Cadmium nitrate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Study period:

no information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented but not according to GLP nor to specific test guidelines.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

A comparative study of the effects of inhaled cadmium chloride and cadmium oxide: pulmonary response

Author:

Grose EC, Richards JH, Jaskot RH, Ménache MG, Graham JA and Dauterman WC

Year:

1987

Bibliographic source:

J. Toxicol. Environ. Health 21:219-232

Materials and methods

Principles of method if other than guideline:

The acute inahalation effects of the test material aerosols on the pulmonary biochemistry and histology was studied in the Sprague- Dawley rats. The test material aerosols were exposed to the rats at 0.25, 0.45 and 4.5 mgCd/m3 for 2 h and were observed for 72 h followed by examination of lung biochemical parameters and histology.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Cadmium chloride

EC Number:

233-296-7

EC Name:

Cadmium chloride

Cas Number:

10108-64-2

IUPAC Name:

cadmium dichloride

Details on test material:

- Name of test material : CdCl2

- IMPURITY/ADDITIVE/ETC.: No information

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 65 d

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

other:

Details on inhalation exposure:

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
MMAD (µm): CdCl2
0.50 ± 0.14 (aerosol of 0.25 mg Cd/m3)
0.63 ± 0.14 (aerosol of 0.45 mg Cd/m3)
0.56 ± 0.07 (aerosol of 4.5 mg Cd/m3)

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

2 h

Concentrations:

0.25, 0.45 and 4.5 mgCd/m3

No. of animals per sex per dose:

24

Control animals:

no

Details on study design:

- Duration of observation period following administration: 72 h
- Necropsy of survivors performed: yes

Statistics:

ANOVA and t-test with Bonferroni correction

Results and discussion

Preliminary study:

Not applicable

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

> 4.5 mg/m³ air

Exp. duration:

2 h

Remarks on result:

other: highest dose tested; effects: proliferative pneumonitis; biochemical changes, increased number of alveolar macrophages, decreased lung/body weight at lower conc.

Effect levels 2

Sex:

male

Dose descriptor:

other: LOAEL

Effect level:

0.45 mg/m³ air

Exp. duration:

2 h

Remarks on result:

other: increase in lung weight and lung-to-body weight ratio but no change in body weight, biochemical changes

Effect levels 3

Sex:

male

Dose descriptor:

other: LOAEL

Effect level:

4.5 mg/m³ air

Exp. duration:

2 h

Remarks on result:

other: proliferative pneumonitis

Mortality:

- Number of deaths at each dose level:
Three exposed rats (only one cause of death was determined)

Clinical signs:

other: No information

Body weight:

No information

Gross pathology:

No information

Other findings:

Toxic effects: majority of the effects occurred 72 h after exposure with significant increases in body weight, lung weight, lung-to-body weight ratio, GSH reductase, GSH transferase, and G-6-PDH.

NECROPSY FINDINGS:
0.25 mg Cd/m3: no significant treatment related lesions.
0.45 mg Cd/m3: slight increase in the number of alveolar macrophages at lung examination.
4.5 mg Cd/m3: severe proliferative pneumonitis characterised by hyperplasia of type II pneumocytes and spindle-shaped, fibrocytic-like
cells. At this dose, CdCl2 produced biochemical changes like increased G-6-PDH and GSH-Rd activity

- Potential target organs : only lung is explored

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

other:

Remarks:

Criteria used for interpretation of results: expert judgment

Conclusions:

Both compounds caused multifocal, interstitial pneumonitis but the CdO lesion was more severe. The majority of effects occurred 72 hours after
exposure. Response pattern in the rabbit resembled that of the rat. Based on the parameters used in the study, inhaled CdO appeared to be more
toxic to the lung than CdCl2 in both rat and rabbit, extrapolation of CdCl2 effects to potential CdO effects could be scientifically vulnerable (Grose et al., 1987).

Executive summary:

The acute inahalation effects of the test material aerosols on the pulmonary biochemistry and histology was studied in the Sprague- Dawley rats.

The test material aerosols were exposed to the rats at 0.25, 0.45 and 4.5 mgCd/m3 for 2 h and were observed for 72 h followed by examination of lung biochemical parameters and histology.

Inhalation by the rats at 0.45 mg Cd/m³ did not cause any significant treatment-related histopathological lesions. The test material caused multifocal, interstitial pneumonitis and increase in GSH reductase, GSH transferase, and G-6-PDH activity at 72 h after exposure to 4.5 mg/m³.

Hence, under the conditions of the test, the test material caused multifocal, interstitial pneumonitis and increase in lung biochemical parameters in rats at a concentration of 4.5 mg Cd/m3 exposed for 2 h.