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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
5-23 June 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
Report date:
2009

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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
(Z)-N-(3-aminopropyl)-N'-9-octadecenylpropane-1,3-diamine
EC Number:
249-276-6
EC Name:
(Z)-N-(3-aminopropyl)-N'-9-octadecenylpropane-1,3-diamine
Cas Number:
28872-01-7
Molecular formula:
C24H51N3
IUPAC Name:
N-[3-[[(Z)-octadec-9-enyl]amino]propyl]propane-1,3-diamine
Details on test material:
- Name of test material (as cited in study report): Oleyl dipropylenetriamine
- Substance type: Off white turbid liquid (determined at NOTOX)
- Physical state: liquid
- Analytical purity: see certificate of analysis
- Impurities (identity and concentrations): See Certificate of Analysis
- Composition of test material, percentage of components: See Certificate of Analysis
- Purity test date: See Certificate of Analysis
- Lot/batch No.: S001256
- Expiration date of the lot/batch: 24 May 2017
- Stability under test conditions: Stable
- Storage condition of test material: At room temperature in the dark under nitrogen

Test animals

Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: approx. 9-10 weeks old
- Weight at study initiation: 170-200 grams. Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: yes, overnight prior to dosing and until 3-4 hours after administration of the test substance
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material and paper as cage-enrichment.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period:at least 5 days before start of treatment under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.4 – 21.0ºC
- Humidity (%): 40 - 73%
- Air changes (per hr): approx.15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 5 June 2009 To: 23 June 2009

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 300 mg/kg: 30 mg/mL, and 2000 mg/kg: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg


DOSAGE PREPARATION (if unusual):
The formulations (w/w) were prepared within 4 hours prior to dosing, and were flushed with nitrogen. Homogeneity was accomplished to a visually acceptable level. In order to obtain homogeneity, the test substance formulations were heated in a water bath with a maximum temperature of 45ºC for a maximum of 11 minutes. The test substance (formulations) were allowed to cool down to a temperature of maximally 40ºC prior to dosing. Adjustment was made for specific gravity of the vehicle and for density of the test substance. The concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of mL/kg body weight.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on anticipated toxicity at 2000 mg/kg.
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
300 mg/kg: two groups of 3 females
2000 mg/kg: one group of 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. Weighing: Days 1 (pre-administration), 8 and 15 and at death (if found dead after Day 1).
- Necropsy of survivors performed: yes
- Other examinations performed: none.
Statistics:
Not applicable.

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 300 - <= 2 000 mg/kg bw
Mortality:
The incidence of mortality was as follows, presented in chronological order of treatment:
Dose level Mortality Date of treatment
300 mg/kg 0/3 05 June 2009
300 mg/kg 0/3 09 June 2009
2000 mg/kg 3/3 16 June 2009

The decedents were found on Day 2 or 4 post-treatment.
Clinical signs:
Animals at 300 mg/kg showed hunched posture, uncoordinated movements and/or piloerection between days 1 and 3.

Animals at 2000 mg/kg showed hunched posture, lethargy, piloerection, uncoordinated movements, laboured respiration, rales, ptosis, hypothermia, watery discharge from the eyes and/or chromodacryorrhoea prior to death.
Body weight:
The body weight gain shown by animals at 300 mg/kg/day over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Animals at 2000 mg/kg showed weight loss of reduced weight gain prior to death.
Gross pathology:
One animal at 2000 mg/kg showed a stage of beginning autolysis. No macroscopic abnormalities were noted in the other animals at 2000 mg/kg, and in the animals at 300 mg/kg.
Other findings:
None

Any other information on results incl. tables

None.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The oral LD50 value of Oleyl dipropylenetriamine in Wistar rats was established to be within the range of 300-2000 mg/kg body weight, with a cut-off value of 500 mg/kgbw.
Executive summary:

Oleyl dipropylenetriamine (Triameen OV) was tested for acute oral toxicity by Acute Toxic Class method. Test substance was dissolved in PG and dosed by gavage at 10 mL/kg bw.

The incidence of mortality was as follows, presented in chronological order of treatment:

Dose level                    Mortality                       Date of treatment

300 mg/kg                    0/3                               05 June 2009

300 mg/kg                    0/3                               09 June 2009

2000 mg/kg                  3/3                               16 June 2009

The decedents were found on Day 2 or 4 post-treatment.

Animals at 300 mg/kg showed hunched posture, uncoordinated movements and/or piloerection between days 1 and 3.

Animals at 2000 mg/kg showed hunched posture, lethargy, piloerection, uncoordinated movements, laboured respiration, rales, ptosis, hypothermia, watery discharge from the eyes and/or chromodacryorrhoea prior to death.

The body weight gain shown by animals at 300 mg/kg/day over the study period was considered to be normal.

Animals at 2000 mg/kg showed weight loss of reduced weight gain prior to death.

One animal at 2000 mg/kg showed a stage of beginning autolysis. No macroscopic abnormalities were noted in the other animals at 2000 mg/kg, and in the animals at 300 mg/kg.

The oral LD50value of Oleyl dipropylenetriamine in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.