2-Oxepanone, polymer with 1,6-hexanediol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

The study on a similar substance serves as data source for the endpoint study record "CAPA 203 acute oral toxicity: Snoeij & Buse-Pot, 1992 [TARGET]" and the justification for read-across is provided there.

Adequacy of study:

key study

Study period:

16th September 1991 - 15th January 1992.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Study serves as data source; read-across justification is found in Target record.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

16th September 1991 - 15th January 1992.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

See attached justification

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Principles of method if other than guideline:

Not applicable.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan/CPB, Zeist, The Netherlands.
- Age at study initiation: No information provided.
- Weight at study initiation: Males: 175 - 200 g, Females:150 - 175 g
- Fasting period before study: Rats were fasted for 18.5 hours prior to start of the study.
- Housing: Housed continuously in Macrolon cages with two or three animals per cage.
- Diet (e.g. ad libitum): Free access to food which was a standard labortory diet RHM-TM, except during the fasting period.
- Water (e.g. ad libitum): Water was available as libitum.
- Acclimation period: Acclimatisation period was 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 22°C
- Humidity (%): 50 - 70%
- Air changes (per hr): No information provided
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Final concentration was 0.2 g/mL
- Amount of vehicle (if gavage): No information provided.
- Justification for choice of vehicle: No information provided.
- Lot/batch no. (if required): No information provided.
- Purity: No information provided.

MAXIMUM DOSE VOLUME APPLIED: Volumes of 10 ml/kg bw, equivalent to 2000 mg/kg bw were administered.

DOSAGE PREPARATION: The test material was suspended in a 1.25% tragacanth solution in distilled water.

Doses:

2000 mg/kg w

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed at 0-0.5hr and at 1.5, 3, 6 and 26.5 hours after application and on each day until the end of the study. Body weights were recorded the day prior to dosing, day of dosing (day 0) and at 2, 7 and 14 days after treatment.
- Necropsy of survivors performed: yes, including inspection of external appearance, the cervical area, the thoracic and abdominal cavities.

Statistics:

Not required

Preliminary study:

No information provided.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no mortalities following administration of a single oral dose of 2000 mg/kg bw CAPA 203.

Clinical signs:

other: Clinical signs observed in males included decreased respiratory rate, respiratory difficulties, decreased alertness, decreased startle response, and strech movements. Clinical signs in females included exophthalmia and increased body and limb tone. Othe

Gross pathology:

2 males and 1 female rat had alopecia of the anterior body wall. Another male rat had a slightly swollen liver. No abnormalities were noted in the other animals.

Other findings:

No additional information provided.

Mean body weight-gain (g) of groups of five male and five female rats given a single oral dose of CAPA 203:

Sex	Dose (mg/kg bw)	Day-1 to 2	Day 2 to 7	Day 7 to 14	Day -1 to 14
Male	2000	12.0	28.0	35.8	75.8
Female	2000	0.6	2.4	9.4	12.4

The clinical signs were mostly indicative of effects on motor coordination, muscle tone and on the autonomic nervous system.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Oral administration of a single dose of 2000 mg/kg bw of the read-across substance CAPA 203 caused no mortalities among male and female rats during the 14 day observation period. Therefore, the acute oral LD50 is >2000 mg/kg bw in rats. Based on read-across, CAPA 2047A does not require classification for acute oral toxicity according to CLP criteria.

Executive summary:

An acute oral toxicity study was conducted in accordance with GLP and with EEC method B.1 to determine the acute oral toxicity of the read-across substance CAPA 203 in male and female rats. A single oral dose of 2000 mg/kg bw CAPA 203 (suspended in 1.25% aqueous tragacanth solution) was given by stomach tube to groups of five male and five female fasted Wistar rats. Rats were weighed one day before dosing, at the day of dosing and at Days 2, 7 and 14. There was no mortality during the study. Clinical signs observed were mostly indicative of effects on motor coordination (decreased locomotor activity, abnormal gait and posture), on muscle tone (increased body and limb tone) and on the autonomic nervous system (decreased respiratory rate and breathing difficulties). There was no effect on mean bodyweight gain by male rats, but reduced bodyweight gain was reported for females during the first week of the study. Gross necropsy did not reveal any findings considered to be treatment-related. The acute oral LD50 of CAPA 203 in the rat was therefore established to be >2000 mg/kg bw. Based on read-across, low acute oral toxicity is also predcited for CAPA 2047A.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

Principles of method if other than guideline:

Not applicable.

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-Oxepanone, polymer with 1,4-butanediol

Cas Number:

31831-53-5

IUPAC Name:

2-Oxepanone, polymer with 1,4-butanediol

Constituent 2

Reference substance name:

CAPA 2043

IUPAC Name:

CAPA 2043

Constituent 3

Reference substance name:

Reference substance 001

EC Number:

932-682-9

Cas Number:

31831-53-5

Constituent 4

Reference substance name:

2-Oxepanone, polymer with 1,4-butanediol

EC Number:

608-670-1

Cas Number:

31831-53-5

Molecular formula:

l(HO(CH2)5CO)-O(CH2)4O-(CO(CH2)5OH)m

IUPAC Name:

2-Oxepanone, polymer with 1,4-butanediol

Test material form:

other: liquid.

Details on test material:

- Name of test material (as cited in study report): Capa 2043
- Physical state: Colourless liquid.
- Analytical purity: 97%
- Lot/batch No.: WAC000392
- Expiration date of the lot/batch: 17th February 2014
- Storage condition of test material: Stored in the dark at room temperature.

Specific details on test material used for the study:

CAPA 203 (2-oxepanone, polymer with 1,4-butanediol) now known as CAPA 2043

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan/CPB, Zeist, The Netherlands.
- Age at study initiation: No information provided.
- Weight at study initiation: Males: 175 - 200 g, Females:150 - 175 g
- Fasting period before study: Rats were fasted for 18.5 hours prior to start of the study.
- Housing: Housed continuously in Macrolon cages with two or three animals per cage.
- Diet (e.g. ad libitum): Free access to food which was a standard labortory diet RHM-TM, except during the fasting period.
- Water (e.g. ad libitum): Water was available as libitum.
- Acclimation period: Acclimatisation period was 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 22°C
- Humidity (%): 50 - 70%
- Air changes (per hr): No information provided
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Final concentration was 0.2 g/mL
- Amount of vehicle (if gavage): No information provided.
- Justification for choice of vehicle: No information provided.
- Lot/batch no. (if required): No information provided.
- Purity: No information provided.

MAXIMUM DOSE VOLUME APPLIED: Volumes of 10 ml/kg bw, equivalent to 2000 mg/kg bw were administered.

DOSAGE PREPARATION: The test material was suspended in a 1.25% tragacanth solution in distilled water.

Doses:

2000 mg/kg w

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed at 0-0.5hr and at 1.5, 3, 6 and 26.5 hours after application and on each day until the end of the study. Body weights were recorded the day prior to dosing, day of dosing (day 0) and at 2, 7 and 14 days after treatment.
- Necropsy of survivors performed: yes, including inspection of external appearance, the cervical area, the thoracic and abdominal cavities.

Statistics:

Not required

Results and discussion

Preliminary study:

No information provided.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no mortalities following administration of a single oral dose of 2000 mg/kg bw CAPA 203.

Clinical signs:

other: Clinical signs observed in males included decreased respiratory rate, respiratory difficulties, decreased alertness, decreased startle response, and strech movements. Clinical signs in females included exophthalmia and increased body and limb tone. Othe

Gross pathology:

2 males and 1 female rat had alopecia of the anterior body wall. Another male rat had a slightly swollen liver. No abnormalities were noted in the other animals.

Other findings:

No additional information provided.

Any other information on results incl. tables

Mean body weight-gain (g) of groups of five male and five female rats given a single oral dose of CAPA 203:

Sex	Dose (mg/kg bw)	Day-1 to 2	Day 2 to 7	Day 7 to 14	Day -1 to 14
Male	2000	12.0	28.0	35.8	75.8
Female	2000	0.6	2.4	9.4	12.4

The clinical signs were mostly indicative of effects on motor coordination, muscle tone and on the autonomic nervous system.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Oral administration of a single dose of 2000 mg/kg bw CAPA 203 caused no mortalities among male and female rats during the 14 day observation period. Therefore, the acute oral LD50 is >2000 mg/kg bw in rats. CAPA 203 does not require classification for acute oral toxicity according to CLP criteria.

Executive summary:

An acute oral toxicity study was conducted in accordance with GLP and with EEC method B.1 to determine the acute oral toxicity of CAPA 203 in male and female rats. A single oral dose of 2000 mg/kg bw CAPA 203 (suspended in 1.25% aqueous tragacanth solution) was given by stomach tube to groups of five male and five female fasted Wistar rats. Rats were weighed one day before dosing, at the day of dosing and at Days 2, 7 and 14. There was no mortality during the study. Clinical signs observed were mostly indicative of effects on motor coordination (decreased locomotor activity, abnormal gait and posture), on muscle tone (increased body and limb tone) and on the autonomic nervous system (decreased respiratory rate and breathing difficulties). There was no effect on mean bodyweight gain by male rats, but reduced bodyweight gain was reported for females during the first week of the study. Gross necropsy did not reveal any findings considered to be treatment-related. The acute oral LD50 of CAPA 203 in the rat was therefore established to be >2000 mg/kg bw.