Cadmium hydroxide

Repeated dose toxicity: inhalation

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-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:

Early signs of oral and inhalative cadmium uptake in rats

Author:

Prigge E

Year:

1978

Bibliographic source:

Arch. Toxicol. 40:231-247

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

Test material information

Constituent 1

Reference substance name:

Cadmium oxide

EC Number:

215-146-2

EC Name:

Cadmium oxide

Cas Number:

1306-19-0

Molecular formula:

CdO

IUPAC Name:

oxocadmium

Details on test material:

-Name of the test material - CdO

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system 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/m^3)	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).