Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
7th February 2012 to 21st June 2012.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted in accordance with the relevant testing guidelines.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
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:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): OLEIC_DimerFA_TETA_PAA
- Physical state: Yellow liquid with a brown hue.
- Analytical purity: 100%
- Lot/batch No.: BB100860V1
- Expiration date of the lot/batch: 30th April 2012
- Storage condition of test material: When not in use the test article was stored in a sealed container, at room temperature in the dark.

Test animals

Species:
rat
Strain:
other: HsdHan:WIST
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester.
- Age at study initiation: 8 to 10 weeks of age.
- Weight at study initiation:
- Fasting period before study: There was a period of fasting from the evening of the day prior to dosing (Day -1) 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, from Special Diets Services Ltd, Witham, UK was freely available to the animals at all times except during the fasting period.
- Water (e.g. ad libitum): Mains water was provided, ad libitum, via cage-mounted water bottles.
- Acclimation period: 9 - 14 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): 12 hours light and 12 hours dark.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Corn oil.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg.

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. This deviation does not impact on the integrity of the study. The formulated concentrations were calculated from the selected dose level and the dose volume of 10 mL/kg. All formulations were used within two hours of preparation.
The formulations were maintained on a magnetic stirrer 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 bw, the first dose level was 2000 mg/kg bw.
Doses:
Dose Level: 2000 mg/kg bw
No. of animals per sex per dose:
3 females per group.
Control animals:
no
Details on study design:
Two groups of three females were administered 2000 mg/kg bw OLEIC_DimerFA_TETA_PAA by oral gavage, in a maximum dose volume of 10 mL/kg. Treatment of animals was sequential, with sufficient time allowed between each group to confirm the survival of the previously dosed animals.
Dose levels were expressed gravimetrically and in terms of test article received (without regard to purity or active content).
Individual dose volumes (mL) were calculated using the fasted body weights of the rats on the morning of dosing (Day 1) and the dose volume of 10 mL/kg.

Observations were recorded over the 14 days observation period.
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 required.

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 OLEIC_DimerFA_TETA_PAA at 2000 mg/kg bw.
Clinical signs:
No clinical signs were observed during the observation period.
Body weight:
All rats achieved body weight gains during the first and second weeks of the study, with the exception of one animal which lost weight during the second week 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 employed in this study, the acute median lethal oral dose level of the test article, OLEIC_DimerFA_TETA_PAA, was found to exceed 2000 mg/kg bw.
Executive summary:

A study was conducted on three female HsdHan:WIST rats to determine the acute oral toxicity of OLEIC_DimerFA_TETA_PAA when administered as a single dose by oral gavage. The study was conducted according to OECD Test Guideline 423 and Method B.1 tris of Council Regulation (EC) No 440/2008 and was compliant with GLP.

Two groups of three female rats were administered the test article dispersed in corn oil at a dose level of 2000 mg/kg bw and a maximum dose volume of 10 mL/kg bw. The rats were observed for 14 days during which, clinical signs, body weight changes and mortality were noted. Rats were euthanised on day 15 and subjected to a macroscopic examination.

There were no deaths among rats dosed at 2000 mg/kg bw. There were no clinical signs and all rats achieved body weight gains during the first and second weeks of the study, with the exception of one animal which lost weight during the second week of the observation period. 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, OLEIC_DimerFA_TETA_PAA, was found to exceed 2000 mg/kg bw.