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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class 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: White powder
- Lot/batch No.: 2625

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: Harlan U. K. Ltd., Bicester, Oxon, England
- Age at study initiation: 5-7 weeks
- Weight at study initiation: 90-118 g
- Fasting period before study: overnight
- Housing: Groups of 3 rats of the same sex in metal cages within the treatment group
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days prior to the start of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C):18.5-20
- Humidity (%):34-55%
- Photoperiod (hrs dark / hrs light): 12 h dark/ 12 h artificial light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1% w/v aqueous methylcellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% w/v

DOSAGE PREPARATION (if unusual): on the day of dosing

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 Female, Dose 2000 mg/kg
3 Male, Dose 2000 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Weight Record: Days 1, 8 and 15; Rats were checked daily at least for mortalities.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0

Clinical signs:

Signs of toxicity related to dose levels: Clinical signs of reaction to treatment comprised of piloerection, salivation and hunched posture, seen in all animals on Day 1. In addition, abnormal gait and wet fur were observed in all females on Day 1. There were no other signs of reaction to treatment and recovery was complete in all males by Day 3 and in all females by Day 4.

Body weight:

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

Gross pathology:

No abnormalities were revealed at the macroscopic examination at study termination on Day 15.

Any other information on results incl. tables

Table 1: Mortality data:

Dose level (mg/Kg)	Sex	Nº of animals treated	Deaths
2000	Female	3	0
2000	Male	3	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

CLP Implementation.

Conclusions:

The acute toxicity study was realized according to OECD 423 guideline and EU method B.1 tris. The LD50 for the LAE is greater than 2000 mg/kg/bw.

Executive summary:

According to OECD 423 guideline and EU method B.1 tris, this study was performed with the purpose of ranging LD50 for the test substance: N^α-Lauroyl-L-arginine ethyl ester monohydrochloride (LAE).

With this objective, a group of 6 fasted rats (three males and three females) received a single oral gavage dose of the test substance, formulated in 1%w/v aqueous methylcellulose and administered at a dose level of 2000 mg/kg bodyweight.

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

No abnormalities were revealed in any of the animals at the macroscopic examination at study termination on Day 15.

The acute lethal oral dose to rats of LAE was demonstrated in this study to be greater than 2000 mg/kg bodyweight.