Magnesium zirconium oxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

no data

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Insufficient information provided on methods or results to accurately evaluate the study. Only lung and pulmonary lymph node tissue concentrations of zirconium were examined.

Data source

Reference

Reference Type:

publication

Title:

Inhalation Toxicity of Zirconium Compounds: Short-Term Studies

Author:

Spiegl, C.J., Calkins, M.C., DeVoldre, J.J., Scott, J.K.

Year:

1956

Bibliographic source:

Atomic Energy Commission Project, Rep. No. UR-460, University of Rochester, Rochester, NY, pages 1-26

Materials and methods

Objective of study:

other: study of the toxicity of zirconium compounds after repeated exposure via inhalation

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Repeated dose toxicity study in which, next to toxicity, as well tissue concentrations of zirconium were examined in lung and pulmonary lymph node tissue following inhalation exposure to zirconium dioxide for 30 or 60 days.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Zirconium dioxide

EC Number:

215-227-2

EC Name:

Zirconium dioxide

Cas Number:

1314-23-4

Molecular formula:

O2Zr

IUPAC Name:

dioxozirconium

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): zirconium dioxide
- Physical state: dust, particle size 1.5 µm.
- Analytical purity: > 90%
- Impurities (identity and concentrations):
For the 60-day experiment: Al (.001%), B (.00002%), Ba (.0002%), Ca (.002%), Cr (.0001%), Cu (.0025%), Fe (.0025%), Mg (.0001%), Ni (.0003%), Pb (.0225%), Si (.001%), Ti (.006%), V (.0004%)
For the 30-day experiment: Al (0.026%), B (trace), Ba (0.062%), Ca (0.071%), Cr (trace), Cu (0.008%), Fe (0.049%), Mg (0.16%), Si (< 0.47%), Ti (0.18%)

Radiolabelling:

no

Test animals

Species:

other: cat, dog, guinea pig, rabbit, rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

ENVIRONMENTAL CONDITIONS
- Temperature: 22 - 24 deg C
- Humidity (%): 47 +/- 6

Administration / exposure

Route of administration:

inhalation: dust

Vehicle:

unchanged (no vehicle)

Details on exposure:

TYPE OF INHALATION EXPOSURE: whole body


GENERATION OF TEST ATMOSPHERE / CHAMPER DESCRIPTION
- Exposure apparatus: Copper-lined chamber 6 x 8 x 6 ft high volume 288 cubic ft.
- Source and rate of air: test substance was ground twice in a Mikropulverizer to a mean bulk particle size of 1.5 u and fed into the inlet air stream by a Wright dust feed.
- Method of conditioning air: A centrally located duct in the ceiling of the chamber served as the inlet for exposure. Baffles below the inlet and two fans near the ceiling dispersed the test substance and distributed the test substance uniformly throughout the chamber. In the four bottom corners were outlets connected to an exhaust system. Air turnover during exposure was approximately 140 cfm, or one change every two minutes with no recycling.
- System of generating particulates/aerosols: Wright dust feed



TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 30-day exposure: 1.5 microns; 60-day exposure: 1.6 microns

Duration and frequency of treatment / exposure:

6 hours/ day, 5 days/week
Method 1: 30 Days,
Method 2: 60 Days

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

100.8 mg/m³ air

Remarks:

Method 1 (eq. to 75 mg Zr/m3)

Doses / concentrations 2

Dose / conc.:

15.4 mg/m³ air

Remarks:

Method 2 (eq. to 11 mg Zr/m3)

No. of animals per sex per dose / concentration:

30-day exposure
2 dogs
10 rats
6 rabbits
60-day exposure
4 dogs
4 cats
10 rats
10 rabbits
18 guinea pigs

Control animals:

no

Positive control reference chemical:

no data

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

The values reported below are not the result of distribution in tissue but pattern of deposition after inhalation of 30 or 60 days.

75 mg/m3 dose - 30 days exposure
Mean Zr concentration
rats: 220 µg/g in the lung and 21 µg/g in the pulmonary lymph node
dogs: 129 µg/g in the lung and 362 µg/g in the pulmonary lymph node
rabbits: 24 µg/g in the lung

11 mg/m3 dose - 60 days exposure
Mean Zr concentration
rats: 158 µg/g in the lung and 17 µg/g in the pulmonary lymph node
dogs: 73 µg/g in the lung and 731 µg/g in the pulmonary lymph node
rabbits: 16 µg/g in the lung
cats: 20 µg/g in the lung
guinea pigs: 71 µg/g in the lung

Metabolite characterisation studies

Metabolites identified:

not measured

Applicant's summary and conclusion

Conclusions:

The deposition of zirconium dioxide in the lung is typical of insoluble material. The concentration indicated in the lymph nodes appears to be more related to dissemination due to overload than true distribution.