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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Justification for type of information:
The test was performed on a bio-available salt of chromium III that is commonly used in dietary supplements. The counter ion, picolinate, is itself under checks for possible reproductive effects, but a negative response in this study means that it is good evidence that neight chromium III or picolinate are hazarous for reproduction.

Data source

Reference
Reference Type:
publication
Title:
Potential of Chromium(III) Picolinate for Reproductive or Developmental Toxicity Following Exposure of Male CD-1 Mice Prior to Mating
Author:
DeAna McAdory et al
Year:
2011
Bibliographic source:
Biol Trace Elem Res (2011) 143:1666–1672

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.3800 (Reproduction and Fertility Effects)
Principles of method if other than guideline:
Four weeks prior to mating, the males were fed a diet providing 200 mg/kg/day [Cr(pic)3] for comparison with untreated controls. Females were not treated. Each male was mated with two females, which were sacrificed on gestation day 17, and their litters were examined for adverse effects.
GLP compliance:
no
Limit test:
yes
Justification for study design:
Valid assessment method to examine potential effects on fertility.

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
CD-1
Details on species / strain selection:
Charles River Breeding Laboratories, International (Wilmington, MA)
Sex:
male/female
Details on test animals and environmental conditions:
22±2°C, with 40–60% humidity and a 12-h photoperiod

Administration / exposure

Route of administration:
oral: feed
Details on exposure:
200 mg/kg body mass per day (25 mg Cr per kilogram body mass per day) mixed into feed, based on data from previous studies, which indicated that CD-1 mice consume an average of 7 g diet per day
Details on mating procedure:
Animals were mated naturally, two females with one male, for 1 week.Observation of a copulation plug in the vagina designated gestation day 0 (GD 0). Mated females were individually housed in shoe box-type cages with hardwood bedding and given Harlan Teklad rodent chow and water ad libitum.
Details on analytical verification of doses or concentrations:
Males were fed the appropriate test diet for 4 weeks prior to mating
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
Diet
Doses / concentrationsopen allclose all
Dose / conc.:
200 mg/kg bw/day (nominal)
Remarks:
Of the test substance in feed
Dose / conc.:
25 mg/kg bw/day (nominal)
Remarks:
Cr 3+ equivalent
No. of animals per sex per dose:
24 females, 12 males
Control animals:
yes, plain diet

Examinations

Litter observations:
Yes
Reproductive indices:
Yes

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
not examined
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined

Reproductive function / performance (P0)

Reproductive performance:
no effects observed
Description (incidence and severity):
The mating indices for control and treated males were identical

Effect levels (P0)

Key result
Dose descriptor:
NOAEL
Effect level:
> 25 mg/kg bw/day (nominal)
Based on:
element
Remarks:
Chromium III
Sex:
male
Remarks on result:
not determinable due to absence of adverse toxic effects

Results: F1 generation

Effect levels (F1)

Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
> 25 mg/kg bw/day (nominal)
Based on:
element
Remarks:
Cr3+
Remarks on result:
not determinable due to absence of adverse toxic effects

Overall reproductive toxicity

Key result
Reproductive effects observed:
no
Lowest effective dose / conc.:
25 mg/kg bw/day (nominal)

Any other information on results incl. tables

An increase in the average number of total resorbed or dead fetuses was observed in the treated group as compared to controls; however, the increase was not statistically significant. No significant effect of exposure was seen on gross or skeletal malformations (split cervical arch) or skeletal variations (rudimentary or supernumerary ribs). Fetuses sired by exposed males weighed significantly more than fetuses of unexposed males. However, this difference is extremely small and is probably a statistical anomaly.

Applicant's summary and conclusion

Conclusions:
No adverse fertility or developmental effects observed when male mice were treated at 25 mg/kg/day for 4 weeks prior to meting.
Executive summary:

The test was performed on a bio-available salt of chromium III that is commonly used in dietary supplements. The counter ion, picolinate, is itself under checks for possible reproductive effects, but a negative response in this study means that it is good evidence that neither chromium III or picolinate are hazarous for reproduction.