Indium und seine anorganischen Verbindungen
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 indium [7440-74-6] and its inorganic compounds 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 Relevant studies were identified from a literature search and also unpublished study reports were used.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 of indium and its inorganic compounds after inhalation exposure are pulmonary toxicity in humans and rodents and lung carcinogenicity in rodents. Indium tin oxide (ITO) and indium phosphide induced bronchioalveolar adenomas and carcinomas in mice and rats. Very rare adenosquamous and squamous cell carcinomas also occurred in the lungs of rats after exposure to ITO. Additionally, indium phosphide caused phaeochromocytomas of the adrenal glands in male rats and hepatocellular adenomas and carcinomas in mice.
Chronic inflammation, interstitial fibrosis and/or pulmonary alveolar proteinosis have been found in the lungs of rodents exposed to various inorganic indium compounds. Workers exposed to indium have shown similar signs of pulmonary toxicity, known as "indium lung". These toxic effects are thought to be induced mainly by dissolved indium ions that cause inflammation and the formation of reactive oxygen and nitrogen species, leading ultimately to indirect genotoxicity. For this reason, all inorganic indium compounds have been included in the evaluation. The exact mechanism of action, however, has not been fully elucidated and particle overload effects may contribute to toxicity. As a NOAEC (no observed effect concentration) and a MAK value cannot be derived for either the inflammatory lung effects in humans and rodents or the carcinogenic effects in animals, indium and its inorganic compounds have been classified in Carcinogen Category 2.
Inorganic indium compounds caused (nitrative) DNA damage and clastogenic effects in vitro. In vivo exposure led to micronuclei in the blood and bone marrow of rats and mice and in the lungs of rats. These effects were often accompanied by the induction of reactive oxygen species and markers of inflammation. Although no distinction can be made between cytotoxicity and genotoxicity based on the available data, secondary genotoxic effects cannot be ruled out, as indium has been found to accumulate in the testes of animals. Indium and its inorganic compounds have therefore been assigned to Germ Cell Mutagenicity Category 3 B.
Based on the findings of an in vitro skin absorption study, percutaneous absorption is expected. As indium is genotoxic and a safe exposure limit could not be derived, indium and its inorganic compounds have been designated with an "H".
The available studies do not provide clear evidence of a skin sensitizing potential for inorganic indium com-pounds. There are no data for sensitizing effects on the respiratory tract.
