IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

FUMONISIN B 1
were decreased and the incidence of ossification deficits, short and wavy ribs and hydrocephalus
was increased at the 50- and 100-mg/kg bw doses (Gross et al., 1994).
Pregnant Charles River CD-1 mice were administered 0 to 100 mg/kg bw pure fumonisin
B 1 by gavage on gestation days 7–15. Doses ≥ 25 mg/kg bw induced maternal liver
lesions and a dose-dependent increase in the incidence and severity of hydrocephalus in
the fetuses. Reduced fetal body weight was found at ≥ 50 mg/kg bw, while increased
frequency of resorptions and decreased litter size were present only at 100 mg/kg bw.
Doses ≥ 25 mg/kg bw increased the sphinganine/sphingosine ratios in maternal but not
fetal livers. The effects of fumonisin B 1 on the fetuses and the alteration of the sphinganine/sphingosine
ratio in maternal but not fetal liver suggest that the effects of
fumonisin B 1 on the fetuses are not mediated by changes in sphinganine/sphingosine
ratios in the fetuses. The association with effects on the maternal liver may indicate that
developmental effects are mediated by maternal hepatotoxicity (Reddy et al., 1996).
Six groups of Syrian hamsters were dosed with 0–18 mg/kg bw purified
fumonisin B 1 by gavage daily on days 8–12 of gestation and killed on day 15. The
treatment caused fetal death, decreased fetal body weight and skeletal variations
consistent with delayed development in a dose-dependent manner, without causing
maternal toxicity (Penner et al., 1998).
In timed-bred Syrian hamsters dosed daily with 0–12 mg/kg bw fumonisin B 1 by
gavage on gestation days 8–10 or 12, reduced maternal weight gain was observed at
doses ≥ 8 mg/kg bw. Maternal aspartate transaminase and total bilirubin, used as indices
of maternal hepatotoxicity, showed no significant difference between groups. At doses
higher than 2 mg/kg bw fumonisin B 1, there was an increased incidence of prenatal loss
(death and resorptions). At 12 mg/kg bw, all litters were affected and 100% of the fetuses
were dead and resorbing (Floss et al., 1994a).
A significant increase in litters with fetal deaths occurred in Syrian hamsters given
18 mg/kg bw purified fumonisin B 1 or culture-extracted fumonisins (18 mg fumonisin B 1
plus 4.5 mg fumonisin B 2) by gavage on gestation days 8 and 9. There were no clinical
signs of maternal intoxication (Floss et al., 1994b).
New Zealand White rabbits were dosed by gavage on gestation days 3–19 with purified
fumonisin B 1 at 0.1, 0.5 or 1.0 mg/kg bw. Maternal lethality occurred at the 0.5- and
1.0-mg/kg bw doses (10–20%), but there was no difference in maternal weight gain
during pregnancy. Fetal weight and liver and kidney weights were decreased at 0.5 and
1.0 mg/kg bw. Increased sphinganine/sphingosine ratios were found in maternal serum,
liver and kidney, but there was no significant effect of fumonisin B 1 on the sphinganine/sphingosine
ratio in fetal brain, liver or kidney (LaBorde et al., 1997).
Diet formulated with culture material of F. verticillioides strain MRC 826 to provide
0, 1, 10 or 55 mg fumonisin B 1 per kg diet was fed to male and female rats beginning 9
and 2 weeks before mating, respectively, and continuing throughout the mating, gestational
and lactational phases of the study. Nephropathy was found in males at dietary
doses of ≥ 10 mg/kg and in females fed 55 mg/kg diet. No significant reproductive
effects were found in males or dams and fetuses examined on gestation day 15, or dams
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