Mentha citrata, ext.

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic 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:

Hagan et al

Year:

1967

Bibliographic source:

Fd Cosmet. Toxicol

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Chronic toxicity study for the test chemical was studied in rats

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,5-dimethyl-1-vinylhex-4-enyl isobutyrate

EC Number:

201-108-2

EC Name:

1,5-dimethyl-1-vinylhex-4-enyl isobutyrate

Cas Number:

78-35-3

Molecular formula:

C14H24O2

IUPAC Name:

1,5-dimethyl-1-vinylhex-4-en-1-yl 2-methylpropanoate

Details on test material:

- Name of test material: Linalyl isobutyrate
- IUPAC name: 1,5-dimethyl-1-vinylhex-4-en-1-yl 2-methylpropanoate
- Molecular formula: C14H24O2
- Molecular weight: 224.342 g/mol
- Substance type: Organic
- Physical state: No data
- Impurities (identity and concentrations): No data available

Test animals

Species:

rat

Strain:

Osborne-Mendel

Details on species / strain selection:

No data

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data available
- Age at study initiation: weanling rats
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: housed individually in wire cages
- Diet (e.g. ad libitum): food ad libitum
- Water (e.g. ad libitum): water ad libitum
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

IN-LIFE DATES: From: To: No data available

Administration / exposure

Route of administration:

oral: feed

Details on route of administration:

No data

Vehicle:

other: Feed

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: The test chemical was mixed with feed at dose level of 0, 1000, 2500 or 10000 ppm (0, 50, 125 or 500 mg/Kg/day).

DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food): Details not specified
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): Food
- Concentration in vehicle: 0, 1000, 2500 or 10000 ppm (0, 100, 250 or 1000 mg/Kg/day).
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Duration of treatment / exposure:

18 weeks

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

0, 1000, 2500 or 10000 ppm (0, 50, 125 or 500 mg/Kg/day)

No. of animals per sex per dose:

Total: 80 (40 males and 40 females)
0 mg/Kg bw: 10/sex/dose
50 mg/Kg bw: 10/sex/dose
125 mg/Kg bw: 10/sex/dose
500 mg/Kg bw: 10/sex/dose

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: No data available
- Rationale for animal assignment (if not random): No data available
- Rationale for selecting satellite groups: No data available
- Post-exposure recovery period in satellite groups: No data available
- Section schedule rationale (if not random): No data available

Positive control:

No data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Weekly
- Cage side observations checked in table [No.?] were included. General condition

DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule: No data

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, weekly
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations:

OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at termination
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. White cell counts, red cell counts, haemoglobins and haematocrits.

CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data

URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data - Parameters checked in table [No.?] were examined. No data

NEUROBEHAVIOURAL EXAMINATION: No data No data
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:

OTHER: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, The tissues of all the rats were examined macroscopically at the time of sacrifice. The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed.

HISTOPATHOLOGY: Yes, The viscera were removed and the liver, kidneys, spleen, heart, and testes were weighed. These organs, the remaining abdominal and thoracic viscera, and one hind leg, for bone, bone marrow, and muscle, were preserved in 10 % buffered formalin-saline solution for histopathological examination.

For routine histopathology, sections were embedded in paraffin wax and stained with haematoxylin and eosin

Other examinations:

No data

Statistics:

No data

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

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:

no effects observed

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Description (incidence and severity):

No macroscopic effects were noted in the 100 and 250 mg/Kg group

Other effects:

not specified

Effect levels

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No effects were noted at the mentioned dose level

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The no observed Adverse Effect Level (NOAEL) for the test chemical using Osborne-Mendel rats for a duration of 18 weeks is considered to be 500 mg/Kg bw.

Executive summary:

Chronic toxicity oral study for the test compound was studied in male and female Osborne-Mendel rats. The test compound was fed through the diet at a concentration of 0, 1000, 2500 or 10000 ppm (0, 100, 250 or 1000 mg/Kg bw) for 18 weeks. The animals were observed weekly for weight, food intake and general condition. Haematological examinations were made at termination. These examinations included white cell counts, red cell counts, haemoglobins and haematocrits. No effects were noted in the treated animals at the mentioned dose level. Based on the observations made, the no observed Adverse Effect Level (NOAEL) for the test compound in Osborne-Mendel rats is considered to be 500 mg/Kg bw.