Thoughts on NAS Thoughts on NAS Science and Decisions (2009)Science and Decisions (2009)

John P. Christopher, Ph.D., D.A.B.T.John P. Christopher, Ph.D., D.A.B.T.

California Department of Toxic Substances ControlCalifornia Department of Toxic Substances Controlandand

TERA FellowTERA Fellow

Two QuestionsTwo Questions

Should toxicodynamic phenomena be Should toxicodynamic phenomena be modeled as a continuous function of dose modeled as a continuous function of dose through the low dose region?through the low dose region?

Does the NAS paradigm for risk assessment Does the NAS paradigm for risk assessment omit the inevitable connections to risk-omit the inevitable connections to risk-benefit and risk management?benefit and risk management?

Continuous Variable?Continuous Variable?

Considering all the levels at which an organism Considering all the levels at which an organism responds to a chemical stressor - responds to a chemical stressor -

And moving upward through those levels of And moving upward through those levels of organization (increasing dose and response) - organization (increasing dose and response) -

Is it valid to describe toxicodynamics with a smoothly Is it valid to describe toxicodynamics with a smoothly increasing function of dose increasing function of dose in the low-dose in the low-dose regionregion??

Continuous Variable?Continuous Variable?

Martin et al., Environmental Health Perspectives, Martin et al., Environmental Health Perspectives, , 117(3): 392–399,, 117(3): 392–399, 20092009

Continuous Variable? Continuous Variable?

Taken from Wikipedia CommonsTaken from Wikipedia Commons

Continuous Variable? Continuous Variable?

Pupillary Response, http://autonomy.caltech.edu/biomedicine/modelling.html Pupillary Response, http://autonomy.caltech.edu/biomedicine/modelling.html

Continuous Variable?Continuous Variable?

Thyroid Pituitary Axis, Thyroid Pituitary Axis, http://www.abc.net.au/health/library/stories/2005/06/16/1831822.htm http://www.abc.net.au/health/library/stories/2005/06/16/1831822.htm

Continuous Variable?Continuous Variable?

Integration throughout the Organism via the Pituitary GlandIntegration throughout the Organism via the Pituitary Gland

Continuous Variable?Continuous Variable?

Continuous Variable?Continuous Variable?

My Viewpoint:My Viewpoint:

Classical dose-response functions are clearly Classical dose-response functions are clearly valid in the region of observable adverse valid in the region of observable adverse effects,effects,

BUTBUTLet us keep our minds open to the evolving Let us keep our minds open to the evolving

descriptions coming from Systems Biology.descriptions coming from Systems Biology.

Risk Assessment ParadigmRisk Assessment Paradigm

HAZARDIDENTIFICATION

RISKCHARACTERIZATION

EXPOSUREASSESSMENT

DOSE-RESPONSEASSESSMENT

Risk Assessment ParadigmRisk Assessment Paradigm

HAZARDIDENTIFICATION

RISKCHARACTERIZATION

EXPOSUREASSESSMENT

DOSE-RESPONSEASSESSMENT

RISKCOMMUNICATION

Risk-Benefit is the Inescapable Matrix for Risk-Benefit is the Inescapable Matrix for Risk Assessment and Risk ManagementRisk Assessment and Risk Management

HAZARDIDENTIFICATION

RISKCHARACTERIZATION

EXPOSUREASSESSMENT

DOSE-RESPONSEASSESSMENT

RISKCOMMUNICATION

Risk Benefit Risk Benefit MatrixMatrix

Our common metric is Our common metric is Risk.Risk.

Everyone else’s is Everyone else’s is Money.Money.

So, build bridges with the social scientists who So, build bridges with the social scientists who monitize riskmonitize risk for the managers of the world. for the managers of the world.

$ $ ££ €€ ¥¥ рубруб ₨₨

Advice from Prof. EinsteinAdvice from Prof. Einstein

"God does not care about our mathematical difficulties. He "God does not care about our mathematical difficulties. He integrates empirically." integrates empirically."

““I have little use for scientists who find the thinnest part of a I have little use for scientists who find the thinnest part of a board of wood and drill a large number of holes.”board of wood and drill a large number of holes.”

"Anyone who has never made a mistake has never tried "Anyone who has never made a mistake has never tried anything new." anything new."

““Learn from yesterday, live for today, hope for tomorrow. The Learn from yesterday, live for today, hope for tomorrow. The important thing is not to stop questioning.”important thing is not to stop questioning.”