Editing Animal testing (section)

===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
| pmid = 26018957
| pmc = 4446337
| year = 2015
| last1 = Burden
| first1 = N
| title = Testing Chemical Safety: What Is Needed to Ensure the Widespread Application of Non-animal Approaches?
| journal = PLOS Biol
| volume = 13
| issue = 5
| pages =  e1002156
| last2 = Sewell
| first2 = F
| last3 = Chapman
| first3 = K
| doi = 10.1371/journal.pbio.1002156
| doi-access = free
}}</ref>
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
| pmid = 27653274
| pmc = 5031998
| year = 2016
| last1 = Moczko
| first1 = E
| title = Fluorescence-based assay as a new screening tool for toxic chemicals
| journal = Scientific Reports
| volume = 6
| pages = 33922
| last2 = Mirkes
| first2 = EM
| last3 = Cáceres
| first3 = C
| last4 = Gorban
| first4 = AN
| last5 = Piletsky
| first5 = S
| 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>