3-(Hydroxymethyl)-1-pentene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 25, 2006 - December 01, 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

12-2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

09-1996

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-ethylbut-3-en-1-ol

EC Number:

610-949-8

Cas Number:

53045-70-8

Molecular formula:

C6H12O

IUPAC Name:

2-ethylbut-3-en-1-ol

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

HsdCpb:WU

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 6 - 8 weeks
- Weight at study initiation: 156 - 174 g
- Fasting period before study: 17 hours before until up to 4 hours after dosing
- Housing: separately in type III Makrolon cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22
- Humidity (%): 51 - 80
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From days 1 to 15

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

Methocel® K4M Premium solution

Details on oral exposure:

Dose volume: 10 or 2.37 mL/kg
The test was started with 2000 mg/kg. Therefore at the dose of 2000 mg/kg the liquid test material was administered undiluted. At the dose of 300 mg/kg the test material volume of the undiluted test material was minimal. Therefore the test material was prepared directly before administration with aqueous Methocel® K4M Premium solution as the vehicle.

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

300 mg/kg: 3 m / 3 f
2000 mg/kg: 3 f

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: days 0, 2, 4, 6, 8, 11, 13 and 15
- Necropsy of survivors performed: yes (gross pathology)

Statistics:

Standard statistical methods have been applied for data processing.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

300 mg/kg: 0/3 m, 0/3 f
2000 mg/kg: 3/3 f

Clinical signs:

other: 300 mg/kg: Signs of toxicity were seen immediately after dosing up to 60 minutes after dosing. They consisted of locomotor disturbance, dyspnoea, and one female rat showed abdominal position. 2000 mg/kg: All rats died within 50 minutes to 23 hours after d

Gross pathology:

All male and female rats dosed with 300 mg/kg were sacrificed at the end of the study. They exhibited no macroscopic abnormalities at necropsy except for one male rat with focal white discolorations in liver and spleen. At histology no abnormalities were detected in these organs.
In rats dosed with 2000 mg/kg gross pathology revealed fluid matter in the stomach in all these rats. In one rat this matter was ill malodorous and pungent combined with mucosal swelling. At histology a submucosal oedema with some granulocytes was diagnosed in this rat combined with moderate autolysis. In the two other rats a massive autolysis of the stomach or a single cell necrosis of epithelial cells and increased amounts of viable and degenerating neutrophilic granulocytes in the lamina propria were detected. All findings are related to the local irritating properties of the test item at high concentrations.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

For regulatory purposes, the median lethal dose (LD50) can be declared between 300 - 2000 mg/kg.

Executive summary:

Study design

The test item was tested for acute toxicity in rats after oral administration of 300 and 2000 mg/kg body weight. The test was started with 2000 mg/kg. Therefore at the dose of 2000 mg/kg the liquid test material was administered undiluted. At the dose of 300 mg/kg the test material volume of the undiluted test material was minimal. Therefore the test material was prepared directly before administration with aqueous Methocel® K4M Premium solution as the vehicle. This GLP study was performed according to the "Acute toxic class method" (ATC) as described in the OECD GL 423.

 

Results

The rats treated with 300 mg/kg survived until the end of the observation period, whereas all rats treated with 2000 mg/kg died 50 minutes up to 23 hours after dosing. Signs of toxicity were seen in the rats treated with 300 mg/kg immediately after oral administration up to 60 minutes. They consisted of locomotor disturbance, dyspnoea, and one female rat showed abdominal position. The body weight development was inconspicuous. In rats treated with 2000 mg/kg clinical signs were seen immediately after oral administration up to the end of the first observation day. They consisted of salivation, abdominal position, locomotor disturbance, and dyspnoea. Gross pathology and histopathology did not reveal any abnormalities in rats treated with 300 mg/kg. Rats treated with 2000 mg/kg revealed fluid matter in the stomach, which was malodorous and pungent in one animal. Beside autolysis, histology revealed signs of acute inflammation (oedema, neutrophilic infiltration) which was most pronounced in the animal which survived for 23 hours. All findings are considered to be related to local irritating properties of the test item at high concentrations.

 

Conclusion

According to the results of this study with the test item, the LD50 value is expected to be between 300 – 2000 mg/kg.