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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From March 16, 2000 to July 27, 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:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

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: Powder
- Lot/batch No.: 2625
- Expiration date of the lot/batch: Not advised
- Storage condition of test material: 4ºC in the dark

Specific details on test material used for the study:

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

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hsd: Sprague-Dawley obtained from Harlan U.K. Ltd., Bicester, Oxon, England
- Age at study initiation: 8-12 weeks prior to dosing
- Weight at study initiation: 206-256 g
- Housing: Individually in metal cages fitted with grid floors to ensure rapid removal of waste material to undertrays.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days prior to the start of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5-20ºC
- Humidity (%): 42-56%
- Photoperiod (hrs dark / hrs light): 12 h artificial light each 24 hour period

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: 1% w/v aqueous methylcellulose

Details on dermal exposure:

TEST SITE
- Area of exposure: 50 mmx50 mm
- % coverage: 10%
- Type of wrap if used: Porous gauze with a non-irritating dressing, further covered by a waterproof dressing encircled firmly around the trunk of the animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): With warm water (30-40ºC)
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 3.0 ml/kg bw
- Concentration (if solution): 667 mg/ml in 1% w/v methylcellulose

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

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

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations twice daily; The bodyweight of each rat was recorded on Days 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic appearance

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

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:

Signs of toxicity related to dose levels:
There was no evidence of a systemic response in any animal throughout the study.


All animals were considered to have achieved satisfactory
bodyweight gains throughout the study.

Body weight:

All animals were considered to have achieved satisfactory bodyweight gains throughout the study.

Gross pathology:

Effects on organs:
No macroscopic abnormalities were observed for animals killed at study termination on Day 15, with the exception of scabbing on the dose sites of three rats, plus thickening of the tissues on one.

Other findings:

Signs of toxicity (local):
There were no deaths and no clinical signs of reaction to treatment observed in any animal throughout the study.

Well-defined irritation (erythema and oedema up to Grade 2) was notable in all rats following removal of the dressings on Day 2 and persistent at this level throughout the following days before resolving in all but two instances by Day 9. In two rats a dermal response persisted through to Day 12 or 14 before resolving. Associated with the dermal irritation were reactions characterised by blanching of the skin, localised spots and/or scabbing and/or thickening of the skin and desquamation. These responses had resolved in all but three instances by Day 15.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

CLP Implementation.

Conclusions:

Nα-Lauroyl-L-arginine ethyl ester monohydrochloride (L.A.E) was demonstrated to be greater than 2000 mg/kg bw.

Executive summary:

According to the OECD Guideline Nº 402 and EU method B.3, a group of 10 rats, 5 males and 5 females, received a single topical application of the test substance formulated in 1% w/v aqueous methylcellulose and administered at a dosage of 2000 mg/kg bodyweight.

There were no clinical signs of reaction to N^α-Lauroyl-L-arginine ethyl ester monohydrochloride (L.A.E) treatment observed in any animal throughout the study.

Well-defined irritation (erythema and oedema up to Grade 2) was notable in all rats following removal of the dressings on Day 2 and persistent at this level throughout the following days before resolving in all but two instances by Day 9. In two rats a dermal response persisted through to Day 12 or 14 before resolving. Associated with the dermal irritation were reactions characterised by blanching of the skin, localised spots and/or scabbing and/or thickening of the skin and desquamation. These responses had resolved in all but three instances by Day 15.

No macroscopies abnormalities were observed for animals killed at study termination on Day 15, with the exception of scabbing on the dose sites of three rats, plus thickened tissues on one.

The acute lethal dermal dose to rats of L.A.E. was demonstrated to be greater than 2000 mg/kg bodyweight.