Why might route-to-route extrapolation be necessary in toxicology, and what uncertainties does it introduce?

• A. Different exposure routes affect absorption and first-pass metabolism; extrapolating doses between oral, inhalation, and dermal routes introduces uncertainties of bioavailability and kinetics.
• B. Route-to-route extrapolation is always straightforward with no uncertainties.
• C. Route-to-route extrapolation only applies to inhalation exposures.
• D. Route-to-route extrapolation eliminates bioavailability concerns.

Answer: (A)