1,3-dimethylbut-3-enyl isobutyrate

Eye irritation

Administrative data

Endpoint:

eye irritation, other

Remarks:

Old in-vivo study from 1979 so no new amnimals have been used.

Type of information:

experimental study

Adequacy of study:

key study

Study period:

December 13, 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was performed according to 16 CFR 1500.42 (US) test guideline. The study was conducted prior to the OECD Test Guideline No. 405 but the protocol is similar to that guidance.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Section 1500.42 - Hazardous Substances and Articles, Administration and Enforcement Regulations, Federal Register, Vol. 38. No. 187, p. 27019, 27 September 1973.

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

(no details on test animals and environmental conditions)

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,3-dimethylbut-3-enyl isobutyrate

EC Number:

279-399-0

EC Name:

1,3-dimethylbut-3-enyl isobutyrate

Cas Number:

80118-06-5

Molecular formula:

C10H18O2

IUPAC Name:

4-methylpent-4-en-2-yl 2-methylpropanoate

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): MT-102 Methylpentenol isobutyrate
- Physical state: Clear colorless liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: approved USDA supplier
- Weight at study initiation: 2.18-3.26 g

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): Undiluted

Duration of treatment / exposure:

No wash: The eyes of six animals were not washed out after instillation of the test material.
Washout: The eyes of three animals were washed out 4 seconds after instillation of the test material, with distilled water for approximately 10 seconds or until all test material was removed from the eye.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

No wash: six animals
Washout: three animals

Details on study design:

PRETREATMENT
The eyes of each rabbit were examined with sodium fluorescein and an ultraviolet lamp (prior to instillation of the test material) and only those rabbits whose eyes were free of irritation and corneal lesions were used.

REMOVAL OF TEST SUBSTANCE
- No wash: The eyes of six animals were not washed out after instillation of the test material.
- Washout: The eyes of three animals were washed out 4 seconds after instillation of the test material, with distilled water for approximately 10 seconds or until all test material was removed from the eye.

SCORING SYSTEM: Draize method

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: no wash out

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

2

Remarks on result:

other: no wash out

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

6 animals

Time point:

other: 24, 48 and 72 h

Score:

0.5

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: no wash out

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

6 animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: no wash out

Results 5

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

3 animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: wash out

Results 6

Irritation parameter:

iris score

Basis:

mean

Remarks:

3 animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

2

Remarks on result:

other: wash out

Results 7

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

3 animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

3

Remarks on result:

other: wash out

Results 8

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

3 animals

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Remarks on result:

other: wash out

Irritant / corrosive response data:

One animal in the 4-second washout group of the original study was observed to have corneal damage after 72 h. This finding was thought to be an artifact, as even the no washout group demonstrated absolutely no corneal damage. The 4 second washout group was repeated and no corneal damage was observed.

No wash out: Conjunctival effects were observed in three animals. This effect cleared in one animal during the 48 h reading and two animals cleared during the 7-day observation period.

Wash out: No ocular reactions were observed.

Other effects:

None

Any other information on results incl. tables

Table 7.3.2/1: Eye irritation response data for each animal at each observation time

Score at time point	Cornea		Iris (/2)	Conjunctivae
	Opacity (/4)	Area (/4)		Redness (/3)	Chemosis (/4)	Discharge (/3)
Washout
24 h (Day 1)	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0
48 h (Day 2)	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0
72 h (Day 3)	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0
Day 7	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0
Mean individual score 24, 48 and 72 h	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0
Reversibility	-	-	-	-	-	-
No wash
24 h (Day 1)	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	2 / 0 / 1 / 0 / 0 / 1	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0
48 h (Day 2)	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	2 / 0 / 1 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0
72 h (Day 3)	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	1 / 0 / 1 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0
Day 7	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0
Mean individual score 24, 48 and 72 h	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0	1.67 / 0 / 1.00 / 0 / 0 / 0.33	0 / 0 / 0 / 0 / 0 / 0	0 / 0 / 0 / 0 / 0 / 0
Reversibility	-	-	-	fully reversible within: 7 days	-	-

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information cannot be evaluated Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the test material induced mild irritation being reversible within 7 days. Therefore, the test material is not classified as irritant to the eyes.

Executive summary:

In an eye irritation study, 0.1 mL of undiluted test material was instilled into one eye of 9 New Zealand white rabbits while the untreated eye remained untreated and served as control. In Group 1, the eyes of six animals were not washed out after instillation of the test material. In Group 2, the eyes of three animals were washed out 4 seconds after instillation of the test material, with distilled water for approximately 10 seconds or until all test material was removed from the eye. Animals were observed at 24, 48 and 72 h after instillation of test material and then on Days 7. The reactions in the conjunctivae (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the Draize scale.

One animal in the 4-second washout group of the original study was observed to have corneal damage after 72 h. This finding was thought to be an artifact, as even the no washout group demonstrated absolutely no corneal damage. The 4 second washout group was repeated and no corneal damage was observed. 

Conjunctival effects (redness) were observed in three animals of the unwashed group. Those conjunctival redness, calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, were below the limit of classification (1.67 / 1 / 0.33 ≤ 2), cleared in one animal during the 48 h reading and in the two other animals during the 7-day observation period. 

 

Under the test conditions, the test material is not classified as irritating to the eyes according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

Although some details on test animals and experimental conditions were missing, this study is considered as acceptable and satisfies the requirement for eye irritation endpoint.