Sevofluran
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 data for sevoflurane [28523-86-6] to derive an occupational exposure limit value (maximum concentration at the workplace, MAK value) considering all toxicological end points. Relevant studies were identified from a literature search. The critical effects are neurotoxicity in humans and probable effects on sperm in animals. In analogy to halothane, a NAEC of 197 ml/m3 is estimated for neurotoxic effects induced by sevoflurane in humans. Two studies, each of which investigated non-anaesthetic concentrations of sevoflurane, found effects on sperm and female reproduction in rats. However, these studies are not suitable for evaluating these end points. As the data for sevoflurane cannot be used to derive a MAK value, a MAK value of 2 ml/m3 has been set in analogy to the value for isoflurane, which is also a fluorocarbon with the same mechanism of action and very similar toxicodynamic properties with regards to neurotoxicity and reproductive toxicity. At the same concentration in air, the sevoflurane concentration in the blood is about half that of isoflurane; therefore, the MAK value derived for sevoflurane could be higher than that of isoflurane. As a result, the MAK value of 2 ml/m3 also protects against effects on sperm and female reproduction. 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. Sevoflurane has been assigned to Pregnancy Group D because there are no valid developmental toxicity studies. No new studies on the carcinogenic effects of sevoflurane are available. A specific genotoxic potential cannot be determined for sevoflurane based on the available data and further clarification is needed, particularly in the concentration ranges that occur at the workplace. Skin contact is expected to make a relatively minor contribution to systemic toxicity. Limited data do not show clear evidence of a sensitizing potential.
