IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

FUMONISIN B 1
The kinetics of absorption of fumonisin B 1 and of fumonisin B 2 in rats are similar,
involving rapid distribution and elimination (Shephard et al., 1995c). In vervet monkeys
(Cercopithecus aethiops), the bioavailability of fumonisin B 2 may be less than that of
fumonisin B 1 and proportionally less fumonisin B 2 is excreted in bile (Shephard &
Snijman, 1999).
The quantity of fumonisin B 1 detected in plasma after oral administration to pigs,
laying hens, vervet monkeys, dairy cows and rats was very low. In rats (BD IX, Fischer
344, Sprague-Dawley, Wistar) given [ 14 C]fumonisin B 1 orally, accumulation of radioactivity
in tissues was also very low. This demonstrates that absorption is very poor
(< 4% of dose) (Shephard et al., 1992b,c; Norred et al., 1993; Shephard et al., 1994c).
Fumonisins are also poorly absorbed (2–< 6% of dose) in vervet monkeys, dairy cows
and pigs (Prelusky et al., 1994; Shephard et al., 1994a,b; Prelusky et al., 1996b). In
orally dosed laying hens and dairy cows, systemic absorption based on plasma levels and
accumulation of radioactivity in tissues was estimated to be < 1% of the dose (Scott
et al., 1994; Vudathala et al., 1994; Prelusky et al., 1995).
In rats and pigs given [ 14 C]fumonisin B 1 via the diet or by gavage, 14 C was distributed
to various tissues, with the liver and kidney containing the highest concentration
of radiolabel (Norred et al., 1993; Prelusky et al., 1994, 1996b). In chickens given a
single oral dose of [ 14 C]fumonisin B 1, trace amounts of radioactivity were recovered in
tissues, but no residues were detectable in eggs laid during the 24-h period after dosing
(Vudathala et al., 1994). No fumonisin B 1 or aminopentol hydrolysis products were recovered
in milk from cows that had received an oral dose of fumonisin B 1 (Scott et al.,
1994). In pregnant rats dosed intravenously with [ 14 C]fumonisin B 1, approximately 14%
and 4% of the dose was recovered in liver and kidney, respectively, after 1 h. In contrast,
the uteri contained 0.24–0.44%, individual placentae contained 0–0.04% and total fetal
recovery of radioactivity was ≤ 0.015% of the dose per dam (Voss et al., 1996b).
When [ 14 C]fumonisin B 1 was administered by intraperitoneal or intravenous injection
to rats (BD IX, Sprague-Dawley, Wistar), initial elimination (subsequent to the
distribution phase) was rapid (half-life, approximately 10–20 min) with little evidence of
metabolism (Shephard et al., 1992b; Norred et al., 1993; Shephard et al., 1994c). In rats,
the elimination kinetics based on intraperitoneal or intravenous dosing of fumonisin B 1
are consistent with a one- (Shephard et al., 1992b) or two-compartment model (Norred
et al., 1993). However, one study using Wistar rats dosed orally with fumonisin B 1 indicated
that the kinetics were probably best described by a three-compartment model
(Martinez-Larranaga et al., 1999), as was the case in swine (see below).
In vervet monkeys, as in rats, the radioactivity was widely distributed and rapidly eliminated
(mean half-life, 40 min) after intravenous injection of [ 14 C]fumonisin B 1
(Shephard et al., 1994a). The elimination kinetics after oral dosing in non-human
primates have not been determined; however, peak plasma levels of fumonisin B 1 and B 2
occurred between one and several hours after a gavage dose of 7.5 mg/kg bw in vervet
monkeys and the plasma concentrations ranged from 25–40 ng/mL for fumonisin B 2 to
nearly 210 ng/mL for fumonisin B 1 (Shephard et al., 1995b; Shephard & Snijman, 1999).
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