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

Endpoint summary

Description of key information

Acute oral toxicity

OECD 420 (2018) - In an acute oral toxicity study (OECD 423), groups of fasted, 8-9 week old, female Wistar (RccHan™:WIST) 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 doses 2000 and 300 mg/kg bw and observed for 14 days.

Oral LD50 female rats = 2000 mg/kg bw.

According to the UN GHS classification, the test item does not meet the criteria for acute oral toxicity.

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:

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.

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

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

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

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

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The endpoint is concluded based on a single key study with a Klimisch rating of 1. No effects were observed up to the limit dose of 2,000 mg/kg.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with Annex VIII, Section 8.5.2, Column 2 of REACH, testing by the inhalation route does not need to be conducted if:
If exposure of humans via inhalation is unlikely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

The acute inhalation toxicity study was waived in accordance with Annex VIII, Section 8.5.2

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with Annex VIII, Section 8.5.3, Column 2 of REACH, testing by the dermal route does not need to be conducted if:
- the substance does not meet the criteria for classification as acutely toxic or STOT SE by the oral route and
- no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation) or, in the absence of an in vivo study by the oral route, no systemic effects after dermal exposure are predicted on the basis of non-testing approaches (e.g. read across, QSAR studies)
For this substance, no systemic effects were observed in the in vivo acute oral toxicity study (OECD 420), or in the LLNA study (OECD 429) where 10 % (w/w) solution was tested at the highest dose level.

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

The acute dermal toxicity study was waived in accordance with Annex VIII, Section 8.5.3, Column 2.

Additional information

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 the test item 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.

Justification for classification or non-classification

Oral LD50 females rat reported at 2000 mg/kg bw, according to the UN GHS classification, the test item does not meet the criteria for acute oral toxicity.