efsa-opinion-chromium-food-drinking-water
efsa-opinion-chromium-food-drinking-water
efsa-opinion-chromium-food-drinking-water
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7.2.2.3. Developmental and reproductive toxicity<br />
Chromium in <strong>food</strong> and <strong>drinking</strong> <strong>water</strong><br />
A number of studies have investigated the induction of reproductive effects in animals orally exposed<br />
to Cr(VI).<br />
Detailed review of these studies has been reported by EPA (U.S. EPA 1998b; CA EPA, 2009) and<br />
ATSDR (2012). NOAELs and LOAELs of the studies are reported in Table 17 and the studies are<br />
described in details in Table H6 (see Appendix H).<br />
No treatment-related effects on fertility or reproductive performance have been observed in<br />
2-generation studies on mice exposed via the diet to potassium dichromate up to 400 mg/kg diet<br />
(corresponding to 30 mg Cr(VI)/kg b.w. per day) (NTP, 1997). In studies conducted on Sprague-<br />
Dawley rats or BALB/c mice exposed up to 400 mg/kg diet potassium dichromate daily<br />
(corresponding to 12.7 and 40.7 mg Cr(VI)/kg b.w. per day, respectively) for 9 weeks followed by a<br />
recovery period of 8 weeks, no effect on the testis and epididymes or spermatogenesis have been<br />
observed (NTP, 1996a, b, 1997). Similarly, exposure to sodium dichromate dihydrate in <strong>drinking</strong><br />
<strong>water</strong> did not produce morphological changes to male reproductive organs of B6C3F1 mice exposed<br />
to 27.9 or 5.9 mg Cr(VI)/kg b.w. per day or F344 rats exposed to 20.9 or 5.9 mg Cr(VI)/kg b.w. per<br />
day for 3 months or 2 years, respectively (NTP, 2007, 2008) or affect sperm count or motility in<br />
B6C3F1, BALB/c and C57BL/6N mice exposed to 9.1 mg Cr(VI)/kg b.w. per day for 3 months (NTP,<br />
2007).<br />
Other studies on Cr(VI) showed adverse reproductive effects, with the male reproductive system<br />
exhibiting the highest sensitivity. An inhibitory effect on sexual and aggressive behaviour has been<br />
observed in male rats treated with potassium dichromate via <strong>drinking</strong> <strong>water</strong>, as well as effects on the<br />
reproductive organs (decrease testes, seminal vesicles and preputial gland weights) at a dose of<br />
1000 mg/L (corresponding to 32 mg Cr(VI)/kg b.w. per day) (Bataineh et al., 1997). In a study in mice<br />
potassium dichromate reduced seminal vesicles and preputial glands weight (Elbetieha and<br />
Al-Hamood, 1997). Reduction of epididymal sperm counts, increased frequency of abnormal sperm<br />
and decreased diameter of seminiferous tubules have been reported in rats dietary exposed to<br />
10 mg/kg <strong>chromium</strong> trioxide (5 mg Cr(VI)/kg b.w. per day) (Li et al., 2001) (Li et al., 2001). Low<br />
doses of sodium dichromate (≤ 7.9 mg Cr(VI)/kg b.w. per day) caused partial loss of cellular activity<br />
in testicular tissues of rats whereas treatment with higher dose of <strong>chromium</strong> (≥ 15.9 mg/kg b.w. per<br />
day) caused deleterious effects both on spermatogenic and steroidogenic activity (Chowdhury and<br />
Mitra, 1995).<br />
The effect of Cr(VI) on spermatogenesis was studied in BALB/c mice (Zahid et al., 1990). Mice were<br />
given 100, 200 or 400 mg potassium dichromate/kg diet (corresponding to 16, 28 or 63 mg Cr(VI)/kg<br />
b.w. per day) for 7 weeks. Histological examination of the testes of treated animals revealed<br />
degeneration of the outermost cellular layers of seminiferous tubules with no spermatogenesis present<br />
and reported increase in the number of resting spermatocytes. Undegenerated tubules without<br />
spermatogenesis were significantly increased in all treated groups. Epididymal sperm count was lower<br />
at 200 and 400 mg/kg diet and the percentage of morphologically abnormal sperm was higher.<br />
Chromium treatment was reported to cause accumulation of germ cells in resting spermatocyte stage.<br />
These data are of questionable value because the methods described by the authors were not sufficient<br />
to show that they could identify spermatogonia. The methods used to evaluate the epididymal sperm<br />
very probably resulted in clumped sperm and poorly reproducible counts and the reduction in<br />
spermatogonia numbers concurrent with unchanged spermatocyte and spermatid numbers is<br />
biologically implausible. Moreover there are inconsistencies regarding the number of mice used in the<br />
study, the sizes of the experimental groups do not satisfy minimal requirements for such toxicity study<br />
and inappropriate statistical methods were used (Finley et al., 1993; NTP, 1996b). Moreover, no<br />
effects have been observed in a similar study performed by the NTP (1996b). Therefore, the<br />
CONTAM Panel did not take into account the results of the Zahid et al. (1990) study for the<br />
evaluation of the reproductive toxicity of Cr(VI).<br />
Effects on testes and epididymal weights as well as on sperm have also been reported in rabbits<br />
exposed to potassium dichromate (Yousef et al., 2006).<br />
EFSA Journal 2014;12(3):3595 85