CD7 TK

Question 1

In evaluating dose-response relationships, the benchmark dose approach offers what advantage over the NOAEL approach?
A. establishes a mode-of-action for threshold effects
B. provides greater certainty with fewer animals
C. establishes a mode-of-action for nonthreshold effects
D. includes a measure of variability in the data set

Answer 1

D. includes a measure of variability in the data set

Explanation and Reference:
The benchmark dose includes a measure of variability whereas the NOAEL does not. It also allows consideration of the shape of the entire dose-response curve and permits a specified benchmark response (BMR) level for RfD calculations. C&D 8th, p. 134-135

Question 2

The following dosages of a test drug were administered to male rats by oral gavage daily for 28 days: 10, 50, and 100 mg/kg. The only observed toxicity was focal hepatocyte necrosis, observed at the 100-mg/kg dose level. Based on these data, what is the no-observed adverse effect (NOAEL)?
A. 10 mg/kg
B. greater than 50 mg/kg, but less than 100 mg/kg
C. 100 mg/kg
D. 50 mg/kg

Answer 2

D. 50 mg/kg

Explanation and Reference:
The NOAEL is a professional opinion based on the design of the study, indication of the drug, expected pharmacology, and spectrum of off-target effects. It requires a decision of what findings are adverse to the test system under the conditions of study. http://www.fda.gov/CDER/guidance/5541fnl.pdf “Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers”; C&D 8th p. 134 (also C&D 9th, pp. 36-37)