Assessment of chemicals

Integrated Approaches to Testing and Assessment (IATA)

 

what's new?

OECD publishes a Guidance Document on the Use of Adverse Outcome Pathways in developing Integrated Approaches to Testing and Assessment (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.

 

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

IATA based on the AOP concept

AOP IATA figure

 

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.

 

OECD INITIATIVES

RELATED OECD INITIATIVES

 

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.

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 
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
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 
2016 1 Repeated-Dose Toxicity of Phenolic Benzotriazoles Grouping (Read-across) Repeated dose toxicity Under review
2016 2 Pesticide Cumulative Risk Assessment & Assessment of Lifestage Susceptibility Grouping  Neurotoxicity Under review
2016 3 90-Day Rat Oral Repeated-Dose Toxicity for Selected n-Alkanols: Read-Across Grouping (Read-across) Repeated dose toxicity Under review
2016 4 90-Day Rat Oral Repeated-Dose Toxicity for Selected 2-Alkyl-1-alkanols: Read-Across Grouping (Read-across) Repeated dose toxicity Under review
2016 5 Chemical Safety Assessment Workflow Based on Exposure Considerations and Non-animal Methods Other Repeated dose toxicity Under review

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)

 

 

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