1. Decision Contexts in a Changing Toxicology Paradigm
Gary Ginsberg
Connecticut Dept of Public Health
November 20, 2017
NAS Emerging Science Workshop

2. Decision-Makers & Confidence Needs
Govt Regulator
Screening/Prioritization
Testing criteria
TSCA/Pesticides approvals
Standard Setting
Emergency Responder
Urgent decisions
Data poor chemicals
Industries
Screening new chems
Consumers/NGOs
Water quality
Consumer products
Extensive ??
Minimal

3. Where Does Confidence Come From?
Predictive
In vitro -----> In vivo anchoring
Low false (+), false (-)
Logical/Mechanistic
Covers range of vulnerability
Prior success – case studies
Social and Psychological Determinants
Beliefs/dogma about what is required

4. General Context: Advancing HHRA
HHRA and PH Decisions Limited By:
Data gaps
Data poor chemicals
Incomplete assessment of endpoints
Gaps in understanding mixtures and aggregate risk
Gaps in mechanistic understanding
How do chemicals act (AOP)?
What happens at low dose?
Gaps in understanding vulnerability
Life stage / Lifestyle / Pre-existing conditions
Where Can New Tox Paradigm Help?

5. General Context Which decisions can they inform?
Qualitative: Hazard Characterization?
Is chemical a carcinogen, mutagen, EDC, etc.
Screening and prioritization
Quantitative: Standard-setting? Cost-Benefit?
Which methods best for HHRA vs EcoRisk?

6. Regulatory Decisions: TSCA
Mandate to Use New Methods to:
↓ Animal use
↓ Data gaps
↑ Efficiency
Strategy needed to integrate new information into existing TSCA methods (QSAR  In vivo)
Evaluate data poor chemicals in inventory
New chemicals review
Consumer Products
Toxicity of data poor ingredients
Screening alternative ingredients

7. Decision Context: Testing Criteria Replacement of Animal Testing
What is enough evidence?
Example – replacement of EDC uterotrophic
USEPA OPP - in vitro screens for acute package
How to integrate new data into existing databases and programs
eg. Can cytotoxicity replace LD50s in MSDSs?

8. Decisions during Emergency Response
Rapid decisions about toxicity on
Released chemicals/mixtures
Combustion byproducts
Mitigation chemicals (e.g., dispersants)

9. Decisions Regarding Environmental Quality
Evaluation of bioactivity of complex mixtures
Is “recycled water” suitable for human use?
Are there exposures of concern from
packaging
consumer products
indoor environments

10. Summary
Many decisions need to be better informed by advanced tox methods
TSCA may lead the way?
Already seeing applications in Pesticides, Environmental Quality, Emergency Response
Today’s Workshop
Where and how can new methods be useful?
What is the level of confidence needed?
How is this confidence/acceptance achieved?