3-((C12-18)-acylamino)-N-(2-((2-hydroxyethyl)amino)-2-oxoethyl)-N,N-dimethyl-1-propanaminium chloride

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline, GLP study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

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:

-

EC Number:

427-370-1

EC Name:

-

Cas Number:

164288-56-6

Molecular formula:

C21H44N3O3Cl

IUPAC Name:

{[(2-hydroxyethyl)carbamoyl]methyl}dimethyl(3-octadecanamidopropyl)azanium chloride

impurity 1

Reference substance name:

Sodium chloride

EC Number:

231-598-3

EC Name:

Sodium chloride

Cas Number:

7647-14-5

Molecular formula:

ClNa

IUPAC Name:

sodium chloride

impurity 2

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Water

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

AnimaIs and Animal Husbandry
Male and female Sprague-Dawley CD (Crl:CD® (SD) IGS BR) strain rats supplied by Charles River (UK) Ltd, Margate, Kent, UK were used. At the start of the study the males weighed 202 ta 220g, and the females 208 to 225g, and were eight to twelve weeks old. After a minimum acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card.
The animals were housed in groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.
The animal room was maintained at a temperature of 19 ta 21°C and relative humidity of 37 to 67%. The rate of air exchange was approximately
15 changes per hour and the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

dose level: 500 mg/kg
concentration: 50 mg/mL
dose volume: 10 mL/kg

Doses:

preliminery study:2000 and 500 mg/kg bw
main study: 500 mg/kg bw

No. of animals per sex per dose:

Preliminary sighting study: 1 (male)
Preliminary sighting study: 1 (female)
Main study: 5 (male)
Main study: 5 (female)

Results and discussion

Preliminary study:

The female treated with 2000 mg/kg was found dead one day after dosing. Clinical signs of toxicity noted in the male treated with 2000 mg/kg were hunched posture, lethargy, pilo-erection, decreased respiratory rate, Iaboured respiration, diarrhoea, dehydration and emaciation. Signs of toxicity noted in animals treated with 500 mg/kg were hunched posture and lethargy.
The male treated with 2000 mg/kg recovered twelve days after dosing and the animals treated with 500 mg/kg recovered six days after dosing.
Based on this information, a dose level of 500 mg/kg bodyweight was selected for the main study.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

500 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: Common clinical signs of toxicity noted during the study were hunched posture with incidents of noisy respiration. Animals recovered two to four days after dosing.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The discriminatory dose was identified as 500 mg/kg bodyweight.
The acute oral median lethal dose (LD50 of the test item in the Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight. The test material may be of some concern if swallowed due to the nature of the toxic effects noted, but did not meet the criteria for classification under EU labelling regulations. No symbol or risk phrase are required.

Executive summary:

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method complied with that described in the OECD Guidelines for Testing of Chemicals No. 420 "Acute Oral Toxicity - Fixed Dose Method" (adopted 1 7 July 1992) and Method B1 bis in Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

 

Following a preliminary study at dose levels of 2000 and 500 mg/kg, a group of ten fasted animals (five males and five females) was given a single oral dose of test material, as a solution in distilled water at a dose level of 500 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed and subjected to gross necropsy.

 

There were no deaths. Clinical signs of toxicity noted during the study were hunched posture and noisy respiration. Animals recovered two to four days after dosing.

 

All animals showed expected gains in bodyweight during the 14-day study period.

 

No abnormalities were noted at necropsy.

 

The discriminatory dose was identified as 500 mg/kg bodyweight.

The acute oral median lethal dose (LD50 of the test material, notified substance (i.e. 100% active matter), in the Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight. The test material may be of some concern if swallowed due to the nature of the toxic effects noted, but did not meet the criteria for classification under EU labelling regulations. No symbol or risk phrase are required.

This result is in compliance with those noted in the supporting study performed the diluted presentation the test item (i.e. LD 0 > 2000 mg/kg in a fixed dose).