Reaction mass of heptachromium tricarbide and trichromium dicarbide

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Read-across to chromium(III) chloride. This salt is more soluble than trichromium dicarbide, and therefore the results obtained with this substance can be regarded as "worst case" situations also for chromium carbide exposure. Acceptable, well documented study report which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Exposure of pregnant mice to chromium picolinate results in skeletal defects in their offspring.

Author:

Bailey, M. M., J. G. Boohaker, et al.

Year:

2006

Bibliographic source:

Birth Defects Res B Dev Reprod Toxicol.77(3): 244-9.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Pregnant CD-1 mice were fed diets containing chromium chloride (200 mg/ kg bodyweight / day) during gestation days 6-17. Dams were sacrificed on GD 17, and their litters were examined for adverse effects.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

chromium(III) chloride

IUPAC Name:

chromium(III) chloride

Details on test material:

Chromium chloride (CrCl3) obtained from Fischer Scientific (Pittsburgh, PA, USA). No other details given.

Test animals

Species:

mouse

Strain:

CD-1

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CD-1 mice from Charles River Breeding Laboratories, International (Wilmington, MA, USA)
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: mated females housed individually in shoe-box type cages with hardwood bedding
- Diet (e.g. ad libitum): Milled rodent diet from Harlan Teklad (Madison, WI, USA) ad libitum
- Water (e.g. ad libitum): yes, ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS: AAAlAC-approved animal facility
- Temperature (°C): 22 ± 2 C
- Humidity (%): 40-60%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light

Administration / exposure

Route of administration:

oral: feed

Details on exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): no data. Stability studies indicate that chromium compounds are extremely stable and no degradation in the diet would be expected.
- Mixing appropriate amounts with (Type of food): Milled rodent diet
- Storage temperature of food: no data

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

Calculations based on data from previous studies indicating that pregnant CD-1 mice consume an average of 7 g diet/day.

Details on mating procedure:

- Animals were bred naturally, two females with one male.
- Proof of pregnancy: [vaginal plug ] referred to as [day 0] of pregnancy

Duration of treatment / exposure:

12 days (during gestation days 6-17)

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
200 mg/kg bw/day (=39 mg Cr(3+))
Basis:
nominal in diet

No. of animals per sex per dose:

14

Control animals:

yes, plain diet

Details on study design:

Random assignment into groups.

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily


BODY WEIGHT: Yes
- Time schedule for examinations: no data


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data




POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 17
- Organs examined: uterus weight


OTHER:

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes / No / No data
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: No data
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other:

Fetal examinations:

- External examinations: Yes: [all per litter ] (live fetuses examined for gross malformations)
- Soft tissue examinations: No data
- Skeletal examinations: Yes: [all per litter ]
- Head examinations: No data

Statistics:

The data from each study replicate were calculated independetly, tested for for homogeneity of variance by the Levene statistic, and then pooled and analyzed together. Data were analyzed either by ANOVA followed by an LSD post-hoc test to determine specific significant differences (P<0.05) pr by a Pearson chi-square test (P<0.05).

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Maternal weight gain was not affected by treatment with CrCl3.No signs of maternal toxicity were observed (no details given).

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

ca. 200 mg/kg bw/day (nominal)

Basis for effect level:

body weight and weight gain

2

Dose descriptor:

NOAEL

Effect level:

ca. 200 mg/kg bw/day (nominal)

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The results showed no differences between the foetuses of the CrCl3 group compared with the control group, when assessing foetal weight, percentage of resorbed/dead foetuses, and malformations.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

ca. 200 mg/kg bw/day

Sex:

male/female

Basis for effect level:

other: Maternal dose 200 mg CrCl3/kg bw/ day. Basis: foetal weight, percentage of dead foetuses

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Maternal treatment with 200 mg chromium chloride/kg bw/day during gestation days 6-17 did not result in any signs of developmental toxicity.

Executive summary:

The effect of chromium chloride was studied by administering a diet containing 200 mg/kg bw/day CrCl₃ during gestation days 6-17 to pregnant CD-1 mice. The results showed no differences between the foetuses of the CrCl₃ group compared with the control group, when assessing foetal weight, percentage of resorbed/dead foetuses, and malformations. No signs of maternal toxicity were observed either, a fact which decreases the relevance of the results, as it is quite evident that a higher dose would be need for reaching a level with a potential to cause developmental toxicity.