SOT FDA Colloquium February 19: “Route-to-Route Extrapolation in the 21st Century”

February 19 SOT FDA Colloquium Banner.png

SOT and the US Food and Drug Administration Center for Food Safety and Applied Nutrition (US FDA/CFSAN) cordially invite you to join us for our February 19 colloquium, “Route-to-Route Extrapolation in the 21st Century.” This session is open to the public to attend in person or via webcast at no charge. These colloquia are an update on toxicological science rather than a public forum for discussion of toxicology regulatory issues. The colloquium will take place from 8:30 am to 12:50 pm (ET) in the Wiley Auditorium at US FDA in College Park, Maryland. The Chair of the colloquium is Harvey J. Clewell III of Ramboll, and the Co-Chair is Jeffrey Fisher of the US FDA National Center for Toxicological Research.

The toxicity and pharmacokinetic profiles of substances may vary with the exposure route. If appropriately conducted studies are available for a relevant route of exposure, generally the point of departure (POD) is calculated based on the data from the studies. However, if adequate data based on the relevant route of exposure are not available, a route-to-route extrapolation methodology may be employed to predict toxicity and estimate POD for risk assessment. This methodology evaluates data from studies based on other nonrelevant routes of exposure, provided that the observed toxicity or biomarkers of toxicity are systemic and not related to portal of entry. Route-to-route-extrapolation-based approaches utilize equivalent internal dose rather than external dose for predicting effects. Physiologically based pharmacokinetic (PBPK) models enable route-to-route extrapolations of pharmacokinetics and systemic toxicity by normalizing internal dosimetrics for different routes of exposure. Given that route-to-route extrapolations do not incorporate differences in modes of action between exposure routes, there could be a certain degree of uncertainty associated with the model. However, extrapolation uncertainty reduces with the incorporation of additional data or assumptions (such as 100% absorption, in vitro, or QSAR-based predictions), when enough information is available to support the changes to the model. Although route-to-route-extrapolation-based approaches are being explored for predicting effects and estimating POD, there are some inconsistencies in methods used by different organizations, which may introduce variability. This session will present considerations for conducting route-to-route extrapolations and discuss the possibility of developing consistent methods for utilizing such extrapolations for risk assessment.


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 Registration deadline for participants who are
 not federal employees: February 4, 2020


Presentations include:

8:00 AM–8:30 AM

Badge Pickup

 8:30 AM–8:40 AM

Welcome (TBD), US FDA, College Park, MD
Speaker Introductions
Harvey J. Clewell III, Ramboll, Research Triangle Park, NC

8:40 AM–9:15 AM


Introduction to Route-to-Route Exposure
Harvey J. Clewell III, Ramboll, Research Triangle Park, NC

9:15 AM–9:50 AM

OECD Guidance on the Characterization, Validation, and Reporting of Physiologically Based Kinetic (PBK) Models
Alicia Paini, European Commission Joint Research Centre, Ispra, Italy (via webcast)

 9:50 AM–10:25 AM

In Vitro to In Vivo Extrapolation of Metabolism Data to Support Physiologically Based Modeling for Route-to-Route Extrapolation
John C. Lipscomb, Center for Toxicology & Environmental Health, Little Rock, AR

10:25 AM–10:40 AM


10:40 AM–11:15 AM

Determination of an Internal Margin of Exposure between Rodent Oral and Human Dermal Exposures to Phenoxyethanol Using Physiologically Based Modeling
John Troutman, Procter & Gamble, Cincinnati, OH

11:15 AM–11:50 AM


Examples of Route-to-Route Extrapolation Conducted at the US FDA Center for Food Safety and Nutrition
Shruti K. Kabadi, US FDA, College Park, MD


11:50 AM–12:50 PM

Roundtable Discussion
Moderator: Harvey J. Clewell III
All speakers
Jeffrey Fisher

Questions concerning the regulatory science are encouraged from the audience on-site and from webcast participants for the roundtable discussion. Regulatory policy will not be discussed.

The SOT FDA Colloquia on Emerging Toxicological Science: Challenges in Food and Ingredient Safety present scientific training that is high-quality, cutting-edge, future-oriented toxicological science for US FDA employees and are open to the public at no cost.

Recordings and slides from the previous colloquia are available for free via the “SOT FDA Colloquia” web page, including the December 12, 2019, session, “Dermal Absorption and Toxicity: Concepts for Application to Safety Assessment.”

Additional 2020 colloquia include:

  • April: “Artificial Intelligence in Food and Cosmetic Safety”
  • May: “Integrated Approaches to Testing and Assessment—The Future of Predictive Toxicology” (webcast only)
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