Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
6th 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 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:
no
Qualifier:
according to guideline
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

Constituent 1
Reference substance name:
Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and tetraethylenepentamine
EC Number:
500-289-8
EC Name:
Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and tetraethylenepentamine
IUPAC Name:
Reaction product of Fatty acids, C18 alkyl with amines, polyethylenepoly-tetraethylenepentamine fraction
Constituent 2
Reference substance name:
TOFA_DimerFA_TEPA_PAA
IUPAC Name:
TOFA_DimerFA_TEPA_PAA
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): TOFA_DimerFA_TEPA_PAA
- Physical state: Yellow liquid with a brown hue.
- Analytical purity: 100%
- Lot/batch No.: BB000649V1
- Expiration date of the lot/batch: 31st March 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 or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester
- Age at study initiation: 8 to 10 weeks of age.
- Weight at study initiation: The weight variation did not exceed ±20% of the mean weight.
- Fasting period before study: Animals were fasted for a period of time 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.
- Diet: SQC(E) Rat and Mouse Maintenance Diet No 1 was freely available at all times, except during the fasting period.
- Water: Mains water was provided, ad libitum, via cage-mounted water bottles.
- Acclimation period: 9 to 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 bw.

DOSAGE PREPARATION (if unusual):
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 on a magnetic stirrer prior to administration to ensure homogeneity.

CLASS METHOD (if applicable)
- 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.

Treatment of animals was sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals.
Doses:
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 3 female rats were administered 2000 mg/kg bw test material in a dose volume of 10 mL/kg bw. The treatment of the animals was sequential, with sufficient time allowed between the dosing of each group to allow time for confirmation of the survival of the previously dosed animals. 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 bw.

Rats were observed for clinical signs of reaction to treatment immediately post dose and 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.

Body weights were recorded on the day prior to dosing and on days 1, 4, 8 and 15.

Rats were killed day 15. Examination of all 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 was conducted. No tissue preservation or histopathological assessment of tissues was performed.
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 TOFA_DimerFA_TEPA_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, with the exception of one animal which did not gain 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 of this study, the acute median lethal oral dose level of the test article, TOFA_DimerFA_TEPA_PAA, was found to exceed 2000 mg/kg bw.
Executive summary:

The acute oral toxicity of TOFA_DimerFA_TEPA_PAA was evaluated in a GLP study conducted according to OECD Test Guideline 423 and Method B.1 tris of Council Regulation (EC) No 440/2008. Two groups of three female HsdHan:WIST rats were administered a single dose of TOFA_DimerFA_TEPA_PAA via 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 bw.

All test animals were observed for 14 days and clinical signs, body weight and mortality were recorded. All test animals were killed on Day 15 and subsequently underwent a full necropsy. There were no deaths following a single oral dose of TOFA_DimerFA_TEPA_PAA at 2000 mg/kg bw. There were no clinical signs. All rats gained weight during the first and second weeks of the observation period, with the exception of one animal which did not gain weight during the second week of the observation period. Macroscopic examination of these animals revealed no abnormalities. The acute median lethal oral dose level of the test article, TOFA_DimerFA_TEPA_PAA, was found to exceed 2000 mg/kg bw.