As a result of a workshop held at Täljöviken, Åkersberga, Sweden, on 27–29 May 1991, a multicentre collaborative research project was established, with the purpose of developing the concept of integrated in vitro toxicity testing. The first priority was the selection of tests within eight appropriate areas: basal cytotoxicity, irritancy, developmental toxicity, hepatotoxicity, nephrotoxicity, immunotoxicity, neurotoxicity and biokinetics. An ideal battery of tests for each area was identified. Since it was realised that it would not be feasible to include the full ideal list of tests in the project, a minimum test list was also agreed. For each area, ten calibration chemicals were selected. From these 80 compounds, 30 were selected for inclusion, together with 20 of the OECD test programme chemicals, in a first test set of chemicals. The toxicity of these 50 test set chemicals will be investigated in the minimum integrated test scheme.
The aim of the project is to employ non-animal methods to assess the toxicological properties of chemicals, and to improve this assessment through the use of knowledge about mechanisms of toxic action. The information produced will contribute to the establishment of a more-scientific and more-efficient toxicological procedure for hazard assessment. Questions concerning which parameters need to be investigated and combined to make hazard assessments, and which parameters relevant to in vivo toxicity can be determined in non-whole animal test systems, will also be addressed.
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BallsM., BothamP., CordierA., FumeroS., KayserD., KoëterH., KoundakjianP., LindquistN-G., MeyerO., PiodaL., ReinhardtC., RozemondH., SmyrniotisT., SpielmannH., Van LooyH., van der VenneM.T., and WalumE. (1990). Report and recommendations of an international workshop on promotion of the regulatory acceptance of validated non-animal toxicity test procedures.ATLA18, 339–344.
3.
WalumE., VarnboI., and PetersonA. (1986). A multiple cell culture toxicity test system based on neuroblastoma C1300 cells and differentiated primary cultures of brain, muscle, heart and liver cells.Food and Chemical Toxicology24, 567–568.
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BondessonI., EkwallB., HellbergS., RomertL., StenbergK., and WalumE. (1989). MEIC — a new multicenter project to evaluate the relevance to human toxicity of in vitro cytotoxicity tests.Cell Biology and Toxicology5, 331–348.
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EkwallB. (1992). Validation of in vitro cytotoxicity tests. In Alternative In Vitro Models to Animal Experimentation in Pharmacotoxicology (ed. Gömez-LechönM-J., & CastellJ.V.), in press.
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BabichH., and BorenfreundE. (1990). Application of the neutral red cytotoxicity assay to in vitro toxicology.ATLA18, 129–144.
8.
KnoxP., UphillP.F., FryJ.R., BenfordD., and BallsM. (1986). The FRAME multicentre project on in vitro toxicology.Food and Chemical Toxicology28, 457–463.
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ClothierR.H., HulmeL., AhmedA.B., ReevesH.L., SmithM., and BallsM. (1988). In vitro cytotoxicity of 150 chemicals to 3T3-L1 cells, assessed by the FRAME kenacid blue method.ATLA16, 84–95.
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BallsM., and HornerS.A. (1985). The FRAME interlaboratory programme on in vitro cytotoxicity assay to in vitro toxicology.Food and Chemical Toxicology23, 209–213.
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KalweitS., BesokeR., GenerI., and SpielmannH. (1990). A national validation project of alternative methods to the Draize rabbit eye test.Toxicology in Vitro4, 702–706.
13.
FryJ.R., GarleM.J., and HammondA.H. (1988). Choice of acute toxicity measures for comparison of in vivo/in vitro toxicity.ATLA16, 175–179.
14.
BrancherM., FallerC., SpenglerJ., and ReinhardtC.A. (1987). Comparison of in vitro cell toxicity with in vivo eye irritation.Molecular Toxicology1, 561–570.
15.
SterzelW., BartnikF.G., MatthiesW., KästnerW., and KunstlerK. (1990). Comparison of two in vitro and in vivo methods for the measurement of irritancy.Toxicology in Vitro4, 598–701.
16.
EkwallB., BondessonI., CastellJ.V., Gömez-LechönM.J., HellbergS., HögbergJ., JoverR., PonsodaX., RomertL., StenbergK., and WalumE. (1989). Cytotoxicity evaluation of the first ten MEIC chemicals: acute lethal toxicity in man predicted by cytotoxicity in five cellular assays and by oral LD50 tests in rodents.ATLA17, 83–100.
17.
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20.
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27.
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28.
GuillouzoA., MorelF., RatanasaD., ChesneC., and GuguenguC. (1990). Long-term culture of functional hepatocytes.Toxicology in Vitro4, 415–427.
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FisherR., SipesI.G., GandolfiA.J., & BrendelK. (1990). Toxicity assessment in cryopreserved human kidney and liver slices.The Toxicologist10, 283, Abstract 1,132.
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FisherR., GandolfiA.J., and BrendelK. (1991). Availability of human kidney slices for nephrotoxicity studies.The Toxicologist11, 135, Abstract 464.
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BloomJ.C., ThiemP.A., and MorganD.G. (1987). The role of conventional pathology and toxicology in evaluating the immunotoxic potential of xenobiotics.Toxicologic Pathology15, 283–293.
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AtterwillC.K. (1989). Brain reaggregate cultures in neurotoxicological investigations: studies with cholinergic neurotoxins.ATLA16, 221–230.
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