Bis(ethyl acetoacetato-O1',O3)bis(2-methylpropan-1-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:

October 23, 1978 - December 22, 1978

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: This study predates current guideline and the study report does not include details on test substance, test animals and test procedure.

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. Because of the rapid hydrolysis, the influence of the mode of administration through inhalation, dermal and oral is related to the organic degradation products released from the substance. Based on the toxicological properties of these degradation products the hazard assessment concentrates on the most hazardous degradation product (alcohols). The testing conducted with analogue substances of the category (category 1 and 2) proves that the toxicity is similar to the toxicity of alcohol released when the target substance comes in contact with moisture. The identification of degradation products from the hydrolysis study conducted for the target substance verifies that there are no impurities released from the target substance which might change the toxicity of the target substance compared to the toxicity of the pure alcohol or ethyl acetoacetate. 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 and therefore the read-across from the most hazardous degradation products can be used to evaluate the toxicological effects of the target substance. In addition, as all the titanates in category 1 and 2 have similar hydrolyzing behavior, the test results of analogue category members releasing same alcohols can be used to read-across the short-term and long-term toxicity, skin and eye irritation, sensitization, and genotoxicity of the target substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

0.1 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 tap 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, three, seven, fourteen and twenty-one 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 tetrakis(butan-1-olato)

Details on test material:

- Name of test material (as cited in study report): Titanic acid, tetrabutyl ester; Haskell Number 12,678
- Substance type: organometal
- Physical state: liquid

Test animals / tissue source

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

Rabbits were described albino rabbits. There were no details on environmental conditions.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

Test substance was placed into the right conjunctival sac. Observations were made at 1, 4, 24, 48, 72 hours, and at days 7, 14, and/or 21.

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

24

Details on study design:

0.1 ml test substance was placed into the right conjunctival sac. Total of 2 animals were treated. After 20 seconds treated eye of the one rabbit was washed with tap water for one minute. The treated eye of the other rabbit was not washed. Observations of the cornea, iris and conjunctiva were made with hand-slit lamp at 1, 4, 24, 48, 72 hours, and at days 7, 14, and 21. Fluor-i-strip stain and a biomicroscope were used at examinations after the day of treatment.

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:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Results 3

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Results 4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not determinable

Any other information on results incl. tables

Animal/treatment	Cornea	Iris	Conjunctiva
0.1 ml undiluted liquid, Eye not washed	Cornea not seen 1 -4 hrs. due to conjunctival swelling. Generalized moderate opacity with severe corneal swelling 1 -14 days. Moderate area of moderate opacity with moderate to severe swelling at 21 days.	Iris not seen 1 -4 hrs. due to conjunctival swelling. Moderate to severe irritis with a flare 1 -3 days; moderate at 7 days; slight injection at 14 days.	Redness: Severe 1 hr.-7 days with blanching at 1 hr. - 1 day; moderate at 14 days. Swelling:. Severe 1 - 4hrs.; moderate 1 -4 days; mild at 7 days; slight at 14 days Discharge: Copious Hemastix -Positive 1hr-2 days; moderate Hemastix-Positive at 3 days; mild at 7 days
0.1 ml undiluted liquid, Eye washed after 20 seconds	Generalized mild opacity 1 hr.-3 days with severe corneal swelling 1 -2 days and moderate to severe swelling at 3 days; Moderate area of slight opacity with mild to moderate swelling at 7 days; Small area of slight opacity with mild corneal swelling 14 -21 days	Moderate iritis 1hr.-3 days with a flare 1 -2 days	Redness: Severe 1 hr-3 days with blanching at 1 hr-1 day. Swelling: Moderate at 1 hr.; moderate to severe at 4hrs.; moderate 1 -2 days; mild at 3 days Discharge: Copious Hemastix-Positive 1 hr.-1 day; moderate at 2 days; mild at 3 days

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye)

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. The test material caused persistent lesions which were not fully reversible within an observation period of 21 days and is thus classified in Category 1 eye irritant by the applicant.

Executive summary:

Titanium tetrabutanolate was applied undiluted into the eyes of two rabbits. After 20 seconds, treated eye of one rabbit was washed with water. The treated eye of the other rabbit was not washed. Observations were made at 1 and 4 hours, and at 1, 2, 3, 7, 14, and 21 days for the treated eyes. Titanium tetrabutanolate severely irritated the cornea and conjunctiva and moderately to severily irritated the iris of both the washed and unwashed rabbit eyes. At 21 days, the unwashed eye had moderate to severe corneal irritation and the washed eye had mild corneal irritation.

This study was regarded as non reliable, since the study report does not include details on test material and test procedure. Furthermore, tabulation of irritant/corrosive response data for each animal at each observation time point is missing.

This study does not satisfy the guideline requirements for the eye irritation study and thus the result of this study is used as a supporting evidence for hazard assessment