Genetic variation in glutathione S-transferase omega-1, arsenic methyltransferase and methylene-tetrahydrofolate reductase, arsenic exposure and bladder cancer: a case-control study.

BACKGROUND: Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer. METHODS: Single nucleotide polymorphisms (SNPs) in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a case-control study in Southeastern Michigan and exposed to low to moderate (<50 µg/L) levels of arsenic in their drinking water. A time-weighted measure of arsenic exposure was constructed using measures from household water samples combined with past residential history, geocoded and merged with archived arsenic data predicted from multiple resources. RESULTS: While no single SNP in As3MT was significantly associated with bladder cancer overall, several SNPs were associated with bladder cancer among those exposed to higher arsenic levels. Individuals with one or more copies of the C allele in rs11191439 (the Met287Thr polymorphism) had an elevated risk of bladder cancer (OR = 1.17; 95% CI = 1.04-1.32 per 1 µg/L increase in average exposure). However, no association was observed between average arsenic exposure and bladder cancer among TT homozygotes in the same SNP. Bladder cancer cases were also 60% less likely to be homozygotes for the A allele in rs1476413 in MTHFR compared to controls (OR = 0.40; 95% CI = 0.18-0.88). CONCLUSIONS: Variation in As3MT and MTHFR is associated with bladder cancer among those exposed to relatively low concentrations of inorganic arsenic. Further investigation is warranted to confirm these findings.

Lead poisoning and asthma among low-income and African American children in Saginaw, Michigan.

OBJECTIVE: We sought to ascertain whether asthmatic children are more likely to have elevated blood lead levels (EBLLs), BLLs ≥ 10 µg/dL, than non-asthmatic children. Household risk factors associated with both lead and asthma were examined. METHOD: We undertook a cross-sectional study involving children residing in mainly low-income and minority households in Michigan which were identified by the Statewide Systemic Tracking of Elevated Lead Levels and Remediation database (STELLAR) (n=356 children). RESULTS: Of the 356 index children, 19% had EBLLs and 15% were doctor-diagnosed asthmatic. After adjusting for confounders known to be related to lead poisoning and/or asthma, association remained between asthmatic children and EBLL children (AOR: 5.17; 95% CI (1.25-21.37)). CONCLUSIONS: The results of our study show that asthmatic children are over 5 times more likely to have EBLLs than non-asthmatics (AOR: 5.17; 95% CI (1.25-21.37)). Intervention strategies designed to address lead poisoning prevention may be effective in reducing incidence of asthma. Further study is required.

Multiple metals exposure in a small-scale artisanal gold mining community.

Urinary metals were characterized in 57 male residents of a small-scale gold mining community in Ghana. Chromium and arsenic exceeded health guideline values for 52% and 34%, respectively, of all participants. About 10-40% of the participants had urinary levels of aluminum, copper, manganese, nickel, selenium, and zinc that fell outside the U.S. reference range. Exposures appear ubiquitous across the community as none of the elements were associated with occupation, age, and diet.

Lifetime exposure to arsenic in drinking water and bladder cancer: a population-based case-control study in Michigan, USA.

OBJECTIVE: Arsenic in drinking water has been linked with the risk of urinary bladder cancer, but the dose-response relationships for arsenic exposures below 100 microg/L remain equivocal. We conducted a population-based case-control study in southeastern Michigan, USA, where approximately 230,000 people were exposed to arsenic concentrations between 10 and 100 microg/L. METHODS: This study included 411 bladder cancer cases diagnosed between 2000 and 2004, and 566 controls recruited during the same period. Individual lifetime exposure profiles were reconstructed, and residential water source histories, water consumption practices, and water arsenic measurements or modeled estimates were determined at all residences. Arsenic exposure was estimated for 99% of participants' person-years. RESULTS: Overall, an increase in bladder cancer risk was not found for time-weighted average lifetime arsenic exposure >10 microg/L when compared with a reference group exposed to <1 microg/L (odds ratio (OR) = 1.10; 95% confidence interval (CI): 0.65, 1.86). Among ever-smokers, risks from arsenic exposure >10 microg/L were similarly not elevated when compared to the reference group (OR = 0.94; 95% CI: 0.50, 1.78). CONCLUSIONS: We did not find persuasive evidence of an association between low-level arsenic exposure and bladder cancer. Selecting the appropriate exposure metric needs to be thoughtfully considered when investigating risk from low-level arsenic exposure.

Influence of groundwater recharge and well characteristics on dissolved arsenic concentrations in southeastern Michigan groundwater.

Arsenic concentrations exceeding 10 microg/l, the United States maximum contaminant level and the World Health Organization guideline value, are frequently reported in groundwater from bedrock and unconsolidated aquifers of southeastern Michigan. Although arsenic-bearing minerals (including arsenian pyrite and oxide/hydroxide phases) have been identified in Marshall Sandstone bedrock of the Mississippian aquifer system and in tills of the unconsolidated aquifer system, mechanisms responsible for arsenic mobilization and subsequent transport in groundwater are equivocal. Recent evidence has begun to suggest that groundwater recharge and characteristics of well construction may affect arsenic mobilization and transport. Therefore, we investigated the relationship between dissolved arsenic concentrations, reported groundwater recharge rates, well construction characteristics, and geology in unconsolidated and bedrock aquifers. Results of multiple linear regression analyses indicate that arsenic contamination is more prevalent in bedrock wells that are cased in proximity to the bedrock-unconsolidated interface; no other factors were associated with arsenic contamination in water drawn from bedrock or unconsolidated aquifers. Conditions appropriate for arsenic mobilization may be found along the bedrock-unconsolidated interface, including changes in reduction/oxidation potential and enhanced biogeochemical activity because of differences between geologic strata. These results are valuable for understanding arsenic mobilization and guiding well construction practices in southeastern Michigan, and may also provide insights for other regions faced with groundwater arsenic contamination.

Occupational and environmental exposures to heavy metals: risk factors for male infertility in Lebanon?

A case-control study was conducted to examine whether occupational or environmental exposures, particularly to heavy metals, are associated with male infertility in Lebanon, a war-torn country with a history of environmental degradation. Seventy-four infertile cases and 76 fertile controls were selected from 2 major fertility clinics in Beirut. Data collection involved risk-factor interviews, semen analysis, and blood collection for heavy metal analysis. Multiple regression analysis showed that men with reported occupational exposures were twice as likely to be infertile as unexposed men. However, none of the subcategories of infertile men (based on semen analysis results) had significantly higher whole blood concentrations of heavy metals when compared to fertile controls. Blood concentrations were well within the range for referent populations of healthy individuals. Thus, despite Lebanon's poor record of occupational and environmental stewardship, exposure to metal pollutants does not appear to represent an important risk factor for male infertility.

Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: a standardized mortality ratio analysis.

BACKGROUND: Exposure to arsenic concentrations in drinking water in excess of 300 microg/L is associated with diseases of the circulatory and respiratory system, several types of cancer, and diabetes; however, little is known about the health consequences of exposure to low-to-moderate levels of arsenic (10-100 microg/L). METHODS: A standardized mortality ratio (SMR) analysis was conducted in a contiguous six county study area of southeastern Michigan to investigate the relationship between moderate arsenic levels and twenty-three selected disease outcomes. Disease outcomes included several types of cancer, diseases of the circulatory and respiratory system, diabetes mellitus, and kidney and liver diseases. Arsenic data were compiled from 9251 well water samples tested by the Michigan Department of Environmental Quality from 1983 through 2002. Michigan Resident Death Files data were amassed for 1979 through 1997 and sex-specific SMR analyses were conducted with indirect adjustment for age and race; 99% confidence intervals (CI) were reported. RESULTS: The six county study area had a population-weighted mean arsenic concentration of 11.00 microg/L and a population-weighted median of 7.58 microg/L. SMR analyses were conducted for the entire six county study area, for only Genesee County (the most populous and urban county), and for the five counties besides Genesee. Concordance of results across analyses is used to interpret the findings. Elevated mortality rates were observed for both males (M) and females (F) for all diseases of the circulatory system (M SMR, 1.11; CI, 1.09-1.13; F SMR, 1.15; CI, 1.13,-1.17), cerebrovascular diseases (M SMR, 1.19; CI, 1.14-1.25; F SMR, 1.19; CI, 1.15-1.23), diabetes mellitus (M SMR, 1.28; CI, 1.18-1.37; F SMR, 1.27; CI, 1.19-1.35), and kidney diseases (M SMR, 1.28; CI, 1.15-1.42; F SMR, 1.38; CI, 1.25-1.52). CONCLUSION: This is some of the first evidence to suggest that exposure to low-to-moderate levels of arsenic in drinking water may be associated with several of the leading causes of mortality, although further epidemiologic studies are required to confirm the results suggested by this ecologic SMR analysis.

Toenails as a biomarker of inorganic arsenic intake from drinking water and foods.

Toenails were used recently in epidemiological and environmental health studies as a means of assessing exposure to arsenic from drinking water. While positive correlations between toenail and drinking-water arsenic concentrations were reported in the literature, a significant percentage of the variation in toenail arsenic concentration remains unexplained by drinking-water concentration alone. Here, the influence of water consumption at home and work, food intake, and drinking-water concentration on toenail arsenic concentration was investigated using data from a case-control study being conducted in 11 counties of Michigan. The results from 440 controls are presented. Log-transformed drinking-water arsenic concentration at home was a significant predictor (p < .05) of toenail arsenic concentration (R2 = .32). When arsenic intake from consumption of tap water and beverages made from tap water (microg/L arsenic x L/d = microg/d) was used as a predictor variable, the correlation was markedly increased for individuals with >1 microg/L arsenic (R2 = .48). Increased intake of seafood and intake of arsenic from water at work were independently and significantly associated with increased toenail arsenic concentration. However, when added to intake at home, work drinking-water exposure and food intake had little influence on the overall correlation. These results suggest that arsenic exposure from drinking-water consumption is an important determinant of toenail arsenic concentration, and therefore should be considered when validating and applying toenails as a biomarker of arsenic exposure.

Major contributors to inorganic arsenic intake in southeastern Michigan.

Accurate estimates of inorganic arsenic intake are critical for evaluating potential health risks. Intake estimates have not been critically examined in regions of the United States where people are at risk from arsenic concentrations in drinking water exceeding the maximum contaminant limit of 10 microg/l. In southeastern Michigan, approximately 8% of the population is exposed to arsenic in drinking water >10 microg/l. Four hundred and forty participants of a control group in this region, frequency matched to cases in a population-based bladder cancer case-control study, answered a questionnaire about water and food consumption and smoking history. Water samples were collected from participants' current residences and analyzed for arsenic. Water arsenic data were combined with questionnaire data and published data of inorganic arsenic concentrations in select foods and cigarettes to examine the influence of arsenic in water at home, at work, and at other places, as well as inorganic arsenic intake from food and cigarettes. Monte Carlo simulations and analyses of individual-level intake estimates were conducted to quantify the variability attributed to different parameters in this primarily elderly white male population of southeastern Michigan. The 95th percentile of total inorganic arsenic intake ranges from 11 to 24 microg/day, depending on the intake metric selected. Results indicate that arsenic in home drinking water is the largest source of inorganic arsenic, accounting for 55.1% of the variance in the intake estimates. Food intake explains 37.3% of the variance, with rice being the largest contributor. In the upper decile of intake, consumption of plain water and beverages made with water at home, and ingestion of arsenic in water at work, also contribute to intake estimates. Water used for cooking and arsenic from smoking, however, only minimally alter the intake estimates. This is due to a relatively small volume of water absorbed into cooked foods and low concentrations of arsenic in cigarettes. Results from this study will assist investigators in better characterizing exposure to inorganic arsenic.

Effects of time and point-of-use devices on arsenic levels in Southeastern Michigan drinking water, USA.

Health effects associated with chronic, low-level exposures to arsenic in drinking water (<100 microg/L) remain unclear, in part due to uncertainties in assessing exposure. Drinking water concentrations have been used to assess past exposure to arsenic in epidemiological studies, under the assumption that a single measurement can be used to estimate historical exposure. This study aims to better understand (1) temporal variability in arsenic concentrations in drinking water and (2) the impact of point-of-use (POU) treatment devices on arsenic exposure measurements, and on reliability of the exposure measurement for population-level studies. Multiple drinking water samples were collected at two points in time (an average of fourteen months apart) for 261 individuals enrolled in a case-control study of arsenic exposure and bladder cancer in Michigan. Sources of drinking water included private wells (n = 221), public water supplies (n = 33), and bottled water (n = 7); mean arsenic concentration was highest in private wells (7.28 microg/L) and lowest in bottled water samples (0.28 microg/L). Arsenic concentrations in primary drinking water samples were highly correlated (r = 0.88, p < 0.0001, n = 196), with 3% of the water sources exceeding the United States Environmental Protection Agency's Maximum Contaminant Level (MCL) in one sample but not in the other sample. Measurement reproducibility did not vary by type of POU device (e.g., softener, filter, reverse osmosis system). Arsenic concentrations did differ, however, between samples treated with POU devices and untreated samples taken on the same day. Substantial differences in arsenic concentrations were consistently observed for reverse osmosis systems; other POU devices had variable effects on arsenic concentrations. These results indicate that while a single residential arsenic measurement may be used to represent exposure in this region, researchers must obtain information on changes in water source and POU treatment devices to better characterize population exposures over time.

Lead contamination in cocoa and cocoa products: isotopic evidence of global contamination.

In this article we present lead concentrations and isotopic compositions from analyses of cocoa beans, their shells, and soils from six Nigerian cocoa farms, and analyses of manufactured cocoa and chocolate products. The average lead concentration of cocoa beans was

Mercury removal from water using activated carbons derived from organic sewage sludge.

Various types of activated carbons were developed from organic sewage sludge (SS) using H(2)SO(4), H(3)PO(4) and ZnCl(2) as chemical activation reagents, and the removal of Hg(II) from aqueous solution by these carbons was effectively demonstrated. The quality of the activated carbons was dramatically improved owing to chemical activation. ZnCl(2) activated carbon had the highest capability for Hg(II) adsorption, followed by H(3)PO(4) and H(2)SO(4) activated carbons. The adsorption was greatly affected by Hg(II) concentration, solution pH and carbon dosage, and followed Lagergren first order rate equation and Freundlich isotherm model. Desorption results indicated that around 60% to 80% of the adsorbed Hg(II) could be recovered from the carbons to 0.1 M HNO(3) solution by sonication treatment. Accordingly, it is believed that the activated carbons developed in this study are effective and practical for utilization in industrial wastewater treatment for mercury removal.

Profiles of trace elements in toenails of Arab-Americans in the Detroit area, Michigan.

Exposure to environmental contaminants is complicated by factors related to socioeconomic status, diet, and other culturally conditioned risk behaviors. Determination of a trace element profile in toenails can be used as a tool in biomonitoring the exposure history or assessing the deficiency of a particular element in a study population, which can lead to a better understanding of environmental and disease risks. Toenail clippings from 259 Arab Americans (163 adults, 96 children) residing in a highly industrialized area were analyzed for Al, V, Cr, Mn, Co, Ni, Cu, As, Se, Mo, Cd, Ba, Tl, and Pb using an inductively coupled plasma-mass spectrometer. Mean concentrations were compared with published values, and the influence of age, gender, and other demographic factors were explored. Elevated levels of Ni in this population warrant further investigation. Significant differences in the mean concentration of Al, V, Cr, Mn, Cd, Pb, and Se exist between toenails of adults and children. Pearson correlation coefficients reveal strong significant associations among Cd, Cr, and Tl (p<0.05), in addition to other elements. These investigations provide insight into exposures and factors influencing exposures in this population while adding to the growing fund of knowledge surrounding use of toenails as a marker of exposure.

Elevated prenatal methylmercury exposure in Nigeria: evidence from maternal and cord blood.

Methylmercury is a neurodevelopmental toxicant that is globally distributed though little is known about prenatal exposures in sub-Saharan Africa. The objective of the current study was to measure total mercury levels in cord blood and maternal blood from 95 mother-newborn pairs recruited from hospitals in Nnewi, Nigeria. The secondary aims of the study were to explore if demographic and dietary factors were associated with blood mercury levels, and to explore if mercury levels were associated with any self-reported health outcome and childbirth outcome. Maternal blood mercury levels averaged 3.6 µg L(-1) and ranged from 1.1 µg L(-1) to 9.5 µg L(-1). Cord blood mercury averaged 5.1 µg L(-1) and ranged from 1.2 µg L(-1) to 10.6 µg L(-1). The mean ratio of mercury in paired cord blood to maternal blood was 1.5 and it ranged from 0.4 to 3.2. Mercury in maternal and cord blood were significantly correlated (r=0.471). More than one-third of mothers reported eating fish at least once per day, and a weak (p=0.08) fish consumption-related increase in blood mercury was found. Cord blood mercury was positively and significantly associated with birth weight and length, and head and chest circumference. Mercury levels in 36% of the participants exceeded the biomonitoring guideline associated with the United States Environmental Protection Agency (U.S. EPA) reference dose for mercury. The study shows that pregnant women and their newborns are exposed to methylmercury and that their exposures are higher compared to general populations sampled from other regions of the world.

Visualization and exploratory analysis of epidemiologic data using a novel space time information system.

BACKGROUND: Recent years have seen an expansion in the use of Geographic Information Systems (GIS) in environmental health research. In this field GIS can be used to detect disease clustering, to analyze access to hospital emergency care, to predict environmental outbreaks, and to estimate exposure to toxic compounds. Despite these advances the inability of GIS to properly handle temporal information is increasingly recognised as a significant constraint. The effective representation and visualization of both spatial and temporal dimensions therefore is expected to significantly enhance our ability to undertake environmental health research using time-referenced geospatial data. Especially for diseases with long latency periods (such as cancer) the ability to represent, quantify and model individual exposure through time is a critical component of risk estimation. In response to this need a STIS - a Space Time Information System has been developed to visualize and analyze objects simultaneously through space and time. RESULTS: In this paper we present a "first use" of a STIS in a case-control study of the relationship between arsenic exposure and bladder cancer in south eastern Michigan. Individual arsenic exposure is reconstructed by incorporating spatiotemporal data including residential mobility and drinking water habits. The unique contribution of the STIS is its ability to visualize and analyze residential histories over different temporal scales. Participant information is viewed and statistically analyzed using dynamic views in which values of an attribute change through time. These views include tables, graphs (such as histograms and scatterplots), and maps. In addition, these views can be linked and synchronized for complex data exploration using cartographic brushing, statistical brushing, and animation. CONCLUSION: The STIS provides new and powerful ways to visualize and analyze how individual exposure and associated environmental variables change through time. We expect to see innovative space-time methods being utilized in future environmental health research now that the successful "first use" of a STIS in exposure reconstruction has been accomplished.

Urinary arsenic species, toenail arsenic, and arsenic intake estimates in a Michigan population with low levels of arsenic in drinking water.

The large disparity between arsenic concentrations in drinking water and urine remains unexplained. This study aims to evaluate predictors of urinary arsenic in a population exposed to low concentrations (≤50 µg/l) of arsenic in drinking water. Urine and drinking water samples were collected from a subsample (n=343) of a population enrolled in a bladder cancer case-control study in southeastern Michigan. Total arsenic in water and arsenic species in urine were determined using ICP-MS: arsenobetaine (AsB), arsenite (As[III]), arsenate (As[V]), methylarsenic acid (MMA[V]), and dimethylarsenic acid (DMA[V]). The sum of As[III], As[V], MMA[V], and DMA[V] was denoted as SumAs. Dietary information was obtained through a self-reported food intake questionnaire. Log(10)-transformed drinking water arsenic concentration at home was a significant (P<0.0001) predictor of SumAs (R(2)=0.18). Associations improved (R(2)=0.29, P<0.0001) when individuals with less than 1 µg/l of arsenic in drinking water were removed and further improved when analyses were applied to individuals who consumed amounts of home drinking water above the median volume (R(2)=0.40, P<0.0001). A separate analysis indicated that AsB and DMA[V] were significantly correlated with fish and shellfish consumption, which may suggest that seafood intake influences DMA[V] excretion. The Spearman correlation between arsenic concentration in toenails and SumAs was 0.36 and between arsenic concentration in toenails and arsenic concentration in water was 0.42. Results show that arsenic exposure from drinking water consumption is an important determinant of urinary arsenic concentrations, even in a population exposed to relatively low levels of arsenic in drinking water, and suggest that seafood intake may influence urinary DMA[V] concentrations.

Low-level determination of six arsenic species in urine by High Performance Liquid Chromatography-Inductively Coupled Plasma-Mass Spectrometry (HPLC-ICP-MS).

Many methods that have been used to speciate arsenic metabolites in urine are unable to adequately resolve the chromatographic peaks for arsenite (As[iii]) and arsenobetaine (AsB). We present a High Performance Liquid Chromatography-Inductively Coupled Plasma-Mass Spectrometry (HPLC-ICP-MS) method that has been optimized to reliably measure the following six arsenic species in human urine: As[iii], arsenate (As[v]), monomethylarsonous acid (MMA[iii]), monomethylarsonic acid (MMA[v]), dimethylarsinic acid (DMA[v]) and AsB. The method was evaluated with regards to changes in mobile phase, accuracy and precision. The ability to quantify the six species in a given sample depended on the low detection limits of the method-0.06 µg L-1 for AsB, 0.11 µg L-1 for As[iii], 0.08 µg L-1 for DMA[v], 0.12 µg L-1 for MMA[v] and 0.15 µg L-1 for As[v]. The procedure was used to measure the six arsenic species in urine samples from 387 individuals in southeast Michigan who are chronically exposed to slightly elevated levels of arsenic in their drinking water. The DMA[v] was detected in 99.2% of samples, AsB in 98.2%, MMA[v] in 73.4%, As[iii] in 45.0%, and As[v] in 27.1%. No MMA[iii] was detected even in samples analyzed within 6 hours after collection. The results raise some doubt as to whether MMA[iii] is a significant metabolite in urine of people exposed to arsenic concentrations below 20 µg L-1 in their drinking water.