Genotoxicty and mutagenicity.
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Biomedical subjects
Publications and source records attributed to Marcus Kleber.
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Natural and synthetic chemicals are often used in the fragrance industry. A toxicological profile of the synthetic fragrance booster, 4-cycloocten-1-carbaldehyde, was generated using a test program including the following methods: acute oral toxicity, acute dermal toxicity, acute skin and eye irritation, skin sensitization, subchronic toxicity, and mutagenicity. The substance was strongly irritating to the skin but only weakly irritating to the eye. It gave a clear indication of having skin-sensitizing properties. Based on the comprehensive data from a mutagenicity test battery, 4-cycloocten-1-carbaldehyde was assessed to be nonmutagenic. Although its acute toxicological profile shows no toxicity after oral or dermal application, 4-cycloocten-1-carbaldehyde displays a complex toxicological response after repeated dosing over 13 weeks. 4-Cycloocten-1-carbaldehyde or its metabolites show clear nephrotoxic properties focusing on tubular cells of the kidney. In view of these data no no-effect level can be derived from this study with 4-cycloocten-1-carbaldehyde. A broad interaction of the test substance with various tissue types and cell parameters together with severe and irreversible organic defects even at low doses leads to the conclusion that 4-cycloocten-1-carbaldehyde is unsuitable for the intended use in industrial fragrance formulations.
Emulsions of water-soluble cutting fluids (wsCF) and non-water-soluble cutting fluids are used in large quantities for machining processes in the metal processing industry. From toxicological and epidemiological studies health risks resulting from handling of cutting fluids are well-known. Recently, the new technology of "minimist lubricant supply" (MLS) has been introduced which uses only minimal amounts of cutting fluids, in order to reduce the costs for use and disposal. This involves higher temperatures to which the fluids are subjected. Water-soluble cutting fluids supplemented with formaldehyde donors as biocides may lead to mutagenic potential. Current data show that attention should be given to generation of other genotoxic aldehydes from cutting fluids under condition of use, referring to both conventional and "minimist lubricant supply" technologies.
Emulsions of water-soluble cutting fluids (wsCF) are used in large quantities in the metal industry. In order to reduce the costs for use and disposal of these fluids, new technologies are being introduced. Minimist Lubricant Supply (MLS) uses only minimal amounts of cutting fluids. In contrast to conventional wsCF, which are complex multicompound mixtures, MLS cutting fluids are composed of one or two components only, like fatty alcohols and fatty acid esters. The aim of the study was to identify and compare the mutagenic potential of these cutting fluids as a first indicator of a possible hazard of systemic effects after inhalation or dermal absorption of the fluids at the workplace. The Salmonella typhimurium assay (Ames assay) was used as a screening method to detect mutagenic effects of cutting fluids. Conventional wsCF and MLS cutting fluids were tested in the strains TA 98, TA 100, TA 102 and TA 104, in the presence and absence of an external metabolizing enzyme system (rat liver S9-mix), using a preincubation (20 min) test protocol. For MLS fluids, no mutagenicity was found in a concentration range between 1 and 10 mg/plate in the Ames assay. Among five tested conventional wsCF, two were mutagenic in the Ames assay at concentration ranges between 2.5 and 15 mg/plate. In cooperation with the manufacturer, 18 defined components of cutting fluids were tested separately. The results revealed that formaldehyde generators, derivatives of oxazolidine and hexahydrotriazine used as biocides for preservation of the fluids, were mutagenic. Four components were nonmutagenic but cytotoxic, whereas the remaining components displayed no bacterial mutagenicity. The present results show the potential hazard of biocides for workers handling these fluids. An exposure via inhalation and/or dermal absorption could cause an additional risk due to mutagenic ingredients. Under aspects of workers' safety, a further discussion about the use of specific components in cutting fluids is recommended.