TOXICOLOGICAL PROFILE FOR CHROMIUM - Davidborowski.com

CHROMIUM 2072. HEALTH EFFECTSwas found in the livers of rats that had been exposed to potassium chromate in the drinking water at$6 mg chromium(VI)/kg/day for 3 or 6 weeks (Coogan et al. 1991a). Bone marrow cells from male micefed chromium(VI) trioxide at 20 mg chromium(VI)/kg by gavage had a 4.4 fold increase in chromosomalberration over controls (Sarkar et al. 1993). Significant DNA alterations were seen in the lung, but notthe liver, of rats exposed to chromium (VI) by intratrachael instillation of sodium dichromate (Izzotti etal. 1998). Micronucleated polychromatic erythrocytes were found in mice following intraperitoneal, butnot oral, exposure to chromium(VI) as potassium chromate (Chorvatovi…ová et al. 1993; Itoh andShimada 1996, 1997; Mirsalis et al. 1996; Shindo et al. 1989; Wild 1978; Wroûska-Nofer et al. 1999).No unscheduled DNA synthesis was found in rat hepatocytes after the rats were exposed to potassiumchromate in drinking water (Mirsalis et al. 1996). The contrasting results may relate to route-specificdifferences in absorption or metabolic fate of chromate in vivo. Furthermore, intraperitoneal exposure tochromium(VI) as potassium dichromate induced dominant lethality in mice (Paschin et al. 1982) and asignificant increase in mutant frequency within mouse hepatocytes (Itoh and Shimada 1997, 1998) andbone marrow cells (Itoh and Shimada 1998). Intraperitoneal injection in rats with sodium dichromate(chromium(VI)) resulted in DNA cross-links in liver, kidney, and lung nuclei (Tsapakos et al. 1983b),while similar injection in rats with chromium(III) trichloride did not cause DNA interstrand cross-links,DNA-protein cross-links, or DNA strand breaks in liver and kidney nuclei (Cupo and Wetterhahn 1985).Chromium caused slight but significant elevation in micronucleic over controls in newts (9.55% versus9.00%) (Le Curieux et al. 1992). In addition, studies in Drosophila melanogaster showed an induction ofgene mutations after exposure to chromium(VI) (Gava et al. 1989a; Rasmuson 1985; Rodriquez-Arnaizand Martinez 1986; Olvera et al. 1993; Zimmering et al. 1985).In vitro studies indicated that soluble chromium(VI) compounds are mutagenic in Salmonellatyphimurium reverse mutation assays (Bennicelli et al. 1983; De Flora 1978, 1981; Haworth et al. 1983;Nakamura et al. 1987; Venier et al. 1982; Watanabe et al. 1998a). In addition, lead chromate, a waterinsoluble compound, was mutagenic in bacteria when dissolved in sodium hydroxide or sulfuric acid(Nestmann et al. 1979). Only one study reported negative results with chromium(VI) in all tested strains(Kanematsu et al. 1980). In contrast, studies with chromium(III) did not report the induction of reversemutations in S. typhimurium (Bennicelli et al. 1983; De Flora 1981; Petrilli and De Flora 1978b; Venier etal. 1982). After preincubation with mammalian microsomes, the mutagenicity of chromium(VI)compounds was reduced or abolished due to concentrations of the reductant glutathione, cysteine, orNADPH capable of converting chromium(VI) to chromium(III) compounds (Bennicelli et al. 1983; DeFlora 1978,1981; Nestmann et al. 1979). Chromium(VI) compounds caused gene mutations in Bacillussubtilis (Kanematsu et al. 1980; Nakamuro et al. 1978; Nishioka 1975) and Escherichia coli (Llagostera