Titanium tetrabutanolate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

October 3, 1984 - November 16, 1984

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study pre-dates GLP and performed according to a non-guideline method. Insufficient data is provided on study methods and results. However, the test material contained only 25 % titanium tetrabutanolate. The main component of the test material was kerosene (75 %).

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:

The test material was evaluated for primary skin irritation potential in male and female rabbits. Prior treatment, the dorsal area of each rabbit was clipped free of hair. 0,5ml aliquot of the test material was applied under a one by one square gauze patch which was secured in place with adhesive tape. The trunk of each rabbit was wrapped with impervious rubber damming and the rabbits were then immobilized in stocks for 24hours. Twenty-four hours following application, the test substance was removed and the exposure sites were wiped with propylene glycol. Dermal responses were graded and scored at 24. 48. 72 and 96 hours and 7 days.

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(4+) tetrakis(butan-1-olate)

Details on test material:

- Name of test material (as cited in study report): 1-butanol, titanium (4+) Salt, Haskell No. 15,538
- Substance type:organometal
- Physical state: liquid
- Analytical purity: 95-100%
- Impurities (identity and concentrations): Possibly 1-butanol 0-5%
- Composition of test material, percentage of components: 25 % titanium tetrabutanolate, 75 % kerosene
- Storage condition of test material: at room temparature

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Dutchland. Inc., Denver, Pennsylvania
- Housing: individually in elevated wire-mesh cages
- Diet (e.g. ad libitum): commercial rabbit ration (Purina Lab Rabbit Chow #5321) ad libitum except during 24 hours immobilization period
- Water (e.g. ad libitum): tap water ad libitum except during 24 hours immobilization period
- Acclimation period: minimum of seven days

After observation period of 7 days all rabbits were sacrificed with T61 euthanasia solution and discarded without necropsy

Test system

Type of coverage:

not specified

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0,5ml
- Concentration (if solution): 100%

Duration of treatment / exposure:

24 hours

Observation period:

At 24, 48, 72 and 96 hours and 7 days after test material application the skin responses were recorded

Number of animals:

6

Details on study design:

TEST SITE
The dorsal area of each rabbit was clipped free of hair. Test material was applied under a one by one square gauze patch which was secured in place with adhesive tape. The trunk of each rabbit was wrapped with impervious rubber damming and the rabbits were then immobilized in stocks for 24hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): exposure sites were wiped with propylene glycol
- Time after start of exposure: 24h

SCORING SYSTEM:
Draize scale for scoring primary skin irritation

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Remarks on result:

positive indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Remarks on result:

positive indication of irritation

Results 3

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Remarks on result:

positive indication of irritation

Results 4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Remarks on result:

positive indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Remarks on result:

positive indication of irritation

Results 6

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Remarks on result:

positive indication of irritation

Results 7

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Remarks on result:

positive indication of irritation

Results 8

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Remarks on result:

positive indication of irritation

Results 9

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2

Max. score:

4

Remarks on result:

positive indication of irritation

Results 10

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Remarks on result:

positive indication of irritation

Results 11

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Remarks on result:

positive indication of irritation

Results 12

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Remarks on result:

positive indication of irritation

Results 13

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

1.74

Reversibility:

not reversible

Remarks on result:

other: Skin blanching, thickening, fissuring and necrosis was observed

Irritant / corrosive response data:

Titanium tetrabutanolate produced well-defined erythema (Grade 2) in five animals and moderate to severe erythema (Grade 3) in one animal at 24 hours. Well-defined erythema (Grade2) was noted also in five animals at 48 hours, in all animals at 72 hours, and in only one animal at 96 hours. Very slight erythema (Grade 1) was noted in one animal at 48 hours and in five animals at 96 hours. Moderate to severe edema (Grades 3 or 4) was noted in all animals at 24 hours, subsiding to very slight edema in all animals at 48 hours and in three animals at 72 hours. Other dermal effects noted during this study were skin blanching, thickening, fissuring, and necrosis. No mortality occurred during the study.

Other effects:

Animal Other dermal effects
Number Sex 24h 48h 72h 96h 7d
E36661 M B BT TN N N
E36662 M B BT BT N N
E36663 M B BTF TN N N
E36702 F B BTF BTF TNF N
E36103 F B BTF BTF NF NF
E36704 F B TF BTF N N

B-Blanching
T-Thickening
F-Fissuring
N-Necrosis

Any other information on results incl. tables

Animal		Erythema score							Edema score
Number	Sex	24h	48h	72h	96h	7d	avg 24/48/72		24h	48h	72h	96h	7d	avg 24/48/72
E36661	M	2	2	2	1	0	2,0		3	1	0	0	0	1,3
E36662	M	2	2	2	1	0	2,0		3	1	1	0	0	1,7
E36663	M	2	2	2	1	0	2,0		3	1	0	0	0	1,3
E36702	F	2	2	2	2	0	2,0		4	1	0	0	0	1,7
E36103	F	3	2	2	1	0	2,3		3	1	1	0	0	1,7
E36704	F	1	1	2	1	0	1,3		3	1	1	0	0	1,7

Applicant's summary and conclusion

Interpretation of results:

highly irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The primary dermal irritation/corrosion potential of the test substane (25 % titanium tetrabutanolate, 75 % kerosene) was evaluated when applied to the skin of rabbits for 24 hour. By the study report, the test substance is considered to be severely irritating.

Executive summary:

This study was regarded not reliable, since the study pre-dates GLP and performed according to a non-guideline method. Insufficient data is provided on study methods and results. By the study report, the test substance is severe skin irritant.

The result of this study cannot be used to evaluate the skin irritation of titanium tetrabutanolate, since the composition of the tested material was 25 % titanium tetrabutanolate and 75% kerosene. Thus, the result is used as a weight of evidence in hazard assessment.