DL-menthol

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

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

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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:

DL-menthol

EC Number:

216-074-4

EC Name:

DL-menthol

Cas Number:

1490-04-6

Molecular formula:

C10H20O

IUPAC Name:

2-isopropyl-5-methylcyclohexanol

Constituent 2

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

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

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

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

ca. 375 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

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.