Vanadium und seine anorganischen Verbindungen
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 Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re-evaluated vanadium [7440-62-2] and its inorganic compounds considering all toxicological end points. The critical effects are irritation in the upper respiratory tract and carcinogenicity in the lungs of rats and mice. The available data do not provide sufficient evidence of carcinogenic effects in humans. Under physiological conditions, vanadium occurs as the tetravalent vanadyl cation or the pentavalent vanadate anion; these two forms readily convert from one to the other. As the cytotoxic, irritant and carcinogenic effects are induced by the vanadium ions, all inorganic vanadium compounds of varying solubility are included in the evaluation. Inorganic vanadium compounds cause (oxidative) DNA damage, clastogenicity and aneugenicity in mice and rats after administration by inhalation, intraperitoneal injection or with the drinking water. The induction of (oxidative) DNA damage is the most sensitive genotoxic effect. However, the primary carcinogenic mode of action is assumed to be initiated by inflammation leading to an increase in cell proliferation. Thus, it is possible to establish a concentration at which these effects do not occur and vanadium and its inorganic compounds have been classified in Carcinogen Category 4. The subacute NOAEC for the induction of inflammatory, histopathological and genotoxic effects in the lungs of mice was 0.14 mg vanadium/m3 (respirable fraction). On this basis, a concentration of 0.005 mg/m3 was derived for the respirable fraction at which no carcinogenic effects are to be expected. No NOAEC can be determined for effects on the upper respiratory tract from either animal data or data in humans. Therefore, the NOAEC of 0.14 mg vanadium/m3 for the induction of inflammatory, histopathological and genotoxic effects in the lungs of mice after subacute exposure is used to derive a limit value for the inhalable fraction to keep these effects from occurring in the upper respiratory tract. The concentration of 0.005 mg/m3 that was derived for the respirable fraction is set as the MAK value for the inhalable fraction. As the critical effect of vanadium and its inorganic compounds is systemic, the substances have been assigned to Peak Limitation Category II. Based on human data, an excursion factor of 2 has been set. Neurotoxic effects were observed in humans at mean concentrations of 0.216 mg/m3. As there are no studies suitable for deriving a NOAEC for developmental neurotoxic effects, vanadium and its inorganic compounds have been assigned to Pregnancy Risk Group D. Germ cell mutagenicity is observed in animal studies only at very high doses. As no appreciable contribution to the genetic risk in humans is to be expected if the MAK value is observed, vanadium and its inorganic compounds have been classified in Category 5 for germ cell mutagens. Limited data show no sensitization. There are no data indicating that vanadium and its inorganic compounds are absorbed through the skin.
