Registration Dossier

Administrative data

Description of key information

A study of acute oral toxicity is available for the submission substance.

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:
16th September 1991 - 15th January 1992.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
CAPA 203 (2-oxepanone, polymer with 1,4-butanediol) now known as CAPA 2043
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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 bw
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:
Clinical signs observed in males included decreased respiratory rate, respiratory difficulties, decreased alertness, decreased startle response, and stretch movements. Clinical signs in females included exophthalmia and increased body and limb tone. Other clinical signs observed also included decreased locomotor activity, abnormal gait and posture. The time of onset of the first signs was within 30 minutes in males and females. Signs were slight to moderate in intensity in both sexes. All signs had disappeared by 26.5 hours after treatment.
Body weight:
Fasting on the day prior to dosing caused a small weight loss in all animals. Oral administration of 2000 mg/kg bw CAPA 203 had no effect on mean body weights and weight-gains of male rats during the observation period. Female rats given the same treatment showed a reduced weight gain during the first week of the study. In the second week, body weight gains recovered.
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 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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Klimisch score = 1. study compliant with current test guidelines and GLP

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity

The acute oral toxicity of the submission substance (2 -oxepanone, polymer with 1,4-butanediol) is low: an oral LD50 of the substance was determined to be >2000 mg/kg bw in an acute oral toxicity study conducted in rats. The study was carried out with one test group of rats consisting of five male and five female animals, each given a dose of 2-Oxepanone, polymer with 1,4-butanediol at 2000 mg/kg body weight. None of the treated animals died during 14 days of observation. Clinical signs observed were mostly indicative of effects on motor co-ordination, muscle tone and on the autonomic nervous system. No effects were observed on bodyweight and no macroscopic abnormalities were observed during autopsies performed at the end of the observation period. Based on the study, the acute oral LD50 of 2-Oxepanone, polymer with 1,4-butanediol was found to be greater than 2000 mg/kg bw in rats.

Acute dermal toxicity

No acute dermal toxicity studies on the substance are available. A waiver is proposed for this endpoint on scientific grounds and for reasons of animal welfare. No mortalities were seen in an acute oral toxicity study performed with the substance at a limit dose of 2000 mg/kg bw. No signs of systemic toxicity were seen in skin and eye irritation studies or in a skin sensitisation study using the substance. It can therefore be concluded that the substance has low acute toxicity. Dermal absorption of the substance is unlikely to exceed oral absorption and significant differences in the toxicity of the substance due to the route of exposure are not predicted. Testing of the substance is therefore not considered to be scientifically justified and additionally cannot be supported on grounds of animal welfare.

 

Acute inhalation toxicity

A waiver is proposed for acute inhalation toxicity studies in accordance with Column 2 of Annex VIII of the REACH Regulation for this endpoint. Inhalation is not predicted to be a significant route of exposure based on the physicochemical properties of the substance. The substance is a non-volatile liquid and the use pattern indicates that significant inhalation exposure is unlikely. No additional testing is required.

Justification for classification or non-classification

The acute oral LD50 of the submission substance (2 -oxepanone, polymer with 1,4 -butanediol) in rats is >2000 mg/kg bw. The substance does not therefore meet the criteria for classification for acute oral toxicity according to the CLP Regulation.