Titanium(4+) ethanolate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04 July 2012 - 23 January 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study is carried out based on the OECD No. 423 Acute Oral Toxicity, Acute Toxic Class Method and in compliance with OECD principles of Good Laboratory Paractice (GLP)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF guidelines (2011)

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Titanium(4+) ethanolate

EC Number:

221-410-8

EC Name:

Titanium(4+) ethanolate

Cas Number:

3087-36-3

Molecular formula:

C8H20O4Ti

IUPAC Name:

Titanium tetrakis(ethan-1-olato) 

Details on test material:

- Name of test material (as cited in study report): titanium(4+) ethanolate
- Molecular formula (if other than submission substance): C8H20O4Ti
- Molecular weight (if other than submission substance): 228,11
- Physical state:liquid
- Analytical purity: 100%
- Purity test date: 18 June 2012
- Lot/batch No.: 621
- Expiration date of the lot/batch: 02 August 2013
- Storage condition of test material: At room temperature in the dark under nitrogen

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks old
- Weight at study initiation: first group 161, 160, 165 grams, second group 168, 181, 170
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance.
- Housing: 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum):Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum):Free access to tap water.
- Acclimation period:at least 5 days before start of treatment under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):18 to 24°C
- Humidity (%):40 to 70%
- Air changes (per hr):approximately 15 room air changes/hour
- Photoperiod (hrs dark / hrs light):12-hour light/12-hour dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2000mg/kg (1,805 ml/kg) body weight

Doses:

2000mg/kg bw

No. of animals per sex per dose:

six females (2 groups of three females)

Details on study design:

The toxicity of the test substance was assessed in a limit test by treatment of six females (2 groups of three females in a stepwise manner) at a dose level of 2000 mg/kg body weight.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality twice daily, clinical signs at 0, 2 and 4 hours on the day of dosing (Day 1) and once daily there after, until Day 15. Body weights at Day 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, necropsy

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred. See attached results, table 1.

Clinical signs:

other: Hunched posture was noted in three animals on Day 1. See attached results, table 2.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals. See attached results, table 4

Other findings:

no findings noted

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 value of Titanium(4+) ethanolate in Wistar rats was established to exceed 2000 mg/kg body weight. This study was conducted according to the OECD 423 method and in compliance with GLP.

Executive summary:

The objective of this study was to assess the toxicity of the titanium(4 +) ethanolate when administered in a single oral dose (2000 mg/kg bw) to female rats. The oral route was selected as it is a possible route of human exposure during manufacture, handling or use of the test substance. No mortalities was observed at the tested dose level. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

The study is considered reliable without restrictions since the study is carried out based on the OECD No. 423 guideline and in compliance with principles of Good Laboratory Paractice (GLP).

Based on these results, Titanium(4 +) ethanolate does not have to be classified and has no obligatory labeling requirement for acute oral toxicity according to CLP Regulation 1272/2008 and Directive 67/548/EEC.