[μ-[carbonato(2-)-O:O']]dihydroxydioxodizirconium

Endpoint summary

Description of key information

Acute toxicity: oral
One study was performed according to a method similar to OECD Guideline No. 401 on albino rats with hydrated zirconium basic carbonate (Harrison, 1951). In this study the LD50 is determined to be > 47 850 mg/kg bw (based on test material).
Acute toxicity: inhalation
One study was performed according to OECD Guideline No. 436 on Crl:CD (SD) rats with zirconium basic carbonate (Smith, 2013). In this study the LC50 was determined to be > 4.74 mg/L air (analytical, based on test material). 
Acute toxicity: dermal
No study available for this endpoint.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Non GLP study. The study was conducted according to a method equivalent to the OECD 401 guideline without major deviations. However, no data on test conditions are reported. Follow-up of body weight was done weekly, however no individual animal data were reported.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: 7 to 8 months old
- Weight at study initiation: 350 g (preliminary test), 180 g (second more extensive test)
- Fasting period before study: 24 hours
- Housing: all rats were housed individually
- Diet (e.g. ad libitum): normal diet
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data

Route of administration:

oral: feed

Vehicle:

not specified

Details on oral exposure:

Each rat was individually supplied once with a mixture of cheese and hydrated zirconium carbonate (HZC), calculated to provide single doses equivalent to 2,4, 8 or 10 gZrO2/kg bw (respectively 9.6, 19.1, 38.3, 47.85 g/kg bw of HZC)

Doses:

2, 4, 8 or 10 gZrO2/kg bw (respectively 9.6, 19.1, 38.3, 47.85 g/kg bw of HZC)

No. of animals per sex per dose:

five adult rats were used per dose (preliminary study)
50 young adult male rats were used in a second more extensive acute test

Control animals:

yes

Details on study design:

- Duration of observation period following administration: all rats were observed for 60 days, during wich period they received a normal diet
- Frequency of observations and weighing: Their general condition was noted daily and they were weighed weekly, as a check against delayed effects
- Necropsy of survivors performed: yes
- Other examinations performed: gross necropsy

Statistics:

No data

Sex:

male

Dose descriptor:

LD50

Effect level:

> 47 850 other: mg /kg bw

Based on:

test mat.

Mortality:

No deaths occurred during either the preliminary test with the group of 20 adult male rats or the more extensive test with 50 younger adult male rats.

Clinical signs:

other: All animals continued to grow at a normal rate. No significant differences were noted among the test groups and the controls indicating that the acute oral toxicity of the zirconium carbonate was very low.

Gross pathology:

Gross examination of the autopsied animals revealed nothing abnormal.

Other findings:

No data

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No deaths occured during either the preliminary test with the group of 20 adult male rats or the more extensive test with 50 younger adult male rats. All animals continued to grow at a normal rate and gross examination of the autopsied animals revealed nothing abnormal up to a dose of 47850 mg/kg bw (based on test material).

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:

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.

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

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

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.

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute toxicity: oral

One key study was identified (Klimisch 1). Harrison (1951) performed an acute oral toxicity study (feed) in Sprague-Dawley rats according to a similar method as that described in the OECD 401 test guideline. After exposure to a single dose of zirconium basic carbonate hydrated form, all animals (five adult rats were used per dose (preliminary study) and 50 young adult male rats were used in a second more extensive acute test) were observed for 60 days. During this period they received a normal diet. No deaths occurred during either the preliminary test with the group of 20 adult male rats or the more extensive test with 50 younger adult male rats. All animals continued to grow at a normal rate and gross examination of the autopsied animals revealed nothing abnormal up to a dose of 47850 mg/kg bw (based on test material).

Acute toxicity inhalation

Smith (2013) performed an acute inhalation toxicity study in Crl:CD (SD) rats (one test group, which consisted of 3 male and 3 female animals) according to OECD Guideline 436 (single 4-hour nose-only exposure) with zirconium basic carbonate (hydrated form).

The target concentration was 5 mg/L. The maximum mean achieved aerosol concentration was 4.74 mg/L (based on test material). The observation period lasted 14 days. There were no unscheduled deaths. Wet fur was evident in all animals immediately after the exposure and persisted in one female until 1 hour post dose. In addition signs of noisy breathing (1/3 males and 1/3 females), red staining of the snout and jaw (1/3 males and 1/3 females) and test substance staining to the snout (1/3 males and 1/3 females) were observed immediately after the exposure. Noisy breathing remained evident in the female until 2 hours post dose, from day 2 and for the remainder of the observation period all animals were considered normal. On the day following the exposure slight body weight losses were evident in one male and all females, growth was observed at the next weighing occasion (day 4) and continued for the remainder of the observation period. The macroscopic examination performed after a single administration followed by a 14 day observation period revealed no findings of note. The nature and incidence of all findings were consistent with the commonly seen back group of macroscopic changes. Under the conditions of this study the LD50 (4-hour) for zirconium basic carbonate is in excess of 4.74 mg/L (test material based) for male and female rats.

Acute toxicity: dermal

Data are available for both the oral and the dermal route of exposure. According to the REACH Regulation, only one additional route of exposure should be tested other than the oral route of exposure for acute toxicity (column 2, annex VIII, section 8.5). Therefore, it is not necessary to perform an acute toxicity study via the dermal route of exposure.

In addition, the dermal route is not the most appropriate route as exposure via inhalation is more likely and there is no indication from the physicochemical properties of significant absorption through the skin (Annex VIII, 8.5.3, Column 2 adaptation).

Justification for selection of acute toxicity – oral endpoint
Only one study available

Justification for selection of acute toxicity – inhalation endpoint
Only one study available

Justification for selection of acute toxicity – dermal endpoint
Data are available for both the oral and the inhalationl route of exposure. According to the REACH Regulation, only one additional route of exposure should be tested other than the oral route of exposure for acute toxicity (column 2, annex VIII, section 8.5). Therefore, it is not necessary to perform an acute toxicity study via the dermal route of exposure.

Justification for classification or non-classification

Based on the available data and according to DSD/CLP criteria, zirconium basic carbonate should not be classified for acute toxicity via the oral nor via the inhalation route of exposure.