Consensus Modeling of Median Chemical Intake for the U.S. Population Based on Predictions of Exposure Pathways

Ring, Caroline; Arnot, Jon A.; Bennett, Deborah H.; Egeghy, Peter; Fantke, Peter; Huang, Lei; Isaacs, Kristin; Jolliet, Olivier; Phillips, Katherine A.; Price, Paul S.; Shin, Hyeong‐Moo; Westgate, John N.; Setzer, R. Woodrow; Wambaugh, John F.

doi:10.1021/acs.est.8b04056

Cited by 93 publications

(133 citation statements)

References 94 publications

(186 reference statements)

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“…A comparison of the SHEDS values with biomonitoring data in Biryol et al (2017) demonstrated that the SHEDS-HT values were likely over-estimates by at least two orders of magnitude. Recent work has integrated multiple SHEDS models (as well as other mechanistic exposure models) with NHANES biomonitoring data in an evaluation framework called the Systematic Empirical Evaluation of Models (SEEM)( Ring et al, 2019 ). These efforts will allow for the integration of food contact pathways into next-generation ExpoCast exposure values while simultaneously correcting over-conservative models for individual pathways.…”

Section: Discussionmentioning

confidence: 99%

Incorporating new approach methodologies in toxicity testing and exposure assessment for tiered risk assessment using the RISK21 approach: Case studies on food contact chemicals

Turley

Isaacs

Wetmore

et al. 2019

Food and Chemical Toxicology

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Programs including the ToxCast project have generated large amounts of in vitro high‒throughput screening (HTS) data, and best approaches for the interpretation and use of HTS data, including for chemical safety assessment, remain to be evaluated. To fill this gap, we conducted case studies of two indirect food additive chemicals where ToxCast data were compared with in vivo toxicity data using the RISK21 approach. Two food contact substances, sodium (2-pyridylthio)-N-oxide and dibutyltin dichloride, were selected, and available exposure data, toxicity data, and model predictions were compiled and assessed. Oral equivalent doses for the ToxCast bioactivity data were determined by in-vitro in-vivo extrapolation (IVIVE). For sodium (2-pyridylthio)-N-oxide, bioactive concentrations in ToxCast assays corresponded to low-and no-observed adverse effect levels in animal studies. For dibutyltin dichloride, the ToxCast bioactive concentrations were below the dose range that demonstrated toxicity in animals; however, this was confounded by the lack of toxicokinetic data, necessitating the use of conservative toxicokinetic parameter estimates for IVIVE calculations. This study highlights the potential utility of the RISK21 approach for interpretation of the ToxCast HTS data, as well as the challenges involved in integrating in vitro HTS data into safety assessments.

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Section: Discussionmentioning

confidence: 99%

Incorporating new approach methodologies in toxicity testing and exposure assessment for tiered risk assessment using the RISK21 approach: Case studies on food contact chemicals

Turley

Isaacs

Wetmore

et al. 2019

Food and Chemical Toxicology

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“…Related emerging topics are the 'exposome' concept [44,45] or 'safe-by-design' initiatives [46]. Underlying exposure data generation increasingly builds on highthroughput and spatial methods [47][48][49][50][51], and harmonized biomonitoring efforts [43,52], which will influence the availability, quality and complexity of exposure information. Various important achievements including exposomics, intake fraction modelling, and personal exposure sampling are further detailed elsewhere (e.g.…”

Section: Considering Major Scientific Trendsmentioning

confidence: 99%

Building a European exposure science strategy

Fantke

Goetz

Schlüter

et al. 2019

J Expo Sci Environ Epidemiol

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Exposure information is a critical element in various regulatory and non-regulatory frameworks in Europe and elsewhere. Exposure science supports to ensure safe environments, reduce human health risks, and foster a sustainable future. However, increasing diversity in regulations and the lack of a professional identity as exposure scientists currently hamper developing the field and uptake into European policy. In response, we discuss trends, and identify three key needs for advancing and harmonizing exposure science and its application in Europe. We provide overarching building blocks and define six long-term activities to address the identified key needs, and to iteratively improve guidelines, tools, data, and education. More specifically, we propose creating European networks to maximize synergies with adjacent fields and identify funding opportunities, building common exposure assessment approaches across regulations, providing tiered education and training programmes, developing an aligned and integrated exposure assessment framework, offering best practices guidance, and launching an exposure information exchange platform. Dedicated working groups will further specify these activities in a consistent action plan. Together, these elements form the foundation for establishing goals and an action roadmap for successfully developing and implementing a 'European Exposure Science Strategy' 2020-2030, which is aligned with advances in science and technology.

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“…These data may be used to prioritize chemicals for a database. For example EPA's modeling predicted 1880 chemicals would have median population exposures above 0.1 mg/kg-day [27]. Chemical databases should also be developed that feature chemicals shown to be active in breast cancer-related pathways, such as estrogen receptor activation or DNA Data resources that are now available from the US Environmental Protection Agency (EPA) and other sources provide valuable information to help build environmental chemical databases that are relevant to breast cancer.…”

Section: Capturing Molecular Information Using Omicsmentioning

confidence: 99%

Section: Capturing Molecular Information Using Omicsmentioning

confidence: 99%

Mapping the Human Exposome to Uncover the Causes of Breast Cancer

Bessonneau

Rudel

2019

IJERPH

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Breast cancer is an important cause of morbidity and mortality for women, yet a significant proportion of variation in individual risk is unexplained. It is reasonable to infer that unexplained breast cancer risks are caused by a myriad of exposures and their interactions with genetic factors. Most epidemiological studies investigating environmental contribution to breast cancer risk have focused on a limited set of exposures and outcomes based on a priori knowledge. We hypothesize that by measuring a rich set of molecular information with omics (e.g., metabolomics and adductomics) and comparing these profiles using a case-control design we can pinpoint novel environmental risk factors. Specifically, exposome-wide association study approaches can be used to compare molecular profiles between controls and either breast cancer cases or participants with phenotypic measures associated with breast cancer (e.g., high breast density, chronic inflammation). Current challenges in annotating compound peaks from biological samples can be addressed by creating libraries of environmental chemicals that are breast cancer relevant using publicly available high throughput exposure and toxicity data, and by mass spectra fragmentation. This line of discovery and innovation will extend understanding of how environmental exposures interact with genetics to affect health, and provide evidence to support new breast cancer prevention strategies.

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Consensus Modeling of Median Chemical Intake for the U.S. Population Based on Predictions of Exposure Pathways

Cited by 93 publications

References 94 publications

Incorporating new approach methodologies in toxicity testing and exposure assessment for tiered risk assessment using the RISK21 approach: Case studies on food contact chemicals

Incorporating new approach methodologies in toxicity testing and exposure assessment for tiered risk assessment using the RISK21 approach: Case studies on food contact chemicals

Building a European exposure science strategy

Mapping the Human Exposome to Uncover the Causes of Breast Cancer

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