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

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Table 3 (c<strong>on</strong>td)<br />

Strain (sex) Initiator, dose, route<br />

<str<strong>on</strong>g>and</str<strong>on</strong>g> durati<strong>on</strong><br />

Sprague-<br />

Dawley (M)<br />

B[a]P, 4 mg/rat ig × 6<br />

(24 h after PH)<br />

D<strong>on</strong>ryu (M) 3′-Me-DAB, 0.06%<br />

diet, 3 weeks<br />

CD1 (M) AAF, 0.02% diet,<br />

2 weeks<br />

ACI (M<br />

<str<strong>on</strong>g>and</str<strong>on</strong>g> F)<br />

Cycasin, 100 mg/kg<br />

bw, ig × 1<br />

CD (F) N-OH-AABP or<br />

N-OH-FABP, 0.4<br />

mmol/kg bw, ip × 1<br />

(24 h after PH)<br />

Sprague-<br />

Dawley (M)<br />

NDEA, 40 or 50<br />

mg/kg bw, ip (18 h<br />

after PH)<br />

Wistar (M) NDEA, ~ 10 mg/kg bw<br />

in water, 2, 4 or 6<br />

weeks<br />

Interval<br />

between<br />

initiator <str<strong>on</strong>g>and</str<strong>on</strong>g><br />

promoter<br />

Dose <str<strong>on</strong>g>and</str<strong>on</strong>g> durati<strong>on</strong> of PB or<br />

NaPB <str<strong>on</strong>g>and</str<strong>on</strong>g> route<br />

Promoting or anti-promoting effects<br />

<strong>on</strong> preneoplastic or neoplastic<br />

hepatocellular lesi<strong>on</strong>s<br />

2 weeks PB, 0.05% diet, 50 weeks B[a]P given ig followed by PB<br />

produced tumours in 6/15 rats;<br />

PB al<strong>on</strong>e, 0/10<br />

2 weeks PB, 0.05% diet with initiator<br />

<str<strong>on</strong>g>and</str<strong>on</strong>g>/or given as a promoter<br />

for 35 weeks<br />

1 week PB, 0.002–0.25% diet<br />

(various c<strong>on</strong>centrati<strong>on</strong>s),<br />

78–84 weeks<br />

1 week PB, 0.05% diet, up to 480<br />

days<br />

Inhibiti<strong>on</strong> of EAIs when given with<br />

initiator; promoti<strong>on</strong> when given after<br />

initiati<strong>on</strong><br />

Dose-dependent tumour-promoting<br />

effects<br />

γ-GT-positive foci; incidence<br />

significantly greater in females than<br />

in males<br />

2 days PB, 0.05% diet, 64 weeks γ-GT-positive foci; no growth with<br />

PB al<strong>on</strong>e; growth initiated by<br />

PH + PB<br />

1 week PB 0.06% with cholinesufficient<br />

diet for 6 or 7<br />

weeks or choline-deficient<br />

diet for 8 weeks<br />

1 week PB, ~ 15 mg/kg bw per day<br />

in water, 4, 6 or 8 weeks<br />

γ-GT-positive foci; choline-sufficient<br />

+ PB, increased; choline-deficient<br />

+ PB, synergistic promoting acti<strong>on</strong><br />

PB treatment reduced latency for<br />

development of neoplastic nodules by<br />

3–6 m<strong>on</strong>ths<br />

Reference<br />

Kitagawa et al.<br />

(1980)<br />

Narita et al.<br />

(1980)<br />

Peraino et al.<br />

(1980)<br />

Uchida &<br />

Hir<strong>on</strong>o (1981)<br />

Shirai et al.<br />

(1981)<br />

Shinozuka<br />

et al. (1982)<br />

Barbas<strong>on</strong> et al.<br />

(1983)<br />

188<br />

<str<strong>on</strong>g>IARC</str<strong>on</strong>g> MONOGRAPHS VOLUME 79

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