Toxicokinetics of fumonisin B1 and B2:: Comparative studies in rats and hon-human primates

Toxicokinetic studies were conducted using single doses of fumonisin B-1 (FB1) and B-2 (FB2) in rats and vervet monkeys. After ip injection in rats (7.5 mg fumonisin/kg body weight), both toxins were rapidly absorbed and their levels in plasma reached a maximum within 20 min. The subsequent elimination phases were characterised by mono-exponential declines in plasma levels with half-lives of 18 and 26 min for each toxin, respectively. After a similar gavage dose, no toxin was detected in plasma (<50 ng/ml). The toxins were recovered unmetabolised from excreta After ip injection, up to 32% of FB1 (as determined by radioactivity) and 1.2% of FB2 were recovered in urine, compared to 0.1% and 0.2% in urine after dosing by gavage. The remainder of the dose was recovered in faeces. Both toxin analogues were rapidly eliminated from plasma of vervet monkeys following iv injection (1.6 - 2 mg/kg body weight). After a short distributional phase, the elimination phase was characterised by a half life of 40 min for FB1 and 18 min for FB1. Following a gavage dose of 6.4 and 7.5 mg/kg body weight for FB1 and FB2 respectively, only limited amounts were absorbed. For FB1, plasma levels peaked after 1 - 2 hr with maximum levels below 210 ng/ml, while FB2 showed a maximum level of 40 ng/ml after 5 hr. Urinary excretion was significant after iv dosing (mean 13.1% for FB1 and 4.1% for FB2 dose), but considerably less after the gavage dose (mean 1.3% and 0.2%, respectively). Analysis of faeces for up to 7 days after dosing failed to recover the full dose and also indicated that, for both analogues, significant removal by hydrolysis of one of the tricarballylic acid moieties of fumonisin had occurred, yielding the corresponding partially hydrolysed fumonisin. Although the fully hydrolysed backbones of both analogues were detected, they accounted for less than 2% of the dose.