Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007-11-21 to 2008-01-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008

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
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:
Amines, N-C12-18-alkyltrimethylenedi-
EC Number:
268-957-9
EC Name:
Amines, N-C12-18-alkyltrimethylenedi-
Cas Number:
68155-37-3
Molecular formula:
R-NH-(CH2)3-NH2
IUPAC Name:
N-C12-18-alkyl-propane-1,3-diamine
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): N-Coco-1,3-diaminopropane
- Physical state: liquid
- Composition of test material, percentage of components:

Total Primary amines: 8.3 %
Total Diamines: 91.7 %
Iodine number: 12 g I/100g
Water: 0.28 % (0-1 %)
C8 N Primary amine: 0.3 %
C10 N Primary amine: 0.5 %
C12 N Primary amine: 4.2 %
C14 N Primary amine: 1.6 %
C16 N Primary amine: 0.9 %
C18:1 N Primary amine: 0.6 %
C18:0 N Primary amine: 0.2 %
C8 Diamine: 4.0 %
C10 Diamine: 5.3 %
C12 Diamine: 45.5 %
C14 Diamine: 16.5 %
C16 Diamine: 9.5 %
C18:1 Diamine: 7.5 %
C18:0 Diamine: 3.6 %
Acrylnitrile: <4 ppm
Fatty acids: <1 %
Fatty alkyl nitriles: <1 %

- Purity test date: 2007-10-15
- Lot/batch No.: S000903
- Expiration date of the lot/batch: 2010-09-30
- Storage condition of test material: at RT

Test animals

Species:
rat
Strain:
other: HsdRccHan: WIST (Full-Barrier)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- Weight at study initiation:
Step 1: 168 g (1 animal)
Step 2: 170-186 g
Step 3: 141-177 g
Step 4: 135-158 g
Step 5: 128-131 g

- Fasting period before study: overnight and 3-4 hours after dosing
- Housing: macrolon cages on Altromin saw fibre bedding
- Diet: ad libitum (Altromin 1324 (TPF)
- Water: ad libitum (drinking water)
- Acclimation period: at least 5 days
- Other: marked individually by tail painting, SPF animals

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
cotton seed oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle:
Step 1: 1.0 g/ 5 mL
Step 2: 0.3 g/ 10 mL
Step 3: 0.3 g/ 10 mL
Step 4: 0.1 g/ 20 mL
Step 5: 0.1 g/ 20 mL
- Amount of vehicle: 10 mL/ kg body weight
- Justification for choice of vehicle: non-toxic and lipophil
- Lot/batch no. : Lot 067K0116, Sigma Chemicals

MAXIMUM DOSE VOLUME APPLIED: 1.86 mL

DOSAGE PREPARATION : freshly mixed prior to administration

CLASS METHOD
- Rationale for the selection of the starting dose:
preliminary test with one animal performed (2000 mg/kg), due to immeadiate preacute lethality
the starting dose was choosen to be 300 mg/kg bw
Doses:
Step 1: 2000 mg/kg bw
Step 2: 300 mg/kg bw
Step 3: 300 mg/kg bw
Step 4: 50 mg/kg bw
Step 5: 50 mg/kg bw
No. of animals per sex per dose:
Step 1 (2000 mg/kg bw): 1 female rat
Step 2 (300 mg/kg bw): 3 female rats
Step 3 (300 mg/kg bw): 3 female rats
Step 4 (50 mg/kg bw): 3 female rats
Step 5 (50 mg/kg bw): 3 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: A careful clinical examination was made several times on the day of dosing.
Parts of this were at least three observations within the first four hours post-dose.
Animals were observed once a day thereafter.
The animals were weighed prior to the administration and once a week thereafter.

- Necropsy of survivors performed: yes

- Other examinations performed: Cage side observations included changes in the skin and fur, eyes and mucous membranes.
Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity
and behaviour pattern were examined. Particular attention was directed to observations of tremor,
convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Statistics:
not applicable

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
300 mg/kg bw
Remarks on result:
other: acute toxic class method; according to GHS (Globally Harmonized Classification System) the test item N-coco-1,3-diaminopropane was classified into Category 3
Mortality:
Step 1 (2000 mg/kg bw, 1 female rat): within 1 h 30 min post-dose the animal was found dead
Step 2 (300 mg/kg bw): no deaths observed within the observation period
Step 3 (300 mg/kg bw): Animal 2 was found dead five days and animal 3 three days post-dose
Step 4 and 5 ( 50 mg/kg bw): no deaths observed within the observation period

Clinical signs:
other: see remarks on results including tables and figures
Gross pathology:
Animal no. 1 of step 1 (2000 mg/ kg bw):
The stomach showed haemorrhage with a foamy content. The small intestine
also showed haemorrhage with a bloody content. The large intestine and appendix were bloody.
Animal no.2 of step 3 (300 mg/ kg bw):
The animal was found dead in a lateral position and exhibited piloerection.The anus was smeared with
faeces.
Animal no. 3 of step 3 (300 mg/ kg bw):
The stomach was bloody. The small intestine was slightly bloody.

Any other information on results incl. tables

Signs of toxicity related to dose level used, time of onset and duration:

Animal no. 1 of step 1 (2000 mg/kg bw): 30 min post-dose: moderately reduced spontaneous activity, salivation, face down position.1 h 30 min post-dose: this animal was found dead.

Animal no. 1 of step 2 (300 mg/kg bw): 25 min post-dose: slightly reduced spontaneous activity, apathy, piloerection.1 h 45 min post-dose: slightly reduced spontaneous activity, piloerection, half eyelid-closure. 5 h 45 min post-dose: slightly reduced spontaneous activity, piloerection, sunken flank. 22 h 45 min as well as 28 h 45 min post-dose: slightly reduced spontaneous activity, piloerection, sunken flank, diarrhoea. 46 h 45 min post-dose: slightly reduced spontaneous activity, piloerection, diarrhoea, bloody snout, bloody mouth. 50 h 45 min post-dose: slightly reduced spontaneous activity, piloerection, diarrhoea, weight loss. 78 h 15 min post-dose: piloerection, diarrhoea, weight loss. 98 h 10 min post-dose: slightly reduced spontaneous activity, piloerection, diarrhoea, heavy breathing (rattling). 119 h 45 min post-dose: slightly reduced spontaneous activity, piloerection, apathy, weight loss. 143 h 45 min post-dose: apathy, piloerection.166 h 45 min post-dose: weight gain.

Animal No. 2 and 3 of step 2 (300 mg/kg bw): 30 min post-dose: slightly reduced spontaneous activity, apathy, salivation. 2 h 15 min post-dose: slightly reduced spontaneous activity (animal no. 3), moderately reduced spontaneous activity (animal no. 2), piloerection, half eyelid-closure. 4 h 15 min post-dose: moderately reduced spontaneous activity, piloerection. 23 h 15 min post-dose: slightly reduced spontaneous activity, piloerection. 28 h 15 min post-dose: moderately reduced spontaneous activity, piloerection, half eyelid-closure. 2 days post-dose until the end of the observation period: no further symptoms were observed.

Animal no. 1 of step 3 (300 mg/kg bw): 15 min post-dose: slightly reduced spontaneous activity, apathy, piloerection. 2 h as well as 4 h 30 min, 22 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, half eyelid-closure. 47 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, half eyelid-closure, diarrhoea, bloody snout, anal discharge. 71 h post-dose: slightly reduced spontaneous activity, apathy, piloerection, diarrhoea, weight loss. 97 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, diarrhoea, weight loss. 121 h post-dose: slightly reduced spontaneous activity, piloerection, diarrhoea. 144 h post-dose: slightly reduced spontaneous activity, piloerection. 7 days post-dose until the end of the observation period: no further symptoms were observed.

Animal no. 2 of step 3 (300 mg/kg bw): 15 min post-dose: slightly reduced spontaneous activity, apathy, piloerection. 2 h as well as 4 h, 22 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, half eyelid-closure. 47 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, half eyelid-closure, diarrhoea, anal discharge. 71 h post-dose: slightly reduced spontaneous activity, apathy, piloerection, diarrhoea, weight loss. 97 h post-dose: severely reduced spontaneous activity, piloerection, diarrhoea, weight loss. 5 days post-dose the animal was found dead.

Animal no.3 of step 3 (300 mg/kg bw): 15 min post-dose: slightly reduced spontaneous activity, apathy, piloerection. 2 h as well as 4 h, 22 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, half eyelid-closure. 47 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, half eyelid-closure, diarrhoea, anal discharge, bloody snout.3 days post-dose the animal was found dead.

Animal no. 1, 2 and 3 of step 4 and 5 (50 mg/kg bw): No compound related mortality was recorded for any animal.

Absolute body weights in g :

Animal No.

  Sex

Day 0

Day 7

Day 14

Step 1 (2000 mg/kg bw)

 

1

 female

168

This animal was found dead.

 

Step 2 (300 mg/kg bw)

1

female

170

150

190

2

 female

180

189

205

3

 female

 186

196 

213

Step 3 (300 mg/kg bw)

 

 

 

 

1

 female

177

180

201

2

 female

141

92-this animal was found dead

3

 female

149

This animal was found dead.

Step 4 (50 mg/kg bw)

 

 

 

 

1

 female

135

138

142

2

 female

158

191

206

3

 female

158

183

197

Step 5 (50 mg/kg bw)

1

 female

128

162

177

2

 female

131

161

176

3

 female

130

163

174

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
Considering the reported data of this toxicity test it can be stated that the test item N-Coco-1,3-diaminopropane showed acute oral toxic characteristics.
According to GHS (Globally Harmonized Classification System) the test item N-Coco-1,3-diaminopropane was classified into Category 3 (LD50 cutoff:300 mg/kg bw).
Executive summary:

The acute toxic class method for oral toxicity was performed on nulliparous female HsdRccHan:WIST rats, who received a single exposure of N-Coco-1,3-diaminopropane via oral gavage.

A careful clinical examination was made several times on the day of dosing. Parts of this were at least three observations within the first four hours post-dose. Animals were observed once a day thereafter for 14 days. Cage side observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma. At the end of the observation period the animals were sacrificed by an overdosage of pentobarbital. All animals were subjected to gross necropsy. All gross pathological changes were recorded.

In step 1 single female rat was dosed by oral gavage with 2000 mg N-coco-1,3-diaminopropane/ kg body weight in cotton seed oil. Severe, immediate toxicity indicated by salivation, face down position and moderately reduced spontaneous activity was observed in this animal, followed by death at 1 h and 30 min post-dose. In step 2 three female rats were dosed with 300 mg N-coco-1,3-diaminopropane/ kg body weight. Animal 1 showed severe signs of toxicity indicated by immediate piloerection followed by half eyelid closure, sunken flank, diarrhoea, bloody snout and mouth, weight loss and heavy breathing . 7 days post-dosing the animal gained weight again and recovered. Animal 2 and 3 showed reduction in spontaneous activity, apathy, salvation, piloerection and half eyelid-closure shortly after dosing. 2 days post-dose until the end of the observation period no further symptoms were evident. In step 3 three female rats were dosed with 300 mg N-coco-1,3 -diaminopropane/ kg body weight. Observed signs of toxicity of animal 1 were reduced spontaneous activity, piloerection, apathy, half eyelid-closure, diarrhoea, bloody snout, anal discharge and weight loss until 7 days post-dose. The animal showed no symptoms thereafter. Animal 2 of step 3 displayed increasing signs of toxicity indicated by reduced spontaneous activity, piloerection, apathy, half eyelid-closure, diarrhoea, anal discharge as well as weight loss and was found dead on day 5 post-dose. Animal 3 of step 3 displayed increasing signs of toxicity indicated by reduced spontaneous activity, piloerection, apathy, half eyelid-closure, diarrhoea, bloody snout, anal discharge and weight loss and was found dead on day 3 post-dose. Animal no. 1, 2 and 3 of step 4 and 5 received 50 mg N-coco-1,3-diaminopropane/ kg body weight by oral gavage. No compound related mortality was recorded for any of the animals.

According to the toxic class regime no further testing was required.

Following pathological changes were observed in the step 1 animal (2000 mg/kg bw): The stomach showed haemorrhage with a foamy content. The small intestine also showed haemorrhage with a bloody content. The large intestine and appendix were bloody. Animal 2 of step 3 (300 mg/kg bw) that was found dead after 5 days in a lateral position exhibited piloerection. Its anus was smeared with faeces. Animal no. 3 of step 3 (300 mg/ kg bw) had a bloody stomach. Its small intestine was slightly bloody.

Considering the reported data of this toxicity test it can be stated that the test item N-coco-1,3-diaminopropane showed acute oral toxic characteristics. On basis of the test results and in conformity with the criteria given in Annex VI of the Directive 2001/59/EC the substance should be classified as toxic. According to GHS (Globally Harmonized Classification System) the test item N-Coco-1,3-diaminopropane was classified into Category 3 (LD50 cut-off: 300 mg/kg bw).

The acute oral toxicity test was conducted under GLP according to the guidelines for the acute toxic class method OECD 423, EU method B1.tris and OPPTS 870.110 without deviation.