Table 3.1Studies of cancer in experimental animals exposed to chlorambucil

Species, strain (sex)
Duration
Reference
Route
Dosing regimen
Animals/group at start
Incidence of tumoursSignificanceComments
Mouse, S (NR)
22 wk
Salaman & Roe (1956)
Skin
0, 2.7 mg total dose in methanol, administered by skin painting once weekly for 10 wk; croton oil used as promoter (from Week 5 to Week 22)
20 (control), 25
Skin (papillomas): Purity NR
0/17, 11/19 (58%)P < 0.01
Mouse, A/J (M, F)
39 wk
Shimkin et al. (1966)
i.p.
0, 9.6, 37, 150, 420 mg/kg bw (total dose), 3 ×/wk for 4 wk
45, 60, 60, 60, 173 (male control), 157 (female control)
Lung (adenomas and adenocarcinomas):Purity NR
43% (0.53 tumours/mouse);
32% (0.42 tumours/mouse);
18/38 (47%, 0.6 tumours/mouse);
48/56 (86%, 1.6 tumours/mouse);[P < 0.001]
45/47 (96%, 5.1 tumours/mouse);[P < 0.001]
30/30 (100%, 8.9 tumours/mouse)[P < 0.001]
Mouse, Swiss-Webster (M, F)
15 mo
Weisburger et al. (1975)
i.p.
3 mg/kg bw (MTD) or 1.5 mg/kg bw, 3 ×/wk for 6 mo
25/sex/group
Lung: Results reported had been combined for the two doses
M–22/35P < 0.001,
F–20/28
(controls: 10/101 M, 21/153 F)
P < 0.001
Lymphoma-myeloid leukaemia:
M–6/35P = 0.004,
F–4/28
(controls: 3/101 M, 3/153 F)
P = 0.012
Ovary:
F–10/28
(controls: 6/153 F)
P < 0.001
Rat, Sprague-Dawley (M, F)
15 mo
Weisburger et al. (1975)
i.p.
4.5 mg/kg bw (MTD) or 2.2 mg/kg bw, 3 ×/wk for 6 mo
25/sex/group
Haematopoietic/lymphatic system: Results reported had been combined for the two doses
M–8/33
(control: 2/179 M, 1/181 F)
P < 0.001
Rat, Sprague-Dawley (F)
Lifetime (3 yr)
Berger et al. (1985)
Oral
0, 3, 6, 13.5, 27 mg/kg bw per mo by gavage for 18 mo
30/group, 120 controls
Mammary gland (malignant): Purity > 99%
The dose of 3 mg/kg bw was kept constant over all treatment groups. To increase the dose, the frequency of administrations was increased
8/120, 2/30, 4/30, 10/30, 5/30[P < 0.001]
(27 mg/kg)
Central & peripheral nervous tissue (malignant):
2/120, 2/30, 1/30, 3/30, 3/30[P < 0.05]
(13.5 and 27 mg/kg)
Haematopoietic & lymphatic tissue:
1/120, 0/30, 4/30, 0/30, 0/30[P < 0.05]
(6 mg/kg)
External auditory canal (malignant):
0/120, 2/30, 0/30, 0/30, 3/30
Mouse, BALB/c (M, F)
Lifetime (2 yr)
Cavaliere et al. (1990)
Oral
0 or 1 mg/kg bw by gavage 5 ×/wk for 12 wk
53 males, 54 females, 50 (male control), 50 (female control)
Lymphoreticular system: Purity > 99%
Survival was reduced in treated animals of both sexes (P < 0.001)
5/50, 4/50, 7/53, 24/53P < 0.01 (F)
Lung (adenomas):
19/50, 7/50, 47/53, 46/54P < 0.001 (M, F)
Mammary gland:
0/50, 2/50, 0/53, 4/54P < 0.05 (F)

bw, body weight; d, day or days; F, female; i.p., intraperitoneal; M, male; mo, month or months; MTD, maximum tolerated dose; NR, not reported; wk, week or weeks; yr, year or years

From: CHLORAMBUCIL

Cover of Pharmaceuticals
Pharmaceuticals.
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 100A.
IARC Working Group on the Evaluation of Carcinogenic Risks to Humans.
© International Agency for Research on Cancer, 2012. For more information contact publications@iarc.fr.

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