Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework

Teeguarden, Justin G.; Tan, Yu‐Mei; Edwards, Stephen W.; Leonard, Jeremy A.; Anderson, Kim A.; Corley, Richard A.; Kile, Molly L.; Simonich, Staci Massey; Stone, David L.; Tanguay, Robert L.; Waters, Katrina M.; Harper, Stacey L.; Williams, David E.

doi:10.1021/acs.est.5b05311

Cited by 104 publications

(104 citation statements)

References 35 publications

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“…It may be relevant to exposure assessment, risk assessment, epidemiology, or all three. The target site exposure (the terminal outcome of the AEP), along with the molecular initiating event from the AOP, represent the point of integration between an AEP and an AOP' (Teeguarden et al, 2016). Antagonism…”

Section: Adverse Effectmentioning

confidence: 99%

Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals

More¹,

Bampidis²,

Benford³

et al. 2019

EFS2

256

348

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This Guidance document describes harmonised risk assessment methodologies for combined exposure to multiple chemicals for all relevant areas within EFSA's remit, i.e. human health, animal health and ecological areas. First, a short review of the key terms, scientific basis for combined exposure risk assessment and approaches to assessing (eco)toxicology is given, including existing frameworks for these risk assessments. This background was evaluated, resulting in a harmonised framework for risk assessment of combined exposure to multiple chemicals. The framework is based on the risk assessment steps (problem formulation, exposure assessment, hazard identification and characterisation, and risk characterisation including uncertainty analysis), with tiered and stepwise approaches for both whole mixture approaches and component‐based approaches. Specific considerations are given to component‐based approaches including the grouping of chemicals into common assessment groups, the use of dose addition as a default assumption, approaches to integrate evidence of interactions and the refinement of assessment groups. Case studies are annexed in this guidance document to explore the feasibility and spectrum of applications of the proposed methods and approaches for human and animal health and ecological risk assessment. The Scientific Committee considers that this Guidance is fit for purpose for risk assessments of combined exposure to multiple chemicals and should be applied in all relevant areas of EFSA's work. Future work and research are recommended.

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Section: Adverse Effectmentioning

confidence: 99%

Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals

More¹,

Bampidis²,

Benford³

et al. 2019

EFS2

256

348

View full text Add to dashboard Cite

show abstract

“…Another area of progress is the development of Aggregate Exposure Pathways which will provide information to derive models from. 104 There are a number of SAR approaches that can be used to screen out compounds that are not likely to reach the site of the MIE. Very commonly used (especially as a drug design tool) is the Lipinski Rule of 5 105 and various adaptions.…”

Section: Models For Exposure and Bioavailability -Adding Value To Aopsmentioning

confidence: 99%

Relationship Between Adverse Outcome Pathways and Chemistry-BasedIn SilicoModels to Predict Toxicity

Cronin

RicharzAndrea-Nicole

2017

Applied In Vitro Toxicology

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The current landscape of Adverse Outcome Pathways (AOPs) provides a means of organising information relating to the adverse effects elicited following exposure to chemicals. As such, AOPs are an excellent driver for the development and application of in silico models for predictive toxicology allowing for the direct relationship between chemistry and adverse effects to be established. Information may be extracted from AOPs to support the creation of (quantitative) structure-activity relationships ((Q)SARs) as well as to increase confidence in grouping and read-across. Any part of an AOP can be linked to these various types of in silico models. There is, however, an emphasis on using information from known Molecular Initiating Events (MIEs) to create models including 2D and 3D structural alerts, SARs and QSARs. MIEs can be classified according to the nature of the interaction e.g. covalent reactivity, oxidative stress, phototoxicity, chronic receptor mediated, acute enzyme inhibition, unspecific, physical and other effects. Different types of MIEs require different approaches to their in silico modelling. Modelling Key Events and Key Event Relationships is useful if they represent the rate limiting step or key determinant of toxicity. Modelling of metabolism and chemical interactions will become part of AOP networks, which are also driving species-specific extrapolation and respective adaptation of models. With more information and data being captured, in silico approaches will increasingly support the application of knowledge from AOPs to build weight of evidence and support risk assessment, e.g. in the context of Integrated Assessment and Testing Approaches (IATAs).

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“…Major challenges include how to integrate and interpret data in a meaningful way, how to account for shared exposures, how to integrate data across multiple spatial and temporal scales and methodological approaches, and how to account for measurement errors. The aggregate exposure pathway (AEP) framework, a conceptual framework that complements the adverse outcome pathways (AOP) concept, organizes exposure and toxicological data from source to dose and to outcome (97). Together, the two frameworks complete the view of the exposure-outcome continuum to enable knowledge integration and better understanding of the health impacts of chemical exposure.…”

Section: Data Analysis and Interpretationmentioning

confidence: 99%

Assessing the Exposome with External Measures: Commentary on the State of the Science and Research Recommendations

Turner

Nieuwenhuijsen

Anderson

et al. 2017

Annu. Rev. Public Health

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The exposome comprises all environmental exposures that a person experiences from conception throughout the life course. Here we review the state of the science for assessing external exposures within the exposome. This article reviews (a) categories of exposures that can be assessed externally, (b) the current state of the science in external exposure assessment, (c) current tools available for external exposure assessment, and (d ) priority research needs. We describe major scientific and technological advances that inform external assessment of the exposome, including geographic information systems; remote sensing; global positioning system and geolocation technologies; portable and personal sensing, including smartphone-based sensors and assessments; and self-reported questionnaire assessments, which increasingly rely on Internet-based platforms. We also discuss priority research needs related to methodological and technological improvement, data analysis and interpretation, data sharing, and other practical considerations, including improved assessment of exposure variability as well as exposure in multiple, critical life stages.

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Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework

Cited by 104 publications

References 35 publications

Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals

Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals

Relationship Between Adverse Outcome Pathways and Chemistry-BasedIn SilicoModels to Predict Toxicity

Assessing the Exposome with External Measures: Commentary on the State of the Science and Research Recommendations

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