Tetra-n-butyl titanate, polymer with water

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Remarks:

no data

Type of information:

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

Adequacy of study:

key study

Study period:

October 3, 1984 - October 6, 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP and non-giudeline study, but the method and results are well documented and scientfically acceptable.

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:

eye irritation: in vivo

Remarks:

no data

Type of information:

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

Adequacy of study:

key study

Study period:

October 3, 1984 - October 6, 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP and non-giudeline study, but the method and results are well documented and scientfically acceptable.

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:

0,01 ml of the undiluted test substance was placed into the right conjunctival sac of two albino rabbit. After 20 seconds treated eye was washed with 25% propylene glycol in distilled water for one minute. The treated eye of the other rabbit was not washed. Observations of the cornea, iris and conjunctiva were made at one and four hours, and at one, two and three days.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazleton Dutcland Inc., Denver, Pennsylvania
- Housing: individually in elevated wire-mesh cages
- Diet (e.g. ad libitum): Purina Lab Rabbit Chow #5321 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: minimun of seven days

IN-LIFE DATES: From: To: All surviving rabbits were sacrificed at 72 hours postinstillation

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.01 ml

Duration of treatment / exposure:

Test material was placed into right conjunctival sac in each of 2 rabbits. After 20 seconds the eye of one rabbit was washed for 1 minute with 25% propylene glycol in distilled water. The second was dosed in a similar manner, but no washing was performed. Observations were made up to day 72 hours.

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

2 (one male/one female)

Details on study design:

0.01 ml of undiluted test material was placed into the right conjunctival sac of each of 2 rabbits. After 20 seconds, 1 treated eye was washed with a 25% propylene glycol/water solution to see if effects after washing with this solution were less than with water. The treated eye of the other rabbit was not washed. Ophthalmoscopic examinations of the cornea, iris and conjunctiva were made at 1, 4, 24, 48 and 72 hours. Fluorescein staining of right eye was peformed at 24, 48 and 72 hour time points for corneal defects.
At termination (72 hours postinstillation), all surviving rabbits were sacrificed with T-61 Euthanasia solution (Taylor Pharma Company, Dacatur, Illinois) and discarded without necropsy.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Irritation parameter:

overall irritation score

Basis:

animal #1

Remarks:

washed

Time point:

24 h

Score:

0

Reversibility:

fully reversible within: 24h

Irritation parameter:

overall irritation score

Basis:

animal #1

Remarks:

washed

Time point:

72 h

Score:

0

Reversibility:

fully reversible within: 24h

Irritation parameter:

overall irritation score

Basis:

animal #2

Remarks:

not washed

Time point:

24 h

Score:

2

Reversibility:

fully reversible within: 72h

Irritation parameter:

overall irritation score

Basis:

animal #2

Remarks:

not washed

Time point:

72 h

Score:

0

Reversibility:

fully reversible within: 72h

Test material caused conjunctival irritation (redness, grade 2) in the washed eye at 1 and 4 hours but subsided to grade 1 at 24 and 48 hours. Chemosis (grade 1) was noted in the unwashed and washed eyes at 1 and 4 hours. A discharge (grade 1) was observed in both the unwashed and washed eye at 1 and 4 hours only. No opacity or iritis was observed in either eye at any observation interval throughout the study. Fluorescein and ophthalmoscopic examinations were negative in both eyes at all observation periods.  

Rabbit No E36664	Observation intervals
unwashed eye (male)	1h	4h	24h	48h	72h
Cornea
Opacity	0	0	0	0	0
Area involved	0	0	0	0	0
Subtotal	0	0	0	0	0
Iris	0	0	0	0	0
Subtotal	0	0	0	0	0
Conjunctivae
Redness	1	1	0	0	0
Chemosis	1	1	0	0	0
Discharge	1	1	0	0	0
Subtotal	6	6	0	0	0
Total Score	6	6	0	0	0

Rabbit No E36705	Observation intervals
washed eye (female)	1h	4h	24h	48h	72h
Cornea
Opacity	0	0	0	0	0
Area involved	0	0	0	0	0
Subtotal	0	0	0	0	0
Iris	0	0	0	0	0
Subtotal	0	0	0	0	0
Conjunctivae
Redness	2	2	1	1	0
Chemosis	1	1	0	0	0
Discharge	1	1	0	0	0
Subtotal	8	8	2	2	0
Total Score	8	8	2	2	0

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The eye irritation potential of titanium tetrabutanolate was evaluated when introduced to the eyes of rabbits. According study report, the test material was considered a eye irritant.

Executive summary:

Test material was applied undiluted into the eyes of two rabbits. After 20 seconds, treated eye of one rabbit was washed with 25% propylene glycol in water. The treated eye of the other rabbit was not washed. Observations were made at 1, 4, 24, 48 and 72 hours . Test material caused conjunctival irritation (redness, grade 2) in the washed eye at 1 and 4 hours but subsided to grade 1 at 24 and 48 hours. Chemosis (grade 1) was noted in the unwashed and washed eyes at 1 and 4 hours. A discharge (grade 1) was observed in both the unwashed and washed eye at 1 and 4 hours only. No opacity or iritis was observed in either eye at any observation interval throughout the study. Fluorescein and ophthalmoscopic examinations were negative in both eyes at all observation periods.

This study was regarded reliable with restrictions. Though, this study is non-GLP and non-giudeline study, the method and results are well documented and scientifically acceptable. Thus, this study is used as a key study for hazard assessment.

This toxicity study from this analogue category member (Titanium tetrabutanolate) is used for the weight of evidence to justify that the eye irritation of Tetra-n-butyl titanate, polymer with water. Eye irritation result of Tetra-n-butyl titanate and the use of read-across data from 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:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

0,01 ml of the undiluted test substance was placed into the right conjunctival sac of two albino rabbit. After 20 seconds treated eye was washed with 25% propylene glycol in distilled water for one minute. The treated eye of the other rabbit was not washed. Observations of the cornea, iris and conjunctiva were made at one and four hours, and at one, two and three days.

GLP compliance:

not specified

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): 1-Butanol, titanium (4+) Salt, Haskell No. 15,538. Other codes: TLF-6171, lot 1
- Composition of test material, percentage of components: 25% titanium tetrabutanolate
75% kerosene

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazleton Dutcland Inc., Denver, Pennsylvania
- Housing: individually in elevated wire-mesh cages
- Diet (e.g. ad libitum): Purina Lab Rabbit Chow #5321 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: minimun of seven days

IN-LIFE DATES: From: To: All surviving rabbits were sacrificed at 72 hours postinstillation

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.01 ml

Duration of treatment / exposure:

Test material was placed into right conjunctival sac in each of 2 rabbits. After 20 seconds the eye of one rabbit was washed for 1 minute with 25% propylene glycol in distilled water. The second was dosed in a similar manner, but no washing was performed. Observations were made up to day 72 hours.

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

2 (one male/one female)

Details on study design:

0.01 ml of undiluted test material was placed into the right conjunctival sac of each of 2 rabbits. After 20 seconds, 1 treated eye was washed with a 25% propylene glycol/water solution to see if effects after washing with this solution were less than with water. The treated eye of the other rabbit was not washed. Ophthalmoscopic examinations of the cornea, iris and conjunctiva were made at 1, 4, 24, 48 and 72 hours. Fluorescein staining of right eye was peformed at 24, 48 and 72 hour time points for corneal defects.
At termination (72 hours postinstillation), all surviving rabbits were sacrificed with T-61 Euthanasia solution (Taylor Pharma Company, Dacatur, Illinois) and discarded without necropsy.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Results 5

Irritation parameter:

overall irritation score

Basis:

animal #1

Remarks:

washed

Time point:

24 h

Score:

0

Reversibility:

fully reversible within: 24h

Results 6

Irritation parameter:

overall irritation score

Basis:

animal #1

Remarks:

washed

Time point:

72 h

Score:

0

Reversibility:

fully reversible within: 24h

Results 7

Irritation parameter:

overall irritation score

Basis:

animal #2

Remarks:

not washed

Time point:

24 h

Score:

2

Reversibility:

fully reversible within: 72h

Results 8

Irritation parameter:

overall irritation score

Basis:

animal #2

Remarks:

not washed

Time point:

72 h

Score:

0

Reversibility:

fully reversible within: 72h

Any other information on results incl. tables

Test material caused conjunctival irritation (redness, grade 2) in the washed eye at 1 and 4 hours but subsided to grade 1 at 24 and 48 hours. Chemosis (grade 1) was noted in the unwashed and washed eyes at 1 and 4 hours. A discharge (grade 1) was observed in both the unwashed and washed eye at 1 and 4 hours only. No opacity or iritis was observed in either eye at any observation interval throughout the study. Fluorescein and ophthalmoscopic examinations were negative in both eyes at all observation periods.  

Rabbit No E36664	Observation intervals
unwashed eye (male)	1h	4h	24h	48h	72h
Cornea
Opacity	0	0	0	0	0
Area involved	0	0	0	0	0
Subtotal	0	0	0	0	0
Iris	0	0	0	0	0
Subtotal	0	0	0	0	0
Conjunctivae
Redness	1	1	0	0	0
Chemosis	1	1	0	0	0
Discharge	1	1	0	0	0
Subtotal	6	6	0	0	0
Total Score	6	6	0	0	0

Rabbit No E36705	Observation intervals
washed eye (female)	1h	4h	24h	48h	72h
Cornea
Opacity	0	0	0	0	0
Area involved	0	0	0	0	0
Subtotal	0	0	0	0	0
Iris	0	0	0	0	0
Subtotal	0	0	0	0	0
Conjunctivae
Redness	2	2	1	1	0
Chemosis	1	1	0	0	0
Discharge	1	1	0	0	0
Subtotal	8	8	2	2	0
Total Score	8	8	2	2	0

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The eye irritation potential of titanium tetrabutanolate was evaluated when introduced to the eyes of rabbits. According study report, the test material was considered a eye irritant.

Executive summary:

Test material was applied undiluted into the eyes of two rabbits. After 20 seconds, treated eye of one rabbit was washed with 25% propylene glycol in water. The treated eye of the other rabbit was not washed. Observations were made at 1, 4, 24, 48 and 72 hours . Test material caused conjunctival irritation (redness, grade 2) in the washed eye at 1 and 4 hours but subsided to grade 1 at 24 and 48 hours. Chemosis (grade 1) was noted in the unwashed and washed eyes at 1 and 4 hours. A discharge (grade 1) was observed in both the unwashed and washed eye at 1 and 4 hours only. No opacity or iritis was observed in either eye at any observation interval throughout the study. Fluorescein and ophthalmoscopic examinations were negative in both eyes at all observation periods.

This study was regarded reliable with restrictions. Though, this study is non-GLP and non-giudeline study, the method and results are well documented and scientifically acceptable. Thus, this study is used as a key study for hazard assessment.

This toxicity study from this analogue category member (Titanium tetrabutanolate) is used for the weight of evidence to justify that the eye irritation of Tetra-n-butyl titanate, polymer with water. Eye irritation result of Tetra-n-butyl titanate and the use of read-across data from Titanium tetrabutanolate is justified.

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