efsa-opinion-chromium-food-drinking-water
efsa-opinion-chromium-food-drinking-water
efsa-opinion-chromium-food-drinking-water
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Genotoxicity and carcinogenicity<br />
Chromium in <strong>food</strong> and <strong>drinking</strong> <strong>water</strong><br />
Cr(III) compounds have the potential to react with DNA in acellular systems, however<br />
restricted cellular access limits or prevents genotoxicity.<br />
Cr(III) compounds did not induce genotoxicity in the majority of bacterial assays; mixed<br />
results were reported in mammalian cells and results in standard in vivo assays by oral route<br />
of exposure were negative.<br />
Several in vitro and in vivo studies showed that Cr(III) compounds at high concentrations<br />
cause oxidatively-generated DNA damage.<br />
Cr(III) is not carcinogenic in experimental animals after oral intake.<br />
Hexavalent <strong>chromium</strong><br />
Repeat dose toxicity (non neoplastic effects)<br />
After repeated oral administration, the major target organs of Cr(VI) compounds in rats and<br />
mice are the haematological system, liver, kidney and the gastrointestinal tract.<br />
The lowest NOAEL in a 2-year rat study was 0.21 mg Cr(VI)/kg b.w. per day based on<br />
haematological effects, liver toxicity, hystiocytic cellular infiltration in mesenteric lymph<br />
nodes and the duodenum observed at 0.77 mg Cr(VI)/kg b.w. per day.<br />
No NOAEL was established in a 2-year mouse study, based on haematological effects, liver<br />
toxicity, hystiocytic cellular infiltration in mesenteric lymph nodes and hyperplasia in the<br />
duodenum observed at the lowest tested dose of 0.38 mg Cr(VI)/kg b.w. per day.<br />
Developmental and reproductive toxicity<br />
Studies in animals show that acute- and intermediate-duration exposure to Cr(VI) produce<br />
adverse reproductive effects, with the male reproductive system exhibiting the highest<br />
sensitivity.<br />
Developmental effects (embryotoxicity, fetotoxicity and increased frequency of gross, visceral<br />
and skeletal malformations) have been observed in rats or mice treated with Cr(VI) during<br />
gestation.<br />
Cr(VI) has been shown to cross the placental barrier and accumulate in fetal tissues.<br />
Effects on reproduction and development occur at higher doses than the effects on the<br />
haematological system, liver and duodenum.<br />
Genotoxicity and carcinogenicity<br />
Cr(VI) compounds are genotoxic in bacterial and mammalian cell assays.<br />
Genotoxicity was also observed in some but not all in vivo studies upon oral administration.<br />
Cr(VI) was clearly genotoxic following intraperitoneal administration, indicating that the<br />
reductive capacity of the GI tract influences the genotoxic effects of Cr(VI) in vivo.<br />
Cr(VI) is carcinogenic in experimental animals after oral administration. Increased incidences<br />
of tumors of the squamous epithelium of the oral cavity were reported in male and female rats<br />
and of epithelial tissues of the small intestine in male and female mice.<br />
Intracellular reduction of Cr(VI) generates lower Cr valences, facilitating the production of<br />
reactive oxygen species, and ultimately Cr(III), which generates DNA adducts, representing<br />
the two possible modes of action for induction of carcinogenicity.<br />
EFSA Journal 2014;12(3):3595 124