Improving Animal Welfare in Regulatory TestingTesting and Animal Welfare: introduction and overview....
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House rodents in House rodents in cages with solid cages with solid bottoms, bedding bottoms, bedding and environmental and environmental enrichment. enrichment. Improving Animal Welfare in Regulatory Testing Improving Animal Welfare in Regulatory Testing Allison Guy, MSc, Julie Dale, MES, & Gilly Griffin, PhD Canadian Council on Animal Care • 1510-130 Albert, Ottawa ON, Canada K1P 5G4 • www.ccac.ca Introduction Regulatory testing ensures that consumer products entering the marketplace are either safe for use or are appropriately labeled to convey the risk of their use. However, this safety testing requires the use of a large number of animals, and can cause them considerable pain and distress. While the Canadian public expects gov- ernment to protect them from unsafe products, the public supports animal use in sci- ence only when mechanisms are in place to minimize pain and distress (Canadian Public Health Association, 2001; IPsos MORI, 2000). The CCAC is the national organization that acts on behalf of the people of Canada to set and maintain standards for the care and use of animals in science (www.ccac.ca). In June 2001, the CCAC, in partnership with the International Council for Laboratory Animal Science (ICLAS), held an international symposium in Québec City, entitled Regulatory Testing and Animal Welfare, to discuss ways of improving the care and use of animals used for regulatory testing (Griffin et al., 2002). Outcomes from the symposium were published as proceedings in the US National Academies of Science Institute for Laboratory Animal Research ILAR Journal. Recommendations on imple- mentation of the Three Rs emerged in seven distinct areas: acute local skin and eye toxicity testing; acute systems toxicity testing; subchronic/chronic toxicity and car- cinogenicity testing; safety evaluation using non-rodent species; animal care in regu- latory toxicology; the safety and potency evaluations of biologicals; and animal care committees and animal use oversight. As a follow-up to the ICLAS/CCAC International Symposium, the CCAC offered its second fellowship in animal policy development in the area of regulatory testing. The two-year fellowship project is designed to examine the extent to which the Symposium recommendations are being implemented, both in Canada and internationally. This poster summarizes the key recommendations made concerning animal care for regula- tory testing and examines the challenges and opportunities for their implementation. ICLAS/CCAC Symposium Recommendations The following recommendations that emerged from the ICLAS/CCAC International Symposium on Regulatory Testing and Animal Welfare concerning animal care are presented alongside the associated challenges and opportunities, as observed from contract research organizations (CRO) in Canada and abroad. Challenges • Wire-bottom cages are still widely used for rodent toxicology studies in North America with the following justification: where there are active metabolites in feces, rodents may increase their expo- sure to a test compound if housed in a solid-bottom cage; as most toxicology studies are less than a year in duration, it is argued that housing rodents in wire-bottom cages for short studies should not adversely affect health or humane care (Peace et al., 2001; Sauer et al., 2006); and in cases where solid bottom cages are not well ventilated, nose lesions have been observed due to the build up of dust and ammonia levels. Opportunities • Solid-bottom cages are the standard in the EU. • Despite scientifically-based arguments to continue housing rodents on wire-bot- tom cages for toxicology studies, rats prefer solid-bottom cages and exhibit fewer stress-related behaviors than when housed in wire-bottom cages (Rock et al., 1997). • Cages with perforated stainless steel bottoms have been developed which reduce the exposure of the rodents to active metabolites, provide a larger, more comfort- able surface area for the animals’ paws, and reduce the instance of foot lesions (this type of flooring is becoming more popular in North America). Acknowledgment The authors wish to thank Emily Verlinden for her considerable assistance in the preparation of this poster. Canadian Public Health Association (2001) Animal to Human Transplantation: Should Canada Proceed? Public Consultation on Xenotransplantation Final Report. 51pp. Canadian Public Health Association: Ottawa Canada. http://www.xeno.cpha.ca/ english/finalrep/reporte.pdf (accessed May 4, 2007). Griffin G., Stokes W.S., Pakes S.P. & Gauthier C. (2002) The ICLAS/CCAC International Symposium on Regulatory Testing and Animal Welfare: introduction and overview. ILAR Journal 43 (supplement): S1-S4. Home Office. Animals (Scientific Procedures) Act 1986. Guidance on the Conduct of Regulatory Toxicology and Safety Evalution Studies. Animals in Scientific Procedures, 2.10. IPsos MORI Poll for UK Coalition for Medical Progress (2005) http://www.ipsos-mori.com/polls/2002/cmp.shtml (accessed May 4, 2007). Morris T., Goulet S. & Morton D. (2002) The International Symposium on Regulatory Testing and Animal Welfare: recommendations on best scientific practices for animal care in regulatory toxicology. ILAR Journal, S43: S123-S125. Peace T.A., Singer A.W., Niemuth N.A. & Shaw M.E. (2001) Effects of caging type and animal source on the develop- ment of foot lesions in Sprague Dawley rat (Rattus norvegicus). Contemporary Topics in Laboratory Animal Science, 40(5): 17-21. Rock F.M., Landi M.S., Hughes H.C. & Gagnon R.C. (1997) Effects of caging type and group size on selected physiolog- ic variables in rats. Contemporary Topics in Laboratory Animal Science, 36(2): 69-72. Sauer M.B., Dulac H., Clark S., Moffitt K.M., Price J., Dambach D., Mosher H., Bounous D. & Keller L. (2006) Clinical pathology laboratory values of rats housed in wire-bottom cages compared with those of rats housed in solid-bottom cages. Journal of the American Association for Laboratory Animal Sciences, 45(1): 30-5. References Challenges • Options for enrichment require validation to ensure they are acceptable to regula- tory testing authorities. Opportunities • A wide range of enrichment methods currently exist for the entire range of species used for regulatory testing. In addition to pair-housing and visual, auditory, and olfactory access to other animals, potential species-specific environmental enrich- ment methods include: NHPs – television, music, plastic toys, perches/swings, mirrors, treats and for- aging opportunities; dogs – television, music, plastic toys, treats, interaction with humans and exercise; rats – contact bedding, resting pads (if on wire mesh flooring), chew toys and plastic tubes for hiding; and mice – contact bedding and nesting materials. • Where validated materials used for enrichment can be ingested by the animals, they are accompanied by certification that they are non-toxic and will not interfere with the results of testing. Conclusion Progress has been made in Canada and abroad to implement the recommendations from the ICLAS/CCAC International Symposium on Regulatory Testing and Animal Welfare in the area of housing and husbandry. Particular advancement has been made in socially housing animals used for regulatory testing and providing environmental enrichment. However, further effort is needed to reach the “best practice” standard, for example, Canada and the US currently lag behind the European Union in switch- ing from wire-bottom to solid-bottom cages. Do not house Do not house social animals social animals singly. singly. Challenges • Social housing requires that study designs and schedules be adapted in terms of: numbers of animals used per group and per sex; selection of animals for the recov- ery phase of a study; sample collection; and recording of clinical signs as suspect- ed or observed (e.g., vomit found in a cage would be a suspected clinical sign for each animal). • Pair-housing is inappropriate in infusion studies in nonhuman primates (NHPs) where the animals are tethered and have an implanted catheter. Opportunities • To reduce the uncertainty of suspected clinical signs, animals can be separated, for a maximum period of 6 hours for dosing, feeding, examination for clinical signs, and recording of food consumption. • For infusion studies in NHPs, there has been success in using cages that separate two animals with wire mesh, allowing them tactile contact with their neighbour. • Success in pair-housing NHPs for regulatory testing in the UK (Home Office, 1986) influenced Canadian CROs to attempt social housing in the late 1990s; since the CCAC/ICLAS symposium, pair-housing has gradually been implemented for all species used in toxicology studies in Canada. Enrichment Enrichment methods should methods should be developed for be developed for incorporation into incorporation into safety studies, safety studies, with the goal of with the goal of improving the improving the quality of the data quality of the data and animal welfare. and animal welfare. Challenges • Socially housing animals may lead to stress and aggression. Opportunities • Animals should be grouped appropriately, e.g., only group-house female and cas- trated male mice and rabbits to avoid aggressive behaviour. • NHPs should be acclimatized to group caging to establish hierarchy before begin- ning the study. • Dogs should be fed during the time they are separated from their penmate. Ensure that socially Ensure that socially housed animals are housed animals are compatible. compatible.
Transcript of Improving Animal Welfare in Regulatory TestingTesting and Animal Welfare: introduction and overview....
House rodents inHouse rodents incages with solidcages with solidbottoms, beddingbottoms, beddingand environmentaland environmentalenrichment.enrichment.
Improving Animal Welfare in Regulatory TestingImproving Animal Welfare in Regulatory TestingAllison Guy, MSc, Julie Dale, MES, & Gilly Griffin, PhDCanadian Council on Animal Care • 1510-130 Albert, Ottawa ON, Canada K1P 5G4 • www.ccac.ca
IntroductionRegulatory testing ensures that consumer products entering the marketplace areeither safe for use or are appropriately labeled to convey the risk of their use.However, this safety testing requires the use of a large number of animals, and cancause them considerable pain and distress. While the Canadian public expects gov-ernment to protect them from unsafe products, the public supports animal use in sci-ence only when mechanisms are in place to minimize pain and distress (CanadianPublic Health Association, 2001; IPsos MORI, 2000).
The CCAC is the national organization that acts on behalf of the people of Canada toset and maintain standards for the care and use of animals in science (www.ccac.ca).In June 2001, the CCAC, in partnership with the International Council for LaboratoryAnimal Science (ICLAS), held an international symposium in Québec City, entitledRegulatory Testing and Animal Welfare, to discuss ways of improving the care anduse of animals used for regulatory testing (Griffin et al., 2002). Outcomes from thesymposium were published as proceedings in the US National Academies of ScienceInstitute for Laboratory Animal Research ILAR Journal. Recommendations on imple-mentation of the Three Rs emerged in seven distinct areas: acute local skin and eyetoxicity testing; acute systems toxicity testing; subchronic/chronic toxicity and car-cinogenicity testing; safety evaluation using non-rodent species; animal care in regu-latory toxicology; the safety and potency evaluations of biologicals; and animal carecommittees and animal use oversight.
As a follow-up to the ICLAS/CCAC International Symposium, the CCAC offered itssecond fellowship in animal policy development in the area of regulatory testing. Thetwo-year fellowship project is designed to examine the extent to which the Symposiumrecommendations are being implemented, both in Canada and internationally. Thisposter summarizes the key recommendations made concerning animal care for regula-tory testing and examines the challenges and opportunities for their implementation.
ICLAS/CCAC Symposium RecommendationsThe following recommendations that emerged from the ICLAS/CCAC InternationalSymposium on Regulatory Testing and Animal Welfare concerning animal care arepresented alongside the associated challenges and opportunities, as observed fromcontract research organizations (CRO) in Canada and abroad.
Challenges
• Wire-bottom cages are still widely used for rodent toxicology studies in NorthAmerica with the following justification:
� where there are active metabolites in feces, rodents may increase their expo-sure to a test compound if housed in a solid-bottom cage;
� as most toxicology studies are less than a year in duration, it is argued thathousing rodents in wire-bottom cages for short studies should not adverselyaffect health or humane care (Peace et al., 2001; Sauer et al., 2006); and
� in cases where solid bottom cages are not well ventilated, nose lesions havebeen observed due to the build up of dust and ammonia levels.
Opportunities
• Solid-bottom cages are the standard in the EU.
• Despite scientifically-based arguments to continue housing rodents on wire-bot-tom cages for toxicology studies, rats prefer solid-bottom cages and exhibit fewerstress-related behaviors than when housed in wire-bottom cages (Rock et al.,1997).
• Cages with perforated stainless steel bottoms have been developed which reducethe exposure of the rodents to active metabolites, provide a larger, more comfort-able surface area for the animals’ paws, and reduce the instance of foot lesions(this type of flooring is becoming more popular in North America).
Acknowledgment
The authors wish to thank Emily Verlinden for her considerable assistance in the preparation of this poster.
Canadian Public Health Association (2001) Animal to Human Transplantation: Should Canada Proceed? Public Consultation onXenotransplantation Final Report. 51pp. Canadian Public Health Association: Ottawa Canada. http://www.xeno.cpha.ca/english/finalrep/reporte.pdf (accessed May 4, 2007).
Griffin G., Stokes W.S., Pakes S.P. & Gauthier C. (2002) The ICLAS/CCAC International Symposium on RegulatoryTesting and Animal Welfare: introduction and overview. ILAR Journal 43 (supplement): S1-S4.
Home Office. Animals (Scientific Procedures) Act 1986. Guidance on the Conduct of Regulatory Toxicology and SafetyEvalution Studies. Animals in Scientific Procedures, 2.10.
IPsos MORI Poll for UK Coalition for Medical Progress (2005) http://www.ipsos-mori.com/polls/2002/cmp.shtml(accessed May 4, 2007).
Morris T., Goulet S. & Morton D. (2002) The International Symposium on Regulatory Testing and Animal Welfare: recommendations on best scientific practices for animal care in regulatory toxicology. ILAR Journal, S43: S123-S125.
Peace T.A., Singer A.W., Niemuth N.A. & Shaw M.E. (2001) Effects of caging type and animal source on the develop-ment of foot lesions in Sprague Dawley rat (Rattus norvegicus). Contemporary Topics in Laboratory Animal Science, 40(5):17-21.
Rock F.M., Landi M.S., Hughes H.C. & Gagnon R.C. (1997) Effects of caging type and group size on selected physiolog-ic variables in rats. Contemporary Topics in Laboratory Animal Science, 36(2): 69-72.
Sauer M.B., Dulac H., Clark S., Moffitt K.M., Price J., Dambach D., Mosher H., Bounous D. & Keller L. (2006) Clinicalpathology laboratory values of rats housed in wire-bottom cages compared with those of rats housed in solid-bottomcages. Journal of the American Association for Laboratory Animal Sciences, 45(1): 30-5.
References
Challenges
• Options for enrichment require validation to ensure they are acceptable to regula-tory testing authorities.
Opportunities
• A wide range of enrichment methods currently exist for the entire range of speciesused for regulatory testing. In addition to pair-housing and visual, auditory, andolfactory access to other animals, potential species-specific environmental enrich-ment methods include:
� NHPs – television, music, plastic toys, perches/swings, mirrors, treats and for-aging opportunities;
� dogs – television, music, plastic toys, treats, interaction with humans and exercise;
� rats – contact bedding, resting pads (if on wire mesh flooring), chew toys andplastic tubes for hiding; and
� mice – contact bedding and nesting materials.
• Where validated materials used for enrichment can be ingested by the animals,they are accompanied by certification that they are non-toxic and will not interferewith the results of testing.
ConclusionProgress has been made in Canada and abroad to implement the recommendationsfrom the ICLAS/CCAC International Symposium on Regulatory Testing and AnimalWelfare in the area of housing and husbandry. Particular advancement has been madein socially housing animals used for regulatory testing and providing environmentalenrichment. However, further effort is needed to reach the “best practice” standard,for example, Canada and the US currently lag behind the European Union in switch-ing from wire-bottom to solid-bottom cages.
Do not houseDo not housesocial animalssocial animalssingly.singly.
Challenges
• Social housing requires that study designs and schedules be adapted in terms of:numbers of animals used per group and per sex; selection of animals for the recov-ery phase of a study; sample collection; and recording of clinical signs as suspect-ed or observed (e.g., vomit found in a cage would be a suspected clinical sign foreach animal).
• Pair-housing is inappropriate in infusion studies in nonhuman primates (NHPs)where the animals are tethered and have an implanted catheter.
Opportunities
• To reduce the uncertainty of suspected clinical signs, animals can be separated, fora maximum period of 6 hours for dosing, feeding, examination for clinical signs,and recording of food consumption.
• For infusion studies in NHPs, there has been success in using cages that separatetwo animals with wire mesh, allowing them tactile contact with their neighbour.
• Success in pair-housing NHPs for regulatory testing in the UK (Home Office,1986) influenced Canadian CROs to attempt social housing in the late 1990s; sincethe CCAC/ICLAS symposium, pair-housing has gradually been implemented forall species used in toxicology studies in Canada.
Enrichment Enrichment methods should methods should be developed for be developed for incorporation intoincorporation intosafety studies, safety studies, with the goal ofwith the goal ofimproving the improving the quality of the dataquality of the dataand animal welfare.and animal welfare.
Challenges
• Socially housing animals may lead to stress and aggression.
Opportunities
• Animals should be grouped appropriately, e.g., only group-house female and cas-trated male mice and rabbits to avoid aggressive behaviour.
• NHPs should be acclimatized to group caging to establish hierarchy before begin-ning the study.
• Dogs should be fed during the time they are separated from their penmate.
Ensure that socially Ensure that sociallyhoused animals arehoused animals arecompatible. compatible.
