Zirconium tetrachloride

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The ZrCl4 upon dissolving in water was converted to hydrate forms of zirconium and HCl. So during the experiment, the degradation products of ZrCl4 were inhaled but not ZrCl4. We can assume that the symptoms that were observed following exposure are associated to degradation products, in particular HCl.

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

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

Deviations:

yes

Remarks:

(see rationale for reliability)

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Zirconium tetrachloride

EC Number:

233-058-2

EC Name:

Zirconium tetrachloride

Cas Number:

10026-11-6

Molecular formula:

Cl4Zr

IUPAC Name:

zirconium tetrachloride

Details on test material:

- Name of test material (as cited in study report): Zirconium tetrachloride
- Physical state: mist
- Impurities (identity and concentrations): Al (0.005%), Ba (trace), Ca (0.008%), Cu (trace), Fe (0.004%), Mg (0.006%), Si (0.01%), Ti (0.001%).

Test animals

Species:

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

Strain:

not specified

Sex:

not specified

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: no data

Remarks on MMAD:

MMAD / GSD: MMAD: 0.57 µm

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- The ZrCl4 was aspirated as a solution and it was dissolved in water to give a specific gravity of 1.020 (43.5g/L) at 20°C
- Exposure apparatus: copper-lined chamber constructed of wood with observation windows on three sides, 6 x 8 x 6 ft high and volume of 288 cubic feet.
- Method of conditioning air: A centrally located duct in the ceiling of the chamber served as the inlet for the test substance. 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.
- Temperature, humidity, pressure in air chamber: 74 +/- 3 degrees F; 47% +/- 6%; few hundredths of an inch of water less than atmospheric pressure.
- Air flow rate: 140 cfm or one change every two minutes.
- Method of particle size determination: test substance was twice ground in a Mikropulverizer to a mean bulk particle size.
- Treatment of exhaust air: not recycled

TEST ATMOSPHERE
- Brief description of analytical method used: Hourly samples were taken with a filter paper sampler and weighed on an analytical balance, spectrographic analysis of each day's accumulation of filter paper samples was used to verify the weight-samples and to make such slight adjustments in concentration results as might occasionally arise from varying amounts of nuisance dust.
- Samples taken from breathing zone: yes, hourly

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Hourly samples were taken with a filter paper sampler and weighed on an analytical balance, spectrographic analysis of each day's accumulation of filter paper samples was used to verify the weight-samples and to make such slight adjustments in concentration results as might occasionally arise from varying amounts of nuisance dust.

Duration of treatment / exposure:

60 days

Frequency of treatment:

6hours/day, 5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
14.9mg ZrCl4/m3
Basis:
no data

No. of animals per sex per dose:

Cat: 4
Dog: 8
Guinea Pig: 20
Rabbit: 20
Rat: 72

Control animals:

other: yes, only control rabbits and rats were used

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data

MORTALITY: Yes

BODY WEIGHT: Yes
- Time schedule for examinations: No data

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: weekly
- Animals fasted: No data
- How many animals: 3 dogs
- Parameters: Red blood cell and differential white cell counts, as well as determinations of hemoglobin, mean corpuscular cell volume and clotting time

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: semi-monthly
- Animals fasted: No data
- How many animals: 4 dogs and 4 rabbits
- Parameters: Blood nonprotein nitrogen

URINALYSIS: Yes
- Time schedule for collection of blood: semi-monthly
- Animals fasted: No data
- How many animals: 4 dogs and 4 rabbits
- Parameters: urinary protein

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

HISTOPATHOLOGY: Yes, lung, kidney, liver. Other tissues were evaluated, but a complete list of other tissues was not provided.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

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:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY: Eight rats and three guinea pigs died during exposure to the test substances; however, this matched the control group. The cause of death was not well established by appeared to be an intercurrent respiratory infection. No death during the first week, a few during the second and the third, with 55 % of the total during the fourth week

BODY WEIGHT AND WEIGHT GAIN: Throughout the exposure periods, there was no pronounced effect on growth except loss of weight of animals a few days before death.

HAEMATOLOGY: All dogs showed a decrease in the amount of hemoglobin in the blood following the start of exposure; a minimum was reached after approximately 4 weeks. Depressions in red cell counts were not as uniform as those in hemoglobin content. The lowest depression occurred in the period of approximately 5 to 7 weeks after start of exposure but was not uniform for all 3 animals. No other hematological changes of any significance were found.

CLINICAL CHEMISTRY: No significant blood changes were found among the criteria studied. Blood fibrinogen levels also remained constant during exposure of animals to the test substance.

URINALYSIS: No significant urine changes were found among the criteria studied.
 
HISTOPATHOLOGY- NON-NEOPLASTIC: There are no reported histological changes that could be attributed to the test substance. The abnormalities that were reported were similar for all species regardless of dose, duration of exposure or test substance inhaled.

Effect levels

Dose descriptor:

NOAEC

Effect level:

> 14.9 mg/m³ air

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: Increased mortality in rats and guinea pigs was reported

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

This study resulted in increased mortality in rats and guinea pigs and a decrease "of borderline significance" in blood hemoglobin and red blood cell levels in dogs. But ZrCl4 was administered via the drinking water and ZrCl4 decomposed into ZrOCl2 and HCl. So during the experiment, the degradation products of ZrCl4 are inhaled but not ZrCl4. This study is therefore judged not relevant for ZrCl4.