Arginine

Endpoint summary

Description of key information

L-Arginine is not considered to have irritating or corrosive properties to human skin or eye or to the respiratory system.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984-04-04 to 1984-04-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline Study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(OECD Guideline for Testing of Chemicals, 1981)

GLP compliance:

no

Remarks:

Study performed prior to implementation of GLP

Species:

rabbit

Strain:

other: White russian (Albino)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Asta-Werke AG, Bielefeld, Germany
- Age at study initiation: 4 months
- Weight at study initiation: 2.0 - 2.1 kg
- Housing: Stainless steel cages, model Asta
- Diet (e.g. ad libitum): standardised test animal diet Altromin
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- according to guideline

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Remarks:

500 mg of test substance were moistened with 0.4 ml Aqua demin

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.4 ml
- Purity: demineralised water

Duration of treatment / exposure:

4 hours

Observation period:

Observation times: 1 h, 24 h, 48 h and 72 h after removal of the patches. Total observation period: 3 days

Number of animals:

3

Details on study design:

TEST SITE
- % coverage: 100 %
- Type of wrap: The site of application was covered with a linen patch (ca. 6.25 cm²) sticking on a synthetic adhesive film.
A bandage was wrapped around the trunk (Acrylastic, Nr. 2408, width 8 cm, supplied by P. Beiersdorf and Co. AG, Hamburg).

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 h

SCORING SYSTEM:
Irritation index (Draize Grade) for
- erythema and eschar
- edema
Primary irritation index

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: Score was "0" for all animals at any of the 4 observation times

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: Score was "0" for all animals at any of the 4 observation times

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 72 h

Score:

0

Max. score:

8

Remarks on result:

other: Score was "0" for all animals at any of the 4 observation times

Interpretation of results:

GHS criteria not met

Conclusions:

L-Arginine did not show any skin irritating or skin corrosive effects. Systemic toxic effects could not be detected.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-12-06 to 2013-03-13

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: LPT Laboratory of Pharmacology and Toxicology GmbH & Co. KG, branch Löhndorf, Germany
- Age at study initiation: Approx. 7 - 8 months
- Weight at study initiation: Animal no. 1: 3.4 kg; Animal no. 2: 2.2 kg; Animal no. 3: 3.5 kg
- Housing:
For 8 hours following test item application, the animals were kept singly in restrainers which allowed free movement of the head but prevented a complete body turn, wiping of the eyes with the paws and excluded irritation of the eye by excrements and urine.
During the acclimatisation period and after the 8-hour period in restrainers, the animals were kept singly in cages with dimensions of 380 mm x 425 mm x 600 mm (manufacturer: Dipl.Ing. W. EHRET GmbH, 16352 Schönwalde, Germany).
- Diet (e.g. ad libitum): Commercial diet, ssniff® K-H V2333 (provided by ssniff Spezialdiäten GmbH, Soest, Germany). The food was available ad libitum before and after the exposure period.
- Water (e.g. ad libitum): Tap water (drinking water) was offered ad libitum before and after the exposure period.
- Acclimation period: At least 20 adaptation days

ENVIRONMENTAL CONDITIONS
- according to guideline

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 female rabbits

Details on study design:

The test item was placed into the conjunctival sac of the right eye of each animal. The left eye, which remained untreated, served as a control.
The test was performed initially using one animal. As no corrosive or severe irritant effects were observed in this animal, 2 further animals were employed 24 hours after start of the initial test.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes were rinsed with 20 mL NaCl solution.
- Time after start of exposure: One hour after instillation

SCORING SYSTEM:
Reactions were scored according to the following scheme:

CORNEA
Opacity: degree of density (area most dense taken for reading)
no ulceration or opacity: 0
scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible: 1
easily discernible translucent area, details of iris slightly obscured: 2
nacreous areas, no details of iris visible, size of pupil barely discernible: 3
opaque cornea, iris not discernible through the opacity: 4

IRIS
normal: 0
markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, iris reactive to light (a sluggish reaction is considered to be an effect): 1
haemorrhage, gross destruction, or no reaction to light: 2

CONJUNCTIVAE
Redness (refers to palpebral and bulbar conjunctivae, excluding cornea and iris)
normal: 0
some blood vessels hyperaemic (injected): 1
diffuse, crimson colour; individual vessels not easily discernible: 2
diffuse beefy red: 3

CHEMOSIS
Swelling: refers to lids and/or nictitating membranes
normal: 0
some swelling above normal: 1
obvious swelling with partial eversion of lid: 2
swelling with lids about half-closed: 3
swelling with lids more than half-closed: 4

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 1h, 24h, 48h and 72h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1h, 24h, 48h and 72h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 1h, 24h, 48h and 72h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1h, 24h, 48h and 72h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Under the present test conditions, a single instillation of 100 mg L-Arginine per animal into the conjunctival sac of the right eye of three rabbits did not cause any changes.
The corneae, irises and conjunctivae were not affected by instillation of the test item.
There were no systemic intolerance reactions.

Interpretation of results:

not irritating

Conclusions:

The eye irritant potential of L-arginine was assessed in a GLP study by application of the dry product to the eyes of three rabbits according to EC method B.5. (Regulation (EC) No. 440/2008) and OECD guideline 405.
The instillation of L-arginine did not cause any changes at the rabbits eyes. The corneae, irises and conjunctivae were not affected by instillation of the test item.
L-arginine is classified as not-irritating to eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin

The dermal irritant potential of L-arginine was assessed by application of the moistened product to the skin of three rabbits in accordance with OECD guideline 404. No signs of irritation were seen at any point after application, thus the product is classified as not-irritating to human skin.

  

 Eye

The eye irritant potential of L-arginine was assessed in an up to date in vivo GLP study by application of the dry product to the eyes of three rabbits according to EC method B.5. (Regulation (EC) No. 440/2008) and OECD guideline 405.

No signs of irritation were seen at any point after application, thus the product is classified as not-irritating to human eye.

This study was considered most reliable and chosen as key study for this endpoint, as it is an up to date GLP study (with certificate) and shows unambiguous results.

 Respiratory System

There are no data available which indicate that L-arginine is irritant to the respiratory system.

Justification for selection of skin irritation / corrosion endpoint:

Key study

Justification for selection of eye irritation endpoint:

Key study

Justification for classification or non-classification

The in vivo guideline study for skin irritation did not show any corrosive properties to the skin.

The up to date in vivo GLP guideline study for eye irritation/corrosion did not show any corrosive properties to the eye.