|Ehrenfreid, Kathy - ELANCO ANIMAL HEALTH|
|Dalidowicz, John - ELANCO ANIMAL HEALTH|
|Turberg, Michael - ELANCO ANIMAL HEALTH|
Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 30, 2002
Publication Date: July 30, 2002
Citation: Smith, D.J., Ehrenfreid, K.E., Dalidowicz, J.D., Turberg, M.P. 2002. Binding of ractopamine HCl to ocular tissues of cattle and turkeys in vivo and to melanin in vitro. Journal of Animal Science 80:2931-2941. Interpretive Summary: Beta-adrenergic agents have been used illegally in Europe, Asia, and the United States to improve carcass characteristics of several livestock species. Because the inappropriate, and unregulated, use of some beta- agonists has caused human food poisoning, many countries routinely screen animal carcasses for exposure to beta agonists. Ocular tissues are particularly useful for screening assays because some beta-agonists are retained by retinal tissues for weeks after the last drug exposure. No previous research had investigated the degree to which ractopamine HCl binds to ocular tissues. This study showed that ractopamine binds to melanin, the dark pigment present in eyes, fairly well when tests are conducted in the test tube. In live animals, however, ractopamine residues in ocular tissues were very low relative to what might be expected relative to other beta-agonists. The major metabolite of ractopamine, ractopamine glucuronide, did not bind to melanin in vitro. We hypothesized that ractopamine binding in ocular tissues in live animals is prevented by ractopamine's rapid metabolism and excretion.
Technical Abstract: Experiments were conducted to determine the total residues remaining in ocular tissues of cattle and turkeys after oral administration of 14-C ractopamine HCl. Twelve cattle were intraruminally dosed with 0.9 mg/kg of ractopamine HCl for seven consecutive days. Four cattle each were slaughtered with withdrawal periods of 48, 96, and 144 hours. Radioactive residues were not detectable in whole-eye homogenates from the cattle. Eight male and eight female turkeys per treatment received either 7.5, 22.5, or 30 ppm dietary 14-C ractopamine HCl (0.33, 1.02, and 1.36 mg/kg per day; treatment groups 1, 2, and 3, respectively) for 7 days and the birds were slaughtered with a 0-d withdrawal period. Eyes were dissected into retina/choroid/schlera (RCS), cornea/iris (CI), and aqueous humor (AH) fractions. Residues in RCS, CI, and AH of treatment-1 turkeys were not detectable. Residues of AH were < 0.02 ppm in treatment groups 2 and 3. Mean residues in RCS ranged from 0.15 to 0.25 ppm, and mean CI residues ranged from < 0.09 to 0.17 ppm for treatment groups 2 and 3, respectively. In vitro studies showed that radioactive ractopamine HCl binds to melanin and is displaced from melanin by other beta-agonists. Glucuronidation of ractopamine prevented binding to melanin. These studies demonstrate that the propensity for the in vivo binding of ractopamine HCl to pigmented ocular tissues is less than that reported for clenbuterol.