Cerdioxid
MAK-Begründung
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) summarized and evaluated the data for cerium dioxide [1306-38-3] 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 Relevant studies were identified from a literature search and also unpublished study reports were used. The critical effects are inflammation and fibrosis in the lungs of humans and rats. With decreasing particle size, the ratio of the two stable cerium valence states Ce3+/Ce4+ increases in favour of Ce3+. This leads to altered physico-chemical properties, including an increased redox potential (Ce3+/Ce4+) and higher solubility. In a biological system, the toxicity of cerium dioxide particles is primarily due to their redox potential at the particle surface. However, a toxic effect due to partly solubilized cerium dioxide cannot be excluded. In a long-term inhalation study with nanoscale cerium dioxide particles (NM-212), cerium phosphate and cerium oxide were clearly detected in rat bone tissue but it remains unknown in which form cerium dioxide enters the bones and is incorporated there as cerium phosphate. In a 2-year inhalation study in rats, using nanoscale cerium dioxide particles with a more extensive investigation of the lung, granulomatous inflammation and interstitial fibrosis in the lung occurred at the lowest concentration tested of 0.1 mg/m3 and above. Therefore, a NOAEC cannot be established and 0.1 mg/m3 of cerium dioxide is regarded as LOAEC. Corresponding to the LOAEC, a human equivalent concentration of 11.2 μg/m3 was calculated and a MAK value of 2 μg cerium dioxide/m3 has been set for the respirable fraction. Additionally, the substance has been classified in Peak Limitation Category II with an excursion factor of 8. In the absence of a prenatal developmental toxicity study which encompasses the entire organogenesis and includes complete teratogenicity testing, cerium dioxide has been assigned to Pregnancy Risk Group D. Carcinogenic effects in humans cannot be derived for cerium dioxide. The NOAEL for clastogenic effects of cerium dioxide in rats was 30 mg/kg body weight and day. After applying toxicokinetic scaling, this corresponds to an air concentration of 5.26 mg/m3. As the margin to the MAK value is sufficiently large, cerium dioxide has been assigned to Germ Cell Mutagen Category 5. Cerium dioxide is not absorbed through the skin in toxicologically relevant amounts. Available data demonstrate no sensitizing potential.
