Association of glutathione S-transferase Ω 1-1 polymorphisms (A140D and E208K) with the expression of interleukin-8 (IL-8), transforming growth factor beta (TGF-ß), and apoptotic protease-activating factor 1 (Apaf-1) in humans chronically exposed to arsenic in drinking water.

Human exposure to arsenicals is associated with inflammatory-related diseases including different kinds of cancer as well as non-cancerous diseases like neuro-degenerative diseases, atherosclerosis, hypertension, and diabetes. Interindividual susceptibility has been mainly addressed by evaluating the role of genetic polymorphism in metabolic enzymes in inorganic arsenic (iAs) metabolism. Glutathione S-transferase omega 1-1 (GSTO1-1), which had been associated with iAs metabolism, is also known to participate in inflammatory and apoptotic cellular responses. The polymorphism A140D of GSTO1-1 has been not only associated with distinct urinary profile of arsenic metabolites in populations chronically exposed to iAs in drinking water, but also with higher risk of childhood leukemia and lung disease in non-exposed populations, suggesting that GSTO1-1 involvement in other physiologic processes different from toxics metabolism could be more relevant than is thought. We evaluated the association of the presence of A140D and E208K polymorphisms of GSTO1-1 gene with the expression of genes codifying for proteins involved in the inflammatory and apoptotic response in a human population chronically exposed to iAs through drinking water. A140D polymorphism was associated with higher expression of genes codifying for IL-8 and Apaf-1 mainly in heterozygous individuals, while E208K was associated with higher expression of IL-8 and TGF- gene, in both cases, the association was independently of iAs exposure level; however, the exposure to iAs increased slightly but significantly the influence of A140D and E208K polymorphisms on such genes expression. These results suggest an important role of GSTO1-1 in the inflammatory response and the apoptotic process and indicate that A140D and E208K polymorphisms could increase the risk of developing inflammatory and apoptosis-related diseases in As-exposed populations.

Impact of Cadmium Mediated by Tobacco Use in Musculoskeletal Diseases.

Tobacco use has a negative impact on health due to its relationship with the development of high-mortality diseases, such as pulmonary cancer. However, the effect of cadmium (Cd), present in tobacco smoke, on the development of joint diseases has been scarcely studied. The objective of this review is to discuss the evidence regarding the mechanisms by which Cd exposure, through tobacco smoke, may lead to the development of osteoarthritis (OA), osteoporosis (OP), and rheumatoid arthritis (RA). There's evidence suggesting a string association between moderate to severe OA development and tobacco use, and that a higher blood concentration of Cd can trigger oxidative stress (OS) and inflammation, favoring cartilage loss. At the bone level, the Cd that is inhaled through tobacco smoke affects bone mineral density, resulting in OP mediated by a decrease in the antioxidant enzymes, which favors the bone resorption process. In RA, tobacco use promotes the citrullination process through Cd exposure and increases OS and inflammation. Understanding how tobacco use can increase the damage at the articular level mediated by a toxic metal, i.e., Cd, is important. Finally, we propose prevention, control, and treatment strategies for frequently disabling diseases, such as OA, OP, and RA to reduce its prevalence in the population.

Effect of cadmium on the concentration of essential metals in a human chondrocyte micromass culture.

BACKGROUND: An essential element imbalance in the joint might favor gradual degeneration of the articular cartilage. It has been reported that cadmium (Cd) plays an antagonistic role with regards to the presence of essential elements, such as zinc (Zn), iron (Fe), and manganese (Mn), which may favor the development of disabling diseases, like osteoarthritis (OA) and osteoporosis. METHODS: 3D cultures of human chondrocytes were phenotyped with the Western blot technique and structurally evaluated with histological staining. The samples were exposed to 1, 5, and 10 µM of CdCl2 for 12 h, with a non-exposed culture as control. The concentration of Cd, Fe, Mn, Zn, chromium (Cr), and nickel (Ni) was quantified through plasma mass spectrometry (ICP-MS). The data were analyzed with a Kruskal Wallis test, a Kendall's Tau test and Spearman's correlation coefficient with the Stata program, version 14. RESULTS: Our results suggest that Cd exposure affects the structure of micromass cultures and plays an antagonistic role on the concentration of essential metals, such as Zn, Ni, Fe, Mn, and Cr. CONCLUSION: Cd exposure may be a risk factor for developing joint diseases like OA, as it can interfere with cartilage absorption of other essential elements that maintain cartilage homeostasis.

Prenatal exposure to metals modified DNA methylation and the expression of antioxidant- and DNA defense-related genes in newborns in an urban area.

The developmental period in utero is a critical window for environmental exposure. Epigenetic fetal programming via DNA methylation is a pathway through which metal exposure influences the risk of developing diseases later in life. Genetic damage repair can be modified by alterations in DNA methylation, which, in turn, may modulate gene expression due to metal exposure. We investigated the impact of prenatal metal exposure on global and gene-specific DNA methylation and mRNA expression in 181 umbilical cord blood samples from newborns in Mexico City. Global (LINE1) and promoter methylation of DNA-repair (OGG1 and PARP1) and antioxidant (Nrf2) genes was evaluated by pyrosequencing. Prenatal metal exposure (As, Cu, Hg, Mn, Mo, Pb, Se, and Zn) was determined by ICP-MS analysis of maternal urine samples. Multiple regression analyses revealed that DNA methylation of LINE1, Nrf2, OGG1, and PARP1 was associated with potentially toxic (As, Hg, Mn, Mo, and Pb) and essential (Cu, Se, and Zn) elements, and with their interactions. We also evaluated the association between gene expression (mRNA levels quantified by p-PCR) and DNA methylation. An increase in OGG1 methylation at all sites and at CpG2, CpG3, and CpG4 sites was associated with reduced mRNA levels; likewise, methylation at the CpG5, CpG8, and CpG11 sites of PARP1 was associated with reduced mRNA expression. In contrast, methylation at the PARP1 CpG7 site was positively associated with its mRNA levels. No associations between Nrf2 expression and CpG site methylation were observed. Our data suggest that DNA methylation can be influenced by prenatal metal exposure, which may contribute to alterations in the expression of repair genes, and therefore, result in a lower capacity for DNA damage repair in newborns.

Effects of inorganic arsenic exposure on glucose transporters and insulin receptor in the hippocampus of C57BL/6 male mice.

Children and adolescent populations chronically exposed to high doses of inorganic arsenic (iAs) in drinking water in some regions around the world have shown behavioral and memory deficits. Recent studies have also associated iAs exposure with dysregulation of glucose metabolism. The hippocampus is a cerebral region well known for its role in learning and memory. Studies in vitro and in vivo have shown that the hippocampus is vulnerable to iAs exposure, and to changes in glucose metabolism. The glucose transporters (GLUTs) and insulin receptor (IR) regulate glucose metabolism in brain; they are expressed by hippocampal cells, and alterations in these proteins have been associated with memory deficits. The aims of this study were to evaluate the effects of iAs exposure via drinking water (DW) on GLUT1, GLUT3 and insulin receptor (INSR) mRNA expression in the hippocampus, on performance in a spatial memory task, and on peripheral glucose regulation. C57Bl/6 male mice were exposed to 50 mg iAs/L via DW for one, two, or three months. The qRT-PCR analyses indicated that, compared to a control group, GLUT1 and GLUT3 mRNA levels were decreased, while INSR mRNA levels were increased in the hippocampus of iAs exposed animals. The levels of iAs and its methylated species in the hippocampus of the iAs-exposed group were significantly higher than in controls. Mice exposed to iAs learned the spatial task but showed increased latency to find the submerged platform 48 h after the last training session; these animals also showed dysregulation of peripheral glucose. These results suggest that the effects of iAs exposure on a spatial memory task performance could be mediated by disruptions of glucose regulation in the CNS.

Tissue distribution and urinary excretion of inorganic arsenic and its methylated metabolites in mice following acute oral administration of arsenate.

The relationship of exposure dose and tissue concentration of parent chemical and metabolites is a critical issue in cases where toxicity may be mediated by a metabolite or by parent chemical and metabolite acting together. This has emerged as an issue for inorganic arsenic (iAs), because both its trivalent and pentavalent methylated metabolites have unique toxicities; the methylated trivalent metabolites also exhibit greater potency than trivalent inorganic arsenic (arsenite, As(III)) for some endpoints. In this study, the time-course tissue distributions for iAs and its methylated metabolites were determined in blood, liver, lung, and kidney of female B6C3F1 mice given a single oral dose of 0, 10, or 100 micromol As/kg (sodium arsenate, As(V)). Compared to other organs, blood concentrations of iAs, mono- (MMA), and dimethylated arsenic (DMA) were uniformly lower across both dose levels and time points. Liver and kidney concentrations of iAs were similar at both dose levels and peaked at 1 h post dosing. Inorganic As was the predominant arsenical in liver and kidney up to 1 and 2 h post dosing, with 10 and 100 micromol As/kg, respectively. At later times, DMA was the predominant metabolite in liver and kidney. By 1 h post dosing, concentrations of MMA in kidney were 3- to 4-fold higher compared to other tissues. Peak concentrations of DMA in kidney were achieved at 2 h post dosing for both dose levels. Notably, DMA was the predominant metabolite in lung at all time points following dosing with 10 micromol As/kg. DMA concentration in lung equaled or exceeded that of other tissues from 4 h post dosing onward for both dose levels. These data demonstrate distinct organ-specific differences in the distribution and methylation of iAs and its methylated metabolites after exposure to As(V) that should be considered when investigating mechanisms of arsenic-induced toxicity and carcinogenicity.

Glutathione reductase inhibition and methylated arsenic distribution in Cd1 mice brain and liver.

Inorganic arsenic exposure via drinking water has been associated with cancer and serious injury in various internal organs, as well as with peripheral neuropathy and diverse effects in the nervous system. Alterations in memory and attention processes have been reported in exposed children, whereas adults acutely exposed to high amounts of inorganic arsenic showed impairments in learning, memory, and concentration. Glutathione (GSH) is extensively involved in the metabolism of inorganic arsenic, and both arsenite and its methylated metabolites have been shown to be potent inhibitors of glutathione reductase (GR) in vitro. Brain would be more susceptible to GR inhibition because of the decreased activities of superoxide dismutase (SOD) and catalase reported in this tissue. To investigate whether GR inhibition could be documented in vivo, we determined the activity and levels of GR in brain as well as in liver, the main organ of arsenic metabolism in mice exposed to 2.5, 5, or 10 mg/kg/day of sodium arsenite over a period of 9 days. In contrast to what has been observed in vitro, significant inhibition of the expression and activity of GR was observed only at the highest concentration used (10 mg/kg/day) in both organs. Although the disposition of arsenicals was higher in liver, significant amounts of inorganic and methylated arsenic forms were determined in the brain of exposed animals. The formation of monomethylarsenic (MMA) and dimethylarsenic (DMA) metabolites in the brain was confirmed by incubating brain slices for 24, 48, and 72 h with sodium arsenite.

Effects of arsenite on cell cycle progression in a human bladder cancer cell line.

Bladder cancer is one of the most important diseases associated with arsenic (As) exposure in view of its high prevalence and mortality rate. Experimental studies have shown that As exposure induces cell proliferation in the bladder of sodium arsenite (iAsIII) subchronically treated mice. However, there is little available information on its effects on the cell cycle of bladder cells. Thus, our purpose was to evaluate the effects of iAsIII on cell cycle progression and the response of p53 and p21 on the human-derived epithelial bladder cell line HT1197. iAsIII treatment (1-10 microM) for 24 h induced a dose-dependent increase in the proportion of cells in S-phase, which reached 65% at the highest dose. A progressive reduction in cell proliferation was also observed. BrdU was incorporated to cellular DNA in an interrupted form, suggesting an incomplete DNA synthesis. The time-course of iAsIII effects (10 microM) showed an increase in p53 protein content and a transient increase in p21 protein levels accompanying the changes in S-phase. These effects were correlated with iAs concentrations inside the cells, which were not able to metabolize inorganic arsenic. Our findings suggest that p21 was not able to block CDK2-cyclin E complex activity and was therefore unable to arrest cells in G1 allowing their progression into the S-phase. Further studies are needed to ascertain the mechanisms underlying the effects of iAsIII on the G1 to S phase transition in bladder cells.

Studies on the mechanisms of arsenic-induced self tolerance developed in liver epithelial cells through continuous low-level arsenite exposure.

Arsenic (As) is a human carcinogen. Our prior work showed that chronic (>18 weeks) low level (500 nM) arsenite (As3+) exposure induced malignant transformation in a rat liver epithelial cell line (TRL 1215). In these cells, metallothionein (MT) is hyper-expressible, a trait often linked to metal tolerance. Thus, this study examined whether the adverse effects of arsenicals and other metals were altered in these chronic arsenite-exposed (CAsE) cells. CAsE cells, which had been continuously exposed to 500 nM arsenite for 18 to 20 weeks, and control cells, were exposed to As3+, arsenate (As5+), dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), antimony (Sb3+), cadmium (Cd2+), cisplatin (cis-Pt), and nickel (Ni2+) for 24 h and cell viability was determined by metabolic integrity. The lethal concentration for 50% of exposed cells (LC50) for As3+ was 140 microM in CAsE cells as compared to 26 microM in control cells, a 5.4-fold increase in tolerance. CAsE cells were also very tolerant to the acute toxic effects of As5+ (LC50 > 4000 microM) compared to control (LC50 = 180 microM). The LC50 for DMA was 4.4-fold higher in CAsE cells than in control cells, but the LC50 for MMA was unchanged. There was a modest cross-tolerance to Sb3+, Cd2+, and cis-Pt in CAsE cells (LC50 1.5-2.0-fold higher) as compared to control. CAsE cells were very tolerant to Ni2+ (LC50 > 8-fold higher). Culturing CAsE cells in As(3+)-free medium for 5 weeks did not alter As3+ tolerance, implicating an irreversible phenotypic change. Cellular accumulation of As was 87% less in CAsE cells than control and the accumulated As was more readily eliminated. Although accumulating much less As, a greater portion was converted to DMA in CAsE cells. Altered glutathione (GSH) levels were not linked with As tolerance. A maximal induction of MT by Zn produced only a 2.5-fold increase in tolerance to As3+ in control cells. Cell lines derived from MT normal mice (MT+/+) were only slightly more resistant (1.6-fold) to As3+ than cells from MT null mice (MT-/-). These results show that CAsE cells acquire tolerance to As3+, As5+, and DMA. It appears that this self-tolerance is based primarily on reduced cellular disposition of the metalloid and is not accounted for by changes in GSH or MT.

Dose-dependent effects on tissue distribution and metabolism of dimethylarsinic acid in the mouse after intravenous administration.

Most mammals methylate inorganic arsenic to dimethylarsinic acid (DMA). This organic arsenical causes organ-specific toxicity and is a multi-organ tumor promoter. The objective of this study was to examine whether dose could affect the distribution and metabolism of DMA. Female B6C3F1 mice (3-4/time point) were administered 1.11 or 111 mg/kg of DMA (1 microCi of [14C] or unlabeled) intravenously and killed serially (5-480 min). Blood was separated into plasma and red blood cell fractions and liver, kidney and lung were removed, weighed and homogenized. Tissue samples were oxidized and analyzed for DMA-derived radioactivity. Blood and several organs of the non-radioactive DMA-treated animals were digested in acid and analyzed by hydride generation atomic absorption spectrophotometry for DMA and metabolites. Concentration-time profiles showed a biexponential decrease of DMA-derived radioactivity in all tissues examined. Kidney had the highest concentration (1-20% dose/gm) of radioactivity of all tissues up to 60 min post-administration. Concentration of radioactivity was greater in plasma than red blood cells at 5 and 15 min and then was similar for the remaining time points. A dose-dependent effect on the concentration of radioactivity was observed in the lung. The retention of radioactivity in the lung was altered compared with liver and kidney, with a much longer t1/2beta and a disproportionate increase in area under the curve with increased dose. No methylated or demethylated products of DMA were detected in blood or any organ up to 8 h post-exposure. The dose-dependent distribution of DMA in the lung may have a role in the toxic effects DMA elicits in this organ.

Uric acid levels in plasma and urine in rats chronically exposed to inorganic As (III) and As(V).

The effect of inorganic arsenic (III) and arsenic (V) on renal excretion and plasma levels of uric acid was examined in rats. Oral administration of 1200 micrograms As/kg/day for 6 weeks diminished uric acid levels in plasma by 67.1% and 26.5% of control after the administration of As(III) and As(V), respectively. Renal excretion of uric acid was significantly reduced during the first 3 weeks following As (III) administration, with a subsequent increase to approach control values at the end of the treatment. When As(V) was administered, the diminution in renal excretion was significant at 6 weeks.

Alteration in bilirubin excretion in individuals chronically exposed to arsenic in Mexico.

We have studied hepatic function in individuals chronically exposed to arsenic (As) via drinking water in Region Lagunera, Mexico. We studied 51 individuals living in three villages exposed to As in water. Nazareno (0.014 mgAs/l), Santa Ana (0.1 mgAs/l) and Benito Juárez (0.3 mgAs/l). We determined the serum activity of aspartate aminotransferase (SAT) and alanine aminotransferase (ALT) as indicators of hepatocellular injury and that of gamma-glutamyl-transpeptidase (GGT) and alkaline phosphatase (ALP) as indicators of cholestasic injury. Serum bilirubin was used as an indicator of organic conjugated anion transport. Total proteins, albumin and globulin fraction in serum were used as indicators of biosynthetic liver capacity. The main findings of this study were the predominantly conjugated hyperbilirubinemia and increased serum ALP activity which were related to the concentration of total arsenic (TAs) in urine, suggesting the presence of cholestasis in As-exposed individuals. No significant changes were observed in the other parameters studied.

Lymphocyte proliferation kinetics and genotoxic findings in a pilot study on individuals chronically exposed to arsenic in Mexico.

In the search for early biological markers to detect genetic damage, a pilot study on a hydroarsenicism-exposed group was designed. Blood and urine samples were taken from 11 individuals chronically exposed and from 13 individuals with lower exposure to the metal. Lymphocyte cultures for cytogenetic studies and HGPRT assay were done with coded peripheral blood samples, while arsenic levels and the "rec assay" in B. subtilis were determined in urine samples. The highly exposed group excreted greater amounts of As, nevertheless the rec assay showed negative results. An interesting finding is that the cell-cycle kinetics exhibited a significant difference between the groups studied, the average generation time (AGT) was longer in the highly exposed group. The percentages of chromosomal aberrations and the frequencies of sister-chromatid exchanges were similar in both populations, although complex aberrations were more frequent in the highly exposed group, which also showed a higher average variation frequency in the HGPRT assay, but the 2 latter observations were not statistically significant. The lag in lymphocyte proliferation could mean an impairment of the immune response due to arsenic exposure.

Increased cytogenetic damage in outdoor painters.

Painters are exposed to an extensive variety of hazardous substances such as organic solvents, lead-containing pigments and residual plastic monomers. In this particular case, workers used commercially available exterior paints and occasionally gasoline or thinner as solvents. The application or removal of paints was performed without protection (masks or gloves). To determine occupational exposure risk, a monitoring study was designed. Group selection was made after a questionnaire administration, which included questions about lifestyle and medical history to exclude exposure to other potential sources of genotoxics. Smoking and drinking habits were also considered. Blood and buccal cell samples were obtained from 25 public building male painters and from a similar number of age- and gender-matched controls. Lead levels were measured in paint samples and in individuals' blood. Organic solvents and/or its metabolites were also determined in blood. Chromosomal aberrations (CA) and sister chromatid exchanges (SCE) were determined in peripheral blood lymphocyte cultures. Also, the frequency of micronuclei (MN) in buccal cells was investigated. Painters had higher lead levels in blood (p<0.05); CA and SCE in lymphocytes and MN in epithelial cells were also elevated (p<0.05). Cytogenetic damage was significantly associated with occupational exposure time but not with the levels of lead found in blood.

Lymphocyte replicating ability in individuals exposed to arsenic via drinking water.

A human monitoring study was carried out to explore the effect on lymphocyte proliferation of chronic exposure to arsenic (As) via drinking water. Blood and urine samples were taken from volunteers from a town where levels of As in the drinking water averaged 412 micrograms/l, and from a matched group of individuals, with similar socioeconomic status, that drank water with As average levels of 37.2 micrograms/l. Exposure was assessed by questionnaires and by determining the levels of As in urine and water samples. The evaluation of the peripheral blood lymphocyte proliferation was done at different culture times using labelling (LI), mitotic (MI) and replication indexes (RI) as endpoints. No significant differences were seen for either LI or MI, except for MI in 72 h cultures and in LI in males and females with skin lesions vs. those without lesions. Significant differences in RI were seen for exposed females but not for males. Correlations between LI and MI showed that progression from the initial S-to M-phase is altered in exposed individuals. Arsenic exposure as well as lead and mercury affect cellular immune response, making the endpoints of cell proliferation variables of interest in population monitoring study design, since they might provide information in health impairment due to exposure, which is important in risk assessment.

Cytogenetic effects in human exposure to arsenic.

The cytogenetic effects of arsenic exposure were studied among rural populations that live in the same geographical area and have similar socioeconomic status, but different degree of exposure to inorganic arsenic (As) via drinking water. A group of inhabitants of Santa Ana (408.17 micrograms/l of As in drinking water) were considered the exposed individuals and a group of inhabitants of Nazareno (29.88 micrograms/l) were considered as controls. Blood and urine samples were obtained from volunteers. Past and current exposure, health, and nutritional status as well as the presence of arsenic skin lesions were ascertained in study participants through questionnaires and physical examination. The frequencies and types of chromosomal aberrations in first-division metaphases were studied in whole blood lymphocyte cultures while the presence of micronuclei (MN) was studied in exfoliated epithelial cells obtained from the oral mucosa and from urine samples. Total arsenic (TAs) content, and the relative proportions of inorganic arsenic (IAs), and the metabolites monomethylarsonic (MMA) and dimethylarsinic (DMA) acid were determined in urine samples. Exposed individuals showed a significant increase in the frequency of chromatid and isochromatid deletions in lymphocytes and of MN in oral and urinary epithelial cells. Males were more affected than females, and a higher number of micronucleated oral cells were found among those individuals with skin lesions. The type of cytogenetic damage observed gives evidence of arsenic as a clastogenic/aneugenic carcinogen.

Arsenic levels in cooked food and assessment of adult dietary intake of arsenic in the Region Lagunera, Mexico.

The aim of this paper is to estimate the levels of arsenic (As) ingestion through cooked foods consumed in an arsenic endemic area and the assessment of their dietary intake of As. The study was conducted in two villages: a population chronically exposed to a high concentration of As via drinking water (410+/-35 microg/l) and to a low-exposure group (12+/-4 microg/l). A 24-h dietary recall questionnaire was applied to about 25 adult participants in each community. Samples of cooked food, ready for intake, were collected separately from each family's participants. To obtain the As estimate for each food item consumed, the mean quantity of food ingested in grams (wet weight) was calculated and the concentrations of total arsenic (TAs) in each cooked food were determined. The estimations of TAs intake were based on the sum over mean of As ingested from each food item consumed during the 24-h period for each participant. For the estimation of total daily As intake, we summed the mean obtained from food, plain water and hot beverage intakes. The TAs average intakes calculated for low-As-exposure group were 0.94 and 0.76 microg/kg body weight/day, for both summer and winter exposure scenarios, respectively. These values are 44.7 and 36% of the provisional tolerable daily intake (PTDI) for inorganic arsenic (2.14 microg/kg body weight/day), established by the World Health Organization (WHO) in 1989. The WHO reference value was obtained on a weekly basis intake estimation assuming an average body weight of 68 kg in adults. In contrast, for the high-exposure group the TAs average intakes were 16.6 and 12.3 microg/kg body weight/day for summer and winter, respectively. Ingestion via cooked food represented 32.5 and 43.9% of the total daily As intake in the high-exposure group; for summer and winter, respectively. None the less, the bioavailability of As through food can be different than via drinking water.

Lead exposure in children living in a smelter community in region Lagunera, Mexico.

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 Torreon, Coahuila. The third school is located in Comez 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 microg/dl (3.54-29.61) in the remote school, 21.8 microg/dl (8.37-52.08) in the intermediate school and 27.6 microg/dl (7.37-58.53) in children attending the close school. The percentage of children with PbB > 15 microg/dl was 6.80%, 84.9%, and 92.1% respectively. In this order, the geometric means (range) of Pb concentrations in air were 2.5 microg/m3 (1.1-7.5), 5.8 microg/m3 (4.3-8.5), and 6.1 microg/m3 (1.6-14.9). The Pb concentrations in dust from playgrounds areas in the intermediate and close school settings ranged from 1,457 to 4,162.5 mg/kg. Pb concentrations in drinking water were less than 5 microg/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.

The oxidation states of arsenic in well-water from a chronic arsenicism area of northern Mexico.

Aquifers in the Región Lagunera in northern Mexico are heavily contaminated with arsenic. The range of total arsenic concentrations in 128 water samples analyzed was 0.008 to 0.624 mg litre(-1), and concentrations greater than 0.05 mg litre(-1) were found in 50% of them. Approximately 400 000 people living in rural areas were exposed to high As concentrations. Most of the As was in inorganic form and pentavalent arsenic [As(V)] was the predominant species in 93% of the samples. In 36% of the samples, however, variable percentages (20-50) of trivalent As [As(III)] were found. Organic arsenicals were present in very small amounts. Since As(III) is several times more toxic than As(V), we suggest that periodic studies be performed on the As(III)/As(V) ratio in wells whose total As concentrations are above 0.05 mg litre(-1), in combination with epidemiological studies to evaluate possible differences in health effects produced by different As species.