TOXICOLOGICAL PROFILE FOR CHROMIUM - Davidborowski.com
TOXICOLOGICAL PROFILE FOR CHROMIUM - Davidborowski.com TOXICOLOGICAL PROFILE FOR CHROMIUM - Davidborowski.com
CHROMIUM 2082. HEALTH EFFECTSet al. 1986; Kanematsu et al. 1980; Kortenkamp et al. 1996b; Nakamuro et al. 1978; Nestmann et al.1979; Olivier and Marzin 1987; Venitt and Levy 1974; Watanabe et al. 1998a). Forward mutations werenot induced in E. coli in one study (Nestmann et al. 1979). Negative or weakly positive results werereported in B. subtilis with chromium(III) (Kanematsu et al. 1980; Matsui 1980; Nakamuro et al. 1978;Nishioka 1975) and mostly negative results in E. coli (Llagostera et al. 1986; Olivier and Marzin 1987;Venier et al. 1989).A chromium(IV) ester was synthesized with 2,4-dimethyl-pentane-2,4-diol to examined its ability tocause DNA double strand breaks (Luo et al. 1996). Calf thymus DNA was reacted with thechromium(IV) complex (1.3 mg/mL) in the presence of 2 mM hydrogen peroxide for 6 days at pH 6.8.The results showed that the complex in the presence of hydrogen peroxide significantly damaged DNA bycausing double strand breaks. Neither chromium(IV) or hydrogen peroxide alone damaged DNA. Thekinetics of the reaction of chromium(IV) with hydrogen peroxide, showed the formation of proportionalamounts of hydroxyl radical with chromium(V). Use of a free radical scavenger prevented DNA strandbreaks. Other studies have shown that chromium(IV) is a better Fenton reagent than chromium(V) forreducing hydrogen peroxide and thus chromium(IV)-type damage by generating hydroxyl radicals mayalso be a contributor of in vivo genotoxicity.Studies in eukaryotic organisms indicated that chromium(VI) was genotoxic in Saccharomyces cerevisiae(Fukunaga et al. 1982; Nestmann et al. 1979; Singh 1983) and in Schizosaccharomyces pombe (Bonatti etal. 1976). One study demonstrated the genotoxicity of chromium(III) in S. cerevisiae (Bronzetti et al.1986). Sodium chromate induced DNA damage (DNA interstrand crosslinks, DNA strand breaks, DNAproteincrosslinks) in cultured chick embryo hepatocytes (Tsapakos et al. 1983a). The vast majority ofstudies reported genotoxic effects of chromium(VI) in mammalian cells in vitro (Briggs and Briggs 1988;DiPaolo and Casto 1979; Douglas et al. 1980; Elias et al. 1989b; Fornace et al. 1981; Gomez-Arroyo etal. 1981; Koshi 1979; Koshi and Iwasaki 1983; Kowalski et al. 1996; Levis and Majone 1979; MacRae etal. 1979; Majone and Levis 1979; Montaldi et al. 1987; Nakamuro et al. 1978; Newbold et al. 1979; Ohnoet al. 1982; Raffetto et al. 1977; Sarto et al. 1980; Stella et al. 1982; Sugiyama et al. 1986; Tsuda andKato 1977; Umeda and Nishimura 1979; Venier et al. 1982; Whiting et al. 1979; Yang et al. 1992).Although no increase in DNA damage was observed in Chinese hamster ovary cells exposed to leadchromate, probably due to the limited solubility of the tested compound (Douglas et al. 1980), an increasein chromosome aberrations was found in Chinese hamster ovary cells treated with lead chromate inanother study (Wise et al. 1993).
CHROMIUM 2092. HEALTH EFFECTSIn contrast, mostly negative results were reported for chromium(III) in mammalian cells (Fornace et al.1981; Levis and Majone 1979; MacRae et al. 1979; Newbold et al. 1979; Ohno et al. 1982; Raffetto et al.1977; Sarto et al. 1980; Stella et al. 1982; Tsuda and Kato 1977; Umeda and Nishimura 1979; Venier etal. 1982; Whiting et al. 1979) and chick embryo hepatocytes (Tsapakos et al. 1983a). The only positiveresults were obtained in Chinese hamster ovary cells (Levis and Majone 1979), mouse fetal cells (Raffettoet al. 1977), and weakly positive responses were observed in human cell lines (Nakamuro et al. 1978;Stella et al. 1982). However, it should be noted that in positive studies, the genotoxic potency ofchromium(III) compounds was several orders lower than that of chromium(VI) compounds tested in thesame systems. Positive results of chromium(III) in intact cells could be due to contamination of the testcompounds with traces of chromium(VI) (De Flora et al. 1990; IARC 1990), nonspecific effects at veryhigh doses, experimental conditions that would increase the penetration of chromium(III) into cells (e.g.,detergents), or a technical artifact formed during the extraction procedures (De Flora et al. 1990). In onecase, chromium(III) compounds showed genotoxicity that was linked to redox cycling of a chromium-DNA complex (Sugden et al. 1990). Although chromium(III) compounds are less toxic thanchromium(VI) compounds because of their relative inability to cross cell membranes, chromium(III) ismore genotoxic than chromium(VI) when tested in vitro in subcellular targets (Bridgewater et al. 1994a,1994b, 1998; Fornace et al. 1981; Snow 1991; Snow and Xu 1989).In conclusion, chromium(VI) compounds were positive in the majority of tests reported, and theirgenotoxicity was related to the solubility and, therefore, to the bioavailability to the targets.Chromium(III) was more genotoxic in subcellular targets, but lost this ability in cellular systems. Thereduction of chromium(VI) in the cells to chromium(III) and its subsequent genotoxicity may be greatlyresponsible for the final genotoxic effects (Beyersmann and Koster 1987). Reduction of chromium(VI)can also result in the formation of chromium(V), which is highly reactive and capable of interaction withDNA (Jennette 1982; Norseth 1986).Cancer. Epidemiology studies discussed in Section 2.2.1.8 clearly indicate an increased respiratorycancer risk in workers engaged in chromate production and chromate pigment production and use.Studies in chrome platers, who are exposed to chromium(VI) and other agents, including nickel, generallysupport the conclusion that chromium(VI) is carcinogenic. Many of the studies in stainless steel workersexposed to chromium(VI) and other chemicals, and in ferrochromium alloy workers, who are exposedmainly to chromium(0) and chromium(III), but also to some chromium(VI), were inconclusive. However,in a recent update by (Mancuso 1997a) of his 1975 study of lung cancer in workers employed in chromatemanufacturing that were first employed between 1931 and 1937, the author concluded that the lung
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<strong>CHROMIUM</strong> 2082. HEALTH EFFECTSet al. 1986; Kanematsu et al. 1980; Kortenkamp et al. 1996b; Nakamuro et al. 1978; Nestmann et al.1979; Olivier and Marzin 1987; Venitt and Levy 1974; Watanabe et al. 1998a). Forward mutations werenot induced in E. coli in one study (Nestmann et al. 1979). Negative or weakly positive results werereported in B. subtilis with chromium(III) (Kanematsu et al. 1980; Matsui 1980; Nakamuro et al. 1978;Nishioka 1975) and mostly negative results in E. coli (Llagostera et al. 1986; Olivier and Marzin 1987;Venier et al. 1989).A chromium(IV) ester was synthesized with 2,4-dimethyl-pentane-2,4-diol to examined its ability tocause DNA double strand breaks (Luo et al. 1996). Calf thymus DNA was reacted with thechromium(IV) <strong>com</strong>plex (1.3 mg/mL) in the presence of 2 mM hydrogen peroxide for 6 days at pH 6.8.The results showed that the <strong>com</strong>plex in the presence of hydrogen peroxide significantly damaged DNA bycausing double strand breaks. Neither chromium(IV) or hydrogen peroxide alone damaged DNA. Thekinetics of the reaction of chromium(IV) with hydrogen peroxide, showed the formation of proportionalamounts of hydroxyl radical with chromium(V). Use of a free radical scavenger prevented DNA strandbreaks. Other studies have shown that chromium(IV) is a better Fenton reagent than chromium(V) forreducing hydrogen peroxide and thus chromium(IV)-type damage by generating hydroxyl radicals mayalso be a contributor of in vivo genotoxicity.Studies in eukaryotic organisms indicated that chromium(VI) was genotoxic in Saccharomyces cerevisiae(Fukunaga et al. 1982; Nestmann et al. 1979; Singh 1983) and in Schizosaccharomyces pombe (Bonatti etal. 1976). One study demonstrated the genotoxicity of chromium(III) in S. cerevisiae (Bronzetti et al.1986). Sodium chromate induced DNA damage (DNA interstrand crosslinks, DNA strand breaks, DNAproteincrosslinks) in cultured chick embryo hepatocytes (Tsapakos et al. 1983a). The vast majority ofstudies reported genotoxic effects of chromium(VI) in mammalian cells in vitro (Briggs and Briggs 1988;DiPaolo and Casto 1979; Douglas et al. 1980; Elias et al. 1989b; Fornace et al. 1981; Gomez-Arroyo etal. 1981; Koshi 1979; Koshi and Iwasaki 1983; Kowalski et al. 1996; Levis and Majone 1979; MacRae etal. 1979; Majone and Levis 1979; Montaldi et al. 1987; Nakamuro et al. 1978; Newbold et al. 1979; Ohnoet al. 1982; Raffetto et al. 1977; Sarto et al. 1980; Stella et al. 1982; Sugiyama et al. 1986; Tsuda andKato 1977; Umeda and Nishimura 1979; Venier et al. 1982; Whiting et al. 1979; Yang et al. 1992).Although no increase in DNA damage was observed in Chinese hamster ovary cells exposed to leadchromate, probably due to the limited solubility of the tested <strong>com</strong>pound (Douglas et al. 1980), an increasein chromosome aberrations was found in Chinese hamster ovary cells treated with lead chromate inanother study (Wise et al. 1993).