N-(3-aminopropyl)-N- (C12-18 even numbered) alkyl-propane-1,3-diamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 June 2009 - 01 July 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study has been performed according to OECD and/or EC guidelines and according to GLP principles.

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

Report date:

2009

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 4

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:

None.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

91771-18-5

Cas Number:

91771-18-5

IUPAC Name:

91771-18-5

Constituent 2

Reference substance name:

Amines, N-(3-aminopropyl)-N (or N')-coco alkyltrimethylenedi-

EC Number:

294-908-6

EC Name:

Amines, N-(3-aminopropyl)-N (or N')-coco alkyltrimethylenedi-

IUPAC Name:

294-908-6

Details on test material:

- Name of test material (as cited in study report): Coco dipropylene triamine
- Substance type: Yellow clear to turbid liquid with flakes (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.: S001254
- Expiration date of the lot/batch: 4 October 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. 8-10 weeks old
- Weight at study initiation: 148-183 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 - 79%
- Air changes (per hr): approx.15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 05 June 2009 To: 01 July 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 50 mg/kg: 5 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 43ºC 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 50 mg/kg

No. of animals per sex per dose:

300 mg/kg: one group of 3 females
50 mg/kg: two groups 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

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off = 200 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 3/3 05 June 2009
50 mg/kg 0/3 09 June 2009
50 mg/kg 0/3 17 June 2009

The decedents were found on Day 2 post-treatment.

Clinical signs:

other: Animals at 300 mg/kg showed lethargy, hunched posture, uncoordinated movements, piloerection and/or ptosis prior to death. Animals at 50 mg/kg showed hunched posture, salivation, piloerection and/or rales between days 1 and 6.

Gross pathology:

Two animals at 300 mg/kg showed a stage of beginning autolysis, along with red foci on the glandular mucosa in one of these animals. No macroscopic abnormalities were noted in the other animal at 300 mg/kg, and in the animals at 50 mg/kg.

Other findings:

none.

Any other information on results incl. tables

none.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The oral LD50 value of Coco dipropylene triamine in Wistar rats was established to be within the range of 50-300 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 200 mg/kg body weight.

Executive summary:

The acute toxicity of Cocodipropylenetriamine was determined according to OECD Guideline 423 in compliance with GLP. A group of young female rats received an oral gavage dose of the test substance in propylene glycol (10 mL/kg bw), at a dose level of 300 (one test group comprising 3 females) and 50 mg/kg bw (two test groups comprising 3 females).

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

Dose level                    Mortality

300 mg/kg                    3/3

50 mg/kg                      0/3

50 mg/kg                      0/3

 

The decedents were found on Day 2 post-treatment.

 

Animals at 300 mg/kg showed lethargy, hunched posture, uncoordinated movements, piloerection and/or ptosis prior to death.

Animals at 50 mg/kg showed hunched posture, salivation, piloerection and/or rales between days 1 and 6.

 

Animals found dead at 300 mg/kg showed slight body weight loss. 

The body weight gain shown by the animals at 50 mg/kg over the study period was considered to be normal.

 

Two animals at 300 mg/kg showed a stage of beginning autolysis, along with red foci on the glandular mucosa in one of these animals. No macroscopic abnormalities were noted in the other animal at 300 mg/kg, and in the animals at 50 mg/kg.

 

The oral LD50 value of cocodipropylene triamine in Wistar rats was established to be within the range of 50-300 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 200 mg/kg body weight.