Leach residues, zinc ore-calcine, zinc cobalt

Carcinogenicity

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-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:

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

Test material information

Constituent 1

Reference substance name:

Cadmium oxide

EC Number:

215-146-2

EC Name:

Cadmium oxide

Cas Number:

1306-19-0

IUPAC Name:

oxocadmium

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 or test system 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

1

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)

2

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.