Methods using animals have been accepted by toxicologists and other investigators as necessary to provide assurance of safety for environmental agents. The development of alternative approaches to the use of animals focuses on reducing and, in some instances, eliminating the use of animals. It will be easier to develop alternative tests for certain methods in toxicology than for others. The most difficult areas will be those of systemic toxicology, i.e., subchronic and chronic toxicity. There are a number of points that should be considered in the development of alternative tests. Among these are the biological or physiological relevance of the end-point used in the alternative test, where the test fits into a testing scheme, i.e., replacement or as a complement to the animal test, and the necessary quantitative and qualitative validational steps.
References
1.
1. Bruce, R.D. (1985). An up-and-down procedure for acute toxicity testing. Fund. Appl. Toxicol.5, 151–157.
2.
2. Muller, H., and Kley, H.P. (1982). Retrospective study on the reliability of an “approximate LD50” determined with a small number of animals. Arch. Toxicol.51, 189–196.
3.
3. Byard, J.L., and Dougherty, K.K. (1985). Comparative metabolism and toxicity of chemical carcinogens in primary cultures of hepatocytes. In Vitro Cell. Devel. Biol.21, 489–494.
4.
4. Acosta, D., and Ramos, K. (1984). Cardiotoxicity of tricyclic antidepressants in primary cultures of rat myocardial cells. J. Toxicol. Environ. Health14, 137–143.
5.
5. Tennant, R.W., Margolin, B.H., Shelby, M.D., Zeiger, E., Haseman, J.K., Spalding, J., Caspary, W., Resnick, M., Stasiewicz, S., Anderson, B., and Minor, R. (1987). Prediction of chemical carcinogenicity in rodents from in vitro genetic toxicity assays. Science236, 933–941.
6.
6. New, D.A.T. (1978). Whole-embryo culture and the study of mammalian embryos during organogenesis. Biol. Rev.53, 81–122.
7.
7. Sadler, T.W. (1979). Culture of early somite mouse embryos during organogenesis. J. Embryol. Exp. Morphol.49, 17–25.
8.
8. Hassell, J.R., Pennypacker, J.P., and Lewis, C.A. (1978). Chondrogenesis and cell proliferation in limb bud cell cultures treated with cytosine aralsinoside and vitamin A. Exp. Cell Res.112, 409–417.
9.
9. Hassell, J.R., and Horigan, E.A. (1982). Chondrogenesis: A model developmental system for measuring teratogenic potential of compounds. Teratogenesis Carcinog. Mutagen.2, 325–331.
10.
10. Flint, O.P., and Orton, T.C. (1984). An in vitro assay for teratogens with cultures of rat embryo midbrain and limb bud cells. Toxicol. Appl. Pharmacol.76, 383–395.
11.
11. Draize, J.H., Woodward, G., and Calvery, H.O. (1944). Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membrane. J. Pharmacol. Exp. Ther.82, 377–389.
12.
12. Griffith, J.F., Nixon, G.A., Bruce, R.D., Reed, P.J., and Bannan, E.A. (1980). Dose-response studies with chemical irritants in the albino rabbit eye as a basis for selecting optimum testing conditions for predicting hazard to the human eye. Toxicol. Appl. Pharmacol.55, 501–513.
13.
13. Leighton, J., Nassaver, J., Tchao, R., and Verdone, J. (1983). Development of a procedure using the chick egg as an alternative to the Draize rabbit test. In: Proceedings of the Symposium, Product Safety Evaluation, Development of New Methodological Approaches.A.M. Goldberg (ed.). New York: Mary Ann Liebert.
14.
14. Edelhauser, H.F. (1980). In vitro studies of corneal toxicity. In: Proceedings of the CTFA Ocular Safety Testing Workshop, In Vivo and In Vitro Approaches. Washington, DC: The Cosmetic, Toiletry and Fragrance Association (CTFA).
15.
15. Stern, M.E., Edelhauser, E., Pederson, H., and Staatz, W. (1981). Effects of ionophores X537A and A23187 and calcium-free medium on corneal endothelial morphology. Invest. Opthalmol. Vis. Sci.20, 497.
16.
16. Gordon, V.C., and Bergman, H.C. (1987). Eyetex, an in vitro method for evaluation of ocular irritancy. In: In Vitro Toxicology, Approaches to Validation.A.M. Goldberg (ed.). New York: Mary Ann Liebert, pp. 293–302.
17.
17. Green, S. (1987). Regulatory issues associated with use of alternative tests. In: Advances in Modern Environmental Toxicology.M. Mehlman (ed.). Princeton, NJ: Princeton Scientific, pp. 107–116.
