title: In vitro and in vivo studies of drug residue accumulation in pigmented tissues.
abstract: A procedure was developed to enable ready isolation of melanin granules from pigmented tissues of the bovine eye. The granules were used in a simple in vitro test to model the potential for a range of veterinary drugs to accumulate in melanin-containing tissues such as hair and the choroid/pigmented retinal epithelium (choroid/PRE) of the eye. The beta-agonists clenbuterol and salmeterol, but not salbutamol, showed appreciable binding, as did the beta-blockers propranolol and carazolol and the tranquillizers azaperone and xylazine. All of the natural and synthetic growth promoters tested gave rise to significant binding (17 beta-estradiol, testosterone, alpha-zeranol, diethylstilbestrol and 19-nortestosterone) but progesterone and 17 alpha-trenbolone bound to a lesser extent. To provide a preliminary indication of the validity of the model, animals were treated with clenbuterol for 21 d, to enable the assessment of accumulation in vivo. Clenbuterol was detected in choroid/PRE and hair at high concentrations from the last day of treatment (1779 ng g-1 and 424 ng g-1, respectively) until the end of the study period, 63 d later (512 ng g-1 and 483 ng g-1, respectively). These studies clearly indicate the wider potential for pigmented tissue analysis in monitoring for the use of veterinary drugs (particularly unlicensed substances) in food producing animals. Hair analysis may offer particular advantages for on-farm monitoring and in providing historic information.
authors.affiliation: Biochemistry Department, Central Veterinary Laboratory, Addlestone, Surrey, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Sauer
authors.forename: S P
authors.initials: SP
authors.lastname: Anderson
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D002250:Carbon Radioisotopes; D002417:Cattle; D002469:Cell Separation / Q000379:methods; D002829:Choroid / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002976:Clenbuterol / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism* / Q000648:ultrastructure; D004350:Drug Residues / Q000032:analysis / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D006197:Hair / Q000737:chemistry / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008297:Male; D008543:Melanins / Q000378:metabolism; D011865:Radioisotope Dilution Technique; D015203:Reproducibility of Results; D013997:Time Factors; D014316:Tritium
chemical_list: D000728:Androgens; D002250:Carbon Radioisotopes; D004967:Estrogens; D008543:Melanins; D014316:Tritium; D002976:Clenbuterol