Bioavailability of bound residues of [14C]febantel to rats

The presence of pesticide and drug residues in crops and livestock is a major consideration in the regulation of pesticide and veterinary drug use in the agricultural industry. Furthermore, these is increasing interest in determining the toxicological significance of residues present in food, especially those which remain bound following traditional extraction techniques. Treatment of cattle with Febantel ([N'-N double-prime-bis-methoxycarbonyl-guanidino-3-methoxy-acetamido, 5-phenylthio, benzene]), an anthelmintic, results in residues, a portion of which remain bound following extraction of liver with water and ethyl acetate. We have examined the bioavailability of these bound residues in beef liver excised 7 days after oral administration of [14C]Febantel. No radiocarbon was detected in bile, urine of any of the tissues, however 99.9% of the administered dose was eliminated in the feces indicating 0% bioavailability. For comparison, beef liver was identically extracted then fortified with [14C]Febantel prior to administration to cannulated rats. In this case the bile and urine contained 31.4 and 51.9% of the dose respectively, whereas the feces contained 11.5% and the gastrointestinal tract and remaining tissues accounted for 2.4%. Therefore, Febantel administered in this manner is 85.7% bioavailable. These findings strongly suggest that though Febantel is readily absorbed, bound residues in beef treated with Febantel are not absorbed and are therefore not likely to present a toxicological risk