IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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4.3.2 Experimental systems
IARC MONOGRAPHS VOLUME 82
(a) Developmental and reproductive toxicity studies
Pregnant CD CRL rats were given oral doses of 0, 1.875, 3.75, 7.5 or 15 mg/kg bw
fumonisin B 1 per day on gestation days 3–16. Feed consumption and body weight gain
were significantly decreased at the 15-mg/kg bw dose. Fetal body weights at day 17 were
similar in control and treated groups, but in day-20 fetuses, female weight and
crown–rump length were significantly decreased at the highest dose. In day-17 animals,
dose-related increases in sphinganine/sphingosine ratios were seen in maternal livers,
kidneys and serum. Sphinganine/sphingosine ratios in maternal brains were not affected,
nor were those of fetal kidneys, livers or brains (Collins et al., 1998a). In a similar study
using dose levels of 0, 6.25, 12.5, 25 or 50 mg/kg bw fumonisin B 1 per day, maternal
toxicity and fetal toxicity were seen at the 50-mg/kg bw dose. The effects on the fetuses
included increased numbers of late deaths, decreased body weight and crown–rump
length and increased incidence of hydrocephalus and skeletal anomalies. Dose-related
increases in sphinganine/sphingosine ratios were seen in maternal livers, kidneys, serum
and brain, but not in fetal livers, kidneys or brain (Collins et al., 1998b). The data from
these two studies suggest either that fumonisin B 1 does not cross the placenta, the
observed fetal toxicity being a secondary consequence of maternal toxicity, or that a
potential direct effect of fumonisin B 1 on fetal development is not related to changes in
sphinganine/sphingosine ratios in the fetuses.
Groups of pregnant Fischer 344 rats were dosed by gavage daily on gestation days 8
to 12 with 30 or 60 mg/kg bw purified fumonisin B 1 or with a fat-soluble extract of
F. proliferatum/corn culture that would provide a dose of approximately 60 mg fumonisin
B 1 per kg body weight. Lower fetal litter weight and delayed ossification were
observed in the rats given 60 mg/kg bw fumonisin B 1, but not in rats given 30 mg/kg bw
fumonisin B 1 or the fat-soluble extract (Lebepe-Mazur et al., 1995).
The neurobehavioural and developmental effects of fumonisin B 1 were studied in
Sprague-Dawley rats treated by gavage on gestation days 13–20 with 0, 0.8 or 1.6 mg/kg
bw fumonisin B 1 obtained from culture material or 0, 1.6 or 9.6 mg/kg bw purified fumonisin
B 1. There was no effect on reproductive outcomes or offspring body weight through
adulthood in either experiment. Some effects on acoustic startle response and play
behaviour were found in male but not in female offspring prenatally treated with any
dose of purified fumonisin B 1. Fumonisin B 1 treatment had no effect on complex maze
performance or open field and running wheel activity (Ferguson et al., 1997).
Pregnant Charles River CD-1 mice were treated orally with a semipurified extract of
F. verticillioides culture providing 0, 12.5, 25, 50 or 100 mg/kg bw fumonisin B 1 daily
on gestation days 7–15. Maternal mortality was observed at doses of 50 and 100 mg/kg
bw. Signs of liver damage and decreased maternal body weight gain were observed at
≥ 25 mg/kg bw. The percentage of implants resorbed was increased at all doses in a dosedependent
manner. The number of live fetuses per litter and the mean fetal body weight