Title: In Vitro Tests to Evaluate Immunotoxicity: A Preliminary Study
Authors: CARFI' MARIAGENNARI AlessandraMALERBA IlariaPALLARDY MarcCORSINI EmanuelaPIETERS RaymondHENK Van LoverenWERNER VOHR HansHARTUNG THOMASGRIBALDO LAURA
Citation: TOXICOLOGY vol. 229 no. 1/2 p. 11-22
Publisher: ELSEVIER IRELAND LTD
Publication Year: 2007
JRC N°: JRC35816
URI: http://publications.jrc.ec.europa.eu/repository/handle/JRC35816
Type: Articles in Journals
Abstract: The implementation of REACH (Registration, Evaluation and Authorisation of new and existing Chemicals) will increase the number of laboratory animals used, if alternative methods will not be available. In the meantime, REACH promotes the use of in vitro tests and, therefore, a set of appropriated alternative testing methods and assessment strategies are needed. The immune system can be a target for many chemicals including environmental contaminants and drugs with potential adverse effects on human health. The aim of this study was to evaluate the predictivity of a set of in vitro assays to detect immunosuppression. The tests have been performed on human, rat and murine cells. Different endpoints have been assessed: cytotoxicity, cytokine release, myelotoxicity and mitogen responsiveness. For each of these endpoints IC50s values have been calculated. Six chemical substances, representative of the full range of in vivo responses and for which good human and/or animal data are available either from databases or literature, have been selected: 2 chemicals classified as not immunotoxic (Urethane and Furosemide), and 4 (tributyltin chloride (TBTC), Verapamil, Cyclosporin A, Benzo(a)pyrene) with different effect on immune system. All the tests confirmed the strong immunotoxic effect of TBTC as well as they confirmed the negative controls. For one chemical (Verapamil) the IC50 is similar through the different tests. The IC50s obtained with the other chemicals depend on the endpoints and on the animal species. The clonogenic test (CFU-GM) and the mitogen responsiveness showed similar IC50s between human and rodent cells except for Cyclosporin A and TBTC. All different tests classified the compounds analyzed in the same way.
JRC Institute:Institute for Health and Consumer Protection

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