Reaction product of Fatty acids, C18 alkyl with amines, polyethylenepoly-tetraethylenepentamine fraction

Acute Toxicity: oral

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

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

Test material information

Constituent 1

Reference substance name:

High moecular weight adducts of Fatty acids, C16-18 sat. C18 unsat., linear, dimers, and trimers, with Amines, polyethylenepoly-, triethylenetetramine fraction

IUPAC Name:

High moecular weight adducts of Fatty acids, C16-18 sat. C18 unsat., linear, dimers, and trimers, with Amines, polyethylenepoly-, triethylenetetramine fraction

Constituent 2

Reference substance name:

Higher molecular weight adducts of C18 Fatty acids linear (unsat & sat) with amines,polyethylenepoly-, tetraethylenepentamine fraction

IUPAC Name:

Higher molecular weight adducts of C18 Fatty acids linear (unsat & sat) with amines,polyethylenepoly-, tetraethylenepentamine fraction

Constituent 3

Reference substance name:

Amines, polyethylenepoly-, tetraethylenepentamine fraction

EC Number:

292-587-7

EC Name:

Amines, polyethylenepoly-, tetraethylenepentamine fraction

Cas Number:

90640-66-7

IUPAC Name:

Amines, polyethylenepoly-, tetraethylenepentamine fraction

Constituent 4

Reference substance name:

lower molecular weight adducts of C18 Fatty acids linear (unsat & sat) amines,polyethylenepoly-, tetraethylenepentamine fraction

Molecular formula:

for example : C26H53N5O, C26H55N5O...

IUPAC Name:

lower molecular weight adducts of C18 Fatty acids linear (unsat & sat) amines,polyethylenepoly-, tetraethylenepentamine fraction

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report):TOFA DimerFA TEPA PAA
- Physical state:Yellow-red, transparent, viscous liquid
- Analytical purity: 9% free amine
- Storage condition of test material:Room temperature (15°C to 30°C)
-Sponsor batch: BB000649V1

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:

other: No clinical signs were observed.

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.