Trichromium dicarbide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across based on grouping of substances (category approach)

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, well-documented publication which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Physico-chemical fate of chromium compounds in the sheep lung model

Author:

Perrault G, Dufresne A, Strati G, McNeil M, Michaud D, Baril M, Bégin R, Labbé J, Larivière P, Eeckhaoudt S and Van Grieken R.

Year:

1995

Bibliographic source:

J Toxicol Environ Health 44, 247-262

Materials and methods

Objective of study:

distribution

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The test substance was instilled into the tracheal lobe of sheep. The fate of the test substance was followed by analysis of bronchoalveolar lavage samples collected at days 2, 3, 5 and 30 after instillation, and by analysing lung samples prepared at day 31 after sacrifice.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

chromic oxide

IUPAC Name:

chromic oxide

Details on test material:

Chromic oxide Cr2O3
Obtained from Fluka Chimika, Switzerland.
No data on purity or other details.

Radiolabelling:

no

Test animals

Species:

sheep

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: 1 year
- Weight at study initiation: 25-45 kg
- Fasting period before study: no data
- Housing: animal care facility of CHUS (no abbreviation key given)
- Individual metabolism cages: yes/no: no data
- Diet (e.g. ad libitum): hay and multigrain feeding given once a day
- Water (e.g. ad libitum): yes (except on the day of examination)
- 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


IN-LIFE DATES: no

Administration / exposure

Route of administration:

intratracheal

Vehicle:

other: phosphate buffered saline pH 7.4

Details on exposure:

Chromium oxide in PBS was instilled via bronchoscopic catherization of the tracheal lobe bronchus and slow infusion of the suspensio in the lobe.

Duration and frequency of treatment / exposure:

Single instillation

Doses / concentrations

Remarks:

Doses / Concentrations:
100 mg chromium oxide in 100 ml PBS

No. of animals per sex per dose / concentration:

5 animals (no data on sex)

Control animals:

yes, concurrent vehicle

Positive control reference chemical:

No real positive controls, but other groups exposed to lead chromate, chromium sulphate and chromium trioxide.

Details on study design:

- Dose selection rationale: no data

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled : bronchoalveolar lavage (BAL) and lung samples
- Time and frequency of sampling: BAL samples taken at days 2, 3, 5, and 30. Lung specimens collected at day 31.

Statistics:

Data from BAL and lung samples were log-transformed to stabilize the variance and to obtain a more symmetric distribution. A value of half the limit of detection was used for nondetected results.
Analysis of variance was used to compare the exposure groups with respect to particle concentration levels and particle size distribution.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

The geometric means of the concentrations of Cr2O3 in BAL samples and lung samples are presented in table 1.
The clearance pattern observed is typical for insoluble particles cleared in the BAL. The clearance half-life could be approximated at about 11 days.

Any other information on results incl. tables

Table 1
BAL AND LUNG SAMPLE CONCENTRATIONS
IN SHEEP AFTER INTRATRACHEAL INSTILLATION
OF CHROMIC OXIDE (Cr2O3)
BAL samples	concentration*
day 2	30.2 (1.9)
day 3	51.3 (1.5)
day 5	35.5 (2.2)
day 30	8.32 (1.9)
Lung samples
day 31	0.23 (5.0)
* geometric means (and geometric standard deviations)
number of particles x 10^-5per ml BAL or gram of dry lung

The transmission electron microscope analysis and the surface composition and valency analyses indicated that the size of chromium oxide particles remained unchanged over the 30 days, and the state of oxidation did not show any measurable changes.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Bronchoalveolar lavage samples of sheep given chromic oxide intratracheally, showed that the half-time of elimination is about 11 days for this substance. The transmission electron microscope analysis and the surface composition and valency analyses indicated that the size of chromium oxide particles remained unchanged over the 30 days, and the state of oxidation did not show any measurable changes.

Executive summary:

Bronchoalveolar lavage samples of sheep given chromic oxide intratracheally, showed that the half-time of lung elimination is about 11 days for this substance. The transmission electron microscope analysis and the surface composition and valency analyses indicated that the size of chromium oxide particles remained unchanged over the 30 days, and the state of oxidation did not show any measurable changes.