Abstract
All drugs have the potential to produce toxicity. The degree to which such toxicity occurs in a compound as balanced against its therapeutic activity is termed the therapeutic index. Toxicity should be clearly dissociable from efficacy. The goal of toxicity testing is therefore to determine the adverse effects of drugs in well- defined biological systems, which have their own unique susceptibility to toxicity. Once determined, these effect(s) of a drug and its metabolites are extrapolated to humans so that potential risks can be weighed against potential benefits. The ultimate objective is to evaluate the probability that a drug will not produce significant damage under specific conditions of use (Health and Welfare, Canada, 1981).
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References
Cooper, J. A., Seraci, R., and Cole, P. (1979) Describing the validity of carcinogen screening tests. Br. J. Cancer 39, 87–89.
de Serres, F. J. and Matsushima, T. (1984) Meeting report—environmental mutagenesis and carcinogenesis: Test method development, validation and utilization. Mutation Res. 130, 353–359.
Dews, P. B. and Wenger, G. R. (1979) Testing for behavioral effects of agents. Neurobehav. Toxicol. 1 (suppl. 1) 119–127.
Dunkel, V. C., Pienta, R.J., Sinah, A., and Traul, K. A. (1981) Comparative neoplastic transformation responses of Balb/3T3 cells, Syrian hamster embryo cells and Rayscher murine leukemia virus-infected Fischer 344 rat embrvo cells to chemical compounds. J. Natl. Can. Instx 67, 1303–1312.
Enslein, K. (1984) Estimation of toxicological endpoints by structure- activity relationships. Pharmacol. Rev. 36, 131S–135S.
Farber, E. (1982) Chemical carcinogenesis. A biological perspective. Am.J. Pathol. 106. 271–296.
Federal Register (1978) Good laboratory practice for nonclinical laboratory studies. 43, 29–36.
Hassell, J. R. and Horigan, E. A. (1982) A model developmental system for measuring teratogenic potential of compounds. Teratogen Carcinogen Mutagen. 2, 353–359.
Health and Welfare, Canada. (1981) Preclinical Toxicologic Guidelines.
Heinze,J. E. and Poulsen, N..K. (1983) The optimal design of batteries of short-term tests for detecting carcinogens. Mutation Res. 117, 259–269.
Hollstein, M., McCann,J., Angelosanto, F., and Nichols, W. (1979) Short- term tests for carcinogens and mutagensMutation Res 65, 133–226.
Jackson, E. M. (1983) Editorial. Are food, drugs and cosmetics different or the same? J. Toxicol. Cut. Ocular Toxicol. 2, 79–80
Jakobovits, A., Banda, M. J., and Martin, G. R. (1985) Embryonal Carcinoma-Derived Growth Factors: Specific Growth-Promoting and Differentiation-Inhibiting Activities, in Cancer Cells 3. Growth Factors and Transformation Cold Spring Harbor Laboratories, New York.
Kolbye, A. C. (1980) Impact of Short-Term Screening Tests on Regulatory Action, in Applied Methods in Oncology vol. 3 The Predictive Value of Short-Term Screening Tests in Carcinogenicity Evaluation ( Williams, G., Kroes, R., Waaijers, H. W., and van de Poll, K. W., eds.) Elsevier North-Holland Biomedical, New York.
Kroes, R. and Feron, V. J. (1984) General toxicity testing: Sense and non-sense, science and policy. Fund. Appl. Toxicol. 4, S298 - S308.
Loose, L. D. (1985) Immunotoxicology—1984. in The Year In Immunology 1984-1985. ( Cruse, J. M. and Lewis, R. E., Jr., eds.) Karger, Basei.
Martin, G. R. and Evans, M. J. (1975a) Multiple differentiation of clonal teratocarcinoma stem cells following embrvoid body formation in vitro. Cell 6, 467–475.
Martin, G. R. and Evans, M. J. (1976b) Differentiation of clonal lines of teratocarcinoma cells: Formation of embrvoid bodies in vitro. Proc. Natl. Acad. Sci. 72, 1441–1445.
Miller, E. C. and Miller, J. A. (1981) Mechanisms of chemical car-cinogenesis. Cancer 47, 1055–1064.
Nardonne, R. M. and Bradlaw, J. A. (1983) Toxicity testing with in vitro svstems. I. Occular tissue culture. J. Toxicol. Cut. Ocular Toxicol. 2, 81–98.
National Toxicology Program (1984) Report of the ad hoc fxmel on chemical carcinogenesis testing and evaluation. Board of Scientific Counselors National Toxicology Program, U.S. Department of Health and Human Services Public Health Service.
Russell, W. M. S. and Burch, R. L. (1959) The Principles of Humane Experimental Techniques. Methuen, London.
Rowan, A. N. (1985) Perspectives on alternatives to current animal testing techniques in preclinical toxicology. Ann. Rev. Pharmacol. Toxicol. 25, 225–247.
Squire, R. A. (1984) Carcinogenicity testing and safety assessment. Fund. Appl. Toxicol. 4, S326–S334.
Tilson, H. A., Mitchell, C. L., and Cabe, P. A. (1979) Screening for neurobehavioral toxicity. The need for examples of validation of testing procedures. Neurohehav. Toxicol. 1 (suppl. 1), 137–148.
Traina, V. M. (1983) The role of toxicology in drug research and development. Med. Res. Rev. 3, 43–72.
Williams, G. M. and Weisburger, J. H. (1983) New approaches to car-cinogen bioassay in safety evaluation and regulation of chemicals. 1st Int. Conf., Boston, Massachusetts.
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Cavagnaro, J., Lewis, R.M. (1987). Toxicological Evaluation of Drugs. In: Williams, M., Malick, J.B. (eds) Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-4612-4828-6_10
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DOI: https://doi.org/10.1007/978-1-4612-4828-6_10
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