Estimating the Oral Bioavailability of Methylmercury to Channel Catfish (ictalurus Punctatus)

In classical pharmacology, oral bioavailability of a toxicant is defined as that fraction of an orally administered dose reaching the systemic circulation of the animal. The present study estimates the bioavailability of methylmercury in channel catfish (Ictalurus punctatus) by comparing concentrations in the blood through time after oral and intra-arterial (IA) administration. Catfish were cannulated in the dorsal aorta and gavaged a pelleted feed that had been spiked with methylmercury. Each catfish was gavaged an increasing amount of spiked feed. Following oral dosing, serial blood samples were removed for more than 1,500 h. One month after removal of the last blood sample, the same fish were injected IA with methylmercury and serial blood samples were removed for more than 3,000 h. The area under the curve of the blood concentration–time curve extrapolated to infinity (AUC0→`) was calculated from fish dosed orally and IA using both noncompartmental (trapezoidal) and compartmental methods. Bioavailability was estimated as the ratio of the dose-corrected oral AUC0→` to the IA AUC0→`. Average bioavailability estimates from this approach were 33% using noncompartmental (range 14–55%) and 29% using compartmental (range 12–42%) methods and were correlated with the amount of food gavaged to the fish (r2 5 0.95, p 5 0.026). Bioavailability estimates using the present methods were much lower than estimates using more conventional methods (i.e., assimilation efficiency estimates using mass balance), suggesting that conventional methods may overestimate the true bioavailability of toxicants in fish. Keywords—Oral bioavailability Methylmercury Channel catfish Elimination Uptake