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  1. Article ; Online: Invited Perspective: Challenges in Evaluating the Effect of Per- and Polyfluoroalkyl Substance Mixtures on Polycystic Ovarian Syndrome.

    Radke, Elizabeth G / Christensen, Krista

    Environmental health perspectives

    2023  Volume 131, Issue 5, Page(s) 51301

    MeSH term(s) Female ; Humans ; Polycystic Ovary Syndrome ; Follicle Stimulating Hormone ; Fluorocarbons
    Chemical Substances Follicle Stimulating Hormone (9002-68-0) ; Fluorocarbons
    Language English
    Publishing date 2023-05-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 195189-0
    ISSN 1552-9924 ; 0091-6765 ; 1078-0475
    ISSN (online) 1552-9924
    ISSN 0091-6765 ; 1078-0475
    DOI 10.1289/EHP12783
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: ‘Omics in environmental epidemiological studies of chemical exposures: a systematic evidence map

    Kim, Stephanie / Hollinger, Hillary / Radke, Elizabeth G.

    Environment international. 2022 Apr. 10,

    2022  

    Abstract: Systematic evidence maps are increasingly used to develop chemical risk assessments. These maps can provide an overview of available studies and relevant study information to be used for various research objectives and applications. Environmental ... ...

    Abstract Systematic evidence maps are increasingly used to develop chemical risk assessments. These maps can provide an overview of available studies and relevant study information to be used for various research objectives and applications. Environmental epidemiological studies that examine the impact of chemical exposures on various ‘omic profiles in human populations provide relevant mechanistic information and can be used for benchmark dose modeling to derive potential human health reference values. To create a systematic evidence map of environmental epidemiological studies examining environmental contaminant exposures with ‘omics in order to characterize the extent of available studies for future research needs. Systematic review methods were used to search and screen the literature and included the use of machine learning methods to facilitate screening studies. The Populations, Exposures, Comparators and Outcomes (PECO) criteria were developed to identify and screen relevant studies. Studies that met the PECO criteria after full-text review were summarized with information such as study population, study design, sample size, exposure measurement, and ‘omics analysis. Over 10,000 studies were identified from scientific databases. Screening processes were used to identify 84 studies considered PECO-relevant after full-text review. Various contaminants (e.g. phthalate, benzene, arsenic, etc.) were investigated in epidemiological studies that used one or more of the four ‘omics of interest: epigenomics, transcriptomics, proteomics, and metabolomics . The epidemiological study designs that were used to explore single or integrated ‘omic research questions with contaminant exposures were cohort studies, controlled trials, cross-sectional, and case-control studies. An interactive web-based systematic evidence map was created to display more study-related information. This systematic evidence map is a novel tool to visually characterize the available environmental epidemiological studies investigating contaminants and biological effects using ‘omics technology and serves as a resource for investigators and allows for a range of applications in chemical research and risk assessment needs.
    Keywords Internet ; arsenic ; benzene ; environment ; epigenetics ; experimental design ; human health ; humans ; metabolomics ; phthalates ; proteomics ; risk ; risk assessment ; sample size ; systematic review ; transcriptomics
    Language English
    Dates of publication 2022-0410
    Publishing place Elsevier Ltd
    Document type Article
    Note Pre-press version
    ZDB-ID 554791-x
    ISSN 1873-6750 ; 0160-4120
    ISSN (online) 1873-6750
    ISSN 0160-4120
    DOI 10.1016/j.envint.2022.107243
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  3. Article ; Online: 'Omics in environmental epidemiological studies of chemical exposures: A systematic evidence map.

    Kim, Stephanie / Hollinger, Hillary / Radke, Elizabeth G

    Environment international

    2022  Volume 164, Page(s) 107243

    Abstract: Background: Systematic evidence maps are increasingly used to develop chemical risk assessments. These maps can provide an overview of available studies and relevant study information to be used for various research objectives and applications. ... ...

    Abstract Background: Systematic evidence maps are increasingly used to develop chemical risk assessments. These maps can provide an overview of available studies and relevant study information to be used for various research objectives and applications. Environmental epidemiological studies that examine the impact of chemical exposures on various 'omic profiles in human populations provide relevant mechanistic information and can be used for benchmark dose modeling to derive potential human health reference values.
    Objectives: To create a systematic evidence map of environmental epidemiological studies examining environmental contaminant exposures with 'omics in order to characterize the extent of available studies for future research needs.
    Methods: Systematic review methods were used to search and screen the literature and included the use of machine learning methods to facilitate screening studies. The Populations, Exposures, Comparators and Outcomes (PECO) criteria were developed to identify and screen relevant studies. Studies that met the PECO criteria after full-text review were summarized with information such as study population, study design, sample size, exposure measurement, and 'omics analysis.
    Results: Over 10,000 studies were identified from scientific databases. Screening processes were used to identify 84 studies considered PECO-relevant after full-text review. Various contaminants (e.g. phthalate, benzene, arsenic, etc.) were investigated in epidemiological studies that used one or more of the four 'omics of interest: epigenomics, transcriptomics, proteomics, and metabolomics . The epidemiological study designs that were used to explore single or integrated 'omic research questions with contaminant exposures were cohort studies, controlled trials, cross-sectional, and case-control studies. An interactive web-based systematic evidence map was created to display more study-related information.
    Conclusions: This systematic evidence map is a novel tool to visually characterize the available environmental epidemiological studies investigating contaminants and biological effects using 'omics technology and serves as a resource for investigators and allows for a range of applications in chemical research and risk assessment needs.
    MeSH term(s) Cross-Sectional Studies ; Environmental Exposure/adverse effects ; Epidemiologic Studies ; Humans ; Reference Values ; Risk Assessment
    Language English
    Publishing date 2022-04-12
    Publishing country Netherlands
    Document type Journal Article ; Review ; Systematic Review
    ZDB-ID 554791-x
    ISSN 1873-6750 ; 0160-4120
    ISSN (online) 1873-6750
    ISSN 0160-4120
    DOI 10.1016/j.envint.2022.107243
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Harmonization of transcriptomic and methylomic analysis in environmental epidemiology studies for potential application in chemical risk assessment.

    Kim, Stephanie / White, Shana M / Radke, Elizabeth G / Dean, Jeffry L

    Environment international

    2022  Volume 164, Page(s) 107278

    Abstract: Recent efforts have posited the utility of transcriptomic-based approaches to understand chemical-related perturbations in the context of human health risk assessment. Epigenetic modification (e.g., DNA methylation) can influence gene expression changes ... ...

    Abstract Recent efforts have posited the utility of transcriptomic-based approaches to understand chemical-related perturbations in the context of human health risk assessment. Epigenetic modification (e.g., DNA methylation) can influence gene expression changes and is known to occur as a molecular response to some chemical exposures. Characterization of these methylation events is critical to understand the molecular consequences of chemical exposures. In this context, a novel workflow was developed to interrogate publicly available epidemiological transcriptomic and methylomic data to identify relevant pathway level changes in response to chemical exposure, using inorganic arsenic as a case study. Gene Set Enrichment Analysis (GSEA) was used to identify causal methylation events that result in concomitant downstream transcriptional deregulation. This analysis demonstrated an unequal distribution of differentially methylated regions across the human genome. After mapping these events to known genes, significant enrichment of a subset of these pathways suggested that arsenic-mediated methylation may be both specific and non-specific. Parallel GSEA performed on matched transcriptomic samples determined that a substantially reduced subset of these pathways are enriched and that not all chemically-induced methylation results in a downstream alteration in gene expression. The resulting pathways were found to be representative of well-established molecular events known to occur in response to arsenic exposure. The harmonization of enriched transcriptional patterns with those identified from the methylomic platform promoted the characterization of plausibly causal molecular signaling events. The workflow described here enables significant gene and methylation-specific pathways to be identified from whole blood samples of individuals exposed to environmentally relevant chemical levels. As future efforts solidify specific causal relationships between these molecular events and relevant apical endpoints, this novel workflow could aid risk assessments by identifying molecular targets serving as biomarkers of hazard, informing mechanistic understanding, and characterizing dose ranges that promote relevant molecular/epigenetic signaling events occuring in response to chemical exposures.
    MeSH term(s) Arsenic/toxicity ; DNA Methylation ; Epigenomics/methods ; Humans ; Risk Assessment ; Transcriptome
    Chemical Substances Arsenic (N712M78A8G)
    Language English
    Publishing date 2022-05-05
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 554791-x
    ISSN 1873-6750 ; 0160-4120
    ISSN (online) 1873-6750
    ISSN 0160-4120
    DOI 10.1016/j.envint.2022.107278
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Integrated Risk Information System (IRIS) response to "Assessing risk of bias in human environmental epidemiology studies using three tools: different conclusions from different tools".

    Radke, Elizabeth G / Glenn, Barbara S / Kraft, Andrew D

    Systematic reviews

    2021  Volume 10, Issue 1, Page(s) 235

    Abstract: Assessing risk of bias in human environmental epidemiology studies using three tools: different conclusions from different tools," a recent publication in this journal, applied the study evaluation approach developed by the U.S. Environmental Protection ...

    Abstract "Assessing risk of bias in human environmental epidemiology studies using three tools: different conclusions from different tools," a recent publication in this journal, applied the study evaluation approach developed by the U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS), as well as other approaches, to a set of studies examining polybrominated diphenyl ethers (PBDEs) and neurodevelopment. They concluded that use of the IRIS approach resulted in exclusion of studies, which would lead to hazard conclusions based on an incomplete body of evidence. As scientists in the IRIS program, we support the comparison of approaches to improve systematic review methods for environmental exposures; however, we believe the IRIS approach was misrepresented. In this letter, we demonstrate that the ratings attributed to the IRIS approach were not consistent with our own application of the tool. We also clarify the use of studies rated as "low confidence" and the use of an overall study confidence rating in our systematic reviews. In conclusion, the IRIS study evaluation approach is a transparent method to inform certainty in our evidence synthesis decisions and ensures consistency in the development of IRIS health assessments.
    MeSH term(s) Bias ; Environmental Exposure/adverse effects ; Environmental Health ; Humans ; Information Systems ; Research Design
    Language English
    Publishing date 2021-08-21
    Publishing country England
    Document type Letter ; Comment
    ZDB-ID 2662257-9
    ISSN 2046-4053 ; 2046-4053
    ISSN (online) 2046-4053
    ISSN 2046-4053
    DOI 10.1186/s13643-021-01783-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Total Blood Mercury Predicts Methylmercury Exposure in Fish and Shellfish Consumers

    Wells, Ellen M. / Kopylev, Leonid / Nachman, Rebecca / Radke, Elizabeth G. / Congleton, Johanna / Segal, Deborah

    Biological trace element research. 2022 Aug., v. 200, no. 8

    2022  

    Abstract: Many studies evaluating methylmercury (MeHg) toxicity rely on whole blood total mercury (THg) measurements to estimate MeHg exposure. However, whole blood THg includes other forms of mercury (Hg), such as inorganic Hg, which have different exposure ... ...

    Abstract Many studies evaluating methylmercury (MeHg) toxicity rely on whole blood total mercury (THg) measurements to estimate MeHg exposure. However, whole blood THg includes other forms of mercury (Hg), such as inorganic Hg, which have different exposure sources and toxicological effects than MeHg. Therefore, estimating the whole blood MeHg/THg ratio is critical to predicting MeHg exposure and, subsequently, efforts to establish an exposure–response relationship for use in risk assessment. A large, representative dataset (National Health and Nutrition Examination Survey (NHANES) 2011–2016) was used to determine the whole blood MeHg/THg ratio among (a) self-reported fish and shellfish consumers, ≥ 15 years of age (the “full adult” population (N = 5268 training dataset; N = 2336 test dataset)) and (b) female fish and shellfish consumers, 15–44 years of age (the “women of reproductive age” population (N = 1285 training dataset; N = 560 test dataset)). Unadjusted and adjusted linear and spline models with direct measurements for both THg and MeHg were evaluated. The mean whole blood MeHg/THg ratio was 0.75 (95% confidence interval (CI): 0.74, 0.75). This ratio was significantly higher among those with higher THg concentrations. All models exhibited excellent fit (adjusted R² from 0.957 to 0.982). Performance was slightly improved in spline versus linear models. For the full adult population and women of reproductive age, the unadjusted spline model predicted whole blood MeHg concentrations of 5.65 µg/L and 5.55 µg/L, respectively, when the THg concentration was 5.80 µg/L. These results suggest that whole blood THg is a good predictor of whole blood MeHg among fish and shellfish consumers.
    Keywords National Health and Nutrition Examination Survey ; adults ; blood ; confidence interval ; data collection ; females ; fish ; mercury ; methylmercury compounds ; research ; risk assessment ; shellfish ; toxicity ; toxicology ; trace elements
    Language English
    Dates of publication 2022-08
    Size p. 3867-3875.
    Publishing place Springer US
    Document type Article
    ZDB-ID 445336-0
    ISSN 1559-0720 ; 0163-4984
    ISSN (online) 1559-0720
    ISSN 0163-4984
    DOI 10.1007/s12011-021-02968-9
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  7. Article: Harmonization of transcriptomic and methylomic analysis in environmental epidemiology studies for potential application in chemical risk assessment

    Kim, Stephanie / White, Shana M. / Radke, Elizabeth G. / Dean, Jeffry L.

    Environment international. 2022 June, v. 164

    2022  

    Abstract: Recent efforts have posited the utility of transcriptomic-based approaches to understand chemical-related perturbations in the context of human health risk assessment. Epigenetic modification (e.g., DNA methylation) can influence gene expression changes ... ...

    Abstract Recent efforts have posited the utility of transcriptomic-based approaches to understand chemical-related perturbations in the context of human health risk assessment. Epigenetic modification (e.g., DNA methylation) can influence gene expression changes and is known to occur as a molecular response to some chemical exposures. Characterization of these methylation events is critical to understand the molecular consequences of chemical exposures. In this context, a novel workflow was developed to interrogate publicly available epidemiological transcriptomic and methylomic data to identify relevant pathway level changes in response to chemical exposure, using inorganic arsenic as a case study. Gene Set Enrichment Analysis (GSEA) was used to identify causal methylation events that result in concomitant downstream transcriptional deregulation. This analysis demonstrated an unequal distribution of differentially methylated regions across the human genome. After mapping these events to known genes, significant enrichment of a subset of these pathways suggested that arsenic-mediated methylation may be both specific and non-specific. Parallel GSEA performed on matched transcriptomic samples determined that a substantially reduced subset of these pathways are enriched and that not all chemically-induced methylation results in a downstream alteration in gene expression. The resulting pathways were found to be representative of well-established molecular events known to occur in response to arsenic exposure. The harmonization of enriched transcriptional patterns with those identified from the methylomic platform promoted the characterization of plausibly causal molecular signaling events. The workflow described here enables significant gene and methylation-specific pathways to be identified from whole blood samples of individuals exposed to environmentally relevant chemical levels. As future efforts solidify specific causal relationships between these molecular events and relevant apical endpoints, this novel workflow could aid risk assessments by identifying molecular targets serving as biomarkers of hazard, informing mechanistic understanding, and characterizing dose ranges that promote relevant molecular/epigenetic signaling events occuring in response to chemical exposures.
    Keywords DNA methylation ; arsenic ; biomarkers ; blood ; case studies ; chemical risk assessment ; environment ; epidemiology ; epigenetics ; gene expression ; gene expression regulation ; genes ; health effects assessments ; human health ; humans ; risk ; transcription (genetics) ; transcriptomics
    Language English
    Dates of publication 2022-06
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 554791-x
    ISSN 1873-6750 ; 0160-4120
    ISSN (online) 1873-6750
    ISSN 0160-4120
    DOI 10.1016/j.envint.2022.107278
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  8. Article ; Online: Phthalate exposure and neurodevelopment: A systematic review and meta-analysis of human epidemiological evidence.

    Radke, Elizabeth G / Braun, Joseph M / Nachman, Rebecca M / Cooper, Glinda S

    Environment international

    2020  Volume 137, Page(s) 105408

    Abstract: Objective: We performed a systematic review of the epidemiology literature to identify the neurodevelopmental effects associated with phthalate exposure.: Data sources and study eligibility criteria: Six phthalates were included in the review: di(2- ... ...

    Abstract Objective: We performed a systematic review of the epidemiology literature to identify the neurodevelopmental effects associated with phthalate exposure.
    Data sources and study eligibility criteria: Six phthalates were included in the review: di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), dibutyl phthalate (DBP), diisobutyl phthalate (DIBP), butyl benzyl phthalate (BBP), and diethyl phthalate (DEP). The initial literature search (of PubMed, Web of Science, and Toxline) included all studies of neurodevelopmental effects in humans, and outcomes were selected for full systematic review based on data availability.
    Study evaluation and synthesis methods: Studies of neurodevelopmental effects were evaluated using criteria defined a priori for risk of bias and sensitivity by two reviewers using a domain-based approach. Evidence was synthesized by outcome and phthalate and strength of evidence was summarized using a structured framework. For studies of cognition and motor effects in children ≤4 years old, a random effects meta-analysis was performed.
    Results: The primary outcomes reviewed here are (number of studies in parentheses): cognition (14), motor effects (9), behavior, including attention deficit hyperactivity disorder (20), infant behavior (3), and social behavior, including autism spectrum disorder (7). For each phthalate/outcome combination, there was slight or indeterminate evidence of an association, with the exception of motor effects for BBP, which had moderate evidence.
    Conclusions and implications of key findings: Overall, there is not a clear pattern of association between prenatal phthalate exposures and neurodevelopment. There are several possible reasons for the observed null associations related to exposure misclassification, periods of heightened susceptibility, sex-specific effects, and the effects of phthalate mixtures. Until these limitations are adequately addressed in the epidemiology literature, these findings should not be interpreted as evidence that there are no neurodevelopmental effects of phthalate exposure. The views expressed are those of the authors and do not necessarily represent the views or policies of the U.S. EPA.
    MeSH term(s) Autism Spectrum Disorder/chemically induced ; Child ; Child Development/drug effects ; Child, Preschool ; Cognition ; Environmental Exposure ; Female ; Humans ; Infant ; Infant Behavior ; Male ; Nervous System/drug effects ; Nervous System/growth & development ; Phthalic Acids/toxicity ; Pregnancy
    Chemical Substances Phthalic Acids ; phthalic acid (6O7F7IX66E)
    Language English
    Publishing date 2020-02-08
    Publishing country Netherlands
    Document type Journal Article ; Meta-Analysis ; Systematic Review
    ZDB-ID 554791-x
    ISSN 1873-6750 ; 0160-4120
    ISSN (online) 1873-6750
    ISSN 0160-4120
    DOI 10.1016/j.envint.2019.105408
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Total Blood Mercury Predicts Methylmercury Exposure in Fish and Shellfish Consumers.

    Wells, Ellen M / Kopylev, Leonid / Nachman, Rebecca / Radke, Elizabeth G / Congleton, Johanna / Segal, Deborah

    Biological trace element research

    2021  Volume 200, Issue 8, Page(s) 3867–3875

    Abstract: Many studies evaluating methylmercury (MeHg) toxicity rely on whole blood total mercury (THg) measurements to estimate MeHg exposure. However, whole blood THg includes other forms of mercury (Hg), such as inorganic Hg, which have different exposure ... ...

    Abstract Many studies evaluating methylmercury (MeHg) toxicity rely on whole blood total mercury (THg) measurements to estimate MeHg exposure. However, whole blood THg includes other forms of mercury (Hg), such as inorganic Hg, which have different exposure sources and toxicological effects than MeHg. Therefore, estimating the whole blood MeHg/THg ratio is critical to predicting MeHg exposure and, subsequently, efforts to establish an exposure-response relationship for use in risk assessment. A large, representative dataset (National Health and Nutrition Examination Survey (NHANES) 2011-2016) was used to determine the whole blood MeHg/THg ratio among (a) self-reported fish and shellfish consumers, ≥ 15 years of age (the "full adult" population (N = 5268 training dataset; N = 2336 test dataset)) and (b) female fish and shellfish consumers, 15-44 years of age (the "women of reproductive age" population (N = 1285 training dataset; N = 560 test dataset)). Unadjusted and adjusted linear and spline models with direct measurements for both THg and MeHg were evaluated. The mean whole blood MeHg/THg ratio was 0.75 (95% confidence interval (CI): 0.74, 0.75). This ratio was significantly higher among those with higher THg concentrations. All models exhibited excellent fit (adjusted R
    MeSH term(s) Animals ; Environmental Monitoring ; Female ; Fishes ; Humans ; Mercury/analysis ; Methylmercury Compounds ; Nutrition Surveys ; Seafood ; Shellfish ; Water Pollutants, Chemical/analysis
    Chemical Substances Methylmercury Compounds ; Water Pollutants, Chemical ; Mercury (FXS1BY2PGL)
    Language English
    Publishing date 2021-10-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 445336-0
    ISSN 1559-0720 ; 0163-4984
    ISSN (online) 1559-0720
    ISSN 0163-4984
    DOI 10.1007/s12011-021-02968-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Phthalate exposure and neurodevelopment: A systematic review and meta-analysis of human epidemiological evidence

    Radke, Elizabeth G / Braun, Joseph M / Cooper, Glinda S / Nachman, Rebecca M

    Environment international. 2020 Apr., v. 137

    2020  

    Abstract: We performed a systematic review of the epidemiology literature to identify the neurodevelopmental effects associated with phthalate exposure.Six phthalates were included in the review: di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), ... ...

    Abstract We performed a systematic review of the epidemiology literature to identify the neurodevelopmental effects associated with phthalate exposure.Six phthalates were included in the review: di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), dibutyl phthalate (DBP), diisobutyl phthalate (DIBP), butyl benzyl phthalate (BBP), and diethyl phthalate (DEP). The initial literature search (of PubMed, Web of Science, and Toxline) included all studies of neurodevelopmental effects in humans, and outcomes were selected for full systematic review based on data availability.Studies of neurodevelopmental effects were evaluated using criteria defined a priori for risk of bias and sensitivity by two reviewers using a domain-based approach. Evidence was synthesized by outcome and phthalate and strength of evidence was summarized using a structured framework. For studies of cognition and motor effects in children ≤4 years old, a random effects meta-analysis was performed.The primary outcomes reviewed here are (number of studies in parentheses): cognition (14), motor effects (9), behavior, including attention deficit hyperactivity disorder (20), infant behavior (3), and social behavior, including autism spectrum disorder (7). For each phthalate/outcome combination, there was slight or indeterminate evidence of an association, with the exception of motor effects for BBP, which had moderate evidence.Overall, there is not a clear pattern of association between prenatal phthalate exposures and neurodevelopment. There are several possible reasons for the observed null associations related to exposure misclassification, periods of heightened susceptibility, sex-specific effects, and the effects of phthalate mixtures. Until these limitations are adequately addressed in the epidemiology literature, these findings should not be interpreted as evidence that there are no neurodevelopmental effects of phthalate exposure.The views expressed are those of the authors and do not necessarily represent the views or policies of the U.S. EPA.
    Keywords autism ; children ; cognition ; dibutyl phthalate ; diethyl phthalate ; epidemiology ; issues and policy ; meta-analysis ; neurodevelopment ; risk ; social behavior ; systematic review
    Language English
    Dates of publication 2020-04
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 554791-x
    ISSN 1873-6750 ; 0160-4120
    ISSN (online) 1873-6750
    ISSN 0160-4120
    DOI 10.1016/j.envint.2019.105408
    Database NAL-Catalogue (AGRICOLA)

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