Spontaneous Malformations of the New Zealand White Rabbit: The Background to Safety Evaluation Tests

Abstract

The present interest in malformations of the rabbit stems almost entirely from a chain of events that originated in the thalidomide disaster and expanded through a multiplicity of animal studies which, among other things, demon-strated that thalidomide consistently causes malformations in the rabbit embryo. Culmination of the chain was the acceptance of the rabbit as a suitable species for teratogenicity screening tests in the safety evaluation of new drugs (Table 1). It is now evident that, for drug evaluation studies, susceptibility of the test species to thalidomide is a somewhat doubtful recommendation. Thalidomide is unique and atypical so that a positive result obtained with it is not necessarily indicative that a species will be susceptible to teratogens that depend on quite different modes of action. Fortunately the rabbit (especiaIly the New Zealand White) possesses a number of basic characteristics that are an asset in teratology studies. Some of these characteristics, and the advantages that spring from them, are: domesticated and of moderate size (foetus 40 g, adult 3-4 kg)~easily visible defects, moderate drug need, ease of handling and maintenance, short gestation (32 days); prolonged oestrus and induced ovulation~pregnancy easily and accurat-ely timed, artificial insemination possible; high fertility and polytocous---+high pregnancy rate (80 per cent +), large litters (7-10); relatively high incidence of varied anomalies~sensitive to teratogens. These primary advantages in turn give rise to further advantages-low cost, short duration of studies, and the existence of a considerable background of data from published studies in reproduction and genetics. at PENNSYLVANIA STATE UNIV on May 10, 2016lan.sagepub.comDownloaded from