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) oxide. The release of chromium from chromium carbide is very similar to the release from chromium metal and chromium(III) oxide and therefore the results obtained with these substances can readily be used in the assessment of trichromium dicarbide. Acceptable study report.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Absence of toxic and carcinogenic effects after administration of high doses of chromic oxide pigment in subacute and long-term feeding experiments in rats.

Author:

Ivankovic, S. and R. Preussman

Year:

1975

Bibliographic source:

Food Cosmet Toxicol.13(3): 347-51.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Chromium(III) oxide was baked into bread at concentrations of 2% and 5% and this bread was fed to animals 5 days/week for a period of 90 days. After 60 days, 9 male and 9 female rats / treatment group were paired.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Chromium(III) oxide

IUPAC Name:

Chromium(III) oxide

Details on test material:

- Name of test material (as cited in study report): Chromium oxide green (Schultz no 1451; Colour Index no. 77288; pigment green 17)
- Molecular formula (if other than submission substance): Cr2O3
- Molecular weight (if other than submission substance): 152
- Substance type: pure substance (non-hydrated from)
- Physical state: fine green powder
- Analytical purity: maximum content of 3 ppm Cr(III)
- Impurities (identity and concentrations): free from chromate CrO4(2-). With respect to heavy-metal impurities the product compiled with the specifications of the Deutsche Forschungsgemeinschaft, Farbstoff-Kommission (1959)
- Composition of test material, percentage of components: pure Cr2O3 (no data on %)
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:

rat

Strain:

other: (BD rats)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: inbread BD rats, no data on source
- Age at study initiation: about 100 days
- Weight at study initiation: about 200 g
- Fasting period before study: no data
- Housing: in groups of four rats in Makrolon cages
- Diet (e.g. ad libitum): Altromin standard diet ad libitum for controls. Bread (2835 g flour, 150 g milk powder, 150 g mixed salts (NaCl, CaHPO4 and Cu, Zn, Co, Mn and K), 150 g cooking oil, 150 g cod-liver oil, 300 g malt extract, 600 g sugar, 80 g yeast and 900 ml water) containing 2% or 5% of the test substance for test groups (ad libitum). At weekends the treatment groups received the control diet with a vegetable supplement.
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: bread

Details on exposure:

DIET PREPARATION
- Rate of preparation of diet (frequency): twice weekly
- Mixing appropriate amounts with (Type of food): Incorporationg 2% or 5% of the test substance into a dough made from 2835 g flour, 150 g milk powder, 150 g mixed salts (NaCl, CaHPO4 and Cu, Zn, Co, Mn and K), 150 g cooking oil, 150 g cod-liver oil, 300 g malt extract, 600 g sugar, 80 g yeast and 900 ml water, and subsequently baked
- Storage temperature of food: no data


VEHICLE
- Justification for use and choice of vehicle (if other than water): bread
- Concentration in vehicle: 2% and 5%

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The bread given to the rats was weighed, and the uneaten bread was weighed in order to determined the amount consumed. There were only small losses from crumbs. The estimated uptake of Cr(III) based on the Cr2O3 concentrations in the bread consumed was 568 mg/kg/day for males and 547 mg/kg/day for males in the 2% group, and 1368 mg/kg/day for males and 1216 mg/kg/day for females in the 5% group.

Details on mating procedure:

9 male and 9 female rats No data given on mating procedure.

Duration of treatment / exposure:

90 days

Frequency of treatment:

daily

Duration of test:

Follow up period of some of the progeny through their whole lifetime or maximum 600 days.

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
2 or 5%
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
568 or 1368 mg/kg/day for males; 547 or 1216 mg/kg/day for females
Basis:
other: average Cr3+ intake

No. of animals per sex per dose:

9

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: The doses were selected to be higher than the 1% in feed recommended by national (Deutsche Forschungsgemenschaft) and international (WHO) authorities
- Rationale for animal assignment (if not random): no data
- Rationale for selecting satellite groups: no satellite groups

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: No data


DETAILED CLINICAL OBSERVATIONS: No data


BODY WEIGHT: Yes
- Time schedule for examinations: every second week


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes (4 animals per cage, average food consumption per animal)
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data


OPHTHALMOSCOPIC EXAMINATION: No data

OTHER:
HAEMATOLOGY: Yes
- Time schedule for collection of blood: The blood picture was teremined before the beginning of the experiment and monthly during feeding. At the end of the study, the animals were fasted fro 24 hours, after which blood samples were taken from retrobulbar plexus and from the tail vein.
- Anaesthetic used for blood collection: No data
- Animals fasted: Yes
- How many animals: All
- Parameters checked in table 1 were examined.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood:
- Animals fasted: Yes / No / No data
- How many animals:
- Parameters checked in table 2 were examined.

URINALYSIS: Yes
- Time schedule for collection of urine: Random samples were taken during the course of the study and from all animals in the last week of the experiment
- Metabolism cages used for collection of urine: No data
- Animals fasted: No
- Parameters checked in table 3 were examined.

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # : Sacrifice within 1 week after the end of the 90-day feeding period, except for those which were still suckling, which were killed immediately after given birth.
- Organs examined:

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Ovarian weight.

Fetal examinations:

Malformations and other adverse effects observed (no details given)

Statistics:

No statistics

Indices:

No data

Historical control data:

No data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
No effects. All rats became pregnant. Litter sizes were normal.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

1 368 mg/kg bw/day

Based on:

element

Remarks:

Cr(III)

Basis for effect level:

other: No effects. All rats became pregnant. Litter sizes were normal.

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No obvious malformations in the offspring of chromium(III) oxide treated female rats could be seen. No tumours were detected during a 600 day observation period among pups selected for lifetime observation.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

1 216 mg/kg bw/day

Based on:

element

Remarks:

Cr(III)

Basis for effect level:

other: Basis: malformations or adverse effects at birth, tumour frequency during 600 days observation period

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

No malformations were observed among the offspring of chromium(III) oxide treated mothers (n=9/group, 547 or 1216 mg Cr(3+)/kg/day). Based on this, oral intake of chromium(III) oxide does not cause developmental effects in the offspring. NOAEL was 1216 mg Cr(3+)/kg/day.

Executive summary:

Chromium(III) oxide was baked into bread at concentrations of 2% and 5% and fed to animals 5 days/week for a period of 90 days. After 60 days, 9 male and 9 female rats / treatment group were paired. No malformations were observed among the offspring of chromium(III) oxide treated mothers (n=9/group, 547 or 1216 mg Cr(3+)/kg/day). Based on this, oral intake of chromium(III) oxide does not cause developmental effects in the offspring. NOAEL was 1216 mg Cr(3+)/kg bw/day.