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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
No information
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Reliable without restriction. Well documented and scientifically acceptable although not according to GLP nor according to testing guidelines.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Bioavailability indicators of inhaled cadmium compounds
Author:
Glaser U, Klöppel H and Hochrainer D
Year:
1986
Bibliographic source:
Ecotoxicol. Environ. Saf. 11(3):261-271

Materials and methods

Objective of study:
absorption
toxicokinetics
Principles of method if other than guideline:
A 30-d inhalation study was conducted to evaluate the accuracy of several methods indicating the pulmonary bioavailability of inhaled cadmium. During the study, male Wistar rats were continuously exposed to submicron aerosols of CdCl2, CdO (0.1 mg/m3) and CdS (1 mg/m3).
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): CdO
- Analytical purity: highest commercially available purity
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 6-7 wk

Administration / exposure

Route of administration:
inhalation: aerosol
Vehicle:
unchanged (no vehicle)
Details on exposure:
none
Duration and frequency of treatment / exposure:
22 h/d; 7 d/wk, 30 d
Doses / concentrations
Remarks:
Doses / Concentrations:
Males: control; treatment: 0.1 mg/m3 CdO
No. of animals per sex per dose:
Males: 12
Females: 0
Control animals:
yes
Positive control:
None
Details on study design:
none
Details on dosing and sampling:
PHARMACOKINETIC STUDY
- Tissues and body fluids sampled: lung and serum
Statistics:
Student's t-test

Results and discussion

Preliminary studies:
None

Toxicokinetic / pharmacokinetic studies

Details on absorption:
cfr remarks on results
Details on distribution in tissues:
No information
Details on excretion:
No information

Metabolite characterisation studies

Metabolites identified:
not specified
Details on metabolites:
Not applicable

Any other information on results incl. tables

Sex

Dose/Conc

Compound

Number of animals

M

M

M

M

0.1 mg/m3

0.1 mg/m3

1.0 mg/m3

-

Cadmium oxide

Cadmium chloride

Cadmium sulphide

air

12

12

12

12

six animals of each group were sacrificed after 30 d, the remaining six were killed after an additional 2-month period in which they were exposed to fresh air.

* body weight: mean body weight of all experimental animals did not differ from that of controls

* clinical observations:

- No death occurred.

- No effect of exposure on RBC (red blood cell) counts. Mean white blood cell counts were elevated at the end of the inhalation period for all exposed rats but recovered after the 2-month observation period.

- GPT in serum activity was elevated only for the CdO exposed rats. Mean urinary cadmium content showed a slight but statistically significant increase for the cadmium sulphide and cadmium oxide groups at the end of the observation period.

* Broncho-alveolar lavage:

- elevation of the mean alveolar macrophage cell count at the end of exposure for the three exposed groups. Size of these cells had increased and there was an increased abundance of leukocytes and of macrophages with more than a nucleus.

- cadmium exposure had a cytotoxic effect [protein content, activities of LDH and (-) glucuronidase in lavage fluid]. CdO and CdS resulted in greater effects than cadmium chloride. After the 2 months post-exposure period, most of these values were not significantly different from controls.

* Cadmium body burden:

Cadmium chloride exposure resulted in a low cadmium body burden. The liver and kidney burden of the CdO and CdS groups were comparatively much higher at the end of the inhalation as well as after the post-exposure observation period.

* Cadmium retention in the lung:

Total cadmium (wet digested homogenates): lung cadmium retention were two times lower for the CdCl2 exposed rats, than for the CdO group. Subcellullar compartmental cadmium retention in the lung: For both the cadmium chloride and cadmium oxide exposed rats most of the lung cadmium was distributed to the cytosolic compartment. CdS exposure resulted in increased accumulation in lung compartments which could not be determined by this method (extracellular, intracellular, nuclear and other fractions). In the CdO and CdS exposed rats lung cytosolic cadmium were about two times higher than in the cadmium chloride treated animals. At the end of the post-exposure period, 70% of the cytosolic cadmium was measured to be bound to metallothionein (for the CdO and the CdCl2 groups). Both total and cytosolic cadmium were cleared from the lungs similarly in all groups at the rate of 53 to 60% during the 2 month- period after inhalation.

* Metallothionein (MT) contents in the lung:

Compared to controls inhalation of cadmium chloride resulted in a three times higher MT both at the end of the inhalation and of the post-exposure period. MT induction in the lungs of the CdO and CdS exposed rats had increased five times compared to controls.



Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
Under the test conditions, it was observed in male Wistar rats that inhaled CdO is more available to lung tissue than the very soluble CdCl2, and CdO has an availability 10 times as much as CdS.
Executive summary:

In a thirty-day inhalation study, male Wistar rats were continuously exposed to submicron aerosols of CdCl2 (0.1 mg/m3), CdO (0.1 mg/m3) and CdS (1 mg/m3).

For CdCl2 and CdO, most of the cadmium was found in the lung cytosolic compartment, but for CdS only 30% of the cadmium was retrieved from the lung cytosols. This was observed both at the end of the inhalation and also after an additional 2-month period in fresh air. After 1 month of Cd inhalation and also after the observation period, the lung cadmium retention was twice lower for the CdCl2 exposed rats than for the CdO group. The cadmium content of the lung homogenates, cytosols, and the lung cytosolic metallothionein were found to be twice as much in case of exposure to CdO than in case of exposure to CdCl2. For exposure to CdS at cadmium concentrations 10 times higher the same cadmium levels were found as for CdO. These results were confirmed by results from alveolar lavage analysis indicating that inhaled CdO is more available to lung tissue than the very soluble CdCl2, and CdO has an availability 10 times as much as CdS. In comparison to the controls, the mean urinary cadmium content showed a slight but statistically significant increase for the CdS group at the end of the inhalation period as well as in the CdO group at the end of the observation period. It should be noted that the CdS data have been questioned due to probable oxidation to the sulfate as a function of the aerosol generating system used.

Under the test conditions, it was observed in male Wistar rats that inhaled CdO is more available to lung tissue than the very soluble CdCl2, and CdO has an availability 10 times higher than CdS.