore, DNA damage usingthe comet assay was assessed in the exposed children. Our results showed that almost 50% of the studied children had urinary arsenic and blood lead levels higher than the CDC´s guidelines (50 ug/g creatinin for urinary arsenic and 10 ug/dL for lead in blood). With regard to DNA damage 35% of the children had damage values above the control population.

Exposure to arsenic and lead of children living near a copper-smelter in San Luis Potosi, Mexico: Importance of soil contamination for exposure of children.

The objective of this study was to assess the levels of soil contamination and child exposure in areas next to a primary smelter (arsenic-copper metallurgical) located in the community of Morales in San Luis Potosi, Mexico. In Morales, 90% of the soil samples studied in this work were above 400 mg/kg of lead, and above 100 mg/kg of arsenic, which are guidelines recommended by the United States Environmental Protection Agency (EPA). Bioaccessibility of these metals was studied in vitro in 10 soil samples; the median values of bioaccessibility obtained in these samples were 46.5% and 32.5% for arsenic and lead. Since the concentrations of arsenic and lead in soil were above normal values, and taking into account the bioaccessibility results, exposure to these metals was evaluated in children. Regarding lead, children aged 3-6 years had the highest mean blood lead levels; furthermore, 90% of them had concentrations above 10 microg/dl (CDC's action level). Total urinary arsenic was higher in children aged 8-9 yr; however, the percentage of children with concentrations above 50 microg/g creatinine (CDC's action level) or 100 microg/g creatinine (World Health Organization [WHO] action level) was similar among different age groups. Using the EPAs integrated exposure uptake biokinetic model for lead in children (IEUBK), we estimated that 87% of the total lead in blood is obtained from the soil/dust pathway. The exposure dose to arsenic, estimated for the children living in Morales using Monte Carlo analysis and the arsenic concentrations found in soil, was above the EPA's reference dose. With all these results, it is evident that studies are needed in order to identify adverse health effects in children living in Morales; nevertheless, it is more important to develop a risk reduction program as soon as possible.

Effect of acute exposure to arsenic on formalin-induced nociception and tramadol-mediated antinociception in mice.

In vitro studies have suggested that arsenic can modify the activity of macrophages in the mouse producing an over-regulation of the COX-2 and increased concentrations of PGE2 in endothelial cells. These effects may lead in vivo to enhancement of inflammatory and painful responses. In this study we studied the effect of an acute intoxication with sodium arsenite (1, 5, 10, 36 and 100 nmol/kg s.c.) on the nociceptive response of mice in the formalin test. On the other hand, the effect of arsenic on the antinociceptive response mediated by tramadol was evaluated in mice administered with a single dose of the analgesic agent (10 mg/kg s.c.). Arsenic levels in the liver were measured as a marker of the intoxication degree. Our results indicated that the arsenic acute exposure increases the nociceptive behavior in mice in a dose-dependent manner. Accordingly, the exposure to arsenic partially blocked the analgesic effect of tramadol although no statistical differences were reached. These results support the previous in vitro evidences regarding the alterations in the inflammatory-painful processes produced by the acute exposure to arsenic. Moreover, our results suggest that the intoxication with arsenic might exacerbate the pathological state in inflammatory diseases.

DNA damage in blood cells from children exposed to arsenic and lead in a mining area.

In this work, we studied the frequency of DNA damage in children living in Villa de la Paz, Mexico, a mining site contaminated with arsenic and lead. DNA damage in blood cells was assessed using the Comet assay, and the results were compared to those found in children living in a less exposed town (Matehuala). In Villa de la Paz, high concentrations of arsenic and lead in surface soil and household dust were found. All of the soil samples had concentrations above 100 mg/kg of arsenic, and 58% of the samples were higher than 400 mg/kg of lead (these concentrations are used as intervention guidelines by the United States Environmental Protection Agency). In agreement with the environmental results, urinary arsenic in children living in Villa de la Paz (geometric mean 136 microg/g creatinine) was significantly higher than that found in children living in Matehuala (34 microg/g creatinine). Blood lead levels were also significantly higher in children from Villa de la Paz (11.6 microg/dL) than in children from Matehuala (8.3 microg/dL). The results of the Comet assay showed that the tail length and the tail moment in children living in Villa de la Paz were higher than those observed for children in Matehuala (P<0.05). Taking all the data into account, our study has shown increased DNA damage in children exposed to arsenic and lead in the mining site of Villa de la Paz.

Fluoride-induced disruption of reproductive hormones in men.

Fluoride-induced reproductive effects have been reported in experimental models and in humans. However, these effects were found in heavily exposed scenarios. Therefore, in this work our objective was to study reproductive parameters in a population exposed to fluoride at doses of 3-27 mg/day (high-fluoride-exposed group-HFEG). Urinary fluoride levels, semen parameters, and reproductive hormones in serum (LH, FSH, estradiol, prolactin, inhibin-B, free and total testosterone) were measured. Results were compared with a group of individuals exposed to fluoride at lower doses: 2-13 mg/day (low-fluoride-exposed group-LFEG). A significant increase in FSH (P<0.05) and a reduction of inhibin-B, free testosterone, and prolactin in serum (P<0.05) were noticed in the HFEG. When HFEG was compared to LFEG, a decreased sensitivity was found in the FSH response to inhibin-B (P<0.05). A significant negative partial correlation was observed between urinary fluoride and serum levels of inhibin-B (r=-0.333, P=0.028) in LFEG. Furthermore, a significant partial correlation was observed between a chronic exposure index for fluoride and the serum concentrations of inhibin-B (r=-0.163, P=0.037) in HFEG. No abnormalities were found in the semen parameters studied in the present work, neither in the HFEG, nor in the LFEG. The results obtained indicate that a fluoride exposure of 3-27 mg/day induces a subclinical reproductive effect that can be explained by a fluoride-induced toxic effect in both Sertoli cells and gonadotrophs.

Overview of human health and chemical mixtures: problems facing developing countries.

In developing countries, chemical mixtures within the vicinity of small-scale enterprises, smelters, mines, agricultural areas, toxic waste disposal sites, etc., often present a health hazard to the populations within those vicinities. Therefore, in these countries, there is a need to study the toxicological effects of mixtures of metals, pesticides, and organic compounds. However, the study of mixtures containing substances such as DDT (dichlorodiphenyltrichloroethane, an insecticide banned in developed nations), and mixtures containing contaminants such as fluoride (of concern only in developing countries) merit special attention. Although the studies may have to take into account simultaneous exposures to metals and organic compounds, there is also a need to consider the interaction between chemicals and other specific factors such as nutritional conditions, alcoholism, smoking, infectious diseases, and ethnicity.