4-methylpent-3-en-2-one

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Mesityl Oxide

IUPAC Name:

Mesityl Oxide

Constituent 2

Reference substance name:

4-methylpent-3-en-2-one

EC Number:

205-502-5

EC Name:

4-methylpent-3-en-2-one

Cas Number:

141-79-7

Molecular formula:

C6H10O

IUPAC Name:

4-methylpent-3-en-2-one

Details on test material:

- Name of test material (as cited in study report): Mesityl Oxide, oxyde de mesityle
- Substance type:
- Physical state: liqid
- Composition of test material, percentage of components: 99%
- Purity test date: 16-Apr-2010
- Lot/batch No.: A1YB3N010101
- Expiration date of the lot/batch: 16-Apr-2012
- Storage condition of test material: Ambient condition

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Italy
- Age at study initiation: 9-10 weeks
- Weight at study initiation: approx. 200-250 gr
- Fasting period before study: Overnight prior to dosing (Day –1) up to 4 hours after dosing.
- Housing: 5 if 1 sex/cage during acclimatisation; 3 if 1 sex/cage during study
- Diet (e.g. ad libitum): with the exception of the fasting procedure described above
- Water (e.g. ad libitum):
- Acclimation period: aproximately 3-4 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 2°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): Approximately 15 to 25 air changes per hour
- Photoperiod (hrs dark / hrs light): Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours

IN-LIFE DATES: From: 3-jun-2010 To: 29-jun-2010

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5 % in water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 and 30 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

3 female animals at 2000 mg/kg
6 female animals at 300 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy performed: yes (including early decedent)
- Other examinations performed: clinical signs, body weight

Statistics:

None

Results and discussion

Preliminary study:

A first sub-group of three female animals was dosed at 2000 mg/kg body weight (step 1). The three animals were found dead at 30 minutes, 4 hours after dosing and, the last one, on Day 2. The clinical signs recorded on the day of dosing were: salivation, lachrymation, difficult breathing, lack of consciousness, mucosal reddening. At necropsy examination, no abnormalities were recorded with the exception of a single animal (died between 2 and 4 hours post dose) which showed abnormal, clear content in the stomach.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Mortality:

2000 mg/kg: 3/3 animals. The three animals were found dead at 30 minutes, 4 hours after dosing and, the last one, on Day 2
300 mg/kg: 0/6 animals.

Clinical signs:

other: 2000 mg/kg: salivation, lachrymation, difficult breathing, lack of consciousness, mucosal reddening. 300 mg/kg: lethargy (or, later, hunched posture), reduced activity lachrymation, semiclosed eyes and piloerection. Presence of clinical signs arose at 30

Gross pathology:

2000 mg/kg: no abnormalities were recorded with the exception of a single animal (died between 2 and 4 hours post dose) which showed abnormal, clear content in the stomach.
300 mg/kg: no abnormalities were recorded at post mortem examination.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

These results indicate that the test item, Mesityl oxide, has severe toxic effects at 2000 mg/kg while some toxic effect, shortly reversible, were observed following oral administration of a single dose at a level of 300 mg/kg.
The mortality pattern demonstrates the LD50 to be greater than 300 but less than 2000 mg/kg body weight.

Executive summary:

The acute toxicity of Mesityl oxide (purity 99.87%) was investigated after a single oral administration to female Sprague Dawley rats followed by a 14-day observation period (Dose volume: 10 ml/kg; Vehicle:0.5% carboxymethylcellulose acqueous solution). The animals were sacrificed at the end of the observation period and subjected to necropsy examination. A first sub-group of three female animals was dosed at 2000 mg/kg body weight (step 1). The three animals were found dead at 30 minutes, 4 hours after dosing and, the last one, on Day 2. The clinical signs recorded on the day of dosing were: salivation, lachrymation, difficult breathing, lack of consciousness, mucosal reddening. At necropsy examination, no abnormalities were recorded with the exception of a single animal (died between 2 and 4 hours post dose) which showed abnormal, clear content in the stomach. Two sub-groups of three female animals were subsequently dosed at 300 mg/kg body weight (steps 2 and 3). In step 2, the following clinical signs were recorded: lethargy (or, later, hunched posture), lachrymation, semiclosed eyes and piloerection. In step 3, clinical signs were as follows: hunched posture, reduced activity, lachrymation and piloerection. In both steps, presence of clinical signs arose at 30 minutes after dosing. Recovery started from 4 hours after dosing and was completed by Day 2. No toxicologically relevant effects on the body weight gain were observed and no abnormalities were recorded at post mortem examination in these animals. These results indicate that Mesityl oxide, has severe toxic effects at 2000 mg/kg while some toxic effect, shortly reversible, were observed following oral administration of a single dose at a level of 300 mg/kg. The mortality pattern demonstrates the LD₅₀to be greater than 300 but less than 2000 mg/kg body weight.