Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008-07-07 to 2008-08-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 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)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: solidified melt
Details on test material:
98.9 % Decamethylenediamine
1.1% unidentified components

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ORGANISMS: 
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- Strain: RhsdRccHan: WIST
- body weight: 153 - 176 g
- Fasting period before study: overnight
- Diet: ad libitum, Altromin 1324
- Water: ad libitum
- Acclimatisation period: at least 5 days
- Temperature (°C): 22 °C +/- 3° C
- Humidity (%): 55% +/- 10 %
- Illumination: 12 hours artifical fluorescent light and 12 hours dark
- Air change: 10 per hour

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
cotton seed oil
Details on oral exposure:
ADMINISTRATION: 
- Frequency: single dosage on day 1
- Dose volume: 10 ml/kg b.w.
- DOSAGE PREPARATION: For all animals of the first and second step, 0.3 g of the test item was diluted with the vehicle ad 10 ml to gain a dosis of
300 mg/kg bw . For the animals of the third step, 2 g of the test item was diluted with the vehicle ad 10 ml to gain a dosis of 2000 mg/kg bw.
The administration volume was 10 mL/kg b.w.
- CLASS METHOD: acute-toxic-class methode
first step: 3 female rats are treated with 300 mg/kg b.w., one animal was found dead
second step: 3 female rats are treated with 300 mg/kg b.w., all survieved
third step: 3 female rats are treated with 2000 mg/kg b.w., all died
Doses:
300 mg/kg bw and 2000 mg/kg
No. of animals per sex per dose:
6 female 300 mg/kg
3 female 2000 mg/kg
Control animals:
no
Details on study design:
- Preparation of the animals: The animals were marked for individual identification by tail painting.
- Administration: The test item was aministered in a single dose by gavage using an intubation cannula.
- Duration of observation period following administration: 14 days
- Frequency of observations: before administration, at least three observations within the first four hours postdose and at least once daily thereafter, until day 14; Cageside 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.
- Body weight: The animals were weighed prior to the administration and once a week thereafter.
- Necropsy: All survived animals were sacrificed by an overdosage of pentobarbital. All animals were subjected to gross necrospy. All gross pathological changes were recorded.
Statistics:
not required

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
other: LD50 cut-off
Effect level:
500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut-off: 500 mg/kg bw
Mortality:
300 mg/kg bw :1 female of 6 fenale rats
2000 mg/kg bw: 3 female of 3 female rats
Clinical signs:
Animals of step 1 and 2 (300 mg/KG bw) showed slightly reduced spontaneous activity, staggering and apathy 5 - 20 minutes after administration. 35 min up to 2 hours they showed moderately reduced spontaneous activity, piloreaction and eyelid closure. One female were free of
symptoms after 2 days , 5 females after 6 and 7 days.
Animals of step 3 (2000 mg/kg bw) showed similar symptoms, but died after 3 hours (2 females) and 5 hours.
Body weight:
Throughout the 14-days observation period no weight loss was recoverd in any surviving animal. The weight gain was within the expected range.
Gross pathology:
1 animal of step I: The stomach was partially infiltrated with blood, the small as well as the large intestine were bloated.
2 animals of step 3: The stomach was bloated and infiltrated with blood, the small intestine was also infiltrated with blood and the liver showed a darkish discolouration.
1 animal of step 3: The stomach was bloated and infiltrated with blood and, the small intestine was infiltrated with blood as well and the milt was slightly enlarged.
Other findings:
no other findings

Any other information on results incl. tables

no other information

Applicant's summary and conclusion

Conclusions:
Considering the reported data of this toxicity test it can be stated that the test item decamethylenediamine showed acute orally toxic characteristics. The LD50 cut-off value (oral) of the test substance was estimated to be 500 mg/kg bw.
Executive summary:

The test item was given to female WISTAR rats by oral administration to obtain information on the toxicity, in particular lethality, of the test item. The Acute Toxic Class Method was employed to establish the required information for hazard assessment and hazard classification.

The acute toxic class method was performed with the test item decamethylenediamine. In the first step the test item was given at a dose of 300 mg/kg body weight to a group of 3 female rats. Compound-related mortality was found in one animal of step 1 within 2 days. Based on the results of the first step and in accordance with the acute toxic class regime, the second step was performed with the same dose in the same manner to a further groups of 3 female rats. No compound-related mortality was found in any animal of step 2. Based on the results of the second step and in accordance with the acute toxic class regime, the third step was performed at a dose of 2000 mg/kg body weight to a group of 3 female rats. Compound-related mortality was found in all 3 animals of step 3 within 5 hours.

Based on the results of the third step and in accordance with the acute toxic class regime, no further testing was required since compound-related mortality was found in all animals of step 3.

Animals of step 1 and 2 (300 mg/KG bw) showed slightly reduced spontaneous activity, staggering and apathy 5 - 20 minutes after administration. 35 min up to 2 hours they showed moderately reduced spontaneous activity, piloreaction and eyelid closure. One female were free of symptoms after 2 days , 5 females after 6 and 7 days. Animals of step 3 (2000 mg/kg bw) showed similar symptoms up to the death.