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Toxicological information

Repeated dose toxicity: oral

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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:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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.