Skip to main content
SpringerLink
Log in

The Future of Alternative Approaches in Reproductive Toxicity Testing

  • Chapter
Animals and Alternatives in Toxicology

  • 17 Accesses

Abstract

The remit of this Working Party was to review and assess the current scientific and regulatory requirements in the field of reproductive toxicology. Attention was given to compliance with the Three Rs in current testing methods and the achievement of reduction, refinement and replacement in animal testing by both current methods and research development. This report will comprise three sections covering regulatory aspects, in vitro and in vivo prescreens, and research. Recommendations are listed at the end of each section, and a list of specific recommendations is included at the end of the report, which are directed at industry and the regulatory authorities for their consideration.

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

Access this chapter

Log in via an institution

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

REFERENCES

  1. Kistler, A. (1987). Limb bud cell cultures for estimating the teratogenic potential of compounds: validation of the test with retinoids. Archives of Toxicology 60, 403–414.

    Article  PubMed  CAS  Google Scholar 

  2. Flint, O.P. & Boyle, F.T. (1985). An in vitro test for teratogens: its application in the selection of non-teratogenic triazole antifungals. Concepts in Toxicology 3, 29–35.

    CAS  Google Scholar 

  3. Fu, Li-J., Johnson, E.M. & Newman, L.M. (1990). Prediction of the developmental toxicity: hazard potential of halogenate drinking water disinfection by-products tested by the in vitro hydra assay. Regulatory Toxicology and Pharmacology 11, 213–219.

    Article  PubMed  CAS  Google Scholar 

  4. Phillips, J.C., Gibson, W.B., Yam, J., Alden, C.L. & Hard, G.C. (1990). Survey of the QSAR and in vitro approaches for developing non-animal methods to supersede the in vivo LD50 test. Food and Chemical Toxicology 28, 375–394.

    Article  PubMed  CAS  Google Scholar 

  5. Kavlock, R.J., Hall, L., Olgesby, L.A., McCoy, M.E. & Copeland, F. (1990). In vivo and in vitro structure-dosimetry-activity relationships and substituted phenols. In Abstracts of the In Vitro Culture of Postimplantation Rodent Embryos Meeting, Louvain-la-Neuve, Belgium, 3–6 April, 1990.

    Google Scholar 

  6. Chernoff, N. & Kavlock, R.J. (1990). An in vivo teratology screen utilising pregnant mice. Journal of Toxicology and Environmental Health 10, 541–550.

    Article  Google Scholar 

  7. Wickramaratne, G.A. (1987). The Chernoff-Kavlock assay: its validation and application in rat. Terato genesis, Carcinogenesis, Mutagenesis 7, 73–83.

    Article  CAS  Google Scholar 

  8. Hardin, B.D., Becker, R.A., Kavlock, R.J., Seidenberg, J.M. & Chernoff, N. (1987). Overview and summary: workshop on the Chernoff-Kavlock preliminary developmental toxicity test. Teratogenesis, Carcinogenesis, Mutagenesis 7, 119–127.

    Article  PubMed  CAS  Google Scholar 

  9. Cave, D.A. & Foster, P.M.D. (1990). Modulation of m-dinitrobenzene and m-nitrosonitrobenzene toxicity in rat Sertoli-germ cell co-cultures. Fundamental and Applied Toxicology 14, 199–207.

    Article  PubMed  CAS  Google Scholar 

  10. Moore, H.D.M. (1986). In vitro manipulation of gametes and embryos for evaluating the effect of chemicals on germ cell function and developmental potential. Food and Chemical Toxicology 24, 607–613.

    Article  PubMed  CAS  Google Scholar 

  11. Holloway, A.J., Moore, H.D.M. & Foster P.M.D. (1990). The use of in vitro fertilisation to detect reductions in the fertility of male rats exposed to 1,3-dinitrobenzene. Fundamental and Applied Toxicology 14, 113–122.

    Article  PubMed  CAS  Google Scholar 

  12. Spielmann, H., Kruger, C. & Vogel, R. (1985). Embryotoxicity testing during the pre-implantation period. Concepts in Toxicology 3, 22–28.

    CAS  Google Scholar 

  13. Freeman, S.J. & Brown, N.A. (1987). Sub-mammalian and sub-vertebrate models in teratogenicity screening. In In Vitro Methods in Toxicology (ed. C.K. Atterwill & C.E. Steel), pp. 391–409. Cambridge: Cambridge University Press.

    Google Scholar 

  14. Brown, N.A. (1987). Teratogenicity testing in vitro: status of validation studies. Archives of Toxicology, Suppl. 11, 105–114.

    Google Scholar 

  15. Fort, D.J., Dawson, D.A. & Bantle, J.A. (1988). Development of a metabolic activation system for the frog embryo teratogenesis assay: Xenopus (FETAX). Teratogenesis, Carcinogenesis, Mutagenesis 8, 251–263.

    Article  PubMed  CAS  Google Scholar 

  16. Jelinek, R., Peterka, M. & Rychter, Z. (1985). Chick embryotoxicity screening test—130 substances tested. Indian Journal of Experimental Biology 23, 588–595.

    PubMed  CAS  Google Scholar 

  17. Bechter, R. & Schmid, B.P. (1987). Teratogenicity in vitro: a comparative study of four antimycotic drugs using the whole-embryo culture system. Toxicology in Vitro 1, 11–15.

    CAS  Google Scholar 

  18. Cicurel, L. & Schmid, B.P. (1988). Postimplantation embryo culture for the assessment of teratogenic potential and potency of compounds. Experientia 44, 833–840.

    Article  PubMed  CAS  Google Scholar 

  19. Piersma, A.H., Attenon, J., Govers, M.J.A.P., Peters, P.W.J., Picard J.J., Schimdt, B.P., Stadler, J., Van Maele-Fabry, G., Verhoef, A. & Verseil, C. (1990). Rodent postimplantation embryo culture: interlaboratory validation as a screening test for teratogenic compounds. In Abstracts of the In Vitro Culture of Postimplantation Rodent Embryos Meeting, Louvain-la-Neuve, Belgium, 3–6 April, 1990.

    Google Scholar 

  20. Wiger, R., Stottum, A. & Brunborg, G. (1988). Estimating chemical developmental hazard in a chicken embryo limb bud micromass system. Pharmacology and Toxicology 2, 32–37.

    Article  Google Scholar 

  21. Hassel, J.R. & Horigan, E.A. (1982). Chondrogenesis: a model developmental system for measuring teratogenic potential of compounds. Teratogenesis, Carcinogenesis, Mutagenesis 2, 325–331.

    Article  Google Scholar 

  22. Wise, L.D., Clark, R.L., Rundell, J.O. & Robertson, R.T. (1990). Examination of a rodent limb bud micromass assay as a screen for developmental toxicity. Teratology 41, 341–351.

    Article  PubMed  CAS  Google Scholar 

  23. Kistler, A. (1985). Inhibition of chondrogenesis by retinoids: limb bud cell cultures as a test system to measure the teratogenic potential of compounds. Concepts Toxicology 3, 86–100.

    CAS  Google Scholar 

  24. Renault, J-Y., Melcion, C. & Cordier, A. (1989). Limb bud cell culture for in vitro teratogen screening: validation of an improved assessment method using 51 compounds. Teratogenesis, Carcinogenesis, Mutagenesis 9, 83–96.

    Article  PubMed  CAS  Google Scholar 

  25. Flint, O.P. & Orton, T.C. (1984). An in vitro assay for teratogens with cultures of rat embryo mid-brain and limb bud cells. Toxicology and Applied Pharmacology 76, 383–395.

    Article  PubMed  CAS  Google Scholar 

  26. Steele, V.E., Morrissey, R.E., Elmore, E.L., Rocha, D.G., Wilkinson, B.P., Curren, R.D., Schmetter, B.S., Louie, A.T., Lamb, J.C. & Yang, L.L. (1988). Evaluation of two in vitro assays to screen for potential development toxicants. Fundamental and Applied Toxicology 11, 673–684.

    Article  PubMed  CAS  Google Scholar 

  27. Smith, M.K., Kimmel, G.L., Kochhas, D.M., Shephard, T.H., Spielberg, S.P. & Wilson, J.G. (1983). A selection of candidate compounds for in vitro teratogenesis test validation. Teratogenesis, Carcinogenesis, Mutagenesis 3, 461–480.

    Article  PubMed  CAS  Google Scholar 

  28. Johnson, E.M., Newman, L.M. & Giacobbi, R.L. (1990). Some fundamental problems with in vitro developmental toxicity prescreeing assays as illustrated with bean seedlings. Teratology 41, 568.

    Google Scholar 

  29. Uphill, P.F., Wilkins, S.R. & Allen, J.A. (1990). In vitro micromass teratogen test results from a blind trial of 25 compounds and the effects of differing S9 treatment regimes on response to cyclophosphamide. Toxicology in Vitro, in press.

    Google Scholar 

  30. New, D.A.T. (1978). Whole-embryo culture and the study of mammalian embryos during organogenesis. Biological Review 53, 81–122.

    Article  CAS  Google Scholar 

  31. Rogers, J.M., Daston, G.P. & Ebron, M.T. (1985). Studies on the mechanism of trypan blue teratogenesis in the rat developing in vivo and in vitro. Teratology 31, 389–399.

    Google Scholar 

  32. Brown, N.A., Farmer, P.B. & Coakley, M.E. (1985). Valproic acid teratogenesis: demonstration that the biochemical mechanism differs from that of valproate hepatoxicity. Biochemical Society Transactions 13, 75–77.

    Article  PubMed  CAS  Google Scholar 

  33. Coakley, M.E., Rawlings, S.J. & Brown N.A. (1987). Short-chain carboxylic acids, a new class of teratogens: studies of potential biochemical mechanisms. Environmental Health Perspectives.

    Google Scholar 

  34. Spielmann, H. & Vogel, R. (1989). Unique role of studies on pre-implantation embryos to understand mechanisms of embryotoxicity in early pregnancy. Critical Reviews in Toxicology 20, 51–64.

    Article  PubMed  CAS  Google Scholar 

  35. Welsh, F., ed. (1987). Approaches to Elucidate Mechanisms in Teratogenesis, 285 pp. Washington, DC: Hemisphere.

    Google Scholar 

  36. Nau, H. (1990). Pharmacokinetic aspects of in vitro teratogenicity studies: comparison to in vivo. In In Vitro Methods in Developmental Toxicology (ed. G.L. Kimmel & D.M. Kochhar), pp. 29–43. Boca Ratan, FL, USA: CRC Press.

    Google Scholar 

  37. Feuston, M.H. & Scott W.J. (1985). Cadmium-induced forelimb ectrodactyly: a proposed mechanism of teratogenesis. Teratology 32, 407–419.

    Article  PubMed  CAS  Google Scholar 

  38. Pratt, R.M. (1985). Receptor-dependent mechanisms of glucocorticoid and dioxin-induced cleft palate. Environmental Health Perspectives 61, 35–40.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  39. Honda, A., Iwama, M., Umeda, T. & Mori, Y. (1982). The teratogenic mechanism of 6-aminonicotinamide on limb formation of chick embryos: abnormalities in the biosynthesis of glycosaminoglycans and proteoglycans in micromelia. Journal of Biochemistry 91, 1959–1970.

    PubMed  Google Scholar 

  40. Loch-Caruso, R. (1990). Application of cell-cell communication assays to problems of developmental toxicology. In In Vitro Methods in Developmental Toxicology (ed. G.L. Kimmel & D.M. Kochhar), 45–67. Boca Ratan, FL, USA: CRC Press.

    Google Scholar 

  41. Horton, W.E., Cleveland J., Rapp, U., Kohno, K., Yamada, Y., Miyashita, T. & Hasell, J.R. (1990). The regulation of genes encoding extracellular matrix proteins: in vitro studies and relationships to teratogenic mechanisms. In In Vitro Methods in Developmental Toxicology (ed. G.L. Kimmel & D.M. Kochhar), pp. 143–161. Boca Ratan, FL, USA: CRC Press.

    Google Scholar 

  42. Knudsen, T.B. (1990). In vitro approaches to the study of embryonic cell death in developmental toxicology. In In Vitro Methods in Developmental Toxicology (ed. G.L. Kimmel & D.M. Kochhor), 129–142. Boca Ratan, FL, USA: CRC Press.

    Google Scholar 

  43. Scott, W.J., Duggan, C.A., Schreiner, C.M. & Collins, M.D. (1990). Reduction of embryonic intracellular pH: a potential mechanism of acetazolamide-induced limb malformations. Toxicology and Applied Pharmcology 103, 238–254.

    Article  CAS  Google Scholar 

  44. Ranganathan, S., Churchill, P.F. & Hood, R.D. (1989). Inhibition of mitochondrial respiration of cationic rhodamines as a possible teratogenicity mechanism. Toxicology and Applied Pharmacology 99, 81–89.

    Article  PubMed  CAS  Google Scholar 

  45. Fantel, A.G., Juchau, M.R., Tracey, J.W., Burrows, C.J. & Person, R.E. (1989). Studies of the mechanisms of niridazole-elicited embryotoxicity: evidence against a major role for covalent binding. Teratology 39, 63–74.

    Article  PubMed  CAS  Google Scholar 

  46. Boeklheide, M., Neeley, D. & Sioussat, T M. (1989). The Sertoli cell cytoskeleton: a target for toxicant-induced germ cell loss. Toxicology and Applied Pharmacology 101, 373–389.

    Article  Google Scholar 

  47. Platzek, T., Meister, R., Chahoud, I., Bochert, G., Krowke, R. & Neubert, D. (1987). Studies on the mechanisms of dose-response relationships. In Approaches to Elucidate the Mechanisms in Teratogenesis (ed. F. Welsch), 59–81. Washington, DC, USA: Hemisphere.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Safety of Medicines, ICI Pharmaceuticals Division, Mereside, Alderley Park, Macclesfield, Cheshire, SK0 4TG, UK

    Paul Duffy & Stuart Freeman

  2. Glaxo Group Research Ltd, Park Road, Ware, Hertfordshire, SG12 0DP, UK

    Derek Newall

Authors
  1. Paul Duffy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stuart Freeman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Derek Newall
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Nottingham, UK

    Michael Balls (Professor of Medical Cell Biology) (Professor of Medical Cell Biology)

  2. University of Surrey, Guildford, UK

    James Bridges (Professor of Toxicology) (Professor of Toxicology)

  3. FRAME, Nottingham, UK

    Jacqueline Southee (Scientific Executive) (Scientific Executive)

Copyright information

© 1991 FRAME

About this chapter

Cite this chapter

Duffy, P., Freeman, S., Newall, D. (1991). The Future of Alternative Approaches in Reproductive Toxicity Testing. In: Balls, M., Bridges, J., Southee, J. (eds) Animals and Alternatives in Toxicology. Palgrave, London. https://doi.org/10.1007/978-1-349-12667-5_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-349-12667-5_7

  • Publisher Name: Palgrave, London

  • Print ISBN: 978-1-349-12669-9

  • Online ISBN: 978-1-349-12667-5

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics

Search

Navigation