N-(2-{[C16-18 (even numbered) alkanoyl]amino}ethyl)-N-(2-hydroxyethyl)[C16-18 (even numbered) alkylamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 July 2017 - 15 February 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study was conducted in accordance with international guidelines and in accordance with GLP. All guideline validity criteria were met.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Fatty Acids, C14 and C16 sat., bisamides with 2-[(2-aminoethyl)amino]ethanol

Molecular formula:

C34H68N2O3

IUPAC Name:

Fatty Acids, C14 and C16 sat., bisamides with 2-[(2-aminoethyl)amino]ethanol

Constituent 2

Reference substance name:

Fatty Acids, C15 and C16 sat., bisamides with 2-[(2-aminoethyl)amino]ethanol

Molecular formula:

C35H70N2O3

IUPAC Name:

Fatty Acids, C15 and C16 sat., bisamides with 2-[(2-aminoethyl)amino]ethanol

Constituent 3

Reference substance name:

Fatty Acids, C16 sat., bisamides with 2-[(2-aminoethyl)amino]ethanol

Molecular formula:

C36H72N2O3

IUPAC Name:

Fatty Acids, C16 sat., bisamides with 2-[(2-aminoethyl)amino]ethanol

Constituent 4

Reference substance name:

Fatty Acids, C15 and C18 sat., bisamides with 2-[(2-aminoethyl)amino]ethanol

Molecular formula:

C37H74N2O3

IUPAC Name:

Fatty Acids, C15 and C18 sat., bisamides with 2-[(2-aminoethyl)amino]ethanol

Constituent 5

Reference substance name:

Fatty Acids, C16 and C18 sat., bisamides with 2-[(2-aminoethyl)amino]ethanol

Molecular formula:

C38H76N2O3

IUPAC Name:

Fatty Acids, C16 and C18 sat., bisamides with 2-[(2-aminoethyl)amino]ethanol

Constituent 6

Reference substance name:

Fatty Acids, C17 and C18 sat., bisamides with 2-[(2-aminoethyl)amino]ethanol

Molecular formula:

C39H78N2O3

IUPAC Name:

Fatty Acids, C17 and C18 sat., bisamides with 2-[(2-aminoethyl)amino]ethanol

Constituent 7

Reference substance name:

Fatty Acids, C18 sat., bisamides with 2-[(2-aminoethyl)amino]ethanol

Molecular formula:

C40H80N2O3

IUPAC Name:

Fatty Acids, C18 sat., bisamides with 2-[(2-aminoethyl)amino]ethanol

Constituent 8

Reference substance name:

Stearic acid

EC Number:

200-313-4

EC Name:

Stearic acid

Cas Number:

57-11-4

Molecular formula:

C18H36O2

IUPAC Name:

stearic acid

Constituent 9

Reference substance name:

Palmitic acid

EC Number:

200-312-9

EC Name:

Palmitic acid

Cas Number:

57-10-3

Molecular formula:

C16H32O2

IUPAC Name:

palmitic acid

Constituent 10

Reference substance name:

Myristic acid

EC Number:

208-875-2

EC Name:

Myristic acid

Cas Number:

544-63-8

Molecular formula:

C14H28O2

IUPAC Name:

myristic acid

Constituent 11

Reference substance name:

2-(2-aminoethylamino)ethanol

EC Number:

203-867-5

EC Name:

2-(2-aminoethylamino)ethanol

Cas Number:

111-41-1

Molecular formula:

C4H12N2O

IUPAC Name:

2-(2-aminoethylamino)ethanol

Test material form:

solid

Details on test material:

Identification: N-(2-{[C16-18 (EVEN NUMBERED) ALKANOYL]AMINO}ETHYL)-N-(2-HYDROXYETHYL)[C16-18 (EVEN NUMBERED) ALKYLAMIDE
Storage Conditions: Room temperature

Specific details on test material used for the study:

RADIOLABELLING INFORMATION (if applicable)
- Radiochemical purity: n/a
- Specific activity: n/a
- Locations of the label: n/a
- Expiration date of radiochemical substance: n/a

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark
- Stability under test conditions: Assumed stable
- Solubility and stability of the test substance in the solvent/vehicle: n/a
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: n/a

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: no
- Preliminary purification step (if any): n/a
- Final dilution of a dissolved solid, stock liquid or gel: applied undiluted
- Final preparation of a solid: n/a

FORM AS APPLIED IN THE TEST (if different from that of starting material): applied as supplied

OTHER SPECIFICS: n/a

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: body weight variation did not exceed ±20% of the mean body weight at the start of treatment
- Fasting period before study: yes
- Housing: housed in groups of up to 4 individuals in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): free access to food (2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon, UK)
- Water (e.g. ad libitum): free access to mains drinking water
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr): minimum of 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 : 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

The test item was ground to a fine powder using a mortar and pestle and freshly prepared, as required, as a suspension in 5% Carboxymethylcellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 5% Carboxymethylcellulose
- Amount of vehicle (if gavage): 5%
- Justification for choice of vehicle: the most suitable vehicle
- Lot/batch no. (if required): not specified
- Purity: not specified

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION (if unusual): 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: maximum guideline required concentration - 2000 mg/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Each animal was givena single dose of 10 mL/kg dose volume of 2000 mg/kg of the test item of 200 mg/mL concentration.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.5, 1, 2 and 4 hours after dosing then daily thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight

Statistics:

not required

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No deaths reported

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 2:       Number of animals dead (and with evident toxicity)

Dose (mg/kg bw)	Mortality (# dead / total)			Time range of deaths (hours)	Number with evident toxicity (# / total)
	Male	Female	Combined		Male	Female	Combined
2000	-	0 / 5	0 / 5	n/a	-	0 / 5	0 / 5

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System Unclassified).

Executive summary:

OECD 420 (2018) - In an acute oral toxicity study, a group of fasted, 8-12 week old female Wistar rats were given a single oral dose of

N-(2-{[C16-18 (even numbered) alkanoyl]amino}ethyl)-N-(2-hydroxyethyl)[C16-18 (even numbered) alkylamide

at a single dose rate of 2000 mg/kg bw (limit test) and observed for 14 days.

In the absence of mortality during the observation period, the oral LD50 was estimated to be greater than 2000 mg/kg bw.

In addition, there were no treatment related clinical signs, necropsy findings or changes in body weight observed in any of the individuals.

In conclusion, the test item,

N-(2-{[C16-18 (even numbered) alkanoyl]amino}ethyl)-N-(2-hydroxyethyl)[C16-18 (even numbered) alkylamide

did not meet the criteria for classification according to Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixture.