An Approach to Minimise Dog Use in Regulatory Toxicology: Production of a Best Practice Guide to Study Design

Abstract

The primary non-rodent species used in toxicology is the dog. It is generally agreed that, for ethical reasons, dog use should be reduced to the minimum consistent with maintaining the scientific quality of toxicology studies and ensuring human safety. Dog use in toxicology has been discussed widely, both from a scientific and ethical viewpoint, and there appears to be real potential for achieving significant reductions in the number of dogs used in pharmaceutical safety testing. An industry animal welfare initiative commenced in 2000, with the aim of evaluating and, where possible, putting into practice, scientifically valid approaches to minimise dog use in regulatory toxicology without increasing the use of other non-rodent species, such as non-human primates or minipigs. The study's Steering Group categorised potential reduction approaches into three distinct areas, one of which is the production of a best practice guide on aspects of study design, including: group sizes, use of control animals, single sex studies and design of maximum tolerated dose (MTD) studies. Information on current practice and experience within the pharmaceutical industry is now being analysed, and additional input is invited.

Basic data on the hematology, serum biochemistry, urology, and organ weights of beagle dogs

“…In biomedical research, it is well recognized that individual animal variability can affect study results. To minimize animal variability, researchers should be provided with normal, healthy, well-adapted animals that represent a physiological model characterized by a narrow range of physical, behavioral, and clinical parameters [ 3 - 5 ]. Basic data of the test animal's blood, urine, and blood chemical values have detected many differences depending on sex and age, and the conditions where animals are maintained [ 7 - 9 ].…”

“…Baseline parameters for hematology, urine, and blood chemical values play an important role in estimating target organ effects when it is difficult to observe the changes in tissues or when they are likely to be ignored during histopathological examinations [ 3 - 5 ]. These basic data can provide a foundation for interpreting certain test results more accurately [ 10 , 12 ].…”

Dogs in preclinical research

“…Эвтаназия собак на этих промежуточных точках не проводится, но выполняется анализ показателей, аналогичных запланированным в клинических исследованиях. Предварительная оценка необходимости конкретных исследований может позволить снизить количество собак, участвующих в длительном эксперименте [40].…”

“…Был проведен анализ данных по количеству собак в группе при проведении токсикологических исследований в 12 европейских фармацевтические компаниях [40]. Результаты представлены ниже.…”

“…Как видно из представленных данных, большинство компаний использовали количество животных в группе в соответствии с норма- 11 OECD G UIDELINE FOR THE TESTING OF CHEMICALS 409 Repeated Dose 90-day Oral Toxicity Study in Non-Rodents. тивными требованиями, но тем не менее использовали возможности для оптимизации дизайна [40]. Один из подходов к сокращению количества животных -это уменьшение их числа в группах отсроченного наблюдения.…”