The toxicity of metallic chromium in animals has been inadequately investigated. Very few studies have been conducted on chromium (II compounds; oral LD50 values of 791-3114 mg Cr(II)/kg have been reported for water-soluble chromium (II) compounds in rats. Water-soluble chromium (III), moderate toxicity. [LD50 values 140-422 mg Cr (III)/kg]. In general, negative genotoxicity results were obtained when chromium (III) compounds were tested in vitro for point mutations or DNA damage in bacteria, and for gene mutations, unscheduled DNA synthesis or cell transformation in mammalian cells, consistent with very poor cellular uptake of Cr (III). The results of in vitro tests for clastogenicity were somewhat more equivocal. The genotoxicity of chromium (III) compounds in vivo has been inadequately investigated, although negative results were obtained in the few studies available. Negative results have also been obtained in carcinogenicity studies in animals. Most studies used unrealistic methods of exposure. Effects of chromium (III) compounds on reproduction in animals have been poorly investigated. Intraperitoneal injection of chromium (III) chloride in mice produced embryo/fetolethality and teratogenicity, although it is not clear if such effects were seen only at maternally-toxic doses. Very little toxicological information was available on chromium (IV) compounds. In animals, highly water-soluble chromium (VI) compounds were very toxic by single inhalation exposure, producing damage to the respiratory tract. Cr (VI) induced skin sensitisation in guinea pigs. The Cr (VI) ion in solution gave positive results in a wide range of tests for genotoxicity in vitro. The results of animal carcinogenicity studies indicate that several chromium (VI) compounds of sparing to high water solubility were clearly carcinogenic in rats, producing lung tumours when administered via the respiratory tract (by inhalation, intratracheal instillation or intrabronchial implantation). The very poorly water-soluble chromium (VI) compounds gave equivocal or negative carcinogenic responses. Effects of chromium (VI) compounds on reproduction have been poorly investigated. Metallic chromium, binary chromium-non metal compounds, chromium hexacarbonyl. There was no evidence of adverse health effects in humans as a result of occupational exposure to these forms of chromium. There was no good evidence of adverse health effects in humans arising from occupational exposure to chromium (II) or chromium (III) compounds. There was almost no information available on the effects of chromium (IV) compounds in humans. Single inhalation or oral exposures of humans to highly water-soluble chromium (VI) compounds resulted in irritation and inflammation of the respiratory tract or corrosive burns to the gastrointestinal tract respectively. Repeated occupational exposure to airborne, highly water-soluble Cr (VI) in the chromate production and chromium plating industries has resulted in irritant and corrosive effects on the respiratory tract (nasal septum ulceration and perforation, inflammation of the entire length of the tract, fibrosis and emphysema) and gastrointestinal tract (inflammation and ulceration at various levels along the tract). Some evidence of kidney damage has also been found among workers in these industries. Workers exposed to chromium (VI) compounds of sparing to high water solubility, in chromate production, chromium plating and zinc chromate pigment manufacture, have shown a clear excess in mortality from lung cancer. This excess in lung cancer mortality cannot be related to particular atmospheric Cr (VI) levels in any reliable manner. Although there is some evidence that the incidence of lung cancer has declined among workers entering certain UK and USA chromate production and chromate pigment manufacturing plants in more recent times, it is not yet possible to deduce whether an increased risk of death from lung cancer persists in these industries. There is no good evidence that exposure to very poorly water-soluble chromium (VI) compounds has produced lung cancer in humans, although the evidence available in support of lack of human carcinogenicity for such compounds cannot be considered conclusive. Several investigations have been reported on chromosome damage in circulating lymphocytes from chromate production and chromium plating workers. The results of the better conducted and reported studies have been negative. There was no useful information available on the effects of chromium (VI) compounds on reproduction in humans. (Shortened)
ANIMAL; HUMAN; carcinogenicity; Carcinogens; Case report; epidemiological study; Eye; Gastrointestinal system; Hypersensitivity; irritancy; urinary tract; Liver; toxicokinetics; genetic toxicity; Mutagens; occupational exposure; reproductive effect; Respiratory system; Skin; Teratogens; Acute toxicity; Chronic toxicity; reproductive and developmental tests