The role of multigeneration studies in safety assessment of residues of veterinary drugs and additives.
Multigeneration studies investigate the impact of a chemical on the reproductive function of laboratory rodents following continuous exposure of several (usually 3) generations. Such tests detects the presence of effects sensitively and efficiently; however, it may be necessary to add satellite groups to the basic protocol and/or to undertake more specific studies in order to investigate the nature of the effects observed. The possible enhancement of the chemical's impact along the generations and the use of apical endpoints (fertility, pup mean weight and survival, etc.) make multigeneration tests apt to reveal the cumulative action of minor, detrimental hits. Therefore, they appear especially important in the safety assessment of chemicals not expected to be markedly toxic, like many veterinary drugs or feed additives. The present paper reviews the role played by the data drawn from multigeneration studies in the toxicological evaluation of six compounds, namely: a) a synthetic anabolic steroid with hormonal (antigonadotropic) activity, trenbolone acetate; b) a colouring additive with some cumulative toxicity, canthaxanthin; c) a lipophyllic drug with effects on neuron transmission, ivermectin; d) a teratogenic benzimidazole, albendazole; e) a genotoxic molecule, olaquindox; f) a drug with male reproductive toxicity, closantel. Finally, the endpoints evaluated in the multigeneration studies might be utilized also in field studies aimed at evaluating the long-term reproductive impact of chemicals in farm species.
Mantovani
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Laboratorio di Tossicologia Comparata ed Ecotossicologia, Istituto Superiore di Sanità, Rome, Italy.
D000818:Animals; D003257:Consumer Product Safety; D004350:Drug Residues / Q000633:toxicity*; D064420:Drug-Related Side Effects and Adverse Reactions; D005503:Food Additives / Q000633:toxicity*; D005506:Food Contamination; D051381:Rats; D012098:Reproduction / Q000187:drug effects*; D014730:Veterinary Medicine
D005503:Food Additives