SummaryA variety of bile duct cannulation methods have been used in the study of biliary excretion in the rat . We now report the validation and use of one such method. In this method, the common bile duct and duodenum were cannulated, the free ends of the cannulae tunnelled through the abdominal wall, passed through a trochar and exteriorized at the ventral aspect of the tail. A purpose-designed stainless steel tai l cuff was then attach ed, to protect the cannulae from the rat. T he cannulae were passed through the top of a metabolism cage and attach ed to a dual swivel that allows the rat freedom of movement within the metabolism cage. Where necessary an additi onal cannula could be placed in the femoral vein to allow infusion of test mat erial or blood sam pling. T he results demonstrate that the method is robust and that its use allows a reliable correlation between surgically prepared and intact animals, as physiological parameters are allowed to return to normal prior to inclusion of the animals in the study. T he technique allows the anim als a great deal of freedom and, as such, is considered to minimize stress associat ed with the procedure. T his fact is re¯ected in the reliabilit y and reproducibility of the data obtain ed over the wide range of studies that have been conducted using this method. T his method has been in use for over 4 years at Inveresk and this paper describes the authors' experience with the method to date.

Bile duct cannulation (BDC) studies are usually carried out in the rat to support the absorption, distribution, metabolism and excretion profiling of novel agrochemicals and pharmaceuticals. The different aspects of these studies (e.g. surgical preparation, dosing and collection of bile) can be intricate and/or technically complex. The animals are often kept singly housed for the duration of the studies following surgical implantation of the cannulas. The generation of insufficient data to meet the study objectives, for example due to failure in cannula patency, can result in the need to repeat these studies. A working group of contract research organizations that routinely carry out BDC studies was brought together by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) to share their experiences, and to establish the key factors necessary to ensure routinely high success rates. Through these discussions the group has identified opportunities for best practice across various aspects of the studies. The aim of these recommendations is to support all staff involved in conducting BDC studies to maximize the amount of useful data generated using the fewest animals possible, while ensuring the highest possible standards of animal welfare.

SummaryThe athymic (nude) rat (rnu/rnu) has been used for a number of years in research into various human tumours involving xenotransplantation. We now report the validation of a continuous intravenous infusion method in nude rats using a tail cuff tether, which enables the study of the efficacy of novel anti-cancer materials in this mutant strain, using intravenous infusion and with no restriction of the animals or of the tumour implantation sites by jackets.Ten animals each had a cannula surgically implanted into the vena cava via the femoral vein and exteriorized via a tail cuff. Animals were housed singly in conventional cages following surgery. Following a recovery period of 5 days all animals were continuously infused with physiological saline at an infusion rate of 0.5 ml/h for a further 37 days. Body weights and food consumption were recorded weekly. Blood samples were taken approximately 14 days post-surgery and analysed for haematology and clinical chemistry parameters. All animals were successfully cannulated, and no unexpected adverse clinical signs were noted during the recovery period and the 37 days of infusion.The results demonstrate that it is possible to surgically cannulate the femoral vein of athymic (nude) rats and infuse them in conventional cages for a period of up to 37 days with minimal adverse effects. The minimal restraint required provides benefits both to the animal and to the conduct of studies such as assessment of tumour growth in the absence of a jacket. Recent work has demonstrated that the same techniques can be successfully applied to the nude mouse. Keywords Continuous intravenous infusionj nude rat; anti-cancer agentsEffective rat infusion models have been developed over the last two decades. The most common infusion model consists of a surgically implanted cannula into the jugular vein with exteriorization at the scapular region. The animals wear a jacket connected to a steel spring and tethering device to protect the cannula (Francis et al. 1992).At Inveresk Research we use a modified technique based on a publication by Jones and Hynd 119811 and modified by Cave et al. (1995) for long-term infusion in the rat, involving surgical implantation of a cannula Correspondence to: Hans van Wi;k into the caudal vena cava via the femoral vein, with exteriorization at the tail, within a protective tail cuff.Following safety assessment studies in the Sprague-Dawley rat with a novel anti-cancer compound, an efficacy study was required in athymic (nude) rats. The objective of this efficacy study was to assess the anti-tumour effect of a novel anti-cancer agent on a human tumour subcutaneously implanted in rnu/rnu nude rats (Schuurman 1995), while monitoring treatment-related toxic effects in the same animals, within a Good Laboratory Practice (GLP) environment.

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