Editing Animal testing (section)

==Research classification==
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===Pure research===
Basic or pure research investigates how organisms behave, develop, and function. Those opposed to animal testing object that pure research may have little or no practical purpose, but researchers argue that it forms the necessary basis for the development of applied research, rendering the distinction between pure and applied research—research that has a specific practical aim—unclear.<ref name=Lords3>[https://publications.parliament.uk/pa/ld200102/ldselect/ldanimal/150/15006.htm "Select Committee on Animals in Scientific Procedures Report"], House of Lords, 16 July 2002. See chapter 3: "The purpose and nature of animal experiments." Retrieved 6 July 2010.</ref> Pure research uses larger numbers and a greater variety of animals than applied research. Fruit flies, nematode worms, mice and rats together account for the vast majority, though small numbers of other species are used, ranging from [[California sea slug|sea slugs]] through to [[armadillo]]s.<ref name="ReferenceA">{{cite journal | author = Job CK | title = Nine-banded armadillo and leprosy research | journal = Indian Journal of Pathology & Microbiology | volume = 46 | issue = 4 | pages = 541–50 | year = 2003 | pmid = 15025339 }}</ref> Examples of the types of animals and experiments used in basic research include:
* Studies on ''[[embryogenesis]]'' and ''[[developmental biology]]''. Mutants are created by adding [[transposon]]s into their [[genome]]s, or specific genes are deleted by [[gene targeting]].<ref>{{cite journal |vauthors=Venken KJ, Bellen HJ | title = Emerging technologies for gene manipulation in Drosophila melanogaster | journal = Nature Reviews Genetics | volume = 6 | issue = 3 | pages = 167–78 | year = 2005 | pmid = 15738961 | doi = 10.1038/nrg1553 | s2cid = 21184903 }}</ref><ref>{{cite journal |vauthors=Sung YH, Song J, Lee HW | title = Functional genomics approach using mice | journal = Journal of Biochemistry and Molecular Biology | volume = 37 | issue = 1 | pages = 122–32 | year = 2004 | pmid = 14761310 | doi = 10.5483/BMBRep.2004.37.1.122 | doi-access = free }}</ref> By studying the changes in development these changes produce, scientists aim to understand both how organisms normally develop, and what can go wrong in this process. These studies are particularly powerful since the basic controls of development, such as the [[homeobox]] genes, have similar functions in organisms as diverse as fruit flies and man.<ref>{{cite journal |vauthors=Janies D, DeSalle R | title = Development, evolution, and corroboration | journal = The Anatomical Record | volume = 257 | issue = 1 | pages = 6–14 | year = 1999 | pmid = 10333399 | doi = 10.1002/(SICI)1097-0185(19990215)257:1<6::AID-AR4>3.0.CO;2-I | s2cid = 23492348 | doi-access = free }}</ref><ref>{{cite journal | author = Akam M | title = Hox genes and the evolution of diverse body plans | journal = Philosophical Transactions of the Royal Society B | volume = 349 | issue = 1329 | pages = 313–19 | year = 1995 | pmid = 8577843 | doi = 10.1098/rstb.1995.0119 | bibcode = 1995RSPTB.349..313A }}</ref>
* Experiments into ''behavior'', to understand how organisms detect and interact with each other and their environment, in which fruit flies, worms, mice, and rats are all widely used.<ref>{{cite journal |vauthors=Prasad BC, Reed RR | title = Chemosensation: Molecular mechanisms in worms and mammals | journal = Trends in Genetics | volume = 15 | issue = 4 | pages = 150–53 | year = 1999 | pmid = 10203825 | doi = 10.1016/S0168-9525(99)01695-9 }}</ref><ref>{{cite journal | author = Schafer WR | title = Neurophysiological methods in C. elegans: an introduction | journal = WormBook | pages = 1–4 | year = 2006 | pmid = 18050439 | pmc = 4780964 | doi = 10.1895/wormbook.1.113.1 }}</ref> Studies of brain function, such as memory and social behavior, often use rats and birds.<ref>{{cite journal |last1=Yamamuro |first1=Yutaka |title=Social behavior in laboratory rats: Applications for psycho-neuroethology studies |journal=Animal Science Journal |volume=77 |pages=386–94 |year=2006 |doi=10.1111/j.1740-0929.2006.00363.x |issue=4}}</ref><ref>Marler P., Slabbekoorn H, ''Nature's Music: The Science of Birdsong'', Academic Press, 2004. {{ISBN|0-12-473070-1}}{{page needed|date=December 2010}}</ref> For some species, behavioral research is combined with [[Behavioral enrichment|enrichment]] strategies for animals in captivity because it allows them to engage in a wider range of activities.<ref>For example "in addition to providing the chimpanzees with enrichment, the termite mound is also the focal point of a tool-use study being conducted", from the web page of the {{usurped|1=[https://web.archive.org/web/20080701010656/http://lpzoo.com/info/media-center/index.html Lincoln Park Zoo]}}. Retrieved 25 April 2007.</ref>
* Breeding experiments to study ''[[evolution]]'' and ''[[genetics]]''. Laboratory mice, flies, fish, and worms are [[Inbreeding|inbred]] through many generations to create strains with defined characteristics.<ref>[[Michael Festing|Festing, M.]], ''[http://www.informatics.jax.org/external/festing/mouse/INTRO.shtml "Inbred Strains of Mice and their Characteristics"],'' ''[[The Jackson Laboratory]] ''. Retrieved 30 January 2008.</ref> These provide animals of a known genetic background, an important tool for genetic analyses. Larger mammals are rarely bred specifically for such studies due to their slow rate of reproduction, though some scientists take advantage of [[Selective breeding|inbred domesticated animals]], such as dog or cattle breeds, for [[Comparative genomics|comparative]] purposes. Scientists studying how animals evolve use many animal species to see how variations in where and how an organism lives (their [[ecological niche|niche]]) produce [[adaptation]]s in their physiology and [[Comparative anatomy|morphology]]. As an example, [[stickleback]]s are now being used to study how many and which types of mutations are selected to produce adaptations in animals' morphology during the evolution of new species.<ref>{{cite journal | author = Peichel CL | title = Fishing for the secrets of vertebrate evolution in threespine sticklebacks | journal = Developmental Dynamics | volume = 234 | issue = 4 | pages = 815–23 | year = 2005 | pmid = 16252286 | doi = 10.1002/dvdy.20564 | doi-access = free }}</ref><ref>{{cite journal |vauthors=Peichel CL, Nereng KS, Ohgi KA, Cole BL, Colosimo PF, Buerkle CA, Schluter D, Kingsley DM | title = The genetic architecture of divergence between threespine stickleback species | journal = Nature | volume = 414 | issue = 6866 | pages = 901–05 | year = 2001 | pmid = 11780061 | doi = 10.1038/414901a | bibcode = 2001Natur.414..901P | s2cid = 4304296 | url = http://authors.fhcrc.org/42/1/Peichel_et_al_Nature_2001.pdf }}</ref>

===Applied research===
Applied research aims to solve specific and practical problems. These may involve the use of [[animal model]]s of diseases or conditions, which are often discovered or generated by pure research programmes. In turn, such applied studies may be an early stage in the [[drug discovery]] process. Examples include:
* [[Genetic modification]] of animals to study disease. [[Genetically modified animal|Transgenic animals]] have specific genes inserted, modified or removed, to mimic specific conditions such as [[single gene disorders]], such as [[Huntington's disease]].<ref>{{cite journal |vauthors=Ramaswamy S, McBride JL, Kordower JH | title = Animal models of Huntington's disease | journal = ILAR Journal | volume = 48 | issue = 4 | pages = 356–73 | year = 2007 | pmid = 17712222 | doi = 10.1093/ilar.48.4.356 | doi-access = free }}</ref> Other models mimic complex, multifactorial diseases with genetic components, such as [[Diabetes mellitus|diabetes]],<ref>{{cite journal |vauthors=Rees DA, Alcolado JC | title = Animal models of diabetes mellitus | journal = Diabetic Medicine | volume = 22 | issue = 4 | pages = 359–70 | year = 2005 | pmid = 15787657 | doi = 10.1111/j.1464-5491.2005.01499.x | doi-access = free }}</ref> or even transgenic mice that carry the same mutations that occur during the development of [[cancer]].<ref>{{cite journal |vauthors=Iwakuma T, Lozano G | title = Crippling p53 activities via knock-in mutations in mouse models | journal = Oncogene | volume = 26 | issue = 15 | pages = 2177–84 | year = 2007 | pmid = 17401426 | doi = 10.1038/sj.onc.1210278 | doi-access = free }}</ref> These models allow investigations on how and why the disease develops, as well as providing ways to develop and test new treatments.<ref>{{cite journal |vauthors=Frese KK, Tuveson DA | title = Maximizing mouse cancer models | journal = Nature Reviews Cancer | volume = 7 | issue = 9 | pages = 645–58 | year = 2007 | pmid = 17687385 | doi = 10.1038/nrc2192 | s2cid = 6490409 }}</ref> The vast majority of these transgenic models of human disease are lines of mice, the mammalian species in which genetic modification is most efficient.<ref name=Rosenthal/> Smaller numbers of other animals are also used, including rats, pigs, sheep, fish, birds, and amphibians.<ref name=HOStats/>
* Studies on models of naturally occurring disease and condition. Certain domestic and wild animals have a natural propensity or predisposition for certain conditions that are also found in humans. Cats are used as a model to develop immunodeficiency virus vaccines and to study [[leukemia]] because their natural predisposition to [[FIV]] and [[Feline leukemia virus]].<ref>{{cite journal | author = Dunham SP | title = Lessons from the cat: development of vaccines against lentiviruses | journal = Veterinary Immunology and Immunopathology | volume = 112 | issue = 1–2 | pages = 67–77 | year = 2006 | pmid = 16678276 | doi = 10.1016/j.vetimm.2006.03.013 }}</ref><ref>{{cite journal |vauthors=Vail DM, MacEwen EG | title = Spontaneously occurring tumors of companion animals as models for human cancer | journal = Cancer Investigation | volume = 18 | issue = 8 | pages = 781–92 | year = 2000 | pmid = 11107448 | doi = 10.3109/07357900009012210 | s2cid = 32489790 }}</ref> Certain breeds of dog experience [[narcolepsy]] making them the major model used to study the human condition. [[Armadillo]]s and humans are among only a few animal species that naturally have [[leprosy]]; as the bacteria responsible for this disease cannot yet be grown in culture, armadillos are the primary source of [[bacilli]] used in leprosy vaccines.<ref name="ReferenceA"/>
* Studies on induced animal models of human diseases. Here, an animal is treated so that it develops [[pathology]] and symptoms that resemble a human disease. Examples include restricting blood flow to the brain to induce [[stroke]], or giving [[neurotoxin]]s that cause damage similar to that seen in [[Parkinson's disease]].<ref name=Tolwani/> Much animal research into potential treatments for humans is wasted because it is poorly conducted and not evaluated through systematic reviews.<ref>{{cite journal | vauthors = Pound P, Ebrahim S, Sandercock P, Bracken MB, Roberts I | title = Where is the evidence that animal research benefits humans? | journal = BMJ | volume = 328 | issue = 7438 | pages = 514–47 | year = 2004 | pmid = 14988196 | pmc = 351856 | doi = 10.1136/bmj.328.7438.514 | others = Reviewing Animal Trials Systematically (RATS) Group }}</ref> For example, although such models are now widely used to study Parkinson's disease, the British anti-vivisection interest group [[British Union for the Abolition of Vivisection|BUAV]] argues that these models only superficially resemble the disease symptoms, without the same time course or cellular pathology.<ref>Langley, Gill (2006) [http://www.buav.org/downloads/pdf/BUAV_Report-Next_of_Kin.pdf ''next of kin...A report on the use of primates in experiments''] {{Webarchive|url=https://web.archive.org/web/20080227041454/http://www.buav.org/downloads/pdf/BUAV_Report-Next_of_Kin.pdf |date=27 February 2008 }}, BUAV.</ref> In contrast, scientists assessing the usefulness of [[animal models of Parkinson's disease]], as well as the medical research charity ''The Parkinson's Appeal'', state that these models were invaluable and that they led to improved surgical treatments such as [[pallidotomy]], new drug treatments such as [[levodopa]], and later [[deep brain stimulation]].<ref name=Emborg>{{cite journal | author = Emborg ME | title = Nonhuman primate models of Parkinson's disease | journal = ILAR Journal | volume = 48 | issue = 4 | pages = 339–55 | year = 2007 | pmid = 17712221 | doi = 10.1093/ilar.48.4.339 | doi-access = free }}</ref><ref name=Tolwani>{{cite journal |vauthors=Tolwani RJ, Jakowec MW, Petzinger GM, Green S, Waggie K | title = Experimental models of Parkinson's disease: insights from many models | journal = Laboratory Animal Science | volume = 49 | issue = 4 | pages = 363–71 | year = 1999 | pmid = 10480640 }}</ref><ref>[http://www.parkinsonsappeal.com/pdfs/The%20History%20of%20Deep%20Brain%20Stimulation.pdf The History of Deep Brain Stimulation] {{Webarchive|url=https://web.archive.org/web/20170331165911/http://www.parkinsonsappeal.com/pdfs/The%20History%20of%20Deep%20Brain%20Stimulation.pdf |date=31 March 2017 }}. parkinsonsappeal.com</ref>
* Animal testing has also included the use of [[placebo]] testing. In these cases animals are treated with a substance that produces no pharmacological effect, but is administered in order to determine any biological alterations due to the experience of a substance being administered, and the results are compared with those obtained with an active compound.

====Xenotransplantation====
{{Main|Xenotransplantation}}
[[Xenotransplantation]] research involves transplanting tissues or organs from one species to another, as a way to overcome the shortage of human organs for use in [[organ transplant]]s.<ref>{{cite journal |vauthors=Platt JL, Lin SS | title = The future promises of xenotransplantation | journal = Annals of the New York Academy of Sciences | volume = 862 | issue = 1 | pages = 5–18 | year = 1998 | pmid = 9928201 | doi = 10.1111/j.1749-6632.1998.tb09112.x | bibcode = 1998NYASA.862....5P | s2cid = 72941995 }}</ref> Current research involves using primates as the recipients of organs from pigs that have been genetically modified to reduce the primates' [[immune system|immune response]] against the pig tissue.<ref name=Schuurman>{{cite journal |vauthors=Schuurman HJ, Pierson RN | title = Progress towards clinical xenotransplantation | journal = Frontiers in Bioscience | volume = 13 | issue = 13 | pages = 204–20 | year = 2008 | pmid = 17981539 | doi = 10.2741/2671 | doi-access = free }}</ref> Although [[transplant rejection]] remains a problem,<ref name=Schuurman/> recent clinical trials that involved implanting pig insulin-secreting cells into diabetics did reduce these people's need for insulin.<ref>{{cite journal |vauthors=Valdés-González RA, Dorantes LM, Garibay GN, Bracho-Blanchet E, Mendez AJ, Dávila-Pérez R, Elliott RB, Terán L, White DJ | title = Xenotransplantation of porcine neonatal islets of Langerhans and Sertoli cells: a 4-year study | journal = European Journal of Endocrinology | volume = 153 | issue = 3 | pages = 419–27 | year = 2005 | pmid = 16131605 | doi = 10.1530/eje.1.01982 | doi-access = free }}</ref><ref>{{cite journal |vauthors=Valdés-González RA, White DJ, Dorantes LM, Terán L, Garibay-Nieto GN, Bracho-Blanchet E, Dávila-Pérez R, Evia-Viscarra L, Ormsby CE, Ayala-Sumuano JT, Silva-Torres ML, Ramírez-González B | title = Three-yr follow-up of a type 1 diabetes mellitus patient with an islet xenotransplant | journal = Clinical Transplantation | volume = 21 | issue = 3 | pages = 352–57 | year = 2007 | pmid = 17488384 | doi = 10.1111/j.1399-0012.2007.00648.x | s2cid = 22668776 }}</ref>

Documents released to the news media by the animal rights organization [[Uncaged Campaigns]] showed that, between 1994 and 2000, wild baboons imported to the UK from Africa by Imutran Ltd, a subsidiary of [[Novartis]] Pharma AG, in conjunction with Cambridge University and [[Huntingdon Life Sciences]], to be used in experiments that involved grafting pig tissues, had serious and sometimes fatal injuries. A scandal occurred when it was revealed that the company had communicated with the British government in an attempt to avoid regulation.<ref name=autogenerated2>Townsend, Mark (20 April 2003). [http://observer.guardian.co.uk/uk_news/story/0,6903,940033,00.html "Exposed: secrets of the animal organ lab"]  {{webarchive|url=https://web.archive.org/web/20080706041140/http://observer.guardian.co.uk/uk_news/story/0%2C6903%2C940033%2C00.html |date=6 July 2008 }}, ''The Guardian''.</ref><ref>Curtis, Polly (11 July 2003). [https://www.theguardian.com/education/2003/jul/11/research.highereducation "Home Office under renewed fire in animal rights row"], ''The Guardian''.</ref>

===Toxicology testing===
{{Main|Toxicology testing}}
{{Further|Draize test|LD50|Acute toxicity|Chronic toxicity|Genetically modified food controversies#Animal feeding studies}}

Toxicology testing, also known as safety testing, is conducted by pharmaceutical companies testing drugs, or by contract animal testing facilities, such as [[Huntingdon Life Sciences]], on behalf of a wide variety of customers.<ref name=BUAVHPT>[http://www.buav.org/pdf/HouseholdProductTests.pdf Household Product Tests] {{Webarchive|url=https://web.archive.org/web/20080227041444/http://www.buav.org/pdf/HouseholdProductTests.pdf |date=27 February 2008 }} [[BUAV]]</ref> According to 2005 EU figures, around one million animals are used every year in Europe in toxicology tests; which are about 10% of all procedures.<ref name=EU2005>{{usurped|1=[https://web.archive.org/web/20080216072132/http://ec.europa.eu/environment/chemicals/lab_animals/pdf/5th_stat_rep_lab_animals_en.pdf Fifth Report on the Statistics on the Number of Animals used for Experimental and other Scientific Purposes in the Member States of the European Union]}}, ''Commission of the European Communities'', published November 2007</ref> According to ''Nature'', 5,000 animals are used for each chemical being tested, with 12,000 needed to test pesticides.<ref name=Abbott>{{cite journal|author=Abbott A |title=Animal testing: More than a cosmetic change |journal=Nature |volume=438 |issue=7065 |pages=144–46 |year=2005 |pmid=16281001 |doi=10.1038/438144a |url=http://ethics.ucsd.edu/journal/2006/readings/Animal_Testing_More_than_a_cosmetic_change.pdf |bibcode=2005Natur.438..144A |s2cid=4422086 |archive-url=https://web.archive.org/web/20080227041442/http://ethics.ucsd.edu/journal/2006/readings/Animal_Testing_More_than_a_cosmetic_change.pdf |archive-date=27 February 2008 }}</ref> The tests are conducted without [[anesthesia]], because [[drug interaction|interactions between drugs]] can affect how animals [[xenobiotic metabolism|detoxify]] chemicals, and may interfere with the results.<ref>{{cite journal | author = Watkins JB | title = Exposure of rats to inhalational anesthetics alters the hepatobiliary clearance of cholephilic xenobiotics | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 250 | issue = 2 | pages = 421–27 | year = 1989 | pmid = 2760837 }}</ref><ref>{{cite journal |vauthors=Watt JA, Dickinson RG | title = The effect of diethyl ether, pentobarbitone and urethane anaesthesia on diflunisal conjugation and disposition in rats | journal = Xenobiotica | volume = 20 | issue = 3 | pages = 289–301 | year = 1990 | pmid = 2336839 | doi = 10.3109/00498259009046848 }}</ref>

Toxicology tests are used to examine finished products such as [[pesticide]]s, [[medication]]s, [[food additives]], packing materials, and [[air freshener]], or their chemical ingredients. Most tests involve testing ingredients rather than finished products, but according to [[BUAV]], manufacturers believe these tests overestimate the toxic effects of substances; they therefore repeat the tests using their finished products to obtain a less toxic label.<ref name=BUAVHPT/>

The substances are applied to the skin or dripped into the eyes; injected [[intravenous]]ly, [[intramuscular]]ly, or [[Subcutaneous injection|subcutaneous]]ly; inhaled either by placing a mask over the animals and restraining them, or by placing them in an inhalation chamber; or administered orally, through a tube into the stomach, or simply in the animal's food. Doses may be given once, repeated regularly for many months, or for the lifespan of the animal.<ref>{{cite web |title=Testing of chemicals – OECD |url=https://www.oecd.org/chemicalsafety/testing/ |access-date=2022-05-23 |website=www.oecd.org}}</ref>

There are several different types of [[acute toxicity]] tests. The {{LD50}} ("Lethal Dose 50%") test is used to evaluate the toxicity of a substance by determining the dose required to kill 50% of the test animal [[Statistical population|population]]. This test was removed from [[Organisation for Economic Co-operation and Development|OECD]] international guidelines in 2002, replaced by methods such as the [[Fixed Dose Procedure|fixed dose procedure]], which use fewer animals and cause less suffering.<ref>{{cite journal | author = Walum E | title = Acute oral toxicity | journal = Environmental Health Perspectives | volume = 106 | issue = Suppl 2 | pages = 497–503 | year = 1998 | pmid = 9599698 | pmc = 1533392 | doi = 10.2307/3433801 | jstor = 3433801 }}</ref><ref>{{usurped|1=[https://web.archive.org/web/20081119080934/http://hsus.org/animals_in_research/animals_in_research_news/intergovernmental_organization_eliminates_the_ld50_test.html Inter-Governmental Organization Eliminates the LD50 Test]}}, The Humane Society of the United States (2003-02-05)</ref> Abbott writes that, as of 2005, "the LD50 acute toxicity test ... still accounts for one-third of all animal [toxicity] tests worldwide".<ref name=Abbott/>

Irritancy can be measured using the [[Draize test]], where a test substance is applied to an animal's eyes or skin, usually an albino rabbit. For Draize eye testing, the test involves observing the effects of the substance at intervals and grading any damage or irritation, but the test should be halted and the animal killed if it shows "continuing signs of severe pain or distress".<ref>{{cite web|url=http://213.253.134.43/oecd/pdfs/browseit/9740501E.PDF |title=OECD guideline 405, Organisation for Economic Co-operation and Development |access-date=2015-04-06 |archive-url=https://web.archive.org/web/20080227041440/http://213.253.134.43/oecd/pdfs/browseit/9740501E.PDF |archive-date=27 February 2008 }}</ref> The [[Humane Society of the United States]] writes that the procedure can cause redness, ulceration, hemorrhaging, cloudiness, or even blindness.<ref>{{usurped|1=[https://web.archive.org/web/20090203060123/http://hsus.org/animals_in_research/species_used_in_research/rabbit.html Species Used in Research: Rabbit]}}, Humane Society of the United States</ref> [[Cruelty to animals|This test has also been criticized by scientists for being cruel]] and inaccurate, subjective, over-sensitive, and failing to reflect human exposures in the real world.<ref>{{cite journal | author = Wilhelmus KR | title = The Draize eye test | journal = Survey of Ophthalmology | volume = 45 | issue = 6 | pages = 493–515 | year = 2001 | pmid = 11425356 | doi = 10.1016/S0039-6257(01)00211-9 }}</ref> Although no accepted ''in vitro'' alternatives exist, a modified form of the Draize test called the ''low volume eye test'' may reduce suffering and provide more realistic results and this was adopted as the new standard in September 2009.<ref>{{cite journal |vauthors=Secchi A, Deligianni V | title = Ocular toxicology: the Draize eye test | journal = Current Opinion in Allergy and Clinical Immunology | volume = 6 | issue = 5 | pages = 367–72 | year = 2006 | pmid = 16954791 | doi = 10.1097/01.all.0000244798.26110.00 | s2cid = 24972694 }}</ref><ref name=Hadwen>{{usurped|1=[https://web.archive.org/web/20100327195524/http://www.drhadwentrust.org/news/rabbit-eye-test-replacement Draize rabbit eye test replacement milestone welcomed]}}. ''Dr Hadwen Trust'' (2009-09-21)</ref> However, the Draize test will still be used for substances that are not severe irritants.<ref name=Hadwen/>

The most stringent tests are reserved for drugs and foodstuffs. For these, a number of tests are performed, lasting less than a month (acute), one to three months (subchronic), and more than three months (chronic) to test general toxicity (damage to organs), eye and skin irritancy, [[mutagen]]icity, [[carcinogen]]icity, [[teratogen]]icity, and reproductive problems. The cost of the full complement of tests is several million dollars per substance and it may take three or four years to complete.

These toxicity tests provide, in the words of a 2006 [[United States National Academy of Sciences]] report, "critical information for assessing hazard and risk potential".<ref>[http://books.nap.edu/openbook.php?record_id=11523&page=R1 "Toxicity Testing for Assessment of Environmental Agents"] National Academies Press, (2006), p. 21.</ref> Animal tests may overestimate risk, with [[false positive]] results being a particular problem,<ref name=Abbott/><ref>{{cite journal | author = Hartung T | title = Toxicology for the twenty-first century | journal = Nature | volume = 460 | issue = 7252 | pages = 208–12 | year = 2009 | pmid = 19587762 | doi = 10.1038/460208a | bibcode = 2009Natur.460..208H | s2cid = 851143 }}</ref> but false positives appear not to be prohibitively common.<ref>{{cite web |url= http://protestitalia.wordpress.com/2013/12/09/where-is-the-toxicology-for-the-twenty-first-century/ |title= Where is the toxicology for the twenty-first century? |year= 2013 |publisher= Pro-Test Italia |access-date=30 January 2014}}</ref> Variability in results arises from using the effects of high doses of chemicals in small numbers of laboratory animals to try to predict the effects of low doses in large numbers of humans.<ref>{{cite journal | author = Smith LL | title = Key challenges for toxicologists in the 21st century | journal = Trends Pharmacol. Sci. | volume = 22 | issue = 6 | pages = 281–85 | year = 2001 | pmid = 11395155 | doi = 10.1016/S0165-6147(00)01714-4 }}</ref> Although relationships do exist, opinion is divided on how to use data on one species to predict the exact level of risk in another.<ref>{{cite journal |vauthors=Brown SL, Brett SM, Gough M, Rodricks JV, Tardiff RG, Turnbull D | title = Review of interspecies risk comparisons | journal = Regul. Toxicol. Pharmacol. | volume = 8 | issue = 2 | pages = 191–206 | year = 1988 | pmid = 3051142 | doi = 10.1016/0273-2300(88)90028-1 }}</ref>

Scientists face growing pressure to move away from using traditional animal toxicity tests to determine whether manufactured chemicals are safe.<ref name="Burden2015">{{cite journal
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| title = Testing Chemical Safety: What Is Needed to Ensure the Widespread Application of Non-animal Approaches?
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Among variety of approaches to toxicity evaluation the ones which have attracted increasing interests are in vitro cell-based sensing methods applying fluorescence.<ref name="Moczko2016">{{cite journal
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| pmc = 5031998
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| last1 = Moczko
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| title = Fluorescence-based assay as a new screening tool for toxic chemicals
| journal = Scientific Reports
| volume = 6
| pages = 33922
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| last3 = Cáceres
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| last4 = Gorban
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| doi = 10.1038/srep33922
| bibcode = 2016NatSR...633922M
}}</ref>

====Cosmetics testing====
{{Main|Testing cosmetics on animals}}
[[File:NoAnimalTesting.png|thumb|The "Leaping Bunny" logo: Some products in Europe that are not tested on animals carry this symbol.]]

Cosmetics testing on animals is particularly controversial. Such tests, which are still conducted in the U.S., involve general toxicity, eye and skin irritancy, [[phototoxic]]ity (toxicity triggered by [[ultraviolet]] light) and mutagenicity.<ref>Stephens, Martin & Rowan, Andrew. {{usurped|1=[https://web.archive.org/web/20080308163106/http://www.hsus.org/web-files/PDF/ARI/ARIS_An_Overview_Of_Animal_Testing_Issues.pdf An overview of Animal Testing Issues, Humane Society of the United States]}}</ref>

Cosmetics testing on animals is banned in India, the United Kingdom, the European Union,<ref>{{cite news|url=https://www.ceway.eu/cosmetics-animal-testing-eu/|title=Cosmetics animal testing in the EU|access-date=5 December 2018|archive-date=30 December 2020|archive-url=https://web.archive.org/web/20201230121610/https://www.ceway.eu/cosmetics-animal-testing-eu/|url-status=dead}}</ref> Israel and Norway<ref name="WorldPost">{{cite news|title=India Joins the EU and Israel in Surpassing the US in Cruelty-Free Cosmetics Testing Policy|url=http://www.huffingtonpost.com/monica-engebretson/cruelty-free-cosmetics-testing_b_3605460.html|date=16 March 2014|author =Engebretson, Monica|work=The World Post}}</ref><ref name="US Bill">{{cite press release|title=Cruelty Free International Applauds Congressman Jim Moran for Bill to End Cosmetics Testing on Animals in the United States |url=https://www.reuters.com/article/2014/03/05/bc-cfi-idUSnPnpHM6w1+98+PRN20140305 |date=5 March 2014 |archive-url=https://web.archive.org/web/20140318031816/https://www.reuters.com/article/2014/03/05/bc-cfi-idUSnPnpHM6w1%2B98%2BPRN20140305 |archive-date=18 March 2014 }}</ref> while legislation in the U.S. and Brazil is currently considering similar bans.<ref name="HSUS">{{cite press release|title=Animal Attraction: Federal Bill to End Cosmetics Testing on Animals Introduced in Congress |url=http://www.khou.com/community/blogs/animal-attraction/Animal-Attraction---249254631.html |date=10 March 2014 |author=Fox, Stacy |publisher=Humane Society of the United States |archive-url=https://web.archive.org/web/20140311022116/http://www.khou.com/community/blogs/animal-attraction/Animal-Attraction---249254631.html |archive-date=11 March 2014 }}</ref> In 2002, after 13 years of discussion, the European Union agreed to phase in a near-total ban on the sale of animal-tested cosmetics by 2009, and to ban all cosmetics-related animal testing. France, which is home to the world's largest cosmetics company, [[L'Oreal]], has protested the proposed ban by lodging a case at the [[European Court of Justice]] in [[Luxembourg]], asking that the ban be quashed.<ref name=Osborn/> The ban is also opposed by the European Federation for Cosmetics Ingredients, which represents 70 companies in Switzerland, Belgium, France, Germany, and Italy.<ref name=Osborn>Osborn, Andrew & Gentleman, Amelia.[https://www.theguardian.com/animalrights/story/0,11917,1021527,00.html "Secret French move to block animal-testing ban"], ''The Guardian'' (19 August 2003). Retrieved 27 February 2008.</ref> In October 2014, India passed stricter laws that also ban the importation of any cosmetic products that are tested on animals.<ref>{{cite news|url = http://timesofindia.indiatimes.com/india/India-bans-import-of-cosmetics-tested-on-animals/articleshow/44814398.cms|title = India bans import of cosmetics tested on animals|last = Mohan|first = Vishwa|date = 14 October 2014|work = The Times of India|access-date = 14 October 2014}}</ref>

===Drug testing===
Before the early 20th century, laws regulating drugs were lax. Currently, all new pharmaceuticals undergo rigorous animal testing before being licensed for human use. Tests on pharmaceutical products involve:
* ''metabolic tests'', investigating [[pharmacokinetics]]—how drugs are absorbed, [[Drug metabolism|metabolized]] and [[Excretion|excreted]] by the body when introduced [[wikt:oral|orally]], [[intravenous]]ly, intraperitoneally, [[intramuscular]]ly, or [[Transdermal patch|transdermally]].
* ''toxicology tests'', which gauge [[acute toxicity|acute]], sub-acute, and [[chronic toxicity]]. Acute toxicity is studied by using a rising dose until signs of toxicity become apparent. Current European legislation demands that "acute toxicity tests must be carried out in two or more mammalian species" covering "at least two different routes of administration".<ref name="32001L0083">{{CELEX|32001L0083|text=Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use}}, sub II. PERFORMANCE OF TESTS, A. Toxicity</ref>{{rp|1. Single dose toxicity}} Sub-acute toxicity is where the drug is given to the animals for four to six weeks in doses below the level at which it causes rapid poisoning, in order to discover if any toxic [[drug metabolism|drug metabolites]] build up over time. Testing for chronic toxicity can last up to two years and, in the European Union, is required to involve two species of mammals, one of which must be non-rodent.<ref name="32001L0083"/>{{rp|2. Repeated dose toxicity (sub-acute or chronic toxicity)}}
* ''efficacy studies'', which test whether experimental drugs work by inducing the appropriate illness in animals. The drug is then administered in a [[Randomized controlled trial|double-blind controlled trial]], which allows researchers to determine the effect of the drug and the [[Dose response|dose-response]] curve.
* Specific tests on ''reproductive function'', ''embryonic toxicity'', or ''carcinogenic potential'' can all be required by law, depending on the result of other studies and the type of drug being tested.

===Education===
It is estimated that 20 million animals are used annually for educational purposes in the United States including, classroom observational exercises, dissections and live-animal surgeries.<ref>{{cite journal|last1=Patronek|first1=G|last2=Rauch|first2=A|title=Systematic review of comparative studies examining alternatives to the harmful use of animals in biomedical education|journal=Journal of the American Veterinary Medical Association|date=1 January 2007|volume=230|issue=1|pages=37–43|doi=10.2460/javma.230.1.37|pmid=17199490}}</ref><ref>{{cite book|last1=Hart|first1=L|last2=Hart|first2=B|last3=Wood|first3=M|title=Why Dissection: Animal Use in Education|url=https://archive.org/details/whydissectionani0000hart|url-access=registration|date=2008|publisher=Greenwood Press|location=Westport|isbn=978-0-313-32390-4}}</ref> Frogs, [[fetal pigs]], perch, cats, earthworms, grasshoppers, crayfish and starfish are commonly used in classroom dissections.<ref>{{cite book|last1=Orlans|first1=Barbara|last2=Beauchamp|first2=Tom|author3-link=Rebecca Dresser|last3=Dresser|first3=Rebecca|last4=Morton|first4=David|last5=Gluck|first5=John|title=The Human Use of Animals|date=1998|publisher=Oxford University Press|isbn=978-0-19-511908-4|pages=[https://archive.org/details/humanuseofanimal0000unse/page/213 213]|url=https://archive.org/details/humanuseofanimal0000unse/page/213}}</ref> Alternatives to the use of animals in classroom dissections are widely used, with many U.S. States and school districts mandating students be offered the choice to not dissect.<ref>{{cite news|last1=Downey|first1=Maureen|title=Should students dissect animals or should schools move to virtual dissections?|url=http://www.ajc.com/weblogs/get-schooled/2013/jun/25/should-students-dissect-animals-or-should-schools-/|access-date=7 July 2015|work=The Atlanta Journal-Constitution|date=25 June 2013}}</ref> Citing the wide availability of alternatives and the decimation of local frog species, India banned dissections in 2014.<ref>{{cite news|last1=Pulla|first1=Priyanka|title=Dissections banned in Indian universities|url=https://www.science.org/content/article/dissections-banned-indian-universities|access-date=7 July 2015|agency=Science|date=6 August 2014}}</ref><ref>{{cite news|last1=Shine|first1=Nicole|title=The Battle Over High School Animal Dissection|url=https://psmag.com/environment/battle-high-school-animal-dissection-92391|work=Pacific Standard|access-date=7 July 2015}}</ref>

The Sonoran Arthropod Institute hosts an annual Invertebrates in Education and Conservation Conference to discuss the use of invertebrates in education.<ref>{{cite web |url=http://neurosci.arizona.edu/iecc |title=Invertebrates in Education and Conservation Conference &#124; Department of Neuroscience |publisher=Neurosci.arizona.edu |access-date=2015-04-06 |archive-date=15 December 2018 |archive-url=https://web.archive.org/web/20181215123040/http://neurosci.arizona.edu/iecc }}</ref> There also are efforts in many countries to find alternatives to using animals in education.<ref>{{cite web |last1=Dalal|first1=Rooshin |last2=Even|first2=Megha |last3=Sandusky|first3=Chad |last4=Barnard|first4=Neal |title=Replacement Alternatives in Education: Animal-Free Teaching |url=http://www.pcrm.org/research/animaltestalt/animaltesting/replacement-alternatives-in-education-animal-free |publisher=The Physicians Committee for Responsible Medicine |access-date=9 April 2015 |url-status=live |archive-url=https://web.archive.org/web/20140722162218/http://pcrm.org/research/animaltestalt/animaltesting/replacement-alternatives-in-education-animal-free |archive-date=22 July 2014 |format=Abstract from Fifth World Congress on Alternatives and Animal Use in the Life Sciences, Berlin |date=August 2005}}</ref> The NORINA database, maintained by Norecopa, lists products that may be used as alternatives or supplements to animal use in education, and in the training of personnel who work with animals.<ref>{{cite web|url=http://oslovet.norecopa.no/NORINA |title=The NORINA database of alternatives |publisher=Oslovet.norecopa.no |access-date=2015-04-06}}</ref> These include alternatives to dissection in schools. [[InterNICHE]] has a similar database and a loans system.<ref>{{cite web|url=http://www.interniche.org |title=Welcome |publisher=Interniche.org |access-date=2015-04-06}}</ref>

In November 2013, the U.S.-based company Backyard Brains released for sale to the public what they call the "Roboroach", an "electronic backpack" that can be attached to [[cockroach]]es. The operator is required to amputate a cockroach's [[Antenna (biology)|antennae]], use sandpaper to wear down the shell, insert a wire into the [[thorax]], and then glue the [[electrode]]s and [[Printed circuit board|circuit board]] onto the insect's back. A [[Mobile app|mobile phone app]] can then be used to control it via [[Bluetooth]].<ref name="BBC 09-11-13">{{cite news|url=https://www.bbc.co.uk/news/science-environment-24455141|title=Row over US mobile phone 'cockroach backpack' app|work=BBC News|date=9 November 2013|access-date=9 November 2013}}</ref> It has been suggested that the use of such a device may be a teaching aid that can promote interest in science. The makers of the "Roboroach" have been funded by the [[National Institute of Mental Health]] and state that the device is intended to encourage children to become interested in [[neuroscience]].<ref name="BBC 09-11-13" /><ref name="Time 01-11-13">{{cite magazine|url=https://newsfeed.time.com/2013/11/01/cyborg-cockroaches-are-coming-but-not-if-peta-has-anything-to-say-about-it/|title=Resistance is Futile: PETA Attempts to Halt the Sale of Remote-Controlled Cyborg Cockroaches|magazine=Time|date=1 November 2013|author =Hamilton, Anita|access-date=10 November 2013}}</ref>

===Defense===
Animals are used by the military to develop weapons, vaccines, battlefield surgical techniques, and defensive clothing.<ref name=Lords3/> For example, in 2008 the United States [[DARPA|Defense Advanced Research Projects Agency]] used live pigs to study the effects of [[improvised explosive device]] explosions on internal organs, especially the brain.<ref>Brook, Tom Vanden, "[https://www.usatoday.com/printedition/news/20090407/1apigs07_st.art.htm Brain Study, Animal Rights Collide]", ''[[USA Today]]'' (7 April 2009), p. 1.</ref>

In the US military, [[goat]]s are commonly used to train [[combat medic]]s. (Goats have become the main animal species used for this purpose after the Pentagon phased out using dogs for medical training in the 1980s.<ref name=kelly2013>{{cite news
|title=Who, What, Why: Does shooting goats save soldiers' lives?
|first=Jon|last=Kelly|periodical= BBC News Magazine|date=7 March 2013
|url=https://www.bbc.co.uk/news/magazine-21620521}}</ref>) While modern [[Mannequin#Medical education|mannequins]] used in medical training are quite efficient in simulating the behavior of a human body, some trainees feel that "the goat exercise provide[s] a sense of urgency that only real life trauma can provide".<ref>{{cite news|title=Military is required to justify using animals in medic training after pressure from activists|first=Ernesto|last=Londoño|date=24 February 2013|newspaper=The Washington Post|url=https://www.washingtonpost.com/world/national-security/military-is-required-to-justify-using-animals-in-medic-training-after-pressure-from-activists/2013/02/24/9b19e4ee-7d3e-11e2-82e8-61a46c2cde3d_story.html|url-status=live|archive-url=https://web.archive.org/web/20131215065035/http://articles.washingtonpost.com/2013-02-24/world/37276084_1_animal-activists-human-simulators-civilian-trauma|archive-date=15 December 2013}}</ref> Nevertheless, in 2014, the [[U.S. Coast Guard]] announced that it would reduce the number of animals it uses in its training exercises by half after [[PETA]] released video showing Guard members cutting off the limbs of unconscious goats with tree trimmers and inflicting other injuries with a shotgun, pistol, ax and a scalpel.<ref>{{cite news|last1=Vergakis|first1=Brock|title=Coast Guard reduces use of live animals in training|url=http://hamptonroads.com/2014/02/coast-guard-reduces-use-live-animals-training|access-date=7 July 2015|date=14 February 2014|archive-date=9 July 2015|archive-url=https://web.archive.org/web/20150709080350/http://hamptonroads.com/2014/02/coast-guard-reduces-use-live-animals-training|url-status=dead}}</ref> That same year, citing the availability of human simulators and other alternatives, the Department of Defense announced it would begin reducing the number of animals it uses in various training programs.<ref>{{cite news|last1=Bender|first1=Bryan|title=Military to curtail use of live animals in medical training|url=https://www.bostonglobe.com/news/nation/2014/11/11/pentagon-takes-major-steps-phase-out-use-live-animals-medical-training/2XOfgaevD80qsHs1A1SbNJ/story.html|access-date=7 July 2015|agency=Boston Globe|date=12 November 2014}}</ref> In 2013, several [[United States Navy|Navy]] medical centers stopped using ferrets in intubation exercises after complaints from [[PETA]].<ref>{{cite news|last1=Champaco|first1=Brent|title=PETA: Madigan Army Medical Center Has Stopped 'Cruel' Ferret-Testing|url=http://patch.com/washington/lakewood-jblm/peta-madigan-army-medical-center-has-stopped-ferrettesting|access-date=7 July 2015|agency=Patch|date=15 August 2013}}</ref>

Besides the United States, six out of 28 NATO countries, including Poland and Denmark, use live animals for combat medic training.<ref name=kelly2013/>