UNIT 1 Safety Tests

Question 1

• two species, two routes.
• Determine the no-effect dose, maximum tolerated dose, and median lethal dose (in some cases)

Answer 1

Acute toxicity

Question 2

• Three doses, two species.
• 2 wks to 3 months before clinical trials
• The longer the duration of expected clinical use, the longer the subacute test.
• Determine biochemical, physiologic effects.

Answer 2

Subacute or subchronic toxicity

Question 3

• Rodent and at least one nonrodent species for ≥6 months.
• Required when drug is intended to be used in humans for prolonged periods.
• Usually run concurrently with clinical trials.
• Determine same end points as subacute toxicity tests. ( biochemical and physiologic effects)

Answer 3

Chronic toxicity

Question 4

• Two species, usually one rodent and rabbits.
• Test effects on animal mating behavior, reproduction, parturition, progeny, birth defects, postnatal development.

Answer 4

Effect on reproductive performance

Question 5

• Two years, two species.
• Required when drug is intended to be used in humans for prolonged periods.
• Determine gross and histologic pathology.

Answer 5

Carcinogenic potential

Question 6

• Test effects on genetic stability and mutations in bacteria (Ames test) or mammalian cells in culture; dominant lethal test and clastogenicity in mice.

Answer 6

Mutagenic potential