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Toxicological information

Carcinogenicity

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Description of key information

A bioassay of dl-menthol for possible carcinogenicity was conducted by administrating the test chemical in feed to Fisher 344 rats and B6C3F1 mice.

No carcinogenic effects were observed at the highest applied doses.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: oral
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 acceptable
Reason / purpose:
reference to same study
Principles of method if other than guideline:
A bioassay of dl-menthol for possible carcinogenicity was conducted by administrating the test chemical in feed to Fisher 344 rats.
Groups of 50 rats of each sex were administrated dl-menthol at one of the following doses, either 3750 or 7500 ppm for 103 weeks, then observed for 1 or 2 additional weeks. Matched controls consisted of 50 untreated rats of each sex. All surviving rats were killed at 105 weeks.
GLP compliance:
not specified
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 2 batches test:
Lot No. 4-HTP-6
Lot No. Nl 1-26-74-2054

Identity confirmed
Batch 1:
2 impurites:
0.3 %
1.3 %
Batch 2:
0.2 % Impurity

OTHER SPECIFICS: USP-grade
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Remarks:
diet
Duration of treatment / exposure:
103 w
Frequency of treatment:
daily
Post exposure period:
1 -2 weeks
Remarks:
Doses / Concentrations:
3750 or 7500 ppm (= ca. 188 or 375 mg/kg bw/d)
Basis:

No. of animals per sex per dose:
50 rats of either sex/dose
Control animals:
other: untreated diet containing 2 % corn oil
Details on study design:
Post-exposure period: 2 w
Relevance of carcinogenic effects / potential:
dl-menthol was not carcinogenic under the test conditions used
Dose descriptor:
NOAEL
Effect level:
ca. 375 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no carcinogenic effect at any dose
Remarks on result:
other: Effect type: carcinogenicity

Mean body weights of dosed rats were only slightly lower than those of corresponding controls. No other clinical signs related to administration of the dl-menthol were noted in the dosed groups of animals. Survival at the end of the bioassay was at least 62% in all dosed and control groups of animals and sufficient numbers of animals were at risk for the development of late-appearing tumors.

In both dose groups no increased incidence of neoplasms compared to the controls were observed.

Executive summary:

A bioassay of dl-menthol for possible carcinogenicity was conducted by administrating the test chemical in feed to Fisher 344 rats.

Groups of 50 rats of each sex were administrated dl-menthol at one of the following doses, either 3750 or 7500 ppm for 103 weeks, then observed for 1 or 2 additional weeks. Matched controls consisted of 50 untreated rats of each sex. All surviving rats were killed at 105 weeks.

In male rats, no tumors occured at incidences which were considered to be related to the administration of dl-menthol.

In female rats, no tumors occured at higher incidences in the dosed groups than in the control groups. Fibroadenomas of the mammary gland occured at lower incidences in the low dose (10/49) and high-dose (7/49) groups than in the control group (20/50), and alveolar/bronchiolar adenomas or carcinomas of the lung occured only in the controls (3/50).

There was no evidence of carcinogenicity of D/L-menthol in rats and mice in a study performed in accordance with current standards (highest tested dose levels in rats approx. 375 mg/kg bw). Since D/L-menthol contains the two relevant isomers in a 50:50 ratio it can be assumed that also L- and D-menthol have no carcinogenic properties.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
375 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
scientifically acceptable and well documented.

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In male and female rats the survival rate was not affected by treatment and no carcinogenic effects of D/L-menthol were found in any organ.

In mice of either sex, no tumors occurred in dosed groups at incidences that were significantly different from those for corresponding control groups.

Justification for classification or non-classification

From the available studies a classification according to CLP classification criteria (Regulation (EC) No 1272/2008) is not justified.