(+)-neomenthol

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed publication

Data source

Reference

Reference Type:

publication

Title:

Repeated dose oral toxicity study of the test chemical

Author:

Moorthy et al

Year:

1989

Bibliographic source:

Toxicology

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Repeated dose oral toxicity study was performed to determine the toxic nature of the test chemical

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

trans-menthone

EC Number:

201-941-1

EC Name:

trans-menthone

Cas Number:

89-80-5

Molecular formula:

C10H18O

IUPAC Name:

(2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one

Test material form:

liquid

Details on test material:

- Name of test material (IUPAC name): (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one- Common name: Menthone - Molecular formula: C10H18O- Molecular weight: 154.2512 g/mol- Smiles notation: C1([C@@H](CC[C@@H](C1)C)C(C)C)=O- InChl: 1S/C10H18O/c1-7(2)9-5-4-8(3)6-10(9)11/h7-9H,4-6H2,1-3H3- Substance type: Organic- Physical state: Liquid

Test animals

Species:

rat

Strain:

other: Albino (I.I.Sc. strain)

Details on species / strain selection:

No data

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: No data- Age at study initiation: 3-4 months old- Weight at study initiation: 160-180 g- Fasting period before study: No data- Housing: Rats were housed in groups of 6 animals per cage- Diet (e.g. ad libitum): Ad libitum- Water (e.g. ad libitum): No data- Acclimation period: No dataENVIRONMENTAL CONDITIONS- Temperature (°C): No data- Humidity (%):No data- Air changes (per hr): No data - Photoperiod (hrs dark / hrs light): No dataIN-LIFE DATES: From: To: No data

Administration / exposure

Route of administration:

oral: gavage

Details on route of administration:

No data

Vehicle:

methylcellulose

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: The test chemical was No data at dose level of 0 or 600 mg/Kg/dayDIET PREPARATION- Rate of preparation of diet (frequency): No data- Mixing appropriate amounts with (Type of food): No data- Storage temperature of food: No dataVEHICLE- Justification for use and choice of vehicle (if other than water): No data- Concentration in vehicle: 0 or 600 mg/Kg/day- Amount of vehicle (if gavage): 1mL- Lot/batch no. (if required): No data- Purity: No data

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

3 days

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

0 or 600 mg/Kg/day

No. of animals per sex per dose:

No data

Control animals:

yes, concurrent vehicle

Details on study design:

No data

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

No data

Sacrifice and pathology:

No data

Other examinations:

Enzyme assay: Microsomes were prepared from liver and kidneys by a differential centrifugation method. Cytochromes P-450 and b5, NAD(P)H-cytochrome c reductase activities, heme content {estimated at 557 nm as the pyridine ferrochromogen), protein, SGPT, glucose-6-phosphatase and aminopyrine N-demethylase were determined

Statistics:

All statistical analyses were performed using Student's t-test and levels of significance determined at P < 0.05

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

no effects observed

Description (incidence and severity):

Oral administration of menthone (600 mg/kg per day), for 3 days resulted in a marginal increase (≈13%) in hepatic cytochrome P-450 without affecting cytochrome b5 levels.

Effect levels

Dose descriptor:

NOAEL

Effect level:

600 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No significant effects were noted at the mentioned dose level

Remarks on result:

other: No effect observed

Target system / organ toxicity

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Treatment related:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

The No observed adverse effect level (NOAEL) for the test chemical is considered to be 600 mg/Kg/day.

Executive summary:

Repeated dose oral toxicity study was performed to determine the toxic nature of the test chemical. The study was performed using male rats. The test chemical was dissolved in 1% methyl cellulose and use at dose level of 0 or 600 mg/kg/day. Microsomes were prepared from liver and kidneys by a differential centrifugation method. Cytochromes P-450 and b5, NAD(P)H-cytochrome c reductase activities, heme content {estimated at 557 nm as the pyridine ferrochromogen), protein, SGPT, glucose-6-phosphatase and aminopyrine N-demethylase were determined. Oral administration at 600 mg/kg per day, for 3 days resulted in a marginal increase (≈13%) in hepatic cytochrome P-450 without affecting cytochrome b5 levels. However, the hepatic cytochrome P-450 system was not affected due to test chemical treatment. Based on the observations made, the No observed adverse effect level (NOAEL) for the test chemical is considered to be 600 mg/Kg/day.