Registration Dossier

Administrative data

Description of key information

No data on acute toxicity is available for"Fatty acids C18 unsat, reaction products with triethylenetetramine" (or TO + TETA). Read-across is performed with ""Fatty acids C18 unsat, reaction products with diethylenetetramine" (or TO + DETA).

Acute Oral Toxicity LD50 > 2000 mg/kg for rat (LD50 cut-off: 2500 mg/kg bw). No acute dermal and inhalation toxicity studies were performed on the substance due to its corrosive properties.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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.
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
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
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).
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.
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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 500 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

As explained in the category justification, For cross-reading in general use is made with data of same or lower EA-length where available, and that of Tall oil + DETA representing the worst case. This dossier is for the substance "Fatty acids C18 unsat, reaction products with triethylenetetramine" (or TO + TETA). As for the substance itself no toxicological information is available, cross-reading has been applied to TO + DETA.

Tall oil + DETA was tested for acute oral toxicity in two different studies, both according to acute toxic class method. Both studies show the same outcome showing 1 resp. 2 deaths out of 6 dosed at 2000 mg/kg, and no mortality at 300 mg/kg.

At 300 mg clinical signs included Hunched posture, piloerection, lethargy, uncoordinated movements, hypersalivation, dyspnoea, and/or lean appearance, which in an incidental animal lasted until the end of the observation period.

 

All other studies with AAI substances show similar acute oral toxicity, all with a LD50 > 2000 mg/kg bw. There is possibly a small tendency of decreased toxicity with increasing size of the EA.

 

Acute toxicity amidazolines:

    TO + DETA                    >2000 mg/kg bw ,Cat.5; ATC cut off 2500mg/kg bw

    TO + DETA                    >2000 mg/kg bw, Cat.5; ATC cut off 2500mg/kg bw

    TO + TEPA                    >2000 mg/kg bw, Cat.5; ATC cut off 2500mg/kg bw

    C16-18,C18 unsat+TEPA>2000 mg/kg bw, Cat.5; Limit test 20% mortality

    TO + Poly(Amide)          >2000 mg/kg bw ,Cat.5; ATC cut off 5000mg/kg bw

Acute dermal toxicity: AAI are corrosive to the skin. Testing for acute dermal toxicity is therefore not justified. Toxicity following dermal exposure is characterised by local tissue damage, rather than the result of percutaneously absorbed material.

 

Acute inhalation toxicity: Physical-chemical properties of AAI indicate a low likelihood for exposure via inhalation having a boiling point > 300 °C and a low vapour pressure (0.00017 mPa at 25°C for DETA based AAI).

Furthermore, the substance is classified as corrosive and no acute toxicity testing should normally be conducted.

Justification for classification or non-classification

Acute oral exposure of Tall oil + DETA show limited acute toxicity, with a LD50 above 2000 mg/kg bw. Hence no classification is required.

 

Acute dermal testing with corrosive materials is not justified. As a consequence no classification can be made for acute dermal toxicity. Effects will be characterised by local tissue damage. Systemic uptake via skin is likely to be very limited. The low acute oral toxicity indicate a low systemic toxicity.

No classification for acute dermal toxicity is therefore indicated.

 

Also for acute inhalation toxicity information for classification is lacking, and is testing not justified. Due to very low vapour pressure is the likelihood of exposure low.