title: Oral chromium(VI) does not affect the frequency of micronuclei in hematopoietic cells of adult mice and of transplacentally exposed fetuses.
abstract: Chromium(VI) compounds are genotoxic in a variety of cellular systems. Their potential carcinogenicity is affected by toxicokinetic patterns restricting bioavailability to certain targets, and by metabolic pathways affecting interaction of chromate-derived reactive species with DNA. Epidemiological data indicate that chromium(VI) can be carcinogenic to the human respiratory tract following inhalation at doses that are only achieved in certain occupational settings. However, concern has been raised that adverse effects may also result from oral intake. In order to further explore this issue, we performed studies in BDF1 and Swiss mice of both genders and various age. Sodium dichromate dihydrate and potassium dichromate were administered either with the drinking water, up to a concentration of 500 mg chromium(VI)/l for up to 210 consecutive days, or in a single intragastric dose of 17.7 mg/kg body weight. Under these conditions, no increase of the micronucleus frequency was observed in either bone marrow or peripheral blood erythrocytes. Conversely, the same compounds induced a clastogenic damage following intraperitoneal injection, which by-passes detoxification mechanisms. In addition, due to the hypothesis that susceptibility may be increased during the period of embryogenesis, we treated pregnant mice, up to a concentration of 10mg chromium(VI)/l drinking water. There was no effect on the numbers of fetuses/dam and on body weight of fetuses. Again, no toxic or genotoxic effect was observed either in bone marrow of pregnant mice or in liver and peripheral blood of their fetuses. Thus, even at doses that largely exceed drinking water standards (up to 10,000 times) or by massive intragastric administration, chromium(VI) is not genotoxic to hematopoietic cells of either adult mice or transplacentally exposed fetuses. These conclusions are consistent with the poor toxicity and lack of carcinogenicity of oral chromium(VI), and are mechanistically explained by the high efficiency of chromium(VI) detoxification processes in the gastrointestinal tract.
authors.affiliation: Department of Health Sciences, University of Genoa, via A. Pastore 1, I-16132 Genoa, Italy. sdf@unige.it <sdf@unige.it>
authors.forename: Silvio
authors.initials: S
authors.lastname: De Flora
authors.forename: Marietta
authors.initials: M
authors.lastname: Iltcheva
authors.forename: Roumen M
authors.initials: RM
authors.lastname: Balansky
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002840:Chromates / Q000493:pharmacokinetics / Q000494:pharmacology; D002857:Chromium / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006413:Hematopoietic System / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D011192:Potassium Dichromate / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D002840:Chromates; D002857:Chromium; C074702:chromium hexavalent ion; C016104:sodium bichromate; D011192:Potassium Dichromate