Phenobarbital and its Sodium Salt - IARC Monographs on the ...

Table 3 (contd)
Strain (sex) Initiator, dose, route
<strong>and</strong> duration
Fischer 344
(M)
NDEA, 200 mg/kg bw
or N-OH-AAF,
30 mg/kg bw or AFB 1,
0.5 or 1.0 mg/kg bw,
ip
Wistar (M) NDEA 10 mg/kg bw
per day + PB 15 mg/
rat, for 2, 4 or 6 weeks
Wistar (M) NDEA, 1.1, 3.3, 10 or
30 mg/kg bw, ip × 1
CD (F) NDEA, 10 mg/kg bw,
ig, 20 h after PH
Fischer 344
(F)
NDEA, 10 mg/kg bw,
ig, 20 h after PH
NDEA, 10 mg/kg bw
ig × 1, 24 h after PH
Interval
between
initiator <strong>and</strong>
promoter
Dose <strong>and</strong> duration of PB or
NaPB <strong>and</strong> route
2 weeks PB, 0.05% diet, 6 weeks;
PH end of third week of the
experiment
None (simultaneousadministration)
PB, 15 mg/rat, for 2, 4 or
6 weeks
1 week NaPB, 40, 100 or 1000
μg/mL in water, 12–18
months
1 week PB, 0.05% diet, 6 months;
PB withdrawn for 10 days
1 week PB, 0.05% diet, 3 months,
then high- or low-fat diet for
8 months
1 week PB, 0.05% diet, 4 months;
groups of rats withdrawn
from PB for 5–180 days;
re-administration of PB for
10–90 days
Promoting or anti-promoting effects
on preneoplastic or neoplastic
hepatocellular lesions
γ-GT-positive foci; growth only in
NDEA-initiated rats
PAS-positive; at 6 weeks significant
decrease in number of foci with
NDEA + PB
Liver carcinomas (38%) seen only
after 1000 μg/mL PB promotion <strong>and</strong>
30 mg/kg bw NDEA
γ-GT-positive foci; growth with PB;
decrease in number <strong>and</strong> size of foci
after withdrawal of PB
At 3 months, promotion of mostly
γ-GT-positive foci; high- or low-fat
diet decreased number <strong>and</strong> size of
foci
Altered hepatocellular foci;
withdrawal of PB decreased total
number; re-administration of PB
increased number
Reference
Shirai et al.
(1985)
Barbason et al.
(1986)
Driver &
McLean
(1986a)
Glauert et al.
(1986)
Hendrich et al.
(1986)
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<strong>IARC</strong> MONOGRAPHS VOLUME 79