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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

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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 decisionmaking capability by harnessing new data streams and developing 

new diagnostic tools and biomarkers) and providing process 

recommendations to transition to the new testing paradigm.

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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

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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, Syngenta
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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 

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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 

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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

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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?

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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?

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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)? 

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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? 

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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. 

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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.

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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 

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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. 

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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).

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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