Registration Dossier

Administrative data

Description of key information

L Menthol is :
Skin irritant.
Slightly eye irritant

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

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

Additional information

Skin irritation

The cutaneous irritation potential of L-Menthol at 5 different concentrations in diethylphthalate (DEP) (i.e. 1, 5, 25, 50 and 100%) was assessed following guideline OECD 404. All the tests were performed in the same institute and followed the same protocol.

L Menthol in concentrations higher than 50% shall be classified as skin irritant.

Ocular irritation

Menthols were tested for eye irritation according to the OECD guideline 405.

The vehicle diethylphthalate (DEP) alone revealed no irritating properties.

Slightly irritating effects to the eye have been found using L Menthol concentrations of 29 to 64 %. The L Menthol eye irritation testing results are in line with the eye irritation potential of other Menthol isomers tested in rabbit eyes.

All examinations were performed in the same institute according to the same protocol.

An overview of mean score values from all valid experimental eye irritation studies in rabbits is provided in the following table. Values meeting the classification threshold of the CLP are marked in bold font.

Test item

Test Conc.

Mean scores of the 24-, 48- and 72-hour readings

Study No.

Conjunctiva Discharge

Conjunctiva
Redness

Conjunctiva
Chemosis

Iris

Cornea

Unspecified mixture of menthol isomers

100%

0.3

2.2

0.7

0.0

1.0

1989072

Unspecified mixture of menthol isomers

71%

0.3

2.2

0.7

0.0

1.0

1989031

L Menthol

64.3 %

0.3

2.0

0.6

0.0

1.0

1989070

D Menthol

64.3 %

0.3

2.1

0.3

0.0

0.9

1989071

DL Menthol

64 %

0.3

2.1

0.3

0.0

1.0

1989073

DL Menthol

40 %

0.3

1.9

0.3

0.0

1.0

1989073

DL Menthol

40 %

0.6

1.5

0.6

0.0

0.8

1989028

L Menthol

28.6%

0.3

1.2

0.3

0.0

0.8

1989070

L Menthol

28.6%

0.0

0.6

0.1

0.0

0.2

1989029

D Menthol

28.6%

0.2

1.3

0.1

0.0

0.5

1989071

D Menthol

28.6%

0.5

1.3

0.5

0.0

0.4

1989030

Diethyl phthalate (DEP)

Pure

0.0

0.0

0.0

0.0

0.0

1985152

 

Thus Menthols should be classified as eye irritant category 2 under Regulation (EC) No 1272/2008. However, the data do not meet the criteria of eye irritant under Directive 67/548/EEC




Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin irritation: L Menthol meets the criteria for classification and labelling as skin irritant, as defined in Regulation (EC) No. 1272/2008. The substance showed irritating properties with a maximum oedema score of 2.9 (conc. 100%) and 2.2 at a concentration of 50 %. At the end of the post treatment observation period (14days) the skin was intact but still covered with white-brown scales in the areas treated with 50 and 100% concentration.

A concentration limit for skin irritation Category 2 respectively Xi, R38 according to DSD is set to "> 25% by weight".

Eye irritation: L Menthol when tested as suspension/solution in DEP at 64% caused eye irritation above the classification criteria according to the Classification, Labelling and Packaging Directive (CLP) 1272/2008/EC. Therefore, L Menthol (CAS 2216-51-5) has to be classified as Category 2 Eye Irritant, “Warning”, H319: Causes serious eye irritation.

With regard to classification according to the Dangerous Substances Directive (DSD) 67/548/EEC, neither neat unspecified mixture of Menthol isomers nor L-, D- and DL Menthol when tested as suspension/solution in DEP at 64% or lower concentration caused eye irritation that met the classification thresholds. It is considered unlikely that pure L-, D- or DL Menthol would be more irritating than neat unspecified mixture of Menthol isomers. Therefore, L Menthol has not to be classified with regard to eye irritation according to the Dangerous Substances Directive (DSD) 67/548/EEC.

Respiratory irritation:Menthol was tested several times in 13 weeks inhalation studies (OECD 413) in rats in the context of cigarette smoke. No irritating potential exceeding the irritation of tobacco smoke was reported.