Reaction mass of disodium hexatitanium tridecaoxide and disodium trititanium heptaoxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-05-06 to 2010-05-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP guideline study reliable without restrictions

Justification for type of information:

Disodium titanate substance (EC 234-802-9) has the molecular formula Na2TiO3 and its composition is expressed as (Na2O)x(TiO2), where x is ranging from 0.1 to 6 according to the SIP. This substance, Reaction mass of Disodium Hexatitanate and Sodium Metatitanate, has a value of x = 0.21, calculated from XRF results, has been identified as a mixture of two specific types of disodium titanate and is therefore within the scope of the disodium titanate SIP.
It is assessed therefore that disodium titanate is an acceptable read-across substance for Reaction mass of Disodium Hexatitanate and Sodium Metatitanate

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

, 2001-12-17

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2008-11-12

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Disodium titanate

EC Number:

234-802-9

EC Name:

Disodium titanate

Cas Number:

12034-34-3

Molecular formula:

Na2TiO3

IUPAC Name:

disodium titanate

Details on test material:

- Name of test material (as cited in study report): Disodium titanate
- Physical state: light yellow powder
- Storage condition of test material: At room temperature, in tightly closed container

No further information on the test material was stated.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst / The Netherlands
- Age at study initiation: 10 weeks
- Weight at study initiation: 183.8 g – 199.0 g
- Fasting period before study: rats were fasted for approximately 16 to 19 hours, but with free access to water. Food was presented approximately 3 hours after dosing.
- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding (‘Lignocel’, J. Rettenmaier&Söhne GmbH&CoKG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland). including paper enrichment (Enviro-dri from Lillico, Biotechnology, Surrey, UK).
- Diet (ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 83/09 (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) (except for the overnight fasting period prior to intubation and approximately 3 hours post dose).
- Water (ad libitum): Community tap water from Füllinsdorf
- Acclimation period: Five to eight days under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.
Music played during the daytime light period.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Relative 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.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Source: Carl Roth GmbH & Co., 76185 Karlsruhe / Germany
- Justification for choice of vehicle: The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. The test item formulated at 20% (w/w) in corn oil was described as a clear yellow solution and was considered to be suitable for an oral application.
- Batch no.: 049103168
- Expiry Date: 31-Jan-2014
- Stability of the Vehicle: Stable under storage conditions
- Storage Conditions: At room temperature (range of 20 ± 5 °C), light protected.
- Description: Yellowish oily liquid

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

DOSAGE PREPARATION: The dose formulations were prepared shortly before each dosing occasion using a magnetic stirrer and a spatula as homogenizers.
The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume).
Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.
No further information on the oral exposure was stated.

Doses:

2000 mg/kg

No. of animals per sex per dose:

2 x 3 female rats (Total: 6 female rats)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Viability/mortality was checked daily during acclimatization. Then it was checked once before treatment
and within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after treatment on test day 1 (in common with the clinical signs). After test day 1, viability/mortality was checked twice daily during days 2 – 15. Clinical signs were checked daily during acclimatization. Then clinical signs were checked once before treatment and within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. After test day 1, clinical signs were checked once daily during days 2 – 15. Body weight was measured on test days 1 (prior to administration), 8 and 15.
- Necropsy of survivors performed: Yes
All animals were sacrificed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. An external examination and opening of the abdominal and thoracic cavities for examinations of major organs was performed. The appearance of any macroscopic abnormalities was recorded. No organs or tissues were retained.
No further information on the study design was performed.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No intercurrent deaths occurred during the course of the study.

Clinical signs:

other: No clinical signs were observed throughout the entire observation period.

Gross pathology:

No macroscopic findings were recorded at necropsy.

Other findings:

No data

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The median lethal dose of disodium titanate after single oral administration to female rats, observed over a period of 14 days, is:
LD50 (female rat): > 2000 mg/kg body weight
Based upon regulation (EC) No 1272/2008 and its subsequent amendments, disodium titanate is not classified with respect to acute oral toxicity in the rat.
Also, based upon the Directive 67/548/EEC and its subsequent amendments, disodium titanate is not classified with respect to acute oral toxicity in the rat.