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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 June 2009 - 14 July 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

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
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Reference substance 001
Cas Number:
1219458-14-6
Details on test material:
- Chemial name: Triamine C16-18, C18-unsaturated
- EC Number: 628-863-4

To the best of knowledge, the sample used is representative to the boundary composition share and agreed by each registrant.

Test animals

Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: approx. 9-11 weeks old
- Weight at study initiation: 155-186 grams. Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: yes, overnight prior to dosing and until 3-4 hours after administration of the test substance
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material and paper as cage-enrichment.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period:at least 5 days before start of treatment under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.4 – 21.0ºC
- Humidity (%): 41 - 79%
- Air changes (per hr): approx.15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 24 June 2009 To: 14 July 2009

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 300 mg/kg: 30 mg/mL, and 2000 mg/kg: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg


DOSAGE PREPARATION (if unusual):
The formulations (w/w) were prepared within 4 hours prior to dosing, and were flushed with nitrogen (except the 2000 mg/kg formulation; this was considered not to have adversely affected integrity of the test substance as the test substance itself was flushed with nitrogen and formulated in vehicle afterwards). Homogeneity was accomplished to a visually acceptable level. In order to obtain homogeneity, the test substance (formulations) were heated in a water bath with a maximum temperature of 44ºC for at least 11 minutes. The test substance (formulations) were allowed to cool down to a temperature of maximally 40ºC prior to dosing. Adjustment was made for specific gravity of the vehicle and for density of the test substance. The concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of mL/kg body weight.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on anticipated toxicity at 2000 mg/kg.
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
2000 mg/kg: one group of 3 females
300 mg/kg: two groups of 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. Weighing: Days 1 (pre-administration), 8 and 15 and at death (if found dead after Day 1).
- Necropsy of survivors performed: yes
- Other examinations performed: none.
Statistics:
Not applicable.

Results and discussion

Preliminary study:
Not applicable
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 300 - <= 2 000 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: OECD 423 Cut-off level
Mortality:
The incidence of mortality was as follows, presented in chronological order of treatment:
Dose level Mortality Date of treatment
300 mg/kg 0/3 24 June 2009
300 mg/kg 0/3 30 June 2009
2000 mg/kg 3/3 02 July 2009

At 2000 mg/kg, animals were found dead or sacrificed in moribund condition on Days 2 or 3.
Clinical signs:
other: Clinical signs observed during the study period were as follows: Dose level Clinical signs 300 mg/kg Hunched posture, piloerection, lethargy, chromodacryorrhoea on Days 1 and/or 2. 2000 mg/kg Hunched posture, piloerection, lethargy, ptosis.
Gross pathology:
An advanced stage of autolysis was noted for one animal at 2000 mg/kg found dead on Day 3.
No further abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
None.

Any other information on results incl. tables

None.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: other: GHS, EU 67/548/EEC and 1272/2008
Conclusions:
The oral LD50 value of Tallow dipropylenetriamine in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.
OECD 423 LD50 cut-off value is 500 mg/kg body weight.
Executive summary:

All animals at 2000 mg/kg were found dead or were sacrificed moribund on Days 2 or 3. At 300 mg/kg, no mortality occurred.                             

Clinical signs observed during the study period were as follows:

Dose level                    Clinical signs

300 mg/kg                    Hunched posture, piloerection, lethargy, chromodacryorrhoea on Days 1 and/or 2.

2000 mg/kg                  Hunched posture, piloerection, lethargy, ptosis.

Slight body weight loss was noted for all animals at 2000 mg/kg prior to death.

The mean body weight gain shown by the animals at 300 mg/kg over the study period was considered to be normal.

An advanced stage of autolysis was noted for one animal at 2000 mg/kg found dead on Day 3.

No further abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50value of Tallow dipropylenetriamine in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 500 mg/kg body weight.