1 

# STAKEHOLDER ISSUES

May 24, 2011 FIFRA SAP Consultation Integrated Approaches to Testing and Assessment Strategy: Use of New Computational and Molecular Tools 

### PPDC Work Group on 21st Century Toxicology/New Integrated Testing

Strategies

12



### PPDC Work Group on 21st Century Toxicology/New Integrated Testing Strategies • OBJECTIVE : This work group will focus on communication and transition issues as EPA phases in new predictive and testing methods over the next three to five years. This work group will help to focus EPA’s efforts on the key activities needed for successful communication and transition.

– Key communication activities include: identifying ways to improve understanding and communicate complex science to all stakeholders.

– Key transition activities include: identifying other internal and external applications of this ‘new’ science (e.g., improving agency decision making capability by harnessing new data streams and developing new diagnostic tools and biomarkers) and providing process recommendations to transition to the new testing paradigm. 23



### PPDC Work Group on 21st Century Toxicology/New Integrated Testing Strategies • MEMBERSHIP :

– 29 public members, including: • Non - EPA regulatory agencies • Environmental, animal protection, and worker protection NGOs • Registrants and trade and producer associations • Academia • PURPOSE OF THIS PRESENTATION: To offer for your consideration an overview of the stakeholder issues the workgroup has raised as important for the EPA and stakeholders to consider during this transition period, focusing on science rather than policy today 34



# ISSUES SUBGROUP • Formed June 2009 

### • Members

– Kristie Sullivan, Physicians Committee for 

### Responsible Medicine

– James Roberts, Medical University Of South Carolina



### – Erik Janus, Steptoe & Johnson

– Dave Tamayo, Sacramento County Department of 

### Water Resources

– Timothy Pastoor, Syngenta5



# ISSUES SUBGROUP • CHARGE: Capture salient stakeholder issues 

### related to new testing methods and strategies and present them in Q&A format • First product: Tool for EPA

– Education, Research

– Communication & Outreach 

### • Second product: Tool to inform December FACA meeting participants/discussion 56 

# PROCESS- Question generation • Brainstorming 

### • Quizzing constituents • Comments

– Full PPDC, Tox21 Workgroup, EPA 

### • Parity and Reorganization 

### • Check for duplication with web site • Development of “points to consider” for EPA to use in formulating answers 67



## STAKEHOLDER ISSUES • Stakeholders generally supportive 

### • General & Technical questions • Major themes

– Benefits/drawbacks of paradigm shift

– Demonstrating success during the transition

– Maintaining environmental and health protection

– Importance of planning for follow- up ahead of time 78 

# Costs and Benefits Should be 

# Clearly Communicated
• How will the EPA ensure that the current level of protection of human health and the environment is maintained or enhanced? • How will decision - making be improved by the use of molecular information? • How will the new toxicity testing paradigm increase the efficiency of the pesticide regulation process? What are the expected resource savings for both regulators and the regulated community? 89 

# Costs and Benefits Should be 

# Clearly Communicated
• How will EPA recognize the limitations and uncertainties associated with the use of the newer non - animal testing methods and take them into 

### account during the risk assessment process? • Will the use of molecular tools increase our ability to characterize the possible synergistic or antagonistic effects among mixtures? How? 910 

# Costs and Benefits Should be 

# Clearly Communicated • How will this new testing and assessment 

### paradigm affect our ability to identify health outcomes from chemicals in worker or public populations? • How will this shift help EPA protect wildlife populations? 

### • How will non -systemic toxicities be measured (e.g., skin irritation)? 1011 

# Costs and Benefits Should be 

# Clearly Communicated • How will molecular or in silico methods 

### capture differences between individuals in a human population (i.e., genetic and metabolic)?

– How do these methods compare to the standard suite of animal models used today for regulatory 

### testing? Are they more or less reflective of these inter- individual human differences?

– Can inclusion of ‘omics data help this process? 1112 

# Accomplishing the Paradigm 

# Should be Well - Planned • Understanding the biology resulting in toxicity and developing predictive tools with that knowledge will help improve the basis of safety assessment. • The chemical diversity found in pesticides must be sufficiently understood in order to group them appropriately and must be reflected in the test methods used. • Biomonitoring tools and cell - and tissue - based tests should be used to continually develop and refine one another--the safety assessment process can and should be dynamic and adaptable. 1213 

# Accomplishing the Paradigm 

# Should be Well - Planned • Will moving away from the use of a whole animal and towards the use of a set of in vitro assays miss important biological activities, especially at the organ, system and organism level?

– This question is getting at how the toxicity pathway approach translates to a risk management decision. For example, how does the EPA envision making determinations about a chemical’s potential to cause developmental toxicity or endocrine disruption using in vitro tests?

– Discussion of this issue could address: • The comprehensive nature of the likely battery of in vitro methods • The nature of the toxicity pathways and the interrelatedness that is thought to exist. • The limitations of the current animal models in terms of breadth and depth of analysis possible. 1314 

# Accomplishing the Paradigm 

# Should be Well - Planned • How does EPA plan to incorporate population - level data (epidemiological research, biological surveillance) to assist in the "ground truthing" of molecular pathway- based data? • How does EPA plan to advance the "weight of evidence approach" to consider and integrate all available pertinent data?

– Combining single tests into test batteries

– Statistical techniques to process these data

– Formal WOE decision frameworks

– Interpreting contradictory data 1415 

# Accomplishing the Paradigm 

# Should be Well - Planned • How can we ensure that new scientific tools are 

### developed and implemented in such a way that ensures coordination between the OPP and other departments or agencies which have overlapping 

### responsibilities, such as endangered species, water quality, post- market monitoring, or data requirements? • This lack of coordination in the past has led to different standards, duplicative data generation, and 

### lack of protection for key organisms. 1516 

# Accomplishing the Paradigm Should be Well - Planned • What is the criteria for determining when you can replace one test with another? What does “validation” mean in this [human pathway- based] context? What 

### process will EPA follow to implement and refine tests?

– Methods should be reliable and relevant to their use

– Criteria depends on the question you are trying to 

### answer; tolerance of uncertainty is higher depending on the purpose of tool (Prioritization vs. Risk Assessment). 1617



# Next Steps
• Continue to collect input from stakeholders • Refine discussion questions as EPA continues this process • Planning October 11, 2011 FACA/Stakeholder Meeting

21st CENTURY TOXICOLOGY: Diagnostic Tools and Biomarkers in Pesticide Medical Management, Exposure Surveillance, and

Epidemiologic Research State-of -the-Science, Challenges, and Opportunities