Editing Toxicology (section)

=== ''In vitro'' methods ===
While testing in animal models remains as a method of estimating human effects, there are both ethical and technical concerns with animal testing.<ref>{{cite web |date = 8 September 2011 | title = Existing Non-animal Alternatives | publisher = AltTox.org | url = http://alttox.org/ttrc/existing-alternatives/}}</ref>

Since the late 1950s, the field of toxicology has sought to reduce or eliminate animal testing under the rubric of "[[Three Rs (animal research)|Three Rs]]"&nbsp;– reduce the number of experiments with animals to the minimum necessary; refine experiments to cause less suffering, and replace ''in vivo'' experiments with other types, or use more simple forms of life when possible.<ref name=b1>{{cite web|url=https://www.toxicology.org/script/admin/toxtopics/114517_AM_TT3_InVitro_SOT.pdf|title=Alternative toxicity test methods: reducing, refining and replacing animal use for safety testing|publisher=Society of Toxicology|access-date=2014-12-05|archive-date=2016-03-04|archive-url=https://web.archive.org/web/20160304075550/https://www.toxicology.org/script/admin/toxtopics/114517_AM_TT3_InVitro_SOT.pdf|url-status=dead}}</ref><ref>Alan M. Goldberg. [http://altweb.jhsph.edu/altex/27_2/rPL7_Goldberg2.pdf The Principles of Humane Experimental Technique: Is It Relevant Today?] Altex 27, Special Issue 2010</ref> The historical development of alternative testing methods in toxicology has been published by Balls.<ref>{{Cite book |url=https://www.worldcat.org/oclc/1057893426 |title=The history of alternative test methods in toxicology |date=2019 | vauthors = Balls M, Combes RD, Worth AP |isbn=978-0-12-813698-0 |location=London |oclc=1057893426|publisher=Academic Press}}</ref>

Computer modeling is an example of an alternative [[in vitro toxicology]] testing method;  using computer models of chemicals and proteins, [[Structure–activity relationship|structure-activity relationships]] can be determined, and chemical structures that are likely to bind to, and interfere with, proteins with essential functions, can be identified.<ref name=c1>{{cite book | vauthors = van Leeuwen CJ, Vermeire TG |title= Risk assessment of chemicals: An introduction |publisher=Springer |location=New York |year=2007|pages=451–479 |isbn=978-1-4020-6102-8}}</ref>  This work requires expert knowledge in molecular modeling and statistics together with expert judgment in chemistry, biology and toxicology.<ref name=c1/>

In 2007 the American NGO [[National Academy of Sciences]] published a report called "Toxicity Testing in the 21st Century: A Vision and a Strategy" which opened with a statement: "Change often involves a pivotal event that builds on previous history and opens the door to a new era. Pivotal events in science include the discovery of penicillin, the elucidation of the DNA double helix, and the development of computers. ... Toxicity testing is approaching such a scientific pivot point. It is poised to take advantage of the revolutions in biology and biotechnology. Advances in toxicogenomics, bioinformatics, systems biology, epigenetics, and computational toxicology could transform toxicity testing from a system based on whole-animal testing to one founded primarily on in vitro methods that evaluate changes in biologic processes using cells, cell lines, or cellular components, preferably of human origin."<ref>{{cite book|last1=National Research Council|title=Toxicity Testing in the 21st Century: A Vision and a Strategy|date=2007|publisher=National Academies Press|isbn=978-0-309-15173-3|url=https://www.nap.edu/catalog/11970/toxicity-testing-in-the-21st-century-a-vision-and-a}}  [http://dels.nas.edu/resources/static-assets/materials-based-on-reports/reports-in-brief/Toxicity_Testing_final.pdf Lay summary] {{Webarchive|url=https://web.archive.org/web/20200215102924/http://dels.nas.edu/resources/static-assets/materials-based-on-reports/reports-in-brief/Toxicity_Testing_final.pdf |date=2020-02-15 }}</ref> As of 2014 that vision was still unrealized.<ref name=SocTox2014/><ref>{{cite journal | vauthors = Krewski D, Acosta D, Andersen M, Anderson H, Bailar JC, Boekelheide K, Brent R, Charnley G, Cheung VG, Green S, Kelsey KT, Kerkvliet NI, Li AA, McCray L, Meyer O, Patterson RD, Pennie W, Scala RA, Solomon GM, Stephens M, Yager J, Zeise L | title = Toxicity testing in the 21st century: a vision and a strategy | journal = Journal of Toxicology and Environmental Health Part B: Critical Reviews | volume = 13 | issue = 2–4 | pages = 51–138 | date = February 2010 | pmid = 20574894 | pmc = 4410863 | doi = 10.1080/10937404.2010.483176 | bibcode = 2010JTEHB..13...51K }}</ref>

The [[United States Environmental Protection Agency]] studied 1,065 chemical and drug substances in their ToxCast program (part of the [[CompTox Chemicals Dashboard]]) using ''in silica'' modelling and a human [[pluripotent]] [[stem cell]]-based assay to predict ''[[in vivo]]'' developmental intoxicants based on changes in cellular [[metabolism]] following chemical exposure. Major findings from the analysis of this ToxCast_STM dataset published in 2020 include: (1) 19% of 1065 chemicals yielded a prediction of [[developmental toxicity]], (2) assay performance reached 79%–82% accuracy with high specificity (>&nbsp;84%) but modest sensitivity (<&nbsp;67%) when compared with ''in vivo'' animal models of human prenatal developmental toxicity, (3) sensitivity improved as more stringent weights of evidence requirements were applied to the animal studies, and (4) statistical analysis of the most potent chemical hits on specific biochemical targets in ToxCast revealed positive and negative associations with the STM response, providing insights into the mechanistic underpinnings of the targeted endpoint and its biological domain.<ref>{{cite journal | vauthors = Zurlinden TJ, Saili KS, Rush N, Kothiya P, Judson RS, Houck KA, Hunter ES, Baker NC, Palmer JA, Thomas RS, Knudsen TB | title = Profiling the ToxCast Library With a Pluripotent Human (H9) Stem Cell Line-Based Biomarker Assay for Developmental Toxicity | journal = Toxicological Sciences | volume = 174 | issue = 2 | pages = 189–209 | date = April 2020 | pmid = 32073639 | pmc = 8527599 | doi = 10.1093/toxsci/kfaa014 }}</ref>

In some cases shifts away from animal studies have been mandated by law or regulation; the European Union (EU) prohibited use of animal testing for cosmetics in 2013.<ref>{{cite journal | vauthors = Adler S, Basketter D, Creton S, Pelkonen O, van Benthem J, Zuang V, Andersen KE, Angers-Loustau A, Aptula A, Bal-Price A, Benfenati E, Bernauer U, Bessems J, Bois FY, Boobis A, Brandon E, Bremer S, Broschard T, Casati S, Coecke S, Corvi R, Cronin M, Daston G, Dekant W, Felter S, Grignard E, Gundert-Remy U, Heinonen T, Kimber I, Kleinjans J, Komulainen H, Kreiling R, Kreysa J, Leite SB, Loizou G, Maxwell G, Mazzatorta P, Munn S, Pfuhler S, Phrakonkham P, Piersma A, Poth A, Prieto P, Repetto G, Rogiers V, Schoeters G, Schwarz M, Serafimova R, Tähti H, Testai E, van Delft J, van Loveren H, Vinken M, Worth A, Zaldivar JM | title = Alternative (non-animal) methods for cosmetics testing: current status and future prospects-2010 | journal = Archives of Toxicology | volume = 85 | issue = 5 | pages = 367–485 | date = May 2011 | pmid = 21533817 | doi = 10.1007/s00204-011-0693-2 | s2cid = 28569258 | doi-access = free | bibcode = 2011ArTox..85..367A }}</ref>