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EC number: 215-607-8
CAS number: 1333-82-0
A number of carcinogenicity studies performed with chromium (VI) trioxide have been reported in the literature: two inhalation studies have beenbeen performed in female mice and two studies have been performed in the rat using intrabronchial implantation. A large amount of additional datais 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 lungtumours.
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.
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
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.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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