Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 July 2009 - 13 August 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.

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:
yes
Remarks:
The first group of females inadvertently received a too low dose volume initially (i.e. 2.06 ml/kg bw, corresponding to 412 mg/kg bw). Evaluation: An additional dose was administered to achieve a total dose of 2000 mg/kg bw. In accordance with the OECD 42
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
see OECD 423
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tall oil fatty acids, reaction products with polyethylene-polyamines (Amidoamine)
- Substance type: Bottom phase: yellow to light brown paste, upper phase: clear amber liquid with flakes of the bottom
- Physical state: liquid-paste
- Analytical purity: see Certificate of analysis
- Lot/batch No.: S001681
- Expiration date of the lot/batch: 23 October 2018
- 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: approx. 9 weeks old
- Weight at study initiation: 158-174 grams
- Fasting period before study: Animals were deprived of food overnight prior to dosing until approximately 2-4 hours after the last dosage.
- 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): 19.6 – 20.9ºC
- Humidity (%): 44 - 81%
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- 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): Formulations were heated up to 41.5°C for a maximum of 23 minutes. Formulations were allowed to cool down to below 40°C prior to dosing, and were placed in a waterbath during dosing (maximum 38°C).

Doses:
2000 mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: 0, 2 and 4 hrs after dosing on Day 1 and daily thereafter. Weighing: weekly.
- Necropsy of survivors performed: yes
- Other examinations performed: no

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture and piloerection were observed among all animals on Days 1 and/or 2.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value of Tall oil fatty acids, reaction products with polyethylene-polyamines (Amidoamine) 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 exceed 5000 mg/kg body weight.
Executive summary:

Assessment of acute oral toxicity with Tall oil fatty acids, reaction products with polyethylenepolyamines (Amidoamine) 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.

 

Tall oil fatty acids, reaction products with polyethylene-polyamines (Amidoamine) was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

 

No mortality occurred.

 

Hunched posture and piloerection were observed among all animals on Days 1 and/or 2.

 

The body weight gain shown by the animals over the study period was considered to be normal.

 

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

 

The oral LD50 value of Tall oil fatty acids, reaction products with polyethylene-polyamines (Amidoamine) 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 exceed 5000 mg/kg body weight.

 

Based on these results, Tall oil fatty acids, reaction products with polyethylene-polyamines (Amidoamine) does not have to be classified and has no obligatory labeling requirement for acute oral toxicity according to the:

- Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007),

- Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures,

- EC criteria for classification and labeling of dangerous substances and preparations (Council Directive 67/548/EEC and all adaptations to technical progress and amendments of this Directive published in the Official Journal of the European Union).