IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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5.2 Human carcinogenicity data
No new studies on the human carcinogenicity of fumonisins were available to the
Working Group.
5.3 Animal carcinogenicity data
Fumonisin B 1 has been tested for carcinogenicity by oral administration in one study
in mice, one study in male rats and one study in male and female rats. In female mice, it
caused an increase in hepatocellular adenomas and carcinomas. In one study in male rats,
it caused an increase in cholangiocarcinomas and hepatocellular carcinomas. In the other
rat study, it induced renal tubule carcinomas in male rats, over half of which were
classified as a rare highly malignant variant.
Fumonisin B 1 has also been shown to promote tumours in mouse skin and trout livers
when 7,12-dimethylbenz[a]anthracene and aflatoxin B 1, respectively, were used as
tumour initiators.
5.4 Other relevant data
IARC MONOGRAPHS VOLUME 82
Fumonisins are poorly absorbed, rapidly excreted and not metabolized in animal
systems. The half-life for elimination in animal species is directly related to the average
body weight of the species, suggesting that the half-life in humans will be longer than
those determined experimentally in rats and other animals.
Fumonisin B 1 is hepatotoxic and nephrotoxic in all animal species tested. The earliest
histological change to appear in either the liver or kidney of fumonisin-treated animals is
increased apoptosis followed by regenerative cell proliferation. While the acute toxicity
of fumonisin is low, it is the known cause of two diseases which occur in domestic
animals with rapid onset: equine leukoencephalomalacia and porcine pulmonary oedema
syndrome. Both of these diseases involve disturbed sphingolipid metabolism and cardiovascular
dysfunction.
Fumonisin B 1 causes developmental toxicity in several animal species. In rats, mice
and rabbits, developmental effects occurred at dose levels associated with disruption of
sphingolipid metabolism and maternal toxicity in liver and kidney.
Postnatal dosing causes decreased survival of rat pups and results indicate that
sphingolipid metabolism is vulnerable after birth.
Fumonisin B 1 is inactive in bacterial mutation assays and in the unscheduled DNA
synthesis assay with rat hepatocytes, but induces DNA damage, such as micronuclei,
in vitro and in vivo. In some studies, addition of antioxidants reduced the DNA-damaging
effects of fumonisin B 1, suggesting that the effects may be due to oxidative stress.
Disruption of various aspects of lipid metabolism, membrane structure and signal
transduction pathways mediated by lipid second messengers appears to be an important