efsa-opinion-chromium-food-drinking-water

7.2.1.4. Genotoxicity
Chromium in food and drinking water
The mutagenic potential of Cr(III) compounds has been studied extensively and recently reviewed
(EFSA ANS Panel, 2010a, b; ATSDR, 2012). Although study results vary depending on the test
system, experimental conditions and type of Cr(III) compounds tested, the majority of the assay
systems used provide evidence of lack of genotoxicity of Cr(III) compounds both in vitro and in vivo.
However, it should be noted that the ultimate mutagen that binds DNA is the trivalent form produced
intracellularly from Cr(VI) and therefore the apparent lack of activity of Cr(III) is solely due to its
poor cellular uptake (Léonard and Lauwerys, 1980). Here, we will provide a summary of the literature
and details only for the most relevant studies.
In vitro assays
Bacteria and yeast
No genotoxic effects have been reported for Cr(III) picolinate in Ames assays using a variety of
Salmonella typhimurium strains (BDL, 1995; Esber et al., 1997; NTP, 2010; Juturu and Komorowski,
2002; Whittaker et al., 2005) and concentrations up to 10 000 μg Cr(III) picolinate/plate in the
presence or absence of metabolic activation (NTP, 2010). Neither Cr(III) chloride nor picolinic acid
were mutagenic in the Ames test (Whittaker et al., 2005). Cr picolinate monohydrate was also
negative in assays with Escherichia coli strain WP2uvr/pKM101, when tested with or without
exogenous metabolic activation (S9) (NTP, 2010). Although Cr(III) compounds are largely inactive in
bacterial mutagenicity assays it appears that some Cr(III) complexes are mutagenic in bacterial strains
that are sensitive to oxidative stress. In the study by Sugden et al. (1992) the Cr(III) complexes that
were mutagenic in the S. typhimurium strains TA102 and TA2638 (sensitive to oxidative mutagens),
i.e. cis-[Cr(phen) 2 Cl 2 ] + and cis-[Cr(bipy) 2 Cl 2 ] + , presented characteristics of reversibility and positive
shifts of the Cr(III)/Cr(II) redox couple, as determined by cyclic voltammetry, consistent with the
ability of these Cr(III) complexes to serve as electron donors in Fenton-like reactions. In line with
their chemical properties the mutagenic complexes displayed a nicking activity on plasmid DNA
presumably by the induction of single-strand breaks. The non-mutagenic compounds did not exhibit
these properties. It should be noted that Cr(III) picolinate was negative in Salmonella strains 102 and
104 (Juturu and Komorowski, 2002; NTP, 2010) which are sensitive to oxidative mutagens.
Kirpnick-Sobol et al. (2006) determined the effects of Cr(III) chloride on the frequencies of DNA
deletions measured with the deletion assay in Saccharomyces cerevisiae. A significant increased in the
frequency of DNA deletions was observed and a linear correlation with the intracellular Cr
concentrations was reported. 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.
Mammalian cells
Cr(III) compounds, particularly Cr picolinate, have been tested in numerous bioassays using cultured
mammalian cells with mixed, often positive, results.
Cr(III) chloride induced chromosomal aberrations in phytohemagglutinin(PHA)-stimulated human
lymphocytes (Friedman et al., 1987) that were suppressed by superoxide dismutase (SOD), catalase
and mannitol (specific scavenger of hydroxyl radicals). The authors concluded that the production of
oxygen free radicals could contribute to the effects observed.
Stearns et al. (1995) investigated the potential genotoxicity of chelated Cr(III) picolinate in Chinese
hamster ovary (CHO) AA8 cells. Cr(III) picolinate was clastogenic in a concentration-dependent
manner from 50 μM to 1 mM. Picolinic acid showed dose-dependent chromosome damage up to
2 mM. The data suggest that the picolinic acid rather than the Cr(III) was responsible for the observed
effects, because Cr chloride and Cr nicotinate were not clastogenic at equivalent non toxic Cr
concentrations.
No induction of micronuclei was observed following exposure of V79 Chinese hamster lung cells to a
variety of Cr(III) complexes, except when Cr(III) imine complexes, which could be oxidized to Cr(V)
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