Chromium (III) hydroxide

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

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

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Information from a peer reviewed Assessment Report

Data source

Reference

Reference Type:

other: Peer reviewed assessment report

Title:

Unnamed

Year:

2009

Materials and methods

Principles of method if other than guideline:

A comparable 13-week inhalation toxicity study (guidance based) was conducted.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Chromium (III) oxide

EC Number:

215-160-9

EC Name:

Chromium (III) oxide

Cas Number:

1308-38-9

Constituent 2

Reference substance name:

Chromium(III) oxide

IUPAC Name:

Chromium(III) oxide

Constituent 3

Reference substance name:

Chromium(III) oixde

IUPAC Name:

Chromium(III) oixde

Details on test material:

Chromium(III) oxide

Test animals

Species:

rat

Strain:

other: CDF

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

not specified

Remarks on MMAD:

MMAD / GSD: 1.8-1.9 µm

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

6 h/day
5 days/week

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
4.4 mg/m³
Basis:
no data

Doses / concentrations 2

Remarks:

Doses / Concentrations:
15 mg/m³
Basis:
no data

Doses / concentrations 3

Remarks:

Doses / Concentrations:
44 mg/m³
Basis:
no data

No. of animals per sex per dose:

5

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

Two thirds of the animals were sacrificed immediately after the exposure period, and one third were followed up for an additional 13-week recovery
period.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

·        Lung weight increased in males in the highest concentration group

·        Mean weight of mediastinal lymph nodes increased in the highest concentration group

·        Macroscopic examination showed green dislocation of the lungs and mediastinal lymph nodes of all animals

·        Black pigment was observed at tracheal bifurcation, in the peribronchial lymphoid tissue, and within mediastinal lymph nodes

·        Trace to mild chronic inflammation and septal hyperplasia were observed in alveolar septa surrounding the aggregates of pigmented macrophages in mid- and high exposure animals

·        Lymphoid hyperplasia was present in all exposure groups

·        Pigment deposits and slight inflammatory changes were also observed after the recovery period

·        Also some low dose males exhibit slight inflammatory changes in alveolar septa

Applicant's summary and conclusion

Conclusions:

Effects of repeated inhalation of water-insoluble chromium (III) oxide in rat are restricted to the lungs and include pigment deposition in the lower respiratory tract and peribronchial and mediastinal lymphoid tissue. The accumulation of the pigment was accompanied by mild interstitial inflammation and septal hyperplasia. Some very slight changes were also seen in the low dose males sacrificed after the recovery period. The clearance of the pigment seemed to be low and was most likely to occur via the lymphatic system.
A LOAEC for rats was set to 4.4 mg/m³ for chromium (III) oxide. This concentration is corresponding to 3 mg Cr³ / m³ .

Executive summary:

In a subchronic inhalation toxicity study chromium(III) oxide was administered to rats (5 each sex and each dose). Inhalation exposure concentrations were: 4.4 mg/m³, 15 mg/m³and 44 mg/m³(4.4 µg/L , 15 and 44 resp.) for 6 h/day, 5 days/week and 13 weeks.

Some effects as increased lung weight, increased lymph node weight, lymphoid hyperplasia, mild chronic inflammation in alveolar septa, and pigment deposition could be determined.

A LOAEC for rats was set to 4.4 mg/m³ (4.4 µg/L) for chromium (III) oxide. This concentration is corresponding to 3 mg Cr³ /m³.