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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007-11-16 to 2008-01-03
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:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): N-Oleyl-1,3-diaminopropane
- Physical state: liquid
- Analytical purity: N-Alkyl-1,3-diaminopropanes: 92.3%
N-Alkyl-amines: 7.7%
C-Chain-distribution (R = alkyl):
R = C16: 7%; C18: 91%; C20: 2%
- Lot/batch No.: S000902
- Production date of the test item: August 13, 2007
- Expiration date of the lot/batch: September 30, 2010
- Storage condition of test material: at room temperature
- Product (name): Duomeen OV
- Colour: Max 7 Gardner
- Melting Point: 9 - 20°C
- pH: basic

Test animals

Species:
rat
Strain:
other: HsdRccHan:WIST (Full-Barrier)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- Weight at study initiation:
Step 1: 154-166 g
Step 2: 171-191 g
Step 3: 172-179 g

- Fasting period before study: overnight
- Housing: Macrolon cages on Altromin saw fiber bedding
- Diet: ad libitum, Altromin 1324
- 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 g/ 5 mL and 2 g/10 mL cotton seed oil
Step 2: 0.3 g/ 10 mL cotton seed oil
Step 3: 0.3 g/ 10 mL cotton seed oil
- Amount of vehicle: 10 mL/ kg body weight
- Justification for choice of vehicle: non-toxic characteristic
- Lot/batch no.: Lot 067K0116, Sigma Chemicals

MAXIMUM DOSE VOLUME APPLIED: 1.91 mL

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 2000 mg/ kg was selected as the starting dose
Doses:
Step 1: 2000 mg/ kg
Step 2 and 3: 300 mg/ kg body weight
No. of animals per sex per dose:
female nulliparous rats
2000 mg/ kg dose (Step 1): 3 animals
300 mg/ kg dose (Step 2 and 3): 3 animals + 3 animals
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 postdose.
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. 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.
Statistics:
not applicable

Results and discussion

Preliminary study:
no data
Effect levels
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
500 mg/kg bw
Remarks on result:
other: acute toxic class method; according to GHS (Globally Harmonized Classification System) the test item N-Oleyl-1,3-diaminopropane was classified into Category 4
Mortality:
Step 1 (2000 mg/kg bw): all 3 animals died within 24 h (one was euthanised due to animal welfare reasons, two were found dead in their cages)
Step 2 (300 mg/kg bw): 1 animal was found dead 10 days after treatment
Step 3 (300 mg/kg bw): no mortality observed
Clinical signs:
see remarks on results including tables and figures
Body weight:
Throughout the 14-day observation period weight loss was recorded in 2
animals. The weight gain of the other animals was within the expected range.

For further details see remarks on results including tables and figures.
Gross pathology:
Effect on organs (related to dose level):

Animal no. 1 of step 1 (2000 mg/ kg bw):
The animal was found dead in a lateral position. Rests of the test item were
found in the stomach. The lungs were infiltrated with blood.

Animal no. 2 of step 1 (2000 mg/ kg bw):
Rests of the test item were found in the stomach. The lungs were infiltrated
with blood.

Animal no. 3 of step 1 (2000 mg/ kg bw):
Rests of the test item were found in the stomach, which was bloated. The
small intestine was empty and of a yellow colour. This animal was
euthanised due to animal welfare reasons.

Animal no. 2 of step 2 (300 mg/ kg bw):
Stomach, small and large intestine bloated and empty.

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: salivation. 2 h post-dose: slightly reduced spontaneous activity, apathy, piloerection, salivation, half eyelid-closure. 4 h post-dose: moderately reduced spontaneous activity, piloerection, salivation, full eyelid-closure. 5 h as well as 9 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, salivation, half eyelid-closure. 24 h post-dose the animal was found dead.

Animal no. 2 of step 1 (2000 mg/kg bw): 30 min post-dose: salivation. 2 h post-dose: slightly reduced spontaneous activity, apathy, piloerection, salivation, half eyelid-closure. 4 h post-dose: moderately reduced spontaneous activity, piloerection, salivation, full eyelid-closure. 5 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, salivation, half eyelid-closure. 9 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, salivation, half eyelid-closure, slight articulation. 24 h post-dose the animal was found dead.

Animal No. 3 of step 1 (2000 mg/kg bw): 30 min post-dose: salivation. 2 h post-dose: slightly reduced spontaneous activity, apathy, piloerection, salivation. 4 h post-dose: moderately reduced spontaneous activity, piloerection, salivation, full eyelid-closure. 5 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, salivation, half eyelid-closure. 9 h post-dose: moderately reduced spontaneous activity, apathy, piloerection, salivation, half eyelid-closure, slight articulation. 24 h post-dose: moderately reduced spontaneous activity, piloerection, salivation, half eyelid-closure, severe articulation. 25 h post-dose: for animal welfare reasons this animal was euthanised.

Animal no. 1 of step 2 (300 mg/kg bw): 3 h 25 min as well as 7 h, 24 h, 30 h post-dose: piloerection. 48 h post-dose until the end of the observation period: no symptoms were observed.

Animal no. 2 of step 2 (300 mg/kg bw): 45 min as well as 2 h 45 min post-dose: slightly reduced spontaneous activity, piloerection, half eyelid-closure. 4 h 45 min post-dose: slightly reduced spontaneous activity, piloerection. 23 h 45 min post-dose: weight loss, stertorousness. 47 h 45 min as well as 71 h 45 min, 95 h 45 min, 119 h 45 min, 143 h 45 min, 167 h 45 min, 191 h 45 min post-dose: piloerection, weight loss, stertorousness. 215 h 45 min. post-dose: moderately reduced spontaneous activity, piloerection, weight loss, stertorousness. 10 days (238 h 45 min) post-dose: the animal was found dead.

Animal no. 3 of step 2 (300 mg/kg bw): 1 h 15 min post-dose: piloerection. 2 h 45 min as well as 4 h 45 min post-dose: slightly reduced spontaneous activity, piloerection. 23 h 45 min post-dose until the end of the observation period: no symptoms were observed.

Animal no. 1, 2 and 3 of step 3 (300 mg/kg bw): 15 min as well as 1 h 45 min post-dose: slightly reduced spontaneous activity, piloerection. 3 h 45 min post-dose: moderately reduced spontaneous activity, piloerection. 21 h 45 min as well as 45 h 45 min post-dose: slightly reduced spontaneous activity, piloerection. 69 h 45 min post-dose: piloerection. 93 h 45 min post-dose until the end of the observation period: no 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

154

This animal was found dead.

 

2

 female

157

This animal was found dead.

 

3

 female

 166

This animal was found dead 

 

Step 2 (300 mg/kg bw)

 

 

 

 

1

 female

171

189

212

2

 female

191

137

This animal was found dead.

3

 female

173

187

200

Step 3 (300 mg/kg bw)

 

 

 

 

1

 female

172

180

196

2

 female

179

192

206

3

 female

173

165

182

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information criteria given in Annex VI of the Directive 2001/59/EC Criteria used for interpretation of results: EU
Conclusions:
Considering the reported data of this toxicity test it can be stated that the test item N-Oleyl-1,3-diaminopropane showed acute oral toxic characteristics. According to GHS (Globally Harmonized Classification System) the test item N-Oleyl-1,3-diaminopropane was classified into Category 4 (LD50 cut-off: 500 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-Oleyl-1,3-diaminopropane (liquid) 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 rats were dosed by oral gavage with 2000 mg N-Oleyl-1,3-diaminopropane/ kg body weight in cotton seed oil. Severe toxicity indicated by salivation, apathy, piloerection and half eyelid-closure were observed in this group after the application. Two animals died within 24 h and one was euthanized 25 h post-dose for animal welfare reasons. In step 2 three female rats were dosed with 300 mg N-Oleyl-1,3-diaminopropane/ kg body weight. Two animals showed slight signs of toxicity indicated by piloerection and reduced spontaneous activity until 48 h post-dose and had recovered completely thereafter. One animal showed severe signs of toxicity indicated by reduced spontaneous activity, half eyelid-closure, piloerection, weight loss and stertorousness and was found dead after 10 days. Therefore three additional female rats were dosed with 300 mg N-Oleyl-1,3 -diaminopropane/kg body weight. Observed signs of toxicity were slightly reduced spontaneous activity and piloerection until 4 days post-dose. The animals showed no symptoms thereafter. According to the toxic class regime no further testing was required.

Following pathological changes were observed in the step 1 animals (2000 mg/kg bw): rests of the item were found in the stomach of all three rats, the lungs were infiltrated with blood in all three rats, one animal had a bloated stomach and an empty small intestine of a yellow colour. The animal of step 2 (300 mg/kg bw) that was found dead after 10 days had a bloated and empty stomach and small and large intestine.

Considering the reported data of this toxicity test it can be stated that the test item N-Oleyl-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 harmful. According to GHS (Globally Harmonized Classification System) the test item N-Oleyl-1,3-diaminopropane was classified into Category 4 (LD50 cut-off: 500 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.