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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Reliable with restriction. Not according to GLP Method not in compliance with ER 67/548/EEC, Annex V and OECD test guidelines.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1978

Materials and methods

Principles of method if other than guideline:
A repeated dose inhalation exposure study was conducted in female Wistar rats to determine the effects of the test material on lungs. Female Wistar rats were exposed to concentrations of 25, 50 and 100 μg Cd/m³ (as cadmium oxide), continuous for 90 d in the 25 and 50 μg Cd/m3 groups, and for 63 d in the last group.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
-Name of the test material - CdO

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS

- Weight at study initiation: 170-190 g

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
not specified
Vehicle:
other: unchanged (no vehicle)
Remarks on MMAD:
MMAD / GSD: MMAD: 0.19 µm
Details on inhalation exposure:
Median aerodynamic diameter of the test material particle: 0.19 µm
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
No information
Duration of treatment / exposure:
90 d at 25 and 50 µg Cd/m3; 63 d at 100 µg Cd/m3
Frequency of treatment:
24 hr/d
Doses / concentrations
Remarks:
Doses / Concentrations:
25, 50, 100 µg/ Cd/m3
Basis:
nominal conc.
No. of animals per sex per dose:
12
Control animals:
yes
Details on study design:
Post-exposure period: 63-90 d
Positive control:
No information

Examinations

Observations and examinations performed and frequency:
Clinical observations performed and frequency: no information
Sacrifice and pathology:
Autopsy: microscopic and macroscopic examination: lungs, liver, kidneys (for six rats in each group)
Other examinations:
no
Statistics:
one way analysis of variance, followed by multiple test for differences of means according to Scheffé; Student's t-test

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
not examined
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
not specified
Details on results:
CLINICAL SIGNS AND MORTALITY: 5/12 animals exposed to 100 µg/m3 died between Days 45 and 60

BODY WEIGHT AND WEIGHT GAIN: there were significant dose dependent reductions of body weight gain after inhalative cadmium uptake in the two
higher dosage groups

FOOD CONSUMPTION: no information

FOOD EFFICIENCY: no information

WATER CONSUMPTION: no information

OPHTHALMOSCOPIC EXAMINATION: no information

HAEMATOLOGY: inhalation of cadmium oxide evoked a significant dose dependent increase of hemoglobin and hematocrit

CLINICAL CHEMISTRY: no influence of cadmium oxide on alkaline phosphatase activity (in serum) and on iron concentration (serum). There was a significant decrease of blood pH and pO2 and a significant increase of PCO2 in the high exposure group. 

URINALYSIS: no information

NEUROBEHAVIOUR: no information

ORGAN WEIGHTS: there was a significant increase of lung weight in dependence of the aerosol concentration. No significant change in liver weight

GROSS PATHOLOGY: no information




Effect levels

Dose descriptor:
LOAEL
Effect level:
25 other: µg/m3
Sex:
female
Basis for effect level:
other: cell proliferations of the bronchi, bronchioli and alveoli, indicating hyperplasia of the lungs; histiocytic cell granulomas

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Histopathology incidence and severity


Cd (µg/m3)

Animal Number

Lung Prolife-rations

Emphy-semas

Histio-cytic cell granu-lomas

Xanth-oma cells

Atelec-tasis

Lympho-cytic infiltrates

Hyper-aemic areas

0

1

2

3

4

5

6

 

(+)

 

 

(+)

(+)

++

+

+

+

(+)

(+)

 

 

 

 

(+)

 

+

+

+

+

+

+

+

+

+

+

+

 

25

1

2

3

4

5

6

++

+

+++

++

+++

+++

+

+

++

+

++

++

+

+

+

+

 

+

+

++

+++

+

++

++

+

+

+

+

 

+

+

+

 

+

+++

+

 

 

+

 

+

50

1

2

3

4

5

6

++

++

++

+++

+++

++

+

+++

+

+++

+

+

++

 

++

++

+

 

++

++

+

 

++

+

+

+

+

+

+

+

+

+

+

+

 

 

 

+

++

+++

 

Liver

Kidney

 

Lympho-cytic infiltrates

Hyper-aemic areas

Swollen tubulus

Hype-raemic areas

 

+

+

(+)

(+)

+

+

 

+

+

+

+

+

+

+

+

+

(+)

(+)

+

(+)

+

+

+

(+)

Applicant's summary and conclusion

Conclusions:
A marked increase of lung weight was found together with no signs of oedema. Histologically, there were cell proliferations of the bronchi, bronchioli and alveoli in all exposed animals, indicating hyperplasia of the lungs. Additionally, histiocytic cell granulomas occurred and emphysematic areas
were detected. There was an impairment of gas exchange in the high exposed group. Pulmonary changes did preceed the renal damage (assessed by protein and alkaline phosphatase excretion, histological examination of the kidneys)
Executive summary:

A repeated dose inhalation exposure study was conducted in female Wistar rats to determine the effects of the test material on lungs.

Female Wistar rats were exposed to concentrations of 25, 50 and 100 μg Cd/m³ (as cadmium oxide), continuous for 90 d in the 25 and 50 μg Cd/m3 groups, and for 63 d in the last group (MMAD: 0.19 μm, standard deviation: 1.5).

No clinical signs were reported. A marked increase of lung weight was found together with no signs of oedema. Histologically, there were cell proliferations of the bronchi, bronchioli and alveoli in all exposed animals, indicating hyperplasia of the lungs. Additionally, histiocytic cell granulomas occurred and emphysematic areas were detected. There was an impairment of gas exchange in the high exposed group. Pulmonary changes did preceed the renal damage (assessed by protein and alkaline phosphatase excretion, histological examination of the kidneys).