Alternative (non-animal) methods for cosmetics testing: current status and future prospects—2010
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Aardema MJ, Barnett B, Khambatta ZS, Reisinger K, Ouedrago-Arras G, Faquet B, Ginestet A, Mun GC, Dahl EL, Hewitt NJ, Corvi R, Curren RC (2010) International pre-validation studies of the EpiDerm™ 3D human reconstructed skin micronucleus (RSMN) assay: transferability and reproducibility. Mutat Res 701:123–131
Adler S, Lindqvist J, Uddenberg K, Hyllner J, Strehl R (2008a) Testing potential developmental toxicants with a cytotoxicity assay based on human embryonic stem cells. Altern Lab Anim 36:129–140
Adler S, Pellizzer C, Hareng L, Hartung T, Bremer S (2008b) First steps in establishing a developmental toxicity test method based on human embryonic stem cells. Toxicol In Vitro 22:200–211
Adler S, Bicker G, Bigalke H, Bishop C, Blümel J, Dressler D, Fitzgerald J, Gessler F, Heuschen H, Kegel B, Luch A, Milne C, Pickett A, Ratsch H, Ruhdel I, Sesardic D, Stephens M, Stiens G, Thornton PD, Thürmer R, Vey M, Spielmann H, Grune B, Liebsch M (2010) The current scientific and legal status of alternative methods to the LD50 test for botulinum neurotoxin potency testing. The report and recommendations of a ZEBET expert meeting. Altern Lab Anim 38(4):315–330
Aeby P, Python F, Goebel C (2007) Skin sensitisation: understanding the in vivo situation for the development of reliable in vitro test approaches. ALTEX 24(spec no):3–5
Aleksic M, Thain E, Roger D, Saib O, Davies M, Li J, Aptula A, Zazzeroni R (2009) Reactivity profiling: covalent modification of single nucleophile peptides for skin sensitisation risk assessment. Toxicol Sci 108(2):401–411
Aliahmadi E, Gramlich R, Grützkau A, Hitzler M, Krüger M, Baumgrass R, Schreiner M, Wittig B, Wanner R, Peiser M (2009) TLR2-activated human langerhans cells promote Th17 polarization via IL-1beta, TGF-beta and IL-23. Eur J Immunol 39(5):1221–1230
Allen DD, Geldenhuys WJ (2006) Molecular Modelling of blood-barrier nutrient transporters: in silico basis for evaluation of potential drug delivery to the central nervous system. Life Sci 78:1029–1033
Allen JW, Khetani SR, Bhatia SN (2005) In vitro zonation and toxicity in a hepatocyte bioreactor. Toxicol Sci 84(1):110–119
Allen BC, Hack CE, Clewell HJ (2007) Use of Markov Chain Monte Carlo analysis with a physiologically-based pharmacokinetic model of methylmercury to estimate exposures in US women of childbearing age. Risk Anal 27:947–959
Andersen KE, Maibach HI (1985) Guinea pig sensitisation assays. An overview. In: Andersen KE, Maibach HI (eds) Contact allergy. Predictive tests in guinea pigs. Karger, Basel, pp 263–290
Andersen KE, Vølund AA, Frankild S (1995) The guinea pig maximization test—with a multiple dose design. Acta Derm Venereol 75(6):463–469
Aninat C, Piton A, Glaise D, Le Charpentier T, Langouët S, Morel F, Guguen-Guillouzo C, Guillouzo A (2006) Expression of cytochromes P450, conjugating enzymes and nuclear receptors in human hepatoma RG cells. Drug Metab Dispos 34(1):75–83
Anon (1967) Report of the WHO scientific group. WHO principles for the testing of drugs for teratogenicity. WHO technical reports series 18, p 364
Anon (1998) American society for testing and materials (ASTM). Standard guide for conducting the frog embryo teratogenesis assay—xenopus (FETAX), E1439-91 annual book of ASTM standards. ASTM, Philadelphia, 11.05, pp 826–836
Anon (2003) Globally harmonised system of classification and labelling of chemicals (GHS). Part 3: health and environmental hazards. United Nations Organisation, New York, pp 151–158
Anon (2010a) The official ReProTect Website. http://www.reprotect.eu/ . Accessed on 12 July 2010
Anon (2010b) Embryotoxicity testing in post-implantation embryo culture—method of piersma INVITTOX no 123. http://www.ecvam-dbalm.jrc.ec.europa.eu/public_view_doc2.cfm?id=15BFE9AC6ECC8ED3D7F6DF03B5D5BBE97180BB0BC12CB10496CDA74B54630A05A3291B895581F634 . Accessed on 13 July 2010
Ao L, Liu JY, Liu WB, Gao LH, Hu R, Fang ZJ, Zhen ZX, Huang MH, Yang MS, Cao J (2010) Comparison of gene expression profiles in BALB/c 3T3 transformed foci exposed to tumor promoting agents. Toxicol In Vitro 24:430–438
Api AM, Basketter DA, Cadby PA, Cano MF, Ellis G, Gerberick GF, Griem P, McNamee PM, Ryan CA, Safford B (2008) Dermal sensitisation quantitative risk assessment (QRA) for fragrance ingredients. Regul Toxicol Pharmacol 52(1):3–23
Aptula AO, Roberts DW (2006) Mechanistic applicability domains for non animal-based prediction of toxicological end points: general principles and application to reactive toxicity. Chem Res Toxicol 19(8):1097–1105
Aptula AO, Roberts DW, Pease C (2007) Haptens, prohaptens and prehaptens, or electrophiles and proelectrophiles. Contact Derm 56(1):54–56
Artola-Garicano E, Vaes WH, Hermens JL (2000) Validation of negligible depletion solid-phase microextraction as a tool to determine tissue/blood partition coefficients for semivolatile and nonvolatile organic chemicals. Toxicol Appl Pharmacol 166:138–144
Aschauer L, Wilmes A, Leonard MO, Pfaller W, Jennings P (2010) In vitro perfusion system for semi-automation of long-term repeat dose toxicity testing. ALTEX 27(suppl 2/10):12–13
Ashby J (2001) Expectations for transgenic rodent cancer bioassay models. Toxicol Pathol 29(suppl):177–182
Ashikaga T, Yoshida Y, Hirota M, Yoneyama K, Itagaki H, Sakaguchi H, Miyazawa M, Ito Y, Suzuki H, Toyoda H (2006) Development of an in vitro skin sensitisation test using human cell lines: the human cell line activation test (h-CLAT). I. Optimization of the h-CLAT protocol. Toxicol In Vitro 20(5):767–773
Attardi BJ, Hild SA, Reel JR (2006) Dimethandrolone undecanoate: a new potent orally active androgen with progestational activity. Endocrinology 147:3016–3026
Augustine KA (2009) HESI DART. Alternative assays workshop II: generation and preliminary assessment of a zebrafish teratogenicity assay. http://www.hesiglobal.org/files/public/Committees/DART/Meetings%20and%20Workshops/AlternativeAssayWkshp_Augustine.pdf . Accessed on 11 July 2010
Augustine-Rauch K, Zhang CX, Panzica-Kelly JM (2010) In vitro developmental toxicology assays: a review of the state of the science of rodent and zebrafish whole embryo culture and embryonic stem cell assays. Birth Defects Res C Embryo Today 90:87–98
Baillie TA (2006) Future of toxicology-metabolic activation and drug design: challenges and opportunities in chemical toxicology. Chem Res Toxicol 19:889–893
Baillie TA (2008) Metabolism and toxicity of drugs. Two decades of progress in industrial drug metabolism. Chem Res Toxicol 21:129–137
Balls M, Hellsten E (2002) Statement of the scientific validity of the embryonic stem cell test (EST)—an in Vitro test for embryotoxicity. Altern Lab Anim 30:265–268
Bal-Price A, Suñol C, Dieter G, Weiss G, van Vliet E, Westerink RHS, Costa LG (2008) Application of in vitro neurotoxicity testing for regulatory purposes: symposium III summary and research needs. Neurotoxicology 29(3):520–531
Banas A, Teratani T, Yamamoto Y, Tokuhara M, Takeshita F, Quinn G, Okochi H, Ochiya T (2007) Adipose tissue-derived mesenchymal stem cells as a source of human hepatocytes. Hepatology 46(1):219–228
Bantle JA, Finch RA, Fort DJ, Stover EL, Hull M, Kumsher-King M, Gaudet-Hull AM (1999) Phase III interlaboratory study of FETAX. Part 3. FETAX validation using 12 compounds with and without an exogenous metabolic activation system. J Appl Toxicol 19:447–472
Barlow S (2005) Threshold of toxicological concern (TTC). A tool for assessing substances of unknown toxicity present at low levels in the diet. ILSI Europe concise monograph series, The International Life Sciences Institute (ILSI), Europe
Barratt MD, Castell JV, Chamberlain M, Combes RD, Dearden JC, Fentem JH, Gerner I, Giuliani A, Gray TJB, Livingstone DJ, Provan WML, Rutten F, Verhaar HJM, Zbinden P (1995) The integrated use of alternative approaches for predicting toxic hazard—the report and recommendations of ECVAM workshop-8. ATLA 23:410–429
Barton HA (2009) Biological modeling as a method for data evaluation and integration in toxicology. Hum Exp Toxicol 28(2–3):143–145
Barton HA, Pastoor TP, Baetcke K, Chambers JE, Diliberto J, Doerrer NG, Driver JH, Hastings CE, Iyengar S, Krieger R, Stahl B, Timchalk C (2006) The acquisition and application of absorption, distribution, metabolism, and excretion (ADME) data in agricultural chemical safety assessments. Crit Rev Toxicol 36(1):9–35
Barton HA, Chiu WA, Setzer RW, Andersen ME, Bailer AJ, Bois FY, Dewoskin RS, Hays S, Johanson G, Jones N, Loizou G, Macphail RC, Portier CJ, Spendiff M, Tan YM (2007) Characterizing uncertainty and variability in physiologically based pharmacokinetic models: state of the science and needs for research and implementation. Toxicological
Basketter DA (2009) The human repeated insult patch test in the 21st century: a commentary on ethics and validity. Cutan Ocul Toxicol 28(2):49–53
Basketter DA (2010) Methyldibromoglutaronitrile, skin sensitisation and quantitative risk assessment. Cutan Ocul Toxicol 29(1):4–9
Basketter DA, Kimber I (2010a) Contact hypersensitivity. In: McQueen CA (ed) Comprehensive toxicology, vol 5, 2nd edn edn. Elsevier, Kidlington, pp 397–411
Basketter DA, Kimber I (2010b) Skin sensitization, false positives and false negatives: experience with guinea pig assays. J Appl Toxicol 30(5):381–386
Basketter DA, Lea LJ, Dickens A, Briggs D, Pate I, Dearman RJ, Kimber I (1999) A comparison of statistical approaches to the derivation of EC3 values from local lymph node assay dose responses. J Appl Toxicol 19(4):261–266
Basketter DA, Andersen KE, Lidén C, van Loveren H, Boman A, Kimber I, Alanko K, Berggren E (2005a) Evaluation of the skin sensitising potency of chemicals using existing methods and considerations of relevance for elicitation. Contact Derm 52(1):39–43
Basketter DA, Casati S, Gerberick GF, Griem P, Philips B, Worth A (2005b) Skin Sensitisation. Altern Lab Anim 33(suppl 1):83–103
Basketter DA, Clapp C, Jefferies D, Safford B, Ryan CA, Gerberick GF, Dearman RJ, Kimber I (2005c) Predictive identification of human skin sensitisation thresholds. Contact Derm 53(5):260–267
Basketter DA, Gerberick GF, Kimber I (2007a) The local lymph node assay EC3 value: status of validation. Contact Derm 57(2):70–75
Basketter DA, Kan-King-Yu D, Dierkes P, Jowsey IR (2007b) Does irritation potency contribute to the skin sensitisation potency of contact allergens? Cutan Ocul Toxicol 26(4):279–286
Basketter DA, Casati S, Cronin MTD, Diembeck W, Gerberick GF, Hadgraft J, Kasting G, Marty JP, Nikolaidis E, Patlewicz G, Pease C, Roberts DW, Roggen E, Rovida C, van der Sandt J (2007c) Skin sensitisation and epidermal disposition. Altern Lab Anim 35(1):137–154
Basketter DA, Darlenski R, Fluhr J (2008a) Skin irritation and sensitisation: mechanisms and new approaches for risk assessment. Skin Pharmacol Physiol 21(4):191–202
Basketter DA, Clapp CJ, Safford BJ, Jowsey IR, McNamee PM, Ryan CA, Gerberick GF (2008b) Preservatives and skin sensitisation quantitative risk assessment: risk benefit considerations. Dermatitis 19(1):20–27
Basketter DA, Kimber I (2009) Updating the skin sensitisation in vitro data assessment paradigm in 2009. J Appl Toxicol 29(6):545–550
Battelle (2002) Revised AR binding assay protocol: androgen receptor competitive binding protocol using rat ventral prostate cytosol, SOP no. NHEERL-H/RTD/EB/VW/2002-03-000. In: Quality assurance project plan for work assignment 2-22, Development of Androgen Receptor Binding Data, prepared by Battelle for US environmental protection agency, endocrine disruptor screening program, contract no. 68-W-01-023
Baylin SB, Ohm JE (2006) Epigenetic gene silencing in cancer—a mechanism for early oncogenic pathway addition? Nat Rev Cancer 6:107–116
Benfenati E, Benigni R, DeMarini DM, Helma C, Kirkland D, Martin TM, Mazzatorta P, Ouedraogo-Arras G, Richard AM, Schilter B, Schoonen WGEJ, Snyder RD, Yang C (2009) Predictive models for carcinogenicity and mutagenicity: frameworks, state-of-the-art, and perspectives. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 27(2):57–90
Benigni R, Bossa C, Tcheremenskaia O, Giuliani A (2010) Alternatives to the carcinogenicity bioassay: in silico methods, and the in vitro and in vivo mutagenicity assays. Expert Opin Drug Metab Toxicol 6:809–819
Bercu JP, Morton SM, Deahl JT, Gombar VK, Callis CM, van Lier RB (2010) In silico approaches to predicting cancer potency for risk assessment of genotoxic impurities in drug substances. Regul Toxicol and Pharmacol 57:300–306
Bernillon P, Bois FY (2000) Statistical issues in toxicokinetic modeling: a Bayesian perspective. Environ Health Perspect 108:883–893
Bernshausen T, Noss A, Boehn SN, Fabian E, Kamp HG, Kaufmann T, Koch M, Wessa P, van Ravenzwaay B, Landsiedel R (2009) Metabolic Competences of the Chicken Embryo used in the Toxicity Screening Test (CHEST) as an In Vitro Test System for Teratogenicity and Embryotoxicity. 50. Jahrestagung der DGPT, Mainz, Germany
Bérubé K, Aufderheide M, Breheny D, Clothier R, Combes R, Duffin R, Forbes B, Gaça M, Gray A, Hall I, Kelly M, Lethem M, Liebsch M, Merolla L, Morin JP, Seagrave JC, Swartz MA, Tetley TD, Umachandran M (2009) In Vitro Models of Inhalation Toxicity and Disease. The Report of a FRAME Workshop. Altern Lab Anim 37(1):89-141
Bessems JGM (2009) Opinion on the usefulness of in vitro data for human risk assessment. Suggestions for better use of non-testing approaches. Letter report 320016002/2009 RIVM. http://www.rivm.nl/bibliotheek/rapporten/320016002.pdf . Accessed 15 January 2011
Billinton N, Hastwell PW, Beerens D, Birrell L, Ellis P, Maskell S, Webster TW, Windebank S, Woestenborghs F, Lynch AM, Scott AD, Tweats DJ, van Gompel J, Rees RW, Walmsley RM (2008) Interlaboratory assessment of the GreenScreen HC GADD45a-GFP genotoxicity screening assay: an enabling study for independent validation as an alternative method. Mutat Res 653:23–33
Billinton N, Bruce S, Hansen JR, Hastwell PW, Jagger C, McComb C, Klug ML, Pant K, Rabinowitz A, Rees R, Tate M, Vinggaard AM, Walmsley RM (2010) A pre-validation transferability study of the GreenScreen HC GADD45a-GFP assay with a metabolic activation system (S9). Mutat Res 700:44–50
Bitsch A, Jacobi S, Melber C, Wahnschaffe U, Simetska N, Mangelsdorf I (2006) REPDOSE: a database on repeated dose toxicity studies of commercial chemicals—a multifunctional tool. Regul Toxicol Pharmacol 46(3):202–210
Bittner M, Hilscherova K, Giesy JP (2009) In vitro assessment of AhR-mediated activities of TCDD in mixture with humic substances. Chemosphere 76:1505–1508
Blaauboer BJ (2002) The necessity of biokinetic information in the interpretation of in vitro toxicity data. Altern Lab Anim 30(suppl 2):85–91
Blaauboer BJ (2003) The integration of data on physico-chemical properties, in vitro-derived toxicity data and physiologically based kinetic and dynamic modelling as a tool in hazard and risk assessment. A commentary. Toxicol Lett 138(1-2):161-171
Blaauboer BJ (2008) The contribution of in vitro toxicity data in hazard and risk assessment: current limitations and future perspectives. Toxicol Lett 180(2):81–84
Blaauboer BJ (2010) Biokinetic modeling and in vitro-in vivo extrapolations. J Toxicol Environ Health B Crit Rev 13(2–4):242–252
Blaauboer BJ, Andersen ME (2007) The need for a new toxicity testing and risk analysis paradigm to implement REACH or any other large scale testing initiative. Arch Toxicol 81(5):385–387
Blaauboer BJ, Bayliss MK, Castell JV, Evelo CTA, Frazier JM, Groen K, Gülden M, Guillouzo A, Hissink AM, Houston BJ, Johanson G, de Jongh J, Kedderis GL, Reinhardt CA, van de Sandt JJM, Semino G (1996) The use of biokinetics and in vitro methods in toxicological risk evaluation. ATLA 24:473–497
Blaauboer BJ, Barratt MD, Houston BJ (1999) The integrated use of alternative methods in toxicological risk evaluation: ECVAM integrated testing strategies task force report 1. ATLA 27:229–237
Blackburn K, Stickney JA, Carlson-Lynch HL, McGinnis PA, Chappell L, Felter SP (2005) Application of the threshold of toxicological concern approach to ingredients in personal and household care products. Regul Toxicol and Pharmacol 43:249–259
Boehn SNE, Kaufmann T, Koch M, Wessa P, Kamp HG, Landsiedel R, van Ravenzwaay B (2009) Modification and evaluation of the chicken embryotoxicity screening test (CHEST) as in vitro test system for embryotoxicity. VII World Congress on Alternatives & Animal Use in the Life Sciences, Rome
Boekelheide K, Campion SN (2010) Toxicity testing in the 21st century: using the new toxicity testing paradigm to create a taxonomy of adverse effects. Toxicol Sci 114(1):20–24
Boess F, Kamber M, Romer S, Gasser R, Muller D, Albertini S, Suter L (2003) Gene expression in two hepatic cell lines, cultured primary hepatocytes, and liver slices compared to the in vivo liver gene expression in rats: possible implications for toxicogenomics use of in vitro systems. Toxicol Sci 73(2):386–402
Böhme A, Thaens D, Paschke A, Schüürmann G (2009) Kinetic glutathione chemoassay to quantify thiol reactivity of organic electrophiles application to α,β-unsaturated ketones, acrylates, and propiolates. Chem Res Toxicol 22(4):742–750
Bois FY, Paxman D (1992) An analysis of exposure rate effects for benzene using a physiologically based pharmacokinetic model. Regul Toxicol Pharmacol 15:122–136
Bois FY, Smith T, Gelman A, Chang HY, Smith AE (1999) Optimal design for a study of butadiene toxicokinetics in humans. Toxicol Sci 49:213–224
Bois FY, Jamei M, Clewell HJ (2010) PBPK modelling of inter-individual variability in the pharmacokinetics of environmental chemicals. Toxicology 278(3):256–267
Boobis AR, Cohen SM, Dellarco V, McGregor D, Meek ME, Vickers C, Willcocks D, Farland W (2006) IPCS framework for analyzing the relevance of a cancer mode of action for humans. Crit Rev Toxicol 36(10):781–792
Boobis AR, Doe JE, Heinrich-Hirsch B, Meek ME, Munn S, Ruchirawat M, Schlatter J, Seed J, Vickers C (2008) IPCS framework for analyzing the relevance of a noncancer mode of action for humans. Crit Rev Toxicol 38(2):87–96
Boobis AR, Daston GP, Preston RJ, Olin SS (2009a) Application of key events analysis to chemical carcinogens and noncarcinogens. Crit Rev Food Sci Nutr 49(8):690–707
Boobis AR, Cohen SM, Doerrer NG, Galloway SM, Haley PJ, Hard GC, Hess FG, Macdonald JS, Thibault S, Wolf DC, Wright J (2009b) A data-based assessment of alternative strategies for identification of potential human cancer hazards. Toxicol Pathol 37(6):714–732
Boogaard PJ, Nagelkerke JF, Mulder GJ (1990) Renal proximal tubular cells in suspension or in primary culture as in vitro models to study nephrotoxicity. Chem Biol Interact.76(3):251-291
Bouvier d’Yvoire M, Prieto P, Blaauboer BJ, Bois FY, Boobis A, Brochot C, Coecke S, Freidig A, Gundert-Remy U, Hartung T, Jacobs MN, Lav T, Leahy DE, Lennernäs H, Loizou GD, Meek B, Pease C, Rowland M, Spendiff M, Yang J, Zeilmaker M (2007) Physiologically-based kinetic modelling (PBK modelling): meeting the 3Rs agenda: the report and recommendations of ECVAM workshop 63. ATLA 35:661–671
Bouwman T, Cronin MT, Bessems JG, van de Sandt JJ (2008) Improving the applicability of (Q)SARs for percutaneous penetration in regulatory risk assessment. Hum Exp Toxicol 27:269–276
Brandenberger C, Rothen-Rutishauser B, Mühlfeld C, Schmid O, Ferron GA, Maier KL, Gehr P, Lenz AG (2010) Effects and uptake of gold nanoparticles deposited at the air–liquid interface of a human epithelial airway model. Toxicol Appl Pharmacol 242(1):56–65
Brandon EF, Oomen AG, Rompelberg CJ, Versantvoort CH, van Engelen JG, Sips AJ (2006) Consumer product in vitro digestion model: bioaccessibility of contaminants and its application in risk assessment. Regul Toxicol Pharmacol 44:161–171
Brannen KC, Panzica-Kelly JM, Danberry TL, Augustine-Rauch KA (2010) Development of a zebrafish embryo teratogenicity assay and quantitative prediction model. Birth Defects Res B Dev Reprod Toxicol 89:66–77
Bremer S, Van Dooren M, Paparella M, Kossolov E, Fleischmann B, Hescheler J (1999) Establishment of an embryotoxicity assay with green fluorescence protein-expressing embryonic cell-derived cardiomyocytes. Atla Altern Lab Anim 27:471–484
Bremer S, Pellizzer C, Hoffmann S, Seidle T, Hartung T (2007) The development of new concepts for assessing reproductive toxicity applicable to large scale toxicological programmes. Curr Pharm Des 13:3047–3058
Brown NA, Fabro S (1981) Quantitation of rat embryonic development in vitro: a morphological scoring system. Teratology 24:65–78
Brown NA, Spielmann H, Bechter R, Flint OP, Freeman SJ, Jelinek RJ, Koch E, Nau H, Newall DR, Palmer AK et al (1995) Screening chemicals for reproductive toxicity: the current alternatives; the report and recommendations of an ECVAM/ETS workshop (ECVAM workshop 12). Altern Lab Anim 23(6):868–882
Broxmeyer HE, Srour E, Orschell C, Ingram DA, Cooper S, Plett PA, Mead LE, Yoder MC (2006) Cord blood stem and progenitor cells. Methods Enzymol 419:439–473
Bucher JR (1998) Update on national toxicology program (NTP) assays with genetically altered or “transgenic” mice. Environ Health Perspect 106:619–621
Buesen R, Genschow E, Slawik B, Visan A, Spielmann H, Luch A, Seiler A (2009) Embryonic stem cell test remastered: comparison between the validated EST and the new molecular FACS-EST for assessing developmental toxicity in vitro. Toxicol Sci 108:389–400
Busquet F, Nagel R, von Landenberg F, Mueller SO, Huebler N, Broschard TH (2008) Development of a new screening assay to identify proteratogenic substances using zebrafish Danio rerio embryo combined with an exogenous mammalian metabolic activation system (mDarT). Toxicol Sci 104:177–188
Buzanska L, Sypecka J, Nerini-Molteni S, Compagnoni A, Hogberg HT, del Torchio R, Domanska-Janik K, Zimmer J, Coecke S (2009) A human stem cell-based model for identifying adverse effects of organic and inorganic chemicals on the developing nervous system. Stem Cells 27(10):2591–2601
Caesar software (2010) http://www.caesar-project.eu . Accessed 30 June 2010
Carfí M, Gennari A, Malerba I, Corsini E, Pallardy M, Pieters R, Van Loveren H, Vohr HW, Hartung T, Gribaldo L (2007) In vitro tests to evaluate immunotoxicity: a preliminary study. Toxicology 229(1–2):11–22
Carfí M, Bowe G, Ferrario D, Pieters R, Gribaldo L (2010) Maintenance and characterization of lymphocytes in human long term bone marrow cultures to study immunotoxicity. Toxicol In Vitro 24(5):1395–1403
Carmichael P, Davies M, Dent M, Fentem J, Fletcher S, Gilmour N, MacKay C, Maxwell G, Merolla L, Pease C, Reynolds F, Westmoreland C (2009) Non-animal approaches for consumer safety risk assessments: unilever’s scientific research programme. Altern Lab Anim 37(6):595–610
Carthew P, Clapp C, Gutsell S (2009) Exposure based waiving: the application of the toxicological threshold of concern (TTC) to inhalation exposure for aerosol ingredients in consumer products. Food Chem Toxicol 47:1287–1295
Casati S, Aeby P, Basketter DA, Cavani A, Gennari A, Gerberick GF, Griem P, Hartung T, Kimber I, Lepoittevin JP, Meade BJ, Pallardy M, Rougier N, Rousset F, Rubinstenn G, Sallusto F, Verheyen GR, Zuang V (2005) Report and recommendations of ECVAM workshop 51. Dendritic cells as a tool for the predictive identification of skin sensitisation hazard. Altern Lab Anim 33(1):47–62
Cecchelli R, Berezowski V, Lundquist S, Culot M, Renftel M, Dehouck MP, Fenart L (2007) Modelling of the blood–brain barrier in drug discovery and development. Nat Rev Drug Disc 6(8):650–661
Cefic (2010) http://www.cefic-lri.org/lri-toolbox/ambit . Accessed 30 June 2010
Cezar GG, Quam JA, Smith AM, Rosa GJ, Piekarczyk MS, Brown JF, Gage FH, Muotri AR (2007) Identification of small molecules from human embryonic stem cells using metabolomics. Stem Cells Dev 16:869–882
Chao P, Maguire T, Novik E, Cheng KC, Yarmush ML (2009) Evaluation of a microfluidic based cell culture platform with primari human hepatocytes for the prediction of hepatic. Biochem Pharmacol 78:625–632
Chapin RE, Stedman DB (2009) Endless possibilities: stem cells and the vision for toxicology testing in the 21st century. Toxicol Sci 112(1):17–22
Chapin R, Stedman D, Paquette J, Streck R, Kumpf S, Deng S (2007) Struggles for equivalence: in vitro developmental toxicity model evolution in pharmaceuticals in 2006. Toxicol In Vitro 21:1545–1551
Chaudhry Q, Piclin N, Cotterill J, Pintore M, Price NR, Chrétien JR, Roncaglioni A (2010) Global QSAR models of skin sensitisers for regulatory purposes. Chem Cent J 4(suppl 1):S5
Cheeseman MA, Machuga EJ, Bailey AB (1999) A tiered approach to threshold of regulation. Food Chem Toxicol 37:387–412
Chipinda I, Ajibola RO, Morakinyo MK, Ruwona TB, Simoyi RH, Siegel PD (2010) Rapid and simple kinetics screening assay for electrophilic dermal sensitisers using nitrobenzenethiol. Chem Res Toxicol 23(5):918–925
Choi S, Park SY, Jeong J, Cho E, Phark S, Lee M, Kwak D, Lim JY, Jung WW, Sul D (2010) Identification of toxicological biomarkers of di(2-ethylhexyl) phthalate in proteins secreted by HepG2 cells using proteomic analysis. Proteomics 10(9):1831–1846
Clewell HJ, Tan YM, Campbell JL, Andersen ME (2008) Quantitative interpretation of human biomonitoring data. Toxicol Appl Pharmacol 231:122–133
Coecke S, Rogiers V, Bayliss M, Castell J, Doehmer J, Fabre G, Fry J, Kern A, Westmoreland C (1999) The use of long-term hepatocyte cultures for detection induction of drug metabolising enzymes: the current status. ATLA 27:579–638
Coecke S, Blaauboer BJ, Elaut G, Freeman S, Freidig A, Gensmantel N, Hoet P, Kapoulas VM, Ladstetter B, Langley G, Leahy D, Mannens G, Meneguz A, Monshouwer M, Nemery B, Pelkonen O, Pfaller W, Prieto P, Proctor N, Rogiers V, Rostami-Hodjegan A, Sabbioni E, Steiling W, van de Sandt JJ (2005) Toxicokinetics and metabolism. Altern Lab Anim 33(1):147–175
Coecke S, Ahr H, Blaauboer BJ, Bremer S, Casati S, Castell J, Combes R, Corvi R, Crespi CL, Cunningham ML, Elaut G, Eletti B, Freidig A, Gennari A, Ghersi-Egea JF, Guillouzo A, Hartung T, Hoet P, Ingelman-Sundberg M, Munn S, Janssens W, Ladstetter B, Leahy D, Long A, Meneguz A, Monshouwer M, Morath S, Nagelkerke F, Pelkonen O, Ponti J, Prieto P, Richert L, Sabbioni E, Schaack B, Steiling W, Testai E, Vericat JA, Worth A (2006) Metabolism: a bottleneck in in vitro toxicological test development. The report and recommendations of ECVAM workshop 54. ATLA34(1):49–84
Cohen SM (2004) Human carcinogenic risk evaluation: an alternative approach to the 2-year rodent bioassay. Toxicol Sci 80(2):225–229
Combes R, Balls M, Illing P, Bhogal N, Dale J, Duv‚ G, Feron V, Grindon C, Gülden M, Loizou G, Priston R, Westmoreland C (2006) Possibilities for a new approach to chemicals risk assessment. The report of a FRAME workshop. Altern Lab Anim 34(6):621–649
Conolly RB, Butterworth BE (1995) Biologically based dose response model for hepatic toxicity: a mechanistically based replacement for traditional estimates of noncancer risk. Toxicol Lett 82–83:901–906
Constant S (2010) Assessment of acute, long-term and chronic respiratory toxicity using a long shelf-life 3D model of the human airway epithelium. ALTEX 27(suppl 2/10):29
Contrera JF, Matthews EJ, Kruhlak NL, Benz RD (2004) Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modelling of the human maximum recommended daily dose. Regul Toxicol Pharmacol 40(3):185–206
Contrera JF, Kruhlak NL, Matthews EJ, Benz RD (2007) Comparison of MC4PC and MDL-QSAR rodent carcinogenicity predictions and the enhancement of predictive performance by combining QSAR models. Regul Toxicol Pharmacol 49:172–182
Cooper RL, Lamb JC, Barlow SM, Bentley K, Brady AM, Doerrer NG, Eisenbrandt DL, Fenner-Crisp PA, Hines RN, Irvine LF, Kimmel CA, Koeter H, Li AA, Makris SL, Sheets LP, Speijers G, Whitby KE (2006) A tiered approach to life stages testing for agricultural chemical safety assessment. Crit Rev Toxicol 36:69–98
Cordelli E, Fresegna AM, D’Alessio A, Eleuteri P, Spano M, Pacchierotti F, Villani P (2007) ReProComet: a new in vitro method to assess DNA damage in mammalian sperm. Toxicol Sci 99:545–552
Corsini E, Mitjans M, Galbiati V, Lucchi L, Galli CL, Marinovich M (2009) Use of IL-18 production in a human keratinocyte cell line to discriminate contact sensitisers from irritants and low molecular weight respiratory allergens. Toxicol In Vitro 23(5):789–796
Corvi R, Albertini S, Hartung T, Hoffmann S, Maurici D, Pfuhler S, van Benthem J, Vanparys P (2008) ECVAM retrospective validation of in vitro micronucleus test (MNT). Mutagenesis 23:271–283
Cramer GM, Ford RA, Hall RL (1978) Estimation of toxic hazard—a decision tree approach. Food Cosmet Toxicol 16:255–276
Crean D, Aschauer L, Jennings P, Leonard M (2010) Toxicity profiling of nephrotoxins in the human proximal tubular RPTEC-TERT1 cell line: influence of hypoxia. ALTEX 27(suppl 2/10):31
Creton S, Billington R, Davies W, Dent MP, Hawksworth GM, Parry S, Travis KZ (2009) Application of toxicokinetics to improve chemical risk assessment: implications for the use of animals. Regul Toxicol Pharmacol 55(3):291–299
Crivori P, Poggesi I (2006) Computational approaches for predicting CYP-related metabolism properties in the screening of new drugs. Eur J Med Chem 41(7):795–808
Cronin MTD, Hewitt M (2007) In silico models to predict passage through the skin and other barriers. In: Testa B, van de Waterbeemd H (eds) Comprehensive medicinal chemistry II. Elsevier, Oxford, pp 725–744
Cronin MTD, Worth AP (2008) (Q)SARs for predicting effects relating to reproductive toxicity. Qsar Combinat Sci 27:91–100
Curren RD, Southee JA, Spielmann H, Liebsch M, Fentem JH, Balls M (1995) The role of pre-validation in the development, validation and acceptance of alternative methods. Altern Lab Anim 23:211–217
Curren RD, Mun GC, Gibson DP, Aardema MJ (2006) Development of a method for assessing micronucleus induction in a 3D human skin model EpiDermTM. Mutat Res 607:192–204
Dahl SG, Aarons L, Gundert-Remy U, Karlsson MO, Schneider YJ, Steimer JL, Troc¢niz IF (2010) Incorporating physiological and biochemical mechanisms into pharmacokinetic-pharmacodynamic models: a conceptual framework. Basic Clin Pharmacol Toxicol 106:2–12
Davies M, Pendlington RU, Page L, Roper CS, Sanders DJ, Bourner C, Pease CK, Mackay C (2010) Determining epidermal disposition kinetics for use in an integrated non-animal approach to skin sensitisation risk assessment. Toxicol Sci kfq326v1–kfq326
De Bruyn AMH, Gobas FAPC (2007) The sorptive capacity of animal protein. Environ Toxicol Chem 26:1803–1808
De Buck SS, Sinha VK, Fenu LA, Gilissen RA, Mackie CE, Nijsen MJ (2007) The prediction of drug metabolism, tissue distribution, and bioavailability of 50 structurally diverse compounds in rat using mechanism-based absorption, distribution, and metabolism prediction tools. Drug Metab Dispos 35:649–659
De Gottardi A, Vinciguerra M, Sgroi A, Moukil M, Ravier-Dall’Antonia F, Pazienza V, Pugnale P, Foti M, Hadengue A (2007) Microarray analyses and molecular profiling of steatosis induction in immortalized human hepatocytes. Lab Invest 87(8):792–806
de Graaf C, Vermeulen NP, Feenstra KA (2005) Cytochrome P450 in silico: an integrative modeling approach. J Med Chem 48(8):2725–2755
De Kock J, Vanhaecke T, Biernaskie JA, Rogiers V, Snykers S (2009) Characterization and hepatic differentiation of skin-derived precursors from adult foreskin by sequential exposure to hepatogenic cytokines and growth factors reflecting liver development. Toxicol In Vitro 23(8):1522–1527
de Longueville F, Atienzar FA, Marcq L, Dufrane S, Evrard S, Wouters L, Leroux F, Bertholet V, Gerin B, Whomsley R, Arnould T, Remacle J, Canning M (2003) Use of a low-density microarray for studying gene expression patterns induced by hepatotoxicants on primary cultures of rat hepatocytes. Toxicol Sci 75(2):378–392
De Vries A, van Steeg H, Opperhuizen A (2004) Transgenic mice as alternatives in carcinogenicity testing: current status. RIVM report 340700001
Dearden JC, Barratt MD, Benigni R, Bristol DW, Combes RD, Cronin MTD, Judson PN, Payne MP, Richard AM, Tichy M, Worth AP, Yourick JJ (1997) The development and validation of expert systems for predicting toxicity. Altern Lab Anim 25:223–252
DeJongh J, Forsby A, Houston JB, Beckman M, Combes R, Blaauboer BJ (1999a) An integrated approach to the prediction of systemic toxicity using computer-based biokinetic models and biological in vitro test methods: overview of a prevalidation study based on the ECITTS project. Toxicol In Vitro 13:549–554
DeJongh J, Nordin-Andersson M, Ploeger BA, Forsby A (1999b) Estimation of systemic toxicity of acrylamide by integration on in vitro toxicity data with kinetic simulations. Toxicol Appl Pharmacol 158(3):261–268
Deschl U, Vogel J, Aufderheide M (2010) Development of an in vitro exposure model for investigating the biological effects of therapeutic aerosols on human cells from the respiratory tract. Exp Toxicol Pathol. doi: 10.1016/j.etp.2010.04.013
DiPaolo JA, Donovan P, Nelson R (1969) Quantitative studies of in vitro transformation by chemical carcinogens. J Natl Cancer Inst 42:867–874
Divkovic M, Pease CM, Gerberick GF, Basketter DA (2005) Hapten-protein binding: from theory to practical application in the in vitro prediction of skin sensitisation. Contact Derm 53(4):189–200
Donato MT, Martínez-Romero A, Jiménez N, Negro A, Herrera G, Castell JV, O’Connor JE, Gómez-Lechón MJ (2009) Cytometric analysis for drug-induced steatosis in HepG2 cells. Chem Biol Interact 181(3):417–423
Doull J, Cattley R, Elcombe C, Lake BG, Swenberg J, Wilkinson C, Williams G, van Gemert M (1999) A cancer risk assessment of di(2-ethylhexyl) phthalate: application of the new US EPA risk assessment guidelines. Regul Toxicol Pharmacol 29:327–357
Dr. Hadwen Trust Science Review (2006) Showcasing successes in non-animal research. In Dr. Hadwen Trust Science Review. Dr. Hadwen Trust. http://www.drhadwentrust.org/
Durmus E, Inan O, Celik I, Sur E, Ozkan Y, Acar A, Aydin MF (2005) Use of the fertilized hen’s egg in the evaluation of embryotoxicity of dental alloys. J Biomed Mater Res B Appl Biomater 72:322–327
Eastin WC, Haseman JK, Mahler JF, Bucher JR (1998) The national toxicology program evaluation of genetically altered mice as predictive models for identifying carcinogens. Toxicol Pathol 26:461–473
ECHA (2008) Guidance on information requirements and chemical safety assessment. Chapter R.7a: endpoint specific guidance http://www.echa.europa.eu/about/reach_en.asp . Accessed 15 Jan 2011
ECHA (2010) Practical guide on how to report categories and read-across. http://www.www.echa.europa.eu/doc/publications/practical_guides/pg_report_readacross_categ.pdf
Edginton AN, Theil FP, Schmitt W, Willmann S (2008) Whole body physiologically-based pharmacokinetic models: their use in clinical drug development. Expert Opin Drug Metab Toxicol 4:1143–1152
EFSA, European Food Safety Authority (2004) Scientific panel on food additives, flavourings, processing aids and materials in contact with food. Opinion on flavouring group FGE.03 Acetals of branched- and straight-chain aliphatic saturated primary alcohols and branched- and straight-chain saturated aldehydes, and an orthoester of formic acid, from chemical groups 1 and 2. Opinion expressed on 7 Oct 2004. http://www.efsa.eu.int/science/afc/catindex_en.html
EFSA, European Food Safety Authority (2009) Report of the PPR Unit on the outcome of the public consultation on the revision of the existing guidance document on dermal absorption scientific opinion on the revision of the guidance document on dermal absorption
Elaut G, Henkens T, Papeleu P, Snykers S, Vinken M, Vanhaecke T, Rogiers V (2006) Molecular mechanisms underlying the dedifferentiation process of isolated hepatocytes and their cultures. Curr Drug Metab 7(6):629–660
Elferink MG, Olinga P, Draaisma AL, Merema MT, Bauerschmidt S, Polman J, Schoonen WG, Groothuis GM (2008) Microarray analysis in rat liver slices correctly predicts in vivo hepatotoxicity. Toxicol Appl Pharmacol 229(3):300–309
Ellinger-Ziegelbauer H, Gmuender H, Bandenburg A, Ahr HJ (2008) Prediction of a carcinogenic potential of rat hepatocarcinogens using toxicogenomics analysis of short-term in vivo studies. Mutat Res 637:23–39
Ellinger-Ziegelbauer H, Aubrecht J, Kleinjans JC, Ahr HJ (2009a) Application of toxicogenomics to study mechanisms of genotoxicity and carcinogenicity. Toxicol Lett 186:36–44
Ellinger-Ziegelbauer H, Fostel JM, Aruga C, Bauer D, Boitier E, Deng S, Dickinson D, Le Fevre AC, Fornace AJ Jr, Grenet O, Gu Y, Hoflack JC, Shiiyama M, Smith R, Snyder RD, Spire C, Tanaka G, Aubrecht J (2009b) Characterization and interlaboratory comparison of a gene expression signature for differentiating genotoxic mechanisms. Toxicol Sci 10:341–352
EMEA (2006) European medicines evaluation agency. Committee for medicinal products for human use (CHMP). Guideline on the limits of genotoxic impurities. CPMP/SWP/5199/02. London, 28 June 2006. EMEA/CHMP/QWP/251344/2006. http://www.emea.europa.eu/pdfs/human/swp/519902en.pdf
EMEA (2008) Committee for medicinal products for human use (CHMP). Questions & answers on the CHMP guideline on the limits of genotoxic impurities. Rev 1. London, 26 June 2008. Doc.Ref. EMEA/CHMP/SWP/431994/2007
Emter R, Ellis G, Natsch A (2010) Performance of a novel keratinocyte-based reporter cell line to screen skin sensitisers in vitro. Toxicol Appl Pharmacol 245(3):281–290
Enoch SJ, Cronin MTD (2010) A review of the electrophilic reaction chemistry involved in covalent DNA binding. Crit Rev Toxicol 40:728–748
Enoch SJ, Madden JC, Cronin MT (2008) Identification of mechanisms of toxic action for skin sensitisation using a SMARTS pattern based approach. SAR QSAR Environ Res 19(5–6):555–578
Enoch SJ, Cronin MTD, Madden JC, Hewitt M (2009) Formation of structural categories to allow for read-across for teratogenicity. QSAR Combinat Sci 28:696–708
Enslein K, Gombar VK, Blake BW (1994) International commission for protection against environmental mutagens and carcinogens. Use of SAR in computer-assisted prediction of carcinogenicity and mutagenicity of chemicals by the TOPKAT program. Mutat Res 205:47–61
Eriksson L, Jaworska JS, Worth AP, Cronin MTD, McDowell RM, Gramatica P (2003) Methods for reliability, uncertainty assessment, and applicability evaluations of classification and regression based QSARs. Environmental Health Perspectives 22:1361–1375 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241620/?tool=pubmed
Escher SE, Tluczkiewicz I, Batke M, Bitsch A, Melber C, Kroese ED, Buist HE, Mangelsdorf I (2010) Evaluation of inhalation TTC values with the database RepDose. Regul Toxicol Pharmacol 58:259–274
Eskes C, Zuang V (2005) Alternative (non-animal) methods for cosmetics testing: current status and future prospects. A report prepared in the context of the 7th amendment of the cosmetics directive for establishing the timetable for phasing out animal testing. ATLA 33(suppl 1):19–20
Esteller M (2007) Cancer epigenomics. DNA methylomes and histone-modification maps. Nat Rev Genet 8:286–298
EU (1976) Council directive 76/768/EEC of July 1976 on the approximation of the laws of the member states relating to cosmetic products. Off J L262:169–200
EU (2003) Directive 2003/15/EC of the European parliament and the council of 27 February 2003 amending council directive 76/768/EEC on the approximation of the laws of the members states relating to cosmetic products. Off J Eur Union L66:26–35
EU (2008) Council regulation of 30 May 2008 laying down test methods pursuant to regulation (EC) no. 1907/2006 of the European parliament and of the council on the registration, evaluation, authorisation and restriction of chemicals (REACH). Off J Eur Union L142:1–739
Fabjan E, Hulzebos E, Mennes W, Piersma AH (2006) A category approach for reproductive effects of phthalates. Crit Rev Toxicol 36:695–726
Farkas D, Shader RI, von Moltke LL, Greenblatt DJ (2008) Mechanisms and consequences of drug-drug interactions. In: Gad SC (ed) Preclinical development handbook: ADME and biopharmaceutical properties, chapter 25. Wiley, New York, pp 879–918
Fawcett DW, Leak LV, Heidger PM Jr (1970) Electron microscopic observations on the structural components of the blood-testis barrier. J Reprod Fert Suppl 10:105–122
Felter SP, Robinson MK, Basketter DA, Gerberick GF (2002) A review of the scientific basis for uncertainty factors for use in quantitative risk assessment for the induction of allergic contact dermatitis. Contact Derm 47(5):257–266
Felter SP, Ryan CA, Basketter DA, Gilmour NJ, Gerberick GF (2003) Application of the risk assessment paradigm to the induction of allergic contact dermatitis. Regul Toxicol Pharmacol 37(1):1–10
Felter SP, Lane RW, Latulippe ME, Llewellyn GC, Olin SS, Scimeca JA, Trautman TD (2009) Refining the threshold of toxicological concern (TTC) for risk prioritization of trace chemicals in food. Food Chem Toxicol 47:2236–2245
Ferrari T, Gini G (2010) An open source multistep model to predict mutagenicity from statitistical analysis and relevant structural alerts. Chem Cent J 4(suppl 1):S2. http://www.journal.chemistrycentral.com/content/4/S1/S2
Fielden MR, Brennan R, Gollub J (2007) A gene expression biomarker provides early prediction and mechanistic assessment of hepatic tumor induction by nongenotoxic chemicals. Toxicol Sci 99:90–100
Fielden MR, Nie A, McMillian M, Elangbam CS, Trela BA, Yang Y, Dunn RT, Dragan Y, Fransson-Stehen R, Bogdanffy M, Adams SP, Foster WR, Chen SJ, Rossi P, Kasper P, Jacobson-Kram D, Tatsuoka KS, Wier PJ, Gollub J, Halbert DN, Roter A, Young JK, Sina JF, Marlowe J, Martus HJ, Aubrecht J, Olaharski AJ, Roome N, Nioi P, Pardo I, Snyder R, Perry R, Lord P, Mattes W, Car BD (2008) Interlaboratory evaluation of genomic signatures for predicting carcinogenicity in the rat. Toxicol Sci 103:28–34
Fjodorova N, Vracko M, Novic M, Roncaglioni A, Benfenati E (2010) New public QSAR model for carcinogenicity. Chem Cent J 4(suppl 1):S3
Flint OP, Orton TC (1984) An in vitro assay for teratogens with cultures of rat embryo midbrain and limb bud cells. Toxicol Appl Pharmacol 76:383–395
Fort JD, Paul RRP (2002) Enhancing the predictive validity of frog embryo teratogenesis assay—xenopus (FETAX). J Appl Toxicol 22:185–191
Fowler P, Smith K, Jong J, Jeffrey L, Kirkland D, Pfuhler S, Carmichael P (in preparation) Reduction of misleading (false) positive results in mammalian genotoxicity assays. I. Choice of cell type. Mutat Res
Franchini JL, Propst JT, Comer GR, Yost MJ (2007) Novel tissue engineered tubular heart tissue for in vitro pharmaceutical toxicity testing. Microsc Microanal 13(4):267–271
Frankild S, Vølund A, Wahlberg JE, Andersen KE (2000) Comparison of the sensitivities of the Buehler test and the guinea pig maximization test for predictive testing of contact allergy. Acta Derm Venereol 80(4):256–262
Frankos VH (1985) FDA perspectives on the use of teratology data for human risk assessment. Fundam Appl Toxicol 5:615–625
Freyberger A, Weimer M, Tran HS, Ahr HJ (2009a) Assessment of a recombinant androgen receptor binding assay: initial steps towards validation. Reprod Toxicol 30(1):2–8
Freyberger A, Witters H, Weimer M, Lofink W, Berckmans P, Ahr HJ (2009b) Screening for (anti)androgenic properties using a standard operation protocol based on the human stably transfected androgen sensitive PALM cell line. First steps towards validation. Reprod Toxicol 30(1):9–17
Freyberger A, Wilson V, Weimer M, Tan S, Tran HS, Ahr HJ (2010) Assessment of a robust model protocol with accelerated throughput for a human recombinant full length estrogen receptor-alpha binding assay: protocol optimization and intralaboratory assay performance as initial steps towards validation. Reprod Toxicol 30(1):50–59
Galvão dos Santos G, Reinders J, Ouwehand K, Rustemeyer T, Scheper RJ, Gibbs S (2009) Progress on the development of human in vitro dendritic cell based assays for assessment of the sensitising potential of a compound. Toxicol Appl Pharmacol 236(3):372–382
Garberg P, Ball M, Borg N, Cecchelli R, Fenart L, Hurst RD, Lindmark T, Mabondzo A, Nilsson JE, Raub TJ, Stanimirovic D, Terasaki T, Oberg JO, Osterberg T (2005) In vitro models for the blood–brain barrier. Toxicol In Vitro 19(3):299–334
Garcia-Domenech R, de Julian-Ortiz JV, Besalu E (2006) True prediction of lowest observed adverse effect levels. Mol Divers 10(2):159–168
Gargas ML, Burgess RJ, Voisard DE, Cason GH, Andersen ME (1989) Partition coefficients of low-molecular-weight volatile chemicals in various liquids and tissues. Toxicol Appl Pharmacol 98:87–99
Gelman A, Bois F, Jiang JM (1996) Physiological pharmacokinetic analysis using population modeling and informative prior distributions. J Am Stat Assoc 91:1400–1412
Genschow E, Spielmann H, Scholz G, Seiler A, Brown N, Piersma A, Brady M, Clemann N, Huuskonen H, Paillard F, Bremer S, Becker K (2002) The ECVAM international validation study on in vitro embryotoxicity tests: results of the definitive phase and evaluation of prediction models. European centre for the validation of alternative methods. Altern Lab Anim 30:151–176
Georgopoulos PG, Roy A, Gallo MA (1994) Reconstruction of short-term multi-route exposure to volatile organic compounds using physiologically based pharmacokinetic models. J Expo Anal Environ Epidemiol 4:309–328
Gerberick GF, Robinson MK, Felter SP, White IR, Basketter DA (2001) Understanding fragrance allergy using an exposure-based risk assessment approach. Contact Derm 45(6):333–340
Gerberick GF, Vassallo JD, Bailey RE, Chaney JG, Morrall SW, Lepoittevin JP (2004) Development of a peptide reactivity assay for screening contact allergens. Toxicol Sci 81(2):332–343
Gerberick GF, Vassallo JD, Foertsch LM, Price BB, Chaney JG, Lepoittevin JP (2007) Quantification of chemical peptide reactivity for screening contact allergens: a classification tree model approach. Toxicol Sci 97(2):417–427
Gerberick F, Aleksic M, Basketter D, Casati S, Karlberg AT, Kern P, Kimber I, Lepoittevin JP, Natsch A, Ovigne JM, Rovida C, Sakaguchi H, Schultz T (2008) Chemical reactivity measurement and the predictive identification of skin sensitisers. Altern Lab Anim 36(2):215–242
Gerberick GF, Troutman JA, Foertsch LM, Vassallo JD, Quijano M, Dobson RL, Goebel C, Lepoittevin JP (2009) Investigation of peptide reactivity of prohapten skin sensitisers using a peroxidase-peroxide oxidation system. Toxicol Sci 112(1):164–174
Gerlowski LE, Jain RK (1983) Physiologically based pharmacokinetic modeling: principles and applications. J Pharmacol Sci 72:1103–1127
Ghisari M, Bonefeld-Jorgensen EC (2009) Effects of plasticizers and their mixtures on estrogen receptor and thyroid hormone functions. Toxicol Lett 189:67–77
Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd edn, revised and expanded ed. Marcel Dekker, New York
Gibbs S, van de Sandt JJ, Merk HF, Lockley DJ, Pendlington RU, Pease CK (2007) Xenobiotic metabolism in human skin and 3D human skin reconstructs: a review. Curr Drug Metab 8(8):758–772
Gilani SH, Alibhai Y (1990) Teratogenicity of metals to chick embryos. J Toxicol Environ Health 30:23–31
Gminski R, Tang T, Mersch-Sundermann V (2010) Cytotoxicity and genotoxicity in human lung epithelial A549 cells caused by airborne volatile organic compounds emitted from pine wood and oriented strand boards. Toxicol Lett 196(1):33–41
Gold LS, Manley NB, Slone TH, Garfinkel GB, Ames BN, Rohrbach L, Stern BR, Chow K (1995) Sixth plot of the carcinogenic potency database: results of animal bioassays published in the general literature 1989–1990 and by the national toxicology program 1990–1993. Environ Health Perspect 103(suppl 8):3–122
Gómez-Lechón MJ, Donato MT, Castell JV, Jover R (2003) Human hepatocytes as a tool for studying toxicity and drug metabolism. Curr Drug Metab 4(4):292–312
Gómez-Lechón MJ, Castell JV, Donato MT (2008) An update on metabolism studies using human hepatocytes in primary culture. Expert Opin Drug Metab Toxicol 4(7):837–854
Greim H, Arand M, Autrup H, Bolt HM, Bridges J, Dybing E, Glomot R, Foa V, Schulte-Hermann R (2006) Toxicological comments to the discussion about REACH. Arch Toxicol 80(3):121–124
Griem P, Goebel C, Scheffler H (2003) Proposal for a risk assessment methodology for skin sensitisation based on sensitisation potency data. Regul Toxicol Pharmacol 38(3):269–290
Griffiths CE, Dearman RJ, Cumberbatch M, Kimber I (2005) Cytokines and Langerhans cell mobilisation in mouse and man. Cytokine 32(2):67–70
Grindon C, Combes R, Cronin MT, Roberts DW, Garrod JF (2006) Integrated testing strategies for use in the EU REACH system. Altern Lab Anim 34(4):407–427
Grindon C, Combes R, Cronin MT, Roberts DW, Garrod JF (2008) An integrated decision-tree testing strategy for repeat dose toxicity with respect to the requirements of the EU REACH legislation. Altern Lab Anim 36(suppl 1):93–101
Gubbels-van Hal WM, Blaauboer BJ, Barentsen HM, Hoitink MA, Meerts IA, van der Hoeven JC (2005) An alternative approach for the safety evaluation of new and existing chemicals, an excersise in integrated testing. Regul Toxicol Pharmacol 42(3):284–295
Guguen-Guillouzo C, Corlu A, Guillouzo A (2010) Stem cell-derived hepatocytes and their use in toxicology. Toxicology 270(1):3–9
Guironnet G, Dalbiez-Gauthier C, Rousset F, Schmitt D, Peguet-Navarro J (2000) In vitro human T cell sensitisation to haptens by monocyte-derived dendritic cells. Toxicol In Vitro 14(6):517–522
Gülden M, Seibert H (2003) In vitro-in vivo extrapolation: estimation of human serum concentrations of chemicals equivalent cytotoxic concentrations in vitro. Toxicology 189:211–222
Gülden M, Mörchel S, Seibert H (2001) Factors influencing nominal effective concentrations of chemical compounds in vitro: cell concentration. Toxicol In Vitro 15:233–243
Guo L, Lobenhofer EK, Wang C, Shippy R, Harris SC, Zhang L, Mei N, Chen T, Herman D, Goodsaid FM, Hurban P, Philips KL, Deng QuJ, Sun YA X, Tong W, Dragon WT, Shi L (2006) Rat toxicogenomic study reveals analytical consistency across microarray platforms. Nat Biotechnol 24:1162–1169
Guyton KZ, Kyle AD, Aubrecht J, Cogliano VJ, Eastmond DA, Jackson M, Keshava N, Sandy MS, Sonawane B, Zhang L, Waters MD, Smith MT (2009) Improving prediction of chemical carcinogenicity by considering multiple mechanisms and applying toxicogenomic approaches. Mutat Res 681:230–240
Hah SS (2009) Recent advances in biomedical applications of accelerator mass spectrometry. J Biomed Sci 16:54. doi: 10.1186/1423-0127-16-54
Hallier-Vanuxeem D, Prieto P, Culot M, Diallo H, Landry C, Tati H, Cecchelli R (2009) New strategy for altering central nervous system toxicity: integration of blood brain barrier toxicity and permeability in neurotoxicity assessment. Toxicol In Vitro 23:447–453
Harry GJ, Billingsley M, Bruinink A, Campbell IL, Classen W, Dorman DC, Galli C, Ray D, Smith RA, Tilson HA (1998) In vitro techniques for the assessment of neurotoxicity. Environ Health Perspect 106(suppl 1):131–158
Hartig PC, Cardon MC, Blystone CR, Gray LE Jr, Wilson VS (2008) High throughput adjustable 96-well plate assay for androgen receptor binding: a practical approach for EDC screening using the chimpanzee AR. Toxicol Lett 181:126–131
Hartung T, Bremer S, Casati S, Coecke S, Corvi R, Fortaner S, Gribaldo L, Halder M, Hoffmann S, Roi AJ, Prieto P, Sabbioni E, Scott L, Worth A, Zuang V (2004) A modular approach to the ECVAM principles on test validity. Altern Lab Anim 32:467–472
Hastwell PW, Chai LL, Roberts KJ, Webster TW, Harvey JS, Rees RW, Walmsley RM (2006) High-specificity and high-sensitivity genotoxicity assessment in a human cell line: validation of the GreenScreen HC GADD45a-GFP genotoxicity assay. Mutat Res 607:160–175
Hattis D, Chu M, Rahmioglu N, Goble R, Verma P, Hartman K, Kozlak M (2008) A preliminary operational classification system for nonmutagenic modes of action for carcinogenesis. Critical Rev Toxicol 10:97–138
Hauser C, Katz SI (1990) Generation and characterization of T-helper cells by primary in vitro sensitisation using Langerhans cells. Immunol Rev 117:67–84
Hawksworth GM (2005) Isolation and culture of human renal cortical cells with characteristics of proximal tubules. Methods Mol Med 107:283–290
Hayden P, Letasiova S, Kandarova H, Jackson G, Klausner M (2010) Development of a vapour cup dosing method for evaluation of chemical toxicity in the EpiAirwayTM organotypic in vitro human airway model: an animal alternative model for inhalation toxicity evaluation. ALTEX 27(suppl 2/10):52
Helma C (2006) Lazy structure–activity relationships (lazar) for the prediction of rodent carcinogenicity and salmonella mutagenicity. Mol Divers 10:147–158
Henkens T, Papeleu P, Elaut G, Vinken M, Rogiers V, Vanhaecke T (2007) Trichostatin A, a critical factor in maintaining the functional differentiation of primary cultured rat hepatocytes. Toxicol Appl Pharmacol 218(1):64–71
Heringa MB, Schreurs RHMM, Busser F, van der Saag PT, van der Burg B, Hermens JL (2004) Towards more useful in vitro toxicity data with measured free concentrations. Environ Sci Technol 38:6263–6270
Hernández LG, van Steeg H, Luijten M, van Benthem J (2009) Mechanisms of non-genotoxic carcinogens and importance of a weight of evidence approach. Mutat Res 682:94–109
Hernández LG, Slob W, van Steeg H, van Benthem J (submitted) Carcinogen risk assessment using in vivo genotoxicity data and the benchmark dose approach. Environ Mol Mutagen
Hewitt NJ, Lechón MJ, Houston JB, Hallifax D, Brown HS, Maurel P, Kenna JG, Gustavsson L, Lohmann C, Skonberg C, Guillouzo A, Tuschl G, Li AP, LeCluyse E, Groothuis GM, Hengstler JG (2007a) Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies. Drug Metab Rev 39(1):159–234
Hewitt M, Madden JC, Rowe PH, Cronin MT (2007b) Structure-based modelling in reproductive toxicology: (Q)SARs for the placental barrier. SAR QSAR Environ Res 18:57–76
Hewitt M, Ellison CM, Enoch SJ, Madden JC, Cronin MTD (2010) Integrating (Q)SAR models, expert systems and read-across approaches for the prediction of developmental toxicity. Reprod Toxicol 30(1):147–160
Hirota M, Suzuki M, Hagino S, Kagatani S, Sasaki Y, Aiba S, Itagaki H (2009) Modification of cell-surface thiols elicits the activation of human monocytic cell line THP-1: possible involvement in the effect of haptens, 2–4 dinitrochlorobenzene and nickel sulfate. J Toxicol Sci 34(2):139–150
Hooyberghs J, Schoeters E, Lambrechts N, Nelissen I, Witters H, Schoeters G, Van Den Heuvel R (2008) A cell-based in vitro alternative to identify skin sensitisers by gene expression. Toxicol Appl Pharmacol 231(1):103–111
Houck KA, Kavlock RJ (2008) Understanding mechanisms of toxicity: insights from drug discovery research. Toxicol Appl Pharmacol 227(2):163–178
House RV, Thomas PT (1995) In vitro induction of cytotoxic T lymphocytes. In: Burleson GR, Dean JH, Munson AE (eds) Methods in immunotoxicology. Wiley-Liss, New York, pp 159–171
Houston JB, Galetin A (2008) Methods for predicting in vivo pharmacokinetics using data from in vitro assays. Curr Drug Metab 9(9):940–951
Hu T, Gibson DP, Carr GJ, Torontali SM, Tiesman JP, Chaney JG, Aardema MJ (2004) Identification of a gene expression profile that discriminates indirect-acting genotoxins from direct-acting genotoxins. Mutat Res 549:5–27
Hu T, Kaluzhny Y, Mun GC, Barnett B, Karetsky V, Wilt N, Klausner M, Curren R, Aardema MJ (2009) Intralaboratory and interlaboratory evaluation of the EpiDermTM 3D human reconstructed skin micronucleus (RSMN) assay. Mutat Res 673:100–108
Hu T, Khambatta ZS, Hayden PJ, Bolmarcich J, Binder RL, Robinson MK, Carr GJ, Tiesman JP, Jarrold BB, Osborne R, Reichling TD, Nemeth ST, Aardema MJ (2010) Xenobiotic metabolism gene expression in the EpiDerm in vitro 3D human epidermis model compared to human skin. Toxicol In Vitro 24:1450–1463
Huang S (2009) Standardization and pre-validation of MucilAir: a novel in vitro cell model of the human airway epithelium for testing acute and chronic effects of chemical compounds. 3R research foundation Switzerland 3R-project 106-07. http://www.forschung3r.ch/en/projects/pr_106_07.html . Accessed 15 Jan 2011
Hurtt ME, Cappon GD, Browning A (2003) Proposal for a tiered approach to developmental toxicity testing for veterinary pharmaceutical products for food-producing animals. Food Chem Toxicol 41:611–619
Hwan Sung J, Esch MB, Shuler ML (2010) Integration of in silico and in vitro platforms for pharmacokinetic-pharmacodynamic modeling. Expert Opin Drug Metab Toxicol 6:1–19
ILSI HESI ACT (2001) ILSI HESI alternatives to carcinogenicity testing project. Toxicol Pathol 29(supplement):1–351
Isfort RJ, Kerckaert GA, LeBoeuf RA (1996) Comparison of the standard and reduced pH Syrian hamster embryo (SHE) cell in vitro transformation assays in predicting the carcinogenic potential of chemicals. Mutat Res 356:11–63
Ishihara A, Rahman FB, Leelawatwattana L, Prapunpoj P, Yamauchi K (2009) In vitro thyroid hormone-disrupting activity in effluents and surface waters in Thailand. Environ Toxicol Chem 28:586–594
Jäckh C, Blatz V, Guth K, Reisinger K, Fabian E, van Ravenzwaay B, Landsiedel R (2010) Enzyme activities for xenobiotic metabolism in human reconstructed skin models. ALTEX 27(suppl 2/10):60
Jagger C, Tate M, Cahill PA, Hughes C, Knight AW, Billinton N, Walmsley RM (2009) Assessment of the genotoxicity of S9-generated metabolites using the GreenScreen HC GADD45a-GFP assay. Mutagenesis 24:35–50
Jamei M, Dickinson GL, Rostami-Hodjegan A (2009) A framework for assessing interindividual variability in pharmacokinetics using virtual human populations and integrating general knowledge of physical chemistry, biology, anatomy, physiology and genetics: a tale of ‘bottom-up’ vs ‘top-down’ recognition of covariates. Drug Metab Pharmacokinet 24:53–75
Jaworska J, Nikolova-Jeliazkova N (2007) How can structural similarity analysis help in category formation. SAR QSAR Environ Res 18:195–207
JECFA (1996) A procedure for the safety evaluation of flavouring agents. WHO food additive series 35. Annex 5. World Health Organization, Geneva
JECFA (1997) Safety evaluation of certain food additives and contaminants. Forty-ninth report of the joint FAO/WHO expert committee on food additives. WHO food additive series 40. World Health Organization, Geneva
Jelinek R (1977) The chick embryotoxicity screening test (CHEST). In: Neubert D, Merker HJ, Kwasigroch TE (eds) Methods in pre-natal toxicology. Thieme, Stuttgart, pp 381–386
Jelinek R, Marhan O (1994) Validation of the chick embryotoxicity screening test (CHEST). A comparative study. Funct Dev Morphol 4:317–323
Jelinek R, Peterka M, Rychter Z (1985) Chick embryotoxicity screening test—130 substances tested. Indian J Exp Biol 23:588–595
Jennings P (2010) The role of the Nrf2 pathway in nephrotoxicity. ALTEX 27(suppl 2/10):60–61
Jennings P, Aydin S, Bennett J, McBride R, Weiland C, Tuite N, Gruber LN, Perco P, Gaora PO, Ellinger-Ziegelbauer H, Ahr HJ, Van Kooten C, Daha MR, Prieto P, Ryan MP, Pfaller W, McMorrow T (2009) Inter-laboratory comparison of human renal proximal tubule (HK-2) transcriptome alterations due to Cyclosporine A exposure and medium exhaustion. Toxicol In Vitro 23(3):486–499
Jensen GE, Niemela JR, Wedebye EB, Nikolov NG (2008) QSAR models for reproductive toxicity and endocrine disruption in regulatory use—a preliminary investigation. SAR QSAR Environ Res 19:631–641
Jiang Y, Gerhold DL, Holder DJ, Figueroa DJ, Bailey WJ, Guan P, Skopek TR, Sistare FR, Sina JF (2007) Diagnosis of drug-induced renal tubular toxicity using global gene expression profiles. J Transl Med 5:47
Jones HM, Gardner IB, Watson KJ (2009) Modelling and PBPK simulation in drug discovery. AAPS J 11:155–166
Jonker MJ, Bruning O, van Iterson M, Schaap MM, van der Hoeven TV, Vrieling H, Beems RB, de Vries A, van Steeg H, Breit TM, Luijten M (2009) Finding transcriptomics biomarkers for in vivo identification of (non-)genotoxic carcinogens using wild-type and Xpa/p53 mutant mouse models. Carcinogenesis 30:1805–1812
Jowsey IR, Basketter DA, Westmoreland C, Kimber I (2006) A future approach to measuring relative skin sensitising potency: a proposal. J Appl Toxicol 26:341–350
Kane KL, Ashton FA, Schmitz JL, Folds JD (1996) Determination of natural killer cell function by flow cytometry. Clin Diagn Lab Immunol 3(3):295–300
Kapitulnik J, Pelkonen O, Gundert-Remy U, Dahl SG, Boobis AR (2009) Effects of pharmaceuticals and other active chemicals at biological targets: mechanisms, interactions, and integration into PB-PK/PD models. Expert Opin Therap Targets 13:867–887
Karlberg AT, Basketter D, Goossens A, Lepoittevin JP (1999) Regulatory classification of substances oxidized to skin sensitisers by exposure to the air. Contact Derm 40(4):183–188
Kasting G, Farahmand S, Nitsche J, Kern P, Gerberick F (2010) Epidermal bioavailability of volatile compounds. Application to fragrance disposition and skin sensitization risk assessment. Perfumer Flavorist 35
Kawakami T, Ishimura R, Nohara K, Takeda K, Tohyama C, Ohsako S (2006) Differential susceptibilities of Holtzman and Sprague–Dawley rats to fetal death and placental dysfunction induced by 2,3,7,8-teterachlorodibenzo-p-dioxin (TCDD) despite the identical primary structure of the aryl hydrocarbon receptor. Toxicol Appl Pharmacol 212:224–236
Keller D, Krauledat M, Scheel J (2009) Feasibility study to support a threshold of sensitization concern concept in risk assessment based on human data. Arch Toxicol 83(12):1049–1060
Kemper FH, Luepke NP (1986) Toxicity testing by the hens egg test (het). Food Chem Toxicol 24:647–648
Kettenhofen R, Bohlen H (2008) Preclinical assessment of cardiac toxicity. Drug Discov Today 13(15–16):702–707
Kienhuis AS, Wortelboer HM, Maas WJ, van Herwijnen M, Kleinjans JC, van Delft JH, Stierum RH (2007) A sandwich-cultured rat hepatocyte system with increased metabolic competence evaluated by gene expression profiling. Toxicol In Vitro 21(5):892–901
Kier LD, Neft R, Tang L, Suizu R, Cook T, Onsurez K, Tiegler K, Sakai Y, Ortiz M, Nolan T, Sankar U, Li AP (2004) Applications of microarrays with toxicologically relevant genes (tox genes) for the evaluation of chemical toxicants in Sprague–Dawley rats in vivo and human hepatocytes in vitro. Mutat Res 549(1–2):101–113
Kikkawa R, Yamamoto T, Fukushima T, Yamada H, Horii I (2005) Investigation of a hepatotoxicity screening system in primary cell cultures: “what biomarkers would need to be addressed to estimate toxicity in conventional and new approaches?”. J Toxicol Sci 30(1):61–72
Kikkawa R, Fujikawa M, Yamamoto T, Hamada Y, Yamada H, Horii I (2006) In vivo hepatotoxicity study of rats in comparison with in vitro hepatotoxicity screening system. J Toxicol Sci 31(1):23–34
Kim MS, Lee W, Kim YC, Park JK (2008) Microvalve-assisted patterning platform for measuring cellular dynamics based on 3D cell culture. Biotechnol Bioeng 101(5):1005–1013
Kimber I, Basketter DA (1992) The murine local lymph node assay: a commentary on collaborative studies and new directions. Food Chem Toxicol 30(2):165–169
Kimber I, Cumberbatch M, Dearman RJ, Bhushan M, Griffiths CE (2000) Cytokines and chemokines in the initiation and regulation of epidermal Langerhans cell mobilization. Br J Dermatol 142(3):401–412
Kimber I, Dearman RJ, Betts CJ, Gerberick GF, Ryan CA, Kern PS, Patlewicz GY, Basketter DA (2006) The local lymph node assay and skin sensitisation: a cut-down screen to reduce animal requirements? Contact Derm 54(4):181–185
Kirkland D, Fowler P (2010) Further analysis of Ames-negative rodent carcinogens that are only genotoxic in mammalian cells in vitro at concentrations exceeding 1 mM, including retesting of compounds of concern. Mutagenesis 25:539–553
Kirkland D, Speit G (2008) Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens III. Appropriate follow-up testing in vivo. Mutat Res 654:114–132
Kirkland D, Aardema M, Henderson L, Müller L (2005) Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens I. Sensitivity, specificity and relative predictivity. Mutat Res 584:1–256
Kirkland D, Aardema M, Müller L, Makoto H (2006) Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens II. Further analysis of mammalian cell results, relative predictivity and tumour profiles. Mutat Res 608:29–42
Kirkland D, Pfuhler S, Tweats D, Aardema M, Corvi R, Darroudi F, Elhajouji A, Glatt H, Hastwell P, Hayashi M, Kasper P, Kirchner S, Lynch A, Marzin D, Maurici D, Meunier J-R, Müller L, Nohynek G, Parry J, Parry E, Thybaud V, Tice R, van Benthem J, Vanparys P, White P (2007) How to reduce false positive results when undertaking in vitro genotoxicity testing and thus avoid unnecessary follow-up animal tests: report of an ECVAM workshop. Mutat Res 628:31–55
Kirkland D, Kasper P, Müller L, Corvi R, Speit G (2008) Recommended lists of genotoxic and non-genotoxic chemicals for assessment of the performance of new or improved genotoxicity tests: a follow-up to an ECVAM workshop. Mutat Res 653:99–108
Klaunig JE, Shi Y (2009) Assessment of gap junctional intercellular communication. Curr Protoc Toxicol, chapter 2, unit 2.17
Klaunig JE, Kamendulis LM, Hocevar BA (2010) Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol 38:96–109
Klopman G, Rosenkranz H (1994) Approaches to SAR in carcinogenesis and mutagenesis. Prediction of carcinogenicity/mutagenicity using MULTI-CASE. Mutat Res 305:33–46
Klotz DM, Ladlie BL, Vonier PM, McLachlan JA, Arnold SF (1997) o,p′-DDT and its metabolites inhibit progesterone-dependent responses in yeast and human cells. Mol Cell Endocrinol 129:63–71
Knight A, Jonker MJ, Bruning J (2005) Which drugs cause cancer? BMJ USA 5:477–478
Knight A, Bailey J, Balcombe J (2006) Animal carcinogenicity studies: implications for the REACH system. Altern Lab Anim 34(suppl 1):139–147
Kotwani A (1998) Use of chick embryo in screening for teratogenicity. Indian J Physiol Pharmacol 42:189–204
Kramer NI (2010) Measuring, modeling and increasing the free concentration of test chemicals in cell assays. PhD thesis, Utrecht University
Kramer NI, Hermens JLM, Schirmer K (2009) The influence of modes of action and physicochemical properties of chemicals on the correlation between in vitro and acute fish toxicity data. Toxicol In Vitro 23:1372–1379
Kreiling R, Hollnagel HM, Hareng L, Eigler D, Lee MS, Griem P, Dreesen B, Kleber M, Albrecht A, Garcia C, Wendel A (2008) Comparison of the skin sensitizing potential of unsaturated compounds and assessed by the murine local lymph node assay (LLNA) and the guinea pig maximization test (GPMT). Food Chem Toxicol 46(6):1896–1904
Krewski D, Acosta D Jr, Andersen M, Anderson H, Bailar JC III, Boekelheide K, Brent R, Charnley G, Cheung VG, Green S Jr, Kelsey KT, Kerkvliet NI, Li AA, McCray L, Meyer O, Patterson RD, Pennie W, Scala RA, Solomon GM, Stephens M, Yager J, Zeise L (2010) Toxicity testing in the 21st century: a vision and a strategy. J Toxicol Environ Health B Crit Rev 13:51–138
Kroes R, Kozianowski G (2002) Threshold of toxicological concern (TTC) in food safety assessment. Toxicol Lett 127(1–3):43–46
Kroes R, Renwick AG, Cheeseman M, Kleiner J, Mangelsdorf I, Piersma A, Schilter B, Schlatter J, van Schothorst F, Vos JG, Würtzen G (2004) Structure-based thresholds of toxicological concern (TTC): guidance for application to substances present at low levels in the diet. Food Chem Toxicol 42:65–83
Kroes R, Kleiner J, Renwick A (2005) The threshold of toxicological concern concept in risk assessment. Toxicol Sci 86(2):226–230
Kroes R, Renwick AG, Feron V, Galli CL, Gibney M, Greim H, Guy RH, Lhuguenot JC, van de Sandt JJ (2007) Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients. Food Chem Toxicol 45:2533–2562
Krüse J, Golden D, Wilkinson S, Williams F, Kezic S, Corish J (2007) Analysis, interpretation, and extrapolation of dermal permeation data using diffusion-based mathematical models. J Pharmacol Sci 96:682–703
Kucera P, Burnand MB (1987) Routine teratogenicity test that uses chick embryos in vitro. Teratog Carcinog Mutagen 7:427–447
Kulkarni SA, Zhu J, Blechinger S (2005) In silico techniques for the study and prediction of xenobiotic metabolism: a review. Xenobiotica 35(10–11):955–973
La SG, Farini D, De FM (2010) Estrogenic in vitro assay on mouse embryonic Leydig cells. Int J Dev Biol 54:717–722
Lambrechts N, Vanheel H, Hooyberghs J, De Boever P, Witters H, Van Den Heuvel R, Van Tendeloo V, Nelissen I, Schoeters G (2010) Gene markers in dendritic cells unravel pieces of the skin sensitisation puzzle. Toxicol Lett 196(2):95–103
Lambrot R, Muczynski V, Lecureuil C, Angenard G, Coffigny H, Pairault C, Moison D, Frydman R, Habert R, Rouiller-Fabre V (2009) Phthalates impair germ cell development in the human fetal testis in vitro without change in testosterone production. Environ Health Perspect 117:32–37
Landsiedel R, Fabian E, Gamer A, Kolle S, Ma-Hock L, Schulz M, Wiench K, Wohlleben W, van Ravenzwaay B (2010) The use of alternative methods for toxicity testing of nanomaterials. ALTEX 27 (suppl 2/10):78
Langezaal I, Hoffmann S, Hartung T, Coecke S (2002) Evaluation and prevalidation of an immunotoxicity test based on human whole-blood cytokine release. Altern Lab Anim 30(6):581–595
Lankveld DP, Van Loveren H, Baken KA, Vandebriel RJ (2010) In vitro testing for direct immunotoxicity: state-of-the-art, chapter 26. In: Dietert RR (ed) Immunotoxicity testing: methods and protocols methods in molecular biology. Humana Press Inc., Totowa, pp 401–423
Lappin G, Garner RC (2005) The use of accelerator mass spectrometry to obtain early human ADME/PK data. Expert Opin Drug Metab Toxicol 1(1):23–31
Lazzari G, Tessaro I, Crotti G, Galli C, Hoffmann S, Bremer S, Pellizzer C (2008) Development of an in vitro test battery for assessing chemical effects on bovine germ cells under the ReProTect umbrella. Toxicol Appl Pharmacol 233:360–370
Le Fevre AC, Boitier E, Marchandeau JP, Sarasin A, Thybaud V (2007) Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling. Mutat Res 619:16–29
Lee PJ, Hung PJ, Lee LP (2007) An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. Biotechnol Bioeng 97(5):1340–1346
Legendre A, Froment P, Desmots S, Lecomte A, Habert R, Lemazurier E (2010) An engineered 3D blood-testis barrier model for the assessment of reproductive toxicity potential. Biomaterials 31:4492–4505
Lemeire K, Van Merris V, Cortvrindt R (2007) The antibiotic streptomycin assessed in a battery of in vitro tests for reproductive toxicology. Toxicol In Vitro 21:1348–1353
Lewis DF, Ito Y (2008) Human cytochromes P450 in the metabolism of drugs: new molecular models of enzyme-substrate interactions. Experts Opin Drug Metab Toxicol 4(9):1181–1186
Li AP (2008) In vitro evaluation of metabolic drug-drug interactions: scientific concepts and practical considerations. In: Gad SC (ed) Preclinical development handbook: ADME and biopharmaceutical properties, chapter 24. Wiley, New York, pp 853–878
Li W, Lam M, Choy D, Birkeland A, Sullivan ME, Post JM (2006) Human primary renal cells as a model for toxicity assessment of chemo-therapeutic drugs. Toxicol In Vitro 20(5):669–676
Li HH, Aubrecht J, Fornace AJ Jr (2007) Toxicogenomics: overview and potential applications for the study of non-covalent DNA interacting chemicals. Mutat Res 623:98–108
Liao KH, Tan YM, Clewell HJ (2007) Development of a screening approach to interpret human biomonitoring data on volatile organic compounds: reverse dosimetry on biomonitoring data for trichloroethylene. Risk Anal 27:1223–1236
Lima BS, van der Laan JW (2000) Mechanisms of nongenotoxic carcinogenesis and assessment of the human hazard. Regul Toxicol Pharmacol 32:135–143
Lippman M, Bolan G, Huff K (1976) The effects of estrogens and antiestrogens on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res 36:4595–4601
Loeb LA, Harris CC (2008) Advances in chemical carcinogenesis: a historical review and prospective. Cancer Res 68:6863–6872
Loizou GD, Spendiff M, Barton HA, Bessems J, Bois FY, d’Yvoire MB, Buist H, Clewell HJ III, Gundert-Remy U, Goerlitz G, Meek B Schmitt W (2008) Development of good modelling practice for physiologically based pharmacokinetic models for use in risk assessment: the first steps. Regul Toxicol Pharmacol 50:400–411
Long M, Laier P, Vinggaard AM, Andersen HR, Lynggaard J, Bonefeld-Jorgensen EC (2003) Effects of currently used pesticides in the AhR-CALUX assay: comparison between the human TV101L and the rat H4IIE cell line. Toxicology 194:77–93
López-Lázaro M (2010) A new view of carcinogenesis and an alternative approach to cancer therapy. Mol Med 16:144–153
Luciano AM, Franciosi F, Lodde V, Corbani D, Lazzari G, Crotti G, Galli C, Pellizzer C, Bremer S, Weimer M, Modina SC (2010) Transferability and inter-laboratory variability assessment of the in vitro bovine oocyte maturation (IVM) test within ReProTect. Reprod Toxicol 30(1):81–88
Luijten M, van Beelen VA, Verhoef A, Renkens MF, van Herwijnen MH, Westerman A, van Schooten FJ, Pennings JL, Piersma AH (2010) Transcriptomics analysis of retinoic acid embryotoxicity in rat postimplantation whole embryo culture. Reprod Toxicol 30:333–340
Lyons MA, Yang RSH, Mayeno AN, Reisfeld B (2008) Computational toxicology of chloroform: reverse dosimetry using bayesian inference, markov chain monte carlo simulation, and human biomonitoring data. Environmental and health Perspectives 116:1040–1046
Ma B, Zhang G, Qin J, Lin B (2009) Characterization of drug metabolites and cytotoxicity assay simultaneously using an integrated microfluidic device. Lab Chip 9(2):232–238
Madden JC (2010) In silico approaches for predicting ADME properties. In: Puzyn T, Leszczynski J, Cronin MTD (eds) Recent advances in QSAR studies—methods and applications. Springer, Dordrecht, pp 283–304
Magnusson B, Kligman AM (1970) Allergic contact dermatitis in the guinea pig: identification of contact allergens. Charles C. Thomas, Springfield
MAQC Consortium (2006) The microarray quality control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements. Nat Biotechnol 24:1151–1161
Marchant C, Fisk L, Note R, Patel M, Surez D (2009) An expert system approach to the assessment of hepatotoxic potential. Chem Biodivers 6(11):2107–2114
Martin MT, Judson RS, Reif DM, Kavlock RJ, Dix DJ (2009) Profiling chemicals based on chronic toxicity results from the US EPA ToxRef Database. Environ Health Perspect 117:392–399
Martin SF, Esser PR, Schmucker S, Dietz L, Naisbitt DJ, Park BK, Vocanson M, Nicolas JF, Keller M, Pichler WJ, Peiser M, Luch A, Wanner R, Maggi E, Cavani A, Rustemeyer T, Richter A, Thierse HJ, Sallusto F (2010) T cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays. Cell Mol Life Sci 67(24):4171–4184
Martínez-Jiménez CP, Castell JV, Gómez-Lechón MJ, Jover R (2006) Transcriptional activation of CYP2C9, CYP1A1, and CYP1A2 by hepatocyte nuclear factor 4alpha requires coactivators peroxisomal proliferator activated receptor-gamma coactivator 1alpha and steroid receptor coactivator 1. Mol Pharmacol 70(5):1681–1692
Marx-Stoelting P, Adriaens E, Ahr HJ, Bremer S, Garthoff B, Gelbke HP, Piersma A, Pellizzer C, Reuter U, Rogiers V, Schenk B, Schwengberg S, Seiler A, Spielmann H, Steemans M, Stedman DB, Vanparys P, Vericat JA, Verwei M, van der Water F, Weimer M, Schwarz M (2009) A review of the implementation of the embryonic stem cell test (EST). The report and recommendations of an ECVAM/ReProTect workshop. Altern Lab Anim 37:313–328
Mathijs K, Brauers KJ, Jennen DGJ, Lizarraga D, Kleinjans JCS, van Delft JHM (2010) Gene expression profiling in primary mouse hepatocytes discriminates true from false-positive genotoxic compounds. Mutagenesis 25:561–568
Matthews EJ, Spalding JW, Tennant RW (1993) Transformation of BALB/c-3T3 cells: V. Transformation responses of 168 chemicals compared with mutagenicity in salmonella and carcinogenicity in rodent bioassays. Environ Health Perspect 101(suppl 2):347–482
Matthews EJ, Kruhlak NL, Benz RD, Contrera JF (2004a) Assessment of the health effects of chemicals in humans: I. QSAR estimation of the maximum recommended therapeutic dose (MRTD) and no effect level (NOEL) of organic chemicals based on clinical trial data. Curr Drug Discov Technol 1(1):61–76
Matthews EJ, Kruhlak NL, Weaver JL, Benz RD, Contrera JF (2004b) Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling. Curr Drug Discov Technol 1(4):243–254
Matthews EJ, Kruhlak NL, Benz RD, Contrera JF, Marchant CA, Yang C (2008) Combined use of MC4PC, MDL-QSAR, BioEpisteme, Leadscope PDM, and Derek for Windows Software to achieve high-performance, high-confidence, mode of action-based predictions of chemical carcinogenesis in rodents. Toxicol Mech Methods 18:189–206
Maunz A, Helma C (2008) Prediction of chemical toxicity with local support vector regression and activity-specific kernels. SAR QSAR Environ Res 19(5–6):413–431
Maurici D, Aardema M, Corvi R, Kleber M, Krul C, Laurent C, Loprieno N, Pasanen M, Pfuhler S, Phillips B, Sabbioni E, Sanner T, Vanparys P (2005) Genotoxicty and mutagenicity. Altern Lab Anim 33(suppl 1):117–130
Maxwell G, Mackay C (2008) Application of a systems biology approach to skin allergy risk assessment. Altern Lab Anim 36(5):521–556
Mazzatorta P, Tran L-A, Schilter B, Grigorov M (2007) Integration of structure activity relationship and artificial intelligence systems to improve in silico prediction of Ames test mutagenicity. J Chem Inf Model 47(1):34–38
Mazzatorta P, Estevez MD, Coulet M, Schilter B (2008) Modeling oral rat chronic toxicity. J Chem Inf Model 48(10):1949–1954
McKim JM, Keller DJ, Gorski JR (2010) A new in vitro method for identifying chemical sensitizers combining peptide binding with ARE/EpRE-mediated gene expression in human skin cells. Cutan Ocul Toxicol 29(3):171–192
Meek ME (2004) Biologically motivated computational modeling: contribution to risk assessment. Toxicol Sci 82:1–2
Mehdipour AR, Hamidi M (2009) Brain drug targeting: a computational approach for overcoming blood–brain barrier. Drug Discov Today 14:1030–1036
Mekenyan O, Dimitrov S, Serafimova R, Thompson E, Kotov S, Dimitrova N, Walker JD (2004) Identification of the structural requirements for mutagenicity by incorporating molecular flexibility and metabolic activation of chemicals I: TA100 model. Chem Res Toxicol 17:753–766
Mekenyan O, Todorov M, Serafimova R, Stoeva S, Aptula A, Finking R, Jacob E (2007) Identifying the structural requirements for chromosomal aberration by incorporating molecular flexibility and metabolic activation of chemicals. Chem Res Toxicol 20:1927–1941
Mellman I, Steinman RM (2001) Dendritic cells: specialized and regulated antigen processing machines. Cell 106(3):255–258
Meneses-Lorente G, Watt A, Salim K, Gaskell SJ, Muniappa N, Lawrence J, Guest PC (2006) Identification of early proteomic markers for hepatic steatosis. Chem Res Toxicol 19(8):986–998
Mielke H, Anger LT, Schug M, Hengstler JG, Stahlmann R, Gundert-Remy U (2010) A physiologically based toxicokinetic modelling approach to predict relevant concentrations for in vitro testing. Arch Toxicol [Epub ahead of print]
Miller CL, Eaves CJ (2002) Long-term culture-initiating cell assays for human and murine cells. In: Klug CA, Jordan CT (eds) Haematopoietic stem cell protocols. Humana Press Inc., New Jersey, pp 123–141
Molina-Molina JM, Hillenweck A, Jouanin I, Zalko D, Cravedi JP, Fernandez MF, Pillon A, Nicolas JC, Olea N, Balaguer P (2006) Steroid receptor profiling of vinclozolin and its primary metabolites. Toxicol Appl Pharmacol 216:44–54
Moore P, Ogilvie J, Horridge E, Mellor IR, Clothier RH (2005) The development of an innervated epithelial barrier model using a human corneal cell line and ND7/23 sensory neurons. Eur J Cell Biol 84(5):581–592
Morck TJ, Sorda G, Bechi N, Rasmussen BS, Nielsen JB, Ietta F, Rytting E, Mathiesen L, Paulesu L, Knudsen LE (2010) Placental transport and in vitro effects of Bisphenol A. Reprod Toxicol 30(1):131–137
Mortishire-Smith RJ, Skiles GL, Lawrence JW, Spence S, Nicholls AW, Johnson BA, Nicholson JK (2004) Use of metabonomics to identify impaired fatty acid metabolism as the mechanism of a drug-induced toxicity. Chem Res Toxicol 17(2):165–173
Mose T, Kjaerstad MB, Mathiesen L, Nielsen JB, Edelfors S, Knudsen LE (2008) Placental passage of benzoic acid, caffeine, and glyphosate in an ex vivo human perfusion system. J Toxicol Environ Health A 71:984–991
Moss E, Lynagh S, Smith D, Kelly S, McDaid A, Bunton D (2010) A novel system for the investigation of microvascular dysfunction including vascular permeability and flow-mediated dilatation in pressurised human arteries. J Pharmacol Toxicol Methods 62(1):40-46
Mostrag-Szlichtyng A, Worth A (2010) Review of QSAR models and software tools for predicting biokinetic properties. EUR 24377 EN. European Commission, Luxembourg
Müller L, Mauthe RJ, Riley CM, Andino MM, Antonis DD, Beels C, DeGeorge J, De Knaep AG, Ellison D, Fagerland JA, Frank R, Fritschel B, Galloway S, Harpur E, Humfrey CD, Jacks AS, Jagota N, Mackinnon J, Mohan G, Ness DK, O’Donovan MR, Smith MD, Vudathala G, Yotti L (2006) A rationale for determining, testing, and controlling specific impurities in pharmaceuticals that possess potential for genotoxicity. Regul Toxicol Pharmacol 44:198–211
Mumtaz MM, Knauf LA, Reisman DJ, Peirano WB, DeRosa CT, Gombar VK, Enslein K, Carter JR, Blake BW, Huque KI, Ramanujam MS (1995) Assessment of effect levels of chemicals from quantitative structure–activity relationship (QSAR) models. I. Chronic lowest-observed-adverse effect level (LOAEL). Toxicol Lett 79(1–3):131–143
Mun GC, Aardema MJ, Hu T, Barnett B, Kaluzhny Y, Klausner M, Karetsky V, Dahl EL, Curren RD (2009) Further development of the EpiDermTM 3D reconstructed human skin micronucleus (RSMN) assay. Mutat Res 673:92–99
Munro IC, Ford RA, Kennepohl E, Sprenger JG (1996a) Thresholds of toxicological concern based on structure–activity relationships. Drug Metab Rev 28(1–2):209–217
Munro IC, Ford RA, Kennepohl E, Sprenger JG (1996b) Correlation of structural class with no-observed effect levels: a proposal for establishing a threshold of concern. Food ChemToxicol 34:829–867
Munro IC, Renwick AG, Danielewska-Nikiel B (2008) The threshold of toxicological concern (TTC) in risk assessment. Toxicol Lett 180(2):151–156
Muster W, Breidenbach A, Fischer H, Kirchner S, Muller L, Pahler A (2008) Computational toxicology in drug development. Drug Discov Today 13(7–8):303–310
Myllynen P, Immonen E, Kummu M, Vahakangas K (2009) Developmental expression of drug metabolizing enzymes and transporter proteins in human placenta and fetal tissues. Expert Opin Drug Metab Toxicol 5:1483–1499
Myren M, Mose T, Mathisen L, Knudsen LE (2007) The human placenta—an alternative to foetal exposure. Toxicol In Vitro 21:1332–1340
Nagel R (2002) DarT: the embryo test with the zebrafish danio rerio—a general model in ecotoxicology and toxicology. ALTEX 19(suppl 1):38–48
Naiki T, Nagaki M, Asano T, Kimata T, Moriwaki H (2005) Adenovirus-mediated hepatocyte nuclear factor-4alpha overexpression maintains liver phenotype in cultured rat hepatocytes. Biochem Biophys Res Commun 335(2):496–500
Nakai D, Kumamoto K, Sakikawa Ch, Kosaka T, Tokui T (2004) Evaluation of protein binding ratio of drugs by a micro-scale uktracentrifugation method. J Pharmaceut Sci 93:847–851
Natsch A (2010) The Nrf2-Keap1-ARE toxicity pathway as a cellular sensor for skin sensitisers functional relevance and a hypothesis on innate reactions to skin sensitisers. Toxicol Sci 113(2):284–292
Natsch A, Emter R (2008) Skin sensitisers induce antioxidant response element dependent genes: application to the in vitro testing of the sensitisation potential of chemicals. Toxicol Sci 102(1):110–119
Natsch A, Gfeller H (2008) LC–MS based characterization of the peptide reactivity of chemicals to improve the in vitro prediction of the skin sensitisation potential. Toxicol Sci 106(2):464–478
Natsch A, Emter R, Ellis G (2009) Filling the concept with data: integrating data from different in vitro and in silico assays on skin sensitisers to explore the battery approach for animal-free skin sensitisation testing. Toxicol Sci 107(1):106–121
Nestorov I (2007) Whole-body physiologically based pharmacokinetic models. Expert Opin Drug Metab Toxicol 3:235–249
Nie AY, McMillian M, Parker JB, Leone A, Bryant S, Yieh L, Bittner A, Nelson J, Carmen A, Wan J, Lord PG (2006) Predictive toxicogenomics approaches reveal underlying molecular mechanisms of nongenotoxic carcinogenicity. Mol Carcinog 45:914–933
Nioi P, Pardo ID, Sherratt PJ, Snyder RD (2008) Prediction of non-genotoxic carcinogenesis in rats using changes in gene expression following acute dosing. Chem Biol Interact 172:206–215
Nohynek GJ, Antignac E, Re T, Toutain H (2010) Safety assessment of personal care products/cosmetics and their ingredients. Toxicol Appl Pharmacol 243(2):239–259
NRC, National Research Council (2007) Toxicity testing in the 21st century: a vision and a strategy. National Academies Press, Washington, DC
OECD, Organisation for Economic Cooperation and Development (1981a) Test guideline on repeated dose dermal toxicity: 21/28-day study, Paris
OECD, Organisation for Economic Cooperation and Development (1981b) Test guideline on repeated dose dermal toxicity: 90-day study, Paris
OECD, Organisation for Economic Cooperation and Development (1983) Guideline for the testing of chemicals 415. One-generation reproduction toxicity study, Paris
OECD, Organisation for Economic Cooperation and Development (1992) Skin sensitisation guidelines for testing of chemicals no. 406, Paris
OECD, Organisation for Economic Cooperation and Development (1995) Guideline for the testing of chemicals 421. Reproduction/developmental toxicity screening test, Paris
OECD, Organisation for Economic Cooperation and Development (1996) Guideline for the testing of chemicals 422. Combined repeated dose toxicity study with the reproduction/developmental toxicity screening test, Paris
OECD, Organisation for Economic Cooperation and Development (1998a) Test guideline on repeated Dose 90-day oral toxicity study in rodents, Paris
OECD, Organisation for Economic Cooperation and Development (1998b) Test guideline on repeated dose 90-day oral toxicity study in non-rodents, Paris
OECD, Organisation for Economic Cooperation and Development (2001a) Guideline for the testing of chemicals 414. Prenatal development toxicity study, Paris
OECD, Organisation for Economic Cooperation and Development (2001b) Guideline for the testing of chemicals 416. Two-generation reproduction toxicity, Paris
OECD, Organisation for Economic Cooperation and Development (2002) The local lymph node assay. Guidelines for testing of chemicals no. 429, Paris
OECD, Organisation for Economic Cooperation and Development (2004a) OECD series on testing and assessment number 49. Report from the expert group on (quantitative) structure–activity relationships [(Q)SARs] on the principles for the validation of (Q)SARs, Paris
OECD, Organisation for Economic Cooperation and Development (2004b) Test guideline 428. Skin absorption: in vitro method. Available via http://www.oecdilibrary.org/docserver/download/fulltext/9742801e.pdf?expires=1275558971&id=0000&accname=Dutch+Government&checksum=4396D617A72B24A90D1DE616728D8258
OECD, Organisation for Economic Cooperation and Development (2007a) Guidance document on the validation of (quantitative) structure–activity relationships [(Q)SAR] models, Paris
OECD, Organisation for Economic Cooperation and Development (2007b) Guidance on grouping of chemicals, OECD environment health and safety publications, series on testing and assessment no. 80. http://www.appli1.oecd.org/olis/2007doc.nsf/linkto/env-jm-mono(2007)28
OECD, Organisation for Economic Cooperation and Development (2007c) Guideline for the testing of chemicals 426. Developmental neurotoxicity study, Paris
OECD, Organisation for Economic Cooperation and Development (2007d) Guideline for the testing of chemicals 440. Uterotrophic bioassay in rodents. A short-term screening test for oestrogenic properties, Paris
OECD, Organisation for Economic Cooperation and Development (2007e) Detailed review on cell transformation assays for detection of chemical carcinogens, OECD environment, health and safety publications, series on testing and assessment, no. 31. http://www.oecd.org/officialdocuments/displaydocumentpdf?cote=env/jm/mono(2007)18&doclanguage=en
OECD, Organisation for Economic Cooperation and Development (2008a) Test guideline on repeated Dose 28-day oral toxicity study in rodents, Paris
OECD, Organisation for Economic Cooperation and Development (2008b) Guidance document 43: guidance document on mammalian reproductive toxicity testing and assessment, Paris
OECD, Organisation for Economic Cooperation and Development (2009a) Test guideline on subacute inhalation toxicity: 28-day study, Paris
OECD, Organisation for Economic Cooperation and Development (2009b). OECD guideline for the testing of chemicals 441. Hershberger bioassay in rats. A short-term screening assay for (anti)androgenic properties, Paris
OECD, Organisation for Economic Cooperation and Development (2009c). OECD guideline for the testing of chemicals 455. The stably transfected human estrogen receptor-alpha transcriptional activation assay for detection of estrogenic agonist-activity of chemicals, Paris
OECD, Organisation for Economic Cooperation and Development (2009d). OECD draft proposal for an extended one-generation reproductive toxicity study, Paris
OECD, Organisation for Economic Cooperation and Development (2009e) Test guideline on subchronic inhalation toxicity: 90-day study, Paris
OECD, Organisation for Economic Cooperation and Development (2009f) Test guideline on chronic toxicity studies, Paris
OECD, Organisation for Economic Cooperation and Development (2010a) Guidelines for the testing of chemicals, section 4: health effects. Test no. 417: Toxicokinetics, Paris
OECD, Organisation for Economic Cooperation and Development (2010b) Skin sensitization: local lymph node assay: DA, guidelines for testing of chemicals no. 442A, Paris
OECD, Organisation for Economic Cooperation and Development (2010c) Skin sensitization: local lymph node assay: BrdU-ELISA, guidelines for testing of chemicals no. 442B, Paris
OECD, Organisation for Economic Cooperation and Development (2010d) http://www.oecd.org/dataoecd/33/37/37849783.pdf . Accessed 30 June 2010
OECD, Organisation for Economic Cooperation and Development (2010e) OECD guideline for the testing of chemicals draft proposal for a new guideline 4XX. The H295R steroidogenisis assay, Paris
OECD, Organisation for Economic Co-operation and Development (2004c) Guidance document 28 for the conduct of skin absorption studies, Paris, March, 1–31
Ohmori K, Umeda M, Tanaka N, Takagi H, Yoshimura I, Sasaki K, Asada S, Sakai A, Araki H, Asakura M, Baba H, Fushiwaki Y, Hamada S, Kitou N, Nakamura T, Nakamura Y, Oishi H, Sasaki S, Shimada S, Tsuchiya T, Uno Y, Washizuka M, Yajima S, Yamamoto Y, Yamamura E, Yatsushiro T (2005) Non-genotoxic carcinogen study group in the environmental mutagen society of Japan. An inter-laboratory collaborative study by the non-genotoxic carcinogen study group in Japan, on a cell transformation assay for tumour promoters using Bhas 42 cells. Altern Lab Anim 33:619–639
Olson H, Betton G, Robinson D, Thomas K, Monro A, Kolaja G, Lilly P, Sanders J, Sipes G, Bracken W, Dorato M, Van Deun K, Sith P, Berger B, Heller A (2000) Concordance of the toxicity of pharmaceuticals in humans and animals. Regul Toxicol Pharmacol 32(1):56–67
Oomen AG, Tolls J, Sips AJ, Groten JP (2003) In vitro intestinal lead uptake and transport in relation to speciation. Arch Environ Contam Toxicol 44(1):116–124
Oosterhuis B (2010) Trends in microdosing and other exploratory human pharmacokinetic studies for early drug development. Bioanalysis 2(3):377–379
Orman MA, Arai K, Yarmush ML, Androulakis IP, Berthiaume F, Ierapetritou MG (2010) Metabolic flux determination in perfused livers by mass balance analysis: effect of fasting. Biotechnol Bioeng 107(5):825–835
Osman AM, van Dartel DA, Zwart E, Blokland M, Pennings JL, Piersma AH (2010) Proteome profiling of mouse embryonic stem cells to define markers for cell differentiation and embryotoxicity. Reprod Toxicol 30:322–332
Ott H, Bergström MA, Heise R, Skazik C, Zwadlo-Klarwasser G, Merk HF, Baron JM, Karlberg AT (2009) Cutaneous metabolic activation of carvoxime, a self-activating, skin-sensitizing prohapten. Chem Res Toxicol 22(2):399–405
Ouwehand K, Santegoets SJ, Bruynzeel DP, Scheper RJ, de Gruijl TD, Gibbs S (2008) CXCL12 is essential for migration of activated Langerhans cells from epidermis to dermis. Eur J Immunol 38(11):3050–3059
Ouwehand K, Spiekstra SW, Reinders J, Scheper RJ, de Gruijl TD, Gibbs S (2010) Comparison of a novel CXCL12/CCL5 dependent migration assay with CXCL8 secretion and CD86 expression for distinguishing sensitisers from non-sensitisers using MUTZ-3 Langerhans cells. Toxicol In Vitro 24(2):578–585
Pant K, Sly JE, Bruce SW, Leung C, San RH (2008) Syrian hamster embryo (SHE) cell transformation assay with conditioned media (without X-ray irradiated feeder layer) using 2,4-diaminotoluene, 2,6-diaminotoluene and chloral hydrate. Mutat Res 654:108–113
Paquette JA, Kumpf SW, Streck RD, Thomson JJ, Chapin RE, Stedman DB (2008) Assessment of the embryonic stem cell test and application and use in the pharmaceutical industry. Birth Defects Res B Dev Reprod Toxicol 83:104–111
Park KB, Dalton-Brown E, Hirst C, Williams DP (2006) Selection of new chemical entities with decreased potential for adverse drug reactions. Eur J Pharmacol 549:1–8
Parry JM, Parry E, Phrakonkham P, Corvi R (2010) Analysis of published data for top concentration considerations in mammalian cell genotoxicity testing. Mutagenesis 25:531–538
Patlewicz GY, Worth A (2008) Review of data sources, QSARs and integrated testing strategies for skin sensitisation. EUR 23225 EN
Patlewicz G, Aptula AO, Uriarte E, Roberts DW, Kern PS, Gerberick GF, Kimber I, Dearman RJ, Ryan CA, Basketter DA (2007) An evaluation of selected global (Q)SARs/expert systems for the prediction of skin sensitisation potential. SAR QSAR Environ Res 18(5–6):515–541
Patlewicz G, Jeliazkova N, Gallegos Saliner A, Worth AP (2008) Toxmatch—a new software tool to aid in the development and evaluation of chemically similar groups. SAR QSAR Environ Res 19:397–412
Pauwels M, Rogiers V (2009)The safety evaluation of cosmetic ingredients at the EU level and the use of 3R-alternatives: an update. Poster presentation in the “7th world congress on alternatives & animal use in the life sciences”, Rome, Italy. ALTEX 26(special issue):193
Pauwels M, Rogiers V (2010) Human health safety evaluation of cosmetics in the EU: a legally imposed challenge to science. Toxicol Appl Pharmacol 243:260–274
Pauwels M, Dejaegher B, Vander Heyden Y, Rogiers V (2009) Critical analysis of the SCCNFP/SCCP safety assessment of cosmetic ingredients (2000–2006). Food Chem Toxicol 47(4):898–905
Pedersen F, de Bruijn J, Munn S, van Leeuwen K (2003) Assessment of additional testing needs under REACH—effects of (Q)SARs, risk based testing and voluntary industry initiatives, 33 pp. http://www.ecb.jrc.ec.europa.eu/documents/REACH/PUBLICATIONS/REACH_testing_needs_final.pdf , JRC Report EUR 20863. Accessed 11 July 2010
Peer Consultation on Health Canada Draft Weight of Evidence Framework for Genotoxic Carcinogenicity (2005) http://www.tera.org/peer/comhaz/HC%20QSAR%20Peer%20Consultation%20Overview.pdf
Pelkonen O, Turpeinen M (2007) In vitro-in vivo extrapolation of hepatic clearance: biological tools, scaling factors, model assumptions and correct concentrations. Xenobiotica 37:1066–1089
Pelkonen O, Turpeinen M, Uusitalo J, Rautio A, Raunio H (2005) Prediction of drug metabolism and interactions on the basis of in vitro investigations. Basic Clin Pharmacol Toxicol 96(3):167–175
Pelkonen O, Kapitulnik J, Gundert-Remy U, Boobis AR, Stockis A (2008a) Local kinetics and dynamics of xenobiotics. Crit Rev Toxicol 38:697–720
Pelkonen O, Tolonen A, Turpeinen M, Uusitalo J (2008b) In vitro metabolism in preclinical drug development. In: Gad SC (ed) Preclinical development handbook: ADME and biopharmaceutical properties, chapter 21. Wiley, New York, pp 743–774
Pelkonen O, Turpeinen M, Hakkola J, Honkakoski P, Hukkanen J, Raunio H (2008c) Inhibition and induction of human cytochrome P450 enzymes—current status. Arch Toxicol 82:667–715
Pelkonen O, Tolonen A, Korjamo T, Turpeinen M, Raunio H (2009a) From known knowns to known unknowns: predicting in vivo drug metabolites. Bioanalysis 1:393–414
Pelkonen O, Tolonen A, Rousu T, Tursas L, Turpeinen M, Hokkanen J, Uusitalo J, Bouvier d’Yvoire M, Coecke S (2009b) Comparison of metabolic stability and metabolite identification of 55 ECVAM/ICCVAM validation compounds between human and rat liver homogenates and microsomes—a preliminary analysis. ALTEX.26(3):214–22
Pendlington RU, Minter HJ, Stupart L, MacKay C, Roper CS, Sanders DJ, Pease CK (2008) Development of a modified in vitro skin absorption method to study the epidermal/dermal disposition of a contact allergen in human skin. Cutan Ocul Toxicol 27(4):283–294
Péry AR, Brochot C, Desmots S, Boize M, Sparfel L, Fardel O (2010) Predicting in vivo gene expression in macrophages after exposure to benzo(a)pyrene based on in vitro assays and toxicokinetic/toxicodynamic models. Toxicol Lett 201(1):8–14
Pessina A, Albella B, Bayo M, Bueren J, Brantom P, Casati S, Croera C, Gagliardi G, Foti P, Parchment R, Parent-Massin D, Schoeters G, Sibiril Y, Van Den Heuvel R, Gribaldo L (2003) Application of the CFU-GM assay to predict acute drug-induced neutropenia: an international blind trial to validate a prediction model for the maximum tolerated dose (MTD) of myelosuppressive xenobiotics. Toxicol Sci 75(2):355–367
Pessina A, Malerba I, Gribaldo L (2005) Hematotoxicity testing by cell clonogenic assay in drug development and preclinical trials. Curr Pharm Des 11(8):1055–1065
Pessina A, Bonomi A, Cavicchini L, Albella B, Cerrato L, Parent-Massin D, Sibiril Y, Parchment R, Behrsing H, Verderio P, Pizzamiglio S, Giangreco M, Baglio C, Coccè V, Sisto F, Gribaldo L (2010) Prevalidation of the rat CFU-GM assay for in vitro toxicology applications. Altern Lab Anim 38(2):105–117
Peters AK, Wouwer GV, Weyn B, Verheyen GR, Vanparys P, Gompel JV (2008) Automated analysis of contractility in the embryonic stem cell test, a novel approach to assess embryotoxicity. Toxicol In Vitro 22:1948–1956
Petrak J, Myslivcova D, Man P, Cmejla R, Cmejlova J, Vyoral D (2006) Proteomic analysis of iron overload in human hepatoma cells. Am J Physiol Gastrointest Liver Physiol 290(5):G1059–G1066
Pfaller W, Balls M, Clothier R, Coecke S, Dierickx P, Ekwall B, Hanley BA, Hartung T, Prieto P, Ryan MP, Schmuck G, Sladowski D, Vericat JA, Wendel A, Wolf A, Zimmer J (2001) Novel advanced in vitro methods for long-term toxicity testing: the report and recommendations of ECVAM workshop 45. European centre for the validation of alternative methods. Altern Lab Anim 29(4):393–426
Pfuhler S, Kirkland D, Kasper P, Hayashi M, Vanparys P, Carmichael P, Dertinger S, Eastmond D, Elhajouji A, Krul C, Rothfuss A, Schoening G, Smith A, Speit G, Thomas C, van Benthem J, Corvi R (2009). Reduction of use of animals in regulatory genotoxicity testing: identification and implementation opportunities—report from an ECVAM workshop. Mutat Res 680:31–42
Pfuhler S, Kirst A, Aardema M, Banduhn N, Goebel C, Araki D, Costabel-Farkas M, Dufour E, Fautz R, Harvey J, Hewitt NJ, Hibatallah J, Carmichael P, Macfarlane M, Reisinger K, Rowland J, Schellauf F, Schepky A, Scheel J (2010) A tiered approach to the use of alternatives to animal testing for the safety assessment of cosmetics: genotoxicity. A COLIPA analysis. Regul Toxicol Pharmacol 57:315–324
Piersma AH (2006) Alternative methods for developmental toxicity testing. Basic Clin Pharmacol Toxicol 98:427–431
Podestà M, Piaggio G, Pitto A, Zocchi E, Soracco M, Frassoni F, Luchetti S, Painelli E, Bacigalupo A (2001) Modified in vitro conditions for cord blood-derived long-term culture initiating cells. Exp Hematol 29(3):309–314
Poth A, Kunz S, Heppenheimer A (2007) Bhas cell transformation assay as a predictor of carcinogenicity. ALTEX 14(special issue):519–521
Poulin P, Theil FP (2002) Prediction of pharmacokinetics prior to in vivo studies. 1. Mechanism-based prediction of volume of distribution. J Pharmaceut Sci 91:129–156
Poulin P, Theil FP (2009) Development of a novel method for predicting human volume distribution at steady-state of basic drugs and comparative assessment with existing methods. J Pharmaceut Sci 98:4941–4961
Prieto P (2002) Barriers, nephrotoxicology and chronic testing in vitro. Altern Lab Anim 30(suppl 2):101–105
Prieto P, Baird AW, Blaauboer BJ, Ripoll JV, Corvi R, Dekant W, Dietl P, Gennari A, Gribaldo L, Griffin JL, Hartung T, Heindel JJ, Hoet P, Jennings P, Marocchio L, Noraberg J, Pazos P, Westmoreland C, Wolf A, Wright J, Pfaller W (2006) The assessment of repeated dose toxicity in vitro: a proposed approach. The report and recommendations of ECVAM workshop 56. Altern Lab Anim 34(3):315–341
Prieto P, Hoffmann S, Tirelli V, Tancredi F, Gonzàlez I, Bermejo M, De Angelis I (2010) An exploratory study of two caco-2 cell models for oral absorption: a report on their within-laboratory and between-laboratory variability, and their predictive capacity. ATLA 38(5):367–386
Pritchard JB, French JE, Davis BJ, Haseman JK (2003) The role of transgenic mouse models in carcinogen identification. Environ Health Perspect 111:444–454
Purdy R (1996) A mechanism-mediated model for carcinogenicity: model content and prediction of the outcome of rodent carcinogenicity bioassays currently being conducted on 25 organic chemicals. Environ Health Perspect 104:1085–1094
Python F, Goebel C, Aeby P (2007) Assessment of the U937 cell line for the detection of contact allergens. Toxicol Appl Pharmacol 220(2):113–124
Redfern WS, Ewart L, Hammond TG, Bialecki R, Kinter L, Lindgren S, Pollard CE, Roberts R, Rolf MG, Valentin JP (2010) Impact and frequency of different toxicities throughout the pharmaceutical life cycle (abstract 1081). Toxicologist 114:231
Renwick AG (2004) Toxicology databases and the concept of thresholds of toxicological concern as used by the JECFA for the safety evaluation of flavouring agents. Toxicol Lett 149:223–234
Ridings JE, Barratt MD, Cary R, Earnshaw CG, Eggington CE, Ellis MK, Judson PN, Langowski JJ, Marchant CA, Payne MP, Watson WP, Yih TD (1996) Computer prediction of possible toxic action from chemical structure: an update on the DEREK system. Toxicology 106:267–279
Rietschel RL, Fowler JF (2008) Pathogenesis of allergic contact hypersensitivity. In: Fisher’s contact dermatitis, 6th edn. BC Decker Inc., Hamilton, pp 1–10
Riley RJ, Kenna JG (2004) Cellular models for ADMET predictions and evaluation of drug-drug interactions. Curr Opin Drug Discov Dev 7(1):86–99
Ringerike T, Ullerås E, Völker R, Verlaan B, Eikeset A, Trzaska D, Adamczewska V, Olszewski M, Walczak-Drzewiecka A, Arkusz J, van Loveren H, Nilsson G, Lovik M, Dastych J, Vandebriel RJ (2005) Detection of immunotoxicity using T-cell based cytokine reporter cell lines (‘cell chip’). Toxicology 206(2):257–272
Rivedal E, Sanner T (1982) Promotional effect of different phorbol esters on morphological transformation of hamster embryo cells. Cancer Lett 17:1–8
Roberts DW, Aptula AO (2008) Determinants of skin sensitisation potential. J Appl Toxicol 28(3):377–387
Roberts DW, Patlewicz GY (2008) Nonanimal alternatives for skin sensitization: letter to the editor. Toxicol Sci 106(2):572–574
Roberts DW, Patlewicz GY (2010) Updating the skin sensitization in vitro data assessment paradigm in 2009—a chemistry and QSAR perspective. J Appl Toxicol 30(3):286–288
Roberts DW, Williams DL (1982) The derivation of quantitative correlations between skin sensitisation and physio-chemical parameters for alkylating agents, and their application to experimental data for sultones. J Theor Biol 99(4):807–825
Roberts DW, Aptula AO, Patlewicz G (2007) Electrophilic chemistry related to skin sensitisation. Reaction mechanistic applicability domain classification for a published data set of 106 chemicals tested in the mouse local lymph node assay. Chem Res Toxicol 20(1):44–60
Roberts DW, Schultz T, Wolf E, Aptula AO (2010) Experimental reactivity parameters for toxicity modeling: application to the acute aquatic toxicity of SN2 electrophiles to Tetrahymena pyriformis. Chem Res Tox 23(1):228–234
Robinson JF, van Beelen VA, Verhoef A, Renkens MF, Luijten M, van Herwijnen MH, Westerman A, Pennings JL, Piersma AH (2010) Embryotoxicant-specific transcriptomic responses in rat postimplantation whole-embryo culture. Toxicol Sci 118:675–685
Rohrbeck A, Salinas G, Maaser K, Linge J, Salovaara S, Corvi R, Borlak J (2010) Toxicogenomics applied to in vitro carcinogenicity testing with Balb/c 3T3 cells revealed a gene signature predictive of chemical carcinogens. Toxicol Sci 118:31–41
Rostami-Hodjegan A, Tucker GT (2007) Simulation and prediction of in vivo drug metabolism in human populations from in vitro data. Nat Rev Drug Discov 6:140–148
Rotroff DM, Wetmore BA, Dix DJ, Ferguson SS, Clewell HJ, Houck KA, LeCluyse LE, Andersen ME, Judson RS, Smith CM, Sochaski MA, Kavlock RJ, Boellmann F, Martin MT, Reif DM, Wambaugh JF, Thomas RS (2010) Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening. Toxicol Sci 117:348–358
Rougier N, Redziniak G, Mougin D, Schmitt D, Vincent C (2000) In vitro evaluation of the sensitisation potential of weak contact allergens using Langerhans-like dendritic cells and autologous T cells. Toxicology 145(1):73–82
Rowland M, Balant L, Peck C (2004) Physiologically based pharmacokinetics in drug development and regulatory science: a workshop report (Georgetown University, Washington, DC, May 29–30, 2002). AAPS Pharm Sci 6:E6
Roy A, Georgopoulos PG (1998) Reconstructing week-long exposures to volatile organic compounds using physiologically based pharmacokinetic models. J Expo Anal Environ Epidemiol 8:407–422
Sadikovic B, Al-Romaih K, Squire JA, Zielenska M (2008) Cause and consequences of genetic and epigenetic alterations in human cancer. Curr Genom 9:394–408
Safford RJ (2008) The dermal sensitisation threshold—a TTC approach for allergic contact dermatitis. Regul Toxicol Pharmacol 51(2):195–200
Sakaguchi H, Ashikaga T, Miyazawa M, Yoshida Y, Ito Y, Yoneyama K, Hirota M, Itagaki H, Toyoda H, Suzuki H (2006) Development of an in vitro skin sensitisation test using human cell lines; human cell line activation test (h-CLAT). II. An inter laboratory study of the h-CLAT. Toxicol In Vitro 20(5):774–784
Sakaguchi H, Ashikaga T, Miyazawa M, Kosaka N, Ito Y, Yoneyama K, Sono S, Itagaki H, Toyoda H, Suzuki H (2009) The relationship between CD86/CD54 expression and THP-1 cell viability in an in vitro skin sensitisation test—human cell line activation test (h-CLAT). Cell Biol Toxicol 2592:109–126
Sanderson DM, Earnshaw CG (1991) Computer prediction of possible toxic action from chemical structure; the DEREK system. Hum Exp Toxicol 10:261–273
Sanner T, Dybing E (2005) Comparison of carcinogenic and in vivo genotoxic potency estimates. Basic ClinPharmacol Toxicol 96:131–139
Sawada H, Takami K, Asahi S (2005) A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci 83(2):282–292
SCCNFP, European Commission’s Scientific Committee on Cosmetics and Non-Food Products (2000) Opinion concerning the predictive testing of potentially cutaneous sensitising cosmetic ingredients or mixtures of ingredients, 17 February 2000
SCCNFP, European Commission’s Scientific Committee on Cosmetics and Non-Food Products (2003) Basic criteria for the in vitro assessment of dermal absorption of cosmetic ingredients, SCCNFP/0750/03. SCCNFP, Brussels
SCCP, European Commission’s Scientific Committee on Consumer’s Products (2008) Opinion on dermal sensitisation quantitative risk assessment (citral. farnesol and phenylacetaldehyde), 24 June 2008
SCCP, Scientific Committee on Consumer Products (2006) The SCCP’s note of guidance for the testing of cosmetic ingredients and their safety evaluation, 6th revision, 106
SCCS, European Commission’s Scientific Committee on Consumer Safety (2009) Memorandum on alternative test methods in human safety assessment of cosmetic ingredients in the European Union, 8 December 2009
Schaafsma G, Kroese ED, Tielemans EL, Van de Sandt JJ, Van Leeuwen CJ (2009) REACH, non-testing approaches and the urgent need for a change in mind set. Regul Toxicol Pharmacol 53(1):70–80
Schaefer WR, Fischer L, Deppert WR, Hanjalic-Beck A, Seebacher L, Weimer M, Zahradnik HP (2010) In vitro-Ishikawa cell test for assessing tissue-specific chemical effects on human endometrium. Reprod Toxicol 30(1):89–93
Schenk B, Weimer M, Bremer S, van der Burg B, Cortvrindt R, Freyberger A, Lazzari G, Pellizzer C, Piersma A, Schafer WR, Seiler A, Witters H, Schwarz M (2010) The ReProTect feasibility study, a novel comprehensive in vitro approach to detect reproductive toxicants. Reprod Toxicol 30:200–218
Schmelzer E, Mutig K, Schrade P, Bachmann S, Gerlach JC, Zeilinger K (2009) Effect of human patient plasma ex vivo treatment on gene expression and progenitor cell activation of primary human liver cells in multi-compartment 3D perfusion bioreactors for extra-corporeal liver support. Biotechnol Bioeng 103(4):817–827
Schmidt CW (2009) TOX 21: new dimensions of toxicity testing. Environ Health Perspect 117(8):A348–A353
Schmitt W (2008) General approach for the calculation of tissue to plasma partition coefficients. Toxicol In Vitro 22:457–467
Schneider K, Akkan Z (2004) Quantitative relationship between the local lymph node assay and human skin sensitisation assays. Regul Toxicol Pharmacol 39(3):245–255
Schreiner M, Peiser M, Briechle D, Stahlmann R, Zuberbier T, Wanner R (2007) A loose-fit coculture of activated keratinocytes and dendritic cell-related cells for prediction of sensitising potential. Allergy 62(12):1419–1428
Schroder HJ (1995) Comparative aspects of placental exchange functions. Eur J Obstet Gynecol Reprod Biol 63:81–90
Schultz TW, Yarbrough JW, Johnson EL (2005) Structures-activity relationships for reactivity of carbonyl-containing compounds with glutathione. SAR QSAR Environ Res 16(4):313–322
Schultz TW, Rogers K, Aptula A (2009) Read-across to rank skin sensitisation potential: subcategories for the Michael acceptor domain. Contact Derm 60(1):21–31
Selderslaghs IW, Van Rompay AR, De CW, Witters HE (2009) Development of a screening assay to identify teratogenic and embryotoxic chemicals using the zebrafish embryo. Reprod Toxicol 28:308–320
Sens-it-iv (2010) Novel testing strategies for in vitro assessment of allergens. Available at http://www.sens-it-iv.eu/ . Accessed 14 July 2010
Serafimova R, Todorov M, Pavlov T, Kotov S, Jacob E, Aptula A, Mekenyan O (2007) Identification of the structural requirements for mutagenicity, by incorporating molecular flexibility and metabolic activation of chemicals. II. General Ames mutagenicity model. Chem Res Toxicol 20:662–676
Serafimova R, Fuart Gatnik M, Worth A (2010) Review of QSAR models and software tools for predicting genotoxicity and carcinogenicity. EUR 24427 EN. http://www.ecb.jrc.ec.europa.eu/DOCUMENTS/QSAR/EUR_24427_EN.pdf
Shanks N, Greek R, Greek J (2009) Are animal models predictive for humans? Philos Ethics Humanit Med 4:1–20
Shen O, Du G, Sun H, Wu W, Jiang Y, Song L, Wang X (2009) Comparison of in vitro hormone activities of selected phthalates using reporter gene assays. Toxicol Lett 191:9–14
Smialowicz RJ (1995) Immune function testing for the identification and characterisation of immunotoxicity in rodents. Hum Exp Toxicol 14(1):135–136
Smith CK, Hotchkiss SA (2001) Allergic contact dermatitis. Taylor & Francis, London, pp 1–16
Smithing MP, Darvas F (1992) Hazardexpert: an expert system for predicting chemical toxicity. In: Finlay JW, Robinson SF, Armstrong DJ (eds) Food safety assessment. American Chem Society, Washington, DC, pp 191–200
Snykers S, Vanhaecke T, Papeleu P, Luttun A, Jiang Y, Vander Heyden Y, Verfaillie C, Rogiers V (2006) Sequential exposure to cytokines reflecting embryogenesis: the key for in vitro differentiation of adult bone marrow stem cells into functional hepatocyte-like cells. Toxicol Sci 94:330–341
Snykers S, De Kock J, Vanhaecke T, Rogiers V (2007) Differentiation of neonatal rat epithelial cells from biliary origin into immature hepatic cells by sequential exposure to hepatogenic cytokines and growth factors reflecting liver development. Toxicol In Vitro 21(7):1325–1331
Snykers S, De Kock J, Rogiers V, Vanhaecke T (2009) In vitro differentiation of embryonic and adult stem cells into hepatocytes: state of the art. Stem Cells 27:577–605
Sohn MD, McKone TE, Blancato JN (2004) Reconstructing population exposures from dose biomarkers: inhalation of trichloroethylene (TCE) as a case study. J Expo Anal Environ Epidemiol 14:204–213
Spanhaak S, Cook D, Barnes J, Reynolds J (2008) Species concordance for liver injury: from the safety intelligence program board. BioWisdom, Ltd, Cambridge. Available at http://www.biowisdom.com/files/SIP_Board_Species_Concordance.pdf Accessed 15 Jan 2011
Speit G (2009) How to assess the mutagenic potential of cosmetic products without animal tests? Mutat Res 678:108–112
Spiekstra SW, dos Santos GG, Scheper RJ, Gibbs S (2009) Potential method to determine irritant potency in vitro—comparison of two reconstructed epidermal culture models with different barrier competency. Toxicol In Vitro 23(2):349–355
Sreejit P, Kumar S, Verma RS (2008) An improved protocol for primary culture of cardiomyocyte from neonatal mice. In Vitro Cell Dev Biol Anim 44(3–4):45–50
Steiner G, Suter L, Boess F, Gasser R, de Vera MC, Albertini S, Ruepp S (2004) Discriminating different classes of toxicants by transcript profiling. Environ Health Perspect 112(12):1236–1248
Stemmer K, Ellinger Ziegelbauer H, Ahr HJ, Dietrich DR (2007) Carcinogen-specific gene expression profiles in short-term treated Eker and wild-type rats indicative of pathways involved in renal tumorigenesis. Cancer Res 67:4052–4068
Stummann TC, Bremer S (2008) The possible impact of human embryonic stem cells on safety pharmacological and toxicological assessments in drug discovery and drug development. Curr Stem Cell Res Ther 3:118–131
Stummann TC, Beilmann M, Duker G, Dumotier B, Fredriksson JM, Jones RL, Hasiwa M, Kang YJ, Mandenius CF, Meyer T, Minotti G, Valentin YJ, Zünkler BJ, Bremer S (2009a) Report and recommendations of the workshop of the European centre for the validation of alternative methods for drug-induced cardiotoxicity. Cardiovasc Toxicol 9(3):107–125
Stummann TC, Hareng L, Bremer S (2009b) Hazard assessment of methylmercury toxicity to neuronal induction in embryogenesis using human embryonic stem cells. Toxicology 257:117–126
Sutherland HJ, Lansdorp PM, Henkelman DH, Eaves AC, Eaves CJ (1990) Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers. Proc Natl Acad Sci USA 87(9):3584–3588
Suuronen EJ, Nakamura M, Watsky MA, Stys PK, Muller LJ, Munger R, Shinozaki N, Griffith M (2004) Innervated human corneal equivalents as in vitro models for nerve-target cell interactions. FASEB J 18(1):170–172
Suzuki M, Morihiko H, Hagino S, Itagaki H, Aiba S (2009) Evaluation of changes of cell-surface thiols as a new biomarker for in vitro sensitisation test. Toxicol In Vitro 23(4):687–696
Taléns-Visconti R, Bonora A, Jover R, Mirabet V, Carbonell F, Castell JV, Gómez-Lechón MJ (2006) Hepatogenic differentiation of human mesenchymal stem cells from adipose tissue in comparison with bone marrow mesenchymal stem cells. World J Gastroenterol 12(36):5834–5845
Tan YM, Liao KH, Clewell HJ (2006a) Reverse dosimetry: interpreting trihalomethanes biomonitoring data using physiologically based pharmacokinetic modeling. J Expo Anal Environ Epidemiol 17:591–603
Tan YM, Liao KH, Conolly RB, Blount BC, Mason AM, Clewell HJ (2006b) Use of a physiologically based pharmacokinetic model to identify exposures consistent with human biomonitoring data for chloroform. J Toxicol Environ Health A 69:1727–1756
Tang W, Lu AYH (2010) Metabolic bioactivation and drug-related adverse effects: current status and future directions from a pharmaceutical research perspective. Drug Metab Rev 42:225–249
Tatosian DA, Shuler ML (2009) A novel system for evaluation of drug mixtures for potential efficacy in treating multidrug resistant cancers. Biotechnol Bioeng 103:187–198
Tennant RW, French JE, Spalding JW (1995) Identifying chemical carcinogens and assessing potential risk in short-term bioassays using transgenic mouse models. Environ Health Perspect 103:942–950
Tennant RW, Stasiewicz S, Mennear J, French JE, Spalding JW (1999) Genetically altered mouse models for identifying carcinogens. IARC Sci Publ 146:123–150
Testa B, Balmat AL, Long A (2004) Predicting drug metabolism: concepts and challenges. Pure Appl Chem 76(5):907–914
Theunissen PT, Schulpen SH, van Dartel DA, Hermsen SA, van Schooten FJ, Piersma AH (2010) An abbreviated protocol for multilineage neural differentiation of murine embryonic stem cells and its perturbation by methyl mercury. Reprod Toxicol 29:383–392
Thierbach R, Steinberg P (2009) Automated soft agar assay for the high-throughput screening of anticancer compounds. Anal Biochem 387:318–320
Tilaoui L, Schilter B, Tran LA, Mazzatorta P, Grigorov M (2007) Integrated computational methods for prediction of the lowest observable adverse effect level of food-borne molecules. QSAR Comb Sci 26(1):102–108
Tolonen A, Turpeinen M, Pelkonen O (2009) Liquid chromatography-mass spectrometry in in vitro drug metabolite screening. Drug Discov Today (DDT) 14:120–133
Toropov AA, Toropova AP, Benfenati E (2009) Additive SMILES-based carcinogenicity models: probabilistic principles in the search for robust predictions. Int J Mol Sci 10:3106–3127
ToxCast (2010) http://www.epa.gov/ncct/toxcast/
Tsujimura K, Asamoto M, Suzuki S, Hokaiwado N, Ogawa K, Shirai T (2006) Prediction of carcinogenic potential by a toxicogenomic approach using rat hepatoma cells. Cancer Sci 97:1002–1010
Turpeinen M, Ghiciuc C, Orpitoui M, Kankainen L, Pelkonen O, Pasanen M (2007) Predictive value of animal models for human cytochrome P450 (CYP)-mediated enzymes: a comparative study in vitro. Xenobiotica 37:1367–1377
Uchino T, Taketzava T, Ikarashi Y (2009) Reconstruction of three-dimensional human skin model composed of dendritic cells, keratinocytes and fibroblasts utilizing a handy scaffold of collagen vitrigel membrane. Toxicol In Vitro 23(2):333–337
Uehara T, Hirode M, Ono A, Kiyosawa N, Omura K, Shimizu T, Mizukawa Y, Miyagishima T, Nagao T, Urushidani T (2008) A toxicogenomics approach for early assessment of potential non-genotoxic hepatocarcinogenicity of chemicals in rats. Toxicology 250:15–26
Uibel F, Muhleisen A, Kohle C, Weimer M, Stummann TC, Bremer S, Schwarz M (2009) ReProGlo: a new stem cell-based reporter assay aimed to predict embryotoxic potential of drugs and chemicals. Reprod Toxicol 30(1):103–112
Urani C, Stefanini FM, Bussinelli L, Melchioretto P, Crosta GF (2009) Image analysis and automatic classification of transformed foci. J Microsc 234:269–279
US FDA (1995) Department of health and human services. Food additives; threshold of regulation for substances used in food-contact articles 21 CFR parts 5, 25, 170, 171, and 174
US EPA, US Environmental Protection Agency (2004) In vitro dermal absorption rate testing of certain chemicals of interest to the occupational safety and health administration; final rule. Fed Register 69(80):22402–22441
US EPA, US Environmental Protection Agency (2007a) Integrated summary report for the validation of an androgen receptor binding assay as a potential screen in the endocrine disruptor screening program. http://www.epa.gov/endo/pubs/ar_binding_isr.pdf . Accessed on 6 July 2010
US EPA, US Environmental Protection Agency (2007b) Integrated summary report on aromatase. http://www.epa.gov/endo/pubs/aromatase_isr.pdf . Accessed on 6 July 2010
US EPA, US Environmental Protection Agency (2009) Integrated summary report for validation of an estrogen receptor binding assay using rat uterine cytosol as source of receptor as a potential screen in the endocrine disruptor screening program tier 1 battery. http://www.epa.gov/endo/pubs/assayvalidation/er_ruc_isr.pdf . Accessed on 6 July 2010
Vähäkangas K, Myllynen P (2006) Experimental methods to study human transplacental exposure to genotoxic agents. Mutat Res 608:129–135
Van Calsteren V (2010) Analyse van de herhaalde toedieningstoxiciteitstesten met cosmetische ingrediënten op Europees niveau. Master thesis in pharmaceutical sciences. Dissertation, Vrije Universiteit Brussel
Van Dartel DA, Pennings JL, Hendriksen PJ, van Schooten FJ, Piersma AH (2009) Early gene expression changes during embryonic stem cell differentiation into cardiomyocytes and their modulation by monobutyl phthalate. Reprod Toxicol 27:93–102
Van Dartel DA, Pennings JL, van Schooten FJ, Piersma AH (2010) Transcriptomics-based identification of developmental toxicants through their interference with cardiomyocyte differentiation of embryonic stem cells. Toxicol Appl Pharmacol 243:420–428
van Delft JH, van Agen E, van Breda SG, Herwijnen MH, Staal YC, Kleinjans JC (2005) Comparison of supervised clustering methods to discriminate genotoxic from non-genotoxic carcinogens by gene expression profiling. Mutat Res 575(1–2):17–33
Van der Burg B, Winter R, Man HY, Vangenechten C, Berckmans P, Weimer M, Witters H, van der Linden S (2010a) Optimization and prevalidation of the in vitro AR CALUX method to test androgenic and antiandrogenic activity of compounds. Reprod Toxicol 30(1):18–24
Van der Burg B, Winter R, Weimer M, Berckmans P, Suzuki G, Gijsbers L, Jonas A, van der Linden S, Witters H, Aarts J, Legler J, Kopp-Schneider A, Bremer S (2010b) Optimization and prevalidation of the in vitro ERalpha CALUX method to test estrogenic and antiestrogenic activity of compounds. Reprod Toxicol 30(1):73–80
Van Leeuwen K, Schultz TW, Henry T, Diderich B, Veith GD (2009) Using chemical categories to fill data gaps in hazard assessment. SAR QSAR Environ Res 20:207–220
van Loveren H, Cockshott A, Gebel T, Gundert-Remy U, de Jong WH, Matheson J, McGarry H, Musset L, Selgrade MK, Vickers C (2008) Skin sensitisation in chemical risk assessment: report of a WHO/IPCS international workshop focusing on dose–response assessment. Regul Toxicol Pharmacol 50(2):155–199
Van Merris V, Van Wemmel K, Cortvrindt R (2007) In vitro effects of dexamethasone on mouse ovarian function and pre-implantation embryo development. Reprod Toxicol 23:32–41
Van Och FM, Van Loveren H, Van Wolfswinkel JC, Machielsen AJ, Vandebriel RJ (2005) Assessment of potency of allergenic activity of low molecular weight compounds based on IL-1alpha and IL-18 production by a murine and human keratinocyte cell line. Toxicology 210(2–3):95–109
Vandebriel RJ, van Loveren H (2010) Non-animal sensitisation testing: state-of-the-art. Crit Rev Toxicol 40(5):389–404
Vanparys PH, Corvi R, Aardema M, Gribaldo L, Hayashi M, Hoffmann S, Schechtman L (2010) ECVAM prevalidation of three cell transformation assays. ALTEX 27:267–270
Vedani A, Smiesko M (2009) In silico toxicology in drug discovery—concepts based on three-dimensional models. Altern Lab Anim 37:477–496
Venkatapathy R, Moudgal CJ, Bruce RM (2004) Assessment of the oral rat chronic lowest observed adverse effect level model in TOPKAT, a QSAR software package for toxicity prediction. J Chem Inf Comput Sci 44(5):1623–1629
Vermeire T, van de Bovenkamp M, de Bruin YB, Delmaar C, van Engelen J, Escher S, Marquat H, Meijster T (2010) Exposure-based waiving under REACH. Regul Toxicol Pharmacol 58(3):408–420
Viravaidya K, Shuler ML (2004) Incorporation of 3T3-L1 cells to mimic bioaccumulation in a microscale cell culture analog device for toxicity studies. Biotechnol Prog 20:590–597
Viravaidya K, Sin A, Shuler ML (2004) Development of a microscale cell culture analog to probe naphtalene toxicity. Biotechnol Prog 20:316–323
Viswanath G, Halder S, Divya G, Majumder CB, Roy P (2008) Detection of potential (anti)progestagenic endocrine disruptors using a recombinant human progesterone receptor binding and transactivation assay. Mol Cell Endocrinol 295:1–9
Vocanson M, Cluzel-Tailhardat M, Poyet G, Valeyrie M, Chavagnac C, Levarlet B, Courtellemont P, Rozières A, Hennino A, Nicolas JF (2008) Depletion of human peripheral blood lymphocytes in CD25+ cells allows for the sensitive in vitro screening of contact allergens. J Invest Dermatol 128(8):2119–2122
Vocanson M, Hennino A, RoziŠres A, Poyet G, Nicolas JF (2009) Effector and regulatory mechanisms in allergic contact dermatitis. Allergy 64(12):1699–1714
Wainford RD, Weaver RJ, Hawksworth GM (2009) The immediate early genes, c-fos, c-jun and AP-1, are early markers of platinum analogue toxicity in human proximal tubular cell primary cultures. Toxicol In Vitro 23(5):780–788
Walsh MJ, Bruce SW, Pant K, Carmichael PL, Scott AD, Martin FL (2009) Discrimination of a transformation phenotype in Syrian golden hamster embryo (SHE) cells using ATR-FTIR spectroscopy. Toxicology 258:33–38
Wanner R, Sonnenburg A, Quatchadze M, Schreiner M, Peiser M, Zuberbier T, Stahlmann R (2010) Classification of sensitising and irritative potential in a combined in vitro assay. Toxicol Appl Pharmacol 245(2):211–218
Waters NJ, Jones R, Williams G, Sohal B (2008) Validation of a rapid equilibrium dialysis approach for the measurement of plasma protein binding. J Pharmaceut Sci 97:4586–4595
Waters MD, Jackson M, Lea I (2010) Characterizing and predicting carcinogenicity and mode of action using conventional and toxicogenomics methods. Mutat Res 705:184–200
Webborn PJ, Parker AJ, Denton RL, Riley RJ (2007) In vitro-in vivo extrapolation of hepatic clearance involving active uptake: theoretical and experimental aspects. Xenobiotica 37:1090–1099
Weiland C, Ahr HJ, Vohr HW, Ellinger-Ziegelbauer H (2007) Characterization of primary rat proximal tubular cells by gene expression analysis. Toxicol In Vitro 21(3):466–491
West PR, Weir AM, Smith AM, Donley EL, Cezar GG (2010) Predicting human developmental toxicity of pharmaceuticals using human embryonic stem cells and metabolomics. Toxicol Appl Pharmacol 247:18–27
Westmoreland C, Carmichael P, Dent M, Fentem J, MacKay C, Maxwell G, Pease C, Reynolds F (2010) Assuring safety without animal testing: unilever’s ongoing research programme to deliver novel ways to assure consumer safety. Altex 27 special issue from the world congress on alternatives to animals, Rome, pp 61–65
WHO, World Health Organisation (2008) World health statistics. http://www.who.int/whosis/whostat/2008/en/print.html . Accessed 15 Jan 2011
Wieser M, Stadler G, Jennings P, Streubel B, Pfaller W, Ambros P, Riedl C, Katinger H, Grillari J, Grillari-Voglauer R (2008) hTERT alone immortalizes epithelial cells of renal proximal tubules without changing their functional characteristics. Am J Physiol Renal Physiol 295(5):F1365–F1375
Wilding I, Bell J (2005) Improved early clinical development through human microdosing studies. Drug Discov Today 10(13):890–894
Willemsen P, Scippo ML, Kausel G, Figueroa J, Maghuin-Rogister G, Martial JA, Muller M (2004) Use of reporter cell lines for detection of endocrine-disrupter activity. Anal Bioanal Chem 378:655–663
Wilmes A, Crean D, Aydin S, Pfaller W, Jennings P, Leonard MO (2010) Identification and dissection of the Nrf2 mediated oxidative stress pathway in human renal proximal tubule toxicity. Toxicol In Vitro. doi: 10.1016/j.tiv.2010.12.009
Winkler J, Sotiriadou I, Chen S, Hescheler J, Sachinidis A (2009) The potential of embryonic stem cells combined with -omics technologies as model systems for toxicology. Curr Med Chem 16:4814–4827
Witters H, Freyberger A, Smits K, Vangenechten C, Lofink W, Weimer M, Bremer S, Ahr PH, Berckmans P (2010) The assessment of estrogenic or anti-estrogenic activity of chemicals by the human stably transfected estrogen sensitive MELN cell line: results of test performance and transferability. Reprod Toxicol 30(1):60–72
Wolf T, Niehaus-Rolf C, Banduhn N, Eschrich D, Scheel J, Luepke NP (2008) The hen’s egg test for micronucleus induction (HET-MN): novel analyses with a series of well-characterized substances support the further evaluation of the test system. Mutat Res 650:150–164
Woo YT, Lai DY (2003) Mechanisms of action of chemical carcinogens, and their role in structure–activity relationships (SAR) analysis and risk assessment. In: Benigni R (ed) Quantitative structure–activity relationship (QSAR) models of mutagens and carcinogens. CRC Press, Boca Raton, pp 41–80
Woo YT, Lai DY, Argus MF, Arcos JC (1995) Development of structure–activity relationship rules for predicting carcinogenic potential of chemicals. Toxicol Lett 79:219–228
Wu S, Blackburn K, Amburgey J, Jaworska J, Federle T (2010) A framework for using structural, reactivity, metabolic and physicochemical similarity to evaluate the suitability of analogs for SAR-based toxicological assessments. Regul Toxicol Pharmacol 56:67–81
Xu X, Yang W, Li Y, Wang YH (2010) Discovery of estrogen receptor modulators: a review of virtual screening and SAR efforts. Expert Opin Drug Discov 5:21–31
Yan L, Sheihk-Bahaei S, Park S, Ropella GEP, Hunt CA (2008) Predictions of hepatic disposition properties using a mechanistically realistic, physiologically based model. Drug Metab Dispos 36:759–768
Yang RSH, Thomas RS, Gustafson DL, Campain J, Benjamin SA, Verhaar HJM, Mumtaz MM (1998) Approaches to developing alternative and predictive toxicology based on PBPK/PD and QSAR modeling. Environ Health Perspect 106:1385–1393
Zachow R, Uzumcu M (2006) The methoxychlor metabolite, 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane, inhibits steroidogenesis in rat ovarian granulosa cells in vitro. Reprod Toxicol 22:659–665
Zaldívar JM, Mennecozzi M, Rodrigues R, Bouhifd M (2010) A biology-based dynamic approach for the modelling of toxicity in cell-based assays. Part I: fate modelling, EUR 24374 EN. European Commission, Joint Research Centre, Luxembourg
Zanger UM, Turpeinen M, Klein K, Schwab M (2008) Functional Pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Anal Bioanal Chem 392(6):1093–1108
Zeilinger K, Schreiter T, Darnell M, Lübberstedt M, Müller-Vieira U, Dillner B, Urbaniak T, Knobeloch D, Nüssler A, Gerlach JC, Andersson TB (2010) Human liver cell cultivation in a miniaturized 3D bioreactor system for in vitro studies on hepatic drug toxicity. ALTEX 27(suppl 2/10):148–149
Zhang J, Musson DG (2006) Investigation of high-throughput ultrafiltration for the determination of an unbound compound in human plasma using liquid chromatography and tandem mass spectrometry with electrospray ionization. J Chromatogr B 843:47–56
Zuang V, Eskes C (2005) Alternative (non-animal) methods for cosmetics testing: current status and future prospects—a report prepared in the context of the 7th amendment of the cosmetic directive for establishing the timetable for phasing out animal testing—foreword. Atla Altern Lab Anim 33:1
Zur Nieden NI, Ruf LJ, Kempka G, Hildebrand H, Ahr HJ (2001) Molecular markers in embryonic stem cells. Toxicol In Vitro 15:455–461
Zur Nieden NI, Kempka G, Ahr HJ (2004) Molecular multiple endpoint embryonic stem cell test—a possible approach to test for the teratogenic potential of compounds. Toxicol Appl Pharmacol 194:257–269