Chlorthalonil
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 chlorothalonil [1897‐45‐6], considering all toxicological endpoints. Available publications and unpublished study reports are described in detail.
In several carcinogenicity studies, orally applied chlorothalonil causes kidney toxicity in mice and rats and kidney tubular carcinomas only in F344 rats, but not in Osborne‐Mendel or Sprague Dawley rats. The reason for this strain difference is unknown. In cells of the kidney proximal tubuli thiols are formed which inhibit mitochondrial breathing. This results in cytotoxicity and necrosis followed by cell proliferation, hyperplasia, and tumours. The thiols are generated via β‐lyase which is more active in rats than in humans. As the mechanism of the formation of kidney tumours is evaluated as non‐genotoxic and no carcinomas occurred in Osborne‐Mendel or Sprague Dawley rats at doses higher than those used in F344 rats, chlorothalonil is no longer classified in Category 3 B for carcinogens.
Chlorothalonil is irritating to nose, eyes and throat of workers at about 0.3 to 1.2 mg/m3 and corrosive to the eye of rabbits. A NOAEC after repeated inhalation in humans or animals is not known, therefore no maximum concentration at the workplace (MAK value) can be derived and chlorothalonil is assigned to Section II b of the List of MAK and BAT Values.
Chlorothalonil shows a skin sensitizing potential in humans and animals and labelling with “Sh” (for substances which cause sensitization of the skin), but not with “Sa” (for substances which cause sensitization of the airways) is retained.
Dermal absorption of chlorothalonil is low and does not contribute significantly to systemic toxicity.
