efsa-opinion-chromium-food-drinking-water

Chromium in food and drinking water
(Hepburn et al., 2003) where rats treated with Cr(III) picolinate showed increased urinary excretion of
8-hydroxy-2’deoxyguanosine and increased lipid peroxidation in liver and kidney.
Tan et al. (2008) investigated the effect of excessive Cr(III) picolinate intake on oxidative damage in
pigs. Male pigs were fed a diet withdoses up to 3200 μg of Cr/kg feed as Cr(III) picolinate for 80 days.
At the high dose the superoxide dismutase activity was significantly decreased in serum, also the
catalase activity in the kidneys. However, the levels of malondialdehyde in tissue and serum, urinary
8-hydroxydeoxyguanosine and DNA strand breaks in liver and kidney were not affected.
7.2.1.6. Conclusions on genotoxicity
The extensive literature on genotoxicity of Cr(III) compounds provides conflicting information
regarding their genotoxicity but in general they gave largely negative results in bacterial assays and
mixed, often positive, results in mammalian cell assays (although often at cytotoxic doses). In vivo
tests for genotoxicity were all negative with one exception of a non standard assay (i.e. p(un) reversion
assay in mice). Cr(III) compounds have the potential to react with DNA in acellular systems (see also
Section on mode of action), however in intact cells restricted access limits or prevents genotoxicity. At
high concentrations, multiple studies showed that Cr(III) compounds might cause DNA damage which
is potentially mutagenic and clastogenic. The inhibition of these effects by antioxidants as well as the
detection of oxidized bases both in vitro and in vivo indicates that oxidatively-generated DNA damage
is involved.
7.2.1.7. Carcinogenicity
Cr(III) carcinogenicity has been recently addressed by the NTP in their study on Cr picolinate
monohydrate (Stout et al., 2009; NTP, 2010) which contains Cr(III) chelated with three molecules of
picolinic acid in order to increase the absorption of Cr(III). Chromium picolinate is widely used as
dietary supplement. Chromium picolinate monohydrate studies included a 3-month toxicity study to
select exposure concentrations for the 2-year studies. These studies are described below.
The study was conducted in 50 male and female F344/N rats and B6C3F1 mice exposed in feed to
concentrations from 2000 to 50000 mg/kg for 2 years. A maximal concentration of 50000 mg/kg feed
of chromium picolinate monohydrate was selected in order to prevent alteration of the nutritional
content of the diet. There were no biologically significant changes in survival, body weight, feed
consumption or the occurrence of non-neoplastic lesions in rats or mice in the 2-year studies at
concentrations up to 50000 mg/kg feed. This corresponds to average daily doses of 286.2 and
313.7 mg Cr(III)/kg b.w. per day for male and female rats, respectively, and of 783.0 and
727.5 mg Cr(III)/kg b.w. per day for male and female mice, respectively. In male rats, a statistically
significant increase in the incidence of preputial gland adenomas at 10000 mg/kg feed (corresponding
to 54.9 mg Cr(III)/kg b.w. per day) was reported. However, the incidence of preputial gland
hyperplasia was not increased at any exposure dose, neither preputial gland carcinomas were observed
in exposed males. There were no increases in the incidence of clitoral gland adenomas or hyperplasia
in exposed females (the clitoral gland is the female counterpart of the preputial gland). On the basis of
these data the CONTAM Panel concluded that Cr(III) is not carcinogenic in experimental animals.
7.2.2. Hexavalent chromium
7.2.2.1. Acute toxicity
In general Cr(VI) salts had greater acute toxicity than Cr(III) salts, and female rats appeared to be
more sensitive than males to Cr(VI) salts (ATSDR, 2012). Table 15 shows the oral LD 50 s reported in
the rat.
EFSA Journal 2014;12(3):3595 80