Alternatives to animal testing
Alternatives to animal testing are the development and implementation of test methods that avoid the use of live animals.
There is widespread agreement that a reduction in the number of animals used and the refinement of testing to reduce suffering should be important goals for the industries involved. Two major alternatives to in vivo animal testing are in vitro cell culture techniques and in silico computer simulation. However, some claim they are not true alternatives because simulations use data from prior animal experiments and cell cultures often require animal derived products, such as serum or cells. Others say that they cannot replace animals completely as they are unlikely to ever provide enough information about the complex interactions of living systems. Other alternatives include the use of humans for skin irritancy tests and donated human blood for pyrogenicity studies. Another alternative is so-called microdosing, in which the basic behaviour of drugs is assessed using human volunteers receiving doses well below those expected to produce whole-body effects. While microdosing produces important information about pharmacokinetics and pharmacodynamics it does not reveal information about toxicity or toxicology. Furthermore, it was noted by the Fund for the Replacement of Animals in Medical Experiments that despite the use of microdosing, "animal studies will still be required".
Guiding principles for more ethical use of animals in testing are the Three Rs (3Rs) first described by Russell and Burch in 1959. These principles are now followed in many testing establishments worldwide.
- Replacement refers to the preferred use of non-animal methods over animal methods whenever it is possible to achieve the same scientific aim.
- Reduction refers to methods that enable researchers to obtain comparable levels of information from fewer animals, or to obtain more information from the same number of animals.
- Refinement refers to methods that alleviate or minimize potential pain, suffering or distress, and enhance animal welfare for the animals used.
- 1 Types
- 1.1 Cell culture and tissue engineering
- 1.2 Human-based
- 1.3 Computer simulation
- 1.4 Medical imaging
- 1.5 Fungal model for mammalian drug metabolism
- 1.6 Future alternatives
- 2 Research initiatives
- 3 Scientific congresses
- 4 Industry and corporate initiatives
- 5 Legislation
- 5.1 EU Directive 2010/63/EU
- 5.2 EU cosmetic regulation
- 5.3 EU chemical policy: REACH
- 5.4 EU test methods regulation
- 5.5 EU regulation for food additives, food enzymes and food flavourings
- 6 Animal welfare and animal rights organizations
- 7 Public campaigns and awards
- 8 Education and training
- 9 Institutes and national or international organizations
- 10 See also
- 11 References
- 12 External links
Cell culture and tissue engineering
Cell culture can be an alternative to animal use in some cases. For example, cultured cells have been developed to create monoclonal antibodies, prior to this production required animals to undergo a procedure likely to cause pain and distress. However, even though cell or tissue culture methods may reduce the number of experiments performed on intact animals, the maintenance of cells in culture normally requires the use of animal-derived serum. Although exact figures are difficult to obtain, some have estimated that one million fetal cows are sacrificed each year to obtain the world's supply of fetal bovine serum, used to grow cultured cells.
Skin corrosion and skin irritation
Skin irritation and skin corrosion refer to localized toxic effects resulting from a topical exposure of the skin to a substance. Human skin equivalent tests can be used to replace animal-based corrosive and irritative studies. EpiDerm from Mattek  and EpiSkin and SkinEthic RHE model are derived from human skin cells which have been cultured to produce a model of human skin. These methods are currently accepted replacements in Canada and the European Union (EU). In August 2010, the Organisation for Economic Co-operation and Development (OECD) published the Test Guideline 439 which describes the new procedure for in vitro hazard identification of irritant chemicals.
Another synthetic replacement uses a protein membrane to simulate a skin barrier and is approved as a partial replacement by the US Department of Transportation and European Union.
Several tissue culture methods which measure the rate of chemical absorption by the skin have been approved by the OECD, although they have not yet been approved as a replacement in the US.
Phototoxicity is a rash, swelling or inflammation, like a severe sunburn, caused by exposure to light following exposure to a chemical. The 3T3 Neutral Red Uptake (NRU) Phototoxicity Test, approved by the OECD, detects the viability of 3T3 cells after exposure to a chemical in the presence or absence of light. Although originally derived from a mouse embryo, the 3T3 cell line was developed in 1962.
A skinpatch test has been designed and is used in Canada to measure development of rashes, inflammation, swelling or abnormal tissue growth on human volunteers. Unlike corrosives, substances defined as irritants cause only reversible skin damage.
Another approach has been the development of test methods that use cultured human cells. Human epidermal keratinocytes have been cultured to mimic the human epidermis, and are used to measure skin irritation and dermal corrosion. This method has been accepted by the EU and is intended to replace the Draize rabbit skin irritation test.
Pyrogens are most often pharmaceutical products or intravenous drugs that may cause inflammation or fever when they interact with immune system cells. This interaction can be quickly and accurately tested in vitro.
Modular immune in vitro construct
The modular immune in vitro construct (MIMIC) uses human cells to create a model of the human immune system on which the efficacy of new vaccines and other compounds may be tested, replacing some steps of the vaccine development process that would otherwise be performed on animals. This process is faster and more flexible than previous methods but critics worry that it may be too simple to be useful on a large scale.
Examples of computer simulations available include models of asthma, though potential new medicines identified using these techniques are currently still required to be verified in animal and human tests before licensing. Computer operated mannequins, also known as crash test dummies, complete with internal sensors and video, have replaced live animal trauma testing for automobile crash testing. The first of these was "Sierra Sam" built in 1949 by Alderson Research Labs (ARL) Sierra Engineering. These dummies continue to be refined. Prior to this, live pigs were used as test subjects for crash testing.
Other non-animal simulators have been developed for military use to mimic battlefield induced traumas. TraumaMan and the Combat Trauma Patient Simulator can be used to simulate hemorrhaging, fractures, amputations and burns. Previously, animals were intentionally subjected to various traumas to provide military training. TraumaMan is also now used for training medical students.
Computer models have been constructed to model human metabolism, to study plaque build-up and cardiovascular risk, and to evaluate toxicity of drugs, tasks for which animals are also used. In 2007, US researchers using the world's fastest computer at the time, BlueGene L, modeled half a mouse's brain for just 10 seconds. However, due to limitations in computing power, the simulation could only be run at 1/10th the speed of an actual mouse brain. Although this was an advance in science, its representative power as a model was limited and the researchers were quoted as saying that "although the simulation shared some similarities with a mouse's mental make-up in terms of nerves and connections it lacked the structures seen in real mice brains."
Fungal model for mammalian drug metabolism
Organs on a chip
The Wyss Institute for Biologically Inspired Engineering (US) intends to develop in-vitro organs for drug screening and thereby eliminate the use of animals for this type of testing. One model is the "lung-on-a-chip". This combines microfabrication techniques with modern tissue engineering and mimics the complicated mechanical and biochemical behaviours of a human lung.
Toxicity testing typically involves studying adverse health outcomes in animals subjected to high doses of toxicants with subsequent extrapolation to expected human responses at lower doses. The system relies on the use of a 40+year-old patchwork of animal tests that are expensive (costing more than $3B per year), time-consuming, low-throughput and often provide results of limited predictive value for human health effects. The low-throughput of current toxicity testing approaches (which are largely the same for industrial chemicals, pesticides and drugs) has led to a backlog of more than 80,000 chemicals to which humans are potentially exposed whose potential toxicity remains largely unknown. In 2007, the National Research Council (NRC) released the report "Toxicity Testing in the 21st Century: A Vision and a Strategy", that charted a long-range strategic plan for transforming toxicity testing. The major components of the plan include the use of predictive, high-throughput cell-based assays (of human origin) to evaluate perturbations in key toxicity pathways, and to conduct targeted testing against those pathways. This approach will greatly accelerate our ability to test the vast "storehouses" of chemical compounds using a rational, risk-based approach to chemical prioritization, and provide test results that are hopefully far more predictive of human toxicity than current methods. Although a number of toxicity pathways have already been identified, most are only partially known and no common annotation exists. Mapping the entirety of these pathways (i.e. the Human Toxome) will be a large-scale effort, perhaps on the order of the Human Genome Project.
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SEURAT-1 is a long term strategic target for "Safety Evaluation Ultimately Replacing Animal Testing".. It is called "SEURAT-1" to indicate that more steps have to be taken before the final goal will be reached. SEURAT-1 will develop knowledge and technology building blocks required for the development of solutions for the replacement of current repeated dose systemic toxicity testing in vivo used for the assessment of human safety. SEURAT-1 is composed of six research projects, which started on January 1, 2011 and will run for five years. These projects will closely cooperate with a common goal and combine the research efforts of over 70 European universities, public research institutes and companies. The collaboration between these six research projects, the dissemination of results, the cooperation with other international research teams, and the continuous updating on research priorities will be facilitated by the coordination and support action project “COACH”.
SEURAT-1 was developed through the Framework Programme 7 (FP7) research initiative and was created through a call for proposals by the European Commission (EC) that was published in June 2009. The Cosmetics Europe industry offered to match the EC’s funds to make a total of EUR 50 million available to try to fill current gaps in scientific knowledge and accelerate the development of non-animal test methods.
Laboratory animals are not restricted to rats, mice, dogs, and rabbits, but also include fish, frogs and birds. Research into alternatives to replace these species is often neglected, although fish are the third most widely used laboratory animal used for scientific purposes in the EU. This is also the field where until now only two alternative tests exist worldwide: One guideline (OECD TG 236) and one guidance (OECD series on testing and assessment 126) are so far available.
Euroecotox is a European network for alternative testing strategies in ecotoxicoloy. It was funded by the Seventh Framework Programme (FP7) of the European Commission Environment Programme. The main objectives of the Euroecotox network are: To contribute to the advancement of alternative methods of ecotoxicity testing in Europe. To promote the validation and regulatory acceptance of new alternative ecotoxicity methods. To facilitate the networking of research groups working in the field of alternative ecotoxicology. To provide a gathering point for all stakeholders involved in the development, validation, regulatory acceptance and final use of alternative ecotoxicity testing strategies. To act as the one voice for alternative ecotoxicity testing in Europe.
AXLR8 is a coordination action funded by the European Commission Directorate General for Research & Innovation under the 7 Framework Programme 7 (FP7) Health Theme. The European Commission is currently funding a number of research consortia to develop new 3Rs [replacement, reduction and refinement] test methods and strategies as potential alternatives to the use of animals in safety testing. Monitoring of these 3Rs activities at pan-European, national, and international levels is vital to facilitate swift progress. AXLR8 aims to fulfill this growing need by providing a focal point for dialogue and collaboration. Humane Society International is part of the consortium.
- Dissemination and validation of alternative methods to animal testing
- Promotion of research in the field of the 3Rs
- Reduction of the use of animals for tests in the field of education and continuing education
- Reduction of suffering and stress of laboratory animals by better breeding, keeping, test planning and other accompanying measures
- Experts' guidance and referees' opinion for public and private organizations, companies, universities
- Suitable information for the public and the media
The 1st Latino-Americano Congress on Alternative to Animal Testing took place in 2012. Colama (I Congresso Latino-Americano De Metodos Alternativos Ao Uso De Animais No Ensino, Pesquisa E Industria).
Industry and corporate initiatives
- Cosmetics Europe: Represents the interests of more than 4000 companies in the cosmetic, toiletry and perfumery industry since 1962.
- Unilever: "We do not test finished products on animals unless demanded by the regulatory authorities in the few countries where this is the law. In such cases, we try to convince the local authorities to change the law. Where some testing of ingredients is required by law or currently unavoidable, we aim to minimise the number of animals used."
- BASF: "Systematic screening investigations provide information about important toxicological properties of substances at an early stage of development. [...] We replace animal experiments whenever an alternative method is available that complies with an OECD Test Guideline and is recognized by the authorities."
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EU Directive 2010/63/EU
On January 1, 2013, EU Directive 2010/63/EU "on the protection of animals used for scientific purposes" entered into force for the 28 EU Member States (MS). It repealed the previous Directive 86/609/EEC. Because it is a Directive, it allows Member States certain flexibility in its transposition in the national rules. The status of the implementation of the new Directive in the EU is described by the EC Directorate General Environment (EC DG ENV). One of the purposes of this Directive is to give scope (Articles. 1&3), harmonise the current EU understanding of what defines an animal (Article 1.3), map the resources, identify the competent people and authorities (Articles 47.5 & 48), establish a common framework, and, promote collaboration of the Member States with the EC to promote animal welfare in the EU as incorporated as a European value in Article 13 of the Treaty of the Functioning of the EU (TFEU).
Animal welfare is not an EU policy area per se as it is for agriculture, fisheries, research etc.… but rather that “In formulating and implementing the Union's agriculture, fisheries, transport, internal market, research and technological development and space policies, the Union and the Member States shall, since animals are sentient beings, pay full regard to the welfare requirements of animals, while respecting the legislative or administrative provisions and customs of the Member States relating in particular to religious rites, cultural traditions and regional heritage”. Therefore, no legal action can be taken by the EC when animal welfare is not respected, one must refer directly to the Member States. Nevertheless, promotion and use of alternative test methods and 3Rs are written elsewhere within the EU legislation (e.g. REACH, Cosmetics, PPP, Biocides…). EU agencies (ECHA, EMA, EFSA) also contribute to the protection of laboratory animals used for scientific purposes.
The new EU Directive applies to the following animals: (a) live non-human vertebrate animals, including: (i) independently feeding larval forms; and (ii) foetal forms of mammals from the last third of their normal development; (b) live cephalopods.
The Directive refers directly to the 3Rs: "Principle of replacement, reduction and refinement".
Member States shall assist the Commission in identifying and nominating suitable specialised and qualified laboratories tocarry out such validation studies.
In July 2013, Commission announced the creation of NETVAL (European Union Network of Laboratories for the Validation of Alternative Methods). EU-NETVAL's primary role is to provide support for EURL ECVAM validation projects, including aspects of training and dissemination, and the identification of methods that have a potential to reduce, refine or replace animals used for scientific purposes.  Currently there are 13 test facilities in 9 Member States: Germany (3), The Netherlands (2), Spain (2), Belgium (1), Czech Republic (1), Finland (1), France (1), Italy (1) and Sweden (1).
Any EU laboratory is allowed to apply as long as they follow the elligibilitry criteria listed by the EC such as sufficient scientific staff, adequate equipment and GLP/or ISO certificates.
EU cosmetic regulation
The Cosmetics Directive provides the regulatory framework for the phasing out of animal testing for cosmetics purposes. It establishes prohibitions to (a) test finished cosmetic products and cosmetic ingredients on animals (testing ban), and (b) market in the EU finished cosmetic products and ingredients included in cosmetic products which were tested on animals for cosmetics purposes (marketing ban). The same provisions are contained in the Cosmetics Regulation (EU 1223/2009), which replaces the Cosmetics Directive as of July 11, 2013.
EU chemical policy: REACH
In 2007, EU legislation on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH EC 1907/2006 ) came into force, relating to chemicals and their safe use. The aim of REACH is to improve the protection of human health and the environment through the better and earlier identification of the intrinsic properties of chemical substances. It promotes the use of alternative methods for animal testing but does not oblige the test performer to do so; Article 25.1 - In order to avoid animal testing, testing on vertebrate animals for the purposes of this Regulation shall be undertaken only as a last resort. It is also necessary to take measures limiting duplication of other tests.
EU test methods regulation
In parallel to the adoption of REACH, the EC published standardised and accepted methods for testing hazardous properties of chemicals. These were written into the "Test Methods Regulation" (Commission Regulation (EC) No 440/2008 of 30 May 2008). All the alternative test methods among the in vivo studies are included in PART B; "The European Union is committed to promoting the development and validation of alternative techniques which can provide the same level of information as current animal tests, but which use fewer animals, cause less suffering or avoid the use of animals completely. Such methods, as they become available, must be considered wherever possible for hazard characterisation and consequent classification and labelling for intrinsic hazards and chemical safety assessment."
EU regulation for food additives, food enzymes and food flavourings
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It is envisaged, in particular, that food additives, food enzymes and food flavourings, to the extent that the safety of food flavourings must be assessed in accordance with Regulation (EC) No 1334/2008 [on flavourings and certain food ingredients with flavouring properties for use in and on foods], must not be placed on the market or used in foodstuffs for human consumption, in accordance with the conditions laid down in each sectoral food law, unless they are included on a Community list of authorised substances
Recital (19) of REGULATION (EC) No 1331/2008
Information related to the safety of a substance, including, but not limited to, toxicological studies, other safety studies and raw data as such should under no circumstances be confidential
Guidance for submission for food additive evaluations
Within the guidance document, EU animal welfare law (2010/63/EU) and principles (3Rs) are quoted whenever toxicological test methods are necessary. Moreover, the use of a tier testing approach is developed to encourage the test performers in using in silico, in vitro tests as well as validated test methods under OECD standards, in use for REACH or listed under EC 440/2008.
Animal welfare and animal rights organizations
- Eurogroup for Animals: "An estimated 12.1 million animals – including dogs, rabbits and even our closest genetic relatives, primates – are used in laboratory research throughout Europe every year. Eurogroup focusses on ensuring their protection and works with legislators, experts and industry with the aim of ultimately replacing all animal experiments with viable alternatives. We continue to actively promote the replacement, reduction and refinement of animal tests and do all we can to improve the lives of those animals currently used for research."
- Vier Pfoten (Four Paws) 
- Antidote: "When it is about assessing drug safety, humans are not 70kg rats! It is about time to move on from the actual paradigm on assessing drug safety. The first step would be to eliminate all the regulatory requirements for animal testing and replace these tests by 21st century methods."
- Deutscher Tierschutzbund:
- Lega Anti Vivisezione 
- The ALEXANDRA Association: "...aims at stimulating research and development (R&D) in the area of alternative methods to animal experimentation by providing political, technical and educational support to researchers and entrepreneurs worldwide. In particular alternative methods based on ‘Open Source’ concepts i.e. non-patent protected core technologies for human tissue reconstruction and cell culture technologies will be actively promoted."
- British Union for the Abolition of Vivisection (BUAV): "For over 100 years the BUAV has been campaigning peacefully to create a world where nobody wants or believes we need to experiment on animals."
- New England Anti-Vivisection Society (NEAVS): "Recognition of the inadequacy of animal toxicity testing has resulted in the development of better techniques...NEAVS and its programs will help hasten the inevitable and necessary transition away from animal-based experimentation, testing, and teaching, toward science and science education governed by progressive scientific thought and compassionate ethics."
- Humane Society International (HSI) in the US and UK: "Today, scientific and government authorities worldwide are acknowledging the deficiencies of "animal models" and calling for a new approach to safety testing and health research using state-of-the-art techniques. Advances in biology, genetics, computer science and robotics have given scientists new tools to help identify the root causes of human toxicity and disease."
- People for the Ethical Treatment of Animals (PETA) in the US and UK: "We teamed up with CeeTox, Inc. to fund work on a new humane skin test that could replace painful tests on mice and guinea pigs."
Public campaigns and awards
- Petition to the European Parliament for the abolition of vivisection as a European Citizen Initiative. The threshold of 1 million signatures was reached for the deadline (1/11/2013). The European Commission is currently checking the authenticity of each signature.
- "Go cruelty free"
- HSI's report "Advancing Safety Science and Health Research with Innovative, Non-Animal Tools"
- The Lush Prize: "The Lush Prize is a major initiative which will use resources to bring forward the day when safety testing takes place without the use of animals. The Lush Prize will focus pressure on toxicity testing for consumer products and ingredients in a way which complements the many projects already addressing the use of animals in medical testing."
- EPAA (European Partnership for Alternative Approaches to Animal Testing) will grant a €3000 prize to a laboratory technician involved in implementing and raising awareness of Replacement, Reduction and Refinement of animal testing.
- The Alternatives Research and Development Foundation (ARDF) provides grants to advance the use of non-animal methods in the fields of biomedical testing, research, and education.
- The international NC3Rs 3Rs Prize is awarded to highlight an outstanding original contribution to scientific and technological advances in the 3Rs in medical, biological or veterinary sciences published within the last three years.
- The American Fund for Alternatives to Animal Research (AFAAR) funds a wide and encompassing range of research involving the use, development, or validation of alternatives.
Education and training
- IIVS: The Institute for In Vitro Sciences, Inc. is a non-profit research and testing laboratory dedicated to the advancement of in vitro (non-animal) methods worldwide. Founded in 1997, IIVS has worked with industry and government agencies to implement in vitro testing strategies that limit animal use while supplying key information for product safety and efficacy decisions.
- InterNICHE is the International Network for Humane Education. It has been developed to meet the needs of teachers and trainers, students, ethics committees, alternatives producers and campaigners internationally.
- “Tierschutz macht Schule“ - the Association for Animal Welfare Education - was founded in the course of the implementation of Austria’s nationwide animal welfare law. The animal welfare education association aims to improve the living conditions of pets, farm animals, laboratory animals and wild animals through providing knowledge about their needs and behaviour to children, youth and the public. The association offers a teaching magazine about research animals and animal tests suitable for secondary schools and college, which can be ordered on their website. It aims at explaining alternatives to animal testing in a youth appropriate language and can be used in lessons straight away.
- XCellR8's mission is to support, develop and implement the use of scientifically advanced and ethically sound alternatives to animal testing. They are an exclusively in vitro company, with commitment to promoting non-animal testing strategies at the core of all of their activities.
Institutes and national or international organizations
Institutes and organizations that research or fund alternatives to animal testing include:
Asia - Oceania
- Medical Advances Without Animals Trust
- Alternatives to Animal Experimentation Laboratory, Department of Pharmacology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh.
- Mahatma Gandhi-Doerenkamp Center for Alternatives to Use of Animals in Life Science Education
- Japanese Center for the Validation of Alternative Methods (JACVAM), since 2005
- The Korean Center for the Validation of Alternative Methods (KOCVAM), since 2009
- BraCVAM as the Brazilian Center for the Validation of Alternatives Methods. It was established in 2011.
- Canadian Council on Animal Care
- Health Canada, which does not have a formal validation center, but coordinates health related test method validation and acceptance issues
United States of America
- American Fund for Alternatives to Animal Research (AFAAR): "Over the years, AFAAR has funded alternatives worldwide, including more than 200 human tissue culture tests to replace toxicity and other testing on animals...Today, AFAAR funds a wide and encompassing range of research involving the use, development, or validation of alternatives."
- Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), since 1994;
- Johns Hopkins University Center for Alternatives to Animal Testing
- Physicians Committee for Responsible Medicine
- UC Davis Center for Animal Alternatives
- The EC's involvement in activities targeted to the validation of alternative approaches to animal testing started in 1991, with the launch of ECVAM (European Centre for the Validation of Alternative Methods), hosted by the Joint Research Centre, Institute for Health and Consumer Protection (IHCP). As from 2011, ECVAM's tasks are assigned to EURL ECVAM. Official bodies such as the EURL ECVAM, hosts an online database of toxicological, non-animal alternative test methods DB-ALM,.
- Under the Framework Programmes 6 and 7, the EC funded a significant number of large integrated research projects aiming to develop alternatives to animal testing for about EUR 330 million based on the Review of REACH from February 2013 (the European Chemical Program).
- The European Partnership for Alternative Approaches to Animal Testing (EPAA) as a liaison between the EC and industries.
- The European Consensus Platform for Alternatives (ECOPA) coordinates efforts amongst EU member states.
- Zentrum fuer Ersatz
- Finish Center for Alternative Methods (FICAM), since 2008
- FRANCOPA is the French platform dedicated to development, validation, and dissemination of alternative methods in animal testing. It was created in November 16, 2007 
- Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergänzungsmethoden (ZEBET), since 1989
- Dr Hadwen Trust
- Fund for the Replacement of Animals in Medical Experiments
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), since 2004
International Cooperation on Alternative Test Methods (ICATM): On April 27, 2009 the U.S., Canada, Japan and EU signed a memorandum of cooperation that could reduce the number of animals required for consumer product safety testing worldwide. The agreement will yield globally coordinated scientific recommendations on alternative toxicity testing methods that should speed their adoption in each of these countries, thus reducing the number of animals needed for product safety testing.
The OECD (Organisation for Economic Co-operation and Development) is a forum for discussion where governments express their points of view, share their experiences, and search for common ground, as opposed to a supranational organization. OECD is a forum where alternative test methods also undergo validation and are therereafter accepted for regulatory purposes in more than 35 member countries worldwide. NGOs are represented at the technical level at the OECD, under the ICOPA International Council on Animal Protection in OECD program.
The testing of chemicals is labor-intensive and expensive. Often the same chemical is tested in several countries simultaneously, which means that redundant animal tests are performed. To relieve some of this burden, the OECD Council adopted a decision in 1981, stating that data generated in a member country, in accordance with OECD Test Guidelines and Principles of Good Laboratory Practice (GLP), shall be accepted in other member countries for assessment purposes and other uses relating to the protection of human health and the environment. This principle is referred to using the acronym MAD, for the Mutual Acceptance of Data.
- R E Hester R M Harrison et al. Alternatives To Animal Testing (Issues in Environmental Science and Technology) Royal Society of Chemistry; 1 edition (June 7, 2006) ISBN 978-0-85404-211-1
- Lipinski, Christopher; Hopkins, A (16 December 2004). "Navigating chemical space for biology and medicine". Nature 432 (7019): 855–61. doi:10.1038/nature03193. PMID 15602551.
- Malcolm Rowland (February 2006). "Microdosing and the 3Rs". National Center for the Replacement, Refinement, and Reduction of Animals in Research ( NC3Rs ). Archived from the original on 28 September 2007. Retrieved 2007-09-22.
-  Alternatives to Animal Research
- FRAME (2005). "Human microdosing reduces the number of animals required for pre-clinical pharmaceutical research". Alternatives to Laboratory Animals 33 (439).
- Russell, W.M.S. and Burch, R.L., (1959). The Principles of Humane Experimental Technique, Methuen, London. ISBN 0900767782 
- "Special section: Monoclonal antibodies". Johns Hopkins Bloomberg School ofPublic Health. Archived from the original on 2007-08-20. Retrieved 2007-09-20.
- Brunner, D., Jürgen Frank, Helmut App, Harald Schöffl, Walter Pfaller and Gerhard Gstraunthaler. 2010 Serum-free Cell Culture: The Serum-free Media Interactive Online Database. Altex 27:53-62.
- The Epiderm Skin Model – Manufacturer’s Web Site
- – ECVAM validation of Episkin for skin irritation
- - SkinEthic RHE model validation for skin irritation
- EpiDerm Approved by EU, U.S. Regulators
- OECD (2010). OECD Guidelines for the Testing of Chemicals, Section 4: Test No. 439: In Vitro Skin Irritation Reconstructed Human Epidermis Test Method.
- Comparison of in vivo (draize method) and in vitro (corrositex assay) dermal corrosion values for selected industrial chemicals
- The 3T3 Neutral Red Uptake (NRU) Phototoxicity Assay – MB Research Labs
- "In Vitro Toxicology Testing (Non-Animal Safety Testing)". MatTek Corporation. Retrieved 26 April 2011.
- Guthrie, Catharine (2008). "Putting Immunity in a Test Tube". TIME. Retrieved 2009-12-22
- "Asthma". entelos.com. Archived from the original on 2005-04-15. Retrieved 2007-10-05. (from internet archive)
- The History of Crash Test Dummies
- I Was A Human Crash-Test Dummy
- Home of the TraumaMan system – Simulab Corporation
- TraumaMan Offers Lifelike Practice for Med Students
- Using Computers to Assess the Heart
- BBC News - Mouse Brain simulated on Computer
- alternatives to animal testing, Peta
- Kristian Björnstad, Anders Helander, Peter Hultén & Olof Beck (2009). "Bioanalytical investigation of asarone in connection with Acorus calamus oil intoxications". Journal of Analytical Toxicology 33 (9): 604–609.
- Joanna D. Moody, Donglu Zhang, Thomas M. Heinze and Carl E. Cerniglia (2000). "Transformation of amoxapine by Cunninghamella elegans". Applied and Environmental Microbiology 66 (8): 3646–3649. doi:10.1128/AEM.66.8.3646-3649.2000. PMC 92200. PMID 10919836.
- A. Jaworski, L. Sedlaczek, J. Dlugoński & Ewa Zajaczkowska (1985). "Inducible nature of the steroid 11-hydroxylases in spores of Cunninghamella elegans (Lendner)". Journal of Basic Microbiology 25 (7): 423–427. doi:10.1002/jobm.3620250703.
- Hezari, M.; Davis, P. J. (1993). "Microbial models of mammalian metabolism. Furosemide glucoside formation using the fungus Cunninghamella elegans". Drug metabolism and disposition: the biological fate of chemicals 21 (2): 259–267. PMID 8097695.
- Sharma, KK; Arora, T; Joshi, V; Rathor, N; Mehta, AK; Mehta, KD; Mediratta, PK (2011). "Substitute of animals in drug research: An approach towards fulfillment of 4R′s". Indian Journal of Pharmaceutical Sciences 73 (1): 1–6. doi:10.4103/0250-474X.89750. PMC 3224398. PMID 22131615.
- Committee on Toxicity Testing and Assessment of Environmental Agents, National Research Council (2007). "Toxicity testing in the 21st century: A vision and a strategy". Retrieved August 12, 2013.
- "Sixth Report from the Commission to the Council and the European Parliament on the Statistics on the number of animals used for experimental and other scientific purposes in the member states of the European Union COM(2010) 511/final 2". European Commission. 2010. Retrieved August 20, 2013.
- Cosmetics Europe
- The European Parliament and the Council of the European Union (2010). Directive 2010/63/EU "Directive 2010/63/EU of the European Parliament and of the Council". Retrieved August 12, 2013.
- Cosmetics Regulation
- European Parliament and the Council of the European Union (2006). "Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)". Retrieved August 11, 2013.
- Eurogroup for Animals
- Deutscher Tierschutzbund
- Humane Society International
- stop vivisezione
- Go cruelty free
- HSI end animal testing
- Lush prize
- A Guide to the Alternatives of Animal Experimentation (2009; revised edition 2010). Eds. Syed Ziaur Rahman and Mohd Tariq Salman, Ibn Sina Academy of Medieval Medicine and Sciences, Aligarh, India (ISBN 978-81-906070-4-9)
- Akbarsha, MA; Pereira, Shiranee (Nov-Dec 2010). "Mahatma Gandhi-Doerenkamp Center for Alternatives to Use of Animals in Life Science Education". Pharmacol Pharmacother 1 (2): 108–10. doi:10.4103/0976-500X.72353. PMC 3043344. PMID 21350619.
- Canadian Council on Animal Care Three Rs Microsite
- EURL ECVAM. Accessed 2013-08-19
- EURL ECVAM. Accessed 2013-08-19.
- "Home page". Evcam Database Service on Alternative methods to Animal Experimentation).
- EPAA – Home. Ec.europa.eu. Retrieved on 2013-01-21.
- ecopa – european consensus-platform for alternatives. Ecopa.eu. Retrieved on 2013-01-21.
- Zentrum fuer Ersatz- und Erganzungen Methoden zum Tierversuch
- ZEBET database on alternatives to animal experiments on the Internet (AnimAlt-ZEBET). BfR (2004-09-30). Retrieved on 2013-01-21.
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs)
- ICATM memorandum.
|Wikiversity has learning materials about Alternatives to animal testing|
- Alternatives to Animals: The Latest: Tracks news stories about scientific developments in alternatives to animal use
- International Network for Humane Education
- Go3R: semantic search to avoid animal experiments
- The Use of Databases, Information Centers and Guidelines When Planning Research that May Involve Animals, Animal Welfare Information Center Bulletin, National Agricultural Library. Provides an overview of databases, bibliographies and guidelines that provide useful information on alternative methods when planning research that may involve animals.
- CADASTER Seventh Framework Programme project aimed to develop computational methods to minimize number of experimental tests for REACH – Registration, Evaluation, Authorisation and Restriction of Chemicals