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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007-11-27 to 2007-12-24
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
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-C16-18-alkyl (evennumbered) propane-1,3-diamine
EC Number:
696-364-9
Cas Number:
133779-11-0
Molecular formula:
Not applicable
IUPAC Name:
Amines, N-C16-18-alkyl (evennumbered) propane-1,3-diamine
Test material form:
solid: pellets
Details on test material:
- Substance type: Diamine
- Name of test material (as cited in study report): N-(Hydrogenated tallow)-1,3-diaminopropane
- CAS: 68603-64-5- Physical state: pellets
- Colour: light yellow
- Composition of test material, percentage of components:

Total primary amines: 9.6 %
Total Diamines: 90.4 %
Iodine number: 3 g I/100g (0-10)
Water: 0.6 % (0-1)

C12 N Primary amine: 0.1 %
C14 N Primary amine: 0.2 %
C16 N Primary amine: 3.0 %
C18 N Primary amine: 6.3 %
C12 Diamine: 0.3 %
C14 Diamine: 1.5 %
C16 Diamine: 28.3 %
C18 Diamine: 60.3 %
Acrylnitrile: <4 ppm
Fatty acids: <1 %
Fatty alkyl nitriles: <1 %

- Purity test date: 2007-10-15
- Lot/batch No.: S000905
- Expiration date of the lot/batch: 2010-09-30
- Storage condition of test material: at room temperature

Test animals

Species:
rat
Strain:
other: HsdRccHan: WIST (SPF)
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: 172-180 g
Step 2: 176-177 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
2.0 g/ 10 mL
Step 2: 2.0 g/ 10 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: 1.80 mL

DOSAGE PREPARATION : freshly mixed to homogeneity prior to administration

CLASS METHOD
- Rationale for the selection of the starting dose:
the starting dose was choosen to be 2000 mg/kg bw
Doses:
Step 1: 2000 mg/kg bw
Step 2: 2000 mg/kg bw
No. of animals per sex per dose:
Step 1 (2000 mg/kg bw): 3 female rats
Step 2 (2000 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:
2 500 mg/kg bw
Remarks on result:
other: acute toxic class method; according to GHS (Globally Harmonized Classification System) the test item N-(Hydrogenated tallow)-1,3-diaminopropane was classified into Category 5
Mortality:
Step 1 (2000 mg/kg bw): 28 h post-dose one animal was found dead
Clinical signs:
see remarks on results including tables and figures
Body weight:
Throughout the 14-day observation period weight loss was recorded for two animals (after 7 days, but weight gain was recorded for the same animals after 14 days). Weight gain of the other animals was within the expected range.
For further details see remarks on results including tables and figures.
Gross pathology:
Animal no. 3 of step 1 (2000 mg/ kg bw):
The dead animal was found in a lateral position. Stomach: solid content.
Small and large intestine: partly filled with solid substance.
Animal no.2 of step 2 (2000 mg/ kg bw):
The spleen was enlarged, with a weight of 0.872 g.

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): 20 min as well as 125 min post-dose: slightly reduced spontaneous activity, apathy, piloerection. 21 h 05 min as well as 27 h 5 min, 45 h 05 min post-dose: slightly reduced spontaneous activity, piloerection. 51 h 5 min post-dose: slightly reduced spontaneous activity. 69 h 05 min until the end of the observation period: no further symptoms were observed.

Animal no. 2 of step 1 (2000 mg/kg bw): 30 min as well as 3 h post-dose: slightly reduced spontaneous activity, apathy, piloerection. 24 h as well as 45 h post-dose: slightly reduced spontaneous activity, piloerection. 71 h as well as 94 h, 99 h post-dose: piloerection 117 h until the end of the observation period: no further symptoms were observed.

Animal No. 3 of step 1 (2000 mg/kg bw): 30 min post-dose: slightly reduced spontaneous activity, apathy, piloerection. 2 h post-dose: slightly reduced spontaneous activity, apathy, piloerection, salivation. 4 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, salivation. 28 h post-dose: this animal was found dead.

Animal no. 1 of step 2 (2000 mg/kg bw):1 h post-dose: slightly reduced spontaneous activity, apathy, piloerection, stertorousness. 3 h as well as 22 h, 27 h post-dose: piloerection. 45 h until the end of the observation period: no further symptoms were observed.

Animal no. 2 of step 2 (2000 mg/kg bw): 1 h post-dose: slightly reduced spontaneous activity, apathy, piloerection. 3 h as well as 22 h, 27 h, 45 h post-dose: piloerection. 69 h until the end of the observation period: no further symptoms were observed.

Animal no.3 of step 2 (2000 mg/kg bw): 1 h post-dose: piloerection. 4 h as well as 23 h, 28 h, 46 h post-dose: piloerection. 69 h until the end of the observation period: no further symptoms were observed.

Absolute body weights in g :

Animal No.

  Sex

Day 0

Day 7

Day 14

Step 1 (2000 mg/kg bw)

1

female

180

195

220

2

 female

173

154

193

3

 female

172

157-this animal was found dead.

Step 2 (2000 mg/kg bw)

 

 

 

1

 female

177

158

195

2

 female

177

178

197

3

 female

176

184

190

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Considering the reported data of this toxicity test it can be stated that the test item N-(Hydrogenated tallow)-1,3-diaminopropane showed oral toxic
characteristics.
According to GHS (Globally Harmonized Classification System) the test item N-(Hydrogenated tallow)-1,3-diaminopropane was classified into Category 5. (LD50 cut-off: 2500 mg/kg bw).
Executive summary:

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.

The acute toxic class method for oral toxicity was performed on nulliparous female HsdRccHan:WIST rats, who received a single exposure of N-(Hydrogenated tallow)-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 three female rat were dosed by oral gavage with 2000 mg N-(Hydrogenated tallow)-1,3-diaminopropane/ kg body weight in cotton seed oil. One of the animals died 28 h post-dose. Signs of slight toxicity indicated by apathy, piloerection and reduced spontaneous activity were observed during the first 3 and 5 days in animal 1 and 2 of step 1, respectively. No further symptoms were observed in these two animals until the end of the observation period. In animal 3 apathy, piloerection, reduced spontaneous activity and salvation were evident after dosing and the animal was found dead 28 h post-dose. In step 2 three additional female rats were dosed with 2000 mg N-(Hydrogenated tallow)-1,3-diaminopropane/ kg body weight. No compound related mortality was recorded for any of these animals. Observed signs of toxicity were reduced spontaneous activity, apathy, pilerection and stertorousness. All animals of step 2 recovered within 3 days. According to the toxic class regime no further testing was required.

Following pathological changes were observed in animal 3 of step 1 (2000 mg/kg bw): The dead animal was found in a lateral position. The stomach as well as small and large intestine were at least partly filled with solid content. Following pathological changes were observed in animal 2 of step 2 (2000 mg/kg bw): The spleen was enlarged, with a weight of 0.872 g.

Considering the reported data of this toxicity test it can be stated that the test item N-(Hydrogenated tallow)-1,3-diaminopropane showed oral toxic characteristics.

According to GHS (Globally Harmonized Classification System) the test item N-(Hydrogenated tallow)-1,3-diaminopropane was classified into Category 5 (LD50cut-off: 2500 mg/kg bw).