efsa-opinion-chromium-food-drinking-water

Chromium in food and drinking water
Andersson et al. (2007) measured DNA damage by the Comet assay in cultures of human lymphocytes
and L5178Y mouse lymphoma cells exposed in vitro to 500 μM Cr(III) picolinate for 3 hours. A slight
but statistically significant increase in DNA damage was observed in human lymphocytes, but only
when cells were exposed in the absence of serum.
In vivo assays
Four studies were conducted using Cr(III) compounds in Drosophila melanogaster as model system.
Negative results were obtained in two studies (Amrani et al., 1999; Katz et al., 2001) in which
mutagenic or recombinogeneic events were measured in adult flies treated in the larval stage with Cr
chloride. In contrast, positive results were reported (Hepburn et al., 2003; Stallings et al., 2006) when
Cr(III) picolinate was given in the diet at concentrations up to 2107 μg/kg food (equivalent to
260 μg Cr/kg food). Although no effects on survival, behaviour or fertility of adult Drosophila were
reported, developmental delays and decreased pupation success were observed in larvae.
In contrast to the in vitro studies in mammalian cells, most of the studies that have been conducted on
Cr(III) compounds in animal models have yielded negative results (Table 14) (for detailed information
see Appendix H: Table H3, oral route administration and Table H4, non-oral route administration).
In an NTP study (NTP, 2010) the in vivo micronucleus assay was performed in male F344/N rats
treated with Cr(III) picolinate (anhydrous) (156 to 2500 mg/kg b.w.) by oral gavage three times at
24-hour intervals. Negative results were observed in bone marrow erythrocytes of male rats. In
another NTP study (NTP, 2010) the in vivo micronucleus assay was performed in male and female
B6C3F1 mice administered Cr(III) picolinate monohydrate (80 to 50000 mg/kg diet corresponding to
2-1419 and to 1.7-1090 mg Cr(III)/kg b.w. per day for male and female respectively) in feed for
3 months. Negative results were observed in peripheral blood erythrocytes of the male mice. The weak
increases in the micronuclei frequency observed in erythrocytes of female mice were considered
equivocal findings as the anhydrous form was inactive.
Itoh and Shimada (1996) analysed the clastogenic properties of CrCl 3 in bone marrow cells of Slc:ddY
mice following i.p. administration (up to 125 mg/kg b.w.). Cr(III) chloride was negative for
micronuclei induction.
Kirpnick-Sobol et al. (2006) determined the effects of Cr(III) chloride administered to dams in
drinking water on the frequencies of DNA deletions measured in the in vivo p(un) reversion assay in
C57BL/6J p(un)/p(un) mice. Cr(III) (Cr(III) chloride salt) was used at either 1875 or 3750 mg/L
concentration, which was calculated to yield an average dose of 375 or 750 mg of Cr/kg b.w. per day,
respectively. Exposing mice to Cr(III) significantly increased the frequency of DNA deletions in
embryos harvested at 17.5 days post-coitum. The authors also quantified tissue Cr concentrations in
mice after exposure. The authors concluded that Cr(III) is a potent inducer of DNA deletions (even
more potent than Cr(VI) tested in the same study) when it is absorbed.
De Flora et al. (2006) analysed the frequency of micronuclei in bone marrow and peripheral blood
cells of BDF1 mice, both males and females, administered Cr(III), as CrK(SO 4 ) 2·12H 2 O, in the
drinking water, at concentrations up to 500 mg Cr/L water (corresponding to 165 and
140 mg Cr(III)/kg b.w. per day for male and female respectively), for 7 months. Cr(III) did not affect
the micronuclei frequency at any dose tested.
Andersson et al. (2007) evaluated the potential genotoxicity of Cr(III) picolinate in an in vivo assay.
Mice were given a single intraperitoneal injection (up to 3 mg/kg b.w.) and the frequency of
micronuclei in polychromatic erythrocytes was evaluated in peripheral blood as well as DNA damage
in lymphocytes and hepatocytes by the Comet assay. In all other experiments Cr(III) picolinate was
found to be inactive, both in vitro and in vivo.
The in vivo cytogenetic effects of Cr(III) picolinate were analysed by Komorowski et al. (2008) in rats
in a well conducted study performed according to OECD guideline 475 (1997). The rats received a
single oral dose of 33, 250 or 2000 mg/kg b.w. Cr(III) picolinate (corresponding to 4.1, 30.8 and
EFSA Journal 2014;12(3):3595 77