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

Acute Toxicity: dermal

Administrative data

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: 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 402 (Acute Dermal Toxicity)

Version / remarks:

Méthode B3

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

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:

Five male and five female Sprague-Dawley CD (Crl:CR® (SD) IGS BR) strain rats supplied by Charles River (UK) Ltd, Margate, Kent were used. At the start of the study the males weighed 290 to 300g, and the femaies 232 to 289g, and were approximateiy eight to twelve weeks old. After a minimum acclimatisation period of 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 suspended polypropylene cages furnished with woodfiakes. The animals were housed individuaily during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food (Rat and Mouse SQC Expanded Diet No.1, Speciai Diets Services Limited, Witham, Essex, UK) was ailowed throughout the study.
The animal room was maintained at a temperature of 19 to 21 °C and relative humidity of 44 to 66%. The rate of air exchange was approximateiy fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

On the day before treatment the back and flanks of each animal were clipped free of hair using veterinary clippers.
The calculated volume of the test material formulation was applied uniformly to an area of shorn skin (approximating to 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The animals were caged individually for the 24-hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.
The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.
After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H (1977) “Dermal and Eye Toxicity Tests” .
Any other skin reactions, if present were also recorded.
Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
At the end of the study the animams were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

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:

other: Signs of toxicity related to dose levels: none during the 14-day observation period

Gross pathology:

Effects on organs:
none

Other findings:

Signs of toxicity (local):
Crust formation was noted in all females four to ten days after dosing. No signs of skin irritation were noted in males during the study.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal median lethai dose (LD50) of the test item in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.

Executive summary:

A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted 24 February 1987) and Method B3 of 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 (as adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

 

A group of ten animals (five males and five females) was given a single 24-hour, semi-occluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination.

 

There were no deaths. No signs of systemic toxicity were noted during the study. Crust formation was noted in all females four to ten days after dosing. No signs of skin irritation were noted in males.

 

AIl animals showed an expected gain in bodyweight during the study except for one female which showed a loss in bodyweight during the first week of the study but expected gain in bodyweight during the second week.

 

No abnormalities were noted at necropsy.

 

The acute dermal median lethal dose (LD50) of the test material (i.e. the notified chemical), in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.

Subsequently, the test item (i.e. a 35 -40% aqueouse solution) is concluded with LD50>2000 mg/kg