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Toxicological information

Carcinogenicity

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Administrative data

Endpoint:
carcinogenicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not applicable
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 ( exposure time of 18 months).
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:
1989

Materials and methods

Principles of method if other than guideline:
A study was conducted to evaluate the carcinogenic potential of the test material aerosols in rats. Groups of rats were exposed to the aerosols of the test material at 10 and 30 (CdO fume) and 30 and 90 (CdO dust) µg Cd/m3 continuously for a maximum 18 months followed by a treatment-free observation period of 29 - 31 months. Bodyweight, clinical signs, hematological and clinical chemistry examinations were performed throughout the study. Cadmium contents of lung, liver and kidneys were determined along with the histopathology of the lungs.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
CdO (cadmium oxide) fume was generated with an electric arc aerosol generator, with Cd electrodes quickly forming primary CdO
particles ; particle size: 0.01µm
CdO (cadmium oxide) dust was generated by atomization of acetate solutions of the metals and subsequent pyrolysis inside of tube furnaces at
750°C; particle size: 0.2-0.5 µm (MMAD)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann GmbH & Co, Borchen, FRG
- Housing: stainless steel iwre mesh cages
- Diet: ssniff R standard diet (60ppm Zn) during night
- Water: ad libitum
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12


Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure (if applicable):
not specified
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
max 18 months
Frequency of treatment:
22 hours/day x 7 days/week; 40 hours/week x 6 months
Post exposure period:
29-31 months
Doses / concentrations
Remarks:
Doses / Concentrations:
CdO fumes: 10 and 30 µg Cd/m3; CdO dust: 30 and 90 µg Cd/m³
Basis:
nominal conc.
No. of animals per sex per dose:
CdO fumes: 40 males 10 µg/m3 , 40 males 30 µg/m3
CdO dust: 5 x (20 males + 20 females) + 1 group of 40 males
N1=N2=N5: 30 µg Cd/m³ and N2: zinc reduced diet N5: + 300 µg Zn/m³ (ZnO) - N3=N4=N6: 90 µg/m³ and N6: + 900 µg Zn/m³  (ZnO) - N1=N2=N5=N6 : 22 hours a day x 7 days/ week x 18 months - N3: 22 hours / day x 7 days/week x 7 months (males) or 11 months (females) - N4: 40 hours/week x 6 months 

+ 1 control group: 20 males + 20 females
Control animals:
yes
Details on study design:
Post-exposure period: 29-31 months

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: No
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: No
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No

Statistics:
No statistics reported

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
not examined
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:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
effects observed, treatment-related
Relevance of carcinogenic effects / potential:
The study is actualized in Glaser et al., 1990
Studies in rats provide strong evidence of the lung carcinogenic potential of chronically inhaled cadmium.
relevant study, dose response included

Effect levels

open allclose all
Dose descriptor:
LOAEL
Remarks:
CdO dust
Effect level:
0.03 mg/m³ air
Sex:
male/female
Basis for effect level:
other: lung bronchioalveolar adenomas, adenocarcinomas, and squamous cell carcinomas
Remarks on result:
other: Effect type: carcinogenicity (migrated information)
Dose descriptor:
LOAEL
Remarks:
CdO fume
Effect level:
0.03 mg/m³ air
Sex:
male
Basis for effect level:
other: lung bronchioalveolar adenomas, adenocarcinomas, and squamous cell carcinomas
Remarks on result:
other: Effect type: carcinogenicity (migrated information)

Any other information on results incl. tables

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL: 
CdO dust:

Tumours: Lung,  remote tumours: not detailed, antagonism ZnO/CdO lung
tumours, at low CdO. 

Lower tumour rate related to shorter exposure

CdO fumes:

No remote tumours. Unexplained lower tumour rate with CdO fume than following CdO dust. No significant excess of lung malignancies

Applicant's summary and conclusion

Conclusions:
Oldiges et al. (1989) reported a clear dose response increase in lung tumors in male and female rats from an 18-month continuous exposure to cadmium oxide dusts and fume. Increased lung tumors in males and females were observed with chronic exposures to cadmium oxide dust or fume at 30 μg/m3.
Executive summary:

Oldiges et al. (1989) reported a clear dose response increase in lung tumors in male and female rats from an 18-month continuous exposure to cadmium oxide dusts and fume. Increased lung tumors in males and females were observed with chronic exposures to cadmium oxide dust or fume at 30 μg/m3.