Indexabnormal behavior5, 7, 10, 15, 522524stereotypies7, 522abolishment of harmful animal use27academia79, 163, 244, 250, 265, 653Accreditation Council for Graduate Medical Education (acgme)556acgme.Accreditation Council for Graduate Medical Education (acgme)adhd.Attention Deficit Hyperactivity Disorder (adhd)administrative costs66, 248adrAdverse drug reactions (adrs)Advanced Trauma Life Support (atls)552, 555556Adverse drug reactions (adrs)125, 126, 257, 420, 421, 423, 427, 433adverse outcome367, 613, 615619, 626adverse outcome pathway (aop)30, 367, 590, 595, 596, 598, 615619, 627, 682advertising132134, 136, 137Agricultural Research Service (ars)129, 260, 261agriculture.animal agricultureair bubbles646Alcmaeon of Croton321Alliance of science and research organisations90Allianz der Wissenschaftsorganisationen90. Alliance of science and research organisationsAlternative.Replacementalternative approaches34, 35, 88, 109, 358, 365, 597, 683alternative methods3234, 93, 97, 103, 152, 155, 158, 183, 185, 196, 200, 202, 332, 341, 465, 568, 572578, 587588, 591595, 598, 600, 603, 604, 648, 653, 659, 660, 675, 676, 679, 680, 683development of34, 97, 100, 105, 160, 183, 196, 202, 341, 365, 578, 588, 601, 604, 675, 678validation of34, 88, 599, 676, 680Alzheimer Disease480500American College of Surgeons (acs)555, 556American opposition to animal use in research286amphibian367, 521, 661663analgesia1315, 246, 322, 333Anderson, E.309, 310anesthesia1315, 179, 217, 234, 246, 321, 322, 333, 453, 559anger294, 298animal agriculture90, 97, 109, 110, 112, 124, 129132, 135138, 160, 209, 231, 246, 250, 258259, 261, 265, 266, 282, 309, 313, 343, 446, 452, 554, 659animal agriculture industrial complex259animal agriculture research258259animal behavior15, 518538animal bioassays257animal ethics21, 219, 227, 236, 237, 456, 561, 570, 572Animal Ethics Committees (aecs)21, 227231, 234238, 561animal experimentation3, 88, 124, 152, 174, 194, 209, 224, 245, 276, 289, 305, 321, 341, 378, 392, 432, 460, 485, 532, 568, 595, 657, 675, 693animal free science29, 32, 33, 35, 37, 8896, 98102, 104, 105, 107, 108, 114, 127, 138, 158, 159, 161, 173, 200, 204, 216, 227, 233, 236, 237, 342, 365, 369, 417, 419, 425430, 433, 527, 561, 578, 587, 650, 660, 663, 666, 682684animal health3, 155, 168, 174, 195, 259, 290, 322animal laboratory22, 231, 551561animal law168, 170, 290292animal method109, 157, 158, 431, 645, 650, 680animal modeldevalidation95failure23, 26, 73, 248, 401407limitations204, 324325, 620, 621refinement(Chapter 1)338shortcomings278, 677, 682, 683animal protection80, 96, 155159, 173, 178, 184, 291, 299animal protection law8, 9, 181, 183, 292, 297, 553. animal lawanimal protection organization159, 292, 552, 594, 604, 663animal research3, 73, 89, 124, 151, 169, 203, 209, 234, 244, 275, 289, 305, 321, 341, 378, 392, 425, 443, 480, 553, 568, 605, 657, 675, 691animal research community3, 37, 175, 225, 673animal research industry265.biomedical industrial complexAnimal Research Reporting In Vivo Experiments (arrive) guidelines17, 21, 329331, 379animal rights66, 89, 90, 113, 153, 178182, 198, 199, 201, 225, 281, 308, 392, 579animal safety test417, 423, 428, 432, 433, 676, 678Animals Scientific Procedures Act (aspa)520animal testing11, 32, 33, 35, 9196, 101, 103, 104, 109, 110, 113, 115, 124, 127, 152, 156159, 183, 202, 216218, 245, 246, 257, 258, 295, 297299, 307, 325, 341, 342, 365, 368369, 392, 405, 417433, 465, 486, 487, 570, 587606, 620, 621, 641654, 656, 657, 659, 660, 663, 665668, 675, 676, 678683Animals usein applied research4, 30, 33, 113, 152, 245, 529, 681682in basic research343, 358, 487in education and training138, 568animal welfare5, 20, 27, 37, 113, 132, 152, 158, 173, 198, 225, 237, 262, 283284, 333, 452, 520523Animal Welfare Act (awa)124, 209, 217, 246, 258, 264, 265, 282284, 660, 661animal welfare law93, 94, 227. animal law; Animal Welfare Actanthropomorphism295antibiotic(s)128131, 139, 259, 261, 262, 424antibiotic resistance128129, 131, 139, 259, 261, 262antibodies16, 71, 111, 366, 396, 419, 451, 489, 490, 665antivivisectionismepistemic198ethical198scientific199aop.adverse outcome pathway (aop)ape179, 381, 400, 525, 529, 530, 535, 536, 538applied research4, 30, 33, 90, 107, 111113, 152, 245, 529, 681682aquatic124, 130, 666ars.Agricultural Research Service (ars)aspa.Animals Scientific Procedures Act (aspa)aspirin108, 255, 257, 344, 359363, 423, 621, 678assumption of human-animal similarity249atls.Advanced Trauma Life Support (atls)Attention Deficit Hyperactivity Disorder (adhd)380385Australia137, 183, 225240, 493author guidelines331awa.Animal Welfare Act (awa)awareness11, 15, 26, 29, 30, 132, 137, 140, 161, 225, 227, 278, 322, 330, 344, 368, 369, 386, 480, 551, 560, 568, 569, 571, 572, 577, 651, 662, 667, 679balance of interests175, 177, 178, 180Balls, M.13, 37, 178, 422, 449, 456, 465, 593, 659, 662, 666ban on patenting animals93barren cages5, 523basal ganglia376, 523Basel Declaration197, 226basic science24, 30, 35, 36, 71, 75, 79, 8991, 111, 112, 114, 115, 184, 194, 202, 251, 277, 278, 280, 281, 284, 285, 341343, 357, 358, 386, 392, 405, 450, 481, 483485, 487, 491, 492, 499, 500, 529, 595, 596, 603605, 630, 676BB3R.Berlin-Brandenburg research platform (BB3R)behavior511, 13, 15, 19, 67, 91, 107, 126, 134, 138, 169, 194, 196, 239, 276, 280, 285, 293, 325, 376, 385, 394, 396, 398, 399, 457, 484, 485, 487, 518538, 587, 613, 644, 662, 691abnormal5, 7, 10, 15, 521523stereotypies, stereotypic79, 455, 521behavior adaptation293, 376, 521behavioral research276, 280, 285, 518538behaviorism519Bennett, B.T.196, 657, 658, 664, 668Bentham, J.213, 322Berlin-Brandenburg research platform (BB3R)98, 99Bernard, Claude199, 614, 693best practice331, 617BfR.Bundesinstitut für Riskobewertung (BfR)bia1024, 74, 419bias1621, 25, 26, 29, 133, 161, 178, 235, 252254, 258, 263, 276, 277, 284, 323, 326331, 356, 357, 379, 385, 421, 447, 494, 496, 530, 621, 681. publication biasbiochip426, 622biological(s)10, 22, 30, 35, 75, 90, 91, 101, 103, 107, 111, 112, 184, 199, 201, 202, 216, 245, 264, 278, 322325, 328, 330, 334, 341, 358, 377, 394, 395, 398, 430, 444, 451, 461, 485, 553, 572, 587, 595, 598, 612618, 621, 623628, 643, 646, 647, 649, 681biological products35, 90, 111, 112, 184, 341, 430biomarkers92, 425, 491, 492, 628630BioMed2130biomedical industrial complex (bic)247248biomedical industrial eco-system244biomedical knowledge277biomedical research11, 16, 20, 2834, 6581, 99, 140, 154, 161, 170, 197, 199, 202, 226, 237, 238, 245248, 251, 252, 258, 266, 275, 278, 285, 286, 306, 314, 376386, 392, 421, 431, 444, 461, 462, 518, 529, 531, 534, 538, 660, 661, 678. biomedical scienceBiomedical Research for the 21st Century (BioMed21) Collaboration30. BioMed21biomedical science33, 34, 36, 66, 72, 328, 401, 575bioscience sector155, 160biotransformation620, 643bird209, 217, 246, 343, 367, 521, 523, 538, 660, 662black box warning420, 620blinding18, 212, 263, 276, 326, 327, 329, 408, 433, 692bmbf.Bundesministerium fur Bildung und Forschung (bmbf); German Federal Ministry of Education and Researchbody on a chip622, 628. human on a chip, disease on a chip, lab on a chip, organ on a chipBovine Corneal Opacity and Permeability assay (bcop)663, 666bovine spongiform encephalopathy (bse)260, 261Braithwaite, V.521, 662Brazil398, 567579Brazilian Network for Humane Education578breeding7, 12, 22, 71, 97, 130, 195, 229, 247, 264, 333, 341, 343, 369, 443, 446, 453454, 483, 499, 529, 533538, 575, 576, 662, 676British Union for the Abolition of Vivisection (buav)322. Cruelty Free Internationalbuav.British Union for the Abolition of Vivisection (buav); Cruelty Free InternationalBundesinstitut für Riskobewertung (BfR)34, 90, 97, 100. Federal Institute for risk assessmentBundesministerium für Bildung und Forschung (bmbf)31, 32, 35, 98101, 104, 108Burch, R.L.3, 4, 18, 29, 36, 171, 172, 196, 364, 577, 656659, 664, 668business ethics209, 214, 218220by-pass protein effect260caat.Center for Alternatives to Animal Testing (caat)cadaver321, 555, 558, 573575camarades.Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (camarades)Cambridge Declaration on Consciousness29campaigning136, 151164, 198, 314, 322, 342, 365, 367369, 421, 667Canada133, 175, 333, 334, 369, 420, 556, 561, 651cancer7, 24, 67, 71, 72, 79, 125127, 135, 160, 176, 245, 249, 251, 253, 254, 257, 276, 277, 343, 357, 362, 378, 392, 401, 419, 423, 424, 447452, 454, 455, 459, 460, 462465, 480, 482, 497, 590, 596, 615cancer gene panel277captive welfare8captivity5, 811, 499, 518538, 664carcinogenicity research135, 257, 324, 365, 392care4, 73, 97, 126, 154, 168, 197, 217, 227, 246, 279, 294, 307, 333, 342, 386, 419, 445, 482, 535, 555, 605, 627, 641, 664, 693culture ofculture of carecarnivore521cat257, 281, 283286, 343, 357, 363, 367, 381, 423, 519, 552, 555, 556, 575cell16, 75, 91, 194, 216, 234, 245, 278, 357, 377, 398, 419, 444, 485, 573, 588, 612, 641, 658, 679cell culture92, 106, 107, 245, 462, 573, 588, 596, 606, 615, 621, 626, 629, 641644, 646649, 659, 664, 665, 679cell lineage646Center for Alternatives to Animal Testing (caat)93, 103, 104, 651, 657, 659Center for Open Science20Center for Responsible Science (crs)430Centrum für Ersatzmethoden zum Tierversuch (cerst-nrw)98, 99cephalopod97, 228, 294, 575, 660, 664, 676cerst-nrw.Centrum für Ersatzmethoden zum Tierversuch (cerst-nrw)check-off program136chemotherapy277chest tube insertion555chicken130, 260, 265, 424, 451, 660, 662664, 666chimpanzee248, 249, 255, 285, 286, 323, 324, 381, 399, 400, 403, 461, 525, 526, 529536, 538China160, 453, 495chronic disease125129, 131, 133, 138, 480citation analysis379381Citizen’s Initiative161163, 169, 170, 194class action96classical conditioning519classification27, 156, 175, 176, 195, 220, 234, 297, 301, 394, 402, 575, 598, 599, 657clinical decision making559clinical research26, 75, 79, 216, 251, 257, 334, 362, 376, 377, 425, 491, 500clinical sciencenon-translatable255, 256clinical testing245, 431, 651clinical trial16, 17, 1921, 23, 24, 26, 35, 72, 74, 75, 200, 203, 215, 235, 245, 248, 252258, 278, 307, 328329, 332, 358, 366, 367, 378, 379, 392, 405, 407, 419422, 424, 426, 429, 430, 449, 451, 459, 465, 486489, 492, 495, 498, 570, 596, 619, 620, 644, 645, 651Clustered Regularly Interspaced Short Palindromic Repeats (crispr)31, 444451, 453, 456458, 460, 463465, 612, 613co-culture103, 623, 627, 628cognition5, 29, 194, 203, 258, 280, 293, 311, 314, 325, 420, 458, 461, 481, 484, 485, 487, 491496, 518, 521, 523, 525, 527, 529533, 536, 538, 557, 559, 569, 573, 693cognition research521, 527cognitive abilities518, 521, 529cognitive dissonance311, 314, 569Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (camarades)26, 277, 424Collins, F.17, 28, 251, 278, 424, 426, 570commodification135137, 259, 261, 264, 309communication34, 80, 101, 105, 162, 170, 197, 226, 228, 229, 231234, 300, 376, 385, 396, 428, 432, 484, 522, 529, 556, 557, 559, 560, 575, 576, 622, 628, 642comparative cognition521, 529, 531533comparative studies462compassion1113, 131, 204, 212216, 285, 286, 298, 568complexity science69, 391, 393, 400complex systems69, 70, 72, 251, 277, 393400, 403, 405408, 683compromise7, 8, 157, 199, 249, 254, 291, 293, 325, 427, 492, 494, 524, 534, 538, 649, 675computational modelling196, 200, 266, 307, 400, 401, 425, 426, 527, 605, 613615, 625, 644, 652, 679computer model196, 200, 266, 307, 400, 401, 425, 426, 527, 605, 644, 652, 679Concordat on Openness on Animal Research226, 232confidentiality, confidential231, 235, 292, 368confinement10, 129, 201, 499. husbandryconfirmatory science249Consolidated Standards of Reporting Trials (consort)17, 328, 329consort.Consolidated Standards of Reporting Trials (consort)contextualism298cosmetics32, 89, 93, 102, 103, 109, 115, 156159, 183, 185, 202, 212, 218, 245, 246, 365367, 369, 433, 587, 591, 592, 594, 601, 604, 641, 647, 650, 667, 678, 680testing89, 183, 212, 365, 369, 591, 601, 604, 678Cosmetics Directive156, 157, 159, 183. eu Cosmetics Directive 76/768/eecCosmetics Regulation.eu Cosmetics Directive 76/768/eecCosmetic Toiletry and Fragrance Association (ctfa)103costeconomic646, 650of failed clinical trials257cost-benefit analysis198, 236237, 282. harm-benefit-analysis (hba)Cottee, Y.662Council of Europe3, 168, 172, 176, 177cow130, 259261, 263, 265, 451, 452, 660, 661, 664cannibalism261crab664cricothyroidotomy555, 558Crisis Resource Management (crm), xxiicrispr.Clustered Regularly Interspaced Short Palindromic Repeats (crispr)critical appraisal of animal studies2428critical thinking69, 7981, 427critique of animal experiments194204. political critiquecrm.Crisis Resource Management (crm)crops130, 131, 136, 137, 139crosstalk644crs.Center for Responsible Science (crs)Cruelty Free International212, 292, 322, 358, 457, 594, 603Cruelty to Animals Act152, 171, 322crustacean664ctfa.Cosmetic Toiletry and Fragrance Association (ctfa)culture of care4, 1113Czech Republic154dairy128, 130, 132138, 259, 260, 452, 495darpa.Defense Advanced Research Projects Agency (darpa)Darwin, C.77, 244, 280, 377, 532data publication95decline on ethical grounds104De Denktank Aanfullende financierung alternatieven voor dierproeven110Defense Advanced Research Projects Agency (darpa)103, 109, 643, 644, 647deliberate practice558, 560democracy224, 291, 300Denmark236, 290, 601Department of Defense (DoD)246, 552, 554. us Department of Defensedepression5, 9, 10, 129, 217, 364, 459, 520, 615deprivation8, 217, 297, 519, 522, 523Descartes, R.77, 321desensitization312, 569Deutsche Forschungsgemeinschaft (dfg)90, 98, 108, 194, 196198Deutsches Tierschutzgesetz.German Animal Welfare ActDevelopmental toxicology107dfg.Deutsche Forschungsgemeinschaft (dfg)diabetes9, 24, 125127, 245, 255, 276, 331, 357, 378, 452, 455, 459, 495, 496Diagnostic peritoneal lavage555differentiation24, 622, 628Directive 76/768/eec.eu Cosmetics Directive 76/768/eecDirective 86/609/eec88, 152155, 158, 159, 173, 591, 603Directive 2010/63/eu3, 8, 10, 11, 27, 34, 35, 37, 8897, 102, 109, 115, 152, 154156, 160162, 170173, 175, 179, 181, 182, 233, 234, 236, 239, 282, 289291, 295, 299, 300, 334, 335, 364, 417, 529, 560, 591, 605, 656, 660, 662665, 668, 676Article 3697, 180Article 4994, 97, 113Article 5593, 179, 529discovery research202disease on a chip,body on a chip.human on a chip, lab on a chip, organ on a chipdisparity134, 177, 613disposition22, 179, 296, 309, 310distress4, 9, 13, 14, 18, 22, 26, 28, 37, 9395, 175, 179, 182, 194196, 198, 227, 234, 237, 246, 294, 298, 306, 308, 314, 333, 454, 455, 520, 521, 554, 658, 664, 676diversity139, 298, 456DoD.Department of Defense (DoD); us Department of DefenseDoerenkamp-Zbinden Chair of in-vitro Toxicology and Biomedicine/Alternatives to Animal98, 99dog14, 163, 245, 257, 281, 283286, 297, 343, 357, 358, 362, 363, 365, 368, 378, 379, 381, 401, 419, 422, 423, 452453, 456, 483, 499, 519, 520, 552, 554556, 568, 574, 575, 590, 604, 659double muscled beef cattle263Draize eye irritation test368, 663drugattrition in clinical trials258development24, 29, 31, 68, 79, 258, 391, 403, 406408, 457, 481, 483, 485491, 499, 500, 596, 619623, 630, 645, 677, 678, 682discovery28, 253, 256, 266, 432, 498, 596, 619, 625, 645, 649, 650, 681Dutch Ministry of Economic Affairs110easy care sheep264265ec 1907/2006157. reach Regulationeceae.European Coalition to End Animal Experiments (eceae)echa.European Chemicals Agency (echa)ecological relevance526economic(s)101, 108, 110, 114, 135, 151, 170, 177, 183, 218, 264, 265, 294, 315, 367, 398, 399, 407, 500, 521, 530, 577, 589, 616, 620, 646, 650, 651, 663, 680, 684economic benefits651ecvam.European Centre for the Validation of Alternative Methods (ecvam)education and training11, 21, 29, 3334, 36, 90, 111, 112, 138, 140, 184, 322, 568, 569, 571, 572, 576578.trainingeffectiveness18, 19, 21, 23, 27, 32, 67, 73, 88, 89, 124, 125, 127, 129, 132, 133, 140, 153155, 162, 164, 170, 173, 176, 177, 180, 184, 185, 204, 215, 225, 235, 254256, 265, 279, 307, 308, 314, 322325, 330, 335, 357, 391, 405, 406, 417420, 422424, 429431, 457, 465, 482, 486, 487, 492, 553, 556, 558, 560, 568, 619, 651, 679efficacy16, 3032, 34, 35, 73, 74, 92, 109, 124, 245, 246, 255, 256, 275286, 322, 324, 327, 328, 332, 334, 335, 342, 358, 391, 392, 407, 418, 421, 423, 424, 430, 459, 461, 486488, 500, 555, 587, 588, 596, 597, 619, 621electrodes280, 281, 457, 520embryos106, 363, 379, 445, 446, 449, 453, 454, 458, 462, 591, 621, 656, 661663, 666, 667, 676emotion11, 13, 67, 80, 129, 289, 294301, 560, 569, 691, 693empathy12, 280, 286, 294, 295, 298, 310, 558, 569emst.Early Management of Severe Trauma (emst)endpointexperimental182humane13, 18less-inhumane13enrichment.environmental enrichmententrepreneurship652environment5, 72, 94, 127, 151, 171, 195, 211, 228, 244, 278, 290, 306, 325, 359, 392, 418, 518, 558, 568, 587, 614, 641, 663, 682environmental enrichment5, 6, 8, 325, 331, 334Environmental Protection Agency (epa)94, 102, 103, 246, 429environmental refinement5, 79. environmental enrichmentepa.Environmental Protection Agency (epa)epaa.European Partnership for Alternative Approaches to Animal Testing (epaa)epistemic injustice296epistemology194204, 305, 307, 309, 310, 315problems202equity investment650Estonia290ethicalconflict290consensus285, 290evaluation178, 291review228, 232, 282, 289, 292295, 301, 310, 329, 332, 602, 605Ethical Consumer Research Association32, 667Ethical Principles for Medical Research Involving Human Subjects197. Helsinki Declarationethics12, 21, 22, 36, 139, 183, 194204, 209, 214, 218220, 227229, 236, 237, 275286, 290, 292295, 299, 323, 324, 329, 330, 403, 430, 480500, 531534, 537, 561, 569, 570, 572, 578, 595. animal ethicsethology194, 518, 520521, 524, 526528, 530, 536eu Cosmetics Directive 76/768/eec183eu Cosmetics Product Regulation (ec) No 1223/2009157Eurobarometer292Europe3, 92, 102104, 109, 125, 172, 176, 177, 183, 185, 202, 239, 260, 322, 588, 591, 593, 594, 596, 599601, 603, 604European animal welfare and animal protection laws290.Directive 86/609/eec, Directive 2010/63/euEuropean Centre for the Validation of Alternative Methods (ecvam)33, 91, 94, 104, 105, 152, 156, 157, 593, 598, 600, 659, 665, 666, 680European Chemicals Agency (echa)159, 365, 623European Citizen’s Initiative169European Coalition to End Animal Experiments (eceae)154, 158, 368European Commission (ec)4, 11, 12, 21, 27, 32, 33, 88, 93, 94, 102, 105, 113115, 125, 153157, 159, 161163, 168170, 173, 183, 185, 202, 322, 341, 365, 378, 420, 591, 593, 594, 599, 601, 602, 604, 661, 676European Commission department Directorate-General for Environment94European Convention on Human Rights177European Directive on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes.Directive 86/609/eecEuropean Directive on the protection of animals used for scientific purposes (Directive 2010/63/eu)3, 8, 10, 11, 27, 34, 35, 37, 8898, 102, 109, 115, 151, 152, 154156, 160162, 170173, 175, 179, 181, 182, 233, 234, 236, 239, 282, 289291, 295, 299, 300, 334, 335, 364, 417, 529, 560, 591, 605, 656, 660, 662665, 668, 676European Ombudsman159, 162European Parliament4, 8, 14, 15, 27, 31, 32, 88, 93, 95, 97, 109, 113, 152, 155159, 161, 170, 171, 173, 175, 176, 179, 181183, 233, 236, 282, 289291, 297, 334, 364, 417, 418, 529, 560, 575, 591, 600, 603, 605, 656, 660, 662, 664, 668, 676European Partnership for Alternative Approaches to Animal Testing (epaa)109, 159European Union, Europe (eu)3, 10, 88, 92, 102104, 109, 125, 137, 151, 152, 160, 169, 172, 176, 177, 183, 185, 202, 224, 226, 232235, 239, 246, 260, 282, 289, 322, 341, 417, 443, 526, 529, 560, 588, 591, 593, 594, 596, 599601, 603, 604, 656, 659, 665, 675European Union Reference Laboratory for Alternatives to Animal Testing (eurl-ecvam)33, 91, 94, 104, 105, 152, 156, 157, 659, 665, 666European Union Seventh Framework Programme91eu-ToxRisk91, 101, 102, 106, 107, 432evaluation committee289292, 301evidence-based medicine25, 276evolution29, 69, 70, 72, 77, 79, 106, 151, 152, 172, 174, 184, 199, 219, 220, 249, 260, 263, 277, 280, 285, 322, 376, 391394, 399400, 403, 406, 407, 429, 432, 433, 456, 460, 461, 464, 518, 521, 528, 567579, 681, 684, 692, 693Excellence in Editorial Mandatory Policies for Animal Research (exemplar) Scale330, 331experimental animal26, 37, 110, 244, 278, 281, 284, 404, 432expertise76, 79, 80, 95, 110, 159, 163, 203, 263, 282, 290292, 295, 602, 621, 622eyes30, 105, 212, 280, 365, 368, 396, 431, 433, 455, 589, 656, 660, 663, 666, 678680factory farm128131, 259, 262, 265, 309factory farm-acology262failed clinical trial256, 257fallibilism298false negative200, 257, 325, 401, 402, 423, 424, 487drug toxicity257false positive19, 20, 200, 256, 257, 325, 401, 402, 404, 423, 424, 487animal model success256257drug toxicity257Farm Animal Welfare Committee662farming.animal agriculturefast-food132, 134fat128, 135, 259, 260, 262, 263, 452, 495fbs.fetal bovine serum (fbs)fcs.fetal calf serum (fcs)fda.Food and Drug Administration (fda)fdama.Food and Drug Administration Modernization Act of 1997 (fdama)Federal Institute for Risk Assessment34. Bundesinstitut für Riskobewertung (BfR)feed efficiency259, 262fetal bovine serum (fbs)92, 664, 665fetal calf serum (fcs)664, 665fialuridine419, 426fish130, 171, 209, 228, 246, 281, 343, 367, 446, 521, 529, 538, 659, 661663embryo toxicity (fet) test663, 666farms130five pillar-program90, 113Fleming, A.363, 424flow stress642foi.Freedom of Information (foi)Food and Drug Administration (fda)19, 29, 73, 94, 102, 125, 139, 246, 254258, 343, 418, 420, 427, 429431, 486489, 619Food and Drug Administration Modernization Act of 1997 (fdama)19, 20food deprivation519food service132, 134frame.Fund for the Replacement of Animals in Medical Experiments (frame)France89, 101, 154, 343, 419Fraunhofer Institute for Systems and Innovation Research100Freedom of Information (foi)229232, 421, 553free-living293, 518, 520523, 527fruit, plants, vegetables128, 135137, 497Fund for the Replacement of Animals in Medical Experiments (frame)358, 659funding17, 21, 23, 28, 3033, 35, 36, 66, 73, 76, 78, 80, 81, 9192, 97104, 109, 110, 113, 114, 126, 127, 129, 133134, 136, 137, 152, 155, 159, 160, 162, 164, 183, 226, 237, 238, 244247, 249, 258, 261, 262, 265, 266, 277279, 282, 285, 328, 330332, 358, 365, 385, 386, 425, 429, 465, 481, 491, 497499, 527, 578, 592, 595, 601603, 605, 606, 647, 651, 659, 667, 678redeployment of3536gas-liquid interface647gavage9, 325gene23, 77, 102, 194, 263, 266, 277, 278, 357, 377, 397, 399, 400, 403, 405, 444453, 455, 457463, 465, 483485, 590, 591, 613, 622, 626, 629, 682gene-pharming194general principle of animal welfare173, 174general public67, 73, 76, 78, 105, 531, 660, 675genetically modified animals (gm animals)16, 197, 333, 341, 343, 369, 443465, 483genetic selection259, 262264genomics135, 200, 249, 367, 398, 447449German Animal Welfare Act96, 97, 171, 175, 176, 181German Centre for the Protection of Laboratory Animals (Bf3R)32, 97, 98German Federal Ministry of Education and Research,Bundesministerium für Bildung und Forschung (bmbf)Germany3, 12, 31, 8992, 95, 97102, 104, 106109, 113, 154, 289, 291, 292, 294, 295, 343, 530, 553, 570, 601, 651, 679Glivec423gm animals.genetically modified animals (gm animals)goat258, 451, 552, 555, 664Goldberg, A.3, 103, 172, 179, 657gold standard140, 199, 401, 402, 418, 427, 593, 649, 677Gold Standard Publication Checklist (gspc)17, 21, 329government31, 33, 35, 78, 81, 89, 103, 113, 126, 132, 134, 136, 137, 154, 175, 177, 182184, 211, 226, 229, 231, 232, 234, 235, 237, 238, 244247, 250, 251, 258, 259, 264266, 301, 417, 418, 420, 425, 426, 429, 431, 433, 554, 557, 570, 571, 575, 578, 595, 604, 605, 650, 653, 659, 662, 667, 668, 678Greek, J.69, 72, 78, 124, 176, 277, 393, 403, 405Greek physicians321Greek, R.29, 35, 6581, 124, 127, 176, 178, 199, 204, 236, 321, 323, 391408, 518greenhouse gas130, 131, 138, 139gspc.Gold Standard Publication Checklist (gspc)Habermas, J.312handling9, 12, 13, 18, 195, 293, 325, 331, 499, 569, 643hand-rear523Hansen, L.A.69, 72, 78, 275286, 392, 393, 677harking19, 21harm-benefit-analysis (hba)95, 175, 290, 291, 334, 463harmonization290, 292, 407, 429, 560561, 594, 599, 600, 616, 619harm(s), animal176, 283, 578, 692unnecessary197unjustified37harm(s), human257, 310Hartung, T.20, 23, 30, 96, 101, 200, 216, 324, 325, 332, 363, 366, 423, 427, 433, 593, 615, 620, 621, 650, 675684hazard assessment114hba.harm-benefit-analysis (hba)hci.high content imaging (hci)hcs.high content screening (hcs)health3, 66, 91, 124, 158, 168, 195, 213, 226, 245, 275, 290, 306, 321, 357, 380, 392, 418, 455, 482, 523, 553, 588, 615, 644heart disease79, 125127, 357, 423, 482, 497, 596Helsinki Declaration181, 183, 197. Ethical Principles for Medical Research Involving Human Subjectshierarchy of the 3Rs36, 171174, 184high content imaging (hci)613high content screening (hcs)612, 613, 615high throughput screening (hts)426, 615, 621, 644646, 649, 650, 661hips.Helmholtz Institute for Pharmaceutical Research Saarland (hips)hipsc.human induced pluripotent stem cells (hipsc)history65, 66, 68, 7779, 110, 151, 152, 172, 184, 194, 196201, 210, 219, 221, 254, 277, 278, 285, 309, 315, 363, 376, 378, 393, 423, 428, 497, 519, 528, 554, 555, 557, 558, 568, 570576, 593, 598, 644, 646650, 676, 692Home Office153, 176, 226, 233, 234, 236, 237, 333, 341, 343, 365, 366, 443, 454, 486, 521, 526, 659, 661, 662homeostasis574, 614, 615, 617, 646Honneth, A.306, 309311Horizon 202091, 101horse343, 433, 556, 664horseshoe crab664. crabhousehold products93, 342, 343, 366, 604House of Lords154, 160housing.confinement; husbandryhts.high throughput screening (hts)human3, 65, 92, 124, 151, 168, 194, 209, 225, 245, 275, 290, 305, 321, 341, 376, 391, 417, 443, 480, 518, 551, 568, 587, 612, 641, 657, 676, 691human behavior518, 520, 522human biology-based model28human clinical trial16, 17, 20, 35, 203, 215, 254, 255, 258, 328329, 358, 367, 379, 405, 407, 420, 430, 620humane education367, 567579Humane Research Australia225, 227, 228, 235, 240human healthcare23, 323, 324, 380human induced pluripotent stem cells (hipsc)612, 627, 628, 649human on a chip model103, 105, 107, 366.body on a chip, disease on a chip, lab on-a chip, organ on a chiphuman patient simulator553human primary cells612, 642, 649human-relevant, andmethod341, 358, 367, 433, 481model35, 342, 460, 498, 668science, xxxtest430husbandry411, 18, 22, 237, 264, 329, 523, 535, 661, 662iacucs.Institutional Animal Care and Use Committees (iacucs)iata.Integrated Approaches to Testing and Assessment (iata)iatro-epidemics257ic50646iccvam.Interagency Coordinating Committee on the Validation of Alternative Methods (iccvam)ich.International Council on Harmonisation (ich)inconsistency22, 81, 174, 231, 298, 324, 356, 357, 363, 494, 620, 664incubators649India160, 171, 181183, 212, 366, 422, 495, 554, 555, 561indispensability6, 20, 175, 176, 291, 292individual differences377, 525in dubio pro animale174induced pluripotent stem cells366, 462, 612, 628, 649industrial farming129inequity aversion in mammals293inhalation toxicology106inhumanity3, 4, 196InnoSysTox101innovation index for replacement methods112Innovative Systems Toxicology for Alternative to Animal Testing.InnoSysToxin silico32, 196, 216, 266, 366, 367, 377378, 382, 383, 425, 588, 590, 591, 596, 612630, 650, 679, 681, 683Institutional Animal Care and Use Committees (iacucs)73, 282284, 286instrumentalism279instrumentalization312Integrated Approaches to Testing and Assessment (iata)92integrity65, 177182, 184, 297, 299, 301, 333, 557, 623intention109, 160, 169, 201, 215, 216, 226, 247, 259, 262, 275, 296, 297, 308, 310, 322, 329, 344, 393, 429, 537, 571, 691Interagency Coordinating Committee on the Validation of Alternative Methods (iccvam)94, 266, 431, 593, 663, 666, 680International Council on Harmonisation (ich)430, 594interpretation18, 25, 26, 65, 170, 172, 174, 184, 199, 210212, 228, 291, 365, 492, 613intrinsic value181, 297, 311, 314, 332invasive37, 131, 245, 321, 322, 331, 333, 334, 386, 454, 519521, 527, 528, 534, 552, 554, 572, 597, 691invertebrate155, 403, 575, 656, 659, 661, 664, 667in vitro16, 24, 32, 34, 74, 91, 92, 98, 99, 101, 103, 106, 107, 196, 216, 234, 266, 362, 365367, 377, 382, 383, 419, 423, 425, 426, 429, 430, 432, 450, 463, 573, 588591, 595599, 612630, 641647, 651, 652, 656, 658, 661, 663666, 668, 679, 681, 683in vivo1618, 34, 91, 196, 234, 329, 331, 362, 379, 425, 426, 450, 462, 588, 590, 612, 615, 620622, 624628Ipsos mori225, 233, 418irreproducibility16, 18, 249252, 256, 448isolated chicken eye (ice) test663, 666isolated rabbit eye (ire) test663Israel101, 175, 183, 212, 366Italy154Jenni, K.309Jennings, M.161, 453, 457, 661, 662Kant, I.309Keesler Air Force Base554killing14, 15, 18, 27, 153, 182, 198, 200, 201, 203, 215, 244, 249, 279, 283, 297, 306, 313, 359, 420, 453, 568, 588, 662, 663Klausner, R.254Koëter, H.110Kuhn, T.602, 684, 692labelling598, 599lab on a chip590, 596, 598. body on a chip, disease on a chip, human on a chip, organ on a chiplaboratory4, 66, 89, 125, 152, 169, 196, 209, 227, 245, 282, 293, 305, 321, 341, 427, 445, 483, 518, 551, 574, 593, 643, 656, 677, 692animal.experimental animalanimal research communityanimal research communityanimal science4, 11, 72, 95, 113, 308, 311, 454animal science community4, 11animal welfare282, 286, 521524. welfarebehavioral experiment524, 531behavioral research519520, 528enrichment.environmental enrichmentenvironment518, 519, 522524, 526, 528housing333, 522. confinement; husbandrynoise9, 306, 307, 522, 523stress294stressor523technicians308, 311, 314Lackland Air Force Base553, 554Langley, G.2830, 36, 74, 424, 485, 486, 587, 596, 617, 682lasting harm28, 182, 237, 520, 521law3, 810, 12, 15, 19, 20, 33, 76, 89, 9397, 136, 152, 155, 157, 159, 162, 168, 170173, 175, 177185, 195, 199, 211, 216217, 220, 226, 227, 229, 231, 232, 245, 253, 258, 266, 282, 284286, 289294, 297, 299301, 313, 365, 399, 417, 443, 464, 527, 529, 536, 553, 569571, 577, 578, 594, 603, 643, 664, 693ld50594learned helplessness9, 10, 520legislation3, 4, 29, 34, 78, 134, 154162, 172, 183, 202, 227, 234, 265, 285, 290, 322, 343, 365, 368, 421, 552, 568, 576, 591, 594, 598599, 603, 656, 657, 660662, 664, 675676, 678legislative change35, 365likelihood ratio422limitation6, 14, 23, 26, 27, 3133, 74, 75, 96, 104, 128, 155, 160, 161, 172, 179, 180, 199, 200, 202204, 211, 216, 220, 234, 236, 249, 257, 266, 275, 282, 283, 285, 286, 295, 308, 310312, 314, 324325, 331, 335, 356, 357, 364, 368, 377, 396, 429, 448, 452, 453, 457459, 461, 486, 487, 492, 494, 500, 529, 557, 569, 579, 598, 605, 615, 620622, 624627, 642, 657, 664, 668, 676, 677, 679, 681, 686, 692limulus amoebocyte lysate (lal) assay664limulus polyphemus664literature reviewstructured14, 15systematicsystematic review)liver toxicity612630live tissue training (ltt)552553, 560lock-in427lorcainide422L’Oréal592low clearance compounds646ltt.live tissue training (ltt)Lukács, G.310lung model106Lush Cosmetics667Lush Prize32, 667, 668Lyons, D.152, 153macaque8, 280, 359, 381, 453, 457, 520, 530mad.Mutual Acceptance of Data (mad)Mad Cow Disease259, 265Madigan Health System553, 554magnetic resonance imaging (mri)279Major Depressive Disorder (mdd)380, 381, 383385mammal15, 71, 293, 377, 392, 400, 403, 423, 613, 656, 659662manikin563marc.Meat Animal Research Center (marc)marketing68, 73, 89, 90, 101, 125, 132, 133, 136139, 160, 183, 185, 212, 215, 217, 245, 256258, 262, 263, 291, 359, 363, 365, 366, 394, 402, 407, 420, 430, 456, 619621, 645647, 650, 651, 653, 654, 676, 678Marks, J.36, 660, 666master plan for an end to animal experiments90maternal separation523maximum tolerated dose325mbm.meat and bone meal (mbm)mdd.Major Depressive Disorder (mdd)meat126, 128, 130132, 134138, 259263, 309, 451, 452, 495meat and bone meal (mbm)260, 261Meat Animal Research Center (marc)261265Medical Council of India554medical education552, 556, 560, 571, 572medical research3, 15, 16, 28, 31, 38, 72, 111, 179, 181, 197, 214, 215, 226, 281, 306, 329, 330, 341, 342, 379, 384, 393, 403, 458, 481, 595, 641medical simulation559, 560medical training138139, 552557, 560, 561, 574medication15, 26, 124127, 131, 138, 139, 486, 557medicine23, 68, 89, 127, 184, 194, 235, 244, 276, 292, 322, 341, 385, 391, 417, 446, 486, 553, 572, 594, 613, 682, 692mega farm130memory278, 481, 484, 485, 519, 521, 530Menache, A.69, 78, 127, 178, 403meta-analysis25, 26, 277, 279, 323, 379, 424, 494, 496metabolic signaling642metazoan endoparasite658methodological quality26, 200, 325331, 335Mexico, xxiiimice.mousemicrodosing426, 429, 597microelectronics643microfluidics103, 216, 622, 627, 628, 647, 648microfluidic systems627, 628micro-liver426microphysiological system (mps)31, 103, 641, 643644, 679microtiter plate642, 644military247, 306, 313, 314, 551554, 559, 560, 570miniaturized reproductive tract.repro-on-a-chipmini pig365, 659. pigmoney32, 35, 67, 73, 76, 80, 81, 101, 108, 132, 136, 137, 158, 244266, 276, 279, 285, 293, 429, 497, 500, 667money waste244266monitoring8, 13, 15, 18, 20, 89, 90, 9395, 112, 114, 115, 228, 234, 238, 246, 301, 308, 456, 521, 572, 578, 589monkey93, 247, 257, 281, 358, 362, 363, 378, 381, 399, 419, 422, 452453, 456459, 461, 499, 520, 523, 529, 530, 553, 588, 597, 604, 691, 692moral agency306, 309314moral doubt289301moral injury305315moral status200, 209221, 280, 308, 309, 311, 314, 315moral taboo313morbidity279, 307morphology69, 393, 523, 622, 642mortality77, 264, 279, 307, 455, 487, 491, 496, 664mouse69, 13, 14, 2224, 27, 29, 67, 72, 107, 124, 209, 217, 244249, 251, 254258, 266, 277, 278, 281, 284, 326, 343, 357359, 362, 363, 365, 378, 381, 384, 397, 399, 400, 405, 406, 419, 422, 427, 444448, 452456, 460462, 465, 480, 483485, 487, 499, 521, 524, 573, 577, 588, 590, 591, 596, 599, 659661, 666, 682mps.microphysiological system (mps)mri.magnetic resonance imaging (mri)multi-chamber plates643multidisciplinary cooperation112Multilateral Collaboration in Computational Neuroscience101multiple sclerosis324, 330, 419, 459murine local lymph node assay (llna)596, 599, 666mus381, 660Mutual Acceptance of Data (mad)599myostatin gene263nann.National Association of Neonatal Nurses (nann)narrative review323nas.National Academy of Sciences (nas)National Academy of Sciences (nas)595National Anti-Vivisection Society (navs)33, 246, 251, 322National Association of Neonatal Nurses (nann)555National Center for Computational Toxicology102National Centre for the Replacement, Refinement & Reduction of Animals in Research (nc3Rs)32, 33, 35National competency centers93, 94National Institute of Public Health and Environmental Protection (rivm)110National Institutes of Health (nih)28, 31, 66, 67, 73, 91, 102, 109, 136, 245, 246, 248, 251253, 262, 275, 278, 285, 358, 367, 419, 424, 426, 429, 497, 498, 530, 647National Toxicology Program at the National Institute of Environmental Health Sciences (niehs)102, 246nato.North Atlantic Treaty Organization (nato)natural behavior10, 518520, 522524, 527, 528Naval Medical Center Portsmouth554navs.National Anti-Vivisection Society (navs)NCad.Netherlands National Committee for the protection of animals used for scientific purposes (NCad)necrosis642negative results27, 200, 252, 325, 332, 423Netherlands26, 35, 89, 101, 109114, 179, 290, 341, 433Netherlands National Committee for the protection of animals used for scientific purposes (NCad)35, 89, 90, 96, 109115, 184, 341, 433neurological disease324, 461new drug pipeline245, 254, 487new variant Creutzfeldt-Jakob disease (nvCJD)259, 261ngo.non-governmental organization (ngo)nhp.non-human primate (nhp)nih.National Institutes of Health (nih)noise9, 19, 306, 307, 522, 523non-animal method.animal free sciencenon-animal model.animal free sciencenon-animal research approach266non-animal technology.animal free sciencenon-animal test.animal free sciencenon-governmental organization (ngo)31, 67, 301, 657, 668non-human primate (nhp)8, 14, 27, 93, 152, 160, 178, 179, 183, 229, 234, 239, 255, 281, 326, 343, 357, 358, 365, 378, 400, 424, 453, 456, 457, 483, 519, 529531, 538, 552, 659, 691non-invasive278, 331, 518, 520, 528, 529, 531, 597non-technical skills560Non-technical Summaries (nts)233236, 239, 526North Atlantic Treaty Organization (nato)553, 560Norway10, 33, 366Norwegian Animal Research Authority553ntss.Non-technical Summaries (ntss)numbers of animals used6, 88, 128, 527, 656, 657nutrition36, 127, 132136, 138140, 259, 452, 494nvCJD.new variant Creutzfeldt-Jakob disease (nvCJD)obesity9, 24, 125127, 133, 134, 419, 496objectification309, 569oecd.Organisation for Economic Co-operation and Development (oecd)ombudsman159, 162omics107, 612615, 626, 6286301R197, 667, 668opioid126opportunity cost244, 307organ9, 91, 92, 101103, 105107, 109, 115, 138, 194, 196, 199, 216, 324, 332, 343, 364, 366, 367, 377, 419, 425, 426, 428, 451, 459, 462, 493, 555, 596, 613, 615, 617, 622, 624, 627, 641654, 658, 660, 662, 667, 679, 681, 683Organisation for Economic Co-operation and Development (oecd)92, 159, 367, 407, 589591, 593596, 600, 601, 616, 617, 624, 663, 666, 680, 682organoid24, 91, 106, 462, 622, 642, 643, 646, 684organ on a chip92, 101, 102, 106, 115, 138, 216, 366, 426, 596, 641653.body on a chip, disease on a chip, human on a chip, lab on a chiporgans in a plate643, 645, 649outcome assessment329overhead66, 247, 248, 266pain1216, 18, 22, 28, 37, 9397, 154, 174, 175, 179, 182, 196199, 203, 209, 213, 225, 227, 228, 232, 234, 236, 237, 239, 245, 246, 275, 278283, 285, 286, 294, 297, 306, 307, 333, 362, 419, 420, 423, 444, 447, 452454, 459, 464, 499, 520, 521, 528, 554, 569, 571, 590, 622, 658, 659, 661, 662, 664, 665, 676, 693pals.Pediatric Advanced Life Support (pals)paradigm change34, 35, 89, 90, 95, 109110, 112, 113, 151, 159, 162164, 169, 170, 172, 182184, 200, 201, 209, 239, 284286, 289, 291, 295, 300, 315, 335, 342, 367, 369, 393, 432, 551, 568, 570, 579, 595, 606, 629, 651654, 657, 667, 693paradigm shift.paradigm changepatent(s)93, 106, 245, 247, 257, 647, 678patient(s)animal315, 574human24, 28, 305, 307, 324, 333, 334, 408, 430, 433, 553, 557559expectations38safety368, 433, 560pcrm.Physicians Committee for Responsible Medicine (pcrm)Pediatric Advanced Life Support (pals)555peer review17, 21, 65, 70, 7681, 249, 253, 260, 261, 427, 491, 650Penicillin257, 344, 359364, 424People for Animal Rights Germany–The Federal Association against Vivisection90, 113People for the Ethical Treatment of Animals (peta)32, 159, 368, 552, 553, 555, 556, 663, 666perfusion642, 646pericardiocentesis555peristaltic pump648personalized medicine68, 79, 127, 138, 140, 277, 278, 391, 403, 408, 613, 628Persson, T.153, 155peta.People for the Ethical Treatment of Animals (peta)p-hacking19pharmaceutical12, 19, 23, 29, 30, 73, 92, 94, 98, 99, 103, 138, 139, 160, 215, 224, 244247, 254, 256, 258, 266, 291, 306, 325, 342, 358, 364, 407, 422, 423, 426, 429, 430, 432, 433, 456, 460, 486, 487, 491, 492, 554, 619, 620, 623, 644, 645, 647, 650, 677pharmaceutical industry73, 92, 139, 244, 254, 256, 358, 423, 487, 619, 620, 644, 647, 677Pharmaceutical Research and Manufacturers of America23, 215, 487pharmacodynamics614, 615, 625, 627pharmacokinetics366, 392, 614, 615, 620, 624, 627pharmacology72, 283, 486, 518, 554, 561, 574, 625Pharmacy Council of India554phase-out35, 89, 90, 101, 110115, 172, 183, 185, 341, 433, 527Philippines175physicalactivity129, 133, 493, 494, 497examination558suffering307Physicians Committee for Responsible Medicine (pcrm)135, 136, 368, 553556Physiologically Based Pharmaco-Kinetic (pbpk) models366, 624, 625pig8, 14, 71, 130, 169, 257260, 262, 343, 357, 362, 363, 368, 381, 451, 452, 459, 521, 552, 554, 555, 569, 590, 602, 661pigeon519, 520plant124140, 174, 217, 260, 418, 464, 497, 658plant based124140, 497plausibility97, 289301pluralism579pneumatic103, 648Polish Ministry of National Defense553political critique of animal experiments194204politics, political31, 35, 37, 67, 104, 110, 114, 115, 134, 151164, 169171, 194196, 203204, 218, 285, 293295, 300, 309, 315, 342, 365, 369, 570, 579, 594, 595, 600, 601, 604606poll225, 233, 418, 482Portugal290pragmatism297, 298precautionary principle173, 174, 403preclinicalanimal test421426biomedical experiments248research35, 90, 111, 245, 246, 251, 254, 256, 385, 406, 500science, non-repeatable249, 256testing111, 256, 258, 422, 423, 425, 430, 486, 487trials20, 21, 385Preclinical Trials20, 21predator519, 521, 523predictive value23, 28, 6874, 76, 78, 79, 178, 391, 393, 394, 399408, 417, 427, 492predictivity8, 68, 95, 127, 178, 199, 230, 249, 277, 296, 323, 342, 377, 391, 417, 447, 484, 536, 587, 613, 641, 676preregistrationanimal studies20clinical studies20, 235236preclinical studies20, 235236prescription drugs124126, 139, 140Principles of Humane Experimental Technique3, 196, 364, 657The Principles of Humane Experimental Technique3, 196, 364, 657production efficiency259, 261264, 266professionalism104, 153, 198, 201203, 220, 227, 283, 284, 297, 313, 332, 433, 556, 557, 559, 561, 569, 572, 575, 578, 691professorships for animal-free research methods92project evaluation21, 27, 95, 97, 156proportionality test174178protein135, 259261, 277, 444, 451, 461, 484, 485, 490492, 575, 590, 596, 623proteomics200psychological constructs518psychological suffering519. sufferingpublication bias18, 19, 21, 26, 252254, 276, 357public health16, 36, 110, 126, 128, 133, 134, 158, 247, 282, 322, 324, 334, 429, 430public opinion73, 153, 154, 162, 239, 240, 281, 365, 378, 392puzzle box519pyrogenicity101, 602, 603, 664, 680qsp.quantitative systems pharmacology (qsp)quality management95quantitative systems pharmacology (qsp)625rabbit7, 14, 212, 247, 257, 343, 357, 358, 363, 364, 368, 381, 422, 424, 452, 483, 588591, 594, 598, 599, 602, 603, 660, 663, 664rabbit pyrogen test664randomization17, 18, 26, 276, 326328, 380, 381, 405, 493, 495, 558rat5, 8, 1014, 22, 27, 71, 124, 209, 217, 246, 257, 281, 284, 293, 294, 297, 298, 326, 343, 357, 358, 362364, 381, 406, 419, 422424, 427, 464, 483, 519, 521, 523, 589591, 660, 666, 677rat embryotoxicity assay666rat skin transcutaneous electrical resistance (ter) test666reach.Registration, Evaluation, Authorisation and Restriction of Chemicals (reach)reach Regulation433read-across93, 590, 591, 623, 624, 681recognition28, 67, 108, 158, 181, 280, 296297, 306, 310, 332, 342, 369, 573, 599recording chambers521rede de desenvolvimento humano (RedEH)578, 579RedEH.Brazilian Network for Humane Education; rede de desenvolvimento humano (RedEH)red meat production efficiency262reduction3, 72, 89, 124, 158, 168, 196, 218, 227, 265, 279, 290, 315, 327, 342, 396, 430, 456, 493, 551, 558, 577, 588, 612, 657refinement andexperimental3, 1322of experimental design, conduct and reporting1622, 33housing5, 910R of ultima ratio4reform proposal171180registered reports21Registration, Evaluation, Authorisation and Restriction of Chemicals (reach)157, 365, 433, 677Regulation433Rego, L.4, 31, 152, 168, 443Regulation (ec) No 1223/2009157Regulation (ec) No 1907/2006157, 592. reachregulatory acceptance32, 96, 266, 589591, 593595, 599, 600, 649, 666regulatory approval28, 266, 604, 650, 651regulatory bodies21, 22, 407, 593, 594, 603, 620, 644, 663, 666, 667regulatory preclinical research35, 111regulatory testingsafety testing112, 246, 341, 418, 427, 588toxicity testing363, 659reificationof animals311, 314of humans305315relative replacement658, 661reliability8, 24, 25, 94, 307, 325, 327, 330332, 335, 524, 595, 601, 625Renaissance321rendering66, 68, 80, 177, 182, 199, 211, 212, 260, 299, 400, 443, 444, 451, 485, 619Rennes, France419replacement338, 8891, 93, 96100, 102105, 108, 109, 111113, 151, 152, 154160, 169174, 178, 183185, 196, 227, 228, 233, 239, 290, 291, 330, 332, 342, 358, 364, 366, 367, 369, 377, 418, 430, 432, 433, 457, 481, 490, 494, 500, 519, 527, 551, 555, 557, 568572, 574, 575, 577579, 587589, 592, 596, 599602, 605, 649652, 656668, 676, 678, 679, 681. alternativereplicability6, 8, 524. alternativereportingbias18, 20, 21, 26, 235, 326, 356selective18, 20, 235, 421reproducibility crisis16, 424, 677, 680, 682, 684reproductive toxicology107repro-on-a-chip107reptile217, 661, 662researchbudget100, 136, 261competition291confirmatory19discoverydiscovery research)exploratory19flaws and shortcomings20, 21non-publishable252254quality379scientific rigor)research assessment exercise328Research Initiative R2N–Replace and Reduce98responsibility10, 11, 15, 25, 3537, 88, 94, 113, 114, 135, 136, 182, 185, 211, 224, 227, 229, 232, 233, 238, 265, 279, 311, 324, 365, 368, 378, 420, 423, 430, 456, 464, 481, 484, 523, 553, 576, 603rethink168185, 659retrospective assessment21, 2728, 95, 156, 233235, 368, 676return on investment (roi)239, 247, 266, 358review process65, 76, 77, 289301, 427Rice, M.J.69, 72, 78, 127, 393, 398, 403, 404, 406Rijksinstituut voor Volksgezondheid en Milieu Netherlands (rivm)110risk assessment30, 34, 97, 100, 101, 112, 114, 431, 432, 616, 625627, 641risk of bias (RoB)17, 25, 26, 329, 330rivm.Rijksinstituut voor Volksgezondheid en Milieu Netherlands (rivm)road map89, 90, 113RoB.Risk of Bias (RoB)robotic equipment642, 643rodent8, 12, 14, 28, 30, 171, 325, 358, 365, 426, 451, 453, 456458, 520, 521, 523, 538, 590, 661, 662roi.return on investment (roi)routes of exposure325Royal Society for the Prevention of Cruelty to Animals (rspca)330, 662rspca.Royal Society for the Prevention of Cruelty to Animals (rspca)Russell, W.M.S.3, 4, 18, 29, 36, 171, 172, 196, 197, 364, 577, 656659, 664, 668Safer Medicines Trust433safety of medicines89, 90, 417, 418, 432Saint Bernard of Clairvaux259same-species feeding260sample size18, 327329, 344saturated fat135, 495scaffold575, 642scheer.Scientific Committee on Health Environmental and Emerging Risks (scheer)science-friendly298scientific collaboration3637Scientific Committee on Health Environmental and Emerging Risks (scheer)161, 171, 178scientific output109, 521scientific progress30, 110, 162, 300, 433, 678, 682scientific rigor23, 394, 428search engine for alternative methods34sentience77, 153, 161, 170, 171, 181, 198, 200, 203, 280, 285, 290, 300, 402, 403, 499, 535, 570, 656659, 662, 664serum92, 103, 423, 664, 665, 667Set Foundation98, 100, 101seurat-1, 91, 102, 601severity assessment294severity classification297, 301shame297, 314Shanks, N.69, 71, 78, 124, 199, 202, 204, 277, 307, 393, 403405sheep14, 257, 258, 262, 264265, 284, 343, 357, 452, 454, 521, 555, 556Simulab Corporation555557simulator368, 553560, 573Singapore160, 175Singer, P.213, 214, 217, 218, 308, 691, 692skin andcorrosion366, 598, 666irritation365, 431, 589, 592, 594, 595, 598600, 602sensitization365, 367, 590, 595, 599, 600, 602, 617, 666, 680Skinner box519smafira.smart feature-based interactive ranking algorithm (smafira)smart feature-based interactive ranking algorithm (smafira)34snap.Supplemental Nutrition Assistance Program (snap)social isolation217, 520societal concerns4, 29, 38species differences18, 23, 107, 332, 356, 357, 363, 425, 443, 444, 465, 497, 593, 596speciesism198, 200, 202, 568, 571spheroids642, 644, 647stakeholder66, 74, 90, 93, 94, 104, 105, 109, 110, 112115, 135, 154, 157, 162, 163, 170, 209221, 224, 286, 342, 369, 448, 456, 660theory209, 210, 216, 220standardization5, 6, 9, 195, 588, 603, 619, 625, 643, 648statins162, 173, 293, 362, 364, 368, 423425, 486, 495statistics16, 1820, 25, 31, 76, 79, 130, 195, 199, 216, 228230, 238, 323, 326330, 343, 379, 381385, 422, 429, 443, 454, 482, 496, 521, 652, 662, 676stem cells24, 92, 107, 216, 278, 357, 366, 445, 450, 462, 591, 612, 626, 628, 649, 679stereotactic521stereotypy79, 455, 522. abnormal behaviorstewardship279281Stop Vivisection161163, 169, 170, 194. Citizen’s Initiativestrategy20, 22, 33, 35, 89, 90, 104, 108, 110, 112, 113, 138, 152, 158, 162164, 170, 171, 173, 201, 202, 227, 236, 237, 239, 254, 313, 314, 342, 362, 368, 429, 431433, 452, 530, 535, 557, 577, 589, 590, 603, 615, 617, 651654, 681683stress711, 13, 129, 172, 196, 231, 232, 263, 300, 305, 307, 313, 314, 325, 333, 454, 465, 522, 523, 528, 535, 538, 560, 614, 615, 617, 642, 662stressor5, 8, 10, 305, 307, 325, 333, 518, 523, 614, 616stroke22, 2426, 125, 126, 133, 255, 276, 324, 357, 402, 406, 424, 425, 482, 495The Structure of Scientific Revolutions684, 692subjectivity11, 237, 308, 310, 314, 327, 399, 454, 569, 590subsidies135139, 244, 247, 261, 266, 368suffering13, 92, 124, 153, 168, 194, 210, 225, 248, 275, 290, 306, 321, 342, 377, 403, 420, 444, 499, 519, 569, 594, 652, 656, 675, 692unnecessary300, 301Supplemental Nutrition Assistance Program (snap)134, 137sustainability127, 130132, 137, 266, 652Sweden154, 179, 290, 601Switzerland17, 179, 331symptoms125, 139, 255, 297, 385, 405, 483, 487, 491, 492, 558syrcle.Systematic Review Center for Laboratory Animal Experimentation (syrcle)systematic review6, 15, 17, 2527, 96, 161, 236, 276, 323, 325, 326, 329, 331, 332, 344358, 362, 369, 379, 429, 494496, 681Systematic Review Center for Laboratory Animal Experimentation (syrcle)6, 26, 27system change90systemic models646systems biology101, 216, 613, 614, 621, 625627, 682, 683systems toxicology101, 613615, 630, 682Taiwan183Tamoxifen257, 423target22, 32, 75, 107, 110, 114, 132, 137, 229, 231, 253, 256, 261, 278, 312, 380384, 419, 445450, 452, 454, 455, 457, 458, 460, 463465, 480, 486, 491493, 524, 527, 604606, 615618, 623, 625, 627629, 644, 650, 665, 678taxpayers35, 109, 136, 244, 245, 247, 248, 254, 261266, 499tax-supported animal research245Taylor, K.4, 14, 31, 152, 168, 216, 322, 379, 443, 454, 482, 587606, 647, 666technological development94, 613, 683teratogenicity research324testing3, 65, 88, 124, 151, 170, 194, 209, 227, 244, 281, 289, 306, 322, 341, 381, 391, 417, 448, 486, 521, 569, 587, 615, 641, 656, 675, 691Test Methods Regulation, ec 440/2008600tgn1412366, 419, 426Thailand181theory of mind521, 525, 526, 529, 530, 532, 536, 537Think Tank on Supplementary Financing for Alternatives to Animal Testing1103D andbioprint108cell culture106, 462, 621, 642, 644, 6463D organotypic cultures6273Rshierarchy36, 171174, 184impact4implementation of27, 159, 237, 239, 331, 577Tierschutz-Versuchstierverordnung (Ordinance on the protection of animals used for experimental purposes)96, 292, 297tissues24, 31, 71, 92, 101103, 107, 183, 194, 196, 212, 216, 249, 278, 358, 364, 366, 367, 377, 378, 425, 426, 428, 454, 455, 552, 555, 558, 573, 574, 588, 598, 613, 617, 621, 622, 624, 642, 644, 646, 649, 656, 658, 659, 662, 665667tool use521Tox21.Toxicology in the 21th Century (Tox21)Toxicity in the 21st century (Tox21)29, 89, 92, 102, 367, 426, 432, 595, 612619toxicity testing29, 30, 35, 89, 91, 102, 105, 109111, 114, 152, 158, 159, 184, 236, 244, 245, 322, 341, 342, 362, 363, 365367, 417, 418, 421, 423, 428, 432, 433, 587592, 595, 601603, 620, 659, 660, 676680toxicodynamics324, 332, 624toxicokinetics365toxicology29, 72, 89, 157, 200, 266, 306, 323, 342, 424, 486, 588, 612, 667, 676, 693Toxicology in the 21th Century (Tox21)29, 89, 92, 102, 367, 426, 432, 595, 612619training11, 33, 36, 66, 90, 137, 184, 209, 237, 263, 301, 322, 342, 457, 551, 568, 666, 679.education and trainingtransgenic29, 195, 239, 278, 365, 453, 456, 483485, 492, 659transitionmanagement112113strategy90, 112113to non-animal research35, 89, 110, 113, 114translatability10, 22, 199, 424, 460, 489crisis18translation10, 14, 18, 19, 2225, 31, 73, 75, 90, 101, 102, 111, 112, 124, 125, 151, 180, 199, 245, 252, 254258, 265, 266, 276, 277, 280, 285, 305, 307, 315, 324, 327, 343, 344, 356, 357, 362, 386, 408, 424426, 451, 457, 460, 462, 465, 480, 483, 485487, 489, 499, 620, 621, 652, 657, 680translational research90, 111, 112. applied researchtranslational risk254transparency1921, 27, 34, 37, 93, 94, 115, 134, 156, 158, 160, 162, 163, 197, 224240, 265, 292, 301, 328, 329, 427, 682transportation130, 246, 333Trans-species modeling theory (tsmt)69, 70, 72, 392394, 408trauma23, 276, 313, 499, 551553, 555557, 560TraumaMan555557trauma management552Travis Air Force Base554trial registries20, 253, 332tsmt.Trans-species modeling theory (tsmt)twinner beef cattle263un ghs.United Nations Globally Harmonised System of Classification and Labelling of Chemicals (un ghs)unintended negative consequences244United Kingdom (uk)3, 26, 32, 33, 36, 89, 126, 130, 152155, 159, 160, 174, 176, 179, 185, 196, 225, 226, 232234, 236, 237, 239, 281, 290, 291, 326, 328, 330, 333, 334, 341, 343, 358, 418, 419, 421, 425, 432, 433, 443, 454, 486, 520, 521, 526, 560, 588, 592, 601, 603, 650, 651, 653, 659, 661, 662United Nations Globally Harmonised System of Classification and Labelling of Chemicals (un ghs)599United States of America (usa, us)16, 28, 29, 3133, 66, 73, 89, 91, 92, 94, 101, 102, 104, 109, 124126, 128134, 136, 137, 160, 168, 171, 176, 209, 212, 217, 219, 244251, 253, 254, 257259, 261265, 275, 276, 278, 279, 282, 285, 286, 326, 330, 366, 418420, 422, 424, 426, 427, 429, 431, 432, 445, 452, 456, 461, 481, 482, 486, 497, 498, 529, 530, 534, 538, 551554, 556, 560, 561, 593, 595, 601, 615, 619, 643, 647, 650, 651, 660, 661, 677, 678, 680universities26, 34, 42, 66, 78, 79, 93, 98, 103, 104, 108, 109, 176, 196, 219, 226, 229232, 247, 248, 254, 260, 261, 283, 312, 314, 328, 366, 367, 392, 489, 491, 500, 521, 529, 530, 555, 571575, 578, 587, 602, 628, 647652, 657, 661, 665, 684University of Nebraska-Lincoln (unl)260263unl.University of Nebraska-Lincoln (unl)usda.us Department of Agriculture (usda)us Department of Defense246, 552, 554us epartment of Agriculture (usda)124, 129132, 134136, 209, 246, 258, 260263, 282, 554, 659, 660us National Institutes of Health28, 245, 248, 647. National Institutes of Health (nih)utilitarianism153, 177, 198, 229, 334, 464, 533, 535, 537, 692vaccine32, 35, 67, 90, 111, 112, 184, 245, 246, 248, 249, 255, 259, 266, 306, 341, 378, 379, 406, 424, 489, 538, 587, 588, 644, 659, 664, 678, 680validation30, 3234, 69, 88, 91, 92, 9497, 101, 104106, 114, 152, 155, 157, 162, 170, 178, 256, 266, 278, 366, 418, 425, 427, 431, 433, 463, 486, 492, 592, 593, 595, 598600, 624, 628, 644, 650, 651, 653, 663, 666, 676, 678681, 683validityanimal model22, 392, 522drug screening105construct25external6, 25, 276, 524, 526internal25, 524lack of251, 307predictive24, 394relative174, 176scientific25, 70, 334, 343, 368toxicity screening257van Dam, M.90, 109, 110variation5, 6, 10, 16, 25, 405, 524, 525, 575vascular network642vegetables128, 135137, 497venous cutdown555vertebrates97, 155, 168, 172, 179, 246, 292, 294, 322, 334, 377, 403, 551, 575, 647, 656658, 660, 662665, 667Vesalius, A.321vivisection33, 90, 161163, 169, 170, 194, 199, 201, 227, 228, 275, 276, 283, 285, 286, 322, 571, 661Washington University, St. Louis555wasteanimal lives18, 328, 454funding/funds307money73, 158, 244266, 405resources16, 36, 643welfare.laboratory animal welfarebehavioral indicators of522poor264whitewashing37, 168185who.World Health Organization (who)whole body mannequins557, 558whole food124, 127, 131, 139, 140wild animal219, 518528behavior518528wild-caught519, 522wildlife131, 367, 529, 538workplace environment107, 108World Health Organization (who)36, 135, 174, 380, 482, 588, 664World Organization for Animal Health3, 168Wyss-Institute for Biologically Inspired Engineering, Harvard University103zebrafish365, 446, 460, 656, 658, 661663Zentrum zum Schutz der VersuchstiereGerman Centre for the Protection of Laboratory Animals (Bf3R)Zerhouni, E.28, 29, 74, 248, 278, 429
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