Benzidine and its salts: MAK Value Documentation - Translation of the German version from 2024.

The production and technical use of benzidine [92-87-5] and its salts are prohibited by law in the EU and many other countries. Although benzidine was added to the List of MAK and BAT Values in 1966 and classified in Carcinogen Category 1 in 1975, documentation for the substance had not yet been compiled. To remedy this, the German Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission) has now prepared the documentation and additionally evaluated the end points germ cell mutagenicity, sensitization and skin absorption. Relevant studies and reviews were identified from a literature search. The carcinogenicity of benzidine has not been re-evaluated in detail because there is unequivocal evidence of its carcinogenic potential in humans: Numerous case reports and epidemiological studies from different countries show a strong and consistent association between benzidine exposure and the risk of bladder cancer. Many studies found benzidine to be genotoxic in vitro and in vivo. No studies with germ cells are available. Findings that benzidine dihydrochloride crosses the blood-brain barrier in mice after oral administration suggest that the substance may also be able to pass through the blood-testis barrier. Therefore, benzidine and its salts have been classified in Category 3 A for germ cell mutagens. Benzidine is readily absorbed by rats after dermal application in acetone. The substance is a genotoxic carcinogen and a systemically tolerable dose cannot be derived. Therefore, the designation with "H" (for substances which can be absorbed in toxicologically relevant amounts) has been retained. No studies that investigated benzidine salts are available. Although the salts are probably absorbed less readily, absorption cannot be ruled out and the salts of benzidine also remain designated with "H". There are no studies that investigated the sensitizing effects of benzidine in animals. Studies using alternative test methods are also not available. A limited number of clinical findings show positive reactions to benzidine. As patients with sensitization to aromatic para-amino compounds, such as p-phenylenediamine, often react to other compounds of this substance class as well, cross-reactivity to benzidine is possible. The data available are too limited to draw a conclusion regarding the skin sensitizing potential of benzidine and its salts. Data for respiratory sensitization are not available.