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Description of key information

Acute toxicity: Oral LD50 > 2000 mg/kg for rat (LD50 cut-off: 2500 mg/kg bw)

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
Study period:
15 July 2009 - 12 August 2009
Reliability:
1 (reliable without restriction)
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
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: Wistar strain Crl:WI (Han)
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL and 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 bw
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
6 females/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:0, 2 and 4 hrs after dosing on Day 1 and daily thereafter. Weighing: weekly.
- Necropsy of survivors performed: yes
- Other examinations performed: no
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
One female at 2000 mg/kg was found dead on Day 2. No mortality occurred among other animals at 2000 mg/kg, or among animals at 300 mg/kg.
Clinical signs:
Clinical signs observed during the study period were as follows:
Dose level Clinical signs
300 mg/kg Lethargy, hunched posture, uncoordinated movements and/or piloerection on Day 1.
2000 mg/kg Hunched posture and/or piloerection between Days 1 and 4.
Body weight:
The mean body weight gain shown by the surviving 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.
Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The oral LD50 value of Tall oil, reaction products with tetraethylene-pentamine (Amidoamine/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 reaction products with tetraethylene-pentamine 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 reaction products with tetraethylene-pentamine 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 2. No mortality occurred among other animals at 2000 mg/kg, or among animals at 300 mg/kg.

Clinical signs observed during the study period were as follows:

Dose level Clinical signs

300 mg/kg Lethargy, hunched posture, uncoordinated movements and/or piloerection on Day 1.

2000 mg/kg Hunched posture and/or piloerection between Days 1 and 4.

The mean body weight gain shown by the surviving 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 reaction products with tetraethylene-pentamine 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
Quality of whole database:
Most recent guideline GLP study.

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

Fatty acid C18 unsaturated reaction products with tetraethylenepentamine (FA-TEPA) was tested for acute oral toxicity according to acute toxic class method. The study showed one death out of 6 dosed at 2000 mg/kg, and no mortality at 300 mg/kg. At 300 mg clinical signs included lethargy, hunched posture, uncoordinated movements and/or piloerection on Day 1. At 2000 mg/kg Hunched posture and/or piloerection was observed between Days 1 and 4.

 

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 ethyleneamine part.

 

Acute oral toxicity amidoamines/imidazolines:

Fatty acid C18 unsat + DETA

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

Fatty acid C18 unsat + DETA

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

Fatty acid C18 unsat + 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

Fatty acid C18 unsat + 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, which should limit the systemic uptake of amount needed for systemic toxicity considering the relatively low acute oral toxicity.

 

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 which is considered to have the highest vapour pressure within the AAI) and use applications that do not involve the forming of aerosols, particles or droplets of an inhalable size. 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 + TEPA 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 indicates 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.

 

AAI-substances do not contain containing aliphatic, alicyclic and aromatic hydrocarbons and have a relatively high viscosity and so do not indicate an immediate concern for aspiration hazard.