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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 June 2010 - 09 Feb 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
24 April 2002
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
No. 440/2008
Deviations:
not specified
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: TD-9024390, received November 1, 2010
- Expiration date of the lot/batch: November 1, 2011
- Purity: 99.63%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test item was used as supplied.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: TD-9024390, received November 1, 2010
- Expiration date of the lot/batch: November 1, 2011
- Purity: 99.63%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test item was used as supplied.

OTHER SPECIFICS:
- Appearance: pale yellow liquid
- pH measurement inmediately prior to commencement of the study: undiluted material pH 6.5, diluted (90% v/v) aquous solution pH 5.0.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd., Loughborough, UK
- Age at study initiation: twelve to twenty weeks
- Weight at study initiation: 2.20 to 2.53 kg
- Housing: individually, in suspended cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): undiluted
Duration of treatment / exposure:
The upper and lower eyelids were held together for about one second immediately after treatment.
Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment
Number of animals or in vitro replicates:
3 animals
Details on study design:
SCORING SYSTEM:
The data relating to the conjunctivae were designated by the letters A (redness), B (chemosis) and C (discharge), those relating to the iris designated by the letter D and those relating to the cornea by the letters E (degree of opacity) and F (area of cornea involved). For each tissue the score was calculated as follows:
Score for conjunctivae = (A+ B + C) x 2
Score for iris = Dx5
Score for cornea = (Ex F) x 5

Using the numerical data obtained a modified version of the system described by Kay J Hand Calandra JC (1962), J. Soc. Cosmet. Chem. 13, 281-289 (see Appendix 3) was used to classify the ocular irritancy potential of the test item.

TOOL USED TO ASSESS SCORE: the light source from a standard ophthalmoscope.

OTHERS: One drop of local anaesthetic instilled into both eyes 1 to 2 minutes before treatment

PROJECT NUMBER: 41004217

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: #1, 2 and 3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: #1, 2 and 3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Time point:
other: 48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Time point:
24 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Time point:
48 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Time point:
24/48 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #3
Time point:
72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: #1 and 3
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal: #1 and 3
Time point:
other: 48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
48 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Discharge
Basis:
animal: #1 and 3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Discharge
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 48h
Irritation parameter:
conjunctivae score
Remarks:
Discharge
Basis:
animal #2
Time point:
other: 48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No corneal or iridial effects were noted during the study.

Moderate conjunctival irritation was noted in all treated eyes one hour after treatment.
Moderate conjunctival irritation persisted in one treated eye with minimal conjunctival irritation noted in two treated eyes at the 24-Hour observation.
Minimal conjunctival irritation was noted in two treated eyes at the 48-Hour observation.

One treated eye appeared normal at the 48-Hour observation and two treated eyes appeared normal at the 72-Hour observation.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Remarks:
Based on Annex I of the CLP Regulation (1272/2008/EC
Conclusions:
Based on the results of this study, methyl n-amyl ketone does not need to be classified for eye irritation in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).
Executive summary:

The study was performed to assess the irritancy potential of methyl n-amyl ketone to the eye of the New Zealand White rabbit. The method was designed to be compatible with OECD TG 405 and EC No. 440/2008 Method 85. Three rabbits were exposed to 0.1 mL of the undiluted substance. A single application of the test item to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. One treated eye appeared normal at the 48-hour observation and two treated eyes appeared normal at the 72-Hour observation. As the effects were fully reversible, no corneal opacity or iritis was observed, and conjunctival effects of grade 2 were observed at 24h in one animal only, methyl n-amyl ketone does not need to be classified for eye irritation in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).