efsa-opinion-chromium-food-drinking-water

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