I attended the debate between SOT and EUROTOX during the SOT 2018 Annual Meeting and ToxExpo, where the debaters addressed the proposition “Adverse Outcome Pathways (AOPs) Are the Future for Regulatory Toxicology.” I found it particularly interesting because my current/ongoing dissertation research is aimed at generating AOPs and/or contributing my data to the existing body of knowledge.
Supporting the proposition, representing SOT, was Daniel Villeneuve, US Environmental Protection Agency, and rebutting the proposition, representing EUROTOX, was Brigitte Landesmann, European Commission Joint Research Centre, Directorate F–Health, Consumers, and Reference Materials.
To persuade and appeal to the audience in order to obtain the approval or refusal of the motion, the following relevant evidence and compelling scientific arguments were provided.
Support: AOPs being concerned with the linkage between a direct molecular initiating event and an adverse outcome can help us to:
Organize what we know—from past experience
- Collate an overwhelming amount of information (e.g., from mechanistic studies, weight of evidence)
Infer what we need to know—from practical measurements
- measure less and infer more
Identify the most critical things to learn—to do that better
- identify critical knowledge gaps
Measure only as much as we need to support a decision
- Shift emphasis from measuring more and more under more and more conditions
Rebuttal: AOP is not a tool for risk assessment; it’s just one tool among others to help make a decision given the following reasons:
Plenty of detractors between science and regulation
- No-observed-adverse-effect-levels (NOAEL) and reference doses versus lowest-observed-adverse-effect level (LOAEL) and benchmark dose
Quantitative AOPs—what and how?
- Not quantitative (ADME relationship: KE1 vs KE2)
- Only two computerized AOP models
The AOP model is too complex
- Complexity of biology (kinetics, dynamics, inflammation, etc.)
- Plethora of biological pathways
AOPs in the Wiki—no foreseeable timeframe
- In four years (January 2014 to January 2018), there are 90 AOPs by 63 authors and 38 organizations
- 47 of the 90 AOPs are skeletons and nine have minimal content
- Only about 43 established AOPs in four years averages 10 AOPs per year
- Time consuming with limited resources
Questions from the Audience to Dr. Villeneuve:
- How would AOPs account for the limitations in in vitro models? Answer: Combination of in vitro and in vivo data; AOPs are not chemical specific, and toxicokinetics of chemicals are not considered.
- Can’t AOPs be made into book chapters to be more readable rather than a complex model system? Answer: AOP Wiki is more of a format to pull AOPs from various sources.
Questions from the Audience to Dr. Landesmann:
- Can new technologies help to reduce the time to develop/update AOP? Answer: Technology is still very limited.
Final Audience Vote: There were more people against the proposition.
My personal view/take-home message: AOPs can serve as tools to make regulatory decisions and may be useful in risk assessment.
This blog was prepared by an SOT Reporter. SOT Reporters are SOT members who volunteer to write about sessions and events they attend during the SOT Annual Meeting and ToxExpo. If you are interested in participating in the SOT Reporter program in the future, please email SOT Communications Director Michelle Werts.