Tetra-n-butyl titanate, polymer with water

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

October 23, 1978 - January 12, 1979

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Study pre-dates GLP and performed according to a non-guideline method. Insufficient data is provided on study methods and results.

Justification for type of information:

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.

Cross-reference

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

October 23, 1978 - January 12, 1979

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Study pre-dates GLP and performed according to a non-guideline method. Insufficient data is provided on study methods and results.

Justification for type of information:

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.

Qualifier:

no guideline followed

Principles of method if other than guideline:

One drop (~0,05ml) 5% and 50% solution (vol/vol) of the test material in acetone was applied on shaved, shoulder intact skin of 10 guinea pigs. Skin reaction was observed and recorded at 24h and at 48h after test material application.

GLP compliance:

no

Species:

guinea pig

Strain:

other: albino

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 480g

Type of coverage:

not specified

Preparation of test site:

shaved

Vehicle:

other: acetone

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: One drop (~0,05ml)
- Concentration (if solution): 5% and 50% (vol/vol)

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

Duration of treatment / exposure:

24 hours and 48 hours

Observation period:

At 24 hours and 48 hours after test material application skin reactions were recorded

Number of animals:

10 animals

Details on study design:

TEST SITE
-shoulder skin of the animal

REMOVAL OF TEST SUBSTANCE
-washing of the test substance was not done

SCORING SYSTEM:
+ mild erythema
++ moderate erythema
+++ strong erythema
++++ erythema plus edema
+++++ necrosis

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

other:

Basis:

animal #1

Time point:

48 h

Score:

1

Max. score:

6

Reversibility:

not specified

Remarks on result:

probability of weak irritation

Irritation parameter:

other:

Basis:

animal #2

Time point:

48 h

Score:

1

Max. score:

6

Reversibility:

not specified

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

Titanic acid, tetrabutyl ester caused moderate to no irritation when tested as a 50% suspension in acetone on the shaved, intact skin of guinea pigs and mild to no irritation when tested as a 5% suspension.

Reactions on intact guinea pig skin

	Test group (10 animals)	Test group (10 animals)
Concentration in acetone	50%	5%
Primary irritation test - 24 hours	1+, 9 negative	1+, 9 negative
Primary irritation test - 48 hours	1 +, 9 negative	1+, 9 negative

Reaction codes are as follows: + mild erythema ++moderate erythema +++ strong erythema ++++ erythema plus oedema +++++necrosis

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The primary dermal irritation potential of titanium tetrabutanolate was evaluated when applied to the skin of guinea pigs for 24 hour and for 48 hour. The test substance is considered to be mild skin irritant according to this study.

Executive summary:

Titanium tetrabutanolate was applied in two concentrations (5% and 50% vol/vol in acetone) to two separate test areas on the intact skin on each animal´s back. By the study report the test material is considered to be mild irritant to the skin of guinea pigs.

 

This study was regarded not reliable since the study pre-dates GLP and it is non-guideline study. Furthermore, the study report includes insufficient details on study methods and results. This study does not satisfy the guideline requirements for the skin irritation study.

 

This toxicity study from this analogue category member (Titanium tetrabutanolate) is used for the weight of evidence to justify that the skin irritation of Tetra-n-butyl titanate, polymer with water. Skin irritation result from organometallic category member Titanium tetrabutanolate is justified.

The result of this study is used as a weight of evidence in hazard assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

One drop (~0,05ml) 5% and 50% solution (vol/vol) of the test material in acetone was applied on shaved, shoulder intact skin of 10 guinea pigs. Skin reaction was observed and recorded at 24h and at 48h after test material application.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Titanium tetrabutanolate

EC Number:

227-006-8

EC Name:

Titanium tetrabutanolate

Cas Number:

5593-70-4

Molecular formula:

C16H36O4Ti

IUPAC Name:

titanium tetrakis(butan-1-olato)

Details on test material:

- Name of test material (as cited in study report): Titanic acid, tetrabutyl ester; Haskell No 12,678
- Substance type: organometallic
- Physical state: liquid
- Analytical purity: 95%
- Lot/batch No.: 12,678

Test animals

Species:

guinea pig

Strain:

other: albino

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 480g

Test system

Type of coverage:

not specified

Preparation of test site:

shaved

Vehicle:

other: acetone

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: One drop (~0,05ml)
- Concentration (if solution): 5% and 50% (vol/vol)

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

Duration of treatment / exposure:

24 hours and 48 hours

Observation period:

At 24 hours and 48 hours after test material application skin reactions were recorded

Number of animals:

10 animals

Details on study design:

TEST SITE
-shoulder skin of the animal

REMOVAL OF TEST SUBSTANCE
-washing of the test substance was not done

SCORING SYSTEM:
+ mild erythema
++ moderate erythema
+++ strong erythema
++++ erythema plus edema
+++++ necrosis

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Results 3

Irritation parameter:

other:

Basis:

animal #1

Time point:

48 h

Score:

1

Max. score:

6

Reversibility:

not specified

Remarks on result:

probability of weak irritation

Results 4

Irritation parameter:

other:

Basis:

animal #2

Time point:

48 h

Score:

1

Max. score:

6

Reversibility:

not specified

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

Titanic acid, tetrabutyl ester caused moderate to no irritation when tested as a 50% suspension in acetone on the shaved, intact skin of guinea pigs and mild to no irritation when tested as a 5% suspension.

Any other information on results incl. tables

Reactions on intact guinea pig skin

	Test group (10 animals)	Test group (10 animals)
Concentration in acetone	50%	5%
Primary irritation test - 24 hours	1+, 9 negative	1+, 9 negative
Primary irritation test - 48 hours	1 +, 9 negative	1+, 9 negative

Reaction codes are as follows: + mild erythema ++moderate erythema +++ strong erythema ++++ erythema plus oedema +++++necrosis

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The primary dermal irritation potential of titanium tetrabutanolate was evaluated when applied to the skin of guinea pigs for 24 hour and for 48 hour. The test substance is considered to be mild skin irritant according to this study.

Executive summary:

Titanium tetrabutanolate was applied in two concentrations (5% and 50% vol/vol in acetone) to two separate test areas on the intact skin on each animal´s back. By the study report the test material is considered to be mild irritant to the skin of guinea pigs.

 

This study was regarded not reliable since the study pre-dates GLP and it is non-guideline study. Furthermore, the study report includes insufficient details on study methods and results. This study does not satisfy the guideline requirements for the skin irritation study.

 

This toxicity study from this analogue category member (Titanium tetrabutanolate) is used for the weight of evidence to justify that the skin irritation of Tetra-n-butyl titanate, polymer with water. Skin irritation result from organometallic category member Titanium tetrabutanolate is justified.

The result of this study is used as a weight of evidence in hazard assessment.