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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: carcinogenicity study
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
DL-menthol (CAS 89-78-1), USP-grade
- 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

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
103 w
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
3750 or 7500 ppm (= ca. 188 or 375 mg/kg bw/d)
Basis:
nominal in diet
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

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
ca. 375 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Remarks on result:
other: 375 mg/kg bw was the highest applied dose
Dose descriptor:
NOAEL
Effect level:
ca. 188 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: based on slightly reduced body weight at 375 mg/kg bw
Remarks on result:
other: 375 mg/kg bw was the highest applied dose

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

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.

Applicant's summary and conclusion

Conclusions:
dl-menthol was neither toxic nor carcinogenic to Fisher 344 rats
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.

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.

Based on the histopathologic examination, dl-menthol was neither toxic nor carcinogenic to Fisher 344 rats under the conditions of this bioassay.

The NOAEL in these study can be considered with 375 mg/kg bw/d for male rats. For female rats the NOAEL is 188 mg/kg

based on slightly reduced body weight at 375 mg/kg bw.