Bis(ethyl acetoacetato-O1',O3)bis(2-methylpropan-1-olato)titanium

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 4, 2012 - July 9, 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted in accordance with OECD No. 423 guideline and in compliance with 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:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Bis(ethyl acetoacetato-O1',O3)bis(2-methylpropan-1-olato)titanium

EC Number:

281-161-6

EC Name:

Bis(ethyl acetoacetato-O1',O3)bis(2-methylpropan-1-olato)titanium

Cas Number:

83877-91-2

Molecular formula:

C20H36O8Ti

IUPAC Name:

Bis(ethylacetoacetato‐O1',O3")bis(2‐methylpropan‐1‐olato)titanium

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Bis(ethylacetoacetato-O1', O3") bis(2-methyl propan-1-olato)titanium
- Molecular formula (if other than submission substance): C20H36O8Ti
- Molecular weight (if other than submission substance): 452.36
- Physical state: Yellow to red clear liquid
- Purity/composition: 90-100%
- Lot/batch No.: 304-300146/000019
- Expiration date of the lot/batch: 21 May 2014
- Stability under storage conditions: Stable
- Storage condition of test material: At room temperature in the dark
- Other
Hygroscopic: Yes, store in well-sealed container
Volatile: Not indicated
Reactivity: Reactive to moisture
Test substance handling No specific handling required
Specific Gravity 1.01 to 1.11 at 25ºC

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: Young adult animals (approx. 10-11 weeks old) were selected
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum
- Housing: Group housing of 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: Acclimatization period was 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:2000 mg/kg (1.802 ml/kg) body weight

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations daily, weighing weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

No statistical analysis was performed

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 (Table 1 in attached background material).

Clinical signs:

other: On day 1 hunched posture was noted in three females, and lethargy and uncoordinated movements were noted in one other female. (Table 2 in attached background material).

Gross pathology:

Reddish foci on the thymus was found in one animal at macroscopic post mortem examination. Macroscopic post mortem examination of the other animals did not reveal any abnormalities (Table 4 in attached background material).

Applicant's summary and conclusion

Interpretation of results:

relatively harmless

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Acute toxicity of Bis(ethylacetoacetato-O1', O3") bis(2-methyl propan-1-olato)titanium, was evaluated using OECD 423 Acute toxic class method. The LD50 value in rats was established to exceed 2 000 mg/kg of body weight measured by administering test substance as a single oral dose to female animals.

Executive summary:

Bis(ethylacetoacetato-O1', O3") bis(2-methyl propan-1-olato)titanium was administered as an oral gavage in female rats to evaluate acute toxicity. The test substance did not cause any deaths during the study period and thus the LD50 value was concluded to be > 2 000mg/kg body weight under the conditions of this study.

Based on these results, Bis(ethylacetoacetato-O1', O3") bis(2-methyl propan-1-olato)titanium does not have to be classified according to Regulation (EC) No 1272/2008 (CLP) for acute oral toxicity. This study was regarded reliable without restrictions since the study was conducted in accordance with OECD No. 423 guideline and in compliance with GLP.