Workshop Report 26 – Mode of Action: Recent Developments, Regulatory Application and Future Work

Abstract

WR 26 : Mode of Action: Recent Developments, Regulatory Application and Future Work | 27 June 2013

Workshop Report no.26. Mode of Action: Recent Developments, Regulatory Applications and Future Work 21-22 February 2013, Vienna

ISSN-2078-7200-26 (print)
ISSN-2078-7219-26 (online)
D-2013-3001-228

SCIENCE NEWS FLASH

ECETOC reports on a workshop jointly organised with WHO-IPCS addressing ‘Mode of Action’

 

 

Brussels, June 2013

Mode of Action (MOA) is a method that identifies the important steps in understanding how exposure to a toxic chemical leads to adverse health effects and, if such effects – usually detected in experimental rodents, have human relevance.

The use of MOA as a tool to address/reduce uncertainty about extrapolating toxic effects seen in animals to humans was addressed by ECETOC in 2009 at an ECETOC/ILSI RF/HESI Workshop to exchange views on conceptual approaches to the use of MOAs. One result of the 2009 meeting was that WHO/IPCS formed a global Steering Group, with experts from ECETOC, ECHA, EFSA, Imperial College, JRC, OECD, University of Ottawa, US EPA, ILSI/HESI and WHO, to co-ordinate implementation of an ‘umbrella plan’ of work.

While MOA is now accepted as good science and a value-adding, enabling tool, there is still some reluctance to use MOA in chemical regulation. The second ECETOC/WHO Workshop held in February 2013 explored the progress that had been made since 2009 in using MOA in chemical risk assessment and shared experiences of difficulties encountered in applying the MOA approach in the regulatory environment. The Workshop explored some of their causes and possible solutions together with recommendations how to move forward.

A description and outcome of the MOA Workshop can be found in ECETOC Workshop Report no.26.

Executive summary

An ECETOC/ILSI RF/HESI workshop was held in 2009 to exchange views on conceptual approaches to the use of Mode of Action (MOA) in chemical risk assessment. A number of recommendations emerged, and a global Steering Group was convened by WHO/IPCS to co-ordinate implementation of an ‘umbrella plan’ of work, comprising experts from ECHA, EFSA, Imperial College, JRC, OECD, University of Ottawa, US EPA, ILSI/HESI, and ECETOC. The objectives of the 2013 workshop were to review progress that had been made since 2009. Specifically, these were to share experiences in applying the MOA approach in the regulatory environment, to identify any difficulties or ‘roadblocks’ that had arisen in applying MOA in the regulatory decision-making process, and finally to make recommendations for future work.

The first part of the Workshop focused on providing participants with information on the WHO/IPCS MOA Roadmap, the updated MOA Framework, regulatory application of the Framework, and, then, using case studies, highlighted how MOA can be used in chemical regulation together with some of the challenges encountered in applying the MOA approach – particularly in the US and EU.

In the second part of the meeting, the participants were divided into three breakout groups to explore how MOA can inform risk assessment, be used in defining testing strategies and what further research could be undertaken, including better integration of alternative methods. It was pointed out that the first essential step was problem formulation; only the amount of information and analysis of MOA necessary to answer the question under consideration was required.

Particular considerations were raised, and included:

– MOA being too elaborate and resource intensive.

– How to address multiple MOAs.

– Mutual acceptance of MOA.

– The role of 21st century technologies in MOA analysis.

Suggested areas of improvement included:

– More flexibility in the development and application of non-standard data by stakeholders and regulators.

– Better description of established MOAs in databases and their potential application as a basis to increase common understanding of their development and use.

Areas for future work included:

– Explore the extent to which key steps of known MOAs could be modelled in simpler organisms.

– For the development of data bases, look into the scope for building relevant tools, models and SARs, and in the documentation of normal physiological range and variability in adverse outcome pathways.

– Evolve the efficient and effective application of MOA in regulatory risk assessment, e.g. no guidance on the submission of data is currently available.

– Develop training with regard to the use of MOAs in various aspects of risk assessment and including its application in read-across.

These recommendations inform future work on MOA by the risk assessment community at large; they are, in particular, being considered by the WHO/IPCS Steering Group on MOA.