Chromium (III) hydroxide

Toxicity to reproduction

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

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

Test material information

Constituent 1

Reference substance name:

Tris(2pyridinecarboxylato-N,O)chromium(III) or 2-pyridinecarboxylic acid

Cas Number:

‎14639-25-9

Molecular formula:

Cr(C6 H4 NO2)3

IUPAC Name:

Tris(2pyridinecarboxylato-N,O)chromium(III) or 2-pyridinecarboxylic acid

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 or test system 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 / concentrations

Doses / concentrations 1

Dose / conc.:

200 mg/kg bw/day (nominal)

Remarks:

Of the test substance in feed

Doses / concentrations 2

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 generation)

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

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.