3-(Hydroxymethyl)-1-pentene

Endpoint summary

Description of key information

The test item was tested for acute toxicity in rats after oral administration of 300 and 2000 mg/kg body weight. 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. According to the results of this study with the test item, the LD50 value was determined to be between 300 – 2000 mg/kg falling into category 4 based on GHS criteria.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

12-2001

Deviations:

no

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

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

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

> 300 - < 2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

July 25, 2006 - September 22, 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

02-1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

12-1992

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

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: 7 - 11 weeks
- Weight at study initiation: 222 - 248 g
- Housing: separately in type III Makrolon cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21
- Humidity (%): 51 - 68
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From days 1 to 15

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The backs and abdomens of the rats were shaved with an electric hair clipper not later than one hour before treatment. The test material (2.37 mL/kg) was spread on the shaven skin in an area of 6*6 cm and covered with a gauze patch. This was kept in place by a self-adhesive fabric. The time of exposure was 24 hours. Then the gauze and adhesive fabric were removed and any remaining test material was wiped off carefully

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 m / 5 f

Control animals:

no

Details on study design:

Observation for clinical symptoms: On the day of treatment the general condition and motility of the rats were slightly affected by the tape. It was difficult to distinguish between slight clinical findings and reactions due to fixation by the tape. The behaviour and general condition of all rats were monitored for at least 6 hours after administration and then checked daily.
Bodyweight: All animals were weighed before treatment and on days 2, 4, 6, 8, 11, 13, and 15 of the experimental part.
Pathology: All rats were sacrificed at the end of the experimental part and subjected to a gross pathological investigation.

Statistics:

Standard statistical methods have been applied for data processing.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

All rats survived the observation period.

Clinical signs:

other: No signs of toxicity were detected in any rat.

Gross pathology:

The gross pathological examination revealed no organ alterations.

Interpretation of results:

GHS criteria not met

Conclusions:

In this GLP study performed according to OECD GL 402, the test item was tested for acute toxicity in rats after dermal administration of 2000 mg/kg. Based on the result of this study, the test item can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg.

Executive summary:

Study design

In this GLP study performed according to OECD GL 402, the test item was tested for acute toxicity in rats after dermal administration of 2000 mg/kg. The liquid test material was spread on the shaven skin in an area of 6*6 cm and covered with a gauze patch, which was kept in place by a self-adhesive fabric. The time of exposure was 24 hours, then the gauze and adhesive fabric were removed and any remaining test material was wiped off carefully.

 

Results

No signs of toxicity were detected and there were no deaths during the course of the study. The body weight development was inconspicuous and also the gross pathological examination revealed no organ alterations.

 

Conclusion

Based on the result of this study, the test item can be considered to have no acute toxic potential and to have a LD50 value higher than 2000 mg/kg after dermal application to rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Justification for selection of acute toxicity – oral endpoint
This study was performed according to GLP and the methods applied are fully compliant with OECD TG 423.

Justification for selection of acute toxicity – dermal endpoint

This study was performed according to GLP and the methods applied are fully compliant with OECD TG 402.

Justification for classification or non-classification

Based on the provided information the substance is classified as acute toxic category 4 according to the EU Regulation (EC) No 1272/2008 on Classification,Labelling and Packaging of Substances and Mixtures.