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In Vitro Models

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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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Borenfreund E, Puerner JA. Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicology Letters 24: 119–124, 1984

    Article  Google Scholar 

  • Brusick D. Genotoxicity produce in mammalian cell assays by treatment conditions. Special issue. Mutation Research 189: 1–79, 1987

    CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • Chan KY. An in vitro alternative to the Draize test. Alternative Methods in Toxicology 3: 405–422, 1985

    CAS  Google Scholar 

  • Cockburn A. Development of a cardiotoxicity screening model using the isolated perfused rat heart. Food and Chemical Toxicology 24 (6/7): 597–599, 1986

    Article  CAS  Google Scholar 

  • Cooper JA, Saracci R, Cole P. Describing the validity of carcinogen screening tests. British Journal of Cancer 39: 87–89, 1979

    Article  PubMed  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

  • Flint OP. An in vitro test for teratogens: its practical application. Food and Chemical Toxicology 24 (6/7): 627–633, 1986

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Freshney RI. Culture of animal cells. A manual of basic technique. Alan R Liss Inc., New York, 1988

    Google Scholar 

  • 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

    Google Scholar 

  • Goldberg AM (Ed.) Alternative methods in toxicology. In vitro toxicology approaches to validation, Vol. 5, Mary Ann Liebert Inc., New York, 1987b

    Google Scholar 

  • Goldberg AM (Ed.) Alternative methods in toxicology. Progress in in vitro toxicology, Vol. 6, Mary Ann Liebert Inc., New York, 1989

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Grant ME. Toxicology of the eye. 2nd ed., Thomas CC (Ed.), Springfield, Illinois, 1974

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Langendorff O. Untersuchungen am überlebenden Säugetierherzen. Pflügers Archiv für die Gesamte Physiologie 61: 291, 1895

    Article  Google Scholar 

  • Lowry OH, Rosebraugh NJ, Farr AL, Randall RJ. Protein measurements with Folin phenol reagent. Journal of Biological Chemistry 193: 265–275, 1951

    PubMed  CAS  Google Scholar 

  • Luke JS, Betton GR, Liu RC. The effects of oxymetidine on in vitro platelet aggregation. Food and Chemical Toxicology 24: 593–596, 1986

    Article  CAS  Google Scholar 

  • Maron D, Ames BN. Revised methods for the Salmonella mutagenicity test. Mutation Research 113: 173–215, 1983

    Article  PubMed  CAS  Google Scholar 

  • Miller K, Atkinson HAC. The in vitro effects of tricothecenes on the immune system. Food and Chemical Toxicology 24: 545–551, 1986

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Oliver GJA, Pemberton MA. The identification of corrosive agents for human skin in vitro. Food and Chemical Toxicology 24: 513–517, 1986

    Article  CAS  Google Scholar 

  • Oliver GJA, Pemberton MA, Rhodes C. An in vitro skin corrosivity test — modification and validation. Food and Chemical Toxicology 24: 501–513, 1986

    Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

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  1. British Industrial Biological Research Association, Woodmansterne Rd, Carshalton, Surrey, SM5 4DS, United Kingdom

    Diana Anderson (Assistant Director)

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  1. Diana Anderson
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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

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