Dichloressigsäure und ihre Salze
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 dichloroacetic acid [79‐43‐6] to derive a maximum concentration at the workplace (MAK value) and to review its carcinogenicity classification.
The critical effects are irritation, carcinogenicity in the liver of rats and mice as well as neurotoxicity. After oral application, dichloroacetic acid or its sodium salt have tumour‐promoting effects and are carcinogenic in the liver of rats and mice. The NOAEL for carcinogenic effects in rats is 3.6 mg/kg body weight. In mice, a NOAEL cannot be derived. Dichloroacetic acid is not mutagenic in most tests in vitro and in vivo. The mechanisms involved in the tumour development in the liver are most likely interference with energy metabolism, oxidative stress and inhibition of apoptosis. As the primary mode of action is non‐genotoxic, dichloroacetic acid and its salts are classified in Carcinogen Category 4.
Dichloroacetic acid is corrosive to the eye and the skin of rabbits. As no inhalation studies are available to evaluate possible irritating effects on the respiratory tract, the structurally similar trichloroacetic acid is used as a read‐across. Therefore, a MAK value of 0.2 ml/m3 corresponding to 1.1 mg/m3, is derived for dichloroacetic acid. Accordingly, a MAK value of 1.1 mg/m3 for the inhalable fraction, measured as the acid, is set for the salts. As the local effect is critical, the acid and its salts are assigned to Peak Limitation Category I with an excursion factor of 1.
As skin contact to dichloroacetate may contribute significantly to systemic toxicity, the salts are designated with “H”. Skin contact is not expected to contribute significantly to the systemic toxicity of dichloroacetic acid. Sensitization is not expected from the available data.
