Calcium zirconium oxide

Endpoint summary

Description of key information

1. Information on zirconium dioxide
Acute toxicity: oral
The LD50-value for acute oral toxicity was determined via the acute toxic class method in female Sprague-Dawley rats and was > 5000 mg/kg bw.
Acute toxicity: inhalation
The LC50 was determined in an acute inhalation toxicity study according to the acute toxic class method and was determined to be higher than 4.3 mg/L in male and female Crl:CD(SD) albino rats via nose-only inhalation exposure to dust aerosol of zirconium dioxide.
Acute dermal
No available data
2. Information on calcium oxide
Acute toxicity: oral
The LD50-value for acute oral toxicity determined via the up-and-down procedure in Wistar rats was > 2000 mg/kg bw.
Acute inhalation
No available data
Acute dermal
No available data
3. Conclusion on calcium zirconium oxide 
Acute toxicity: oral
It is expected that the substance will have a similar hazard profile as the individual substances zirconium dioxide and calcium oxide. Based on reliable data available for the individual substances zirconium dioxide and calcium oxide, calcium zirconium oxide is not expected to cause any adverse acute toxic effects after oral intake up to a dose of 2000 mg/kg bw. Based on this information, calcium zirconium oxide does not need to be classified for acute oral toxicity.
Acute toxicity: inhalation
Because for acute oral toxicity, the individual components calcium oxide and zirconium dioxide were found to be equally non-hazardous, read across from the most abundant component in the crystal lattice, i.e. zirconium dioxide, is performed to cover the endpoint of acute inhalation toxicity, with the LC50 being > 4.3 mg/L air (no adverse effects observed). 
Acute toxicity: dermal
No reliable data were available for acute toxicity via the dermal route of exposure, however, no acute toxicity after dermal exposure is to be expected based on the absence of acute toxicity after oral exposure up to and including at the limit test dose of 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2008-01-16 to 2008-04-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

However, 6 animals were dosed at once rather than dosing in steps with 3 animals per step.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Certificate provided by Groupe Interministeriel Des Produits Chimiques

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle, France)
- Age at study initiation: 8 weeks old
- Weight at study initiation: between 188 g and 207 g
- Fasting period before study: 1 day
- Housing: Three healthy female rats were kept in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet: foodstuff provided ad libitum; food was removed at D-1 and then redistributed 4 hours after the test item administration.
- Water: tap-water from public distribution system provided ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 22 degree C
- Humidity (%): 39 and 55%
- Air changes (per hr): not applicable
- Photoperiod (hrs dark / hrs light): 12 hours daily

IN-LIFE DATES: From: 2008-02-05 To: 2008-02-20

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: no data

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

DOSAGE PREPARATION (if unusual): The animals of the treated group received an effective dose of 2000 mg/kg body weight of the test item, diluted in distilled water and administered by gavage under a volume of 10 mL/kg body weight using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 female rats

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed on D0 (just before administering the test item), then on D2, D7, and D14.
Weight changes were calculated and recorded.
- Necropsy of survivors performed: yes; Only those organs likely to be modified in cases of acute toxicity were examined. Those presenting macroscopic anomalies can be removed and preserved in view of microscopic examinations.
- Other examinations performed: Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions 14 days after administration of the test item.
Observations and a mortality report were then carried out every day for 14 days.

Statistics:

no data

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No clinical signs related to the administration of the test substance were observed.

Gross pathology:

The macroscopic examination of the animals at the end of the study did not reveal treatment-related changes.

Other findings:

no data

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of CC10 Zirconium Oxide is higher than 5000 mg/kg body weight by oral route in the rat.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2007-03-22 to 2007-04-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

version adopted 2006-03-23

Deviations:

yes

Remarks:

minor deviations

GLP compliance:

yes (incl. QA statement)

Remarks:

signed November 2005

Test type:

up-and-down procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Füllinsdorf/Switzerland
- Age at study initiation: 11 weeks
- Weight at study initiation: 179.9 to 192.3 g
- Fasting period before study: Approximately 16 to 19 hours; Food was provided again approximately 3 hours after dosing
- Housing: Individually in Makrolon type-3 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz) during treatment and observations
- Diet (ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 80/06 or 89/06 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland)
- Water (ad libitum): Community tap water from Füllinsdorf
- Acclimation period: Seven days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 3°C
- Humidity: 30-70 %
- Air changes: 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated.

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE: Polyethylene glycol 300 (PEG 300)
- Description: Colourless viscous liquid
- Source: FLUKA Chemie GmbH, CH-9471 Buchs
- Stability of vehicle: Stable under storage conditions
- Expiration date: October 2007
- Storage conditions: At room temperature (range of 20 +/- 5°C), light protected
- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. Polyethylene glycol 300 was the most suitable vehicle selected for the test item.
- Lot no.: 1300225
- Concentration in vehicle: 0.2 g/mL

MAXIMUM DOSE VOLUME APPLIED: The application volume was 10 mL/kg body weight.

DOSAGE PREPARATION:
The dose formulations were made shortly (i.e. less than 30 minutes) before each dosing occasion using a magnetic stirrer and a spatula. The test item was weighed into tared glass beakers on a suitable precision balance and the vehicle added (weight:volume). The pH of the freshly prepared dose formulations was mesaured at each occasion following preparation and was found to be between pH 6-7 for the test item. Temperature of the freshly prepared dose formulations were generally between 20-23 °C. Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer. The stability of the test item in the vehicle was not determined in this test. This is not considerd to be required because of the short period between dose preparation and administration to the animals.
No further information on oral exposure was stated.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 female rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations of mortality/viability were made daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on the day of dosing (test day 1; with the clinical signs) and twice daily during days 2-15. Observations of body weights were made on the day prior to the administration of the test item, on the day of administration of the test item (prior to administration of the test item), and on days 8 and 15. Observations on clinical signs were made daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after the administration on test day 1. Once daily during days 2-15.
- Necropsy of survivors performed: Yes
All animals were killed by carbon dioxide asphyxiation and discarded after macroscopic examinations have been performed.
- Other examinations performed: For clinical signs all abnormalities were recorded.
No further information on the study design was stated.

Statistics:

No statistical analysis was performed.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No deaths occurred during the study.

Clinical signs:

other: Slightly ruffled fur was noted at the reading performed within 30 minutes or 1 hour after administration up to the 5-hour observation, day 2, 3 or 6 in all animals. Hunched posture was observed at the 30-minutes reading up to the 3- or 5-hour reading or u

Gross pathology:

No macroscopic findings were observed at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose for the test item Precal 30S (Calcium oxide (burnt lime)) after single oral administration to female rats, observed over a period of 14 days is: LD50 (rat): greater than 2000 mg/kg body weight.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27 April 2010 - 31 May 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

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 Laboratories, Raleigh, NC; animals were received on 20 April 2010
- Age at study initiation: approximately 11 weeks
- Weight at study initiation: body weight values ranged from 316 g to 357 g for males and from 220 g to 238 g for females. Individual body weights at assignment were within ± 20% of the mean for each sex.
- Fasting period before study: during acclimation to restraint and during the exposure period
- Housing: Upon arrival, all animals were housed in individual suspended wire-mesh cages. The animals were maintained by the WIL Animal Husbandry staff in accordance with WIL standard operating procedures (SOPs). On the day of exposure, the animals were placed in nose-only exposure holding tubes in the animal room, transported to the exposure room, exposed for the requisite duration and then returned to their home cages.
- Diet (e.g. ad libitum): The basal diet used in this study, PMI Nutrition International, LLC, Certified Rodent LabDiet 5002, is a certified feed with appropriate analyses performed by the manufacturer and provided to WIL.
- Water (e.g. ad libitum): Municipal water supplying the facility is analyzed for contaminants according to WIL SOP
- No contaminants were present in animal feed or water at concentrations sufficient to interfere with the objectives of this study. The basal diet and municipal water, delivered by an automatic watering system, were provided ad libitum, except during acclimation to restraint and the exposure period.
- Acclimation period: 5 days, the animals were observed twice daily for mortality and moribundity. The animals were subjected to restraint in the nose-only exposure holding tubes for 1 hour on 27 April 2010 prior to the start of exposure. Animals were held in restraint tubes for 35 minutes prior to initiation of exposure.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): The room temperature control was set to maintain environmental conditions of 71°F ± 5°F (22°C ± 3°C) and 50% ± 20% relative humidity. Room temperature was monitored using the Metasys DDC Electronic Environmental control system and schedule for data collection was on an hourly basis. Actual mean daily temperature ranged from 70.3°F to 72.1°F (21.3°C to 22.3°C).
- Humidity (%): The humidity control was set to maintain environmental conditions of 50% ± 20% relative humidity. Relative humidity was monitored using the Metasys DDC Electronic Environmental control system and as scheduled for data collection on an hourly basis. Mean daily relative humidity ranged from 49.2% to 55.9% during the study.
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

IN-LIFE DATES: no data

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: air (for compressed air system) and deionized water (for humidified air system)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: the test substance was delivered using an auger-type feeder (Schenck AccuRate, INc., Whitewater, WI) which fed test substance at a constant rate to a jet mill air micronizer (model 00, Jet-O-Mizer, Fluid Energy Aljet, Hatfield, PA) operating as a particle size reduction and dispersion device.
- Exposure chamber volume: 7.9 L convential nose-only exposure system (designed and fabricated by WIL)
- Method of holding animals in test chamber: Animals were restrained in nose-only exposure holding tubes during exposure
- Source and rate of air: Using 2 regulators, dry compressed air was supplied to the micronizing and inlet ports of the jet mill. The resulting aerosol from the jet mill was delivered to the nose-only exposure system through 22-mm respiratory tubing. A glass cyclone was placed in-line after the jet mill to reduce particle size. A tee fitting was placed at the inlet of the exposure system to provide humidified air. Humidified air was added using a Coilhose Pneumatics regulator and controlled using a rotameter-type flowmeter. Dry compressed air passed through a muffler-type bubbler submerged in a 2-L Erlenmeyer flask filled with deionized water to produce humidified air. The airflows used for the animal exposure is as follows: inlet airflow rate = 28.5-29.2 L/minute, micronizing airflow rate is 18.6L/minute, humidified airflow rate is 7.6 L/minute and total airflow rate is 54.7-55.4 L/minute
- Method of conditioning air: see above (source and rate of air)
- System of generating particulates/aerosols: see above (source and rate of air)
- Method of particle size determination: Three aerosol particle size determinations were conducted for this exposure using a 7-stage stainless steel cascade impactor (model 02-140, In-Tox Products, Moriarty, NM). Pre-weighed, 23-mm stainless steel discs were used as the collection substrates. Samples were collected at approximately 1.8 L/minute for 0.25 minutes. The filters were re-weighed and the particle size calculated based on the impactor stage-cut-offs. The aerosol size was expressed as the mass median aerodynamic diameter (MMAD) and the geometric standard deviation (GSD).
- Treatment of exhaust air: Exhaust atmosphere was filtered using a Solberg filter (Solberg Manufacturing, Inc., Itasca, IL) prior to entering the in-house exhaust system with activated charcoal and HEPA-filtration.
- Temperature, humidity, pressure in air chamber: The room temperature and humidity controls were set to maintain environmental conditions of 71°F±5°F (22°C ± 3°C) and 50%±20% relative humidity. Room temperature and relative humidity were monitored using the Metasys DDC Electronic Environmental control system and were scheduled for data collection on an hourly basis. Actual mean daily temperature ranged from 70.3°F to 72.1°F (21.3°C to 22.3°C) and mean daily relative humidity ranged from 49.2% to 55.9% during the study

TEST ATMOSPHERE
- Actual exposure concentrations: Actual exposure concentrations were determined using standard gravimetric methods. Samples were collected on pre-weighed, 25-mm glass-fiber filters (type A/E, PALL Corporation, Ann Arbor, MI) held in an open-faced filter holder positioned in the animal breathing zone within the nose-only exposure system. Following sample collection, the filters were re-weighed and the concentration calculated as the filter weight difference divided by the sample volume. Samples were collected at approximately 2 L/minute for 0.5 mintues.


VEHICLE
- Composition of vehicle (if applicable): not applicable
- Concentration of test material in vehicle (if applicable): not applicable
- Justification of choice of vehicle: not applicable
- Lot/batch no. (if required): not applicable
- Purity: not applicable

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Effective cut-off diameter: 5.27 µm for stage 1, 4.22 µm for stage 2, 3.20 µm for stage 3, 1.90 µm for stage 4, 1.07 µm for stage 5, 0.41 µm for stage 6 and 0.27 µm for stage 7
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.00 µm (mean MMAD) and 1.75 (Mean GSD)

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: The target exposure concentration was based on toxicity data from similar compounds as outlined in the product MSDS. Under the generation and exposure conditions of this study and requirements for a particle size of 1 to 4 microns and maintenance of a stable concentration for the 4-hour exposure period, it was determined that the maximum obtainable concentration of zirconium dioxide as a dust aerosol was approximately 4.3 mg/L. Since no animals died following exposure to the maximum obtainable concentration of the test substance, additional exposure levels were not required.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Actual exposure concentration: 4.3 mg/L (SD 1.39 mg/L), this is the maximum obtainable mean concentration for a 4-hour exposure. The nominal exposure concentration was 41.4 mg/L.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Body weights were obtained immediately prior to exposure on study day 0 and on post-exposure days 1, 3, 7, and 14.
Mortality: each animal was observed for mortality at the approximate midpoint of exposure, immediately following exposure on study day 0, and twice daily thereafter for 14 days.
Clinical observations: each animal was observed immediately following exposure on study day 0 and once daily thereafter for 14 days.
- Necropsy of survivors performed: yes; animals at the scheduled necropsy were euthanized by isoflurane anesthesia followed by exsanguination. The major organ systems of the cranial, thoracic, and abdominal cavities were examined for all animals.

Statistics:

no data

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.3 other: mg/L (actual exposure concentration: maximum technically achievable concentration)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

None of the animals died during exposure or during the 14-day post-exposure observation period. Based on the data obtained, the LC50 of zirconium dioxide was found to be greater than 4.3 mg/L, the maximum obtainable mean concentration.

Clinical signs:

other: There were no toxicologically significant clinical signs immediately following exposure. Several animals were noted with clear material on the neck, forelimb(s), trunk, and urogenital area, red material around the nose and mouth, and/or yellow material ar

Body weight:

All animals lost weight (10 g to 39 g) from study day 0 to 1. One male lost weight (9 g) from study day 1 to 3. All animals surpassed their initial (study day 0) body weight by study day 14 and were considered normal.

Gross pathology:

There were no macroscopic findings for any animal at the scheduled necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study, the LC50 of zirconium dioxide was greater than 4.3 mg/L, the maximum obtainable mean concentration, when male and female albino rats were exposed to a dust aerosol of the test substance as a single, 4-hour, nose-only exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

1. Information on zirconium dioxide

Acute toxicity: oral

One reliable study was identified. Acute toxicity was determined via the acute toxic class method (OECD Guideline 423 and EU Method B1 tris) in female Sprague-Dawley rats. The LD50-value was > 5000 mg/kg bw.

Acute toxicity: inhalation

One reliable study was performed by WIL Research Laboratories on request of the MOZO Consortium in 2010. Acute inhalation toxicity was tested according to OPPTS Guideline 870.1300 and OECD Guideline 436. Zirconium dioxide was administered to 1 group of 3 male and 3 female Crl:CD(SD) albino rats via nose-only inhalation exposure as a dust aerosol at a concentration of 4.3 mg/L, which was the maximum obtainable mean concentration, for 4 hours. The exposure atmosphere was characterized by a mean mass median aerodynamic diameter (± geometric standard deviation) of 2.0 µm ± 1.75 µm. As no mortality occurred during the study, the LC50 of zirconium dioxide was greater than 4.3 mg/L.

Although the LC50 of zirconium dioxide dust aerosol is higher than 4.3 mg/L, which is lower than the classification cut-off value of 5 mg/L for harmful classification (DSD) or category 4 classification (CLP), further testing was considered not feasible as the maximum obtainable mean concentration for exposure was 4.3 mg/L and no mortality occurred at that concentration. Therefore classification for acute inhalation toxicity was deemed unnecessary.

Acute toxicity: dermal

No data available, however, no acute toxicity after dermal exposure is to be expected based on the absence of acute toxicity after oral exposure up to and including at the limit test dose of 2000 mg/kg bw.

2. Information on calcium oxide

Acute toxicity: oral

A GLP study was performed according to OPPTS Guideline 870.1300 and OECD Guideline 436 in Wistar rats. The LD50-value was > 2000 mg/kg bw (Arcelin, 2007).

Acute toxicity: inhalation

No data available.

Acute toxicity: dermal

No data available, however, no acute toxicity after dermal exposure is to be expected based on the absence of acute toxicity after oral exposure up to and including at the limit test dose of 2000 mg/kg bw.

3. Conclusion on calcium zirconium oxide

Acute toxicity: oral

The acute oral LD50 for zirconium dioxide has been determined to be > 5000 mg/kg bw and that for calcium oxide has been demonstrated to be > 2000 mg/kg bw. No experimental information is available for calcium zirconium oxide. However, it is expected that the substance will have a similar hazard profile as the individual components in its crystal lattice, i.e. zirconium dioxide and calcium oxide. Based on abovementioned information, calcium zirconium oxide is not expected to cause any adverse acute toxic effects after oral intake up to a dose of 2000 mg/kg bw. Therefore, the substance does not need to be classified for acute oral toxicity.

Acute toxicity: inhalation

Because it was already demonstrated for acute oral toxicity that calcium oxide and zirconium dioxide have a similar non-hazardous toxicological profile, it was considered acceptable to cover the acute inhalation toxicity endpoint by key data for zirconium dioxide alone. Here also, no adverse effects have been observed during the study, the LC50 being > 4.3 mg/L, which was the highest technically feasible concentration. Calcium zirconium oxide is expected to be non-hazardous via inhalation too. Consequently, as for zirconium dioxide, no classification would be needed for acute inhalation toxicity either.

Acute toxicity: dermal

No reliable data are available for acute toxicity via the dermal route of exposure. However, according to Annex VIII of the REACH Regulation, in addition to the oral route, for substances other than gases, the information mentioned under section 8.5 shall be provided for at least one other route. As information is provided for the inhalation and the oral route, an acute dermal toxicity study should not be peformed. Moreover, no acute toxicity after dermal exposure is to be expected based on the absence of acute toxicity after oral exposure to zirconium dioxide and calcium oxide up to and including at the limit test dose of 2000 mg/kg bw.

Justification for classification or non-classification

1. Information on zirconium dioxide

- Based on the available data and according to the DSD/CLP criteria, zirconium dioxide should not be classified for acute toxicity via the oral route of exposure.

- No reliable data are available on acute toxicity via the dermal route of exposure. However, no acute toxicity after dermal exposure is to be expected based on the absence of acute toxicity after oral exposure to zirconium dioxide up to and including at the limit test dose of 2000 mg/kg bw.

- Based on the available data and according to the DSD/CLP criteria, zirconium dioxide should not be classified for acute toxicity via the inhalation route of exposure.

2. Information on calcium oxide

- Based on the available data and according to the DSD/CLP criteria, classification of calcium oxide for acute oral toxicity is not warranted.

- No reliable data are available for the inhalation route of exposure.

- No reliable data are available for the dermal route of exposure, however, no acute toxicity after dermal exposure is to be expected based on the absence of acute toxicity after oral exposure to calcium oxide up to and including at the limit test dose of 2000 mg/kg bw.

3. Conclusion on calcium zirconium oxide

Calcium zirconium oxide is a stabilised zirconia, whereby zirconium dioxide and calcium oxide are incorporated in a single crystal lattice. Based on acute toxicity data for the individual components zirconium dioxide and calcium oxide, neither of which are classified for acute toxicity, calcium zirconium oxide can be concluded to be not classified for acute toxicity either according to DSD/CLP Regulations.