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Description of key information

No studies are available for L-menthyl acetate. Reliable data are available with the structural analogue menthyl acetate (CAS 89-48-5).

Skin: The test substance was shown to be not irritating to skin.

Eyes: The test substance was found to be non-irritating to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 2012-05-14 to 2012-08-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study according to OECD TG 439
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
2010
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Version / remarks:
2009
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Justification for test system used:
Because systemic reactions play a minor role in modulating local skin toxicity potential of chemicals, skin irritation potential may be predicted by in vitro systems, provided they are sufficiently complex to mimic human skin barrier and cell reactivity. In an international prevalidation study performed by ECVAM, the in vitro skin irritation test using the human skin model EpiDerm™ and EpiSkin™ and measurement of cell viability by dehydrogenase conversion of MTT into a blue formazan salt have turned out as a sufficiently promising predictor for skin irritancy potential.
Details on test animals or test system and environmental conditions:
not relevant
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 µL
- Concentration (if solution): undiluted
Duration of treatment / exposure:
15 min treatment + 42 h incubation
Number of animals:
not relevant
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with PBS
- Time after start of exposure: 15 min

SCORING SYSTEM:
In vitro result: In vivo prediction:
mean tissue viability ≤ 50 % → irritant (I), H315 (category 2)
mean tissue viability > 50 % → non-irritant (NI)
Irritation / corrosion parameter:
other: other: Relative Absorbance
Value:
105.3
Remarks on result:
other:
Remarks:
Basis: other: Test item on EpiSkin. Max. score: 100.0. Reversibility: no data. Remarks: % of negative control. (migrated information)

Results after treatment with menthyl acetate racemic and controls

Dose group

Treat-ment interval

Absor-bance

540 nm Tissue 1*

Absor-bance

540 nm Tissue 2*

Absor-bance

540 nm Tissue 3*

Mean Absorbance of 3 Tissue

Relative absor-bance

[%] Tissue

1, 2+3**

Stan-dard

De-viation [%]

Rel. Absor-bance

[% of negative control]***

Negative Control

15 min

1.154

1.047

1.032

1.077

107.1

97.2

95.8

6.2

100.0

Positive Control

15 min

0.175

0.142

0.154

0.157

16.3

13.2

14.3

1.6

14.6

Test Item

15 min

1.175

1.050

1.178

1.134

109.0

97.5

109.4

6.8

105.3

*Mean of two replicate after blank correction

**Relative absorbance per tissue [rounded values]: 100xabsorbance (tissue)/mean absorbance (negative control)

***Relative absorbance per treatment group [rounded values]: 100xmean absorbance (test item)/mean anbsorbance (negative control)

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The mean relative absorbance value of the test item, corresponding to the cell viability, did not decrease (105.3%; threshold for irritancy: ≤ 50%), consequently the test item was non irritant to skin.
Executive summary:

This in vitro study was performed to assess the irritation potential of Menthyl Acetate racemic by means of the Human Skin Model Test according to OECD TG 439. Three tissues of the human skin model EpiSkin™ were treated with the test item, the negative or the positive control for 15 minutes. 10 μL of the liquid test item were applied to each tissue, spread to match the tissue size. 10 μL of either the negative control (deionised water) or the positive control (5% Sodium lauryl sulfate) were applied to each tissue. After treatment with the negative control the absorbance values were well within the required acceptability criterion of mean OD  0.6 till ≤ 1.5 for the 15 minutes treatment interval thus showing the quality of the tissues. Treatment with the positive control induced a sufficient decrease in the relative absorbance as compared to the negative control for the 15 minutes treatment interval thus ensuring the validity of the test system. Compared to the value of the negative control, after exposure of the test item Menthyl Acetate racemic the mean relative absorbance value did not decrease (105.3%; threshold for irritancy of ≤ 50%). Therefore, the test item is not considered to possess an irritant potential. In conclusion, it can be stated that in this study and under the experimental conditions reported, the test item Menthyl Acetate racemic is non irritant to skin according to UN GHS and EU CLP regulation.

Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

Please refer to the attached read across justification in section 13.
Reason / purpose for cross-reference:
read-across source
Irritation / corrosion parameter:
other: Relative Absorbance
Value:
105.3
Remarks on result:
other: Basis: other: Test item on EpiSkin. Max. score: 100.0. Reversibility: no data. Remarks: % of negative control. (migrated information)
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
L-menthyl acetate is estimated to be not irritant to skin.
Executive summary:

One study is available from structural analogue menthyl acetate CAS 89-48-5. This in vitro study was performed to assess the irritation potential by means of the Human Skin Model Test according to OECD TG 439. Compared to the value of the negative control, after exposure of the test item the mean relative absorbance value did not decrease (105.3%; threshold for irritancy of ≤ 50%). Therefore, the test item is not considered to possess an irritant potential.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
from February 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
from January 1997
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: not reported
- Weight at study initiation: 2.8 - 3.2 kg bw
- Housing: caged individually in PPO cages (floor area: 2576 cm2) with perforated floor
- Diet (e.g. ad libitum): pelleted complete rabbit diet Altromin 2123 from Altromin, D-32791 Lage/Lippe, Germany, ad libitum
- Water (e.g. ad libitum): free access to domestic quality drinking watet acidified with hydrochloric acid to pH 2.5
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye remained untreated and served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
single administration; after 24 hour reading Fluorescein was instilled and treated eye was washed with 20 mL 0.9% sodium chloride solution
Observation period (in vivo):
The eyes were examined on the day before testing and 1, 24, 48 and 72 hours after the treatment.
Number of animals or in vitro replicates:
4
Details on study design:
REMOVAL OF TEST SUBSTANCE
- substance was not removed from the treated eye

SCORING SYSTEM:
see section "Any other information on materilas and methods incl. tables"

TOOL USED TO ASSESS SCORE:
Fluorescein was instilled after 24 hours, eyes were rinsed with 20 mL 0.9% sodium chloride solution and were examined using UV light
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: mean of scores at 24, 48 and 72 hours
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
One hour after application of the test article all animals showed a diffuse crimson red conjunctiva with individual vessels not easily discernible and some swelling above normal. After 24 hours all animals showed some conjunctival vessels definitely injected. After 48 and 72 hours all animals were free of any signs of eye irritation.
Other effects:
No other effects were reported.
Interpretation of results:
GHS criteria not met
Conclusions:
The substance is non irritating to the rabbit eye.
Executive summary:

The potential for eye irritation was tested for methyl acetate in a GLP study according to OECD guideline No. 405. Four female albino rabbits weighing 2.8 to 3.2 kg were used in the study. The day before testing both eyes of the animals were examined before and after the instillation of Fluorescein to ensure there were no defects or irritation. The next day an aliquot of 0.1 mL of the neat substance was placed in the left eyes of the animals by gently pulling the lower lid away from the eyeball. The lids were then gently hold together for one second. The right eye remained untreated and served as control. The eyes were examined and the grade of ocular reaction was recorded 1 and 24 hours later. After a first reading at 24 hours, Fluorescein was instilled and the treated eye was rinsed with 20 mL 0.9 % sodium chloride solution. Then the eye was examined again using UV-light to detect possible corneal damage. Further gradings were done after 48 and 72 hours after treatment. One hour after application of the test article all animals showed a diffuse crimson red conjunctiva with individual vessels not easily discernible and some swelling above normal. After 24 hours all animals showed some conjunctival vessels definitely injected. After 48 and 72 hours all animals were free of any signs of eye irritation. On the basis of these observations it was concluded that the substance is non-irritating to the rabbit eye.

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:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

Please refer to the attached read across justification in section 13.
Reason / purpose for cross-reference:
read-across source
GLP compliance:
yes
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: mean of scores at 24, 48 and 72 hours
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: mean of scores at 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
One hour after application of the test article all animals showed a diffuse crimson red conjunctiva with individual vessels not easily discernible and some swelling above normal. After 24 hours all animals showed some conjunctival vessels definitely injected. After 48 and 72 hours all animals were free of any signs of eye irritation.
Other effects:
No other effects were reported.
Interpretation of results:
GHS criteria not met
Conclusions:
The substance is estimated to be non irritating to the rabbit eye.
Executive summary:

One study is available from structural analogue menthyl acetate CAS 89 -48 -5. It is concluded that L-menthyl acetate is not irritating to eyes.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin:

An in vitro study was performed to assess the irritation potential of Menthyl Acetate racemic by means of the Human Skin Model Test according to OECD TG 439. Three tissues of the human skin model EpiSkin™ were treated with the test item, the negative or the positive control for 15 minutes. 10 μL of the liquid test item were applied to each tissue, spread to match the tissue size. 10 μL of either the negative control (deionised water) or the positive control (5% Sodium lauryl sulfate) were applied to each tissue. After treatment with the negative control the absorbance values were well within the required acceptability criterion of mean OD  0.6 till ≤ 1.5 for the 15 minutes treatment interval thus showing the quality of the tissues. Treatment with the positive control induced a sufficient decrease in the relative absorbance as compared to the negative control for the 15 minutes treatment interval thus ensuring the validity of the test system. Compared to the value of the negative control, after exposure of the test item Menthyl Acetate racemic the mean relative absorbance value did not decrease (105.3%; threshold for irritancy of ≤ 50%). Therefore, the test item is not considered to possess an irritant potential. In conclusion, it can be stated that in this study and under the experimental conditions reported, the test item Menthyl Acetate racemic is non irritant to skin according to UN GHS and EU CLP regulation.

Eyes:

The potential for eye irritation was tested for methyl acetate racemic in a GLP study according to OECD guideline No. 405. Four female albino rabbits weighing 2.8 to 3.2 kg were used in the study. The day before testing both eyes of the animals were examined before and after the instillation of Fluorescein to ensure there were no defects or irritation. The next day an aliquot of 0.1 mL of the neat substance was placed in the left eyes of the animals by gently pulling the lower lid away from the eyeball. The lids were then gently hold together for one second. The right eye remained untreated and served as control. The eyes were examined and the grade of ocular reaction was recorded 1 and 24 hours later. After a first reading at 24 hours, Fluorescein was instilled and the treated eye was rinsed with 20 mL 0.9 % sodium chloride solution. Then the eye was examined again using UV-light to detect possible corneal damage. Further gradings were done after 48 and 72 hours after treatment. One hour after application of the test article all animals showed a diffuse crimson red conjunctiva with individual vessels not easily discernible and some swelling above normal. After 24 hours all animals showed some conjunctival vessels definitely injected. After 48 and 72 hours all animals were free of any signs of eye irritation. On the basis of these observations it was concluded that the substance is non-irritating to the rabbit eye.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin and eye irritationthe test item is not classifiedaccording to Regulation (EC) No 1272/2008 (CLP), as amended for the eighth time in Regulation (EU) No 2016/918.