Intelligent Testing Strategies

  • C.J. van Leeuwen
  • G.Y. Patlewicz
  • A.P. Worth

In the context of regulatory programs for the safety evaluation of chemicals, there is a need for a paradigm shift. The challenge is to move in a scientifically credible and transparent manner from a paradigm that requires extensive hazard (animal) testing to one in which a hypothesis- and risk-driven approach can be used to identify the most relevant in vivo information [1]. Socalled Intelligent or Integrated Testing Strategies (ITS) are a significant part of the solution to the challenge of carrying out hazard and risk assessments on large numbers of chemicals. ITS (Figure 11.1) are integrated approaches comprising multiple elements aimed at speeding up the risk assessment process while reducing costs and animal tests [1].


Skin Sensitization Aquatic Toxicity Local Lymph Node Assay Risk Base Testing European Chemical Bureau 
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  1. 1.
    Bradbury S, Feijtel T, van Leeuwen K. 2004. Meeting the scientific needs of ecological risk assessment in a regulatory context. Environ Sci Technol38/23: 463a- 470a.CrossRefGoogle Scholar
  2. 2.
    Organization for Economic Co-operation and Development. 1992. Report of the OECD workshop on the extrapolation of laboratory aquatic toxicity data to the real Environment. OECD Environment Monographs 59. OECD, Paris, France.Google Scholar
  3. 3.
    Van Leeuwen CJ, Bro-Rasmussen F, Feijtel TCJ, Arndt R, Bussian BM, Calamari D, Glynn P, Grandy NJ, Hansen B, van Hemmen JJ, Hurst P, King N, Koch R, Müller M, Solbè JF, Speijers GAB, Vermeire T. 1996. Risk assessment and management of new and existing chemicals. Environ Toxicol Pharmacol 2:243-299.CrossRefGoogle Scholar
  4. 4.
    Worth AP. 2004. The tiered approach to toxicity assessment based on the integrated use of alternative (non-animal) tests. In Cronin MTD, Livingstone D, eds, Predicting Chemical Toxicity and Fate. CRC Press, Boca Raton, FL, USA, pp 389-410.Google Scholar
  5. 5.
    Organization for Economic Co-operation and Development. OECD Existing Chemicals Programme. OECD, Paris, France ( Scholar
  6. 6.
    Organization for Economic Co-operation and Development. 2006. Guidelines for the testing of chemicals. OECD, Paris, France.Google Scholar
  7. 7.
    Hansen BG, van Haelst AG, van Leeuwen K, van der Zandt P. 1999. Priority setting for existing chemicals: the European Union risk assessment method. Environ Toxicol Chem 8:772-779.CrossRefGoogle Scholar
  8. 8.
    Bodar CWM, Berthault F, De Bruijn JHM, van Leeuwen CJ, Pronk MEJ, Vermeire TG. 2003. Evaluation of EU risk assessments existing chemicals (EC Regulation 793/93). Chemosphere 53:1039-1047.CrossRefPubMedGoogle Scholar
  9. 9.
    Bodar WM, Pronk MEJ, Sijm DTHM. 2005. The European Union risk assessment on zinc and zinc compounds: the process and the facts. Integrated Environ Assessm Managem 1:301-319.CrossRefGoogle Scholar
  10. 10.
    Pedersen F, De Bruijn J, Munn S, van Leeuwen K. 2003. Assessment of additional testing needs under REACH. Effects of QSARs, risk based testing and voluntary industry initiatives. Report EUR 20863 EN, European Commission, Joint Research Centre, Ispra, Italy.Google Scholar
  11. 11.
    Haigh N, Baillie A. 1992. Final Report on Chemical Control in the European Community in the 1990s. Institute for European Environmental Policy, London, UK.Google Scholar
  12. 12.
    Allanou R, Hansen BG, van Der Bilt Y, 1999. Public availability of data on EU high production volume chemicals. Report EUR 18996 EN. European Commission, Joint Research Centre, Ispra, Italy.Google Scholar
  13. 13.
    US Environmental Protection Agency. 1998. Chemical Hazard Data Availability Study. Government Printing Office, Washington, DC.Google Scholar
  14. 14.
    Commission of the European Communities. 2005. Report from the Commission to the Council and the European Parliament: Fourth report on the statistics on the number of animals used for experimental and other scientific purposes in the Member States of the European Union. COM(2005) 7 final.Google Scholar
  15. 15.
    Van der Jagt K, Munn S, Tørsløv J, De Bruijn J. 2004. Alternative approaches can reduce the use of test animals under REACH. Addendum to the report “Assessment of additional testing needs under REACH. Effects of (Q)SARs, risk based testing and voluntary industry initiatives”. Report EUR 21405. European Commission, Joint Research Centre, Ispra, Italy.Google Scholar
  16. 16.
    Commission of the European Communities. 2003. Proposal for a Regulation of the European Parliament and of the Council concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency and amending Directive 1999/45/EC and Regulation (EC) on Persistent Organic PollutantsProposal for a Directive of the European Parliament and of the Council amending Council Directive 67/548/EEC in order to adapt it to Regulation (EC) of the European Parliament and of the Council concerning the registration, evaluation, authorisation and restriction of chemicals. Brussels, 29 October 2003, Brussels, Belgium.Google Scholar
  17. 17.
    Commission of the European Communities. 2006. Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC. Off J Eur Union, L 396/1 of 30.12.2006.Google Scholar
  18. 18.
    Scientific Committee on Cosmetic Products and Non- Food products intended for Consumers. 2004. The report for establishing the timetable for phasing out animal testing for the purpose of the cosmetics directive issued by ECVAM (30/4/2004). SCCNFP/0834/04. Brussels, Belgium.Google Scholar
  19. 19.
    Combes R, Barratt M, Balls M. 2003. An overall strategy for the testing of chemicals for human hazard and risk assessment under the EU REACH System. ATLA 31:7- 19.PubMedGoogle Scholar
  20. 20.
    European Centre for Ecotoxicology and Toxicology of Chemicals. 2004. Targeted risk assessment. Technical Report No. 93. ECETOC, Brussels, Belgium.Google Scholar
  21. 21.
    European Chemical Industry Council, European Association for Bioindustries and European Commission’s DG Research. 2004. A European Technology Platform for Sustainable Chemistry. Brussels, Belgium.Google Scholar
  22. 22.
    Health Council of the Netherlands. 2001. Toxicity testing: a more efficient approach. Publication no. 2001/24E. The Hague, the Netherlands.Google Scholar
  23. 23.
    Hofer T, Gerner I, Gundert-Remy U, Liebsch M, Schulte A, Spielmann H, Vogel R, Wettig K. 2004. Animal testing and alternative approaches for the human health risk assessment under the proposed new European chemicals regulation. Arch Toxicol 78:549-564.CrossRefPubMedGoogle Scholar
  24. 24.
    Worth AP, Fentem JH, Balls M, Botham PA, Curren RD, Earl LK, Esdaile DJ, Liebsch M. 1998. An evaluation of the proposed OECD testing strategy for skin corrosion. ATLA 26:709-720.Google Scholar
  25. 25.
    European Chemicals Bureau. 2005. Scoping study on the development of a technical guidance document on information requirements on intrinsic properties of substances (RIP 3.3-1). Report prepared by CEFIC, DK-EPA, Environmental Agency of Wales and England, ECETOC, INERIS, KemI and TNO. European Commission, Joint Research Centre, Ispra, Italy.Google Scholar
  26. 26.
    Organization for Economic Co-operation and Development. 2002. Manual for investigation of HPV Chemicals. Section 3.2. Guidance on the development and use of chemical categories. OECD, Paris, France.Google Scholar
  27. 27.
    Hanway RH, Evans PF. 2000. Read-across of toxicological data in the notification of new chemicals. Toxicology Letters116, Suppl 1, 61.Google Scholar
  28. 28.
    US Environmental Protection Agency. 2002. TSCA New Chemicals Program (NCP). ( oppt/newchems/pubs/chemcat.htm). USEPA, Office of Pollution Prevention and Toxics, Washington, DC.Google Scholar
  29. 29.
    Health Canada. 2005. A proposed integrated framework for the health-related components of categorization of the Domestic Substances List under CEPA 1999. Health Canada, Ottawa, Canada.Google Scholar
  30. 30.
    Environment Canada. 2003. Guidance manual for the References 505 categorization of organic and inorganic substances on Canada’s Domestic Substances List. Environment Canada, Ottawa, Canada.Google Scholar
  31. 31.
    US Environmental Protection Agency. 2004. Status and future directions of the High Production Volume Challenge programme. US Environmental Protection Agency. Office of Pollution Prevention and Toxics, Washington, DC.Google Scholar
  32. 32.
    Cronin MTD, Livingstone DJ. 2004. Predicting Chemical Toxicity and Fate. CRC Press, Boca Raton, Florida.Google Scholar
  33. 33.
    Bradbury SP, Russom CL, Ankley GT, Schultz TW, Walker JD. 2003. Overview of data and conceptual approaches for derivation of quantitative structureactivity relationships for ecological effects of organic chemicals. Environ Toxicol Chem 22:1789-1798.CrossRefPubMedGoogle Scholar
  34. 34.
    Jaworska JS, Comber M, Auer C, van Leeuwen CJ. 2003. Summary of a workshop on regulatory acceptance of (Q)SARs for human health and environmental endpoints. Environ Health Persp111/10:1358-1360.CrossRefGoogle Scholar
  35. 35.
    US Environmental Protection Agency. 2004. A Framework for a Computational Toxicology Research Program in ORD. Report No. EPA/600/R 03/065. US Government Printing Office, Washington, DC.Google Scholar
  36. 36.
    Christensen FM, de Bruijn JHM, Hansen BG, Munn SJ, Sokull-Kluttgen B, Pedersen F. 2003. Assessment tools under the new European Union chemicals policy. GMI 41:5-19.Google Scholar
  37. 37.
    Organization for Economic Co-operation and Development. 1992. Report of the OECD Workshop on Quantitative Structure-Activity Relationships in Aquatic Effects Assessment. OECD Environment Monographs 58. OECD, Paris, France.Google Scholar
  38. 38.
    Organization for Economic Co-operation and Development. 1994. US EPA/EC Joint Project on the Evaluation of (Quantitative) Structure-Activity Relationships. OECD Environment Monograph No 88. OECD, Paris, France.Google Scholar
  39. 39.
    European Centre for Ecotoxicology and Toxicology of Chemicals. 2003. (Q)SARs: evaluation of the commercially available software for human health and environmental endpoints with respect to chemical management applications. ECETOC Technical Report No. 89. ECETOC, Brussels, Belgium.Google Scholar
  40. 40.
    Organization for Economic Co-operation and Development. 2006. Report on the regulatory uses and applications in OECD member countries of (quantitative) structure-activity relationship [(Q)SAR] models in the assessment of new and existing chemicals. Environmental Health and Safety Publications. Series on Testing and Assessment 58. OECD, Paris, France.Google Scholar
  41. 41.
    Commission of the European Communities. 2003. Technical Guidance Document in support of Commission Directive 93/67/EEC on risk assessment for new notified substances, Commission Regulation (EC) No 1488/94 on risk assessment for existing substances and Directive 98/8/EC of the European Parliament and of the Council concerning the placing of biocidal products on the market. Joint Research Centre, European Chemicals Bureau, Ispra, Italy.Google Scholar
  42. 42.
    Scientific Committee on Toxicity, Ecotoxicity and the Environment. 2004. Opinion of the Scientific Committee on Toxicity, Ecotoxicity and the Environment (CSTEE) on the BUAV-ECEAE report on “the way forward-Action to end animal toxicity testing”. Adopted by the CSTEE during the 41st plenary meeting of 8 January 2004. Brussels, Belgium.Google Scholar
  43. 43.
    Nordic Council of Ministers. 2005. Threshold of Toxicological Concern (TTC). TemaNord 2005:559. Copenhagen, Denmark.Google Scholar
  44. 44.
    Kroes R, Renwick AG, Cheeseman M, Kleiner J, Mangelsdorf I, Piersma A, Schilter B, Schlatter J, van Schothorst F, Vos JG, Wurtzen 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.CrossRefPubMedGoogle Scholar
  45. 45.
    Kroes R, Kozianowski G. 2002. Threshold of toxicological concern (TTC) in food safety assessment. Toxicol Letters 127:43-46.CrossRefGoogle Scholar
  46. 46.
    De Wolf W, Siebel-Sauer A, Lecloux A, Koch V, Holt M, Feijtel T, Comber M, Boeije G. 2004. Environ Toxicol Chem 24:479-485.Google Scholar
  47. 47.
    Barlow S. 2005. Thresholds of toxicological concern (TTC). A tool for assessing substances of unknown toxicity present at low levels in the diet. ILSI Europe Concise Monograph Series. International Life Sciences Institute, Brussels, Belgium.Google Scholar
  48. 48.
    US Food and Drug Administration. 1995. Food additives: thresholds of regulation for substances used in foodcontact articles. Final Rule. Fed Register 60:36582- 36596.Google Scholar
  49. 49.
    Gold LS, Sawyer CB, Magaw R, Backman GM, De Veciana M, Levinson R, Hooper NK, Havender WR, Bernstein L, Peto R, Pike M, Ames BN. 1984. A carcinogenesis potency database of the standardised results of animal bioassays. Environ Health Perspect 58:9-319.CrossRefPubMedGoogle Scholar
  50. 50.
    Rulis AM, Hatan DG. 1985. FDA’s priority-based assessment of food additives II. General toxicity parameters. Regul Toxicol Pharmacol 5:152-174.CrossRefPubMedGoogle Scholar
  51. 51.
    Munro IC. 1990. Safety assessment procedures for direct food additives, an overview. Regul Toxicol Pharmacol 12:2-12.CrossRefPubMedGoogle Scholar
  52. 52.
    Munro IC, Ford RA, Kennepohl E, Sprenger JG. 1996. Correlation of structural class with no-observed-effect levels: a proposal for establishing a threshold of concern. Food Chem Toxicol 34:829-867.CrossRefPubMedGoogle Scholar
  53. 53.
    Kroes R, Galli C, Munro I, Schilter B, Tran L-A, Walker R, Wurtzen G. 2000. Thresholds of toxicological concern for chemical substances present in the diet: a practical tool for assessing the need for toxicity testing. Food Chem Toxicol 38:255-312CrossRefPubMedGoogle Scholar
  54. 54.
    Cramer GM, Ford RA, Hall RL. 1978. Estimation of toxic hazard – a decision tree approach. Food Cosmet Toxicol 16:255-276.CrossRefPubMedGoogle Scholar
  55. 55.
    Verhaar HJM, van Leeuwen CJ, Hermens JLM. 1992. Classifying environmental pollutants. 1: Structureactivity relationships for prediction of aquatic toxicity. Chemosphere 25:471-491.CrossRefGoogle Scholar
  56. 56.
    Escher BE, Hermens JLM. 2002. Modes of action in ecotoxicology: their role in body burdens, species sensitivity, QSARs, and mixture effects. Environ Sci Technol 36:4201-4217.CrossRefPubMedGoogle Scholar
  57. 57.
    Worth AP, Balls M, eds 2002. Alternative (non-animal) methods for chemical testing: current status and future prospects. A report prepared by ECVAM and the ECVAM Working Group on Chemicals. ATLA30 (Suppl 1):1-125.Google Scholar
  58. 58.
    Eskes C, Zuang V, eds 2005. Alternative (non-animal) methods for cosmetics testing: current status and future prospects. A report prepared in the context of the 7th amendment to the cosmetics directive for establishing the timetable for phasing out animal testing. ATLA33 (Suppl 1):1-228.Google Scholar
  59. 59.
    Fentem JH. 2006. Working together to respond to the challenges of EU policy to replace animal testing. ATLA 34:11-18.PubMedGoogle Scholar
  60. 60.
    Fentem J, Chamberlain M, Sangster B. 2004. The feasibility of replacing animal testing for assessing consumer safety: a suggested future direction. ATLA 32: 617-623.PubMedGoogle Scholar
  61. 61.
    Combes RD, Gaunt I, Balls M. 2004. A scientific and animal welfare assessment of the OECD health effects test guidelines for the safety testing of chemicals under the European Union REACH system. ATLA 32:163-208.PubMedGoogle Scholar
  62. 62.
    Jaram S, Riego Sintes JM, Halder M, Baraibar Fentanes J, Sokull-Klüttgen B, Hutchinson TM. 2005. A strategy to reduce the use of fish in acute ecotoxicity testing of new chemical substances notified in the European Union. Regul Toxicol Pharmacol 42:218-224.CrossRefGoogle Scholar
  63. 63.
    Van Leeuwen CJ, van Der Zandt PTJ, Aldenberg T, Verhaar HJM, Hermens JLM. 1992. Application of QSARs, extrapolation and equilibrium partitioning in aquatic assessment: I. Narcotic industrial pollutants. Environ Toxicol Chem 11:267-282.CrossRefGoogle Scholar
  64. 64.
    European Centre for Ecotoxicology and Toxicology of Chemicals. 2005. Alternative testing approaches in environmental safety assessment. ECETOC Technical Report No. 97. ECETOC, Brussels, Belgium.Google Scholar
  65. 65.
    Barratt MD. 2003. QSAR, read-across and REACH. ATLA 31:463-465.PubMedGoogle Scholar
  66. 66.
    Slooff W, Canton JH, Hermens JLM. 1983. Comparison of the susceptibility of 22 freshwater species to 15 chemical compounds. I. (Sub)acute toxicity tests. Aquatic Toxicol 4:113-128.CrossRefGoogle Scholar
  67. 67.
    Slooff W, Canton JH.1983. Comparison of the susceptibility of 11 freshwater species to 8 chemical compounds. II. (Sub)acute toxicity tests. Aquatic Toxicol 4:113-128.CrossRefGoogle Scholar
  68. 68.
    Posthuma L, Suter II GW, Traas TP, eds. 2002. Species Sensitivity Distributions in Ecotoxicology.Lewis Publ. Boca Raton, Florida, USA.Google Scholar
  69. 69.
    McKim JM, Bradbury SP, Niemi GJ. 1987. Fish acute toxicity syndromes and their use in the QSAR approach to hazard assessment. Environ Health Persp 71:171-186.CrossRefGoogle Scholar
  70. 70.
    Hermens J. 1989. Quantitative structure-activity relationships of environmental pollutants. In O. Hutzinger, ed, Handbook of Environmental Chemistry, Vol. 2E. Springer, Berlin, Germany. pp. 111-162.Google Scholar
  71. 71.
    Verhaar HJM, van Leeuwen CJ, Bol J, Hermens JLM. 1994. Application of QSARs in risk management of existing chemicals. SAR QSAR Environ Res 2:39-58.CrossRefPubMedGoogle Scholar
  72. 72.
    Bol J, Verhaar, HJM, van Leeuwen CJ, Hermens JLM. 1993. Predictions of the aquatic toxicity of high production volume chemicals. Ministry of Housing, Spatial Planning and Environment, The Hague, The Netherlands.Google Scholar
  73. 73.
    Aldenberg, T., W. Slob. 1993. Confidence limits for hazardous concentrations based on logistically distributed NOEC toxicity data. Ecotoxicol Environ Saf 25:48-63.CrossRefPubMedGoogle Scholar
  74. 74.
    Könemann H. 1981. Quantitative structure-actvity relationships in fish toxicity studies. 1. Relationship for industrial pollutants. Toxicology 19:209-221.Google Scholar
  75. 75.
    Veith GD, Call DJ, Brooke LT. 1983. Structure-toxicity relationships for the fathead minnow, Pime-phales promelas: Narcotic industrial chemicals. Can J Fish Aquat Sci 40:743-748.CrossRefGoogle Scholar
  76. 76.
    Hermens J, Broekhuyzen E, Canton H, Wegman R. 1985. Quantitative structure-activity relationships and mixture toxicity studies of alcohols and chlorohydrocarbons: effects on growth of Daphnia magna. Aquat Toxicol 6:209-217.CrossRefGoogle Scholar
  77. 77.
    McCarty LS. 1987. Relationship between toxicity and bioconcentration for some organic chemicals. I. Examination of the relationship. In K.L.E. Kaiser, ed, References 507 QSAR in Environmental Toxicology-II. Reidel, Dordrecht, The Netherlands, pp. 207-220.Google Scholar
  78. 78.
    McCarty LS, Mackay D, Smith AD, Ozburn GW, Dixon DG. 1991. Interpreting aquatic toxicity QSARs: The significance of toxicant body residues at the pharmacological endpoint. Sci Total Environ 109/110:515-525.CrossRefGoogle Scholar
  79. 79.
    Van Hoogen G., Opperhuizen A. 1988. Toxicokinetics of chlorobenzenes in fish. Environ Toxicol Chem 7:213- 219.CrossRefGoogle Scholar
  80. 80.
    Van Der Kooy LA, van De Meent D, van Leeuwen CJ, Bruggeman. WA 1991. Deriving quality criteria for water and sediment from the results of aquatic toxicity tests and product standards: application of the equilibrium partitioning theory. Water Res 25:697-705.CrossRefGoogle Scholar
  81. 81.
    Hutchinson TM, Barrett S, Buzby M, Constable D, Hartmann A, Hayes E, Huggett D, Laenge R, Lillicrapp AD, Staub JO, Thompson RS. A strategy to reduce the use the numbers of fish in acute ecotoxicity testing of pharmaceuticals. Environ Toxicol Chem 22:3031-3036.Google Scholar
  82. 82.
    Von der Ohe PC, Kühne R, Ebert R, Altenburger R, Liess M, Schüürmann G. 2005. Structural alerts - a new classification model to discriminate excess toxicity from narcotic effect levels of organic compounds in the acute daphnid assay. Chem Res Toxicol 18:536-555.CrossRefPubMedGoogle Scholar
  83. 83.
    Walker JD, Gerner I, Hulzebos E, Schlegel K. 2004. (Q)SARs for predicting skin irritation and corrosion: mechanisms, transparency and applicability predictions. QSAR Comb Sci 23:721-725.CrossRefGoogle Scholar
  84. 84.
    Gerner I, Schlegel K, Walker JD, Hulzebos E. 2004. Use of physicochemical property limits to develop rules for identifying chemical substances with no skin irritation or corrosion potential. QSAR Comb Sci 23:726-733.CrossRefGoogle Scholar
  85. 85.
    Patlewicz G, Rodford R, Walker JD. 2003. Quantitative structure-activity relationships for predicting skin and eye irritation. Environ Toxicol Chem 22:1862-1869.CrossRefPubMedGoogle Scholar
  86. 86.
    Hulzebos E, Walker JD, Gerner I, Schlegel K. 2005. Use of structural alerts to develop rules for identifying chemical substances with skin irritation or corrosion potential. QSAR Comb Sci 24:332-342.CrossRefGoogle Scholar
  87. 87.
    Walker JD, Gerner I, Hulzebos E, Schlegel K. 2005. The skin irritation corrosion rules estimation tool (SICRET). QSAR Comb Sci 24:378-384.CrossRefGoogle Scholar
  88. 88.
    Smith CK, Hotchkiss SAM. 2001. Allergic contact dermatitis: chemical and metabolic mechanisms. Taylor & Francis Ltd, London, UK.Google Scholar
  89. 89.
    Dearman RJ, Kimber I. 2003. Factors influencing the induction phase of skin sensitization. Am J Contact Dermatitis 14:188-194.PubMedGoogle Scholar
  90. 90.
    Kimber I, Dearman RJ. 2003. What makes a chemical an allergen? Ann Allergy Asthma Immunol 90:28-31.CrossRefPubMedGoogle Scholar
  91. 91.
    Smith Pease CK, Basketter DA, Patlewicz GY. 2003. Contact allergy: the role of skin chemistry and metabolism. Clin Exp Derm 28:177-83.CrossRefPubMedGoogle Scholar
  92. 92.
    Pease Smith CK. 2003. From xenobiotic chemistry and metabolism to better prediction and risk assessment of skin allergy. Toxicology 192:1-22.CrossRefGoogle Scholar
  93. 93.
    Lepoittevin J-P, Basketter DA, Goossens A, Karlberg A-T. (eds.) 1998. Allergic Contact Dermatitis: The Molecular Basis. Springer-Verlag, Berlin Germany.Google Scholar
  94. 94.
    Kimber I, Basketter DA, Butler M, Gamer A, Garrigue J-L, Gerberick GF, Newsome C, Steiling W, Vohr H-W. 2003. Classification of contact allergens according to potency: proposals. Food Chem Toxicol 41:1799-1809.CrossRefPubMedGoogle Scholar
  95. 95.
    Aptula AO, Patlewicz G, Roberts DW. 2005. Skin sensitization: reaction mechanistic applicability domains for structure-activity relationships. Chem Res Toxicol 18:1420-1426.CrossRefPubMedGoogle Scholar
  96. 96.
    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 81:332-343.CrossRefPubMedGoogle Scholar
  97. 97.
    Divkovic M, Pease CK, Gerberick GF, Basketter DA. 2005. Hapten-protein binding: from theory to practical application in the in vitro prediction of skin sensitization. Contact Dermatitis 53:189-200.CrossRefPubMedGoogle Scholar
  98. 98.
    Aptula AO, Patlewicz G, Roberts DW, Schultz TW. 2006. Non-enzymatic glutathione reactivity and in vitro toxicity: A non-animal approach to skin sensitization. Toxicol In Vitro 20:239-247.CrossRefPubMedGoogle Scholar
  99. 99.
    Ryan CA, Gerberick GF, Gildea LA, Hulette BC, Betts CJ, Cumberbatch M, Dearman RJ, Kimber I. 2005. Interactions of contact allergens with dendritic cells: opportunities and challenges for the development of novel approaches to hazard assessment. Toxicol Sci 88:4- 11.CrossRefPubMedGoogle Scholar
  100. 100.
    Aeby P, Wyss C, Beck H, Grien P, Scheffler H, Goebel C. 2004. Characterization of the sensitizing potential of chemicals by in vitro analysis of dendritic cell activation and skin penetration. J Invest Dermatol 122:1154-1164.CrossRefPubMedGoogle Scholar
  101. 101.
    Straube F, Grenet O, Bruegger P, Ulrich P. 2005. Contact allergens and irritants show discrete differences in the activation of human monocyte-derived dendritic cells: consequences for in vitro detection of contact allergens. Arch Toxicol 79:37-46.CrossRefPubMedGoogle Scholar
  102. 102.
    Toebak MJ, Pohlmann PR, Sampat-Sardjoepersad SC, von Blomberg BME, Bruynzeel DP, Scheper RJ, Rustemeyer T, Gibbs S. 2006. CXCL8 secretion by dendritic cells predicts contact allergens from irritants. Toxicol In Vitro 20:117-124.CrossRefPubMedGoogle Scholar
  103. 103.
    Vandebriel RJ, van Och FMM, van Loveren H. 2005. In vitro assessment of sensitizing activity of low molecular Toxicol Appl Pharmacol207 (Suppl 2):142-148.Google Scholar
  104. 104.
    Kimber I, Dearman R, Betts CJ, Gerberick GF, Ryan CA, Kern PS, Patlewicz GY, Basketter DA. 2006. The local lymph node assay and skin sensitization: a cutdown screen to reduce animal requirements? Contact Dermatitis 54:181-185.CrossRefPubMedGoogle Scholar
  105. 105.
    Gerberick GF, Ryan CA, Kern PS, Schlatter H, Dearman RJ, Kimber I, Patlewicz G, Basketter DA. 2005. Compilation of historical local lymph node assay data for the evaluation of skin sensitization alternatives. Contact Dermatitis 16:157-202.CrossRefGoogle Scholar
  106. 106.
    Jefferies D, Aspinall L, Madrigal A-M, Safford B, Clapp C, Chamberlain M, Basketter DA. 2005. A Bayesian Network model to predict hazard potency for skin sensitization. Poster presented at Society of Toxicology. New Orleans, USA.Google Scholar
  107. 107.
    Jones J. 2006. National Pesticide Program. A new toxicology testing paradigm: meeting common needs. Presented to the National Research Council Committee on toxicity testing and assessment of environmental agents on January 19. Irvine, CA. Office of Pesticide Programs. US Environmental Protection Agency, Washington, DC.Google Scholar
  108. 108.
    Tyler CR, Filby A, Iguchi T, Kramer V, Larsson J, van Aggelen G, van Leeuwen K, Viant M and Tillitt D. 2006. Molecular biology and risk assessment: evaluation of the potential roles of genomics in regulatory ecotoxicology. Proceedings of a SETAC workshop. Pellston, MI, USA (in press).Google Scholar
  109. 109.
    Organization for Economic Co-operation and Development. 1996. Final report of the OECD workshop on harmonization of validation and acceptance criteria for alternative toxicological test methods. OECD, Paris, France.Google Scholar
  110. 110.
    European Commission. 2005. Reducing animal testing: Commission agrees partnership with industry. Europa rapid press releases IP/05/1375 of 07/11/2005.Google Scholar

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© Springer 2007

Authors and Affiliations

  • C.J. van Leeuwen
  • G.Y. Patlewicz
  • A.P. Worth

There are no affiliations available

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