Isofluran
MAK-Begründung, Nachtrag
Andrea Hartwig1 (Vorsitz der Ständigen Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Deutsche Forschungsgemeinschaft)MAK Commission2
1 Institut für Angewandte Biowissenschaften, Abteilung Lebensmittelchemie und Toxikologie, Karlsruher Institut für Technologie (KIT), Adenauerring 20a, Geb. 50.41, 76131 Karlsruhe, Deutschland
2 Ständige Senatskommission zur Prüfung gesundheitsschädlicher Arbeitsstoffe, Deutsche Forschungsgemeinschaft, Kennedyallee 40, 53175 Bonn, Deutschland
Abstract
The German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) re-evaluated the MAK value and the germ cell mutagenicity of isoflurane [26675-46-7]. No new information has become available on carcinogenic effects, dermal absorption, sensitizing effects or developmental toxicity. A NOAEC of 50 ml/m3 was established for reproductive toxicity, the critical effect in male rats. The current MAK value of 2 ml/m3 was established on this basis. A recently published study describes the effects of isoflurane on sperm toxicity parameters after exposure of male mice to 50 ml/m3 (the only concentration tested). However, the study is not considered valid due to a number of shortcomings and cannot be used for the evaluation. The current MAK value of 2 ml/m3 has therefore been retained. If sevoflurane and isoflurane are both present in the workplace air, the two substances must not exceed a total MAK value of 2 ml/m3. In the previous evaluation, isoflurane was not found to have a specific genotoxic potential. Two new cross-sectional studies reported that veterinarians exposed only to isoflurane had an increased incidence of micronuclei in buccal cells and lymphocytes in addition to DNA damage (Comet assay) in peripheral blood cells. However, both studies have limitations. All other recent studies investigated mixed exposure to several inhalation anaesthetics. Thus, it is not possible to attribute a specific genotoxic effect to isoflurane and its genotoxic potential requires further clarification, particularly in the concentration ranges found at the workplace.
