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Administrative data

Endpoint:
neurotoxicity: short-term oral
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
No data
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Publication is very concise but is from the same group as the disregarded repeated dose toxicit studies, and as such mentioned in the endpoint summary on repeated dose toxicity. As the results of these studies could not be reproduced, they were carefully evaluated (extensive evaluation available in endpoint summary). The histopathological findings in the brain were considered to be artefacts of preparation and fixation of the brain tissue. Consequently, the study was considered invalid.

Data source

Reference
Reference Type:
publication
Title:
Neurotoxicity in rats dosed with Peppermint oil and pulegone
Author:
P Olsen and I Thorup
Year:
1984
Bibliographic source:
Arch. Toxicol. Suppl. 7, 408-409 (1984)

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of 10 male and 10 female rats were given by gavage 0, 10, 40 or 100 mg/kg bw/day of Peppermint oil for 28-days. The observations included clinical, biochemical, haematological and pathological parameters. The same experiment was performed for Pulgeone, which is present in Peppermint oil for 2-4% (doses: 0, 20, 80 and 160 mg/kg bw/day).
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
Peppermint oil
IUPAC Name:
Peppermint oil
Details on test material:
- Name of test material (as cited in study report): Peppermint oil
- Composition of test material, percentage of components: 2-4% Pulegone

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
28 days
Frequency of treatment:
Once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
10, 40 and 100 mg/kg bw/day
Basis:

No. of animals per sex per dose:
10
Control animals:
yes, concurrent no treatment

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
10 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Dose-related increase of cyst-like spaces in cerebellum in 40 and 100 mg/kg bw/day group
Remarks on result:
other:

Any other information on results incl. tables

Microscopical examination revealed similar dose-related lesions in the white matter of the brain for both Peppermint oil and Pulegone. Cyst-like spaces were seen scattered in the white matter, especially in the cerebellum, without any cellular reaction in the surrounding tissue. Demyelination could not be demonstrated using staining procedures appropriate for myelin sheets.

Applicant's summary and conclusion

Conclusions:
Under the conditions of this study, Peppermint oil was shown to increase the formation of cyst-like spaces in the cerebellum of rats dosed with 40 and 100 mg/kg bw/day. The NOAEL for neurotoxicity was therefore established to be 10 mg/kg bw/day.
Executive summary:

Groups of 10 male and 10 female rats were given by gavage 0, 10, 40 or 100 mg/kg bw/day of Peppermint oil for 28-days. The experiment included clinical, biochemical, haematological and pathological parameters. The same experiment was performed for Pulegone, which is present in Peppermint oil for 2-4% (doses: 0, 20, 80 and 160 mg/kg bw/day).

Microscopical examination revealed similar dose-related lesions in the white matter of the brain for both Peppermint oil and Pulegone. Cyst-like spaces were seen scattered in the white matter, especially in the cerebellum, without any cellular reaction in the surrounding tissue. Demyelination could not be demonstrated using staining procedures appropriate for myelin sheets.

Under the conditions of this study, Peppermint oil was shown to increase the formation of cyst-like spaces in the cerebellum of rats dosed with 40 and 100 mg/kg bw/day. The NOAEL for neurotoxicity was therefore established to be 10 mg/kg bw/day.

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