Ab initio chemical safety assessment: A workflow based on exposure considerations and non-animal methods

Berggren, Elisabet; White, Andrew; Ouédraogo, Gladys; Paini, Alicia; Richarz, Andrea-Nicole; Bois, Frédéric; Exner, Thomas E.; Leite, Sofia B.; Grunsven, Leo A. van; Worth, Andrew; Mahony, Catherine

doi:10.1016/j.comtox.2017.10.001

Cited by 88 publications

(59 citation statements)

References 70 publications

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“…More broadly, the relationship between AOPs and in silico chemistry based models can be considered as being: i) models using information derived from the AOP, ii) models that support the use or application of information from the AOP e.g. an AOP being used to provide evidence for the ab initio risk assessment of a substance and build a mode-of-action hypothesis, 39 iii) AOPs supporting the mechanistic interpretation of a model or providing evidence to build a weight of evidence to support risk assessment (cf. read-across case studies).…”

Section: Figure 2 Herementioning

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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Section: Figure 2 Herementioning

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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“…These types of NAMs are recommended for further exploration due to their potential to improve systematic review and weight‐of‐evidence approaches based on available data gathered along the innovation funnel. This idea fits fully with current larger project‐based and regulatory agency‐driven initiatives that argue for increased use of weight‐of‐evidence driven bioactivity‐based workflows in safety evaluations 5a,58…”

Section: Discussionmentioning

confidence: 57%

Toward Rigorous Materials Production: New Approach Methodologies Have Extensive Potential to Improve Current Safety Assessment Practices

Nymark

Bakker

Dekkers

et al. 2020

Small

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Advanced material development, including at the nanoscale, comprises costly and complex challenges coupled to ensuring human and environmental safety. Governmental agencies regulating safety have announced interest toward acceptance of safety data generated under the collective term New Approach Methodologies (NAMs), as such technologies/approaches offer marked potential to progress the integration of safety testing measures during innovation from idea to product launch of nanomaterials. Divided in overall eight main categories, searchable databases for grouping and read across purposes, exposure assessment and modeling, in silico modeling of physicochemical structure and hazard data, in vitro high‐throughput and high‐content screening assays, dose‐response assessments and modeling, analyses of biological processes and toxicity pathways, kinetics and dose extrapolation, consideration of relevant exposure levels and biomarker endpoints typify such useful NAMs. Their application generally agrees with articulated stakeholder needs for improvement of safety testing procedures. They further fit for inclusion and add value in nanomaterials risk assessment tools. Overall 37 of 50 evaluated NAMs and tiered workflows applying NAMs are recommended for considering safer‐by‐design innovation, including guidance to the selection of specific NAMs in the eight categories. An innovation funnel enriched with safety methods is ultimately proposed under the central aim of promoting rigorous nanomaterials innovation.

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“…Descriptions of these tools and methods have recently been published in a catalogue by the European Commission Joint Research Centre . As part of the EU SEURAT‐1 project, case studies were prepared to evaluate the use of NAM to facilitate risk assessment, including an ab initio case study and several read‐across case studies …”

Section: New Approach Methods To Enhance Read‐across Predictivitymentioning

confidence: 99%

Relevance and Application of Read‐Across – Mini Review of European Consensus Platform for Alternatives and Scandinavian Society for Cell Toxicology 2017 Workshop Session

Stuard

Heinonen

2018

Basic Clin Pharma Tox

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Structure activity relationship (SAR)-based read-across is an effective approach for addressing data gaps in human health risk assessment for 'data-poor' chemicals. In read-across, available data on chemical structural analogues are used to predict the toxicity potential of the data-poor chemical. This approach has long been recognized by regulatory agencies and used by industry to evaluate the hazards of chemicals for which there are limited direct data. Construction of a scientifically robust SAR-based read-across hazard assessment is a complex and iterative process involving multiple considerations in each step. Traditional in vivo data generated using regulatory guideline compliant study designs typically forms the basis for read-across assessments. Recently, however, new data streams have been explored and incorporated to enhance read-across predictivity. These in vitro and omics data streams may be used in different ways involving identification of hazards or to provide insight into modes of action for observed toxicological responses. These 'new approach methods' can also enable comparison of biological responses across analogues or a category of structurally related chemicals in order to establish a pattern of biological similarity in addition chemical similarity and/or to help address potency differences across a category. The purpose of this workshop session was to inform on practical considerations in conducting SAR-based read-across assessments and to review recent activities related to application of new approach methods to the practice of read-across.

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Ab initio chemical safety assessment: A workflow based on exposure considerations and non-animal methods

Abstract: HighlightsA workflow for an exposure driven chemical safety assessment to avoid animal testing.Hypothesis based on existing data, in silico modelling and biokinetic considerations.A tool to inform targeted and toxicologically relevant in vitro testing.

Cited by 88 publications

References 70 publications

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

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

Toward Rigorous Materials Production: New Approach Methodologies Have Extensive Potential to Improve Current Safety Assessment Practices

Relevance and Application of Read‐Across – Mini Review of European Consensus Platform for Alternatives and Scandinavian Society for Cell Toxicology 2017 Workshop Session

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