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 />
McConnell et al, 1986; Vogelstein et al., 1988; Spigelmann et al., 1994; and Dr. M. Iezzi 17 and Dr.<br />
M. Piantelli 17 , 2013, personal communication), the CONTAM Panel performed a dose-response<br />
evaluation for the neoplastic activity of sodium dichromate dihydrate in the small intestine in mice by<br />
considering both, a) the incidence of adenoma or carcinoma) and b) the incidence of carcinoma only at<br />
the three sites of duodenum, jejunum and ileum (combined). The incidence of adenoma or carcinoma<br />
and the incidence of carcinoma only exhibited a statistically significant dose-response relationship in<br />
both sexes (poly-3 test for trend for adenoma or carcinoma (p < 0.001) and for carcinoma in females<br />
(p < 0.001) and for carcinoma in males (p < 0.05) Since the dose ranges, the range of the observed<br />
carcinoma incidences and the shape of the dose-response were comparable in both sexes the<br />
CONTAM Panel performed also for the data of the small intestine a dose-response evaluation of<br />
males and females combined in the same way as described above for the oral cavity. Table 20(B)<br />
presents the BMD/L 10 values for male and female mice a) for the incidence of adenoma or carcinoma<br />
and b) for carcinoma only at all three sites of the small intestine investigated BMDS software BMDS<br />
2.4 of US-EPA and PROAST (RIVM). Since there were no statistically significant differences<br />
between males and females, the CONTAM Panel derived for the incidence of adenoma or carcinoma<br />
combined a BMDL 10 of 1.0 mg/kg b.w. per day and for the incidence of carcinoma only at all sites a<br />
BMDL 10 of 3.8 mg/kg b.w. per day.<br />
Table 21: BMD analysis of the data on neoplastic effects observed in the 2-year-studies of the NTP<br />
(2007, 2008) on sodium dichromate dihydrate in male and female F344/N rats (A) and in male and<br />
female B6C3F1 mice (B).<br />
BMD 10<br />
(mg/kg b.w. per day)<br />
(A) Dose-response analysis of the neoplastic changes in rat oral cavity<br />
Papilloma or carcinoma of the oral mucosa or tongue<br />
Male rat 1)<br />
5.87<br />
Female rat 1)<br />
4.11<br />
Male and female rats 2) 4.85<br />
Carcinoma of the oral mucosa<br />
Male rat 1)<br />
7.45<br />
Female rat 1)<br />
3.95<br />
Male and female rats 2) 5.09<br />
(B) Dose-response analysis of the neoplastic changes in mouse small intestine<br />
Adenoma or carcinoma in duodenum, jejunum and/or ileum<br />
Male mouse 1)<br />
1.48<br />
Female mouse 1)<br />
1.15<br />
Male and female mice 2) 1.53<br />
Carcinoma in duodenum, jejunum and/or ileum<br />
Male mouse 1)<br />
7.54<br />
Female mouse 1)<br />
6.63<br />
Male and Female mice 2) 6.38<br />
BMDL 10<br />
(mg/kg b.w. per day)<br />
1): using BMDS software for the analysis of single data sets<br />
2): using PROAST software for the analysis of combined data. No statistical differences were observed in dose response<br />
relationship between the two sexes.<br />
7.5.2. Assessment of non-neoplastic effects of Cr(VI)<br />
In order to assess the risk of non-neoplastic effect the CONTAM Panel considered dose-response data<br />
available from the 2-year NTP study on non-neoplastic lesions in liver, duodenum, mesenteric lymph<br />
nodes and pancreas and on haematological effects (NTP, 2008) (see Section 7.2.2.2 and Table 16).<br />
For the non-neoplastic lesions, considering the available data, the CONTAM Panel identified the<br />
occurrence of chronic inflammation of the liver in female rats, diffuse epithelial hyperplasia in the<br />
duodenum in male and female mice, histiocytic cellular infiltration in mesenteric lymph nodes in male<br />
3.30<br />
2.61<br />
3.36<br />
4.07<br />
2.58<br />
3.57<br />
1.08<br />
0.61<br />
1.00<br />
2.53<br />
3.12<br />
3.81<br />
17 Immuno-Oncology Laboratory, Aging Research Center (CeSI), G.d'Annunzio University Foundation of Chieti-Pescara<br />
(Italy),<br />
EFSA Journal 2014;12(3):3595 112