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 />
Table 23: Result of the BMD analysis of haematological effects in male F/334 rat exposed to<br />
sodium dichromate dihydrate in <strong>drinking</strong> <strong>water</strong> for 22 days.<br />
Haematocrit<br />
PROAST Exponential<br />
PROAST Hill<br />
Haemoglobin<br />
PROAST Exponential<br />
PROAST Hill<br />
MCV<br />
PROAST Exponential<br />
PROAST Hill<br />
MCH<br />
PROAST Exponential<br />
PROAST Hill<br />
BMD 05 (mg/kg b.w. per day)<br />
0.64<br />
0.85<br />
0.34<br />
0.31<br />
0.55<br />
0.61<br />
BMDL 05 (mg/kg b.w. per day)<br />
0.53<br />
0.33<br />
0.62<br />
0.49<br />
BMD: benchmark dose; MCV: mean corpuscular volume; MCH: mean corpuscular haemoglobin; BMD: Benchmark dose;<br />
BMDL 05 : 95 % lower confidence limit of BMD.<br />
0.21<br />
0.74<br />
0.27<br />
0.23<br />
0.41<br />
0.50<br />
7.6. Derivation of health-based guidance value(s)/margin of exposure<br />
The CONTAM Panel considered the critical effects of Cr(III) and Cr(VI) in order to derive healthbased<br />
guidance values (HBGV).<br />
Trivalent Chromium<br />
No carcinogenic or other adverse effects have been observed in the sub-chronic or long-term oral<br />
toxicity studies of Cr(III) in mice or rats. The relevant NOAELs derived from these studies<br />
corresponded to 506 and 286 mg Cr(III)/kg b.w. per day for the sub-chronic and long-term toxicity in<br />
the rat, respectively (NTP, 2010). No significant changes in reproductive organ weights in male or<br />
female animals, in sperm parameters, or in estrous cyclicity were reported in the sub-chronic oral<br />
toxicity studies on rats and mice at the highest doses tested (506 mg/kg b.w. per day and 1090 mg/kg<br />
b.w. per day, respectively) (NTP, 2010). However, the CONTAM Panel noted that in some other<br />
studies in rats or mice, reproductive or developmental toxicity by oral exposure to Cr(III) was<br />
reported. The lowest LOAELs for these effects were in the order of 30 mg/kg b.w. per day. The Panel<br />
noted that these studies have methodological limitations and were not designed for establishing<br />
reference doses. Taking together these observations the CONTAM Panel decided to use the relevant<br />
NOAEL in the long-term rat NTP study of 286 mg/kg b.w. per day as a RP for risk characterisation of<br />
Cr(III) and to apply, besides the standard uncertainty factor of 100, an additional factor of 10 to<br />
account for the absence of adequate data on reproductive and developmental toxicity. Therefore, the<br />
CONTAM Panel derived a tolerable daily intake (TDI) of 300 µg Cr(III)/ kg b.w per day.<br />
Hexavalent <strong>chromium</strong><br />
Cr(VI) compounds are genotoxic. Cr(VI) is a human carcinogen by inhalation, and oral exposure via<br />
<strong>drinking</strong> <strong>water</strong> is associated with gastrointestinal system cancers in experimental animals. BMDL 10<br />
values were derived from the animal carcinogenicity data (NTP, 2010). In this study increased<br />
incidence of tumours of the squamous epithelium of the oral cavity and of epithelial tissues of the<br />
small intestine were reported in male and female rats and mice, respectively. Since the adenomacarcinoma<br />
sequence is a well recognised pathway of carcinogenesis in the GI tract, in a conservative<br />
approach, the CONTAM Panel selected the BMDL 10 of 1.0 mg Cr(VI)/kg b.w. per day for combined<br />
adenomas or carcinomas of the small intestine in male and female mice as RP for the estimation of the<br />
margin of exposure (MOE) for neoplastic changes.<br />
After repeated oral administration of Cr(VI), in addition to the cancer effects, several toxic effects<br />
were identified in rats and mice including microcytic, hypochromic anaemia, and non-neoplastic<br />
lesions of the liver, duodenum, mesenteric and pancreatic lymph nodes and pancreas. The lowest<br />
EFSA Journal 2014;12(3):3595 114