Human safety considerations from the use of anabolic agents in foodproducing animals.

Abstract

The various anabolic agents used in food-producing animals may differ in terms of toxicological considerations related to evaluating human safety. Aside from initial toxicological testing, after chemical characterization of the compound to be administered and its related metabolites expected to occur as residues in food, most synthetic anabolic agents are subjected to chronic/carcinogenicity testing because of usage pattern likely to lead to the occurrence of residues in derived edible products. Initial testing requirements include acute and subchronic studies in appropriate rodent species including a reproduction test with the first generation offspring tested for 90 days post-weaning. This subchronic study serves to indicate potential problems with reproductive performance, foetal toxicity, birth deformities, and other chronic or preneoplastic conditions. The Food and Drug Administration (FDA) may grant approval for certain usages of specific compounds using a 2.000-fold safety margin in relation to a "no deleterious effect" level from the subchronic studies, with upper residue limits of 0.1 ppm in tissue and 0.01 ppm in milk or eggs if there are no indications that further testing should be required. If higher residue limits are requested, the petitioner must perform lifetime testing in two rodent species including in utero exposure and a minimum of three dose levels. Other rodent offspring should be carried for a total of three generations. A six to twelve month study in a non-rodent population is required. Teratology studies might be rquired in at least two species. If no carcinogenic potential is observed, a 100-fold safety margin in relation to the no effect level is generally accepted as the safe exposure level for residues. Should a statistically significant increase in tumors be observed in the test animals as compared to controls, the compound will be classified as a carcinogen or a suspect carcinogen depending on histopathological observations...