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Microcystins (MCs) are toxins produced by several cyanobacterial species found worldwide. While MCs have a common structure, the variation of two amino acids in their structure affects their toxicity. As toxicodynamics are very similar between the MC variants, their differential toxicity could rather be explained by toxicokinetic parameters. Microcystin-RR (MC-RR) is the second most abundant congener and induces toxicity through oral exposure. As intestinal permeability is a key parameter of oral toxicokinetics, the apparent permeability of MC-RR across a differentiated intestinal Caco-2 cell monolayer was investigated. We observed a rapid and large decrease of MC-RR levels in the donor compartment. However, irrespective of the loaded concentration and exposure time, the permeabilities were very low from apical to basolateral compartments (from 4 to 15 × 10−8 cm·s−1) and from basolateral to apical compartments (from 2 to 37 × 10−8 cm·s−1). Our results suggested that MC-RR would be poorly absorbed orally. As similar low permeability was reported for the most abundant congener microcystin-LR, and this variant presented a greater acute oral toxicity than MC-RR, we concluded that the intestinal permeability was probably not involved in the differential toxicity between them, in contrast to the hepatic uptake and metabolism. [ABSTRACT FROM AUTHOR]

Due to its toxic properties, high stability, and prevalence, the presence of deoxynivalenol (DON) in the food chain is a major threat to food safety and therefore a health risk for both humans and animals. In this study, experiments were carried out with sows and female rats to examine the kinetics of DON after intravenous and oral administration at 100 μg/kg of body weight. After intravenous administration of DON in pigs, a two-compartment model with rapid initial distribution (0.030 ± 0.019 h) followed by a slower terminal elimination phase (1.53 ± 0.54 h) was fitted to the concentration profile of DON in pig plasma. In rats, a short elimination half-life (0.46 h) and a clearance of 2.59 L/h/kg were estimated by sparse sampling non-compartmental analysis. Following oral exposure, DON was rapidly absorbed and reached maximal plasma concentrations (Cmax) of 42.07 ± 8.48 and 10.44 ± 5.87 μg/L plasma after (tmax) 1.44 ± 0.52 and 0.17 h in pigs and rats, respectively. The mean bioavailability of DON was 70.5% ± 25.6% for pigs and 47.3% for rats. In the framework of DON risk assessment, these two animal models could be useful in an exposure scenario in two different ways because of their different bioavailability. [ABSTRACT FROM AUTHOR]