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Alternatives to
animal testing Animal testing, also known as animal experimentation, animal research, and ''in vivo'' testing, is the use of non-human animals in experiments that seek to control the variables that affect the behavior or biological system under study. This ...
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 Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and p ...
'' animal testing are ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...
''
cell culture Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This tec ...
techniques and ''
in silico In biology and other experimental sciences, an ''in silico'' experiment is one performed on computer or via computer simulation. The phrase is pseudo-Latin for 'in silicon' (correct la, in silicio), referring to silicon in computer chips. It ...
''
computer simulation Computer simulation is the process of mathematical modelling, performed on a computer, which is designed to predict the behaviour of, or the outcome of, a real-world or physical system. The reliability of some mathematical models can be deter ...
. 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 Serum may refer to: * Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity * Serous fluid, any clear bodily fluid *Truth serum, a drug that is likely to mak ...
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 Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...
and
pharmacodynamics Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms ...
it does not reveal information about toxicity or
toxicology Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating e ...
. Furthermore, it was noted by the
Fund for the Replacement of Animals in Medical Experiments Fund for the Replacement of Animals in Medical Experiments (FRAME) is a charity based in Nottingham, UK. FRAME promotes consideration of the ethical and scientific issues involved in the use of laboratory animals for medical research, and the ...
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.Russell, W.M.S. and Burch, R.L., (1959). ''The Principles of Humane Experimental Technique'', Methuen, London.
Digital text
available for free on the website of the Center for Alternatives to Animal Testing.
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.


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 A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. 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 Tissue culture is the growth of tissues or cells in an artificial medium separate from the parent organism. This technique is also called micropropagation. This is typically facilitated via use of a liquid, semi-solid, or solid growth medium, su ...
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 foetal cows are sacrificed each year to obtain the world's supply of foetal bovine serum, used to grow cultured cells. The testing of cosmetic products directly onto an animal can be minimized or eliminated by the use of ''in vitro'' cell growth and development. This can be generalized as the growth of cells outside of the body and tested on without causing harm or pain on the test subject. Much of the time this method of cosmetic testing is less time-consuming and less expensive than alternative choices.


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 The Organisation for Economic Co-operation and Development (OECD; french: Organisation de coopération et de développement économiques, ''OCDE'') is an intergovernmental organisation with 38 member countries, founded in 1961 to stimulate ...
(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.


Skin absorption

Several tissue culture methods that measure the rate of chemical absorption by the skin have been approved by the OECD.


Phototoxicity

Phototoxicity Phototoxicity, also called photoirritation, is a chemically induced skin irritation, requiring light, that does not involve the immune system. It is a type of photosensitivity. The skin response resembles an exaggerated sunburn. The involved chemi ...
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 3T3 cells are several cell lines of mouse embryonic fibroblasts. The original 3T3 cell line (3T3-Swiss albino) was established in 1962 by two scientists then at the Department of Pathology in the New York University School of Medicine, George Tod ...
after exposure to a chemical in the presence or absence of light. The 3T3 cell line was developed in 1962 and is derived from mouse embryonic
fibroblast A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells ...
cells.


Fungal model for mammalian drug metabolism

Fungi like ''
Cunninghamella elegans ''Cunninghamella elegans'' is a species of fungus in the genus '' Cunninghamella'' found in soil. It can be grown in Sabouraud dextrose broth, a liquid medium used for cultivation of yeasts and molds from liquid which are normally sterile. As ...
'' can be used as a microbial
model A model is an informative representation of an object, person or system. The term originally denoted the plans of a building in late 16th-century English, and derived via French and Italian ultimately from Latin ''modulus'', a measure. Models c ...
of mammalian drug metabolism thereby reducing the need for laboratory animals. Prokaryotes are often used as an alternative to animal testing. Prokaryotes include bacteria such as ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'' (''E. coli'') or ''
Bacillus subtilis ''Bacillus subtilis'', known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium, found in soil and the gastrointestinal tract of ruminants, humans and marine sponges. As a member of the genus ''Bacillus ...
''. These bacteria are the ideal model for genetic and molecular studies. Fungi is also used as an alternative for animal testing. Certain fungi can be used for genetic studies or circadian rhythms studies. This may include ''
Neurospora crassa ''Neurospora crassa'' is a type of red bread mold of the phylum Ascomycota. The genus name, meaning "nerve spore" in Greek, refers to the characteristic striations on the spores. The first published account of this fungus was from an infestation ...
'', otherwise known as a type of red mould. Invertebrates are another ideal candidate for testing. One of the most common invertebrates tested on include ''
Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...
'', the fruit fly. Fruit flies are used to find human diseases.


Organoids (3D cell cultures)

Russell and Burch writing six decades ago could not have anticipated some of the technologies that have emerged today. One of these technologies, 3D cell cultures, also known as organoids or mini-organs, have replaced animal models for some types of research. In recent years, scientists have produced organoids that can be used to model disease and test new drugs. Organoids grow ''in vitro'' on scaffolds (biological or synthetic hydrogels such as Matrigel) or in a culture medium. Organoids are derived from three kinds of human or animal stem cells—embryonic pluripotent stem cells (ESCs), adult somatic stem cells (ASCs), and induced pluripotent stem cells (iPSCs). These organoids are grown ''in vitro'' and mimic the structure and function of different organs such as the brain, liver, lung, kidney, and intestine. Organoids have been developed to study infectious disease. Scientists at Johns Hopkins University have developed mini-brain organoids to model how COVID-19 can affect the brain. Researchers have used brain organoids to model how the ''
Zika virus ''Zika virus'' (ZIKV; pronounced or ) is a member of the virus family (biology), family ''Flaviviridae''. It is mosquito-borne disease, spread by daytime-active ''Aedes'' mosquitoes, such as ''Aedes aegypti, A. aegypti'' and ''Aedes albopict ...
'' disrupts foetal brain development. Tumoroids—3D cell cultures derived from cells biopsied from human patients—can be used in studying the genomics and drug resistance of tumours in different organs. Organoids are also used in modelling genetic diseases such as cystic fibrosis, neurodegenerative diseases such as Alzheimer's and Parkinson's, infectious diseases such as MERS-CoV and norovirus, and parasitic infections such as '' Toxoplasma gondii''. Human- and animal-cell-derived organoids are also used extensively in pharmacological and toxicological research.


Human-based


Skin irritation

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
keratinocyte Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes referre ...
s have been cultured to mimic the human
epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water rel ...
, 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.


Pyrogenicity

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.


Medical imaging

Medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to re ...
is able to demonstrate to researchers both how drugs are metabolised by use of microdosing, and the detailed condition of organ tissue.


Computer simulation

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
mannequin A mannequin (also called a dummy, lay figure, or dress form) is a doll, often articulated, used by artists, tailors, dressmakers, window dressers and others, especially to display or fit clothing and show off different fabrics and textiles. ...
s, also known as
crash test dummies Crash Test Dummies are a Canadian rock band from Winnipeg, Manitoba. The band is most identifiable through Brad Roberts (vocals, guitar) and his distinctive bass-baritone voice. The band members have fluctuated over the years, but its best kno ...
, 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. 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, modelled half a
mouse brain The mouse brain refers to the brain of Mus musculus. Various brain atlases exist. For reasons of reproducibility, genetically characterized, stable strains like C57BL/6 were chosen to produce high-resolution images and databases. Well known o ...
for just 10 seconds. However, due to limitations in computing power, the simulation could only be run at one-tenth 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." In pharmacology and toxicology, physiologically based pharmacokinetic models can be used for ''in vitro'' to ''in vivo'' extrapolation and to predict the time-dependent distribution of chemicals in the organism, while
quantitative structure-activity relationship Quantitative may refer to: * Quantitative research, scientific investigation of quantitative properties * Quantitative analysis (disambiguation) * Quantitative verse, a metrical system in poetry * Statistics, also known as quantitative analysis ...
(QSAR) models can be used to predict the physicochemical and hazard properties of chemicals.


Microfluidic chips

Microfluidic chips, which are just wide, can be engraved into a series of small chambers, each containing a sample of tissue from a different part of the body. A substitute of blood flows through micro-channels where the compartments of chips linked. When injected, the test drug circulates around the device, mimicking what goes in the body on a micro scale. Sensors in the chip transfer information for computer analysis. Another name for this chip is the microfluidic chip is cell-bio chips. With the capacity to "perform perfusion culture" and reproduce "physiological conditions such three-dimensional architectures, circulatory flowrate and zonation and multi cellular co-cultures", the biochips have set themselves apart from basic cell cultures analysed in a Petri dish. The effectiveness of these systems is constantly being increased with various new materials that can be used to make it. An ideal material would be gas permeable but still be able to absorb molecules that would be expected to be found in various drugs The choice of the material for chips is still challenging. One of the major materials that can be possibly used in chips is known as
polydimethylsiloxane Polydimethylsiloxane (PDMS), also known as dimethylpolysiloxane or dimethicone, belongs to a group of polymeric organosilicon compounds that are commonly referred to as silicones. PDMS is the most widely used silicon-based organic polymer, as its ...
(PDMS). However, due to lack of facilities for mass production and drug clearance issue, the use of PDMS is still being speculated, even though it has great properties as microfluidic chip. Also, the biological process involved in proliferation and metabolism might be modified when compared to larger scales, because the materials have micro-structured scales comparable in size to cells.


Future alternatives


Organs on a chip

The
Wyss Institute for Biologically Inspired Engineering The Wyss Institute for Biologically Inspired Engineering (pronounced "veese") is a cross-disciplinary research institute at Harvard University focused on bridging the gap between academia and industry (translational medicine) by drawing inspira ...
(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.


Human toxome

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 The Human Genome Project (HGP) was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying, mapping and sequencing all of the genes of the human genome from both ...
.


Research initiatives


SEURAT-1

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.


Euroecotox

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 ecotoxicology. 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

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 fulfil this growing need by providing a focal point for dialogue and collaboration.
Humane Society International Humane Society International (HSI) is the international division of The Humane Society of the United States. Founded in 1991, HSI has expanded The HSUS's activities into Central and South America, Africa, and Asia. HSI's Asian, Australian, Cana ...
is part of the consortium.


Regulation


European Union


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 EU member states (MS), repealing Directive 86/609/EEC. Because it is a directive, it allows
member states A member state is a state that is a member of an international organization or of a federation or confederation. Since the World Trade Organization (WTO) and the International Monetary Fund (IMF) include some members that are not sovereign s ...
certain flexibility in transposition of national rules. The status of the implementation of the new directive in the EU is described by the EC General Environment Directorate. :Article 1.3: The new EU directive applies to the following animals: (a) live non-human
vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with ...
animals, including: (i) independently feeding
larva A larva (; plural larvae ) is a distinct juvenile form many animals undergo before metamorphosis into adults. Animals with indirect development such as insects, amphibians, or cnidarians typically have a larval phase of their life cycle. ...
l forms; and (ii) foetal forms of
mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur ...
s from the last third of their normal development; (b) live cephalopods. :Article 4: The directive refers directly to the 3Rs: "Principle of replacement, reduction and refinement". :Article 47-2: Member states shall assist the commission in identifying and nominating suitable specialised and qualified laboratories to carry out such validation studies. In July 2013, the 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 thirteen test facilities in nine member states:
Germany Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwee ...
(3),
the Netherlands ) , anthem = ( en, "William of Nassau") , image_map = , map_caption = , subdivision_type = Sovereign state , subdivision_name = Kingdom of the Netherlands , established_title = Before independence , established_date = Spanish Netherl ...
(2),
Spain , image_flag = Bandera de España.svg , image_coat = Escudo de España (mazonado).svg , national_motto = '' Plus ultra'' (Latin)(English: "Further Beyond") , national_anthem = (English: "Royal March") , ...
(2),
Belgium Belgium, ; french: Belgique ; german: Belgien officially the Kingdom of Belgium, is a country in Northwestern Europe. The country is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeast, France to ...
(1),
Czech Republic The Czech Republic, or simply Czechia, is a landlocked country in Central Europe. Historically known as Bohemia, it is bordered by Austria to the south, Germany to the west, Poland to the northeast, and Slovakia to the southeast. The ...
(1),
Finland Finland ( fi, Suomi ; sv, Finland ), officially the Republic of Finland (; ), is a Nordic country in Northern Europe. It shares land borders with Sweden to the northwest, Norway to the north, and Russia to the east, with the Gulf of Bot ...
(1),
France France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of Overseas France, overseas regions and territories in the Americas and the Atlantic Ocean, Atlantic, Pacific Ocean, Pac ...
(1),
Italy Italy ( it, Italia ), officially the Italian Republic, ) or the Republic of Italy, is a country in Southern Europe. It is located in the middle of the Mediterranean Sea, and its territory largely coincides with the homonymous geographical ...
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Sweden Sweden, formally the Kingdom of Sweden,The United Nations Group of Experts on Geographical Names states that the country's formal name is the Kingdom of SwedenUNGEGN World Geographical Names, Sweden./ref> is a Nordic countries, Nordic c ...
(1).


Other regulations

The
Cosmetics Directive Council Directive 76/768/EEC of 27 July 1976 on the approximation of the laws of the Member States relating to cosmetic productscosmetics Cosmetics are constituted mixtures of chemical compounds derived from either natural sources, or synthetically created ones. Cosmetics have various purposes. Those designed for personal care and skin care can be used to cleanse or protec ...
purposes. It establishes prohibitions against (a) testing finished cosmetic products and cosmetic ingredients on animals (testing ban), and (b) marketing 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 Cosmetics Regulation EU 1223/2009, which replaces the Cosmetics Directive as of July 11, 2013. In 2007, EU legislation on the
Registration, Evaluation, Authorisation and Restriction of Chemicals Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) is a European Union regulation dating from 18 December 2006. REACH addresses the production and use of chemical substances, and their potential impacts on both human h ...
(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." In parallel to the adoption of REACH, the EC published standardised and accepted methods for testing hazardous properties of
chemical A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., w ...
s. These were written into the "Test Methods Regulation". 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 labeling for intrinsic hazards and chemical safety assessment." EU philosophy on food additives, food
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s, and food flavourings and ingredients intended for human consumption is that none should be put on the market unless they are included on a published Community list of authorised substances, in accordance with the conditions laid down in relevant food law. This approach is intended to bring food producers into compliance with the provisions of Regulation (EC) 1334/2008 that pertain to the safety of food flavourings. As part of the approval process, the EC will require full disclosure of study data, safety issues, and toxicological findings for all such additives. Within the EU animal welfare law (2010/63/EU), the principles of the 3Rs are invoked whenever toxicological test methods are necessary.


Organizations and programs


Scientific congresses

The European Society for Alternatives to Animal Testing (EUSAAT) organises an annual conference in
Linz Linz ( , ; cs, Linec) is the capital of Upper Austria and third-largest city in Austria. In the north of the country, it is on the Danube south of the Czech border. In 2018, the population was 204,846. In 2009, it was a European Capital ...
(
Austria Austria, , bar, Östareich officially the Republic of Austria, is a country in the southern part of Central Europe, lying in the Eastern Alps. It is a federation of nine states, one of which is the capital, Vienna, the most populous ...
) for # 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 World Congress on Alternatives and Animal Use in the Life Sciences takes place every three years. The next conference (10th) will be held in September 2017 in
Seattle Seattle ( ) is a seaport city on the West Coast of the United States. It is the seat of King County, Washington. With a 2020 population of 737,015, it is the largest city in both the state of Washington and the Pacific Northwest region o ...
. 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). The Johns Hopkins University
Center for Alternatives to Animal Testing The Johns Hopkins University Center for Alternatives to Animal Testing (CAAT) has worked with scientists, since 1981, to find new methods to replace the use of laboratory animals in experiments, reduce the number of animals tested, and refine nece ...
(CAAT) co-organizes an annual symposium on the 3Rs with the USDA's Animal Welfare Information Center (AWIC) and NIH's Office of Laboratory Animal Welfare. Previously known as the Social Housing Symposium, the symposium has occurred annually (except for 2015) since 2013 with past symposia archived on video on the AWIC website. Videos of the most recent symposium, "7th Annual 3Rs Symposium: Practical Solutions and Success Stories", held in June 2020, may also be found on the AWIC website.


Industry and corporate initiatives

* Cosmetics Europe: Represents the interests of more than 4000 companies in the cosmetic, toiletry and perfumery industry since 1962. *
Unilever Unilever plc is a British multinational consumer goods company with headquarters in London, England. Unilever products include food, condiments, bottled water, baby food, soft drink, ice cream, instant coffee, cleaning agents, energy dri ...
: "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 BASF SE () is a German multinational chemical company and the largest chemical producer in the world. Its headquarters is located in Ludwigshafen, Germany. The BASF Group comprises subsidiaries and joint ventures in more than 80 countries ...
: "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."


Animal welfare and animal rights organizations

*
Eurogroup for Animals Eurogroup for Animals is an animal protection lobby group based in Brussels, Belgium, that seeks to improve animal welfare standards in the European Union. The association represents animal protection organisations in 26 of the 27 EU Member Sta ...
: "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) (Austria) *Antidote (France) "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 (Germany) *Lega Anti Vivisezione (Italy) *The ALEXANDRA Association (Monaco): "... 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 Cruelty Free International is an animal protection and advocacy group that campaigns for the abolition of all animal experiments. They organise certification of cruelty-free products which are marked with the symbol of a leaping bunny. It wa ...
(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 The New England Anti-Vivisection Society (NEAVS) is a national, registered 501(c)(3) nonprofit organization "dedicated to ending the use of animals in research, testing, and science education" and replacing them with "modern alternatives that are ...
(NEAVS) (United States): "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 Humane Society International (HSI) is the international division of The Humane Society of the United States. Founded in 1991, HSI has expanded The HSUS's activities into Central and South America, Africa, and Asia. HSI's Asian, Australian, Cana ...
(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 People for the Ethical Treatment of Animals (PETA; , stylized as PeTA) is an American animal rights nonprofit organization based in Norfolk, Virginia, and led by Ingrid Newkirk, its international president. PETA reports that PETA entities hav ...
(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 November 2013). The European Commission is currently checking the authenticity of each signature. * "Go cruelty free" The launch of the global "Go Cruelty-Free" campaign occurred in 2012 and every year since the launch there have been more and more contributions from around the globe to help put a stop to using animals for lab testing. The most recent contribution is from Australia in 2019, they banned the use of newly derived animal test data for cosmetics. *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. * NORINA is a database containing details of products which may be used as alternatives or supplements to the use of animals in education and training. NORINA's search engine is linked to those of two other databases: TextBase, which provides information on textbooks and other written material of relevance to laboratory animal science and alternatives, and 3R Guide which gives details of guidelines, information centres, databases, journals and email lists within the field of replacement, reduction and refinement of animal experimentation. The three databases are hosted by Norecopa. *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
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. *The Animal Welfare Information Center at the National Agricultural Library (USDA) holds a workshop several times a year called "Meeting the Information Requirements of the Animal Welfare Act". In the workshop, researchers and other stakeholders learn how to perform literature searches for animal use alternatives as well as the history and evolution of the Animal Welfare Act of 1966 and its amendments, showing how the legislation regulates animal welfare. *EPISKIN Academy is an initiative of the industry to propose training and courses to facilitate the deployment of validated alternative methods to animal testing in toxicology and to prepare next generations of scientists and toxicologists to use these methods. Created in 2012, EPISKIN Academy proposes a modular program ranging from demonstration of these methods to full theoretical and practical laboratory training leading to certification. Based on long-term partnerships with institutional partners in different countries, this program in education allows hands-on training to the methods but also to the scientific and regulatory knowledge important for their implementation and acceptance.


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 (Australia) *Alternatives to Animal Experimentation Laboratory, Department of Pharmacology, Jawaharlal Nehru Medical College,
Aligarh Muslim University Aligarh Muslim University (abbreviated as AMU) is a Public University, public Central University (India), central university in Aligarh, Uttar Pradesh, India, which was originally established by Sir Syed Ahmad Khan as the Muhammadan Anglo-Orie ...
,
Aligarh Aligarh (; formerly known as Allygarh, and Kol) is a city in the state of Uttar Pradesh in India. It is the administrative headquarters of Aligarh district, and lies northwest of state capital Lucknow and approximately southeast of the cap ...
(India). * Mahatma Gandhi-Doerenkamp Center for Alternatives to Use of Animals in Life Science, Bharathidasan university, Trichy, Tamil Nadu, India Education *Japanese Center for the Validation of Alternative Methods (JACVAM), since 2005 *The Korean Center for the Validation of Alternative Methods (KOCVAM), since 2009


South America

* BraCVAM as the Brazilian Center for the Validation of Alternatives Methods. It was established in 2011.


North America

*
Canadian Council on Animal Care The Canadian Council on Animal Care (CCAC) is a Canadian organization that is responsible for "setting and maintaining standards for the care and use of animals in science" within the country. The organization provides ethical standards for the ...
*
Canadian Centre for Alternatives to Animal Methods The Canadian Centre for Alternatives to Animal Methods (CCAAM) and its subsidiary, the Canadian Centre for the Validation of Alternative Methods (CaCVAM), is a research centre founded in 2017 and based at the University of Windsor, in Canada. Its ...
, founded in 2017 at the University of Windsor. * Health Canada, which does not have a formal validation centre, but coordinates health related test method validation and acceptance issues * 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) (United States), since 1994; *
Johns Hopkins University Johns Hopkins University (Johns Hopkins, Hopkins, or JHU) is a private research university in Baltimore, Maryland. Founded in 1876, Johns Hopkins is the oldest research university in the United States and in the western hemisphere. It consi ...
Center for Alternatives to Animal Testing The Johns Hopkins University Center for Alternatives to Animal Testing (CAAT) has worked with scientists, since 1981, to find new methods to replace the use of laboratory animals in experiments, reduce the number of animals tested, and refine nece ...
*
Physicians Committee for Responsible Medicine The Physicians Committee for Responsible Medicine (PCRM) is a non-profit research and advocacy organization based in Washington, D.C., which promotes a plant-based diet, preventive medicine, and alternatives to animal research, and encourages ...
(United States)


Europe

* The European Commission's role in promoting the development, validation and uptake 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 The Joint Research Centre (JRC) is the European Commission's science and knowledge service which employs scientists to carry out research in order to provide independent scientific advice and support to European Union (EU) policy. The JRC is ...
. As from 2011, ECVAM became known as th
EU Reference Laboratory for Alternatives to Animal Testing
(EURL ECVAM). 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 The European Partnership for Alternative Approaches to Animal Testing (EPAA) promotes the application of the 3Rs principles (Replacement, Reduction and Refinement of animal testing) in meeting regulatory requirements for products such as pharma ...
(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 (Austria) *Finnish 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 on November 16, 2007. *Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergänzungsmethoden (ZEBET) (Germany), since 1989
Norecopa
is the Norwegian consensus platform for the replacement, reduction and refinement of animal experiments. It was founded on October 10, 2007. * Romanian Center for Alternative Test Methods (ROCAM) promotes the application of alternative methods in industry and their acceptance by regulators in Romania and also the development of new methods and approaches. ROCAM was established in June 2015 with the main goal to support and promote the 3Rs principles in Romania and regionally. * Dr Hadwen Trust (United Kingdom) *
Fund for the Replacement of Animals in Medical Experiments Fund for the Replacement of Animals in Medical Experiments (FRAME) is a charity based in Nottingham, UK. FRAME promotes consideration of the ethical and scientific issues involved in the use of laboratory animals for medical research, and the ...
(United Kingdom) * National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) (United Kingdom), since 2004


International

* International Cooperation on Alternative Test Methods (ICATM): On April 27, 2009, the United States, 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 The Organisation for Economic Co-operation and Development (OECD; french: Organisation de coopération et de développement économiques, ''OCDE'') is an intergovernmental organisation with 38 member countries, founded in 1961 to stimulate ...
(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.


See also

* Animal products in pharmaceuticals *
Canadian Centre for Alternatives to Animal Methods The Canadian Centre for Alternatives to Animal Methods (CCAAM) and its subsidiary, the Canadian Centre for the Validation of Alternative Methods (CaCVAM), is a research centre founded in 2017 and based at the University of Windsor, in Canada. Its ...
* Humane Research Trust * ''In vitro'' toxicology


References


External links


National Centre for the Replacement, Refinement and Reduction of Animals in Research

Alternatives to Animals: The Latest
Tracks news stories about scientific developments in alternatives to animal use
International Network for Humane Education

Johns Hopkins University Center for Alternatives to Animal TestingAlternatives Literature Searching
Animal Welfare Information Center, National Agricultural Library. Provides tips on searching bibliographic databases for animal use alternatives. Also has information on alternatives literature search training, including the worksho
Meeting the Information Requirements of the Animal Welfare Act

The Use of Databases, Information Centers and Guidelines When Planning Research that May Involve Animals
Animal Welfare Information Center Bulletin,
National Agricultural Library The United States National Agricultural Library (NAL) is one of the world's largest agricultural research libraries, and serves as a national library of the United States and as the library of the United States Department of Agriculture. Located ...
. Provides an overview of databases, bibliographies and guidelines that provide useful information on alternative methods when planning research that may involve animals. {{DEFAULTSORT:Alternatives To Animal Testing