Alternative to vertebrate animal experiments in the study of metabolism of illegal growth promotors and veterinary drugs

The continuous production of new illegal veterinary drugs and related products requires residue laboratories to initiate research into developing fast and accurate extraction and detection methods for the identification (and/or quantification) of the major analyte or metabolites of these compounds. In practice, animal experiments are carried out in which vertebrate animals (bovine, porcine....) are treated orally or intramuscularly with the illegal compound. Different matrices (urine, faeces, blood) are collected over 2 or 3 weeks until the animal is sacrificed. Edible matrices (meat, liver, kidney,...) are collected. Because of the complexity of the animal experiment and the method development, a lot of valuable time and money is consumed. Recent studies have shown that some of these vertebrate experiments can be replaced by invertebrates metabolism studies. Vertebrate-type steroids such as testosterone have been used as substrates to study enzyme systems (cytP450) for the oxidative metabolism in invertebrates. Results from these studies provide information on the degree of similarity to the enzyme systems in vertebrates. These findings are of great importance to the research of illegally used substances but also to the downscaling of vertebrate animal experiments and their considerable cost factors. The invertebrate Neomysis integer (Crustacea, Mysidacea) has been used as an alternative model for the partial replacement of vertebrate animals in metabolism studies with illegal growth promotors and veterinary drugs. The principle of this assay and some examples are described. (C) 2002 Elsevier Science B.V. All rights reserved.