IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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3. Studies of Cancer in Experimental Animals
Studies on the carcinogenicity of aflatoxins in experimental animals completed and
reported up to 1993 have been previously evaluated (IARC, 1993). Oral administration
of aflatoxin mixtures and aflatoxin B 1 in several strains of rats, hamsters, salmon, trout,
ducks, tree shrews and monkeys induced benign and malignant hepatocellular and/or
cholangiocellular tumours. Orally administered aflatoxin B 1 did not induce liver tumours
in mice. Renal cell tumours were also found in rats following oral administration, while
intraperitoneal administration to adult mice increased the incidence of lung adenomas.
Intraperitoneal administration of aflatoxin B 1 to pregnant and lactating rats induced
benign and malignant liver tumours in mothers and their progeny. Oral administration of
aflatoxin B 2 to rats induced liver adenomas, while intraperitoneal administration induced
a low incidence of hepatocellular carcinoma. Oral administration of aflatoxin G 1 induced
hepatocellular adenomas and carcinomas and renal cell tumours in rats and liver-cell
tumours in trout; however, the responses were less than with aflatoxin B 1 at the same
dose level. A similar pattern was reported for aflatoxin M 1 and its metabolite aflatoxicol,
while aflatoxin Q 1 induced a higher incidence of hepatocellular carcinoma in trout than
aflatoxin B 1. Aflatoxin M 1 induced fewer hepatocellular carcinomas following oral administration
to rats and trout than aflatoxin B 1 given at an equivalent dose by the same
route. Aflatoxicol induced hepatocellular carcinomas in both species; the tumour incidences
were lower than that in animals treated with aflatoxin B 1 at the same dose level.
The previous evaluations of aflatoxins (IARC, 1993) were that evidence for carcinogenicity
in experimental animals was sufficient for aflatoxins B 1, G 1 and M 1, limited for
aflatoxin B 2 and inadequate for aflatoxin G 2.
This monograph considers only relevant carcinogenicity studies published since
1993.
3.1 Intraperitoneal administration
3.1.1 Transgenic mouse
IARC MONOGRAPHS VOLUME 82
Groups of 11 wild-type F 1 × F 1 (C57BL/6 × CBA) and 12 transgenic mice overexpressing
porcine transforming growth factor β 1 (TGF-β 1) [sex unspecified], seven days
of age, received aflatoxin B 1 as a single intraperitoneal dose of 6 μg/kg bw. No spontaneous
tumours were detected after 12 months in either nine control wild-type or 19
control transgenic mice. Adenomas [assumed to be hepatocellular adenomas] (2/12 and
3/11) and hepatocellular carcinomas (1/12 and 0/11) were detected after 12 months in the
liver of the aflatoxin-treated transgenic and wild-type mice, respectively (Schnur et al.,
1999). [The Working Group noted the limited reporting of this study.]