Summary
The development of in vitro models is advancing rapidly, with the application of cell culture methods as an alternative to animals in toxicological screening; non-cellular systems are also being used. Any screening test, whether for detecting irritants, carcinogens or teratogens should be well validated against known animal studies. It should, for example, be able to correctly identify a teratogen as well as a non-teratogen. Various types of in vitro systems are utilised. Some validated test systems have been used for several years to detect genotoxins and are acceptable to many regulatory authorities. This is not the case for other in vitro systems, although some for skin irritation and corrosion are acceptable to some authorities. A non-comprehensive range of tests to measure responses in ocular, immune, cardiac, vascular, neurological, sensory, hepatic, testicular and embryological systems are described. Some tests are empirical and others much more closely mimic the animal model they represent. Some of the methods described are much closer to validation than others.
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References
Ames BN, McCann J, Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian microsome mutagenicity test. Mutation Research 31: 347–364, 1975
Anderson D. Genetic toxicology. In Anderson D, Conning DM (Eds) Experimental toxicology — the basic issues, pp. 252–286, Royal Society of Chemistry, 1988a
Anderson D. In vitro methods for teratology testing. In Anderson D, Conning DM (Eds) Experimental toxicology — the basic issues, pp. 335–347, Royal Society of Chemistry, 1988b
Ashby J, Tennant RW. 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, 1988
Ashby J, Tennant RW, Zeiger E, Stasiewicz S. Classification according to chemical structure, mutagenicity to Salmonella and level of carcinogenicity of a further 42 chemicals tested for carcinogenicity by the US National Toxicology Program 223: 73–103, 1989
Atterwill CK, Steele CE (Eds) In vitro methods in toxicology. Cambridge University Press, 1987
Bieri F, Bentley P, Waechter F, Staubi W. Mitogenicity of peroxisome proliferators in monolayers of adult rat hepatocytes. Food and Chemical Toxicology 24 (6/7): 709–710, 1986
Boobis AR, Tee LBG, Hampden CE, Davies DS. Freshly isolated hepatocytes as a model for studying the toxicity of paracetamol. Food and Chemical Toxicology 24 (6/7): 731–737, 1986
Borenfreund E, Borenfreund E, Borrero O. In vitro cytotoxicity assays. Potential alternatives to the Draize ocular irritancy test. Cell Biology and Toxicology 1: 55–65, 1984
Borenfreund E, Puerner JA. Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicology Letters 24: 119–124, 1984
Brusick D. Genotoxicity produce in mammalian cell assays by treatment conditions. Special issue. Mutation Research 189: 1–79, 1987
Chahwala SB, Harpur ES. Renal tubule fragments compared with renal cortical slices for the study of gentamicin binding and uptake in vitro. Food and Chemical Toxicology 24 (6/7): 595–599, 1986
Chan KY. An in vitro alternative to the Draize test. Alternative Methods in Toxicology 3: 405–422, 1985
Cockburn A. Development of a cardiotoxicity screening model using the isolated perfused rat heart. Food and Chemical Toxicology 24 (6/7): 597–599, 1986
Cooper JA, Saracci R, Cole P. Describing the validity of carcinogen screening tests. British Journal of Cancer 39: 87–89, 1979
Draize JH, Woodward G, Calvery HO. Method for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. Journal of Pharmacology and Experimental Therapeutics 82: 377–389, 1944
Flint OP. An in vitro test for teratogens: its practical application. Food and Chemical Toxicology 24 (6/7): 627–633, 1986
Francis A, Anderson D, Jenkinson P, Parke DV. The protective effects of L-ascorbic acid and DL-α-tocopherol on cultured rat embryos treated with xanthine/xanthine oxidase. Mutation Research 214: 137–145, 1989
Frazier JM, Gad SC, Goldberg AM, McCulley JP. Current in vivo testing protocols, procedures and practices. In Goldberg AM (Ed.) Alternative methods in toxicology. A critical evaluation of alternatives to acute ocular irritation testing, Vol. 4, pp. 9–20, Mary Ann Liebert Inc., New York, 1987
Freeberg FE, Griffith JF, Bruce RD, Bay PHS. Correlation of animal test methods with human experience for household products. Journal of Toxicology and Cutaneous Ocular Toxicology 1: 53–64, 1984
Freeman SJ, Steele CE. Post-implantation of whole embryo culture and the study of teratogenesis. Food and Chemical Toxicology 24 (6/7): 619–622, 1986
Freshney RI. Culture of animal cells. A manual of basic technique. Alan R Liss Inc., New York, 1988
Goldberg AM (Ed.) Alternative methods in toxicology. A critical evaluation of alternatives to acute ocular irritation testing, Vol. 4, Mary Ann Liebert Inc., New York 1987a
Goldberg AM (Ed.) Alternative methods in toxicology. In vitro toxicology approaches to validation, Vol. 5, Mary Ann Liebert Inc., New York, 1987b
Goldberg AM (Ed.) Alternative methods in toxicology. Progress in in vitro toxicology, Vol. 6, Mary Ann Liebert Inc., New York, 1989
Gordon VC, Bergman HC. EYETEX™, an in vitro method for evaluation of ocular irritancy. In Goldberg AM (Ed.) Progress in in vitro toxicology, Vol. 5, Mary Ann Liebert Inc., New York, 1987
Gordon VC, Bergman HC. The EYETEX-MPA system. An in vitro method for the evaluation of ocular safety. In Goldberg AM (Ed.) Progress in in vitro toxicology, Vol. 6, pp. 309–316, Mary Ann Liebert Inc., New York, 1988a
Gordon VC, Bergman HC. External evaluation of the standard EYETEX system in six laboratories to determine intra- and inter-laboratory accuracy and precision. In Goldberg AM (Ed.) Progress in in vitro toxicology, Vol. 6, pp. 317–323, Mary Ann Liebert Inc., New York, 1988b
Gordon VC, Bergman HC. External evaluation of the EYETEX and EYETEX-MPA systems in twelve laboratories to determine the correlation of EYETEX results with in vivo results. In Goldberg AM (Ed.) Progress in in vitro toxicology, Vol. 6, pp. 325–331, Mary Ann Libert Inc., New York, 1988c
Grant ME. Toxicology of the eye. 2nd ed., Thomas CC (Ed.), Springfield, Illinois, 1974
Gray TBJ, Beamand JA. Effect of some phthalate esters and other testicular toxins on primary cultures of testicular cells. Food and Chemical Toxicology 22: 123–131, 1984
Griffith JF, Nixon GA, Bruce RD, Reer PJ, Bannan EA. 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. Toxicology and Applied Pharmacology 55: 501–513, 1980
Hockley K, Baxter D. Use of the 3T3 cell-neutral red uptake assay for irritants as an alternative to the rabbit Draize test. Food and Chemical Toxicology 24: 473–475, 1986
Knox P, Uphill PF, Fry JR, Benford J, Balls M. The FRAME mutlticentre project on in vitro cytotoxicity. Food and Chemical Toxicology 24: 457–463, 1986
Langendorff O. Untersuchungen am überlebenden Säugetierherzen. Pflügers Archiv für die Gesamte Physiologie 61: 291, 1895
Lowry OH, Rosebraugh NJ, Farr AL, Randall RJ. Protein measurements with Folin phenol reagent. Journal of Biological Chemistry 193: 265–275, 1951
Luke JS, Betton GR, Liu RC. The effects of oxymetidine on in vitro platelet aggregation. Food and Chemical Toxicology 24: 593–596, 1986
Maron D, Ames BN. Revised methods for the Salmonella mutagenicity test. Mutation Research 113: 173–215, 1983
Miller K, Atkinson HAC. The in vitro effects of tricothecenes on the immune system. Food and Chemical Toxicology 24: 545–551, 1986
North-Root H, Yackvich F, Demetrulias J, Gacula Jr M, Heinze JE. Evaluation of an in vitro cell toxicity test using rabbit corneal cells to predict the eye irritation potential of surfactants. Toxicology Letters 14: 207–212, 1982
Oliver GJA, Pemberton MA. The identification of corrosive agents for human skin in vitro. Food and Chemical Toxicology 24: 513–517, 1986
Oliver GJA, Pemberton MA, Rhodes C. An in vitro skin corrosivity test — modification and validation. Food and Chemical Toxicology 24: 501–513, 1986
Purchase FH, Conning DM, Balls M, Rhodes C, Davies DS, et al. Proceedings of the International Conference on Practical In Vitro Toxicology. Special issue. Food and Chemical Toxicology 24: 417–818, 1986
Renault FY, Melcion C, Cordier A. Limb bud culture for in vitro teratogen screening: validation of an improved assessment method using 51 compounds. Teratogenesis, Carcinogenesis, and Mutagenesis 9: 83–97, 1989
Scala RA. Theoretical approaches to validation. In Goldberg AM (Ed.) Alternative methods in toxicology. In vitro toxicology approaches to validation, Vol. 5, pp. 1–9, Mary Ann Liebert Inc., New York, 1987
Spencer PS, Crain SM, Bornstein MR, Peterson ER, Van de Water T. Chemical neurotoxicity and analysis in organotypic cultures of sensory and motor neurons. Food and Chemical Toxicology 24: 539–545, 1986
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Anderson, D. In Vitro Models. Drug-Safety 5 (Suppl 1), 27–39 (1990). https://doi.org/10.2165/00002018-199000051-00006
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DOI: https://doi.org/10.2165/00002018-199000051-00006