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 />
distribution of <strong>chromium</strong> to the liver and kidney, with liver:kidney ratios being higher in mice than in<br />
rats. The tissue data and PBK model predictions indicated a concentration gradient in the small<br />
intestines (duodenum > jejunum > ileum).<br />
A PBK model for humans orally exposed to Cr(III) and Cr(VI) (Kirman et al., 2013) was also<br />
developed. Ex vivo Cr(VI) reduction studies using fasted human gastric fluids were conducted and<br />
used to characterize reduction of Cr(VI) in human stomach fluid as a mixed second-order, pHdependent<br />
process. Information from the published literature regarding the toxicokinetics for total<br />
<strong>chromium</strong> in human tissues and excreta was used for model development. The PBPK model was<br />
shown to provide a good description of <strong>chromium</strong> toxicokinetics and to be consistent with the<br />
available total <strong>chromium</strong> data from Cr(III) and Cr(VI) exposures in humans. Additional data for<br />
Cr(VI) reduction in both humans and rodents were identified as data needs to further develop key<br />
assumptions made in the PBPK models, and allow improved health risk assessment.<br />
7.2. Toxicity in experimental animals<br />
7.2.1. Trivalent <strong>chromium</strong><br />
In general Cr(III) salts present low oral toxicity (ATSDR, 2012).<br />
7.2.1.1. Acute toxicity<br />
Table 11 shows the oral LD 50 s reported in the rat. The lower toxicity of Cr(III) acetate compared with<br />
Cr(III) nitrate may be related to solubility; Cr(III) acetate is less soluble in <strong>water</strong> than is Cr(III) nitrate.<br />
Signs of toxicity included hypoactivity, lacrimation, mydriasis, diarrhea, and decrease in body weight.<br />
Table 11: Oral LD 50 s determined in rats<br />
Compound LD 50 (mg Cr(III)/kg b.w.) Reference<br />
Chromium acetate 2 365 Smyth et al. (1969)<br />
423 Smyth et al. (1969)<br />
Chromium nitrate<br />
200 (males) Vernot et al. (1977)<br />
183 (females) Vernot et al. (1977)<br />
Cr(III) dinicocysteinate complex > 2 000 Sreejayan et al. (2010)<br />
Chromium propionate complex > 2 000 Staniek et al. (2010)<br />
Chromium nicotinate > 622 Shara et al. (2005)<br />
7.2.1.2. Repeat dose toxicity<br />
Several studies were located in the literature regarding repeated oral exposure (dietary or via <strong>drinking</strong><br />
<strong>water</strong>) to Cr(III). Detailed reviews of these studies have been reported by U.S. EPA (1998a), EFSA<br />
ANS Panel (2010a, b) and ATSDR (2012). The no-observed-adverse-effect levels (NOAELs) from the<br />
relevant studies are reported in Table 12 and the studies are described in details in Appendix H (Table<br />
H1). The NOAELs were always the highest dose tested.<br />
EFSA Journal 2014;12(3):3595 70