Registration Dossier

Administrative data

Description of key information

Analogue based Read Across to Octan-3-one (ethyl amyl ketone)

Methyl n-amyl ketone (MAK):

- Skin irritation (OECD 404): category 2 irritant

- Eye irritation (OECD405): not irritant

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
14 June 2010 - 21 Feb 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 24 April 2002)
Deviations:
not specified
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
No. 440/2008
Deviations:
not specified
GLP compliance:
yes (incl. certificate)
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.
Species:
rabbit
Strain:
New Zealand White
Details on test animals 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: 2.21 or 2.49 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

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Undiluted

Duration of treatment / exposure:
4 hours
Observation period:
Immediately after removal, and after 1, 24, 48 and 72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: Back
- % coverage:2.5 cm x 2.5 cm
- Type of wrap if used: cotton gauze

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test item was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
Immediately after removal, and after 1, 24, 48 and 72 hours, Days 7 and 14

SCORING SYSTEM:
- Method of calculation: The scores for erythema and oedema at the 24 and 72-Hour readings were totalled for the three test rabbits (12 values) and this total was divided by six to give the primary irritation index of the test item. The test item was classified according to the following scheme devised by Draize J H (1959) "Dermal Toxicity" In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, p.46-59

Erythema and Eschar Formation Value
0. No erythema
1. Very slight erythema (barely perceptible)
2. Well-defined erythema
3. Moderate to severe erythema
4. Severe erythema (beef redness) to eschar formation preventing grading of erythema

Oedema Formation
0. No oedema
1. Very slight oedema (barely perceptible)
2. Slight oedema (edges of area well-defined by definite raising)
3. Moderate oedema (raised approximately 1 millimetre)
4. Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure)

Any other skin reactions and clinical signs of toxicity, if present, were also recorded.
Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.
Irritation parameter:
erythema score
Basis:
animal: #1, 2 and 3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks:
Slight desquamation was observed after 14 days in 1 animal
Irritation parameter:
edema score
Basis:
animal: #1, 2 and 3
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks:
at 7 days 1 animal still showed adverse reaction which prevented the accurate evaluation of oedema
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
7 d
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks:
Slight desquamation was observed
Remarks on result:
not determinable
Irritation parameter:
edema score
Basis:
animal #1
Time point:
7 d
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
not determinable
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal: #1, 2 and 3
Time point:
other: 24/72 hours
Score:
3.7
Max. score:
8
Reversibility:
fully reversible within: 14 days
Remarks:
Slight desquamation was observed after 14 days in 1 animal
Remarks on result:
probability of moderate irritation
Irritant / corrosive response data:
Well-defined erythema and slight oedema were noted at one treated skin site immediately and one hour after patch removal. Well-defined erythema and very slight or slight oedema were noted at all treated skin sites at the 24, 48 and 72-Hour observations. Light brown discolouration of the epidermis and loss of skin flexibility and/or elasticity were noted at one treated skin site at the 24, 48 and 72-Hour observations with crust formation, which prevented accurate evaluation of erythema and oedema, noted at this treated skin site at the 7-Day observation and slight desquamation at the 14-Day observation. Slight desquamation was noted at the other two treated skin sites at the 7-Day observation. the Primary Irritation Index was calculated to be 3.7.
Interpretation of results:
other: Category 2 irritant
Remarks:
Annex I of the CLP Regulation (1272/2008/EC).
Conclusions:
Based on the results in this study the compound should be classified as a category 2 irritant 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 skin of the New Zealand White rabbit. The method was compliant with OECD TG 404 and EC Method 84 No. 440/2008. One of the rabbits was initially treated, to determine the effects of exposure after 3-minute and 1-hour semi-occluded applications of the test item to the intact skin. The substance produced no corrosive effects. A single 4-hour, semi-occluded application of the test item to the intact skin of three rabbits produced well-defined erythema and slight immediately and one hour after patch removal. Well-defined erythema and very slight or slight oedema were noted at all treated skin sites at the 24, 48 and 72-Hour observations. Other signs of skin irritation noted were light brown discolouration of the epidermis, loss of skin flexibility and/or elasticity, crust formation and slight desquamation. The test item produced a primary irritation index of 3.7 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. Based on the results in this study the compound should be classified as a category 2 irritant in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See attached justification
Reason / purpose:
read-across source
Irritation parameter:
erythema score
Basis:
animal: #1, 2 and 3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks:
Slight desquamantion was observed after 14 days in 1 animal
Irritation parameter:
edema score
Basis:
animal: #1, 2 and 3
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks:
at 7 days 1 animal still showed adverse reaction wich prevented the accurate evaluation of oedema
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
7 d
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks:
Slight desquamantion was observed
Remarks on result:
not determinable
Irritation parameter:
edema score
Basis:
animal #1
Time point:
7 d
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
not determinable
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
animal: #1, 2 and 3
Time point:
other: 24/72 hours
Score:
3.7
Max. score:
8
Reversibility:
fully reversible within: 14 days
Remarks:
Slight desquamantion was observed after 14 days in 1 animal
Remarks on result:
probability of moderate irritation
Irritant / corrosive response data:
Well-defined erythema and slight oedema were noted at one treated skin site immediately and one hour after patch removal. Well-defined erythema and very slight or slight oedema were noted at all treated skin sites at the 24, 48 and 72-Hour observations. Light brown discolouration of the epidermis and loss of skin flexibility and/or elasticity were noted at one treated skin site at the 24, 48 and 72-Hour observations with crust formation, which prevented accurate evaluation of erythema and oedema, noted at this treated skin site at the 7-Day observation and slight desquamation at the 14-Day observation. Slight desquamation was noted at the other two treated skin sites at the 7-Day observation. the Primary Irritation Index was calculated to be 3.7.
Interpretation of results:
other: Category 2 irritant
Remarks:
Annex I of the CLP Regulation (1272/2008/EC).
Conclusions:
Based on the information on read-across of the dermal irritation to the source substance Methyl n-Amyl Ketone, the target compound Ethyl Amyl Ketone needs to be classified as a category 2 irritant 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 skin of the New Zealand White rabbit. The method was compliant with OECD TG 404 and EC Method 84 No. 440/2008. One of the rabbits was initially treated, to determine the effects of exposure after 3-minute and 1-hour semi-occluded applications of the test item to the intact skin. The substance produced no corrosive effects. A single 4-hour, semi-occluded application of the test item to the intact skin of three rabbits produced well-defined erythema and slight immediately and one hour after patch removal. Well-defined erythema and very slight or slight oedema were noted at all treated skin sites at the 24, 48 and 72-Hour observations. Other signs of skin irritation noted were light brown discolouration of the epidermis, loss of skin flexibility and/or elasticity, crust formation and slight desquamation. The test item produced a primary irritation index of 3.7 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. Based on the results in this study the compound should be classified as a category 2 irritant in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

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
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)
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.
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
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
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.
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).

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See attached justification
Reason / purpose:
read-across source
Controls:
yes
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.
Interpretation of results:
other: Not classified
Remarks:
Based on Annex I of the CLP Regulation (1272/2008/EC
Conclusions:
Based on the information on read-across of the eye irritation using the source substance Methyl n-Amyl Ketone, the target compound Ethyl 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). This result was used for read-across to Ethyl Amyl Ketone (3-octanone). This result was used for read-across to Ethyl Amyl Ketone

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

One key study is available for the source substance Methyl n-amyl ketone which comprised skin and eye irritation (OECD TG 404 and OECD TG 405). The study was used for an analogue based Read Across to 3-octanone (ethyl amyl ketone).

Methyl n-amyl ketone (MAK):

Skin: An acute dermal irritation study was conducted to assess the irritancy potential of methyl n-amyl ketone to the skin of the New Zealand White rabbit. The method was compliant with OECD TG 404 and EC Method 84 No. 440/2008. One of the rabbits was initially treated, to determine the effects of exposure after 3-minute and 1-hour semi-occluded applications of the test item to the intact skin. The substance produced no corrosive effects. A single 4-hour, semi-occluded application of the test item to the intact skin of three rabbits produced well-defined erythema and slight immediately and one hour after patch removal. Well-defined erythema and very slight or slight oedema were noted at all treated skin sites at the 24, 48 and 72-Hour observations. Other signs of skin irritation noted were light brown discolouration of the epidermis, loss of skin flexibility and/or elasticity, crust formation and slight desquamation. The test item produced a primary irritation index of 3.7 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. Based on the results in this study the compound should be classified as a category 2 irritant in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).

 

Eye: An eye irritation 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).

Justification for classification or non-classification

From the available studies and category based Read Across to Octan-3-one (ethyl amyl ketone) it is concluded that 3-octanone (ethyl amyl ketone) needs to be classified as category 2 irritant but does not need to be classified for eye irritation, according to regulation 1272/2008/EC (CLP).