Amines, N-C16-18-alkyltrimethylenedi-

Acute Toxicity: oral

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 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

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:

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:

other: 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).