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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to relevant guidelines.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
not applicable
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
not applicable
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Fatty acids, C18-unsatd., dimers, reaction products with polyethylenepolyamines
EC Number:
614-452-7
Cas Number:
68410-23-1
IUPAC Name:
Fatty acids, C18-unsatd., dimers, reaction products with polyethylenepolyamines
Constituent 2
Reference substance name:
DimerFA_PEPA_PAA
IUPAC Name:
DimerFA_PEPA_PAA
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): DimerFA_PEPA_PAA
- Physical state: Yellow liquid
- Analytical purity: 100%
- Lot/batch No.: BB001694V1
- Expiration date of the lot/batch: 31st August 2013
- Storage condition of test material: Store in a sealed container, at room temperature in the dark.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester.
- Age at study initiation: 8 to 9 weeks old
- Weight at study initiation: The weight variation did not exceed ±20% of the mean weight.
- Fasting period before study: Animals were fasted from the evening of the day prior to dosing until approximately 3 hours after dosing.
- Housing: The animals were housed in groups of up to five during the acclimatisation period. From the day prior to dosing (Day –1), the rats were housed in groups of three in similar cages.
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1, was freely available to the animals at all times, except for a period of fasting from the evening of the day prior to dosing (Day -1) until approximately 3 hours after dosing.
- Water (e.g. ad libitum): Mains water was provided, ad libitum, via cage-mounted water bottles.
- Acclimation period: 7 to 9 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 45 to 65%
- Air changes (per hr): 15 to 20 air changes per hour
- Photoperiod (hrs dark / hrs light): Twelve hours light (illuminated fluorescent strips) anad 12 hours dark.

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw.

DOSAGE PREPARATION: Due to the viscosity of the test article, it had to be diluted in order for it to be dosed. The test article was dispersed in corn oil because the test article did not suspend in purified water. The formulated concentrations were calculated from the selected dose level and the dose volume of 10 mL/kg bw. All formulations were used within two hours of preparation.
The formulations were maintained by multiple inversion or magnetic stirring prior to administration to ensure homogeneity.

CLASS METHOD
- Rationale for the selection of the starting dose: Since there were no data to indicate that deaths may occur at dose levels of less than 2000 mg/kg, the first dose level was 2000 mg/kg bw.
Doses:
Dose level: 2000 mg/kg bw
No. of animals per sex per dose:
3 female animals used per test.
Control animals:
no
Details on study design:
Two groups of fasted animals were treated with 2000 mg/kg bw test material, administered in a dose volume of 10 mL/kg bw. Three animals were in each test group. The treatment of the animals was sequential, with sufficient time between each group to confirm the survival of the previously dosed animals. Individual dose volumes (mL) were calculated using the fased body weights of the rats on the morning of the day of dosing (Day 1) and the dose volume of 10 mL/kg bw.

Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded immediately post-dose, at approximately 15 and 30 minutes post-dose, hourly between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. Individual records of clinical signs were maintained for each treated rat.

All animals were examined at the beginning and end of the working day throughout the acclimatisation and study periods to ensure they were in good health.

Rats were weighed on Day -1 (day before dosing) and on Days 1, 4, 8 and 15.

Rats were killed on Day 15. The necropsy procedure included inspection of external surfaces and orifices, all viscera and tissue within the abdominal, thoracic and cranial cavities, free-hand sectioning of the liver and kidneys and examination of representative sections of mucosal surfaces of the stomach, small and large intestines. No tissue preservation or histopathological assessment of tissues was undertaken.


Statistics:
Not applied.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths following a single oral dose of DimerFA_PEPA_PAA at 2000 mg/kg bw.
Clinical signs:
No clinical signs were observed.
Body weight:
All rats gained weight during the first and second weeks of the observation period.
Gross pathology:
No macroscopic changes were observed for animals killed on Day 15.
Other findings:
No other findings reported.

Any other information on results incl. tables

No additional information.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the acute median lethal oral dose level of the test article, DimerFA_PEPA_PAA, was found to exceed 2000 mg/kg bw.
Executive summary:

A GLP study was conducted to determine the acute oral toxicity of DimerFA_PEPA_PAA in female HsdHan:WIST rats, according to OECD Test Guideline 423 and EU Method B.1 tris.

Two groups of three female fasted rats were given the test article as a single dose on Day 1 by oral gavage at a dose level of 2000 mg/kg bw. The test article was dispersed in corn oil and administered at a dose volume of 10 mL/kg. During the two week observation period, mortality, body weight changes and any adverse clinical signs were recorded. All animals were killed on Day 15 and subsequently underwent a full necropsy.

There were no deaths following a single oral dose of DimerFA_PEPA_PAA at 2000 mg/kg bw. No abnormal clinical signs were observed during the observation period and all rats achieved body weight gains during the first and second weeks of the study. Macroscopic examination of these animals revealed no abnormalities.

Under the conditions of this study, the acute median lethal oral dose level of the test article, DimerFA_PEPA_PAA, was found to exceed 2000 mg/kg bw.