ethyl N2-dodecanoyl-.sc.l.sc.-argininate hydrochloride

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From June 8, 2000 to December 15, 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

Guideline study with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

434-630-6

EC Name:

-

Cas Number:

60372-77-2

Molecular formula:

Hill formula: C20H41N4O3Cl

IUPAC Name:

ethyl N2-dodecanoyl-l-argininate hydrochloride

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material: Nα-Lauroyl-L-arginine ethyl ester monohydrochloride
- Physical state: Granular white powder
- Lot/batch No.: 2625
- Storage condition of test material: Ambient conditions, protected form light.

Specific details on test material used for the study:

Substance: L.A.E.
Batch number: 2625
Expiry date: March 14, 2000.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Italia, S.A.A.
- Age at study initiation: 8-10 weeks
- Weight at study initiation: approximately 2 Kg
- Housing: Individually housed in stainless steel cages measuring 69x45x51 cm and equipped with grid floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 10 days prior to test

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-21ºC
- Humidity (%): 45-65%
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark by fluorescent tubes

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Remarks:

Administered as supplied.

Controls:

no

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 h

Observation period:

14 days
Examinations after dosing: 1, 24, 48 and 72 hours, 7 and 14 days.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5x2.5 cm of animal's dorsum
- Type of wrap if used: Strip of aluminium foil assemblied by encircling the trunk of the animal with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, by gentle swabbing of the skin with cotton wool soaked in water at body temperature
- Time after start of exposure: 4 hours

SCORING SYSTEM:

ERYTHEMA AND ESCHAR FORMATION
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) to eschar formation preventing grading of erythema: 4

OEDEMA FORMATION
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (adges of area defined by definite raising): 2
Moderate oedema (raised approximately 1mm): 3
Severe oedema (raised more than 1 mm and extending beyond area of exposure): 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible within: 72 h

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 14 d

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 14 d

Remarks on result:

other: Day 14: erythema score = 1

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

24/48/72 h

Score:

0

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

24/48/72 h

Score:

0

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 14 d

Irritant / corrosive response data:

Reversibility of any observed effect: Changes fully reversible within 15 days.

Other effects:

A slight erythema was observed in all the three treated animals ca. 1 hour after the end of the exposure period. A slight oedema was also observed in one of the three animals at this examination. The same response was maintained in two of the three animals at 24 and 48 hour examinations, while a well defined erythema and slight oedema were observed in the remaining animals at these examinations. Recovery was observed in one of the three animals ca. 72 hours after the end of the exposure, while the other two animals maintained the same erythema scores. A very slight erythema and oedema were still present in two of the three animals at the 7 Day examination. In addition, desquamation of the treated skin was noted in the three animals. Recovery from irritation occurred on Day 15 in two of the three animals, while the desquamation was still evident in two and a slight erythema in one of the treated animals. There was no indication of a systemic effect of treatment. No changes in bodyweight occurred during the course of the study.

Any other information on results incl. tables

Table 1: Individual data and means

Time after the end of exposure	Erythema/Eschar			Oedema
	Animal Nº			Animal Nº
	1	2	3	1	2	3
1 hour	1	1	1	0	0	1
24 hours	1	1	2	0	0	1
48 hours	1	1	2	0	0	0
72 hours	0	1	2	0	0	0
7 day	0	1	1	0	0	1
14 day	0	0	1	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

CLP Implementation.

Conclusions:

To investigate the degree of irritation of Nα-Lauroyl-L-arginine ethyl ester monohydrochloride (LAE), the presented study was assessed on the intact skin of 3 rabbits. The results of the study showed that LAE had some irritant effect on the skin of the rabbit. The incidence and severity of this reaction were however not sufficient for classification. There was no indication of a systemic effect of treatment.

Executive summary:

The study was performed according to OECD 404 and in agreement with those of B4 detailed in the Council Directive 67/548/EEC EU method.

The purpose of this study was to investigate the degree of irritation produced on the intact skin of the rabbit following 4 hours contact with N^α-Lauroyl-L-arginine ethyl ester monohydrochloride (LAE). A 0.5 g aliquot of the test item was applied to the prepared dorsal skin of 3 animals for a period of 4 hours. The resulting reaction to treatment was assessed approximately 1, 24, 48 and 72 hours, 7 and 14 days after the end of the exposure period.

A slight well defined erythema (scores of 1 and 2) was observed in the 3 treated animals following a 4 hour period of exposure to the test item. A slight erythema was still present 7 days after the end of the exposure period in 2 animals, with a slight oedema also present in one of these 2 animals. One of the 3 animals still exhibited a slight erythema at the Day 15 examination. Desquamation of the treated skin was also noted 7 and 14 days after the end of the exposure.

These results indicate that LAE has an irritant effect on the skin at the rabbit. However, this reaction was not sufficient to require classiffication according to CLP Regulation.