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

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Study period:

There is no study period reported

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

The test procedure predates current guideline, but it is comparable with OECD 405.

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 alcohols, ethyl acetoacetate and hydrated titanium dioxide. The half-life of hydrolysis is < 10 minutes @ 25 ˚C. This rapid hydrolysis is the driving force for the toxicokinetics of target substance. Because of the rapid hydrolysis, the influence of the mode of administration through inhalation, dermal and oral is related to the most hazardous degradation products released from the target substance. In addition, because of rapid hydrolysis the dermal effects of the target substance are similar to the irritating properties of the degradation products. The identification of degradation products from the hydrolysis study conducted for the target substance verifies that there are no impurities in the mixture of particular alcohol and ethyl acetoacetate which might change the hazardous properties of the target substance compared to the properties of the pure alcohol and ethyl acetoacetate. As there is a mechanistic reasoning to the read-across, the unnecessary animal testing is avoided by using the read-across from the most hazardous degradation products (alcohols) to evaluate irritation, sensitization and the short-term and long-term toxicological effects of the target substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Final score at 7 days rather than 21 days. No irritation results presented at 1hour after test item application and at 7 days.

Principles of method if other than guideline:

Test item was applied in the conjuctival sac of one eye. The second, untreated eye, served as a control. Irritation of eyes were observed at 1, 24, 48, 72 hours and 7 days after test item application.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Titanium tetraisopropanolate

EC Number:

208-909-6

EC Name:

Titanium tetraisopropanolate

Cas Number:

546-68-9

Molecular formula:

C12H28O4Ti

IUPAC Name:

Titanium tetrakis(propan-2-olato)

Details on test material:

- Name of test material (as cited in study report): Isopropyl titanate; Inbifo number: S 2575 A1
- Substance type: organometal
- Physical state: liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 3-4 kg
- Housing: stainless steel cage without litter
- Diet (e.g. ad libitum): standard pellet for rabbit ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: >3 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 1 °C
- Humidity (%): 55 ± 10%
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 ml was placed into the conjunctival sac of one eye by means of a tuberculin syringe (without a needle).

Duration of treatment / exposure:

Single treatment followed by 7 day observation period.

Observation period (in vivo):

7 days.

Number of animals or in vitro replicates:

6

Details on study design:

For each animal there was a comparison of treated and untreated eye and classification of findings according to Draize scale. Recordings were made at 1 h, 24 h, 48 h and 72 h after instillation. In case, irritation was observed at 72 hours observation was performed at 7 days.

SCORING SYSTEM:

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Results 2

Irritation parameter:

overall irritation score

Basis:

mean

Remarks:

18 animals

Time point:

24/48/72 h

Score:

30.3

Max. score:

110

Reversibility:

not specified

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

18 animals

Time point:

24/48/72 h

Score:

16.6

Max. score:

80

Reversibility:

not specified

Results 4

Irritation parameter:

iris score

Basis:

mean

Remarks:

18 animals

Time point:

24/48/72 h

Score:

0.9

Max. score:

10

Reversibility:

not specified

Results 5

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

18 animals

Time point:

24/48/72 h

Score:

9.8

Max. score:

20

Reversibility:

not specified

Irritant / corrosive response data:

The irritation index for the titanium tetrapropanolate was 30.3

Other effects:

1 h after application: Redness and swelling of the conjunctiva and strong secretion were recorded. Also recorded was a white-yellowish, sliding pad on the cornea; this was tentatively considered to be the test item
24 h to 72 h after application: Purulent surface in five rabbits was recorded.
7 d after application: No significant change from the 72 h findings was reported.

Any other information on results incl. tables

	24 hours						48 hours						72 hours
Rabbit numbers	1	2	3	4	5	6	1	2	3	4	5	6	1	2	3	4	5	6
Cornea opacity (a)	0	1	0	1	1	1	0	1	0	1	1	1	0	2	0	2	2	1
Area of cornea (b)	0	4	0	4	4	4	0	4	0	4	4	4	0	4	0	4	4	4
1: a x b x 5 (max 80)	0	20	0	20	20	20	0	20	0	20	20	20	0	40	0	40	40	20
Iris score	1	1	1	1	1	1	0	1	0	1	1	1	0	1	0	1	1	1
2: Iris score x 5	5	5	5	5	5	5	0	5	0	5	5	5	0	5	0	5	5	5
Conjunctivae redness (a)	2	2	1	2	1	1	1	1	1	2	2	2	1	1	1	2	2	2
Conjunctivae chemosis (b)	2	2	1	3	4	2	1	2	1	1	3	1	1	2	1	1	1	2
Conjunctivae discharge (c)	3	3	2	3	3	3	1	2	0	3	3	1	0	2	0	0	0	1
3: a x b x c x 2 (max 20)	14	14	8	16	16	12	6	10	4	12	16	8	4	10	4	6	6	10
Score 1 + 2 + 3 (max 110)	19	39	13	41	41	37	6	35	4	37	41	33	4	55	4	51	51	35

Applicant's summary and conclusion

Interpretation of results:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Eye irritation properties of titanium tetraisopropanolate was evaluated after test item administration to rabbit eye. The test substance was classified as moderately irritating.

Executive summary:

Eye irritation potential of titanium tetraisopropanolate was evaluated by administering test substance into eye of six rabbits. Eye responses were recorded at 1h, 24h, 48h, 72h and 7 days after test item application and the responses were evaluated according to Draize scale.

The study is considered reliable with restrictions, since the test procedure predates current guideline, but it is comparable with OECD 405 guideline study. Although the assessment of reversibility of eye responses finished at 7 days after application it was noted that at 7 days there was no significant change from the findings at 72 hours.

By the study report, titanium tetraisopropanolate was classified moderately irritating.