Registration Dossier

Administrative data

Description of key information

Menthol is not considered to have sensitizing properties.

This is in agreement with the OECD SIDS initial assessment that concluded: “All studied isomers of menthol are moderately irritating to the skin and slightly irritating to the eye. The skin sensitization potency of menthol isomers in animals and humans is low.” (OECD SIDS 2003)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well documented and scientifically acceptabl
Reason / purpose:
read-across: supporting information
Principles of method if other than guideline:
The sensitisation potential of a test material, HR 90/000102 (= L-menthol), was investigated by means of the Buehler Test for sensitisation in guinea pigs.
Following dose ranging a concentration of 25% w/v in ethanol:DEP was selected for induction and challenge.
GLP compliance:
yes
Type of study:
Buehler test
Justification for non-LLNA method:
The study was conducted in 1991. At this time an OECD guideline for a LLNA was not available.
Specific details on test material used for the study:
- Source and lot/batch No.of test material: HR 90/000102
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Route:
epicutaneous, occlusive
Vehicle:
other: 25% wv in ethanol:diethylphthalate (1:1)
Concentration / amount:
25 %
Route:
epicutaneous, occlusive
Vehicle:
other: 25% wv in ethanol:diethylphthalate (1:1)
Concentration / amount:
25 %
No. of animals per dose:
test grup: 20 guine pigs
control group: 20 guinea pigs
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
25% in ethanol:DEP (vehicle)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 25% in ethanol:DEP (vehicle). No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
ethanol:DEP (vehicle)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: ethanol:DEP (vehicle). No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
25% in ethanol:DEP (vehicle)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 25% in ethanol:DEP (vehicle). No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
ethanol:DEP (vehicle)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: ethanol:DEP (vehicle). No with. + reactions: 0.0. Total no. in groups: 20.0.

Induction

No irritation was noted in any of the test group animals in Weeks 1, 2 or 3 of induction.

No irritation was noted in the control group animals at any time during induction.

Challenge

No positive responses were noted in any of the animals in the test group or the control group after challenge

with HR 90/000102 at a concentration of 25% w/v in ethanol :DEP.

There were no reactions to challenge with the vehicle in the test or control groups.

Interpretation of results:
GHS criteria not met
Executive summary:

The sensitisation potential of a test material, HR 90/000102 (L-menthol), was investigated by means of the Buehler Test for sensitisation in guinea pigs.

Following dose ranging a concentration of 25% w/v in ethanol:DEP was selected for induction and challenge.

At challenge, none of the test and control group animals treated with HR 90/000102 at a concentration of 25% w/v in ethanol:DEP showed a positive response.

There is no evidence from the test results that HR 90/000102 (L-menthol) is a sensitiser in guinea pigs.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The sensitisation potential of L-menthol (CAS 2216-51-5) was investigated by means of the Buehler Test for sensitisation in guinea pigs. The test procedure followed the OECD guideline 406. A concentration of 25% w/v of the test substance in ethanol:DEP (1:1) was selected for induction and challenge and no sensitization potential was identified (Cutbert 1991). A LLNA with L-menthol (CAS 2216-51-5) is available as a secondary source evaluated within the OECD SIDS initial assessment on the menthols and showed also no skin sensitization potential. In addition a limited skin sensitisation study using a modified Draize procedure reported no sensitization potential for brasilian methol ( racemic, l-enthol, d-menthol) (Hopf, 1974).

The OECD SIDS Initial Assessment Report 2003 evaluated L, D, and racemic L/D menthols together and gives the rational for a menthol category as follows: "Category Rationale: The menthols category is comprised of the isomers L-menthol, D-menthol, the racemate and menthol (unspecified isomers). The menthols can be considered as a category because of their similarity in physico-chemical, toxicological, ecotoxicological and environmental fate properties....In summary, the available toxicity data indicate very similar toxicity profiles for all of the menthol isomers investigated." The category justification is documented in a comprehensive 15 page annex to the SIDS Assessment report (Annex 1: Menthols Category Justification). The annex is attached to the study record entry on the OECD SIDS evaluation in the chapter “Toxicokinetics) as attached background material.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

no data

Justification for classification or non-classification

In a Buehler test the test material is judged to be non-sensitising when topically applied to Hartley guinea pigs. The LLNA was also negative. Based on the available human data a sensitisation potential of the menthol isomers is considered to be low. Therefore a classification is not justified.