Menthol

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Remarks:

other: carcinogenicity study with histopathologic examiniation of male and female reproduction organs

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: other: carcinogenicity study with histopathologic examiniation of male and female reproduction organs

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.
At the end all animals were killed and necropsied; gross and microscopic examination of: all major organs, including reproductive organs; in male rats prostate,testes, epididymis, scrotum; in female rats mammary gland, vagina, uterus, uterus/endometrium, ovary/panovarian, ovary.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Menthol

EC Number:

201-939-0

EC Name:

Menthol

Cas Number:

89-78-1

Molecular formula:

C10H20O

IUPAC Name:

2-isopropyl-5-methylcyclohexanol

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

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Vehicle:

corn oil

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

103 weeks

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

3 570 ppm

Remarks:

ca. 188 mg/kg bw/d

Doses / concentrations 2

Dose / conc.:

7 500 ppm

Remarks:

ca. 375 mg/kg bw/d

No. of animals per sex per dose:

50 rats of either sex/dose

Control animals:

other: untreated diet containing 2 % corn oil

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Effect level:

ca. 375 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Remarks on result:

other: 375 mg/kg bw/d was the highest applied dose

Applicant's summary and conclusion

Conclusions:

Histopathological examinations of the reproduction organs of rats and mice showed no changes in repeated dose toxicity studies with D/L-menthol and also in carcinogenicity studies with D/Lmenthol.
Hence there is no indication of a potential of D/L-menthol to interfere adversely with reproduction.

Executive summary:

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. Body weights and clinical signs were recorded and pathological and histopathological examinations conducted. At the end all animals were killed and necropsied; gross and microscopic examination of: all major organs, including reproductive organs; in male rats prostate,testes, epididymis, scrotum; in female rats mammary gland, vagina, uterus, uterus/endometrium, ovary/panovarian, ovary.

Histopathological examinations of the reproduction organs of rats showed no changes in the repeated dose toxicity studies with D/L-menthol and also in carcinogenicity studies with D/Lmenthol. Hence there is no indication of a potential of D/L-menthol to interfere adversely with reproduction.