efsa-opinion-chromium-food-drinking-water
efsa-opinion-chromium-food-drinking-water efsa-opinion-chromium-food-drinking-water
Chromium in food and bottled water Table H5: Repeated dose toxicity studies with Cr(VI) compounds (continued) Study* NOAEL LOAEL Effect Reference 3-month comparative study in 3 strains of male mice, B6C3F1, BALB/c, am3-C57BL/6 Oral (drinking water) 0, 62.5, 125, 250, mg sodium dichromate dihydrate/L B6C3F1: 8, 15, and 26 mg sodium dichromate dihydrate /kg b.w. per day Doses: 2.8, 5.2, 9.1 mg Cr(VI)/kg b.w. per day (a) BALB/c: 9, 14, and 24 mg sodium dichromate dihydrate /kg b.w. per day Doses: 3.1, 4.9, 8.4 mg Cr(VI)/kg b.w. per day (a) am3-C57BL/6: 8, 15, and 25 mg sodium dichromate dihydrate /kg b.w. per day Doses: 2.8, 5.2, 8.7 mg Cr(VI)/kg b.w. per day (a) - 62.5 mg sodium dichromate dihydrate/ L 2.8/3.1/2.8 mg Cr(VI)/kg b.w. per day Decreases in final mean b.w. and b.w. gain. Decrease water consumption Decrease kidney weight at 125 and kidney, lung, spleen and thymus at 250 mg/L in B6C3F1 mice attributed to changes in b.w. with the exception of thymus weight changes. Haematological changes: mycrocytic hypochromic anemia. Dose-related increased incidences of histiocytic cellular infiltrates and mucosal epithelial hyperplasia were observed in the duodenum. Increases of incidences of glycogen depletion in the liver and minimal secretory depletion in the pancreas. Increases in alanine aminotransferase activity occurred in HD B6C3F1 and am3-C57BL/6 mice and total protein and albumin conc. decreases in the two HD groups B6C3F1 mice. Decreases in heart, kidney and liver were consistent with the reductions in b.w. Reproductive tissue evaluations: decrease in left testis weight related to decreased b.w. in HD am3-C57BL/6 mice. NTP (2007) EFSA Journal 2014;12(3):3595 198
Chromium in food and bottled water Table H5: Repeated dose toxicity studies with Cr(VI) compounds (continued) Study* NOAEL LOAEL Effect Reference 90-day study B6C3F1 mice Oral (drinking water) 0, 0.3, 4, 14, 60, 170 and 520 mg sodium dichromate dihydrate/L Doses: 0, 0.03, 0.3, 1.1, 4.7, 12.2 and 31 mg Cr(VI)/kg b.w. per day (a) 1.1 4.7 Water consumption: significantly lower in the two HC groups. No treatment-related gross lesions. No microscopic lesions in the oral cavity. Significant increases Cr at ≥ 60 mg/L in the oral cavity, glandular stomach, jejunum and ileum. Duodenum: Significant increase Cr at ≥ 14 mg/L Cr. Significant decreases in reduced-to-oxidized glutathione ratio (GSH/GSSG). Intestinal lesions: villous cytoplasmic vacuolisation at ≥ 60 mg/L and atrophy, apoptosis and crypt hyperplasia at ≥170 mg/L. Multinucleated syncitia (fused cells) in the villous lamina propria at 520 mg/L. Increase protein carbonyls at ≥ 4 mg/L. Jejunum: Significant decreases in GSH/GSSG ratio and similar histopathological lesions as in duodenum. 90-day study 0.2 3.6 Water consumption: significantly lower in the two HC groups b.w. per day (a) F344 rats No treatment-related gross lesions Oral (drinking water) No microscopic lesions in the oral cavity. 0, 0.3, 4, 60, 170 and 520 mg sodium Significant increases Cr at ≥ 60 mg/l in the oral cavity, duodenum dichromate dihydrate/L and jejunum. Doses: Significant increases Cr in the glandular stomach and ileum at ≥ 170 0, 0.02, 0.2, 3.6, 8.7 and 24 mg Cr(VI)/kg mg/L and 520 mg/L, respectively. Duodenum: Apoptosis at ≥ 60 mg/L and crypt cell hyperplasia at ≥ 170 mg/L. Histiocytic infiltration at ≥ 60 mg/L. Jejunum: Apoptosis, crypt cell hyperplasia and villous atrophy at concentrations as low as 4 mg/L (incidences not statistically different from control animals and in many instances the lesions were not observed at higher concentrations). Histiocytic infiltration at ≥ 60 mg/L. Significant decreases in GSH/GSSG ratio at 60 mg/L Thompson et al. (2011a) Thompson et al. (2012b) EFSA Journal 2014;12(3):3595 199
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Chromium in <strong>food</strong> and bottled <strong>water</strong><br />
Table H5: Repeated dose toxicity studies with Cr(VI) compounds (continued)<br />
Study* NOAEL LOAEL Effect Reference<br />
90-day study<br />
B6C3F1 mice<br />
Oral (<strong>drinking</strong> <strong>water</strong>)<br />
0, 0.3, 4, 14, 60, 170 and 520 mg sodium<br />
dichromate dihydrate/L<br />
Doses:<br />
0, 0.03, 0.3, 1.1, 4.7, 12.2 and 31 mg<br />
Cr(VI)/kg b.w. per day (a) 1.1 4.7 Water consumption: significantly lower in the two HC groups.<br />
No treatment-related gross lesions.<br />
No microscopic lesions in the oral cavity.<br />
Significant increases Cr at ≥ 60 mg/L in the oral cavity, glandular<br />
stomach, jejunum and ileum.<br />
Duodenum:<br />
Significant increase Cr at ≥ 14 mg/L Cr.<br />
Significant decreases in reduced-to-oxidized glutathione ratio<br />
(GSH/GSSG).<br />
Intestinal lesions: villous cytoplasmic vacuolisation at ≥ 60 mg/L<br />
and atrophy, apoptosis and crypt hyperplasia at ≥170 mg/L.<br />
Multinucleated syncitia (fused cells) in the villous lamina propria at<br />
520 mg/L.<br />
Increase protein carbonyls at ≥ 4 mg/L.<br />
Jejunum:<br />
Significant decreases in GSH/GSSG ratio and similar<br />
histopathological lesions as in duodenum.<br />
90-day study<br />
0.2 3.6 Water consumption: significantly lower in the two HC groups<br />
b.w. per day (a)<br />
F344 rats<br />
No treatment-related gross lesions<br />
Oral (<strong>drinking</strong> <strong>water</strong>)<br />
No microscopic lesions in the oral cavity.<br />
0, 0.3, 4, 60, 170 and 520 mg sodium<br />
Significant increases Cr at ≥ 60 mg/l in the oral cavity, duodenum<br />
dichromate dihydrate/L<br />
and jejunum.<br />
Doses:<br />
Significant increases Cr in the glandular stomach and ileum at ≥ 170<br />
0, 0.02, 0.2, 3.6, 8.7 and 24 mg Cr(VI)/kg<br />
mg/L and 520 mg/L, respectively. Duodenum:<br />
Apoptosis at ≥ 60 mg/L and crypt cell hyperplasia at ≥ 170 mg/L.<br />
Histiocytic infiltration at ≥ 60 mg/L.<br />
Jejunum:<br />
Apoptosis, crypt cell hyperplasia and villous atrophy at<br />
concentrations as low as 4 mg/L (incidences not statistically different<br />
from control animals and in many instances the lesions were not<br />
observed at higher concentrations).<br />
Histiocytic infiltration at ≥ 60 mg/L.<br />
Significant decreases in GSH/GSSG ratio at 60 mg/L<br />
Thompson et al.<br />
(2011a)<br />
Thompson et al.<br />
(2012b)<br />
EFSA Journal 2014;12(3):3595 199
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