Gadolinium zirconium oxide (Gd2Zr2O7)

Endpoint summary

Description of key information

In an acute oral toxicity study (according to OECD 423), two groups, each of three female Wistar rats, were treated with the test item suspended in corn oil by oral gavage administration at a dosage of 2000 mg/kg body weight and were observed for 14 days. No test-item related signs of toxicity were seen during observation nor necropsy. Based on these results the oral LD₅₀was determined to be greater than 2000 mg/kg bw.

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:

2016-08-05 to 2016-11-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: suspension in corn oil (Sigma, Lot no. MKBV2080V, expiry date 08/2016)
- Final dilution of a dissolved solid, stock liquid or gel: 0.2 g/mL

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: step 1: 11-12 weeks old;
step 2: 8-9 weeks old
- Weight at study initiation: step 1: 178-190 g
step 2: 168-180 g
- Fasting period before study: 16-19 h (access to water was permitted)
- Housing: SPF, the animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet (e.g. ad libitum): ad libitum; Altromin 1324 maintenance diet for rats and mice
- Water (e.g. ad libitum): ad libitum, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2g/10mL
- Amount of vehicle (if gavage): 10 mL/kg body weight
- Justification for choice of vehicle: This vehicle was chosen due to its non-toxic characteristics.
- Lot/batch no. (if required): Sigma, lot no. MKBV2080V, expiry date: 08/2016

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose was selected to be 2000 mg/kg body weight, as no toxicity was expected.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3 females per step, 2 steps performed

Control animals:

no

Details on study design:

- Preparation of the Test Item
In order to get the test item in a solution or suspension, which is applicable to the animals, water and corn oil were tested. While in water the test item formed floating aggregates which were predicted not to be applicable to the animals, preparation with corn oil yielded a well applicable suspension. The test item was weighed out into a tared plastic vial on a precision balance. Homogeneity of the test item in the vehicle was maintained by vortexing the prepared suspension thoroughly before each dose administration. For all animals of the first and of the second step, 2 g of the test item was suspended with the vehicle (corn oil) to gain a final volume of 10 mL and to achieve a dose of 2000 mg/kg body weight at a dose volume of 10 mL/kg body weight.
The dose formulations were made shortly before each dosing occasion.

- Preparation of the Animals
Prior to the administration a detailed clinical observation was made of all animals. Only healthy animals were used.
- Food was provided again approximately 4 hours post dosing.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). Thereafter, the animals were observed for clinical signs once daily, weighing on day 1 (prior administration), 8 and 15
- Necropsy of survivors performed: yes, sacrificed with an overdosage of phenobarbital. All animals were subjected to gross necropsy and examined macroscopically for gross pathological changes. In the absence of gross pathological changes no tissues were preserved for a possible histopathological evaluation.
- Examinations performed: Cage-side observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Statistics:

N.A.

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality observed

Clinical signs:

other: No specific findings in any test animal during the whole observation period

Gross pathology:

No specific findings

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study in rats according to OECD 423, no adverse effects were observed for Gadolinium zirconium oxide at the limit dose of 2000 mg/kg bw. Hence, the LD50 value is determined to be greater than 2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study (acute toxic class method, OECD 423), two groups of fasted, 8-11 weeks old, female Wistar rats (3 rats/group) were given a single oral dose of Gadolinium zirconium oxide (> 98% purity) in corn oil at the limit dose of 2000 mg/kg bw and were observed for 14 days. All animals survived until the end of the study without showing any test item related signs of toxicity. Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain. At necropsy, no treatment-related macroscopic findings were observed in any animal of any step. Based on the results from this study, the oral LD50 in rats is considered to be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Guideline study

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The target substance Gadolinium zirconium oxide was tested in an acute oral toxicity study (according to OECD 423). Two groups, each of three female Wistar rats, were treated with the test item suspended in corn oil by oral gavage administration at a dosage of 2000 mg/kg body weight and were observed for 14 days. No test-item related signs of toxicity were seen during observation nor necropsy. Based on these results the oral LD50 was determined to be greater than 2000 mg/kg bw.

Justification for classification or non-classification

Based on the available data, Gadolinium zirconium oxide does not warrant classification for acute toxicity in accordance to regulation (EC) No 1272/2008.