Fatty acids, C18-unsatd., reaction products with ammonia-ethanolamine reaction by-products

Endpoint summary

Description of key information

Oral LD50 = 4000 mg/kg in rat; dermal LD50 > 2000 mg/kg bw in rat.

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Old report, non-GLP. Limited detail reported.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

No body weight recording; No addtional group of the other sex was dosed.

GLP compliance:

no

Remarks:

Pre-GLP; signed authentication form present

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bantin and Kipman Ltd; caesarian-derived, outbread SD
- Age at study initiation:
- Weight at study initiation: 121-145 g
- Fasting period before study: 16 hrs
- Housing: groups of 6 animals in suspended plastic cages
- Diet (e.g. ad libitum): expanded autoclaved small animal diet (Spratt's Lab. Diet No. 1); ad lib
- Water (e.g. ad libitum): source not specified; ad lib
- Acclimation period: 1 week for range finder; 3 weeks for main study.

ENVIRONMENTAL CONDITIONS: not indicated

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): constant volume of 20 ml/kgBW
- Concentration in vehicle: dose between 1.0 to 8 g/kgBW, thus concentration between 50 - 400 g/L
- Justification for choice of vehicle: Leads to acceptable emulsion
- Lot/batch no. (if required): not indicated
- Purity: not indicated

MAXIMUM DOSE VOLUME APPLIED: constant volume of 20 ml/kgBW

Doses:

Range finder: 1 , 2, 4, 6, 8 g/kgBW
Main study: 2.25, 2.92, 3.80, 4.94, 6.42 g/kgBW

No. of animals per sex per dose:

Range finder: 2 animals/group
Main study: 6 animals/group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not indicated. No BW measured
- Necropsy of survivors performed: yes/no
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Clinical signs at least daily. Macroscopic post mortem examination.

Statistics:

LD50 calculated according to Thompson WR (1947) Bact. Reviews 11, 115.

Preliminary study:

dose-range study with 5 dose levels: 1.0, 2.0, 4.0, 6.0 and 8.0 g/kgBW
At 1.0 and 2.0 g/kg no deaths occurred. At higher levels all animals died. (See table for further information)

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 4 000 mg/kg bw

95% CL:

3 400 - 4 800

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Conclusions:

LD50 = 4 g/kgBW

Executive summary:

The acute oral toxicity of Berolamine AA15 was investigated in male Sprague Dawley rats. The Median Lethal Dose and its 95% confidence limits were calculated to be 4.0 (3.4 -4.8) g/kg. As such this material may be classified as category 5 for acute toxicity hazard (GHS).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

4 000 mg/kg bw

Quality of whole database:

Old report, non-GLP, and limited detail reported. Study is in agreement with other available information.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Berolamine 715. OECD guideline, GLP principles.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Remarks:

Following GLP principles; statement SD & QA available

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (U.K.) Limited
- Age at study initiation: no data
- Weight at study initiation: mean weight for 284g males and 229g females.
- Fasting period before study: not applicable
- Housing: in suspended polypropylene cages with stainless steel grid tops and bottoms beneath which was a polypropylene tray containing absorbent paper.
- Diet (e.g. ad libitum): ad libitu, Special Diet Services Expanded Rat and Mouse Maintenance Diet No. 1 with known analysis
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 (21-24)
- Humidity (%): 37 (28-58)
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data


IN-LIFE DATES: no data

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: the back of the animals
- % coverage: no data
- Type of wrap if used: The test material was placed on a piece of gauze which was then placed over the shaved skin and bound with Sleek occlusive tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was wiped with a damp tissue to remove excess test material
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): no data
- Concentration (if solution): no data

Duration of exposure:

24h

Doses:

2000 mg/ kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations and the animals were weighed at dosing after 7 days and at sacrifice
- Necropsy of survivors performed: yes

Statistics:

not performed

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no deaths

Mortality:

None

Clinical signs:

other: No clinical signs were noted at any stage of the test

Gross pathology:

No effects observed

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 > 2000 mg/kb bw

Executive summary:

The acute dermal toxicity of the test substance was investigated in male and female rats of the Sprague-Dawley strain. A single group of 5 male and 5 female rats was treated at a dose level of 2000 mg/kg bw. There were no deaths and no clinical signs were noted at any stage of the test. LD50 > 2000 mg/kg bw.

It is concluded that the test substance would not pose a hazard of percutaneous toxicity in normal use.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Standard study according to OECD guideline, and following GLP principles.

Additional information

This substance, Tall oil + ammonia-ethanolamine reaction by-products (TO + AEA), differs from other substances in the AAI group that are based on fatty acids with polyamines, in that it contains a high amount of hydroxylated polyethylene amines, causing it to display more neutral OH groups, rather than basic primary amine groups. As toxicity is much related to the presence of free primary amine groups, it can be expected that in specifically in aspects of acute toxicity related to direct chemical interactions, this substance shows less effects compared to other AAI substances.

Tall oil + ammonia-ethanolamine reaction by-products was tested for acute oral toxicity in a standard acute oral toxicity according to OECD 401. The LD50 amounted to 4000 mg/kgbw. Animals dosed with levels up to 2250 mg/kg showed piloerection and hypokinesia up to three days, no mortality, and no findings at macroscopic evaluations. At higher dose levels mortality increased, with 100% mortality within one or two days at 6250 mg/kg.

  

All other studies with AAI substances show somewhat higher acute oral toxicity, but 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 data on amidoamines/imidazolines (AAI):

    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 + PolyAmidoamine  >2000 mg/kg bw ,Cat.5; ATC cut off 5000mg/kg bw

    TO + AEA                          4000 mg/kg bw ,Cat.5

 

Acute dermal toxicity: A single group of 5 male and 5 female rats was treated at a dose level of 2000 mg/kg bw. There were no deaths and no clinical signs were noted at any stage of the test. LD50 > 2000 mg/kg bw. 

Acute inhalation toxicity: Physical-chemical properties of Tall oil + ammonia-ethanolamine reaction by-products indicate a low likelihood for exposure via inhalation having a boiling point > 300 °C and a low vapour pressure (8.4 x 10 -8 Pa at 25°C).

Justification for selection of acute toxicity – oral endpoint
Only available study

Justification for selection of acute toxicity – inhalation endpoint
Likelihood of exposures via inhalation is low considering the high boiling point (> 300 °C) and very low vapour pressure (8.4 x 10-8 Pa at 25°C for this substance).

Justification for selection of acute toxicity – dermal endpoint
Only available study

Justification for classification or non-classification

Acute oral exposure of Tall oil + ammonia-ethanolamine reaction by-products show limited acute toxicity, with a LD50 above 2000 mg/kg bw via oral as well as dermal route. Hence no classification is required.

 

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

 

AAI 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.