Registration Dossier

Diss Factsheets

Toxicological information


Currently viewing:

Administrative data

Description of key information

Groups of 48 male and 52 female rats received a pellet containing cholesterol mixed with an equal amount (2 mg) of chromium chloride hexahydrate or basic chromium sulphate via intrabronchial administration. None of the rats in either group exhibited local squamous carcinomas, or carcinomas in situ.  Administration of water-soluble chromium (III) acetate (5 ppm) in drinking water of rats and mice for their lifetime produced no signs of toxicity and tumour incidence was similar to controls. The incidence of lung adenomas were similar between test and control groups following repeated ip injections of mice with 5-27 mg Cr (III) as chromium sulphate for 8 weeks. Studies in leather tanners, who are often exposed to chromium (III) hydroxide sulphate, were consistently negative.

Key value for chemical safety assessment

Justification for classification or non-classification

There are no studies in animals showing clear evidence of carcinogenicity of water-soluble chromium (III) compounds, including chromium hydroxide sulphate. Studies of workers in tanneries reported no association between exposure to chromium (III) and excess risk of cancer. The results of the available studies do not trigger classification according to Directive 67/548/EEC.

Additional information

Study with chromium hydroxide sulphate

No evidence of respiratory tract carcinogenicity was seen in an implantation study using basic chromium sulphate (Levy & Venitt, 1986).

Studies with other Cr (III) compounds

A number of literature reviews have summarized information on the carcinogenicity of water-soluble chromium (III) compounds. A drinking water study in rats and mice showed no increase in tumour incidence compared to controls when administered low concentrations of chromium acetate for their lifetime (HSE review, 1989). Intraperitoneal injections of mice with water-soluble chromium (III) sulphate three times per week for eight weeks showed similar incidences of lung adenomas in test and control groups (HSE review, 1989). Occupational exposure to chromium (III) compounds in tanneries, usually to basic chromium sulphate, has not been associated with an excess risk of cancer (ATSDR review, 2000).

Carcinogenicity studies employing various water-soluble chromium (III) compounds and exposure routes have yielded negative results. Both IARC and EPA have classified chromium (III) as Group C and Group D, respectively, that is, not classifiable as to carcinogenic potential (ATSDR review, 2000).

No effects of treatment were seen in a 2 -year dietary study performed at levels of up to 5% chromium (III) oxide, equivalent to approximately 2000 mg/kg bw/d (Ivankovic & Preussmann, 1975). No evidence of carcinogenicity was seen in two inhalation studies performed in the rat (Hueper & Payne, 1961) and mouse (Nettesheim et al, 1970) although both studies have deficiencies in design and reporting. Some evidence of local inflammation of the respiratory tract was seen in the rat study. No evidence of carcinogenicity was seen in two studies using intratracheal or intrabronchial implantation (Levy & Venitt, 1986; Laskin et al, 1970). A poorly reported study (Dvizhkov & Fedorova, 1975) indicates local tumorigenicity follwoing administration of chromium (III) oxide by intratracheal, pleural interstitial or intraperitoneal administration.

Recently completed NTP carcinogenicity studies in the rat and mouse with the water-soluble complex chromium picolinate produced only equivocal evidence of carcinogenicity in the male rat. Rats (50/sex) were administered chromium picolinate in the diet at 0, 2000, 10000 and 50000 ppm; a slight and non dose-related increase in the incidence of preputial gland adenoma in males. No evidence of carcinogenicity was seen in mice (50/sex/group) administered the same dose levels. It is noted that this highly water-soluble complex is an extreme worst case as systemic absorption of Cr (III) is likely to be considerably higher than from the less soluble chromium (III) hydroxide sulphate.

Epidemiological data

Occupational exposure to chromium (III) compounds in tanneries has not been associated with an excess risk of cancer. It is noted that both IARC and EPA have classified chromium (III) as Group C and Group D, respectively, that is, not classifiable as to carcinogenic potential.

Categories Display