Residential proximity to dioxin-emitting facilities and risk of non-Hodgkin lymphoma in the NIH-AARP Diet and Health Study.

BACKGROUND: Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) are persistent organic pollutants emitted from industrial sources. Residential proximity to these emissions has been associated with risk of non-Hodgkin lymphoma (NHL) in a limited number of studies. METHODS: We evaluated associations between residential proximity to PCDD/F-emitting facilities and NHL in the NIH-AARP Diet and Health Study (N = 451,410), a prospective cohort enrolled in 1995-1996 in 6 states and 2 U.S. cities. We linked enrollment addresses with a U.S. Environmental Protection Agency database of 4,478 historical PCDD/F sources with estimated toxic equivalency quotient (TEQ) emissions. We evaluated associations between NHL and exposures during a historical period prior to enrollment (1980-1995) using an average emissions index, weighted by toxicity, distance, and wind direction (AEI-W [g TEQ/km2]) within 3-, 5- and 10 km of residences. We also evaluated proximity-only metrics indicating the presence/absence of one or more facilities within each distance, and metrics calculated separately for each facility type. We used Cox regression to estimate associations (hazard ratio, HR; 95 % confidence interval, 95 %CI) with NHL and major subtypes, adjusting for demographic, lifestyle, and dietary factors. RESULTS: A total of 6,467 incident cases of NHL were diagnosed through 2011. Participants with an AEI-W ≥ 95th percentile had elevated risk of NHL compared to those unexposed at 3 km (HR = 1.16; 95 %CI = 0.89-1.52; p-trend = 0.24), 5 km (HR = 1.20;95 %CI = 0.99-1.46;p-trend = 0.05) and 10 km (HR = 1.15; 95 %CI = 0.99-1.34; p-trend = 0.04). We found a positive association at 5 km with follicular lymphoma (HR≥95vs.0 = 1.62; 95 %CI = 0.98-2.67; p-trend = 0.05) and a suggestive association for diffuse large B-cell lymphoma (HR≥95vs.0 = 1.40; 95 %CI = 0.91-2.14; p-trend = 0.11). NHL risk was also associated with high emissions from coal-fired power plants within 10 km (HR≥95vs.0 = 1.42; 95 %CI = 1.09-1.84; p-trend = 0.05). CONCLUSIONS: Residential proximity to relatively high dioxin emissions from industrial sources may increase the risk of NHL and specific subtypes.

Integrating different tools and technologies to advance drinking water quality exposure assessments.

Contaminants in drinking water are a major contributor to the human exposome and adverse health effects. Assessing drinking water exposure accurately in health studies is challenging, as several of the following study design domains should be addressed as adequately as possible. In this paper, we identify the domains Time, Space, Data Quality, Data Accessibility, economic considerations of Study Size, and Complex Mixtures. We present case studies for three approaches or technologies that address these domains differently in the context of exposure assessment of drinking water quality: regulated contaminants in monitoring databases, high-resolution mass spectrometry (HRMS)-based wide-scope chemical analysis, and effect-based bioassay methods. While none of these approaches address all the domains sufficiently, together they have the potential to carry out exposure assessments that would complement each other and could advance the state-of-science towards more accurate risk analysis. The aim of our study is to give researchers investigating health effects of drinking water quality the impetus to consider how their exposure assessments relate to the above-mentioned domains and whether it would be worthwhile to integrate the advanced technologies presented into planned risk analyses. We highly suggest this three-pronged approach should be further evaluated in health risk analyses, especially epidemiological studies concerning contaminants in drinking water. The state of the knowledge regarding potential benefits of these technologies, especially when applied in tandem, provides more than sufficient evidence to support future research to determine the implications of combining the approaches described in our case studies in terms of protection of public health.

Comparison of Trihalomethane exposure assessment metrics in epidemiologic analyses of reproductive and developmental outcomes.

BACKGROUND: Researchers have developed exposure assessment metrics for disinfection by-products (DBPs) utilizing drinking water monitoring data and accounting for spatial and temporal variability, water consumption, and showering and bathing time with an expectation of decreasing exposure misclassification compared to the use of measured concentrations at public water supply (PWS) monitoring locations alone. OBJECTIVE: We used exposure data collected for a previous study of DBPs to evaluate how different sources of information impact trihalomethane (THM) exposure estimates. METHODS: We compared gestational exposure estimates to THMs based on water utility monitoring data alone, statistical imputation of daily concentrations to incorporate temporal variability, and personal water consumption and use (bathing and showering). We used Spearman correlation coefficients and ranked kappa statistics to compare exposure classifications. RESULTS: Exposure estimates based on measured or imputed daily THM concentrations, self-reported consumption, or bathing and showering differed substantially from estimates based solely on concentrations from PWS quarterly monitoring reports. Ranked exposure classifications, high to low quartiles or deciles, were generally consistent across each exposure metric (i.e., a subject with "high" exposure based on measured or imputed THM concentrations generally remained in the "high" category across exposure metrics.) The measured concentrations and imputed daily (i.e., spline regression) concentrations were highly correlated (r = 0.98). The weighted kappa statistics comparing exposure estimates using different exposure metrics ranged from 0.27 to 0.89, with the highest values for the ingestion + bathing/showering metrics compared to metrics for bathing/showering only (0.76 and 0.89). Bathing and showering contributed the most to "total" THM exposure estimates. IMPACT STATEMENT: We compare exposure metrics capturing temporal variability and multiple estimates of personal THM exposure with THM concentrations from PWS monitoring data. Our results show exposure estimates based on imputed daily concentrations accounting for temporal variability were very similar to the measured THM concentrations. We observed low agreement between imputed daily concentrations and ingestion-based estimates. Considering additional routes of exposure (e.g., inhalation and dermal) slightly increased agreement with the measured PWS exposure estimate in this population. Overall, the comparison of exposure assessment metrics allows researchers to understand the added value of additional data collection for future epidemiologic analyses of DBPs.

Contributions of nearby agricultural insecticide applications to indoor residential exposures.

BACKGROUND: Pesticide exposure has been associated with adverse health effects. We evaluated relationships between proximity to agricultural insecticide applications and insecticides in household dust, accounting for land use and wind direction. METHODS: We measured concentrations (ng/g) of nine insecticides in carpet-dust samples collected from 598 California homes. Using a geographic information system (GIS), we integrated the California Pesticide Use Reporting (CPUR) database to estimate agricultural use within residential buffers with radii of 0.5 to 4 km. We calculated the density of use (kg/km2) during 30-, 60-, 180-, and 365-day periods prior to dust collection and evaluated relationships between three density metrics (CPUR unit-based, agricultural land area adjusted, and average daily wind direction adjusted) and dust concentrations. We modeled natural-log transformed concentrations using Tobit regression for carbaryl, chlorpyrifos, cypermethrin, diazinon, and permethrin. Odds of detection were modeled with logistic regression for azinphos-methyl, cyfluthrin, malathion, and phosmet. We adjusted for season, year, occupation, and home/garden uses. RESULTS: Chlorpyrifos use within 1-4 km was associated with 1 to 2-times higher dust concentrations in both the 60- and 365-day periods. Carbaryl applications within 2-4 km of homes 60-days prior to dust collection were associated with 3 to 7-times higher concentrations and the 4 km trend was strongest using the wind-adjusted metric (p-trend = 0.04). For diazinon, there were 2-times higher concentrations for the 60-day metrics in the 2 km buffer and for the CPUR and wind-adjusted metrics within 4 km. Cyfluthrin, phosmet, and azinphos-methyl applications within 4 km in the prior 365-days were associated with 2-, 6-, and 3-fold higher odds of detection, respectively. CONCLUSIONS: Agricultural use of six of the nine insecticides within 4 km is an important determinant of indoor contamination. Our findings demonstrated that GIS-based metrics for quantifying potential exposure to fugitive emissions from agriculture should incorporate tailored distances and time periods and support wind-adjustment for some, but not all insecticides.

Agricultural and domestic pesticides in house dust from different agricultural areas in France.

Pesticides have been associated with various pathologies, and there is growing evidence of pesticide presence in domestic environments. However, most available studies focused on a limited number of pesticides or households, and few have been conducted in Europe. We aimed to assess indoor pesticide contamination by screening the prevalence of 276 pesticides and ten pesticide metabolites, in French households from different agricultural and urban areas. We sampled indoor dust from 239 households in 2012, proximate to orchards (n = 69), cereals (n = 66) and vineyard (n = 68) crops, or from urban area (n = 36). we used cellulose wipes moistened with isopropanol and polypropylene dust traps to collect recent (7 and 30 days, respectively) and settled dust (> 6 months). Overall, 125 pesticides and piperonyl butoxide were detected at least once in households, mostly at low prevalence: 97 in recent dust, and 111 in settled dust. In recent dust, the most prevalent compounds were o-phenylphenol (168 households, 70%), pentachlorophenol (86, 36%), and piperonyl butoxide (82, 34%). In addition to agricultural pesticides, we found a high proportion of domestic and banned compounds in recent and settled house dust. Several pesticides were identified in house dust, from different pesticide groups and sources. Our results suggest that domestic usage and persistence of banned pesticides may contribute substantially to indoor pesticide contamination. Graphical abstract 97 pesticides detected in households' recent indoor dust.

Verifying locations of sources of historical environmental releases of dioxin-like compounds in the U.S.: implications for exposure assessment and epidemiologic inference.

Polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) emissions from industrial sources contaminate the surrounding environment. Proximity-based exposure surrogates assume accuracy in the location of PCDD/F sources, but locations are not often verified. We manually reviewed locations (i.e., smokestack geo-coordinates) in a historical database of 4478 PCDD/F-emitting facilities in 2009 and 2016. Given potential changes in imagery and other resources over this period, we re-reviewed a random sample of 5% of facilities (n = 240) in 2016. Comparing the original and re-review of this sample, we evaluated agreement in verification (location confirmed or not) and distances between verified locations (verification error), overall and by facility type. Using the verified location from re-review as a gold standard, we estimated the accuracy of proximity-based exposure metrics and epidemiologic bias. Overall agreement in verification was high (>84%), and verification errors were small (median = 84 m) but varied by facility type. Accuracy of exposure classification (≥1 facility within 5 km) for a hypothetical study population also varied by facility type (sensitivity: 69-96%; specificity: 95-98%). Odds ratios were attenuated 11-69%, with the largest bias for rare facility types. We found good agreement between reviews of PCDD/F source locations, and that exposure prevalence and facility type may influence associations with exposures derived from this database. Our findings highlight the need to consider location error and other contextual factors when using proximity-based exposure metrics.

Bladder Cancer and Water Disinfection By-product Exposures through Multiple Routes: A Population-Based Case-Control Study (New England, USA).

BACKGROUND: Ingestion of disinfection byproducts has been associated with bladder cancer in multiple studies. Although associations with other routes of exposure have been suggested, epidemiologic evidence is limited. OBJECTIVES: We evaluated the relationship between bladder cancer and total, chlorinated, and brominated trihalomethanes (THMs) through various exposure routes. METHODS: In a population-based case­control study in New England (n=(1,213) cases; n=(1,418) controls), we estimated lifetime exposure to THMs from ingestion, showering/bathing, and hours of swimming pool use. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression adjusted for confounders. RESULTS: Adjusted ORs for bladder cancer comparing participants with exposure above the 95th percentile with those in the lowest quartile of exposure (based on the distribution in controls) were statistically significant for average daily intake mg/d of total THMs [OR=1.53 (95% CI: 1.01, 2.32), p-trend=0.16] and brominated THMs [OR=1.98 (95% CI: 1.19, 3.29), p-trend=0.03]. For cumulative intake mg, the OR at the 95th percentile of total THMs was 1.45 (95% CI: 0.95, 2.2), p-trend=0.13; the ORs at the 95th percentile for chlorinated and brominated THMs were 1.77 (95% CI: 1.05, 2,.99), p-trend=0.07 and 1.78 (95% CI: 1.05, 3.00), p-trend=0.02, respectively. The OR in the highest category of showering/bathing for brominated THMs was 1.43 (95% CI: 0.80, 2.42), p-trend=0.10. We found no evidence of an association for bladder cancer and hours of swimming pool use. CONCLUSIONS: We observed a modest association between ingestion of water with higher THMs (>95th percentile vs.<25th percentile) and bladder cancer. Brominated THMs have been a particular concern based on toxicologic evidence, and our suggestive findings for multiple metrics require further study in a population with higher levels of these exposures. Data from this population do not support an association between swimming pool use and bladder cancer. https://doi.org/10.1289/EHP89.

Comparison of industrial emissions and carpet dust concentrations of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans in a multi-center U.S. study.

Proximity to facilities emitting polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F) has been associated with increased risk of non-Hodgkin lymphoma (NHL). There is limited information about whether proximity to industrial sources leads to indoor PCDD/F contamination of homes. We measured carpet dust concentrations (pg/g) of 17 toxic PCDD/F congeners and calculated their toxic equivalence (TEQ) in 100 homes in a population-based case-control study of NHL in Detroit, Los Angeles, Seattle, and Iowa (1998-2000). We took global positioning system readings at residences and obtained coordinates and PCDD/F emissions (ng TEQ/yr) from an Environmental Protection Agency database for 6 facility types: coal-fired electricity generating plants, cement kilns burning non-hazardous waste, hazardous waste incinerators, medical waste incinerators, municipal solid waste incinerators, and sewage sludge incinerators. For each residence, we computed an inverse distance-squared weighted average emission index (AEI [pg TEQ/km2/yr]) for all facilities within 5km from 1983 to 2000. We also computed AEIs for each of the 6 facility types. We evaluated relationships between PCDD/F dust concentrations and the all-facility AEI or categories of facility-type AEIs using multivariable linear regression, adjusting for study center, demographics, and home characteristics. A doubling of the all-facility AEI was associated with a 4-8% increase in PCDD/F dust concentrations of 7 of 17 PCDD/F congeners and the TEQ (p-value<0.1). We also observed positive associations between PCDD/F dust concentrations and facility-type AEIs (highest vs. lowest exposure category) for municipal solid waste incinerators (9 PCDD/F, TEQ), and medical waste incinerators (7 PCDD/F, TEQ) (p<0.1). Our results from diverse geographical areas suggest that industrial PCDD/F emission sources contribute to residential PCDD/F dust concentrations. Our emissions index could be improved by incorporating local meteorological data and terrain characteristics. Future research is needed to better understand the links between nearby emission sources, human exposure pathways, and health risks.

Temporal Trends of Insecticide Concentrations in Carpet Dust in California from 2001 to 2006.

Active ingredients in residential and agricultural insecticides have changed over time, due in part to regulatory restrictions. Few studies have evaluated how changes in active ingredients have impacted insecticide levels measured in homes. We measured concentrations of insecticides in one carpet-dust sample from each of 434 homes in California from 2001 to 2006. Analytes included four insecticides sold for indoor home use during our study period (carbaryl, cypermethrin, permethrin, and propoxur) and four that are no longer sold for indoor use including dichlorodiphenyltrichloroethylene (DDT, removed from the market in 1972), chlordane (1988), chlorpyrifos (2001), and diazinon (2004). We considered other potential determinants of concentrations of insecticides in carpet dust, such as home and garden use, occupational exposure, and nearby agricultural applications. We calculated the percentage change in the concentration of each insecticide per year, adjusting for significant determinants. In adjusted models, concentrations of insecticides in carpet dust decreased for three of four insecticides no longer sold for residential use: chlordane (-15% per year), chlorpyrifos (-31%), diazinon (-48%), and propoxur (-34%), which is currently sold for residential use but with increased restrictions since 1997. Concentrations of other insecticides sold for indoor use (carbaryl, cypermethrin, and permethrin) and DDT did not change over time in our study population.

Elevated Bladder Cancer in Northern New England: The Role of Drinking Water and Arsenic.

BACKGROUND: Bladder cancer mortality rates have been elevated in northern New England for at least five decades. Incidence rates in Maine, New Hampshire, and Vermont are about 20% higher than the United States overall. We explored reasons for this excess, focusing on arsenic in drinking water from private wells, which are particularly prevalent in the region. METHODS: In a population-based case-control study in these three states, 1213 bladder cancer case patients and 1418 control subjects provided information on suspected risk factors. Log transformed arsenic concentrations were estimated by linear regression based on measurements in water samples from current and past homes. All statistical tests were two-sided. RESULTS: Bladder cancer risk increased with increasing water intake (Ptrend = .003). This trend was statistically significant among participants with a history of private well use (Ptrend = .01). Among private well users, this trend was apparent if well water was derived exclusively from shallow dug wells (which are vulnerable to contamination from manmade sources, Ptrend = .002) but not if well water was supplied only by deeper drilled wells (Ptrend = .48). If dug wells were used pre-1960, when arsenical pesticides were widely used in the region, heavier water consumers (>2.2 L/day) had double the risk of light users (<1.1 L/day, Ptrend = .01). Among all participants, cumulative arsenic exposure from all water sources, lagged 40 years, yielded a positive risk gradient (Ptrend = .004); among the highest-exposed participants (97.5th percentile), risk was twice that of the lowest-exposure quartile (odds ratio = 2.24, 95% confidence interval = 1.29 to 3.89). CONCLUSIONS: Our findings support an association between low-to-moderate levels of arsenic in drinking water and bladder cancer risk in New England. In addition, historical consumption of water from private wells, particularly dug wells in an era when arsenical pesticides were widely used, was associated with increased bladder cancer risk and may have contributed to the New England excess.

Efficiency of wipe sampling on hard surfaces for pesticides and PCB residues in dust.

Pesticides and polychlorinated biphenyls (PCBs) are commonly found in house dust and have been described as a valuable matrix to assess indoor pesticide and PCB contamination. The aim of this study was to assess the efficiency and precision of cellulose wipe for collecting 48 pesticides, eight PCBs, and one synergist at environmental concentrations. First, the efficiency and repeatability of wipe collection were determined for pesticide and PCB residues that were directly spiked onto three types of household floors (tile, laminate, and hardwood). Second, synthetic dust was used to assess the capacity of the wipe to collect dust. Third, we assessed the efficiency and repeatability of wipe collection of pesticides and PCB residues that was spiked onto synthetic dust and then applied to tile. In the first experiment, the overall collection efficiency was highest on tile (38%) and laminate (40%) compared to hardwood (34%), p<0.001. The second experiment confirmed that cellulose wipes can efficiently collect dust (82% collection efficiency). The third experiment showed that the overall collection efficiency was higher in the presence of dust (72% vs. 38% without dust, p<0.001). Furthermore, the mean repeatability also improved when compounds were spiked onto dust (<30% for the majority of compounds). To our knowledge, this is the first study to assess the efficiency of wipes as a sampling method using a large number of compounds at environmental concentrations and synthetic dust. Cellulose wipes appear to be efficient to sample the pesticides and PCBs that adsorb onto dust on smooth and hard surfaces.

pH-Dependent entry of chikungunya virus fusion into mosquito cells.

BACKGROUND: Millions of human infections caused by arthropod-borne pathogens are initiated by the feeding of an infected mosquito on a vertebrate. However, interactions between the viruses and the mosquito vector, which facilitates successful infection and transmission of virus to a subsequent vertebrate host, are still not fully understood. FINDING: Here we describe early chikungunya virus (CHIKV) infectious events in cells derived from one of the most important CHIKV vectors, Aedes albopictus. We demonstrated that CHIKV infection of mosquito cells depended on acidification of the endosome as indicated by significant inhibition following prophylactic treatment with the lysosomotropic drugs chloroquine, ammonium chloride, and monensin, which is consistent with observations in mammalian cells. While all three agents inhibited CHIKV infection in C6/36 cells, ammonium chloride was less toxic to cells than the other agents. CONCLUSION: The observation of similar mechanisms for inhibition of CHIKV infection in mosquito and mammalian cell lines suggests that conserved entry pathways are utilized by CHIKV for vertebrate and invertebrate cell types.

Farm residence and lymphohematopoietic cancers in the Iowa Women's Health Study.

BACKGROUND: Cancer incidence in male farmers has been studied extensively; however, less is known about risk among women residing on farms or in agricultural areas, who may be exposed to pesticides by their proximity to crop fields. We extended a previous follow-up of the Iowa Women's Health Study cohort to examine farm residence and the incidence of lymphohematopoietic cancers. Further, we investigated crop acreage within 750 m of residences, which has been associated with higher herbicide levels in Iowa homes. METHODS: We analyzed data for a cohort of 37,099 Iowa women aged 55-69 years who reported their residence location (farm, rural (not a farm), town size based on population) at enrollment in 1986. We identified incident lymphohematopoietic cancers (1986-2009) by linkage with the Iowa Cancer Registry. Using a geographic information system, we geocoded addresses and calculated acreage of pasture and row crops within 750 m of homes using the 1992 National Land Cover Database. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) in multivariate analyses of cancer risk in relation to both residence location and crop acreage. RESULTS: As found in an earlier analysis of residence location, risk of acute myeloid leukemia (AML) was higher among women living on farms (HR=2.23, 95%CI: 1.25-3.99) or rural areas (but not on a farm) (HR=1.95, 95%CI: 0.89-4.29) compared with women living in towns of >10,000 population. We observed no association between farm or rural residence and non-Hodgkin lymphoma (NHL; overall or for major subtypes) or multiple myeloma. In analyses of crop acreage, we observed no association between pasture or row crop acreage within 750 m of homes and risk of leukemia overall or for the AML subtype. Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) risk was nonsignificantly elevated among women with pasture acreage within 750 m of their home (HRs for increasing tertiles=1.8, 1.8 and 1.5) and with row crop acreage within 750 m (HRs for increasing tertiles of acreage=1.4, 1.5 and 1.6) compared to women with no pasture or row crop acreage, respectively. CONCLUSIONS: Iowa women living on a farm or in a rural area were at increased risk of developing AML, which was not related to crop acreage near the home. Living near pasture or row crops may confer an increased risk of CLL/SLL regardless of residence location. Further investigation of specific farm-related exposures and these cancers among women living on farms and in agricultural areas is warranted.

Mutagenesis analysis of T380R mutation in the envelope protein of yellow fever virus.

BACKGROUND: The RGD motif in the mosquito-borne flaviviruses envelope protein domain III (EDIII) FG loop was shown to bind negatively charged cellular molecules and mediate virus entry in mammals. However, its importance in virus entry in the mosquito has not yet been defined. The sequences of RGD motifs are conserved in JEV-serocomplex members primarily transmitted by Culex mosquitoes but absent from members of the DENV serocomplex, which utilize Aedes mosquitoes as vectors. Interestingly, the RGD sequence is present in the attenuated 17D strain of yellow fever virus as a result of the T380R mutation in the EDIII of Asibi strain following extensive in vitro passage in mice and chicken embryos and was found to contribute to the more rapid clearance in mice challenged with 17D. However, viral infectivity and dissemination in mosquitoes had not been evaluated for this mutant. FINDINGS: The study utilized the reverse genetics system of YFV and Ae. aegypti RexD WE mosquitoes to assess the impact of a T380R mutation in YFV Asibi and 17D/Asibi M-E chimera. The T380R mutation led to higher infection rates but similar dissemination rates when introduced into the YFV Asibi strain and 17D/Asibi M-E chimera. CONCLUSIONS: While the increase of the positive charge in EDIII may reduce the virulence of YFV in mice, this mutation favored the establishment of the viral infection in Ae. aegypti. However, such gain in viral infectivity did not increase dissemination in infected mosquitoes.

Assessing exposure and health consequences of chemicals in drinking water: current state of knowledge and research needs.

BACKGROUND: Safe drinking water is essential for well-being. Although microbiological contamination remains the largest cause of water-related morbidity and mortality globally, chemicals in water supplies may also cause disease, and evidence of the human health consequences is limited or lacking for many of them. OBJECTIVES: We aimed to summarize the state of knowledge, identify gaps in understanding, and provide recommendations for epidemiological research relating to chemicals occurring in drinking water. DISCUSSION: Assessing exposure and the health consequences of chemicals in drinking water is challenging. Exposures are typically at low concentrations, measurements in water are frequently insufficient, chemicals are present in mixtures, exposure periods are usually long, multiple exposure routes may be involved, and valid biomarkers reflecting the relevant exposure period are scarce. In addition, the magnitude of the relative risks tends to be small. CONCLUSIONS: Research should include well-designed epidemiological studies covering regions with contrasting contaminant levels and sufficient sample size; comprehensive evaluation of contaminant occurrence in combination with bioassays integrating the effect of complex mixtures; sufficient numbers of measurements in water to evaluate geographical and temporal variability; detailed information on personal habits resulting in exposure (e.g., ingestion, showering, swimming, diet); collection of biological samples to measure relevant biomarkers; and advanced statistical models to estimate exposure and relative risks, considering methods to address measurement error. Last, the incorporation of molecular markers of early biological effects and genetic susceptibility is essential to understand the mechanisms of action. There is a particular knowledge gap and need to evaluate human exposure and the risks of a wide range of emerging contaminants. CITATION: Villanueva CM, Kogevinas M, Cordier S, Templeton MR, Vermeulen R, Nuckols JR, Nieuwenhuijsen MJ, Levallois P. 2014. Assessing exposure and health consequences of chemicals in drinking water: current state of knowledge and research needs. Environ Health Perspect 122:213­221; http://dx.doi.org/10.1289/ehp.1206229

Quantitative proteomic analysis of the Anopheles gambiae (Diptera: Culicidae) midgut infected with o'nyong-nyong virus.

Alphaviruses are arthropod-borne pathogens that infect a range of hosts. In humans and other mammals, alphavirus infection can cause severe disease. In mosquito hosts, however, there are generally few symptoms. Little is known about the cellular responses of mosquitoes that allow them to cope with infection. In this investigation, a six-plex tandem mass tagging proteomic approach was used to study protein accumulation changes in the midgut of Anopheles gambiae (Giles) (Diptera: Culicidae) mosquitoes infected with o'nyong-nyong virus (Togaviridae, Alphavirus). Five hundred thirty-six nonredundant proteins were identified. Twenty-two were found in significantly different quantities in infected midguts compared with controls. Of interest, analysis revealed molecular pathways possibly targeted by virus proteins, such as those involving TAF4 and DNA polymerase phi proteins. Also identified was an FK506-binding protein. FK506-binding protein orthologs have been described as conserved host resistance factors, which suppress dengue and West Nile virus infection in human HeLa cells. This investigation constitutes the first study of the midgut-specific proteome of An. gambiae in relation to alphavirus infection. Our findings offer insight into mosquito immunity, including factors that possibly contribute to the different pathological outcomes observed in vertebrate and insect hosts.

Temporal variability of pesticide concentrations in homes and implications for attenuation bias in epidemiologic studies.

BACKGROUND: Residential pesticide exposure has been linked to adverse health outcomes in adults and children. High-quality exposure estimates are critical for confirming these associations. Past epidemiologic studies have used one measurement of pesticide concentrations in carpet dust to characterize an individual's average long-term exposure. If concentrations vary over time, this approach could substantially misclassify exposure and attenuate risk estimates. OBJECTIVES: We assessed the repeatability of pesticide concentrations in carpet dust samples and the potential attenuation bias in epidemiologic studies relying on one sample. METHODS: We collected repeated carpet dust samples (median = 3; range, 1-7) from 21 homes in Fresno County, California, during 2003-2005. Dust was analyzed for 13 pesticides using gas chromatography-mass spectrometry. We used mixed-effects models to estimate between- and within-home variance. For each pesticide, we computed intraclass correlation coefficients (ICCs) and the estimated attenuation of regression coefficients in a hypothetical case-control study collecting a single dust sample. RESULTS: The median ICC was 0.73 (range, 0.37-0.95), demonstrating higher between-home than within-home variability for most pesticides. The expected magnitude of attenuation bias associated with using a single dust sample was estimated to be ≤ 30% for 7 of the 13 compounds evaluated. CONCLUSIONS: For several pesticides studied, use of one dust sample to represent an exposure period of approximately 2 years would not be expected to substantially attenuate odds ratios. Further study is needed to determine if our findings hold for longer exposure periods and for other pesticides.

Residential proximity to industrial combustion facilities and risk of non-Hodgkin lymphoma: a case-control study.

BACKGROUND: Residence near municipal solid waste incinerators, a major historical source of dioxin emissions, has been associated with increased risk of non-Hodgkin lymphoma (NHL) in European studies. The aim of our study was to evaluate residence near industrial combustion facilities and estimates of dioxin emissions in relation to NHL risk in the United States. METHODS: We conducted a population-based case-control study of NHL (1998-2000) in four National Cancer Institute-Surveillance Epidemiology and End Results centers (Detroit, Iowa, Los Angeles, Seattle). Residential histories 15 years before diagnosis (similar date for controls) were linked to an Environmental Protection Agency database of dioxin-emitting facilities for 969 cases and 749 controls. We evaluated proximity (3 and 5 km) to 10 facility types that accounted for >85% of U.S. emissions and a distance-weighted average emission index (AEI [ng toxic equivalency quotient (TEQ)/year]). RESULTS: Proximity to any dioxin-emitting facility was not associated with NHL risk (3 km OR = 1.0, 95% CI 0.8-1.3). Risk was elevated for residence near cement kilns (5 km OR = 1.7, 95% CI 0.8-3.3; 3 km OR = 3.8, 95% CI 1.1-14.0) and reduced for residence near municipal solid waste incinerators (5 km OR = 0.5, 95% CI 0.3-0.9; 3 km OR = 0.3, 95% CI 0.1-1.4). The AEI was not associated with risk of NHL overall. Risk for marginal zone lymphoma was increased for the highest versus lowest quartile (5 km OR = 2.6, 95% CI 1.0-6.8; 3 km OR = 3.0, 95% CI 1.1-8.3). CONCLUSIONS: Overall, we found no association with residential exposure to dioxins and NHL risk. However, findings for high emissions and marginal zone lymphoma and for specific facility types and all NHL provide some evidence of an association and deserve future study.

The influence of physicochemical properties on the internal dose of trihalomethanes in humans following a controlled showering exposure.

Although disinfection of domestic water supply is crucial for protecting public health from waterborne diseases, this process forms potentially harmful by-products, such as trihalomethanes (THMs). We evaluated the influence of physicochemical properties of four THMs (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) on the internal dose after showering. One hundred volunteers showered for 10 min in a controlled setting with fixed water flow, air flow, and temperature. We measured THMs in shower water, shower air, bathroom air, and blood samples collected at various time intervals. The geometric mean (GM) for total THM concentration in shower water was 96.2 µg/l. The GM of total THM in air increased from 5.8 µg/m(3) pre shower to 351 µg/m(3) during showering. Similarly, the GM of total-blood THM concentration increased from 16.5 ng/l pre shower to 299 ng/l at 10 min post shower. THM levels were significantly correlated between different matrices (e.g. dibromochloromethane levels) in water and air (r=0.941); blood and water (r=0.845); and blood and air (r=0.831). The slopes of best-fit lines for THM levels in water vs air and blood vs air increased with increasing partition coefficient of water/air and blood/air. The slope of the correlation plot of THM levels in water vs air decreased in a linear (r=0.995) fashion with increasing Henry's law constant. The physicochemical properties (volatility, partition coefficients, and Henry's law constant) are useful parameters for predicting THM movement between matrices and understanding THM exposure during showering.