Reaction products of behenic acid, Eicosadioic acid and Polyglyceryl-10

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10.12.2007- 29.01.2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

478-920-0

EC Name:

-

Cas Number:

457632-32-5

Molecular formula:

C22H44O2.4 C20H38O4.1 (C3H8O3).20

IUPAC Name:

1,20-bis({3-[3-(2,3-dihydroxypropoxy)-2-hydroxypropoxy]-2-hydroxypropyl}) icosanedioate

Test material form:

solid: pellets

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 5-4-A
- Expiration date of the lot/batch: October 2008
- Purity test date: not stated

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature, light protected
- Stability under test conditions: unknown in propylene glycol
- Solubility and stability of the test substance in the solvent/vehicle: solubility tested in Non-GLP trial. Dose selection is performed with regard to maximal technically applicable dose.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not stated

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
The test itrem was weighed into a tared glass beaker on a suitable precision balance and the vehicle was added. Afterwards, the test item in the vehicle was warmed up to 250 °C for approximately 1 min. The formulations were prepared using a magnetic stirrer as homogenizer. The test item preparation was kept at room temperature for cooling and was administered at the temperatures of 24.4 °C and 26 °C.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd
- Females (if applicable) nulliparous and non-pregnant: not stated
- Age at study initiation: 11 weeks
- Weight at study initiation: 162.4 - 194.1 g
- Fasting period before study: 17 - 18 hours
- Housing: in groups of 3
- Diet (e.g. ad libitum): pelleted standard diet, ad libitum
- Water (e.g. ad libitum): community tap water ad libitum
- Acclimation period: 7 or 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +-3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10-15 /hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.02g/ml
- Amount of vehicle (if gavage): 20 mL/kg
- Justification for choice of vehicle: propylene glycol was found to be a suitable vehicle. The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date.
- Lot/batch no. (if required): 1326803
- Purity: not stated

DOSAGE PREPARATION (if unusual):
The dose formulations were made shortly before each dosing occasion.
The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle was added (weight:volume). Afterwards, the test item in the vehicle was warmed up to 250°C for approximately 1 minute. The formulations were prepared using a magnetic stirrer as homogenizer. The test item preparation was kept at room temperature for cooling and was administered at the temperatures of 24.4°C and 26°C. The temperature was measured before treatment with a thermometer.
Homogeneity of the test item in the vehicle was maintained during administration using a
magnetic stirer

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: none given

Doses:

200 mg/kg bw according to study report.
based on the dosing volume (20 mL/kg) and the concentration of the substance in the vehicle (0.02 g/ml)

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations daily, weighing weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,

Statistics:

none applied

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD0

Effect level:

200 mg/kg bw

Based on:

test mat.

Mortality:

no deaths occurred duuring the study.

Clinical signs:

other: Approximately 30 m inutes post回dose,a slight to marked poor coordination was observed in all treated females which persisted up to the 5-hour reading. A hunched posture was recorded in four females: in two females within the first 30 minutes up to test da

Gross pathology:

No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

The highest technically applicable dose of 200 mg/kg bw did not lead to any mortality in six (6) tested female rats.

Executive summary:

Two groups, each of three female HanRcc: WIST (SPF) rats, were treated with Nomcort HKP by oral gavage administration at a dosage of 200 mg/kg body weight. The test item was diluted in vehicle (Propylene glycol) at a concentration of 0.02 g/mL and administered at a dosing volume of 20 mL/kg.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period.

Approximately 30 minutes post-dose, a slight to marked poor coordination was observed in all treated females which persisted up to the 5-hourr eading. A hunched posture was recorded in four females: in two females within the first 30 minutes up to test day 3, in one female approximately 30 minutes up to 5 hours after treatment and additionally on test day 3 and in another female 3-5 hours post-dose. All females were found to be slightly to moderately sedated within the first 30 minutes or 1 hour after treatment up to test day 2. A slightly ruffled fur was noted in all females 1 or 2 hours post-dose and persisted up to test day 2 or 3. Furthermore, one female was found with almost to complete shut eyes at the 3 -hour evaluation.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were recorded at necropsy.

The median lethal dose ofNomcort HKP after single oral administration to female rats, observed

over a period of 14 days is:

LD50 (female rat): greater than 200 mg/kg body weight