Reaction mass of heptachromium tricarbide and trichromium dicarbide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Study period:

28 April to 21 May 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Guideline compliant GLP study with chomium(III) oxide. 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 the reaction mass of heptachromium tricarbide and trichromium dicarbide. Reliability score 1, although read-across, due to the very similar release of chromium from trichromium dicarbide and chromium(III) oxide.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Chromium oxide

EC Number:

234-361-2

EC Name:

Chromium oxide

IUPAC Name:

Chromium oxide

Constituent 2

Reference substance name:

Chromium (III) oxide

EC Number:

215-160-9

EC Name:

Chromium (III) oxide

Cas Number:

1308-38-9

Molecular formula:

Cr2O3

IUPAC Name:

chromium (III) oxide

Details on test material:

Chromium (III) oxide, a green powder, batch number: CHC2138-7, purity: 99-99.1%. Stored in a sealed container at room temperature.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals were male and female Han Wistar rats, obtained from Harlan UK Ltd. The animals were weight matched to 200 g ± 15% on arrival and were less than 12 weeks of age at the start of the study.
They animals were housed in groups of five. The room provided a minimum of 15 air changes per hour, temperature was maintained at 19 to 25°C and relative humidity was maintained at 40 to 70 %. The animals were removed from this environment during acclimatisation to tube restraint and during test article exposure. Fluorescent lighting was provided on a 12 hour light/dark cycle.
The rats were provided with wooden 'Aspen' chew blocks as enrichment. They were fed SQC Rat and Mouse Maintenance Diet No.1, Expanded (SDS Ltd., UK) ad libitum. Mains water was provided ad libitum.
All animals were examined for ill health on arrival. They underwent 9 days acclimatisation, the final 3 days of which they underwent acclimatisation to restraint tubes.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The test aerosol was generated from chromium (III) oxide using a Rotating Brush Generator that fed into a flow-through (nose-only) exposure chamber with an internal volume of approximately 40 L. The air flow was 35 L/min and was sufficient to provide a minimum of 12 air changes per hour.
The rats had Vaseline petroleum jelly smeared over their closed eyelids prior to test article exposure as a precautionary measure to avoid adverse irritant effects to the eye.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The achieved aerosol concentration was measured gravimetrically prior to and at approximately half-hourly intervals throughout the exposure.

Duration of exposure:

4 h

Concentrations:

Nominal concentration = 17.6 mg/L. The mean achieved concentration = 5.41 mg/L, with a range of 4.57 to 6.84 mg/L.

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

Five male and five female rats underwent 4 hour nose-only inhalation exposure to the test compound. The dose level initially selected was 5 mg/L to represent the limit dose. All animals were observed daily (for 14 days post-exposure) for signs of ill health or overt toxicity. Animals were observed approximately hourly during the exposure period and for the remainder of the exposure day. Individual body weights were recorded before and after exposure on Day 1, and on Days 2, 8 and 15. Additional body weights were recorded on Days 3, 4 and 5.
All animals were subject to a gross necropsy.

Statistics:

Not performed.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.41 mg/L air (analytical)

Exp. duration:

4 h

Mortality:

No animals died during the study.

Clinical signs:

other: Adverse treatment related clinical signs were increased breathing rate in 4 females and 2 males during exposure, and hunched posture in one female. No adverse clinical signs were observed immediately following exposure or during the remainder of the obser

Body weight:

All animals lost body weight during exposure, but regained their pre-exposure body weight by day 5. As a result of the initial loss, the body weight gain seen during the first week of the study was less than expected for most animals of this age and strain. Animals generally gained more weight during the second week (especially females) and weight gain during this week was more comparable with other rats of this strain and age.

Gross pathology:

Macroscopic findings included green areas in the lung and lymph nodes in the majority of animals. Reddened nasal cavity, mandibular lymph nodes and thymus were also noted in serveral animals. One animal had a pale urinary bladder, however this was not considered to be treatment related.

Other findings:

The mean particle size distribution (MMAD ± GSD) was 2.22 µm ± 2.36.

Any other information on results incl. tables

The LC50 is > 5.41 mg/L.

Applicant's summary and conclusion

Conclusions:

The LC50 is in excess of 5.41 mg/L.

Executive summary:

Male and female Han Wistar rats underwent a single 4 hour nose-only inhalation exposure to chromium (III) oxide at a mean atmospheric exposure level of 5.41 mg/L. Exposure to the test compound was well tolerated and no mortalities occurred. Clinical signs were limited to increased breathing rate during exposure. Adverse clinical signs did not persist into the 14 day observation period. Necropsy revealed green staining in the lung and lymph nodes and reddening of the nasal cavity and mandibular lymph nodes. The LC50 is therefore considered to be in excess of 5.41 mg/L.