Ulrike Bottin-Weber

Publications of Ulrike Bottin-Weber

• Analyzing Cytotoxic Effects of Selected Isothiazol-3-one Biocides Using the Toxic Ratio Concept and Structure-Activity Relationship Considerations.

  Authors: Jürgen Arning, Marianne Matzke, Stefan Stolte, Frauke Nehen, Ulrike Bottin-Weber, Andrea Böschen, Salha Abdulkarim, Bernd Jastorff, Johannes Ranke

  Chemical research in toxicology. 11/2009;

  To demonstrate how baseline toxicity can be separated from other more specific modes of toxic action and to address possible pitfals when dealing with hydrophobic substances, the fourTo demonstrate how baseline toxicity can be separated from other more specific modes of toxic action and to address possible pitfals when dealing with hydrophobic substances, the four isothiazol-3-one biocides N-methylisothiazol-3-one (MIT), 5-chloro-N-methylisothiazol-3-one (CIT), N-octylisothiazol-3-one (OIT), and 4,5-dichloro-N-octylisothiazol-3-one (DCOIT) as an example for reactive electrophilic xenobiotics were tested for their cytotoxic effects on the human hepatoblastoma cell line Hep G2, on the marine bacterium Vibrio fischeri, and on the limnic green alga Scenedesmus vacuolatus. In each of the three test systems, toxic effects were observed in a consistent pattern. The two chlorinated compounds and OIT were found to be significantly more toxic than MIT. As compared to baseline toxicants, the small and polar MIT and CIT exhibited pronounced excess toxicity in each of the three test systems that is presumably triggered by their intrinsic reactivity toward cellular thiols. In contrast, OIT and DCOIT showed mainly toxicities that could be explained by their hydrophobicity. Analyzing and comparing these results using the toxic ratio concept and with data that indicate a dramatic depletion of cellular glutathione levels after incubation with DCOIT reveals that for highly hydrophobic substances, baseline level toxicity in an assay for acute toxicity can lead to an oversight of other more specific modes of toxic action that may cause significant effects that might be less reversible than those caused by unreactive baseline toxicants. This possibility should be taken into account in the hazard assessment of chemicals that are both hydrophobic and reactive.

• Structure-activity relationships for the impact of selected isothiazol-3-one biocides on glutathione metabolism and glutathione reductase of the human liver cell line Hep G2.

  Authors: Jürgen Arning, Ralf Dringen, Maike Schmidt, Anette Thiessen, Stefan Stolte, Marianne Matzke, Ulrike Bottin-Weber, Birgit Caesar-Geertz, Bernd Jastorff, Johannes Ranke

  Toxicology. 05/2008; 246(2-3):203-12.

  To investigate the toxic mode of action of isothiazol-3-one biocides the four compounds N-methylisothiazol-3-one (MIT), 5-chloro-N-methylisothiazol-3-one (CIT), N-octylisothiazol-3-one (OIT) andTo investigate the toxic mode of action of isothiazol-3-one biocides the four compounds N-methylisothiazol-3-one (MIT), 5-chloro-N-methylisothiazol-3-one (CIT), N-octylisothiazol-3-one (OIT) and 4,5-dichloro-N-octylisothiazol-3-one (DCOIT) were purified and tested as single chemical entities for their effects on the human hepatoblastoma cell line Hep G2 and on isolated and cellular glutathione reductase GR). The two chlorinated substances CIT and DCOIT significantly decreased the amount of total cellular glutathione (GSx) in a dose and time dependent manner. Concomitantly, an increase in the level of oxidised glutathione (GSSG) was observed. The resulting shift in the GSH/GSSG ratio entailing the breakdown of the cellular thiol reduction potential was accompanied by necrotic morphological changes like swelling of the plasma membrane and subsequent lysis of the cells. Additionally, CIT and DCOIT were found to inhibit cellular GR in the cells in a concentration dependent manner. The T-SAR-based (thinking in terms of structure-activity relationships) comparison of the chlorine-substituted structures CIT and DCOIT with their non-chlorinated and less active analogues MIT and OIT identified the chlorine substituents and the resulting reaction mechanisms to be the key structural mediators of the observed toxic effects. Furthermore, differences in the activity of both chlorinated substances could be explained using the T-SAR approach to link the lipophilicity and the intrinsic glutathione-reactivity of the compounds to the expected target site concentrations inside the cells.

• Lipophilicity parameters for ionic liquid cations and their correlation to in vitro cytotoxicity.

  Authors: Johannes Ranke, Anja Müller, Ulrike Bottin-Weber, Frauke Stock, Stefan Stolte, Jürgen Arning, Reinhold Störmann, Bernd Jastorff

  Ecotoxicology and environmental safety. 08/2007; 67(3):430-8.

  Regarding the great structural variability of the currently expanding group of ionic liquids, it is highly desirable to understand the basic factors affecting their toxicity in different biologicalRegarding the great structural variability of the currently expanding group of ionic liquids, it is highly desirable to understand the basic factors affecting their toxicity in different biological systems. The present study of a set of 74 ionic liquids with imidazolium, pyrrolidinium, pyridinium, quinolinium, quaternary phosphonium and quaternary ammonium cations and the comparatively small anions Cl(-), Br(-), BF(4)(-), or PF(6)(-) demonstrates the influence of the cation lipophilicity on the cytotoxicity in IPC-81 leukemia cells from rats. The scope of this correlation is limited to ionic liquids with these or similarly small anions that are sufficiently nonreactive under physiological and chromatographic conditions and whose cation lipophilicity does not exceed a certain threshold.

• Progress in evaluation of risk potential of ionic liquids—basis for an eco-design of sustainable products

  Authors: Bernd Jastorff, Kerstin Mölter, Peter Behrend, Ulrike Bottin-Weber, Juliane Filser, Anna Heimers, Bernd Ondruschka, Johannes Ranke, Maike Schaefer, Heike Schröder, Annegret Stark, Piotr Stepnowski, Frauke Stock, Reinhold Störmann, Stefan Stolte ...

  Green Chemistry. 01/2005; 7:362-372.

  Motivated by the prevailing need for a sustainable development and taking the principles of Green Chemistry as a starting point, the present paper describes new and updated findings regarding aMotivated by the prevailing need for a sustainable development and taking the principles of Green Chemistry as a starting point, the present paper describes new and updated findings regarding a sustainable product design for ionic liquids. The focus is on environmental risk. Nevertheless, cytotoxicity testing and first indicative results from a genotoxicity study extend present knowledge also with regard to possible effects on humans. The structural variability of commercially available ionic liquids as well as the abundance of theoretically accessible ionic liquids is illustrated and the consequences for an integrated risk assessment accompanying the development process are discussed. The side chain effect on toxicity for imidazolium type ionic liquids was confounded by more complex biological testing. Also, an influence of an anion on cytotoxicity is shown for the first time. Testing of presumed metabolites of the imidazolium type cations showed a significantly lower biological activity in cytotoxicity studies than their parent compounds. The importance of a purity assessment for ionic liquids is pointed out and a collection of methods that is believed to be adequate is presented. In addition to risk analysis, the use of life cycle analysis for the multi-objective problem of designing ionic liquids is sketched and an eco-design scheme for ionic liquids is proposed. In conclusion, the paper illustrates the complex nature of the development processes ionic liquids are currently undergoing and provides guidance on which aspects have to be kept in mind.