|
NDA
20-358 |
10 |
A)
Ames
Tests
1)
Plate
incorporation method
Results summarized in attached tables. (Data for TA 1538 generated in a separated
experiment because in original experiment vehicle control values were outside normal
range).
Bupropion was considered positive in strain TA 100,
in both presence and absence of metabolic activation. The maximum number of revertants was about 2 x control (which was
the criterion for a positive response in this strain). An increase of about 2.5 x was seen in TA
1535 in the presence of metabolic activation; however the criterion for a
positive response in this strain a 3 x increase.
2)
Preincubation
Method
Results summarized in attached table. As indicated, the pattern of response was
the same as in the plat incorporation assay (i.e., increase in TA 100 with and
without activation in TA 1535 with activation); however in no case was the
stated criterion for a positive response achieved (i.e., 2 x increase for TA
100 and 3 x for TA 1535).
B)
In vivo
cytogenetic study in rats
1)
Dosage
5/sex at 0, 0, 100 (LD), 200 (MD), or 300 (HD)
mg/kg/day of “degraded” drug (i.e., containing impurities), or 300 mg/kg/day of
undegraded drug (this group hereafter referred to as HD*), for 5 consecutive days;
animals sacrificed 24 hr. after last dose for cytogenetic exam of bone marrow.
Strain: Charles River CD
2)
Results
a)
Observed
signs
Salivation at all doses; D-R; no difference in
incidence between HD and HD*.
b)
Mortality
None
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