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 H2: Developmental and reproductive toxicity studies with Cr(III) compounds Study* NOAEL LOAEL Effect Reference 1-generation reproductive toxicity 90-day (5 days/week) oral (diet) rat (Becton Dickinson) 0 %, 2 % or 5 % Cr2O3 baked in bread 9F paired with M from same dosage group 60 days after start of feeding Doses: M: 0; 570; 1368 mg Cr(III)/kg b.w. per day (a) F: 0; 547; 1217 mg Cr(III)/kg b.w. per day (a) M: 1368 mg Cr(III)/kg b.w. per day F: 1217 mg Cr(III)/kg b.w. per day - No effect on fertility, gestation length or litter size. Pups: no malformations or other adverse effects observed. Ivankovic and Preussman, (1975) 12 weeks oral exposure of sexually mature M Sprague-Dawley rats 0, 1000 mg chromium chloride/L (0, 328.4 mg Cr(III)/L) Doses: 0 and 30 mg Cr(III)/kg b.w. per day (b) X untreated F 12 weeks oral exposure of sexually mature M Swiss mice 0, 1000 or 5000 mg chromium chloride/L (0, 328.4 or 1641.8 mg Cr(III)/L) Doses: 0, 49, 246 mg Cr(III)/kg b.w. per day (b) X untreated F 12 weeks oral exposure of sexually mature F Swiss mice 0, 2000 or 5000 mg chromium chloride/L (0, 656.6 or 1641.8 mg Cr(III)/L) Doses: 0, 98, 246 mg Cr(III)/kg b.w. per day (b) X untreated M - 30 mg Cr(III)/kg b.w. per day - 49 mg Cr(III)/kg b.w. per day - 98 mg Cr(III)/kg b.w. per day Fertility studies Inhibitory effect on sexual and aggressive behaviour: reduction number of mounts, increased post-ejaculatory interval, decrease number of M ejaculating, decreased aggressive behaviour towards other M. Decrease b.w., absolute testes, seminal vesicles and preputial glands weights. No effect on fertility of treated M. Increase number of resorptions and dead fetuses in F mated with treated M. No histopathology performed. Decrease b.w., testes weight in treated M, decrease seminal weight in M at HD. Reduction preputial glands in treated M. Decrease fertility in M at 5000 mg/L. Increase number of resorptions and dead fetuses in F impregnated with exposed M. No histopathology performed. Increase ovarian weight and reduction uterine weights in treated F No effect on F fertility (pregnancy rate). Decrease number of implantations and viable fetuses in treated F. Increase number of resorptions in treated F. No histopathology performed. Bataineh et al. (1997) Elbetieha and Al-Hamood (1997) Elbetieha and Al-Hamood (1997) EFSA Journal 2014;12(3):3595 188
Chromium in food and bottled water Table H2: Developmental and reproductive toxicity studies with Cr(III) compounds (continued) Study* NOAEL LOAEL Effect Reference Male CD-1 mice Oral (diet) 0, 200 mg chromium picolinate/kg b.w. per day. Doses: 0, 25 mg Cr(III)/kg b.w. per day (a) for 4 weeks before mating X untreated F F sacrificed on GD 17 25 mg Cr(III)/kg b.w. per day - No significant effect on mating and fertility indices. No effect on the average number of implantations in F. No effect on prenatal mortality, fetal weight or gross or skeletal morphology. McAdory et al. (2011) Mated F Swiss mice Oral (drinking water) 0 or 1000 mg/L chromium chloride day 12 of gestation – day 20 of lactation Doses: 0, 79 mg Cr(III)/kg b.w. per day (c ) - 79 mg Cr(III)/kg b.w. per day Mated F CD-1 mice Oral (diet) GD 6-17 Dams sacrificed GD 17 Doses: 0, 200 mg chromium picolinate (25 mg Cr(III)/kg b.w. per day), 200 mg/kg CrCl 3 (39 mg Cr(III)/kg b.w. per day) (a) - 25 mg Cr(III)/kg b.w. per day Mated F CD-1 mice Oral (diet) GD 6-17 Dams sacrificed GD 17 Doses: 0, 200 mg chromium picolinate (25 mg Cr(III)/kg b.w. per day) or as Cr(III)cation Cr 3 O(O 2 CCH 2 CH 3 ) 6 (H 2 O) 3 ) + 3.3 or 26 mg Cr(III)/kg b.w. per day (a) 25 mg Cr (III)/kg b.w./day Developmental toxicity studies Offsprings: M: decrease number of pregnant females, reduction b.w., testes, seminal vesicles and preputial glands weights. F: delayed sexual maturation (delayed vaginal opening), reduction of fertility (decrease number pregnant females, implantations (not stat signif.) viable fetuses (not stat signif.), b.w., ovaries and uteri weights, increase number of resorptions. impairment of reproductive functions and fertility in adulthood. No histopathology performed No effect on maternal toxicity, no effect on b.w. gain or food consumption. No effect on maternal fertility (number of implantations, resorbed or dead fetuses). No effect on fetal weight. Significant increase in incidence of bifurcated cervical arches in chromium picolinate group (effect not reproducible in other studies). No effect in CrCl 3 group. - No signs of maternal toxicity, no effect on b.w. gain or food consumption. No decrease in fetal weight, no effect on number of resorbed or dead fetuses and no difference in the number of implantations/litter or significantly increased incidence of skeletal defects, no effect on gross malformations. Al-Hamood et al. (1998) Bailey et al. (2006) Bailey et al. (2008a) EFSA Journal 2014;12(3):3595 189
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Chromium in <strong>food</strong> and bottled <strong>water</strong><br />
Table H2: Developmental and reproductive toxicity studies with Cr(III) compounds<br />
Study* NOAEL LOAEL Effect Reference<br />
1-generation reproductive toxicity<br />
90-day (5 days/week) oral (diet) rat (Becton<br />
Dickinson)<br />
0 %, 2 % or 5 % Cr2O3 baked in bread<br />
9F paired with M from same dosage group<br />
60 days after start of feeding<br />
Doses:<br />
M: 0; 570; 1368 mg Cr(III)/kg b.w. per<br />
day (a)<br />
F: 0; 547; 1217 mg Cr(III)/kg b.w. per<br />
day (a)<br />
M: 1368 mg<br />
Cr(III)/kg b.w.<br />
per day<br />
F: 1217 mg<br />
Cr(III)/kg b.w.<br />
per day<br />
- No effect on fertility, gestation length or litter size.<br />
Pups: no malformations or other adverse effects observed.<br />
Ivankovic and<br />
Preussman,<br />
(1975)<br />
12 weeks oral exposure of sexually mature M<br />
Sprague-Dawley rats<br />
0, 1000 mg <strong>chromium</strong> chloride/L (0,<br />
328.4 mg Cr(III)/L)<br />
Doses: 0 and 30 mg Cr(III)/kg b.w. per<br />
day (b)<br />
X untreated F<br />
12 weeks oral exposure of sexually mature M<br />
Swiss mice<br />
0, 1000 or 5000 mg <strong>chromium</strong> chloride/L (0,<br />
328.4 or 1641.8 mg Cr(III)/L)<br />
Doses: 0, 49, 246 mg Cr(III)/kg b.w. per<br />
day (b)<br />
X untreated F<br />
12 weeks oral exposure of sexually mature F<br />
Swiss mice<br />
0, 2000 or 5000 mg <strong>chromium</strong> chloride/L (0,<br />
656.6 or 1641.8 mg Cr(III)/L)<br />
Doses: 0, 98, 246 mg Cr(III)/kg b.w. per<br />
day (b)<br />
X untreated M<br />
- 30 mg<br />
Cr(III)/kg<br />
b.w. per<br />
day<br />
- 49 mg<br />
Cr(III)/kg<br />
b.w. per<br />
day<br />
- 98 mg<br />
Cr(III)/kg<br />
b.w. per<br />
day<br />
Fertility studies<br />
Inhibitory effect on sexual and aggressive behaviour: reduction number of<br />
mounts, increased post-ejaculatory interval, decrease number of M<br />
ejaculating, decreased aggressive behaviour towards other M.<br />
Decrease b.w., absolute testes, seminal vesicles and preputial glands<br />
weights.<br />
No effect on fertility of treated M.<br />
Increase number of resorptions and dead fetuses in F mated with treated M.<br />
No histopathology performed.<br />
Decrease b.w., testes weight in treated M, decrease seminal weight in M at<br />
HD.<br />
Reduction preputial glands in treated M.<br />
Decrease fertility in M at 5000 mg/L. Increase number of resorptions and<br />
dead fetuses in F impregnated with exposed M.<br />
No histopathology performed.<br />
Increase ovarian weight and reduction uterine weights in treated F<br />
No effect on F fertility (pregnancy rate).<br />
Decrease number of implantations and viable fetuses in treated F.<br />
Increase number of resorptions in treated F.<br />
No histopathology performed.<br />
Bataineh et al.<br />
(1997)<br />
Elbetieha and<br />
Al-Hamood<br />
(1997)<br />
Elbetieha and<br />
Al-Hamood<br />
(1997)<br />
EFSA Journal 2014;12(3):3595 188