Dinitrotoluol (Isomerengemische)
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) summarized and re-evaluated the data for dinitrotoluene (mixtures of isomers) [25321-14-6] considering all toxicological end points, especially for a possible re-classification in Carcinogen Category 1. Relevant studies were identified from a literature search. The critical effect of dinitrotoluene (mixtures of isomers) is nephrocarcinogenicity in rats and mice, which was already described in the last evaluation by the Commission. New studies in a collective of workers in a mining company handling explosives with dinitrotoluene suggest a similar effect in humans. The evidence, however, is limited because neither internal nor external exposure was measured. Instead, inhalation and dermal exposure levels were estimated by the former technical director twenty years after cessation of exposure. Additionally, two different compositions were given for the ingredients of the explosive rods. Therefore, the Commission regards the data as insufficient for a classification in Carcinogen Category 1 and dinitrotoluene (mixtures of isomers) remains classified in Carcinogen Category 2. Since the publication of the last evaluation, new studies investigating the genotoxicity of dinitrotoluene have become available. Dinitrotoluene is clastogenic in the liver of rodents, but not in the bone marrow or peripheral blood. 2,4-Dinitrotoluene demonstrated no clastogenic effect in a dominant lethal assay, but 2,6-dinitrotoluene was not evaluated. Data investigating point mutations in germ cells are, however, not available. Due to this data gap, and because it seems likely that the substance can reach the germ cells, dinitrotoluene (mixtures of isomers) has been classified in Germ Cell Mutagenicity Category 3 B. In a developmental toxicity study in rats, dinitrotoluene (mixtures of isomers) had no adverse effects on the foetus up to 150 mg/kg body weight and day; maternal toxicity (methaemoglobinaemia) occurred at 100 mg/kg body weight and day and above. The designation with “H” is confirmed, as according to the findings of a biomonitoring study in workers and the predictions of skin absorption models, dinitrotoluene penetrates the skin and can increase the carcinogenic risk. Valid data to evaluate the sensitizing potential of dinitrotoluene (mixtures of isomers) are not available for humans or for animals.
