Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
Treatment of females gestation days 6 - 17
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Study performed on soluble organic chromium III salt used as a food supplement and cited in reviews on safety of such food supplements.
This is considered to be close enough to oxalate to permit a valid read-across for purposes of chromium effects.

Data source

Reference
Reference Type:
publication
Title:
Comparison of the Potential for Developmental Toxicity of Prenatal Exposure to Two Dietary Chromium Supplements, Chromium Picolinate and [Cr3O(O2CCH2CH3)6(H2O)3]1, in Mice
Author:
M.M. Bailey et al
Year:
2008
Bibliographic source:
Birth Defects Research (Part B) 83:27–31 (2008)

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
From gestation days (GD) 6–17, mated CD-1 female mice were fed diets delivering either 25mg Cr/kg/day as Cr(pic)3, 3.3 or 26mg Cr/kg/day as Cr3 propionate, or the diet only to determine if Cr3 could cause developmental toxicity. Dams were sacrificed on GD 17, and their litters were examined for adverse effects
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
report also refers to chromium picolinate.

Test animals

Species:
mouse
Strain:
CD-1
Details on test animals and environmental conditions:
Male and female CD-1 mice, obtained from Charles River Breeding Laboratories, International (Wilmington, MA) Housed at ca 22C, with 40–60% humidity and a 12-hr photoperiod

Administration / exposure

Route of administration:
oral: feed
Details on exposure:
Females were given treated diets containing ca 25 mg/kg/day Cr III as either picolinate or as propionate from gestation days 6 - 17
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Animals were bred naturally, two females with one male. Observation of a copulation plug was designated GD 0.
Duration of treatment / exposure:
Females were given treated diets containing ca 25 mg/kg/day Cr III as either picolinate or as propionate from gestation days 6 - 17
Frequency of treatment:
Diet
Duration of test:
12 days
Doses / concentrationsopen allclose all
Dose / conc.:
25 mg/kg bw/day (nominal)
Remarks:
Expressed as Cr III either dosed as picolinate or propionate
Dose / conc.:
3.3 mg/kg bw/day (nominal)
Remarks:
Expressed as Cr III dosed as propionate
No. of animals per sex per dose:
Up to 30 females per group.
Control animals:
yes, plain diet

Examinations

Maternal examinations:
Clinical signs, weight, food consumption
Ovaries and uterine content:
Implantations
Fetal examinations:
Foetal weight, viability, skeletal and other defects

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Food consumption was virtually identical among the treatment groups, and average food consumption was approximately 7g diet/day.

Maternal developmental toxicity

Number of abortions:
no effects observed
Pre- and post-implantation loss:
no effects observed
Total litter losses by resorption:
no effects observed
Description (incidence and severity):
Percentage of resorbed or dead fetuses did not differ among treatment groups
Details on maternal toxic effects:
NoneMaternal weight gain was not affected by the administration of Cr(pic)3 or Cr3 (Table 1). No signs of maternal toxicity were observed for dams in any of the groups

Effect levels (maternal animals)

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

Maternal abnormalities

Key result
Abnormalities:
no effects observed

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
Fetal weight and percentage of resorbed or dead fetuses did not differ among treatment groups
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Reduction in number of live offspring:
not examined
Changes in sex ratio:
not examined
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not examined
External malformations:
no effects observed
Skeletal malformations:
no effects observed
Description (incidence and severity):
No skeletal defects in fetuses from Cr(pic)3- or Cr3-treated dams differed in incidence from the control value.
Visceral malformations:
not specified
Other effects:
not specified

Effect levels (fetuses)

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

Fetal abnormalities

Key result
Abnormalities:
no effects observed

Overall developmental toxicity

Key result
Developmental effects observed:
no

Applicant's summary and conclusion

Conclusions:
No signs of maternal toxicity were observed.No decrease in foetal weight or significantly increased incidence of skeletal defects was observed compared to the controlsAlthough exposure was not up to the maternal tolerated limit and the exposure period was relatively short, there were no adverse effects observed.