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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
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.

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:
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
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tall oil diethylenetriamine imidazoline
- Substance type: Clear slightly viscous amber liquid
- Physical state: liquid
- Analytical purity: See Certificate of Analysis
- Purity test date: 11 May 2009
- Lot/batch No.: S000922
- Expiration date of the lot/batch: 02 July 2017
- Stability under test conditions: Stable
- Storage condition of test material: At room temperature in the dark under nitrogen

Test animals

Species:
rat
Strain:
other: Wistar strain Crl:WI (Han)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 9-11 weeks
- Weight at study initiation: 153-195 g
- Fasting period before study: overnight until 3-4 hours after administration
- 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


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 – 21.1
- Humidity (%): 44 - 78
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 08 July 2009 To: 05 August 2009

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml (2000 mg/kg b.w.) or 30 mg/ml (300 mg/kg b.w.)
- Amount of vehicle (if gavage): 10 ml/kg b.w.
- 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 b.w.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose of 300 mg/kg was based on toxicity expected for similar substances.
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations at least once daily. Weighing: weekly.
- Necropsy of survivors performed: yes
- Other examinations performed: no
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One female at 2000 mg/kg was found dead on Day 4. No (further) mortality occurred at 300 and 2000 mg/kg.
Clinical signs:
Clinical signs observed during the study period were as follows:
Dose level Clinical signs
300 mg/kg Hunched posture, piloerection, lethargy, uncoordinated movements, rales, lean appearance and/or ptosis between Days 1 and 2; one female (no. 6) showed hunched posture and rales throughout the observation period, along with lean appearance and piloerection on Day 15.
2000 mg/kg Hunched posture, piloerection and/or lethargy between Days 1 and 5.
Body weight:
One female at 300 mg/kg showed body weight loss throughout the observation period. Other animals at 300 mg/kg showed normal body weight gain.
One female at 2000 mg/kg found dead on Day 4 showed body weight loss between Days 1 and 4. Three other females at 2000 mg/kg showed no body weight gain or slight body weight loss between Days 1 and 8. Body weight gain among the (other) surviving females at 2000 mg/kg during the (remainder of the) observation period was considered to be normal.
Gross pathology:
One female at 300 mg/kg showed gaseous distension of the gastro-intestinal tract. No further macroscopic abnormalities were noted among other animals at 300 mg/kg.
Three females at 2000 mg/kg showed a stomach and right lateral lobe of the liver grown together with the diaphragm. No macroscopic abnormalities were noted in the other animals at 2000 mg/kg, including the female found dead on Day 4.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The oral LD50 value of Tall oil diethylenetriamine imidazoline in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 2500 mg/kg body weight.
Executive summary:

Assessment of acute oral toxicity with Tall oil diethylenetriamine imidazoline in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in:

OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method"

Commission Regulation (EC) No 440/2008, B1 tris: "Acute Oral Toxicity, Acute Toxic Class Method"

EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity"

JMAFF guidelines (2000) including the most recent partial revisions.

 

Initially, Tall oil diethylenetriamine imidazoline was administered by oral gavage to three female Wistar rats at 300 mg/kg body weight. In a stepwise procedure additional groups of females were dosed at 300 and 2000 mg/kg body weight. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

 

One female at 2000 mg/kg was found dead on Day 4. No (further) mortality occurred at 300 and 2000 mg/kg.

 

Clinical signs observed during the study period were as follows:

300 mg/kg:

Hunched posture, piloerection, lethargy, uncoordinated movements, rales, lean appearance and/or ptosis between Days 1 and 2; one female showed hunched posture and rales throughout the observation period, along with lean appearance and piloerection on Day 15.

2000 mg/kg:

Hunched posture, piloerection and/or lethargy between Days 1 and 5.

 

One female at 300 mg/kg showed body weight loss throughout the observation period. Other animals at 300 mg/kg showed normal body weight gain.

One female at 2000 mg/kg found dead on Day 4 showed body weight loss between Days 1 and 4. Three other females at 2000 mg/kg showed no body weight gain or slight body weight loss between Days 1 and 8. Body weight gain among the (other) surviving females at 2000 mg/kg during the (remainder of the) observation period was considered to be normal.

 

One female at 300 mg/kg showed gaseous distension of the gastro-intestinal tract. No further macroscopic abnormalities were noted among other animals at 300 mg/kg.

Three females at 2000 mg/kg showed a stomach and right lateral lobe of the liver grown together with the diaphragm. No macroscopic abnormalities were noted in the other animals at 2000 mg/kg, including the female found dead on Day 4.

No explanation could be found for the differing macroscopic findings between the two treated groups at 2000 mg/kg.

The oral LD50 value of Tall oil diethylenetriamine imidazoline in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 2500 mg/kg body weight.