James S. Bus PhD, DABT, ATS The Dow Chemical Company Society of Toxicology Education Summit

1. The Making of a Toxicologist in the 21st Century: Learning from the Past while Building for the Future James S. Bus PhD, DABT, ATS The Dow Chemical Company Society of Toxicology Education Summit October 20-21, 2011, Baltimore, MD

2. “The times they are a changin” Bob Dylan, 1964 Society of Toxicology Founding: 1961

3. Outline • Drivers of change • Science • Regulatory interventions • Exposure and Dosimetry • Learning from and building on the past • Toxicologists in the 21st Century: Valued partners providing solutions to healthy societies

4. Drivers of Change: Science • Rapidly advancing biology knowledge • Advancing research tools and technologies • Molecular biology, genomics, cell biology, animal models • Computational tools: PBPK to bioinformatics • Increasingly interdisciplinary and collaborative • Toxicology attracts and is dependent on many disciplines • Increasingly complex • Data integration demands from diversified sources • Changing expectations • Costs: more “bang for the buck” • Faster • Less use of animals • More informative for decision-making

5. Driver of Change: Regulatory Interventions • Responsive to societal progress and expectations • “Applied” practice of toxicology • Test methods • Proscribed tools and applications • Logistics • Data requirements for product development & stewardship • Pesticide, drug, and chemical registrations • Data quality: Good Laboratory Practices • Tier-based testing: data “fit for purpose” • Translation to risk (safety) assessment • Standardized defaults to address uncertainties • Defining the issues: • Cancer, development, endocrine, susceptible subpopulations, mixtures, etc. • Mode of action: facilitating lab to health extrapolations • “How much is enough?”

6. Driver of Change: Exposure & Dosimetry • Exposures changing with time • Moving from high to low exposures • Changing composition • Analytical sciences • Environmental detection and modeling • Biomonitoring programs • “The dose makes the poison” • “internal” vs “external” dosimetry • in vitro to in vivo extrapolation

7. Learning from and Building on the Past • Toxicology principles built from study of intact animals • Toxicity represents outcome of complex in vivo interactions: Mode of action key events • “The dose makes the poison” • ADME • Delivered dose • Homeostatic mechanisms • Organ to organ • Cell to cell • Extrapolating in vitro to in vivo is challenging

8. Embracing Change: 21st Century Toxicologists as “Solution Providers” • Society increasingly technology-dependent • Healthy and sufficient food supply • Clean air & water • Disease prevention and treatment • Consumer quality of life expectations • Sustainability: efficient and effective use of increasingly constrained resources • Toxicologists as public health scientists • Driving science-informed decision-making as valued partners to societal progress in a resource constrained world

9. Responsibility of a 21st Century Toxicologist “We want clean air. We want clean water. We want to rid our environment of poisons. But in our quest for material purity we must never forget for an instant that there are poisons, too, of the mind.” Jon Franklin, Society of Toxicology Annual Meeting Keynote Address, 1994