efsa-opinion-chromium-food-drinking-water

Chromium in food and drinking water
Table 12: Repeated dose toxicity studies with Cr(III) compounds. Results for males (M) and females
(F) are reported separately when the data allowed.
Study (a)
Doses in mg Cr(III)/kg b.w. per day
NOAEL
mg Cr(III)/kg b.w.
per day
Reference
M: 1419
13-week oral (diet); B6C3F1 mice
Rhodes et al. (2005)
M/F:0, 2/1.7, 6.2/4.9, 54/44, 273/212, 1419/1090 (b)
chromium picolinate monohydrate
and F: 1090 NTP (2010)
90-day oral (diet); Becton Dickinson rat
Cr 2 O 3 baked in bread
M/F: 0, 570/547, 1368/1217 (b) M: 1368
and F: 1217
Ivankovic and Preussman
(1975)
14-week oral (diet); F344/N rats
chromium picolinate
M/F: 0, 0.8/0.7, 2.4/2.4, 19.1/19.1, 95.4/93, 506/507 (b) M: 506
and F: 507
Rhodes et al. (2005)
NTP (2010)
90-day oral (diet); Sprague-Dawley rats
M: 1.0 Shara et al. (2005)
M/F: 0, 0.04/0.04, 0.40/0.42, 1.0/1.1 (c)
chromium nicotinate
and F: 1.1
24-weeks oral (diet); Harlan Sprague Dawley rats
9 Anderson et al. (1997)
0, 0.45, 2.25, 4.5 and 9.0 (d)
chromium chloride or chromium picolinate
52-week oral (diet); Sprague-Dawley rats
M: 0.17 (e) Shara et al. (2007)
0.17/0.22 (c)
0 or 25 mg/kg diet chromium nicotinate (0, M/F: 0, and F: 0.22
2-year oral (diet); Becton Dickinson rat
Cr 2 O 3 baked in bread
0, 293, 586, 1466 (b) M+F: 1466 Ivankovic and Preussman
(1975)
2-year oral (diet); F344/N rats
M: 286 NTP (2010)
M/F: 0, 10.7/12, 55/61, 286/314 (b)
chromium picolinate monohydrate
and F: 314
2-year oral (diet); B6C3F1 mice
M: 783 NTP (2010)
M/F: 0, 3029, 143/143, 783/728 (b)
chromium picolinate monohydrate
and F: 728
b.w.: body weight; NOAEL: no-observed-adverse-effect level; M: male; F: female.
(a): In the conversions from concentration to daily doses, the molecular weight (MW) of the anhydrous salts were used
when no information on hydration number was available in the original publication.
(b): Conversion using the data reported in the original publication.
(c): Conversion using drinking water/feed consumption data and average body weight reported in the publication.
(d): Conversion using the default correction factor for subacute/subchronic/chronic exposure via drinking water/feed from
EFSA SC (2012).
(e): The only effects observed were statistically significant decreases in body weight gain, between 5.5 and 14.9 %.
In general, Cr(III) displays very little to no toxicity in animals up to the highest dose tested. In the
Shara et al. (2007) study, the only effects observed in rats dietary exposed to 25 mg/kg chromium
nicotinate were statistically significant decreases in body weight gain, between 5.5 and 14.9 %, which
were not considered as adverse by the CONTAM Panel. The lack of toxicity observed at high
concentrations of Cr(III) may reflect the poor absorption of Cr(III) by the oral route of exposure. The
use of baked bread as a vehicle may have further reduced the absorption of chromium in the Ivankovic
and Preussman (1975) study.
The studies conducted by the National Toxicology Program (NTP, 2010) have been performed
according to present scientific guidances and reported a comprehensive assessment of toxicological
endpoints and adequate reporting for estimation of doses in mg Cr(III)/kg b.w. per day. They were
considered by the CONTAM Panel to be the most relevant studies to establish reference doses. No
adverse effects have been observed in the sub-chronic or long-term toxicity studies in mice or rats at
the highest dose tested of 50000 mg CrO 3 or chromium picolinate/kg diet. The relevant NOAELs
corresponded to 506 and 286 mg Cr(III)/kg b.w. per day for the sub-chronic and long-term toxicity in
the rat, respectively (NTP, 2010).
EFSA Journal 2014;12(3):3595 71