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Thomas Hartung

Publications and source records attributed to Thomas Hartung.

130 records · Page 8Linked to original sources
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The integrated project ReProTect: a novel approach in reproductive toxicity hazard assessment.

Validated alternative test methods are urgently needed for safety testing of drugs, chemicals and cosmetics. Whereas some animal tests for topical toxicity have been successfully replaced by alternative methods, systemic toxicity testing requires new test strategies in order to achieve an adequate safety level for the consumer. Substantial numbers of animals are required for the current in vivo assays for drugs, chemicals and cosmetics and a broad range of pioneering alternative methods were already developed. These prerequisites motivate the development of a tiered testing strategy based on alternative tests for reproductive toxicity hazard. In the Integrated Project ReProTect, a consortium set up by the European Centre for the Validation of Alternative Methods (ECVAM) takes the lead to manage the development of a testing strategy in the area of reproductive toxicity. The reproductive cycle can be broken down into well-defined sub-elements, namely male and female fertility, implantation and pre/postnatal development. In this project, in vitro, in silico and sensor technologies will be developed, leading to testing strategies, that shall be implemented and disseminated.

Adult↗
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Evaluation and prevalidation of an immunotoxicity test based on human whole-blood cytokine release.

Immunotoxicology is a relatively new field in toxicology, and is one of emerging importance, because immunotoxicity appears to contribute to the development of cancer, autoimmune disorders, allergies and other diseases. At present, there is a lack of human cell-based immunotoxicity assays for predicting the toxicity of xenobiotics toward the immune system in a simple, fast, economical and reliable way. Existing immunotoxicity tests are mainly performed in animals, although species differences favour human-based testing. Whole-blood cytokine release models have attracted increasing interest, and are broadly used for pharmacological in vitro and ex vivo studies, as well as for pyrogenicity testing. We have adapted those methods for immunotoxicity testing, to permit the potency testing of immunostimulants and immunosuppressants. Following stimulation with a lipopolysaccharide or staphylococcal enterotoxin B, monocytes and lymphocytes release interleukin-1beta and interleukin-4, respectively. Thirty-one pharmaceutical compounds, with known effects on the immune system, were used to optimise and standardise the method, by analysing their effects on cytokine release. The in vitro results were expressed as IC50 values for immunosuppression, and SC(4) (fourfold increase) values for immunostimulation, and compared with therapeutic serum concentrations of the compounds in patients, and in vivo LD50 values from animal studies. The in vitro results correlated well with the in vivo data, so the test appears to reflect immunomodulation. Results were reproducible (CV = 20 +/- 5%), and the method could be transferred to another laboratory (r(2) = 0.99). We therefore propose this method for further validation and for use in immunotoxicity testing strategies.

Adjuvants, Immunologic↗