Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-11-19 to 2013-03-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to OECD Guidelines for Testing of Chemicals No.436 Acute Inhalation Toxicity Acute Toxic Class Method.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
[μ-[carbonato(2-)-O:O']]dihydroxydioxodizirconium
EC Number:
260-633-5
EC Name:
[μ-[carbonato(2-)-O:O']]dihydroxydioxodizirconium
Cas Number:
57219-64-4
Molecular formula:
CH2O7Zr2
IUPAC Name:
[μ-[carbonato(2-)-O:O']]dihydroxydioxodizirconium
Test material form:
aerosol dispenser: not specified
Remarks:
migrated information: aerosol
Details on test material:
- Name of test material (as cited in study report): zirconium basic carbonate (ZBC)
- Physical state: white solid
- Storage condition of test material: refrigerated (2 to 8 degrees C) and protected from light
- Analytical purity: > 99.8%
- Composition: 53.37% of anhydrous zirconium basic carbonate
- Lot/batch No.: 12/017/548
- Expiration date of the lot/batch: 2013-07-23

Test animals

Species:
rat
Strain:
other: Crl:CD (SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd.
- Age at study initiation: 62 to 69 days
- Weight at study initiation: 343 to 357 grams for males and 239 to 258 grams for females
- Housing: Animals were housed inside a restricted entry rodent facility designed and operated to minimise the entry of external biological and chemical agents. The animals were housed four per sex per cage during the acclimatization period and three per sex per cage from the day of exposure in cages made of a polycarbonate with stainless steel mesh lids. Autoclaved wood shavings were used as bedding.
- Diet (e.g. ad libitum): While housed animals were allowed free access to to a standard rodent diet. This diet contained no added antibiotic or other chemotherapeutic or prophylactic agents.
- Water (e.g. ad libitum): Potable water taken from the public supply was freely available.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The temperature was maintained between of 19 to 23 degrees with no significant deviations.
- Humidity (%): The relative humidity was maintained between 40 to 70% with no significant deviations.
- Air changes: Each animal room was supplied with not re-circulated filtered fresh air.
- Photoperiod (hrs dark / hrs light): 12 hours continuous artificial lighting and 12 hours continuous dark per 24 hours

IN-LIFE DATES: From: 22-November-2012 To: 12-December-2012

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: ADG snout-only inhalation exposure chamber
- Exposure chamber volume: Approximately 30 litres
- Method of holding animals in test chamber: Restraining tubes
- Source and rate of air: Filtered and dried compressed air. The compressed air flow rate exiting the dust generator mechanism was initially 25 litres/minute; the extract airflow was set at 26 litres/minute. These airflows were reduced to 23 litres/minute and 24 litres/minute respectively.
- Method of conditioning air: Filtered and dried
- System of generating particulates/aerosols: Wright dust feed designed to produce and maintain atmospheres containing dust by suspending material scraped from the surface of a compressed powder in a stream of dry air.
- Method of particle size determination: Air was drawn through a Marple Model 298 Personal Cascade Impactor using a pump. The stainless steel collection substrates from stages 1 to 8 and the glass microfiber terminal filter were weighed before and after sampling and the mass median aerodynamic diameter and the geometric standard deviation of the powder aerosol were calculated.
- Treatment of exhaust air: Filtration system to remove particulate matter.
- Temperature, humidity, pressure in air chamber: 20.5 -20.7 degrees C 26.9 - 35.6%

TEST ATMOSPHERE
- Brief description of analytical method used: Air was drawn from an unused exposure port through a glass microfibre filter. Eight samples were collected during the exposure. The filters were weighed before and after sampling. The weight collected and the volume of air sampled were used to calculate the aerosol concentration.
- Samples taken from breathing zone: yes
- Particle size distribution: 3.9-4.0 micrometers
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD= 4.0 micrometers GSD 2.76

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
240 min
Concentrations:
Mean achieved aerosol concentration 4.74 mg/L (4.36- 4.99mg/L). The achieved aerosol concentrations values were close to the target of 5 mg/L (limit test).
No. of animals per sex per dose:
Three animals per sex.
Control animals:
other: historical control data
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animal were weighted once during the acclimatization period, prior to dosing on day 1, days 2, 4, 8 and 15. Clinical signs were recorded immediately prior to the start of the exposure, approximately every hour during exposure, immediately following exposure and then 1 hour and 2 hours post-exposure, additional signs were recorded as necessary.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, mortality, body weight, and macropathology
Statistics:
The computer systems with version numbers that were used on this study to acquire and quantify data include:
Xybion Pristima (version 6.3) used for Pharmacy test substance management.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.74 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
240 min
Mortality:
no unscheduled deaths
Clinical signs:
other: Wet fur was evident in all animals immediately after the exposure and persisted in one female until 1 hour post dose. Noisy breathing in one of three males and one of three females, red staining to the snout and jaw in one of three males and one of three
Body weight:
Following exposure slight bodyweight losses were evident in one male and all females Growth was observed at the next weighing occasion on day 4 and continued for the remainder of the observation period.
Gross pathology:
Macroscopic examination revealed no findings of note. The nature and incidence of all findings were consistent with the commonly seen background of macroscopic changes.

Any other information on results incl. tables

Chamber atmosphere conditions - summary data

 Group  Target aerosol concentration (mg/L)  Mean achieved aerosol concentration (mg/L) Particle size MMAD (µm)  Particle size (δ g)
 1  5  4.74  4.0  2.76

The mean achieved aerosol concentration was close to target; in addition the MMAD was within the ideal range of 1 to 4 microns.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The 4-hour LC50 of zirconium basic carbonate is greater than 4.74 mg/L for male and female rats, based on test material as supplied (53.37% of anhydrous zirconium basic carbonate).
Although this LC50 is lower than the classification cut-off value of 5 mg/L (dust aerosol) for harmful classification (DSD) or category 4 classification (CLP), further testing would not be considered feasible as the maximum obtainable mean concentration for exposure was 4.74 mg/L and no mortality occurred at this concentration. Classification for acute inhalation toxicity is therefore deemed unnecessary.
Therefore, under the test conditions, zirconium basic carbonate is unclassified according to DSD and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.