DL-menthol

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable and sufficient documented but no NOAEL determined

Data source

Reference

Reference Type:

publication

Title:

Effects of menthol vapor on the intact animal with special reference to the upper respiratory tract

Author:

Rakieten N, Rakieten ML, Boykin M

Year:

1954

Bibliographic source:

J Am Pharm Assoc 43, 390-392, 1954

Materials and methods

Principles of method if other than guideline:

Rats were exposed to menthol vapour of various concentrations for a period of 71 to 79 days and a study was made of the overall effects

Test material

Test material information

Constituent 1

Reference substance name:

L-menthol

EC Number:

218-690-9

EC Name:

L-menthol

Cas Number:

2216-51-5

IUPAC Name:

2-isopropyl-5-methylcyclohexanol

Details on test material:

l-menthol USP

Test animals

Species:

rat

Strain:

Sherman

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

71, 74, 75, 79 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0.087, 0.148 and 0.259 ppm (according to 0.57, 0.96 and 1.68 mg/m³)
Basis:
other: The exposure concentrations are given as weight of menthol vaporized divided by the volume of air circulated

No. of animals per sex per dose:

Three groups of 12 animals, 6 males and 6 females, were exposed to menthol vapours. One groups of 12 animals was exposed to conditions identical with the menthol groups except for the menthol

Control animals:

yes, concurrent no treatment

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

It was found that there were no gross toxic effects, but a histopathological examination of organ tissues revealed that changes indicative of irritation had occured in the lungs of animals exposed to the highest concentration of menthol.

Applicant's summary and conclusion

Executive summary:

Rats were exposed to menthol vapour of various concentrations for a period of 71 to 79 days and a study was made of the overall effects. It was found that there were no gross toxic effects, but a histopathological examination of organ tissues revealed that changes indicative of irritation had occured in the lungs of animals exposed to the highest concentration of menthol.

As the measurement of the exposure concentration does not seem reliable, this study cannot be used to derive a NOAEL. However, it points to the respiratory system as possible target organ after exposure by inhalation.