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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
12 July 2012 to 31 July 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted in accordance with OECD No. 423 guideline and in compliance with GLP. Read-across justification: The substance is hydrolytically unstable. When it comes in contact with water or moisture complete hydrolysis will take place with no significant reaction products other than the particular alcohol and hydrated titanium dioxide. This rapid hydrolysis (hydrolysis half-life < 3 minutes to < 2 hours) is the driving force for toxicokinetics of the target substance. Because of the rapid hydrolysis the influence of the mode of administration through inhalation, dermal and/or oral is related to the most hazardous degradation product (alcohol) released from the substance. The testing conducted with analogue substances of the category proves that the toxicity is similar to the toxicity of alcohol released from the target substance in contact with moisture. The identification of degradation products from the hydrolysis study conducted for the target substance verifies that there are no impurities in the alcohol released from the target substance which might change the toxicity of the target substance compared to the toxicity of the pure alcohol. The read-across approach from analogue category members are used to justify that the mode of administration through oral, inhalation and/or dermal is similar to the adverse effects of the degradation products. In addition, the test results of analogue category members releasing same alcohols are used to evaluate the short term and long-term toxicity, skin and eye irritation and sensitization, and mutagenic properties of the target substance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No. 8147, April 2011; including the most recent partial revisions.
Qualifier:
according to
Guideline:
other: As required by the Dutch Act on Animal Experimentation (February 1997), this type of protocol was reviewed and agreed by the Laboratory Animal Welfare Officer and the Ethical Committee (DEC 03-42)
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
other: Viscous liquid
Details on test material:
- Name of test material (as cited in study report): Tetra-n-butyl titanate
- Molecular formula (if other than submission substance): Not applicable as the substance is an UVCB
- Physical state: Yellow viscous liquid
- Analytical purity: unknown
- Lot/batch No.: 304-300137/000060
- 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
Reactivity: Reactive to moisture
Specific Gravity: 1.12 at 25ºC
Stability in vehicle: Stable at least six hours
Solubility in vehicle: Suspension

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 11-12 weeks old)
- 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.
- 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.
- 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 degrees C
- Humidity (%): 40 to 70
- Air changes (per hr): 15 room air changes/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hours dark cycle

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Kaydoll mineral oil
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance.

MAXIMUM DOSE VOLUME APPLIED: 2000mg/kg BW
Doses:
2000 mg/kg body weight
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: Day 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology.
Statistics:
No data

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occured
Clinical signs:
Lethargy, hunched/flat posture, slow breathing and/or uncoordinated movements were noted among the animals on Day 1.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals

Any other information on results incl. tables

Read-across justifications and data matrices are presented in IUCLID section 13.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The oral LD50 value of tetra-n-butyl titanate in Wistar rats was established to exceed 2000 mg/kg body weight.

Tetra-n-butyl titanate does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.
Executive summary:

Tetra-n-butyl titanate, polymer with water, analogue category member of titanium tetrabutanolate, was administered as an oral gavage in female rats to evaluate acute toxicity. This study result from analogue category member is used for the weight of evidence to evaluate the acute oral toxicity of titanium tetrabutanolate because both substances release butanol upon hydrolysis.

Tetra-n-butyl titanate, polymer with water did not cause any deaths during the study period and thus the LD50 value was concluded to be > 2 000mg/kg body weight. Based on this result, titanium tetrabutanolate is expected have low acute oral toxicity.

This study was regarded reliable since the study was conducted in accordance with OECD No. 423 guideline and in compliance with GLP.