Animal welfare is about an animal's quality of life. The aim of good welfare is to provide animals with the conditions that allow them to behave much as they do in nature. Studies of dog ethology provide valuable guidance and criteria for welfare. Welfare is therefore measurable and a scientific evidence-based approach is needed when improving animals' well­being.

　Ethics, in contrast, deals with what is good and right in life from the human point of view. Animal ethics deals with what is held by a particular group of people to be sufficiently good in animal life and what is a correct human action in relation to animals. Different animal ethical standards are applied in different societies. The situation becomes more complicated when society has a multicultural background, where the view of certain part of the society on animal ethics differs greatly from another group. In Westem European democracies the view of the majority of the citizens is taken into account and freedom of speech gives opportunity to others to express their opinions in discussions to influence the view of the majority. It is a process of constantly evolving the ideas, where different ethical views are present, and consensus may be reached only after a very long time. The final ethical view is written, codified and enforced by regulatory authorities, given their power by elected governments representing the majority of the people. Ethics is a product of thousands of years of history, where ideas developed in the past are mixed together in the contemporary mix of global cultures. It is not something we can measure.

　Charles River Laboratories, Preclinical Services, Montreal (PCS-Mtl) can conduct dog toxicokinetic, toxicology and safety pharmacology studies in neonatal, juvenile, young adult and / or sexually mature dogs. These studies can be treated by a full range of dose routes and contain a comprehensive array of assessments.

　The dog is the most commonly used non­-rodent species for testing novel pharmaceu­ticals and as a result techniques, procedures and assays are generally available for the majority of requirements.

　Covance Laboratories Europe has performed regulatory toxicology studies in the beagle dog for over 30 years at the Harrogate facility. Prior to the introduction of the requirement to source all scientific animals from a UK recognised supplier as default, beagles were sourced from Hazleton (now Covance) Research Products in the US. Now however, approximately 80% of the beagles used at CLE are sourced from Harlan UK Ltd (Hsdf.Dobe). It is still possible to source animals from alternate suppliers with good scientific justification, thus beagles supplied by Covance Research Products and Marshall are still in use within our laboratory.

　The first attempts to bring some order to the toxicological testing of new drugs came in the 1940s. There was then a lull, before the publication of detailed regulatory guidelines to define test methodology began in the 1960s. The dog, almost exclusively for the last several decades, the beagle, became the principal non-rodent species used in toxicology, this being more formalised in writing (but not as official guidelines) in Europe in 1965 and in the USA in 1977 (see Zbinden [16]). It is not within the scope of this short paper to give a full description of the advantages and the disadvantages of the dog and there any many such papers already available (4, 9, 12) as well as papers reviewing animal/human concordance in toxicity prediction (see 8 and references therein). In this paper, I shall attempt to summarise and discuss some of the data available at Huntingdon Life Sciences and other topics of debate and recent advances surrounding the use of the dog. To provide a source of reference, I shall also make short comments on other reviews to which the researcher may wish to refer.

　Greaves et al (5) provide a recent summary of papers discussing the correlation between observed animal and human toxicity for major drug classes and organ systems. They conclude that the dog is better predictor of human adverse effects than rodents or monkeys based on the particular papers they have reviewed, being particularly useful in predicting gastroin­testinal toxicity but over-predicting hepatic and renal toxicity. It is interesting to note however, that a number of these key papers were published in the 1960s and there seems to be a relative lack of more recent critical reviews of this subject. One of the newer papers cited is by Olson et al (8) describing the outcome of a pharmaceutical industry initiative on this subject and an International Life Sciences Institute work­shop in 1999 at which working parties were ask to identify modified testing strategies which may improve non-clinical screening of drugs in development. They concluded that the dog is often selected with insufficient consideration of whether it is pharmacodynamically, physiologically, biochemi­cally or metabolically the best choice, but they could recommend no alternative species widely applicable in general toxi­cology to replace the dog.

　There is a notable change of emphasis between papers written prior to the mid-1990s and those written more recently concerning the dog. When discussing the disadvantages of the dog, older papers do so from the position that the dog was the only widely used non-rodent species (primates such as rhesus, cynomolgus and marmosets being used in regulatory toxi­cology but expensive and not easy to obtain) and so the disadvantages had to be allowed for and coped with. Newer papers make much greater reference to the need for the use of pharmacodynamically rele­vant species and to the newer available models, particularly the minipig.

　Much of the information on adverse drug reactions in package inserts, both in Japan and elsewhere, is fundamentally uncertain. In most cases we do not know the exact mechanisms of adverse reactions, we are seldom in a position to predict with any confi­dence which patients are most at risk --or their degree of risk --of experiencing specific adverse reactions and even after an adverse event is observed we are usually uncertain about the extent to which it is truly attributable to drug exposure. A central goal of the PV working group is to contribute to the scien­tific understanding of the mechanisms behind adverse reactions to drugs, in part by furthering the collaboration of nonclinical and clinical professionals in drug safety. With this overall goal in mind this symposium examined the interactions between nonclinical and clinical professionals within Japan, introduced a significant new project on the international stage to look at genetic factors related to two categories of significant adverse reactions, and presented the perspective of regulators in Japan on drug safety management. This symposium also benefited from the active support and cooperation of the Japanese Association of Pharmaceutical Medicine (JAPhMed).