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Evaluation des produits chimiques

Integrated Approaches to Testing and Assessment (IATA)

 

What's new

The Integrated Approaches to Testing and Assessment (IATA) Case Studies Project allows countries to share and explore the use of novel methodologies in Integrated Approaches to Testing and Assessment within a regulatory context.

Eight new cases have been published that illustrate diverse read-across approaches based on various type of data from New Approach Methodologies. A considerations document includes considerations topics such as Margins of Internal Exposure, Coverage of the key events in AOP, uncertainty on the use of non-endorsed AOPs  and advantage of the use of AOP networks.

Overview of Concepts and Available Guidance related to Integrated Approaches to Testing and Assessment (IATA) has been published that provides an overview of existing guidance on Integrated Approaches to Testing and Assessment (IATA) and their component parts. The aims, characteristics and key concepts of IATA are explained, including an overview of possible IATA components (information sources). Basic definitions are provided and compared, with a view to identifying inconsistencies in the way terminology is used. A mapping exercise identified 153 guidance documents that are systematically described in a supporting file.

INTRODUCTION TO Integrated Approaches to Testing and Assessment (IATA)

What are IATA? 

IATA are pragmatic, science-based approaches for chemical hazard characterisation that rely on an integrated analysis of existing information coupled with the generation of new information using testing strategies.

IATA follow an iterative approach to answer a defined question in a specific regulatory context, taking into account the acceptable level of uncertainty associated with the decision context. There is a range of IATA - from more flexible, non-formalised judgment based approaches (e.g. grouping and read-across) to more structured, prescriptive, rule based approaches [e.g. Integrated Testing Strategy (ITS)].

IATA can include a combination of methods and can be informed by integrating results from one or many methodological approaches [(Q)SAR, read-across, in chemico, in vitro, ex vivo, in vivo] or omic technologies (e.g. toxicogenomics).

 

Why we use AOPs for IATA?

IATA can include a combination of methods and can be informed by integrating results from one or many methodological approaches [(Q)SAR, read-across, in chemico, in vitro, ex vivo, in vivo] or omic technologies (e.g. toxicogenomics).

Many testing approaches do not result in a mechanistic understanding of the induced toxicity. This is particularly the case with non-animal testing approaches and understanding the relationship between what is tested and the apical toxicity endpoint being predicted. This is one of the reasons why results from novel approaches are not yet widely and consistently used for regulatory decision-making.

An objective and systematic framework is needed to characterise the individual biological and toxicological relevance of novel methods in predicting an adverse effect. The same framework could inform their potential use in combination with other tools and methods to benefit from an integrated approach. The Adverse Outcome Pathway (AOP) concept can be applied as a framework to develop IATA.

Why IATA?

Current regulatory toxicity testing and assessment approaches remain to a large extent based on a checklist of in vivo tests, conducted in accordance with standardised test guidelines or protocols such as OECD Test Guidelines.

While this approach has evolved over the past half century, it is unlikely to efficiently meet legislative mandates that require increased numbers of chemical assessments to be undertaken without a concomitant increase in the use of animals and resources.

New approaches are necessary to close the gap between the number of chemicals in use and the number assessed to date.

 

IATA based on the AOP concept

AOP IATA figure

Guidance Document on the Use of the Adverse Outcome Pathways in developing IATA

The objective of this guidance document is to:

  • Provide a framework for developing and using integrated approaches for testing and assessment (IATA),
  • Describe how IATA can be based on the Adverse Outcome Pathway (AOP concept),
  • Provide examples on how AOPs can be used in the development of IATA.
 

OECD INITIATIVES

RELATED OECD INITIATIVES

OVERVIEW of Concepts and Available Guidance related to Integrated Approaches to Testing and Assessment (IATA)

The aim of this document is to give an overview of existing guidance on Integrated Approaches to Testing and Assessment (IATA) and their component parts. While the number of documents, from different sources, directly or indirectly related to guidance on IATA, is proliferating, the information is fragmented and hard to find.

This overview document is expected to contribute to a common understanding of IATA, by explaining key concepts and providing basic definitions, and to support easier access to existing resources. The document consists of the following sections:

• Chapter 1: Aim of this document.

• Chapter 2: Aims and characteristics of IATA as well as an overview of possible IATA components (information sources).

• Chapter 3: Approach adopted for the mapping of guidance documents, including the inclusion and exclusion criteria applied.

• Chapter 4: Summary of the current status of guidance documents, which may include overarching principles, guidance for specific IATA components, or cross-cutting topics such as data quality, assessment of uncertainty and weight of evidence.

• Chapter 5: Based on the findings of Section 4, identification of gaps, duplications or inconsistencies across the guidance landscape, which may inform the development of further guidance or tools.

A list and short description of the mapped guidance documents is available here.

 

CASE STUDIES PROJECT

The Cooperative Chemicals Assessment Programme (CoCAP) was revised in 2014 to enhance the activity of the development and the application of IATA. This programme provides a forum for scientific exchange of approaches on how novel methods are applied to assess the hazard of chemicals, and establish common and best practices for the use of these methods for assessing different types of chemicals. The approaches described in the case studies are applicable in certain regulatory contexts outlined in the case studies. In other regulatory contexts, their fit for purpose would need to be determined.

Description  The OECD has been developing guidance documents and tools for the use of alternative methods such as (Q)SAR, grouping of chemicals and AOPs. There is a need for the investigation of the practical applicability of these methods/tools, as a part of IATA, for different aspects of regulatory decision-making and to build upon case studies and assessment experience across jurisdictions.

The IATA Case Studies Project was launched in 2015 under the revised CoCAP to increase experience with the use of IATA by developing case studies, which constitute examples of predictions that are fit for regulatory use. This project reviews case studies submitted from member countries every year. The review results are discussed in a project meeting. The discussion includes the following topics:

  • Strongest aspects of case study
  • Uncertainty of case study
  • Areas for further development of guidance
  • Possibility of the use of case study in other regulatory context


In every review cycle, the case studies approved will be published with a considerations document capturing leanings and lessons from the review experience.

Documents Considerations from Case Studies on Integrated Approaches for Testing and Assessment (IATA)

Review Year  Summary  Status 
2019

Various type of grouping methods (read-across) were illustrated by 8 case studies in the fifth review cycle. The various lessons and learnings gained from the review experience of the case studies can be considered for improvement of the grouping guidance in the future as well as development of guidance on justification of negative prediction. The considerations focus on use of information on Adverse Outcome Pathway as well as Margin of Internal Exposure concept. 

Published
2018

2 case studies were reviewed in the fourth review cycle (2018). New lessons and learnings focused on three main aspects: read-across based on metabolism information, use of information from AOPs under development and the use of combinations of high-throughput screening assays and computational models. In addition, the analysis of the uncertainties in six selected read-across case studies is reported.

Published
2017

The review results of the 4 case studies in the third review cycle (2017) are included. New lessons and learnings gained from these case studies include aspects regarding use of IATA for prioritisation and consideration of the properties of nanomaterials for read-across. The read-across case studies from the past three review cycles were examined for learnings on the application of read-across for repeated dose toxicity.

Published
2016 Review results of 5 case studies submitted for the second review cycle (2016) are summarised. Lessons and learnings from case studies developed in the first review cycle (2015) were updated by adding the new review experiences of the 5 case studies. The considerations especially focuses on read-across for repeated dose toxicity based on the  five case studies of this area reviewed in the first and second review cycles. Published
2015 Four case studies that focus on application of IATA to grouping methods (read-across) and were developed along with a reporting template used for these case studies based on the reporting format of the Guidance on Grouping of Chemicals. The considerations document highlights the learnings from the first review cycle. Published 

Case Studies on Integrated Approaches for Testing and Assessment (IATA)

Review Year No.  Title Type of Assessment  Endpoint  Status
2020 1

Case Study on the use of Integrated Approaches for Testing and Assessment for the Systemic Toxicity of Phenoxyethanol when included at 1% in a body lotion

Safety assessment workflow Repeated toxicity Under Review
2019 1

Case Study on the use of an Integrated Approach to Testing and Assessment (IATA) and New Approach Methods to inform a Theoretical Read-Across for Dermal Exposure to Propylparaben from Cosmetics

Safety assessment workflow Reproductive toxicity Published
2019 2

Case Study on the use of Integrated Approaches for Testing and Assessment for Systemic Toxicity Arising from Cosmetic Exposure to Caffeine

Safety assessment workflow Repeated dose toxicity Published
2019 3 Case Study on the Use of Integrated Approaches for Testing and Assessment for 90-Day Rat Oral Repeated-Dose Toxicity of Chlorobenzene-Related Chemicals Grouping (Read-across) Repeated dose toxicity Published
2019 4

Case Study on the Use of Integrated Approaches for Testing and Assessment to Inform Read-across of p-Alkylphenols: Repeated-Dose Toxicity

Grouping (Read-across) Repeated dose toxicity Published
2019 5 Prediction of a 90 day repeated dose toxicity study (OECD 408) for 2-Ethylbutyric acid using a read-across approach from other branched carboxylic acids Grouping (Read-across) Repeated dose toxicity

Published

Annex III

2019 6

Read-across based filling of developmental and reproductive toxicity data gap for methyl hexanoic acid

Grouping (Read-across) Developmental toxicity

Published

Annex II

Annex III

2019 7 Identification and characterisation of parkinsonian hazard liability of deguelin by an AOP-based testing and read across approach Grouping (Read-across)

Neurotoxicity

Published

Annex I

2019 8

Mitochondrial Complex-III-mediated neurotoxicity of - Read-Across to other strobilurins

 Grouping (Read-across) Neurotoxicity

Published

Annex I

2018 1

Case Study on the use of Integrated Approaches for Testing and Assessment for Testicular Toxicity of Ethylene Glycol Methyl Ether (EGME)-Related Chemicals

Grouping (Read-across)

Reproductive toxicity

Published
2018 2

Case Study on the Use of an Integrated Approach to Testing and Assessment for Identifying Estrogen Receptor Active Chemicals 

Screening and prioritisation

Endocrine disruption

Published
2017 1 Estrogenicity of Substituted Phenols Prioritization and hazard characterization  Endocrine disruption Published
2017 2 Prioritization of chemicals using the Integrated Approaches for Testing and Assessment (IATA)-based Ecological Risk Classification Prioritization of chemicals

Ecotoxicity

Published
2017 3 Case study on grouping and read-across for nanomaterials genotoxicity of nano-TiO2  Grouping (Read-across)

Genotoxicity

Published
2017 4 A Case Study on the Use of Integrated Approaches for Testing and Assessment for Sub-Chronic Repeated-Dose Toxicity of Simple Aryl Alcohol Alkyl Carboxylic Esters: Read-Across  Grouping (Read-across) Repeated dose toxicity Published
2016 1 Repeated-Dose Toxicity of Phenolic Benzotriazoles Grouping (Read-across) Repeated dose toxicity Published
2016 2 Pesticide Cumulative Risk Assessment & Assessment of Lifestage Susceptibility Cumulative risk assessment  Neurotoxicity Published
2016 3 90-Day Rat Oral Repeated-Dose Toxicity for Selected n-Alkanols: Read-Across Grouping (Read-across) Repeated dose toxicity Published
2016 4 90-Day Rat Oral Repeated-Dose Toxicity for Selected 2-Alkyl-1-alkanols: Read-Across Grouping (Read-across) Repeated dose toxicity Published
2016 5 Chemical Safety Assessment Workflow Based on Exposure Considerations and Non-animal Methods Safety assessment workflow Repeated dose toxicity Published
2015 1 In Vitro Mutagenicity of 3,3’ Dimethoxybenzidine (DMOB) Based Direct Dyes Grouping (Read-across)  Mutagenicity Published 
2015 2 Repeat Dose Toxicity of Substituted Diphenylamines (SDPA) Grouping (Read-across) Repeated dose toxicity Published 
2015 3  Hepatotoxicity of Allyl Ester Category

Grouping (Read-across)

Repeated dose toxicity  Published 
2015 4 Bioaccumulation Potential of Biodegradation Products of 4,4'-Bis (chloromethyl)-1,1'-biphenyl

Grouping (Read-across)

 
Bioaccumulation  Published  

Reporting of Defined Approaches to be used within Integrated Approaches to Testing and Assessment

Description  While an IATA necessarily includes a degree of expert judgement (for example, in the choice of information sources and their weighting) some elements within an IATA can be standardised (i.e. rule- based). Particularly in certain areas of toxicology (e.g. skin sensitisation, skin corrosion and irritation), progress has been made in the development of defined approaches to testing and assessment, in which data generated by non-animal methods are evaluated by means of a fixed data interpretation procedure.

To standardise the evaluation of IATA in regulatory decision-making, guidance has been developed to provide principles and templates for reporting defined approaches and individual information sources. A second guidance has been developed to illustrate how the reporting templates can be used to document a number of defined approaches (and information sources used within) in the area of skin sensitisation.

Documents 
  Annex 1 of the second Guidance Document includes the following 12 case studies
1 AOP –based "2 out of 3" weight of evidence / integrated testing strategy ("2 out of 3 – Sens ITS") approach to skin hazard identification
2 Sequential Testing Strategy (STS) for hazard identification of skin sensitisers 
3 A non-testing Pipeline approach for skin sensitisation 
4 Stacking meta-model for skin sensitisation hazard identification 
5 Integrated decision strategy for skin sensitisation hazard
6 Classification consensus model of decision trees based on in silico descriptors to predict skin sensitisation hazard 
7 Sensitizer potency prediction based on Key event 1 + 2: Combination of kinetic peptide reactivity data and KeratinoSens™ data 
8 The artificial neural network model for predicting LLNA EC3  
9 Sensitizer potency prediction based on Key event 1+2+3: Bayesian Network ITS/DS for hazard and potency identification of skin sensitizers
10 Sequential testing strategy (STS) for sensitising potency classification based on in chemico and in vitro data 
11 Integrated testing strategy (ITS) for sensitising potency classification based on in silico, in chemico, and in vitro data 
12 DIP for skin allergy risk assessment (SARA)

 

INFORMATION EXCHANGE WEBINAR FOR IATA RELATED PROJECT – NOVEMBER 2017

  • BACKGROUND:
    Since IATA related deliverables have been published from different projects, having an opportunity to share the experiences in IATA related projects was thought to be helpful in advancing IATA related work at OECD.
  • OBJECTIVE:
    To exchange information on experiences in IATA related activities and to provide opportunity to identify synergies and areas for collaboration between OECD IATA working groups.
  • WEBINAR:
    Presented overview of OECD IATA related definitions, overview of current IATA guidance and overviews of 11 OECD IATA related projects. 

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