Registration Dossier

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-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
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
Qualifier:
equivalent or similar to
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

Reference
Name:
Unnamed
Type:
Constituent
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

Resultsopen allclose all
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
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
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
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
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
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
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
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.