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Acute Toxicity: oral

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acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 May 1986 - 26 June 1986
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference Type:
other company data

Materials and methods

Test guideline
according to guideline
other: Annex V 79/831/EEC Method B.1; OECD Guideline 401
GLP compliance:
Test type:
standard acute method
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Test material form:
other: clear liquid
Details on test material:
- Name of test material (as cited in study report): L-carvone
- Physical state: Liquid
- Storage condition of test material: Stored at ambient temperature under conditions of intermittent, subdued artificial light.

Test animals

other: CFY (Sprague Dawley origin)
Details on test animals or test system and environmental conditions:
- Source: Interfauna U.K. Ltd., Huntington, Cambridgshire, UK.
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 90-142g
- Housing: Within treatment groups, by sex, in metal cages with wire mesh floors.
- Diet (e.g. ad libitum): A standard rodent diet (Labsure LAD 1 diet) ad libitum.
- Fasting period before study: Access to food only was prevented overnight prior to and approx. 4 hours after dosing.
- Water (e.g. ad libitum): Drinking water ad libitum
- Acclimation period: 7 days

- Temperature (°C): Mean daily minimum and maximum were 21°C and 23°C
- Humidity (%): Mean daily relative humidity was 59%
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours aritifical light in each 24 hour period

Administration / exposure

Route of administration:
oral: gavage
unchanged (no vehicle)
Details on oral exposure:
3.30 mL/kg : 3.2 g/kg dose
5.15 mL/kg : 5.0 g/kg dose
8.25 mL/kg : 8.0 g/kg

Preliminary test: single dose of 5.0 g/kg bw of undiluted test substance

Main test: 3.2, 5.0, or 8.0 g/kg of undiluted test substance at a dose volume of 3.30, 5.15, or 8.25 mL/kg respectively.
No. of animals per sex per dose:
Preliminary test: 2 male and 2 female animals

Main test: 5 male and 5 female animals
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
Observations: Soon after dosing, frequently on Day 1, on subsequent days once in the morning and the evening; 5 and 14 days observations for preliminary and main tests respectively.
Body weights were recorded on Days 1 (day of dosing), 8, and 15.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, terminal autopsy
The acute median lethal oral dose was calculated by method of Weil.
(Weil, C.S. (1952) Biometrics, 8: 249.)

Results and discussion

Effect levelsopen allclose all
Dose descriptor:
Effect level:
5 400 mg/kg bw
95% CL:
4 600 - 6 300
Dose descriptor:
Effect level:
5 900 mg/kg bw
95% CL:
4 900 - 7 100
Dose descriptor:
Effect level:
4 900 mg/kg bw
95% CL:
3 900 - 6 100
Preliminary test (males and females):
At 5 g/kg bodyweight: 0/4 deaths;

Main test (males):
At 3.2 g/kg: 0/5 deaths;
At 5 g/kg: 1/5 deaths (by day 4);
At 8 g/kg: 5/5 deaths (by day 3).

Main test (females):
At 3.2 g/kg: 0/5 deaths;
At 5 g/kg: 3/5 deaths (by day 4);
At 8 g/kg: 5/5 deaths (by day 5).
Clinical signs:
other: All rats: piloerection, hunched posture, increased salivation; abnormal gait (waddling) in majority of rats; isolated cases of prostration and straub tail. At 3.2 g/kg: lethargy (one male), pallor of extremities, ataxia and body tremors; clinical signs
Gross pathology:
All rats surviving to the end of the observation period were killed on day 15 by cervical dislocation and examined macroscopically.
Terminal necropsy showed no macroscopic abnormalities except for unilateral hydronephrosis of 1 male in the lower dose
Other findings:
- Other observations: Autopsy revealed pallor of the kidneys, liver and/or spleen in all rats that died.

Any other information on results incl. tables

Table 1: Time and number of deaths or rats dosed orally with L-carvone (Main study)

Sex Dose (g/kg) Number of deaths in a group of 5 1 2 3 4 5 6 to 15
a b a b a b a b a b a b
Male 3.2 0
5 1 1
8 5 3 1 1
Female 3.2 0
5 3 2 1
8 5 2 1 2

(a): First observation

(b:) Second observation


Applicant's summary and conclusion

Interpretation of results:
not classified
The acute median lethal oral doses (LD50) and their 95% confidence limits to rats of L-carvone were estimated to be:

LD50 (combined): 5400 mg/kg bw (4600 - 6300 mg/kg bw; 95% C.I)
LD50 (male): 5900 mg/kg bw (4900 - 7100 mg/kg bw; 95% C.I)
LD50 (female): 4900 mg/kg bw (3900 - 6100 mg/kg bw; 95% C.I)
Executive summary:

In an acute oral toxicity study (86771D/ULR 138/AC), groups of fasted, young CFY (Sprague Dawley origin) (5/sex) were given single oral doses of L-carvone undiluted at 3.2, 5.0, or 8.0 g/kg bw and observed for 14 days.

LD50 (combined): 5400 mg/kg bw (4600 - 6300 mg/kg bw; 95% C.I)

LD50 (male): 5900 mg/kg bw (4900 - 7100 mg/kg bw; 95% C.I)

LD50 (female): 4900 mg/kg bw (3900 - 6100 mg/kg bw; 95% C.I)

No mortalities were observed at 3.2 g/kg bw while no rat survived administration of L-carvone of 8 g/kg bw. Clinical signs were noted at all doses and resolved towards the end of the observation period in surviving animals. Body weights were lower during first week of observation but were as anticipated at end of second week of observation. Terminal necropsy showed no treatment-related macroscopic abnormalities.

This acute oral study is classified as acceptable. It does satisfy the guideline requirement for an acute oral study (OECD 401) in the rat.