Animal testing and alternative approaches for the human health risk assessment under the proposed new European chemicals regulation

Archives of Toxicology

Volumn 78, Issue 10, 2004, Pages 549-564

  Höfer, Thomas ^a   Gerner, Ingrid ^a   Gundert Remy, Ursula ^a   Liebsch, Manfred ^a   Schulte, Agnes ^a   Spielmann, Horst ^a   Vogel, Richard ^a   Wettig, Klaus ^a  

^a FEDERAL INSTITUTE FOR RISK ASSESSMENT   (Germany)

Author keywords

Animal experiments; EU chemicals policy; Hazard assessment; Regulatory toxicology; Risk assessment

Indexed keywords

CHEMICAL AGENT;

ANIMAL TESTING ALTERNATIVE; ARTICLE; ENVIRONMENTAL MONITORING; GOVERNMENT REGULATION; HEALTH CARE POLICY; LAW; PRIORITY JOURNAL; REPRODUCTIVE TOXICITY; RISK ASSESSMENT; VALIDATION PROCESS;

ANIMAL TESTING ALTERNATIVES; ANIMALS; EUROPEAN UNION; HAZARDOUS SUBSTANCES; HUMANS; INTERNATIONAL AGENCIES; RISK ASSESSMENT; TOXICITY TESTS;

ANIMALIA;

EID: 9944253258     PISSN: 03405761     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00204-004-0577-9     Document Type: Article

References (94)

1. Balls M, Botham PA, Bruner LH, Spielmann H (1995) The EC/HO international validation study on alternatives to the Draize eye irritation test. Toxicol In Vitro 9(6):871-929
2. Balls M, Berg N, Bruner LH, Curren R, de Silva O, Earl LK, Esdaile DJ, Fentem JH, Liebsch M, Ohno Y, Prinsen MK, Spielmann H, Worth AP (1999) Eye irritation testing: the way forward. Report and recommendations of ECVAM workshop 24. ATLA 27:53-77
3. Bandara LR, Kennedy S (2002) Toxicoproteomics - a new preclinical tool. Drug Discov Today 7:411-418
4. Bradlaw J, Gupta K, Green S, Hill R, Wilcox N (1997) Practical application of non-whole animal alternatives: summary IRAG workshop on eye irritation. Food Chem Toxicol 35:175-178
5. Brantom PG, Bruner LH, Chamberlain M, de Silva O, Dupuis J, Earl LK, Lovell DP, Pape WJW, Uttley M, Bagley DM, Baker FW, Brachter M, Courtellemont P, et al (1997) A summary report of the COLIPA international validation study on alternatives to the Draize rabbit eye irritation test. Toxicology In Vitro 11:141-179
6. Brown NA, Spielmann H, Bechter R, Flint OP, Freeman SJ, Jelinek RJ, Koch E, Nau H, Newall DR, Palmer AK, Renault JY, Repetto MF, Vogel R, Wiger R (1995) Screening chemicals for reproductive toxicity: the current alternatives (ECVAM Workshop 12). ATLA 23:868-882
7. 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
8. Corton JC, Andersen SP, Stauber AJ, Janszen DB, Kimbell JS, Conolly RB (1999) Entering the era of toxicogenomics with DNA microarrays. CIIT Activities 19
9. Cortvrindt R, Daston G, Mantovani A, Maranghi F, Pelkonen O, Ruhdel I, Spielmann H, Bremer S (2003) Reproductive and developmental toxicity; Prepared for the European Commission and the stakeholders for the phasing out of animal experimentation in the field of cosmetics. Unpublished, Brussels
10. Creasy DM (1997) Evaluation of testicular toxicity in safety evaluation studies: the appropriate use of spermatogenic staging. Toxicol Pathol 25:119-131
11. Cronin MTD, Jaworska JS, Walker JD, Comber MHI, Watts CD, Worth AP (2003) Use of QSARs in international decision-making frameworks to predict health effects of chemical substances. Environ Health Perspect 111:1391-1401
12. Danish EPA, Danish Environmental Protection Agency (Danish Ministry of Environment and Energy) (2001) Report on the Advisory list for self classification of dangerous substances. Environmental project No 636. http://www.mst.dk/udgiv/pub-lications/2001/87-7944-694/html
13. Draize JH, Woodward G, Calvery HO (1944) Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. J Pharmacol Exp Ther 82:377-390
14. EC TGD (2003) Technical guidance document on risk assessment 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. Part I-IV, European Chemicals Bureau (ECB), JRC-Ispra (VA), Italy, April 2003. http://ecb.jrc.it/tgdoc
15. ECETOC (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, Brussels, Belgium, pp 164
16. ECVAM, European Centre for the validation of Alternative Methods (2003) Development of a novel approach in hazard and risk assessment of reproductive toxicity by combination and application of in vitro, tissue and sensor technologies. Proposal for a research project (unpublished). JRC, Ispra, Italy
17. Enslein K, Gombar VK, Blake BW (1994) Use of SAR in computer-assisted prediction of carcinogenicity and mutagenicity of chemicals by the TOPKAT program. Mutation Research 305:47-61
18. Eriksson L, Jaworska JS, Worth AP, Cronin MTD, McDowell RM, Gramatica P (2003) Methods for reliability and uncertainty assessment and for applicability evaluations of classification- and regression-based QSARs. Environ Health Perspect 111:1361-1375
19. EU (1986) Council Directive 86/609/EEC of 24 November 1986 on the approximation of laws, regulations and administrative provisions of the Member States regarding the protection of animals used for experimental and other scientific purposes. Official Journal of the European Communities L 358:1-28
20. EU (1998) Council Decision of 23 March 1998 concerning the conclusion by the Community of the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes. Official Journal of the European Communities L 222:29-37
21. EU COM, Commission of the European Communities (2001) White paper, strategy for a future chemicals policy. COM(2001)88final, Brussels
22. EU COM, Commission of the European Communities (2003a) Proposal for a regulation of the European parliament and of the council concerning the registration, evaluation, authorisation and restriction of chemicals (REACH) - consultation document, Brussels
23. EU COM, Commission of the European Communities (2003b) Directorates General Environment and Enterprise Note: proposal for a regulation concerning the Registration, Evaluation, Authorisation and Restrictions of Chemicals (REACH Regulation). D(2003)635170, Brussels
24. EU COM, Commission of the European Communities (2003c) Report from the Commission to the Council and the European Parliament - Third Report from the Commission to the Council and the European Parliament on the Statistics on the number of animals used for experimental and other scientific purposes in the member states of the European Union. COM/2003/0019 final, Brussels
25. EU COM, Commission of the European Communities (2003d) Proposal for a regulation of the European parliament and of the council concerning the registration, evaluation, authorisation and restriction of chemicals (REACH), Brussels September 2003 (draft)
26. EU COM, Commission of the European Communities (2003e) Business impact study. Brussels October 2003
27. EU Parliament (2001) Report on the Commission White paper on strategy for a future chemicals policy, Rapporteur Inger Schörling. Session Document final A5-0356/2001-PE304.693. Brussels-Strasbourg, pp 36
28. Federal Register (2001) Episkin™, EpiDerm™ and rat skin transcutaneous electrical resistance methods: in vitro test methods proposed for assessing the dermal corrosivity potential of chemicals. US Federal Register 66:49685-49686
29. Fentem JH, Archer GEB, Balls M, Botham PA, Curren RD, Earl LK, Esdaile DJ, Holzhütter HG, Liebsch M (1998) The ECVAM International validation study on in vitro tests for skin corrosivity. 2. Results and evaluation by the management team. Toxicol In Vitro 12:483-524
30. Fielden MR, Zacharewski TR (2001) Challenges and limitations of gene expression profiling in mechanistic and predictive toxicology. Toxicology Science 60:6-10
31. Frawley JP (1967) Scientific evidence and common sense as a basis for food-packaging regulations. Fd Cosmet Toxicol 5:293-308
32. Gerner I, Schiede E (2002) Introduction of in vitro data into local irritation/corrosion testing strategies by means of SAR considerations: assessment of chemicals. Toxicology Letters 127:169-175
33. Gerner I, Sivapragasam G, Dudda B, Schiede E, Kayser D (1994) Entwicklung einer neuen Teststrategie zur Bestimmung der akuten dermalen Toxizität im Rahmen des Chemikaliengesetzes (Development of a new test strategy for the determination of the acute dermal toxicity under chemical law). Bundesgesundheitsblatt 11:463-467
34. Gerner I, Zinke S, Graetschel G, Schlede E (2000) Development of a decision support system for the introduction of alternative methods into local irritancy/corrosivity testing strategies. Creation of fundamental rules for a decision support system. ATLA 28:665-698
35. Gerner I, Barratt MD, Zinke S, Schlegel K, Schiede E (2003) Development and pre-validation of a list of SAR rules to be used in expert systems for the prediction of skin sensitising properties of chemicals. ATLA (in press)
36. GESAMP, IMO/FAO/UNESCO-IOC/WMO/WHO/IAEA/UN/ UNEP Joint Group of experts on the Scientific Aspects of Marine Environmental Protection (2002) Revised GESAMP hazard evaluation procedure for chemical substances carried by ships. GESAMP Reports and Studies No. 64. International Maritime Organization, London
37. Gettings SD, Teal JJ, Bagley DM, Demetrulias JL, DiPasquale LC, Hintze KL, Rozen MG, Weise SL, Chudkowski M, Marenus KD, Pape WJW, Roddy M, Schnetzinger R, Silber PM, Glaza SM, Kurtz PJ (1991) The CTFA evaluation of alternatives program: an evaluation of in vitro alternatives to the Draize primary eye irritation test (phase I). In vitro Toxicology 4(4):247-288
38. Gettings SD, DiPasquale LC, Bagley DM, Casterton PL, Chudkowski M, Curren RD (1994) The CTFA evaluation of alternatives program: an evaluation of in vitro alternatives to the Draize primary eye irritation test (phase II). Food Chem Toxicol 32(10):943-976
39. Gettings SD, Lordo RA, Hintze KL, Bagley DM, Casterton PL, Chudkowski M, Curren RD, Demetrulias JL, DiPasquale LC, Earl LK, Feder PI, Galli CL, Glaza SM, Gordon VC, Janus J, Kurtz PJ, Marenus KD, Moral J, Pape WJW, Renskers KJ, Rheins LA, Roddy M, Rozen MG, Tedeschi JP, Zyracki J (1996) The CTFA evaluation of alternatives program: an evaluation of in vitro alternatives to the Draize primary eye irritation test (phase III). Food Chem Toxicol 34:79-117
40. Gillesby BE, Zacharewski TR (1998) Exoestrogens: mechanisms of action and strategies for identification and assessment. Environ Toxicol Chem 17:3-14
41. Halle W (2003) The registry of cytotoxicity: toxicity testing in cell cultures to predict acute toxicity (LD50) and to reduce testing in animals. ATLA 31:89-198
42. Halle W, Liebsch M, Traue D, Spielmann H (1997) Reduktion der Tierzahlen bei der Einstufung von Stoffen in die EU-Toxizitätsklassen für akute orale Toxizität mit Hilfe von Daten aus dem Register der Zytotoxizität (RC). ALTEX 14:8-15
43. Hanway RH, Evans PF (2000) Read-across of toxicological data in the notification of new chemicals. Toxicol Lett 1/116:61
44. Heinrich-Hirsch B, Madle S, Oberemm A, Gundert-Remy U (2001) The use of toxicodynamics in risk assessment. Toxicol Lett 120:131-141
45. Höfer T, Steinhäuser KG (2000) Use of health hazard criteria for estimating the hazard potential of chemicals to water in case of a spill. Regul Toxicol Pharmacol 31:1-12
46. Höfer-Bosse T, Scharmann W (1986) Numbers of animals used in toxicological experiments - with particular reference to the Federal Republic of Germany. ATLA 13:212-219
47. Holzhütter HG, Genschow E, Diener W, Schlede E (2003) Dermal and inhalation acute toxic class methods: test procedures and biometric evaluations for the Globally Harmonized Classification System. Arch Toxicol 77:243-254
48. Huggins J (2003) Alternatives to animal testing: research, trends, validation, regulatory acceptance. ALTEX 20 (in press)
49. Hulzebos EM, Posthumus R (2003) (Q)SARs: gatekeepers against risk on chemicals. SAR QSAR Environ Res 14:285-316
50. Hulzebos EM, Maslankiewicz L, Walker JD (2003) Verification of literature-derived SARs for skin irritation and corrosion. QSAR & Combinatorial Science 22:351-363
51. ICCVAM, Interagency Coordinating Committee on the Validation of Alternative Methods (2001) Annual progress report, http:// iccvam.niehs.nih.gov/ about/annrpt/annrpt01.pdf
52. IEH, Institute for Environment and Health (2001a) Testing requirements for proposals under the EC White Paper "strategy for a future chemicals policy". Web Report W6. www.le.ac.uk/ ieh/webpub/webpub.html. University of Leicester, UK
53. IEH, Institute for Environment and Health (2001b) Assessment of the feasibility of replacing current regulatory in vivo tests with in vitro tests within the framework specified in the EC White Paper "strategy for a future chemicals policy". Web Report W10. University of Leicester, UK
54. IEH, Institute for Environment and Health (2002) Testing requirements for proposals under the EC White Paper "strategy for a future chemicals policy" - an update. University of Leicester, UK
55. Jaworska JS, Comber M, Auer C, van Leeuven CJ (2003) Summary of a workshop on regulatory acceptance of (Q)SAR for Human health and environmental endpoints. Environ Health Perspect 111:1358-1360
56. Klimisch HJ, Andreae M, Tillmann U (1997) A systematic approach for evaluating the quality of experimental toxicological and ecotoxicological data. Regulatory Toxicol Pharmacol 25:1-5
57. Klopman G (1985) Predicting toxicity through a computer automated structure evaluation program. Environ Health Perspect 61:269-274
58. Klopman G, Rosenkranz HS (1994) Prediction of carcinogenicity/ mutagenicity using MULTICASE. Mutation Research 305:33-46
59. Kroes R, Kozianowski G (2002) Threshold of toxicological concern (TTC) in food safety assessment. Toxicol Lett 127:43-46
60. MacGregor JT (2003) The future of regulatory toxicology: impact of the biotechnology revolution. Toxicol Sci 75:236-248
61. Martínez-Alegría R, Ordóñez C, Taboada J (2003) A conceptual model for analyzing the risks involved in the transportation of hazardous goods: implementation in a geographic information system. Human Ecol Risk Assess 9:857-873
62. Merrick A, Tomer KB (2003) Toxicoproteomics: a parallel approach to identifying biomarkers. Environ Health Perspect 111:A578-A579.
63. NICEATM, Interagency Center for the Evaluation of Alternative Toxicological Methods (2001) In vitro test methods for assessing the dermal corrosivity potential of chemicals, Episkin™, EpiDerm™, and rat skin transcutaneous electrical resistance (TER). National Institute of Environmental Health Sciences NIEHS, Research Triangle Park, USA NC 27709
64. NIH/ICCVAM, National Institutes of Health, Interagency Coordinating Committee on the Validation of Alternative Methods (2001a) Report of the International Workshop on In vitro Methods for Assessing Acute Systemic Toxicity. NIH Publication No. 01-4499. NTP Research Triangle Park, NC 27709. http://iccvam.niehs.nih.gov/methods/invidocs/finalall.pdf0
65. NIH/ICCVAM, National Institutes of Health, Interagency Coordinating Committee on the Validation of Alternative Methods (2001b) Guidance document on using in vitro data to estimate in vivo starting doses for acute toxicity. NIH Publication No. 01-4500. NTP Research Triangle Park, NC 27709. http://iccvam.niehs.nih.gov/methods/invidocs/guidance/iv_guide.pdf
66. Oberemm A, Querfurt N, Dieterich A, Meckert C, Brandenburger L, Herzig A, Lindner Y, Krause E, Ittrich C, Kopp-Schneider A, Richter-Reichhelm HB, Gundert-Remy U (2003) Proteomic analysis of TCDD-mediated effects in marmoset liver and thymus. Naunyn Schmiedebergs Arch Pharmacol 367:R153(599)
67. OECD, Organisation for Economic Co-operation and Development (2001) Appraisal of test methods for sex hormone disrupting chemicals. OECD Series on Testing and Assessment No. 21, Paris
68. OECD, Organisation for Economic Co-operation and Development (2003) Guidelines for testing of chemicals. OECD Publication Office, Paris (see http://www.oecd.org/document/55/ 0,2340,en_2649_34377_2349687_1_1_1_1,00.html)
69. Ohno Y, Kaneko T, Inoue T, Morikawa Y, Yoshida T, Fuji A, Masuda M, Ohno T, Hayashi M, Momma J, Uchiyama T, Chiba K, Ikeda N, Imanashi Y, Itakagaki H (1994) Interlaboratory validation of the in vitro eye irritation tests for cosmetic ingredients. (1) Overview of the validation study and Draize scores for the evaluation of the tests. Toxicol In Vitro 13:73-98
70. Pedersen F, de Bruijn J, Munn S, van Leeuwen K (2003) Assesment of additional testing needs under REACH. Effects of (Q)SAR, risk based testing and voluntary industry initiatives. Joint Research Center. http://europa.eu.int/ comm/enterprise/chemicals/ chempol/bia/testingneeds031029.pdf
71. Ramos KS, Goehl TJ (2003) Toxicogenomics: an EHP section. Environ Health Perspect 111:A328-A328
72. Rosenkranz HS (2003) SAR modelling of complex phenomena: probing methodological limitations. ATLA 31:393-399
73. Sanderson DM, Earnshaw CG (1991) Computer prediction of possible toxic action from chemical structure: the DEREK system. Hum Exp Toxicol 10:261-273
74. SCCNFP, European Commission's Scientific Committee on Cosmetics and Non-Food Products (2000) The Scientific Committee on Cosmetics and N on-Food Products Intended for Consumers notes of guidance for testing of cosmetic ingredients for their safety evaluation. SCCNFP/0321/00 final, adpt SCCNFT plenary meeting, 24 Oct 2000
75. SCCNFP, European Commission's Scientific Committee on Cosmetics and Non-Food Products (2003) The SCCNFP's notes of guidance for the testing of cosmetic ingredients and their safety evaluation. SCCNFP/0690/03 final, adpt SCCNFT plenary meeting, 20 Oct 2003
76. Spielmann H, Kalweit S, Liebsch M, Wirnsberger T, Gerner I, Bertram-Neis E, Kreiling R, Krauser K, Miltenburger HG, Pape WJW, Steiling W (1993) Validation study of alternatives to the Draize eye irritation test in Germany: cytotoxicity testing and HET-CAM test with 136 industrial chemicals. Toxicol In Vitro 7:505-510
77. Spielmann H, Liebsch M, Kalweit S, Moldenhauer F, Wirnsberger T, Holzhütter HG, Schneider B, Glaser S, Gerner I, Pape WJW, Kreiling R, Krauser K, Miltenburger HG, Steiling W, Lüpke NP, Müller N, Kreuzer H, Mürmann P, Spengler J, Bertram-Neis E, Siegemund B, Wiebel FJ (1996) Results of a validation study in Germany on two in vitro alternatives to the Draize eye irritation test, the HET-CAM test and the 3T3 NRU cytotoxicity test. ATLA 24:741-858
78. 50) testing in the up and down procedure (UDP) from cytotoxicity data. ATLA 27:957-966
79. Stallard N, Whitehead A, Ridgway P (2002) Statistical evaluation of the revised fixed-dose procedure. Human Exp Toxicol 21:183-196
80. Tennant RW (2002) The national center for toxicogenomics: using new technologies to inform mechanistic toxicology. Environ Health Perspect 110:A8-A10
81. Tong W, Perkins R, Strelitz R, Collantes ER, Keenan S, Welsh WJ, Branham WS, Sheehan DM (1997) Quantitative structure-activity relationships (QSARs) for estrogen binding to the estrogen receptor: predictions across species. Environ Health Perspect 105:1116-1124
82. UN TDG, United Nations Committee of Experts on the Transport of Dangerous Goods (2000) Evolution of the model regulations on the transport of dangerous goods (rationalised development of the regulations). ST/SG/AC. 10/2000/21, Geneva
83. United Nations (2003) Globally harmonized system of classification and labelling of chemicals. UN ST/SG/AC. 10/30, United Nations Publications sales no. E.03.II.E.25. United Nations, New York/Geneva
84. Valli VE, MCGrath JP, Chu I (2002) Hematopoietic system. In: Haschek WM, Rousseaux CG, Wallig MA (ed) Handbook of toxicologic pathology, vol. 2, 2nd edn. Academic Press, pp 647-679
85. Villeneuve DC, Koeter HBWM (1993) Proceedings of the international workshop on in-vitro methods in reproductive toxicology. Reprod Toxicol 7[Suppl]: 1-175
86. Walker JD, Carlsen L, Hulzebos E, Simon-Hettich B (2002) Global government applications of analogues, SARs and QSARs to predict aquatic toxicity, chemical or physical properties, environmental fate parameters and health effects of organic chemicals. SAR QSAR Environ Res 13:607-616
87. Walker JD, Carlsen L, Jaworska J (2003) Improving opportunities for regulatory acceptance of QSARs: the importance of model domain, uncertainty, validity and predictability. Quantitative Structure-Activity Relationships 22:1-5
88. WHO/IPCS (2002a) Report of the meeting on bridging the gap between clinical and regulatory toxicology, Edinburgh, United Kingdom, September 2001
89. WHO/IPCS (2002b) WHO/IPCS meeting on the use of clinical data in risk assessment, Perth, Western Australia, November 2002
90. Worth AP, Balls M (2002) Alternative (non-animal) methods for chemicals testing: current status and future prospects. A report prepared by ECVAM and the ECVAM Working Group on Chemicals. ATLA 30[Suppl 1]: 1-125
91. Worth AP, Cronin MTD (2001) The use of pH measurements to predict the potential of chemicals to cause acute dermal and ocular toxicity. Toxicology 169:119-131
92. 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
93. Zinke S, Gerner I, Graetschel G, Schlede E (2000) Local irritation/ corrosion testing strategies: development of a decision support system for the introduction of alternative methods. ATLA 28:29-40
94. Zuang V, Balls M, Botham PA, Coquette A, Corsini E, Curren RD, Elliot GR, Fentem JH, Heylings JR, Liebsch M, Medina J, Roquet R van de Sandt H, Wiemann C, Worth AP (2002) Follow-up to the ECVAM prevalidation study on in vitro tests for acute skin irritation. ATLA 30:109-129