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