IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

Aristolochic acids
3. Studies of Cancer in Experimental Animals
3.1 Oral administration
SOME TRADITIONAL HERBAL MEDICINES 87
Mouse: A group of 39 female NMRI mice [age not specified] was given daily doses
of 5.0 mg/kg bw aristolochic acids (77.2% aristolochic acid I and 21.2% aristolochic
acid II) by gavage for three weeks. A group of 11 vehicle controls was given solvent
[unspecified]. The mice were kept for up to 56 weeks with interim sacrifice at 3, 9, 18,
26, 37 and 48 weeks. The remaining eight animals were killed at 56 weeks. At 18 and 26
weeks stages, low- to middle-grade papillomatosis was observed in the forestomach of all
mice. Of the mice sacrificed at 37 and 48 weeks, 1/5 mice at each time point had
squamous-cell carcinoma. Forestomach carcinoma was diagnosed in all of the eight mice
killed at 56 weeks. Adenocarcinoma of the glandular stomach was observed in one mouse
at 37 weeks. In addition, cystic papillary adenomas in the renal cortex (6/8 mice),
malignant lymphomas (4/8 mice), alveologenic carcinomas (8/8 mice) and haemangiomas
in the uterus (3/8 mice) were found at 56 weeks. No tumours were detected in 11 control
animals at 56 weeks (Mengs, 1988).
Rat: Groups of 30 male and 30 female Wistar rats, 10 weeks of age, were given aristolochic
acids (77.2% aristolochic acid I and 21.2% aristolochic acid II) as their sodium
salts in distilled water at 10.0 or 1.0 mg/kg bw for three months and held for up to an
additional six months or at 0.1 or 0 mg/kg bw for 3, 6 or 12 months and held for up to
an additional four months. Forestomach carcinomas were observed in 13/18 males and
8/13 females given 10 mg/kg bw for three months and killed at six months. In addition,
renal pelvis carcinomas (8/18) and urinary bladder carcinomas (3/18) were observed in
the males given 10 mg/kg bw. Forestomach carcinomas were observed in 4/4 female rats
treated with 10 mg/kg bw for three months and killed at nine months. In the groups dosed
with 1.0 mg/kg bw for three months, forestomach carcinomas were observed in 3/11
males and 0/10 females after six months and 6/9 males and 2/11 females after nine
months. In rats treated with 0.1 mg/kg bw for three months and killed at 12 months, 2/7
males and 0/6 females had forestomach carcinomas. In rats treated with 0.1 mg/kg bw
for 12 months and killed at 16 months, 4/4 males and 1/5 females had forestomach
tumours. Only one tumour (a spontaneous endometrial polyp) was observed in the
controls (0/30 in males and 1/31 in females) (Mengs et al., 1982).
Two groups of male Wistar rats, eight weeks old, were examined for the histogenesis
of forestomach carcinoma caused by aristolochic acids [77.2% aristolochic acid I and
21.2% aristolochic acid II]. A group of 108 rats was given aristolochic acids daily by
gavage at a dose of 10 mg/kg in distilled water for up to 90 days. A group of 37 controls