Registration Dossier

Administrative data

Description of key information

The substance consists of three structurally similar bisamides: N,N'-ethane-1,2-diylbis(12-hydroxyoctadecanamide), N,N'-hexane-1,6-diylbis(12-hydroxyoctadecanamide) and N,N'-[1,3-phenylenebis(methylene)]bis(12-hydroxyoctadecanamide). Experimental data on this substance are not available. The individual constituents and mixtures of them and similar amides are considered suitable read-across substances.

In guideline studies on three read-across substances, 12-hydroxyoctadecanoic acid, reaction products with 1,3-benzenedimethanamine and hexamethylenediamine, N,N'-ethane-1,2-diylbis(12-hydroxyoctadecanamide) and 1,3-bis[12-hydroxy-octadecamide-N-methylene]-benzene, no oral toxicity on rats was observed at doses up to 2000 mg/kg bodyweight. Due to the high structural similarity of the three-constituent substance to these read-across substances the toxicity via oral route is expected to be comparable and LD50 > 2000 mg/kg bodyweight is assumed.

Consequently, the acute toxic potential via oral route of the substance is considered to be low based on read-across data. Testing of the substance is not considered necessary. The substance does not need to be classified for acute toxicity via oral route according to CLP criteria.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 Jan. 2019 - 22. Mar. 2019
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Slovak Academy of Sciences Dobrá Voda, Slovak Republic
- Age at study initiation: 8-9 weeks; female animals were non-pregnant and nulliparous
- Animal Health: Health condition of animals was examined by a veterinarian before initiation of the study.

ENVIRONMENTAL CONDITIONS
The animals were housed in plastic cages suspended on stainless steel racks, 3 animals per cage in a room equipped with central air conditioning. The average room temperature was maintained within the range of 22.12 ± 0.24 °C, relative humidity within 54.92 ± 2.46 %. The light regimen was set to a 12-hour light /12-hour dark cycle. Sanitation was performed according to the standard operation procedures. The laboratory food ssniff (ssniff Spezialdiäten GmbH, Germany) was available ad libitum. The animals received tap water for human consumption. Supply of drinking water was unlimited. The quality of drinking water is periodically analysed and recorded.
Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
The required amount of the test item (according to the body weight and dose) was mixed with vehicle (Olive oil) shortly before administration. The dose of 2000 mg/kg was administered in a volume of 5 mL/kg body weight.

ADMINISTRATION:
The test item was administered in a single dose by gavage using a metal stomach tube. Animals were fasted 10-12 h prior to dosing (food but not water was withheld over-night). Following a period of fasting, animals were weighed and the test item administered. After test item administration, food was withheld for further 3-4 hours.
Doses:
2000 mg/kg bw.
No. of animals per sex per dose:
3 females per treatment step.
Control animals:
no
Details on study design:
Clinical Observation
Animals were observed individually immediately after administration of the test item and 0.5, 1, 2, and 4 hours later. Each animal was inspected daily for the next 14 days.

Body Weight
Individual weights of animals were measured immediately prior to administration of the test item and weekly thereafter. Weight differences after first and second weeks after administration were calculated and recorded.

Necropsy
All test animals were subjected to gross necropsy and the results were recorded for each animal. Examinations included: external body surface and orifices, the appearance of tissues and organs in the thoracic cavity (trachea, esophagus, heart, aorta, lungs with main stem bronchi, thymus, tracheobronchial lymph node) and in the abdominal cavity (liver, spleen, adrenal glands, kidneys, ovaries, uterus including cervix, urinary bladder, small intestine, large intestine, pancreas, stomach, mesenteric lymph nodes).
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed during the study.
Clinical signs:
During the follow up period, no animals displayed signs of intoxication, change of health, nor any other adverse reaction.
Body weight:
At the end of the study the body weights of all animals were higher than the initial body weights. A slight decrease of body weights in animals No 1 and No 2 was observed between the first and second week after administration of the test item.
Gross pathology:
All animals were necropsied. During necropsy, no macroscopic findings were observed.
Interpretation of results:
GHS criteria not met
Conclusions:
All validity criteria are fulfilled. The study can be considered as valid. Under the study conditions, the oral LD50 of the test substance was considered to be >2,000 mg/kg bw in rats. Therefore, the test substance is not classified as toxic by oral route according to the criteria of EU CLP Regulation (1272/2008/EEC).
Executive summary:

The purpose of the study was to evaluate the potential toxic effect of the test item “Bisamid” when administered as a single oral dose to Wistar rats. The procedure according to OECD Guideline 423 Acute Toxic Class (ATC) method was used. A limit dose of 2000 mg/kg body weight was used as a starting dose. The test item administered to 6 females at a limit dose did not cause death. No signs of toxicity were observed during the first 4 hours in females or the 14-day observation period thereafter. At the end of the study the body weights of all animals were higher than the initial body weights. A slight decrease of body weights in two animals was observed between the first and second week after administration of the test item. During necropsy, no macroscopic findings were observed. The LD50 of the test item “Bisamid” is greater than 2000 mg/kg body weight after single oral administration to Wistar rats. Therefore, the test substance is not classified as toxic by oral route according to the criteria of EU CLP Regulation (1272/2008/EEC).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
92/32/EEC, B1
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Wistar strain Crl:(WI) BR
Sex:
male/female
Vehicle:
corn oil
Doses:
> 2000 mg/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
No mortality occured and no clinical signs of toxicity were observed.
Gross pathology:
Effects on organs:
No abnormalities were found in the animals at macroscopic post mortem examination
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 (oral) of 1,3-bis[12-hydroxy-octadecamide-N-methylene]-benzene for Wistar rats is > 2000 mg/kg bw.
Executive summary:

The acute toxicity (oral) of 1,3-bis[12-hydroxy-octadecamide-N-methylene]-benzene is assessed in a guideline study according to EU Method B.1 using Wistar rats. The LD50, determined in a limit test, is > 2000 mg/kg bw. Consequently, the GHS classification criteria for acute toxicity (oral) are not met.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
Annex V (B1 tris)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Vehicle:
corn oil
Doses:
2000 mg/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels: No deaths were observed. Clinical signs of reaction to treatment were confined to piloerection and hunched posture, seen in all rats accompanied by abnormal faeces and ungroomed appearance in one female. Recovery of rats, as judged by external appearance and behaviour, was complete in all instances by Day 3. All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
Effects on organs: No abnormalities were revealed at the macroscopic examination at study termination on Day 15.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 (oral) of 12-hydroxyoctadecanoic acid, reaction products with 1,3-benzenedimethanamine and hexamethylenediamine for Sprague-Dawley rats is > 2000 mg/kg bw.
Executive summary:

The acute toxicity (oral) of 12-hydroxyoctadecanoic acid, reaction products with 1,3-benzenedimethanamine and hexamethylenediamine is assessed in a guideline study according to EU Method B.1 using Sprague-Dawley rats. The LD50, determined in a limit test, is > 2000 mg/kg bw. Consequently, the GHS classification criteria for acute toxicity (oral) are not met.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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

Justification for classification or non-classification

For the multi-constituent substance Reaction mass of N,N'-ethane-1,2-diylbis(12-hydroxyoctadecanamide), N,N'-hexane-1,6-diylbis(12-hydroxyoctadecanamide) and N,N'-[1,3-phenylenebis(methylene)]bis(12-hydroxyoctadecanamide) a LD50 > 2000 mg/kg bodyweight is assumed from the experimental data of suitable read-across substances. For classification according to EU Regulation No. 1272/2008 an LD50 of equal or less than 2000 mg/kg bw is required. Therefore, the substance does not need to be classifiedfor acute toxicity via oral route.


Route: .live2