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Administrative data

Description of key information

Acute toxicity: oral
A K2 acute oral toxicity test was performed in male and female Sprague Dawley rats according to a guideline similar to OECD Guideline 401 (Cochran et al., 1950).
The acute oral LD50 value in male/female Sprague-Dawley rats was 4100 mg/kg bw.
Acute toxicity: inhalation
No study available for this endpoint. In addition, the substance is marketed/used in aqueous solution and thus inhalation exposure is unlikely.
Acute toxicity: dermal
A K1 acute dermal toxicity test was performed in male and female Sprague-Dawley rats following the OECD 402 Guideline (Longobardi, 2013a).
The acute dermal LD50 value in male/female Sprague-Dawley rats is > 2000 mg/kg bw (limit test).
Acute toxicity: other routes
No reliable studies were 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:
Well documented, scientifically sound study with methods similar to OECD 401 with the following deviations: The number of deaths at each dose were not reported; the specific doses (mg/kg) were not provided; individual clinical observations, body weights, pathology were not reported; sex of the animals was not provided.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
The number of deaths at each dose were not reported; the specific doses (mg/kg) were not provided; individual clinical observations, body weights, pathology were not reported; sex of the animals was not provided
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: adult rats
- Weight at study initiation: between 200 and 300 g
- Fasting period before study: no data
- Housing: maintained in air-conditioned rooms
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
50% aqueous solutions were used.
Doses:
Single dose, no more data
No. of animals per sex per dose:
24 rats in total
Control animals:
no
Details on study design:
- Duration of observation period following administration: 10 days
Statistics:
The LD50 values were obtained from ten day mortality data by using the log-probability method.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 100 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 660 mg/kg bw
Based on:
element
Remarks:
Zr
Mortality:
The rats showed a progressive depression and decrease in activity until death occurred.
No sex differences were noted, and the LD50 value was therefore derived from the combined data on both sexes.
The time of death varied from a few hours to a few days after administration. Few deaths however occurred later than 5 days after administration.
Clinical signs:
No characteristic physiologic changes were observed.
Body weight:
No characteristic physiologic changes were observed.
Gross pathology:
No characteristic gross pathologic changes were observed.
Conclusions:
The acute oral LD50 value in rats via oral gavage route is 4100 mg/kg bw (zirconyl acetate).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
4 100 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 20 February 2013 to 7 March 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented GLP study in accordance with OECD Guideline 402 with no deviations.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy s.r.l., San Pietro al Natisone (UD), Italy
- Age at study initiation: 6 to 8 weeks old
- Weight at study initiation: 176 to 200 grams
- Fasting period before study: none
- Housing: Polysulphone solid bottomed cages measuring 59.5x38x20 cm (during acclimatisation) and 42.5x26.6x18.5 cm (during the study) with nesting material provided into suitable bedding bags
- Diet (e.g. ad libitum): Ad libitum throughout the study
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 2°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): 15 to 20/h
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 5 x 7 cm on dorsal surfaces of the trunk
- % coverage: 10% of body surface
- Type of wrap if used: A patch of surgical gauze covered by a strip of synthetic film was placed over the treated site and the whole assembly held in place by encircling the trunk of the animal with a length of elastic adhesive bandage, this forming a semi-occlusive barrier.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle swabbing of the skin with cotton wool soaked with lukewarm water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Concentration (if solution): 2000 mg/kg
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Twice daily for mortality and morbidity, day -1, 1, 8 and 15 for body weight and day of dosing (on dosing, approximately 1, 2 and 4 hours after dosing) and daily thereafter for 14 days for clinical signs
- Necropsy of survivors performed: yes (day 15): carbon dioxide narcosis; necropsy was carried out on all animals (gross necropsy examination for both external and internal abnormalities, with particular attention to the treatment site).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Remarks:
anhydrous zirconium acetate
Mortality:
No mortality occurred in male or female animals following treatment.
Clinical signs:
No clinical signs were observed.
Body weight:
The body weight changes were within the expected range for this species and age of animals at the end of the study.
Gross pathology:
No significant abnormalities were found at necropsy examination performed on all animals at termination of the study.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
These results indicate that the test item has no systemic toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg of zirconium acetate. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute toxicity: oral:

Cochran et al. (1950) performed an acute oral toxicity study (gavage) in Sprague-Dawley rats according to a procedure similar to the OECD 401 test guideline, using a 50% suspension of zirconyl acetate. After exposure to a single dose, all animals (24 in total) were observed for 10 days. An LD50 value of 4100 mg/kg bw was determined for male and female rats. This study was considered reliable with restrictions (K2).

Acute toxicity: inhalation:

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 inhalation route of exposure. In addition, the substance is marketed/used in aqueous solution and thus inhalation exposure is unlikely.

Acute toxicity: dermal:

Longobardi (2013a) performed an acute dermal toxicity study in male/female Sprague-Dawley rats according to OECD Guideline 402 and EU Method B.3. After exposure to a single dose of 2000 mg/kg bw, all animals (5 per sex) were observed for 14 days. An LD50 value of > 2000 mg/kg bw was reported (no adverse effects observed). This study was considered reliable without restrictions (K1).

Acute toxicity: other routes:

In addition, the acute toxicity was investigated via the intraperitoneal route. The intraperitoneal LD50 value was determined to be 300 mg/kg bw (Cochran et al., 1950), however, this result was not considered reliable (K3).


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

Justification for selection of acute toxicity – dermal endpoint
Only one reliable study available for this endpoint.

Justification for classification or non-classification

Based on the results of the acute oral and dermal toxicity study and according to the criteria of the DSD and CLP Regulation, zirconium acetate should not be classified as an acute oral or dermal toxicant.

No data were available to decide on the classification for the inhalation route.