Registration Dossier

Administrative data

Description of key information

Acute toxicity: oral
An acute oral toxicity test (Klimisch 2) was performed in male and female Sprague Dawley rats according to OECD Guideline 401 (Cuthbert and Jackson, 1992a).
The Median Oral Lethal Dose (LD50) in rats was greater than 5000 mg/kg (test substance).
Acute toxicity: inhalation
No study available for this endpoint.
Acute toxicity: dermal
An acute dermal toxicity test (Klimisch 2 due to read across purposes) was performed in male and female Sprague-Dawley rats according to the OECD Guideline 402 with the read across substance zirconium acetate (Longobardi, 2013). The acute dermal LD50 value in male/female Sprague-Dawley rats was > 2000 mg/kg bw (limit test, based on anhydrous zirconium acetate).

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
Study period:
From 6 February 1992 to 20 February 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Well documented GLP study performed according to OECD and EEC Guidelines. Purity of the test substance is not specified. Mean relative humidity was slightly out of protocol requirements (protocol not available), however, this is not considered to have affected the integrity of the study.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
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: Charles River (UK) Limited, Manston Road, Margate, Kent
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: 154-197 g
- Fasting period before study: rats were deprived of food overnight prior to dosing and 4h post dosing.
- Housing: The rats were housed by sex in polypropylene cages with mesh floors suspended over absorbent paper lined trays, with 5 animals per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): between 20°C and 21°C
- Humidity (%): mean relative humidity was 37%. Mean relative humidity was outwith protocol requirements, however, this is not considered to have affected the integrity of the study.
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5%
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 500 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:
5000 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: The rats were observed frequently on the day of dosing and once daily for 14 days following dosing. They were weighed immediately prior to dosing, 7 days after dosing and at sacrifice at the end of the 14 day observation period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
Mean and standard deviation used in body weight determinations.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths following a single oral dose of Zirconium Basic Sulphate at a dose level of 5000 mg/kg to a group of 5 male and 5 female rats.
Clinical signs:
No abnormalities were detected.
Body weight:
Body weight gains were acceptable. Body weight gain after 14 days: 129 +/- 17 g in males and 67 +/- 12 g in females.
Gross pathology:
No abnormalities were detected.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
There were no deaths following a single oral dose of zirconium basic sulfate (5000 mg/kg test substance) administered to a group of 5 male and 5 female rats. The Median Oral Lethal Dose (LD50) in rats is therefore greater than 5000 mg/kg.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute toxicity: oral

Cuthbert and Jackson (1992a) investigated the acute oral toxicity of zirconium basic sulfate in male/female Sprague-Dawley rats. This Klimisch 2 study (reliable with restrictions) was performed according to OECD Guideline 401. There were no deaths following a single oral dose of zirconium basic sulfate (5000 mg/kg) administered to a group of 5 male and 5 female rats. The Median Oral Lethal Dose (LD50) in rats was greater than 5000 mg/kg (test substance).

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 as a paste and therefore no inhalation exposure is expected.

Acute toxicity: dermal

Longobardi (2013) performed an acute dermal toxicity study in male/female Sprague-Dawley rats according to OECD Guideline 402 with the read across substance zirconium acetate. 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. This study was considered reliable with restrictions (Klimisch 2) because it is used for read across purposes in this dossier. The read across justification is added in Section 13 of IUCLID. Because the behaviour of zirconium acetate (although a 'water soluble' zirconium compound) and zirconium basic sulfate (an insoluble zirconium compound) is basically the same at physiologically relevant pH, read across is justified.


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

Justification for selection of acute toxicity – inhalation endpoint
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 as a paste and therefore no inhalation exposure is expected.

Justification for selection of acute toxicity – dermal endpoint
Study available for this endpoint from the read across substance zirconium acetate.

Justification for classification or non-classification

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

Based on the results of the acute dermal toxicity study with the read across substance zirconium acetate and according to the criteria of the DSD and CLP Regulation, zirconium basic sulfate should not be classified as an acute dermal toxicant.

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