Kinetic Models of Lipophilic Compound Uptake and Bioelimination in Amphibians During the Aquatic Stages

Abstract

During embryonic development, amphibians are particularly sensitive to lipophilic toxic compounds, given their tendency to bioaccumulate from the aquatic environment. On the basis of a series of toxicokinetic experiments with the organophosphorus malathion, we have developed several biomathematical models to explain the behavior of the toxin in an aquatic environment, as well as its biotransformation in amphibian larval stages. Malathion in medium displayed uniexponential bioelimination, while it rapidly accumulated in larvae, decaying according to complex kinetics. Both kinetics were satisfactorily predicted by a model of two compartments in series. In the first compartment, which accounts for bioaccumulation in lipidic tissues, an exponential decline in capacity correlated with progressive depletion of larval lipid reserves was considered. In the second, metabolic biotransformation by several degradative enzymes was considered as a function of the mass of compound present in it. The rapid mass equilibrium between medium and lipidic compartment justifies the apparent uniexponential decay in the first, driven by the overall biotransformation rate constant from the metabolic compartment.