Relay bioavailability and toxicity of isometamidium residues : a model for human risk assessment
Kinabo, L. D.
Bogan, J. A.
The bioavailability and potential toxicity of the residues of the antitrypanosomal drug isometamidium (ISMM) in bovine tissues were investigated in male Sprague-Dawley rats. They were allowed to feed for 7 and 21 days on a standard diet, to which were added lyophilized tissues from a calf treated im with a combination of 45 mg 14C-ISMM and 73 mg unlabelled ISMM (1 mg/kg bodyweight). Cumulative excretion of radioactivity of the residues in feces of the rats was on average 90% of the dose. No radioactivity was detectable in the tissues examined, including the kidney, liver, spleen, muscle, stomach and small intestine. No clinical effects were seen in any of the rats, and both gross and histopathological examinations did not reveal any lesions. In rats given 14C-ISMM (2.245 mg/kg bodyweight) by oral gavage, cumulative excretion of radioactivity in feces after 48 hr amounted to about 93% of the dose, and no radioactivity was detectable in tissues. Similarly, none of the rats showed any clinical effects and no gross lesions were seen at necropsy. This study shows that ISMM residues are not significantly bioavailable and exhibit no subchronic toxicity.