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Description of key information

A number of carcinogenicity studies performed with chromium (VI) trioxide have been reported in the literature: two inhalation studies have been
been performed in female mice and two studies have been performed in the rat using intrabronchial implantation. A large amount of additional data
is available on the carcinogenicity of Cr (VI) compounds using various exposure routes. The respiratory tract effects of chromium (VI) trioxide
appear to be specific to this compound due to its corrosive nature, however once absorbed systemically the different chromium (VI) compounds are cconsidered to be toxicologically equivalent.
Epidemiological data are also available and indicate that occupational exposure to chromium (VI) trioxide is linked to increased incidences of lung

Key value for chemical safety assessment

Justification for classification or non-classification

Chromium (VI) trioxide is listed on Annex I of Directive 67/548/EEC and is classified as a Category 1 carcinogen (R45: 'May cause cancer'). This classification is based on the results of studies in animals, the genotoxicity of chromium (VI) trioxide, and findings of increased lung tumours in occupationally exposed humans. No change to the classification is proposed.

Additional information

Most of the available studies of carcinogenicity performed using chromium (VI) compounds have not been performed to GLP or to recognised guidelines, however the provisional results of two NTP studies (in the rat and mouse) performed using sodium dichromate in the drinking water are available. These studies showed increased incidences of tumours of the oral cavity (rats) and tumours of the small intestine (mice); findings indicate a site-of contact effect associated with chronic irritation. The NTP have provisionally concluded that these studies both provide 'clear evidence' of carcinogenicity.

The results of two published studies in female mice (Adachi et al, 1987; Adachi, 1988) exposed by inhalation to mists of chromic acid (aqueous chromium trioxide) for up to 12 months showed marginally (but not statistically significantly) increased incidences of lung tumours. The findings in these studies were associated with chronic irritation and corrosion of the respiratory tract. Similar findings of marginally increased tumour incidences were reported in one of two rat studies performed using intrabronchial implantation of pellets containing chromium (VI) trioxide (Laskin et al, 1970; Levy et al, 1986). A slight increase in the incidence of respiratory tract (lung and pharynx) tumours was seen at the highest exposure concentration in rats exposed to aerosols of sodium dichromate (Glaser et al, 1986). A clear increase in the incidence of lung tumours was seen in a study using intratracheal instillation of sodium dichromate (Steinhoff et al, 1985).

The carcinogenicity of chromium (VI) trioxide and other chromium (VI) salts have been extensively reviewed by the UK Health and Safety Executive (HSE, 1989); the UK Institute of Occupational Health (IOH, 1997) and most recently in the EU RAR (2005). The EU RAR discussion of the carcinogenicity of chromium (VI) compounds is shown below; this review discusses the results of the inhalation carcinogenicity studies performed with chromium (VI) trioxide, as well as studies with other chromium (VI) salts and incorporates the studies previously reviewed by the HSE and IOH. Occupational (inhalation) exposure to chromium (VI) trioxide has been linked to increased incidences of lung cancer, therefore this compound was considered by the EU RAR to be a human carcinogen.

Relationship to genotoxicity

Water-soluble hexavelent chromium compounds are genotoxic in vitro and in vivo. However the reduction of Cr (VI) to Cr (III) in the body (saliva, gastric juice, erythrocye) may explain the lack of carcinogenicity of Cr (VI) at sites distant from the site of exposure.

Carcinogenicity: via inhalation route (target organ): respiratory: other