Skip to main content
SpringerLink
Log in

Risk assessment: alternatives to animal testing

  • Chapter
Food Chemical Risk Analysis

Abstract

All new chemicals manufactured specifically for use in food are required to be evaluated for safety. Such chemicals which are intentionally incorporated into foods are additives, and this chapter focuses on their safety assessment. Each proposed food additive is subjected to various in vivo and in vitro assays, which may include tests for genotoxicity, acute and subchronic toxicity, carcinogenicity and teratogenicity (Chapter 2). In the UK, on the basis of the results obtained and the estimated daily intake, the additive is assigned an acceptable daily intake (ADI) value as an indication of the levels which may be consumed without the likelihood of adverse effects.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Advisory Committee on Novel Foods and Processes (1991) Guidelines on the assessment of novel foods and processes. Department of Health Reports on Health and Social Subjects, 38. HMSO, London.

    Google Scholar 

  • Animal Procedures Committee (1994) Report to the Home Secretary on Regulatory Toxicity. Home Office Publications, London.

    Google Scholar 

  • Anon. (1993) Zbinden criticises the FDA. FRAME News, 33, 8.

    Google Scholar 

  • Ashby, J. (1992) Prediction of non-genotoxic carcinogenesis. Toxicology Letters, 64/65, 605–612.

    Article  Google Scholar 

  • Ashby, J. and Purchase, I.F.H. (1992) Non-genotoxic carcinogens — an extension of the perspective provided by Perera. Environmental Health Perspectives, 98, 223–226.

    CAS  Google Scholar 

  • Ashby, J. and Purchase, I.F.H. (1993) Will all chemicals be carcinogenic to rodents when adequately evaluated? Mutagenesis, 8, 489–493.

    Article  CAS  Google Scholar 

  • Ashby, J. and Tennant, R.W. (1988) Chemical structure: Salmonella mutagenicity and extent of carcinogenicity as indicators of genotoxic carcinogenesis among 222 chemicals tested in rodents by the US NCI/NTP. Mutation Research, 204, 17–115.

    Article  CAS  Google Scholar 

  • Ashby, J., Brady, A., Elcombe, C.R. et al. (1994) Mechanistically-based human hazard assessment of peroxisome proliferator-induced hepatocarcinogenesis. Human and Experimental Toxicology, 13 (S2).

    Google Scholar 

  • Atterwill, C.K., Simpson, M.G., Evans, R.J. et al. (1991) Alternative methods and their application in neurotoxicity testing. In: Balls, M., Bridges, J. and Southee, J. (eds) Animals and Alternatives in Toxicology: Present Status and Future Prospects. Macmillan Press, London, pp. 121–152.

    Google Scholar 

  • Atterwill, C.K., Davenport-Jones, J., Goonetilleke, S. et al. (1993) New models for the in vitro assessment of neurotoxicity in the nervous system and the preliminary validation stages of a ’tiered-test’ model. Toxicology in Vitro, 7, 569–580.

    Article  CAS  Google Scholar 

  • Atterwill, C.K., Bruinink, A., Drejer, J. et al. (1994) In vitro neurotoxicity testing. The report and recommendation of ECVAM workshop 3. Alternatives to Laboratory Animals, 22, 350–362.

    Google Scholar 

  • Balls, M. and Fentem, J.H. (1992) The use of basal cytotoxicity and target organ toxicity tests in hazard identification and risk assessment. Alternatives to Laboratory Animals, 20, 368–388.

    Google Scholar 

  • Balls, M., Goldberg, A.M., Fentem, J.H. et al. (1995) The Three Rs: the way forward. Alternatives to Laboratory Animals, 23, 838–866.

    Google Scholar 

  • Barratt, M.D., Castell, J.V., Chamberlain, M. et al. (1995) The integrated use of alternative approaches for predicting toxic hazard. The report and recommendations of ECVAM workshop 8. Alternatives to Laboratory Animals, 23, 410–429.

    Google Scholar 

  • Blaauboer, B.J., Boobis, A.R., Castell, J.V. et al. (1994) The practical applicability of hepa- tocyte cultures in routine testing. The report and recommendations of ECVAM workshop 1. Alternatives to Laboratory Animals, 22, 231–241.

    Google Scholar 

  • Blaauboer, B.J., Bayliss, M.K., Castell, J.V. et al. (1996) The use of biokinetics and in vitro methods in toxicological risk evaluation. The report and recommendations of ECVAM workshop 15. Alternatives to Laboratory Animals, 24, 473–497.

    Google Scholar 

  • Brown, S.J., Raja, A.A. and Lewis, D.F.V. (1994) A comparison between COMPACT and Hazardexpert evaluations for 80 chemicals tested by the NTP/NCI rodent bioassay. Alternatives to Laboratory Animals, 22, 482–500.

    Google Scholar 

  • Christian, M.S. (1986) A review of multigeneration studies. Journal of the American College of Toxicology, 5, 161–180.

    Google Scholar 

  • Combes, R.D. (1992) The in vivo relevance of in vitro genotoxicity assays incorporating enzyme activation systems. In: Gibson, G.G. (ed.) Progress in Drug Metabolism, Vol. 13. Taylor and Francis, London, pp. 295–321.

    Google Scholar 

  • Combes, R.D. (1995) Regulatory genotoxicity testing: a critical appraisal. Alternatives to Laboratory Animals, 23, 352–379.

    Google Scholar 

  • Commission of the European Communities (1980) Guidelines for the safety assessment of food additives. Reports of the Scientific Committee for Food (Tenth series) (EUR 6892). CEC, Luxembourg, pp. 5–21.

    Google Scholar 

  • Commission of the European Communities (1994) First 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, COM (94), 195 final, 27 May. CEC, Brussels.

    Google Scholar 

  • Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (1982) Guidelines for the testing of chemicals for toxicity. Department of Health Reports on Health and Social Subjects, 27. HMSO, London.

    Google Scholar 

  • Crespi, C.L., Steimel, D.T., Aoyama, T. et al. (1990a) Stable expression of human cytochrome P4501A2 cDNA in a human lymphoblastoid cell line: role of the enzyme in the metabolic activation of aflatoxin B,. Molecular Carcinogenesis, 3, 5–8.

    Article  CAS  Google Scholar 

  • Crespi, C.L., Langenbach, R. and Penman, B.W. (1990b) The development of a panel of human cell lines expressing specific human cytochrome P450 cDNAs. Progress in Clinical and Biological Research, 340B, 97–106.

    CAS  Google Scholar 

  • De Angelis, I., Hoogenboom, L.A.P., Huveneers-Oorsprong, M.B.M. et al. (1994) Established cell lines for safety assessment of food contaminants: differing furazolidone toxicity to V 79, HEp-2 and Caco-2 cells. Food and Chemical Toxicology, 32, 481–488.

    Article  Google Scholar 

  • Doetschman, T.C., Eistetter, H.R., Schmidt, W. and Kemler, R. (1985) The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. Journal of Embryology and Experimental Morphology, 87, 27–45.

    CAS  Google Scholar 

  • European Economic Community (1976) Council Directive 76/768/EEC of 27 July 1976 on the approximation of the laws of the Member States relating to cosmetic products. Official Journal of the European Communities, L262, 169–172.

    Google Scholar 

  • European Economic Community (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. L358, 1–29.

    Google Scholar 

  • European Economic Community (1993) Council Directive 93/35/EEC of 14 June 1993 amending for the sixth time Directive 76/768/EEC on the approximation of the laws of the Member States relating to cosmetic products. Official Journal of the European Communities, L151, 32–36.

    Google Scholar 

  • FLAIR (1991) Concerted Action no. 8. In vitro toxicological studies and real time analysis in food. In: Hoogenboom, L.A.P. and Broex, N.J.G. (eds) Proceedings of the workshops held in Berlin, 8–9 March 1991, and Swansea, 21–22 March 1991. Rikilt, Wageningen, The Netherlands.

    Google Scholar 

  • Food and Drug Administration (1993) Draft: Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food. US Food and Drug Administration Center for Food Safety and Applied Nutrition, Washington. DC.

    Google Scholar 

  • Francis, E.Z. and Kimmel, G.L. (1988) Proceedings of the workshop on one- vs two-generation reproductive effects studies. Journal of the American College of Toxicology, 7, 911–925.

    Google Scholar 

  • Fund for the Replacement of Animals in Medical Experiments (1983) Report of the FRAME Toxicity Committee. Alternatives to Laboratory Animals, 10. 4–43.

    Google Scholar 

  • Fund for the Replacement of Animals in Medical Experiments (1991) Animals and alternatives in toxicology: present status and future prospects (the Second Report of the FRAME Toxicity Committee). Alternatives to Laboratory Animals. 19, 116–138.

    Google Scholar 

  • Garle, M.J., Fentem, J.H. and Fry, J.R. (1994) In vitro cytotoxicity tests for the prediction of acute toxicity in vivo. Toxicology in Vitro, 8, 1303–1312.

    CAS  Google Scholar 

  • Gatehouse, D., Rowland, I.R., Wilcox, P. et al. (1990) Bacterial mutation assays. In: Kirkland, D.J. (ed.)Basic Mutagenicity Tests: UKEMS Recommended Procedures, UKEMS Subcommittee Report on Guidelines for Mutagenicity Testing, Part I (Revised). Cambridge University Press, Cambridge, pp. 13–61.

    Google Scholar 

  • Gold, L.S. and Stone, T.H. (1993) Prediction of carcinogenicity from two versus four sex- species groups in the Carcinogenic Potency Database. Journal of Toxicology and Environmental Health, 39, 143–157.

    Article  CAS  Google Scholar 

  • Gossen, J.A., De Leeuw, W.J.F., Tan, C.H.T. et al. (1989) Efficient rescue of integrated shuttle vectors from transgenic mice. A model for studying mutations in vivo. Proceedings of the National Academy of Sciences of the USA, 86, 7971–7975.

    Article  CAS  Google Scholar 

  • Gray, T.J.B. (1995) Safety evaluation in vitro: the changing environment. Meeting report. In Vitro Toxicology Society Newsletter, 1, 2–3.

    Google Scholar 

  • Guntakatta, M., Matthew, E.J. and Rundell, J.O. (1984) Development of a mouse embryo limb bud cell culture system for the estimation of chemical teratogenic potential. Teratogenesis, Carcinogenesis and Mutagenesis, 4, 349–364.

    Article  CAS  Google Scholar 

  • Haseman, J.K., Bourbina, J. and Eustis, S.L. (1994) Effect of individual housing and other experimental design factors on tumor incidence in B6C3F1 mice. Fundamental and Applied Toxicology, 23, 44–52.

    Article  CAS  Google Scholar 

  • Heuer, J., Graever, I., Pohl, I. and Spielmann, H. (1994) An in vitro embryotoxicity assay using the differentiation of embryonic mouse stem cells into haematopoietic cells. Toxicology in Vitro, 8, 585–587.

    Article  CAS  Google Scholar 

  • Hiraga, K. and Fujii, T. (1981) Induction of tumours of the urinary system in F-344 rats by dietary administration of sodium o-phenyl phenate. Food and Cosmetic Toxicology, 19, 303–310.

    Article  CAS  Google Scholar 

  • Home Office (1994) Statistics of Scientific Procedures on Living Animals, Great Britain. Cm 3516. HMSO, London.

    Google Scholar 

  • Home Office (1996) Statistics of Scientific Procedures on Living Animals, Great Britain. Cm 3516. HMSO, London.

    Google Scholar 

  • Johnson, E.M., Gorman, R.M., Gabel, B.E.G. and George, M.E. (1982) The Hydra attenuata system for detection of teratogenic hazards. Teratogenesis, Carcinogenesis and Mutagenesis, 2, 263–276.

    Article  CAS  Google Scholar 

  • Joly, B., Fardel, O., Cecchelli, R. et al. (1995) Selective drug transport and P-glycoprotein activity in an in vitro blood-brain barrier model. Toxicology in Vitro, 9, 357–364.

    Article  CAS  Google Scholar 

  • Kohler, S.W., Provest, G.S., Fieck, A. et al. (1991) Spectra of spontaneous and mutagen- induced mutations in the Lac I gene in transgenic mice. Proceedings of the National Academy of Sciences of the USA, 88, 7958–7962.

    Article  CAS  Google Scholar 

  • Lai, D.Y., Baetcke, K.P., Vu, V.T. et al. (1994) Evaluation of reduced protocols for carcinogenicity testing of chemicals: report of a joint EPA/NIEHS workshop. Regulatory Toxicology and Pharmacology, 19, 183–201.

    Article  CAS  Google Scholar 

  • Lefevre, P.A., Tinwell, G., Galloway, S.M. et al. (1994) Evaluation of the genetic toxicity of the peroxisome proliferator and carcinogen methyl clofenapate, including assays using Mutaâ„¢Mouse and Big Blueâ„¢ transgenic mice. Human and Experimental Toxicology, 13, 764–775.

    Article  CAS  Google Scholar 

  • Lewis, D.F.V. (1994) Comparison between rodent carcinogenicity test results of 44 chemicals and a number of predictive systems. Regulatory Toxicology and Pharmacology, 20, 215–222.

    Article  CAS  Google Scholar 

  • Lewis, D.F.V., Moereels, H., Lake, B.G. et al. (1994) Molecular modelling of enzymes and receptors involved in carcinogenesis: QSARs and COMPACT-3D. Drug Metabolism Reviews, 26, 261–285.

    Article  CAS  Google Scholar 

  • Long, A. and Combes, R.D. (1995) Using DEREK to predict the activity of some carcino-gens/mutagens found in foods. Toxicology in Vitro, 9, 563–569.

    Article  CAS  Google Scholar 

  • Mallett, A.K., Rowland, I.R., Bearne, C.A. et al. (1985) Metabolic adaptation of rat faecal microflora to cyclamate in vitro. Food and Chemical Toxicology, 23, 1029.

    Article  CAS  Google Scholar 

  • Moore, C.J. and Mepham, T.B. (1995) Transgenesis and animal welfare. Alternatives to Laboratory Animals, 23, 380–397.

    Google Scholar 

  • Organization for Economic Co-operation and Development (1987) Acute oral toxicity. Guidelines for Testing of Chemicals No. 401. OECD. Paris.

    Google Scholar 

  • Organization for Economic Co-operation and Development (1992) Acute oral toxicity — fixed dose method. Guidelines for Testing of Chemicals No. 420. OECD, Paris.

    Google Scholar 

  • Organization for Economic Co-operation and Development (1994) Guidelines for Testing of Chemicals. OECD, Paris.

    Google Scholar 

  • Reitz, R.H., Fox, T.R. and Quast, J.F. (1984) Biochemical factors involved in the effects of orthophenylphenol (OPP) and sodium orthophenylphenate (SOPP) on the urinary tract of male F-344 rats. Toxicology and Applied Pharmacology, 73. 345–349.

    Article  CAS  Google Scholar 

  • Renwick, A.G. (1993) Data-derived safety factors for the evaluation of food additives and environmental contaminants. Food Additives and Contaminants, 10, 275–305.

    Article  CAS  Google Scholar 

  • Rosenkranz, H.S. and Klopman, G. (1993) Structural relationships between mutagenicity, maximum tolerated dose, and carcinogenicity in rodents. Environmental and Molecular Mutagenesis, 21, 193–206.

    Article  CAS  Google Scholar 

  • Rowland, I.R. (1988) Interactions of the gut microflora and host in toxicology. Toxicology and Pathology, 16, 147–150.

    Article  CAS  Google Scholar 

  • Rumney, C.J. and Rowland, I.R. (1992) In vivo and in vitro models of the human colonic flora. Critical Reviews in Food Science and Nutrition, 31, 299–331.

    Article  CAS  Google Scholar 

  • Russell, W.M.S. and Burch, R.L. (1959) The Principles of Humane Experimental Technique. Methuen, London.

    Google Scholar 

  • Sanderson, D.M. and Earnshaw, C.G. (1991) Computer prediction of possible toxic action from chemical structure: the DEREK system. Human and Experimental Toxicology, 10, 261–273.

    Article  CAS  Google Scholar 

  • Scrable, H.J., Sapienza, C. and Cavanee, W.K. (1990) Genetic and epigenetic losses of heterozygosity in cancer predisposition and progression. Advances in Cancer Research, 54, 25–62.

    Article  CAS  Google Scholar 

  • Seibert, H., Gulden, M. and Voss, J-U. (1994) An in vitro toxicity testing strategy for the classification and labelling of chemicals according to their potential acute lethal potency. Toxicology in Vitro, 8, 847–850.

    Article  CAS  Google Scholar 

  • Skouv, J., Rasmussen, E.S., Frandsen, H. et al. (1995) Activation of c-myc and c-fos proto- oncogenes by the reducing agent DTT (dithiothreitol) in human cells. Alternatives to Laboratory Animals, 23, 497–503.

    Google Scholar 

  • Steele, C.E., New, D.A.T., Ashford, A. and Copping, G.P. (1983) Teratogenic action of hypolipidemic agents: an in vitro study with postimplantation rat embryos. Teratology, 28, 229–236.

    Google Scholar 

  • Stokes, W.S. (1994) Alternative test method development at the National Toxicology Program. In: Proceedings of the Toxicology Forum Winter Meeting, Washington, DC. Toxicology Forum, Washington, DC, pp. 302–312.

    Google Scholar 

  • Straughan, D.W. (1994) First European Commission report on statistics of animal use. Alternatives to Laboratory Animals, 22, 289–292.

    Google Scholar 

  • Tennant, R.W. (1993) A perspective on nonmutagenic mechanisms in carcinogenesis. Environmental Health Perspectives Supplements, 101, 231–236.

    CAS  Google Scholar 

  • Tennant, R.W., Spalding, J.W., Stasiewicz, S. and Ashby, J. (1990) Prediction of the outcome of rodent carcinogenicity bioassays currently being conducted on 44 chemicals by the US NTP. Mutagenesis, 5, 3–14.

    Article  CAS  Google Scholar 

  • Walum, E., Balls, M., Bianchi, V. et al. (1992) ECITTS: an integrated approach to the application of in vitro test systems to the hazard assessment of chemicals. Alternatives to Laboratory Animals, 20, 406–428.

    Google Scholar 

  • Wobus, A.M., Rohwedel, J., Maltsev, V. and Hescheler, J. (1995) In vitro cellular models for cardiac development and pharmacotoxicology. Toxicology in Vitro, 9, 477–488.

    Article  CAS  Google Scholar 

  • Yagi, T., Sato, M., Nishigori, C. and Takebe, H. (1994) Similarity in the molecular profile of mutations induced by UV light in shuttle vector plasmids propagated in mouse and human cells. Mutagenesis, 9, 73–77.

    Article  CAS  Google Scholar 

Download references

Authors
  1. C. L. Broadhead
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. D. Combes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Balls
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. TAS International, Chartwell House, 38 Church Street, Malvern, Worcestershire, London, WR14 2AZ, UK

    David R. Tennant

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Chapman & Hall

About this chapter

Cite this chapter

Broadhead, C.L., Combes, R.D., Balls, M. (1997). Risk assessment: alternatives to animal testing. In: Tennant, D.R. (eds) Food Chemical Risk Analysis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1111-9_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-1111-9_6

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-8422-2

  • Online ISBN: 978-1-4613-1111-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation