efsa-opinion-chromium-food-drinking-water

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