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      Environmental, Dietary, Maternal, and Fetal Predictors of Bulky DNA Adducts in Cord Blood: A European Mother–Child Study (NewGeneris)

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      1 , 2 , 3 , 4 , , 1 , 5 , 6 , 7 , 1 , 2 , 3 , 8 , 9 , 1 , 2 , 3 , 8 , 10 , 11 , 1 , 2 , 3 , 7 , 12 , 13 , 14 , 15 , 16 , 1 , 2 , 3 , 8 , 17 , 6 , 18 , 13 , 19 , 11 , 16 , 6 , 20 , 14 , 21 , 1 , 2 , 3 , 1 , 3 , 22 , 22 , 19 , 8 , 21 , 6 , 23 , 9 , 1 , 2 , 3 , 8
      Environmental Health Perspectives
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          Abstract

          Background:

          Bulky DNA adducts reflect genotoxic exposures, have been associated with lower birth weight, and may predict cancer risk.

          Objective:

          We selected factors known or hypothesized to affect in utero adduct formation and repair and examined their associations with adduct levels in neonates.

          Methods:

          Pregnant women from Greece, Spain, England, Denmark, and Norway were recruited in 2006–2010. Cord blood bulky DNA adduct levels were measured by the 32P-postlabeling technique ( n = 511). Diet and maternal characteristics were assessed via questionnaires. Modeled exposures to air pollutants and drinking-water disinfection by-products, mainly trihalomethanes (THMs), were available for a large proportion of the study population.

          Results:

          Greek and Spanish neonates had higher adduct levels than the northern European neonates [median, 12.1 ( n = 179) vs. 6.8 ( n = 332) adducts per 108 nucleotides, p < 0.001]. Residence in southern European countries, higher maternal body mass index, delivery by cesarean section, male infant sex, low maternal intake of fruits rich in vitamin C, high intake of dairy products, and low adherence to healthy diet score were statistically significantly associated with higher adduct levels in adjusted models. Exposure to fine particulate matter and nitrogen dioxide was associated with significantly higher adducts in the Danish subsample only. Overall, the pooled results for THMs in water show no evidence of association with adduct levels; however, there are country-specific differences in results with a suggestion of an association in England.

          Conclusion:

          These findings suggest that a combination of factors, including unknown country-specific factors, influence the bulky DNA adduct levels in neonates.

          Citation:

          Pedersen M, Mendez MA, Schoket B, Godschalk RW, Espinosa A, Landström A, Villanueva CM, Merlo DF, Fthenou E, Gracia-Lavedan E, van Schooten FJ, Hoek G, Brunborg G, Meltzer HM, Alexander J, Nielsen JK, Sunyer J, Wright J, Kovács K, de Hoogh K, Gutzkow KB, Hardie LJ, Chatzi L, Knudsen LE, Anna L, Ketzel M, Haugen M, Botsivali M, Nieuwenhuijsen MJ, Cirach M, Toledano MB, Smith RB, Fleming S, Agramunt S, Kyrtopoulos SA, Lukács V, Kleinjans JC, Segerbäck D, Kogevinas M. 2015. Environmental, dietary, maternal, and fetal predictors of bulky DNA adducts in cord blood: a European mother–child study (NewGeneris). Environ Health Perspect 123:374–380;  http://dx.doi.org/10.1289/ehp.1408613

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          Most cited references52

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          Development of Land Use Regression models for PM(2.5), PM(2.5) absorbance, PM(10) and PM(coarse) in 20 European study areas; results of the ESCAPE project.

          Land Use Regression (LUR) models have been used increasingly for modeling small-scale spatial variation in air pollution concentrations and estimating individual exposure for participants of cohort studies. Within the ESCAPE project, concentrations of PM(2.5), PM(2.5) absorbance, PM(10), and PM(coarse) were measured in 20 European study areas at 20 sites per area. GIS-derived predictor variables (e.g., traffic intensity, population, and land-use) were evaluated to model spatial variation of annual average concentrations for each study area. The median model explained variance (R(2)) was 71% for PM(2.5) (range across study areas 35-94%). Model R(2) was higher for PM(2.5) absorbance (median 89%, range 56-97%) and lower for PM(coarse) (median 68%, range 32- 81%). Models included between two and five predictor variables, with various traffic indicators as the most common predictors. Lower R(2) was related to small concentration variability or limited availability of predictor variables, especially traffic intensity. Cross validation R(2) results were on average 8-11% lower than model R(2). Careful selection of monitoring sites, examination of influential observations and skewed variable distributions were essential for developing stable LUR models. The final LUR models are used to estimate air pollution concentrations at the home addresses of participants in the health studies involved in ESCAPE.
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            Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: a review and roadmap for research.

            Disinfection by-products (DBPs) are formed when disinfectants (chlorine, ozone, chlorine dioxide, or chloramines) react with naturally occurring organic matter, anthropogenic contaminants, bromide, and iodide during the production of drinking water. Here we review 30 years of research on the occurrence, genotoxicity, and carcinogenicity of 85 DBPs, 11 of which are currently regulated by the U.S., and 74 of which are considered emerging DBPs due to their moderate occurrence levels and/or toxicological properties. These 74 include halonitromethanes, iodo-acids and other unregulated halo-acids, iodo-trihalomethanes (THMs), and other unregulated halomethanes, halofuranones (MX [3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone] and brominated MX DBPs), haloamides, haloacetonitriles, tribromopyrrole, aldehydes, and N-nitrosodimethylamine (NDMA) and other nitrosamines. Alternative disinfection practices result in drinking water from which extracted organic material is less mutagenic than extracts of chlorinated water. However, the levels of many emerging DBPs are increased by alternative disinfectants (primarily ozone or chloramines) compared to chlorination, and many emerging DBPs are more genotoxic than some of the regulated DBPs. Our analysis identified three categories of DBPs of particular interest. Category 1 contains eight DBPs with some or all of the toxicologic characteristics of human carcinogens: four regulated (bromodichloromethane, dichloroacetic acid, dibromoacetic acid, and bromate) and four unregulated DBPs (formaldehyde, acetaldehyde, MX, and NDMA). Categories 2 and 3 contain 43 emerging DBPs that are present at moderate levels (sub- to low-mug/L): category 2 contains 29 of these that are genotoxic (including chloral hydrate and chloroacetaldehyde, which are also a rodent carcinogens); category 3 contains the remaining 14 for which little or no toxicological data are available. In general, the brominated DBPs are both more genotoxic and carcinogenic than are chlorinated compounds, and iodinated DBPs were the most genotoxic of all but have not been tested for carcinogenicity. There were toxicological data gaps for even some of the 11 regulated DBPs, as well as for most of the 74 emerging DBPs. A systematic assessment of DBPs for genotoxicity has been performed for approximately 60 DBPs for DNA damage in mammalian cells and 16 for mutagenicity in Salmonella. A recent epidemiologic study found that much of the risk for bladder cancer associated with drinking water was associated with three factors: THM levels, showering/bathing/swimming (i.e., dermal/inhalation exposure), and genotype (having the GSTT1-1 gene). This finding, along with mechanistic studies, highlights the emerging importance of dermal/inhalation exposure to the THMs, or possibly other DBPs, and the role of genotype for risk for drinking-water-associated bladder cancer. More than 50% of the total organic halogen (TOX) formed by chlorination and more than 50% of the assimilable organic carbon (AOC) formed by ozonation has not been identified chemically. The potential interactions among the 600 identified DBPs in the complex mixture of drinking water to which we are exposed by various routes is not reflected in any of the toxicology studies of individual DBPs. The categories of DBPs described here, the identified data gaps, and the emerging role of dermal/inhalation exposure provide guidance for drinking water and public health research.
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              Development of NO2 and NOx land use regression models for estimating air pollution exposure in 36 study areas in Europe – The ESCAPE project

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                Author and article information

                Journal
                Environ Health Perspect
                Environ. Health Perspect
                EHP
                Environmental Health Perspectives
                NLM-Export
                0091-6765
                1552-9924
                27 January 2015
                April 2015
                : 123
                : 4
                : 374-380
                Affiliations
                [1 ]Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
                [2 ]Universitat Pompeu Fabra, Barcelona, Spain
                [3 ]CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
                [4 ]INSERM (National Institute of Health and Medical Research), U823, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Institute Albert Bonniot, Grenoble, France
                [5 ]Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
                [6 ]Department of Molecular Environmental Epidemiology, National Institute of Environmental Health, Budapest, Hungary
                [7 ]Department of Toxicology, Maastricht University, Maastricht, the Netherlands
                [8 ]IMIM (Hospital del Mar Research Institute), Barcelona, Spain
                [9 ]Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden
                [10 ]Epidemiology, Biostatistics, and Clinical Trials, IRCCS AOU San Martino-IST-National Cancer Research Institute, Genova, Italy
                [11 ]Department of Social Medicine, University of Crete, Heraklion, Greece
                [12 ]Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands
                [13 ]Department of Chemicals and Radiation,
                [14 ]Department of Exposure and Risk Assessment, and
                [15 ]Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway
                [16 ]Department of Public Health, University of Copenhagen, Copenhagen, Denmark
                [17 ]Bradford Institute for Health Research, Bradford Royal Infirmary, Bradford, United Kingdom
                [18 ]Department of Epidemiology and Biostatistics, Imperial College London, London, the United Kingdom
                [19 ]Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom
                [20 ]Department of Environmental Science, Aarhus University, Roskilde, Denmark
                [21 ]Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens, Greece
                [22 ]MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
                [23 ]Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands
                Author notes
                Address correspondence to M. Pedersen, DCRC, Strandboulevarden 49, 2100 Copenhagen 0, Denmark. Telephone: 45 35257616. E-mail: maripe@ 123456cancer.dk
                Article
                ehp.1408613
                10.1289/ehp.1408613
                4383575
                25626179
                907e030d-343b-4141-96f5-0f43110e42b3

                Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, “Reproduced with permission from Environmental Health Perspectives”); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.

                History
                : 27 April 2014
                : 23 January 2015
                : 27 January 2015
                : 01 April 2015
                Categories
                Children's Health

                Public health
                Public health

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