Peppermint, ext.

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Study period:

14 weeks in 2005

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Recent study conducted by NTP similarly to OECD guideline 413 with deviations: food consumption, hematology, ophthalmological examination, some organ weights were not recorded.

Data source

Reference

Reference Type:

other: data available on NTP website

Title:

Unnamed

Year:

2006

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

Deviations:

yes

Remarks:

(food consumption, hematology, ophthalmological examination, some organ weights were not recorded)

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Pin-2(3)-ene

EC Number:

201-291-9

EC Name:

Pin-2(3)-ene

Cas Number:

80-56-8

Molecular formula:

C10H16

IUPAC Name:

4,7,7-trimethylbicyclo[3.1.1]hept-3-ene

Constituent 2

Reference substance name:

4,6,6-trimethylbicyclo[3.1.1]hept-3-ene

IUPAC Name:

4,6,6-trimethylbicyclo[3.1.1]hept-3-ene

Details on test material:

- Purity ≥ 97%

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

After a 10- to 14-day quarantine period, animals are assigned at random to treatment groups.

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

not specified

Remarks on MMAD:

MMAD / GSD: No data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

14 weeks; 6 hours per day

Frequency of treatment:

Five times per week, weekdays only

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
25
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
50 ppm
Basis:
nominal conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
100 ppm
Basis:
nominal conc.

Doses / concentrations 4

Remarks:

Doses / Concentrations:
200 ppm
Basis:
nominal conc.

Doses / concentrations 5

Remarks:

Doses / Concentrations:
400 ppm
Basis:
nominal conc.

No. of animals per sex per dose:

10

Control animals:

yes

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Effect level:

50 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Presence of transitional cell hyperplasia of the urinary bladder.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The NOAEL in male and female rats is 50 ppm based on minimal to moderate hyperplasia observed in the transitional epithelium of the urinary bladder in animals treated at 100 to 400 ppm.

Executive summary:

In a 90-day inhalation study conducted by NTP similarly to OECD guideline 413, groups of 10 animals per dose and per sex were administered for 6 hours per day, 5 weekdays per week at 0, 25, 50, 100, 200 and 400 ppm for a total of 14 weeks. The animals were observed twice per day and weighed once per week. A complete histopathologic evaluation including treatment-related gross lesions was performed on all animals including early death animals. Treatment-related lesions (target organs) were identified and these organs and gross lesions were examined to a no-effect level.

Similar effects were observed in male and female mice from the same dose level (100 ppm): minimal to moderate hyperplasia observed in the transitional epithelium of the urinary bladder.

The NOAEL in male and female rats is 50 ppm based on minimal to moderate hyperplasia observed in the transitional epithelium of the urinary bladder in animals treated at 100 to 400 ppm.