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Toxicological information

Eye irritation

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Administrative data

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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Test guidelineopen allclose all
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)

Test material

Constituent 1
Chemical structure
Reference substance name:
Arginine
EC Number:
200-811-1
EC Name:
Arginine
Cas Number:
74-79-3
Molecular formula:
C6H14N4O2
IUPAC Name:
arginine
Test material form:
not specified

Test animals / tissue source

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

Test system

Vehicle:
unchanged (no vehicle)
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

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
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.

Applicant's summary and conclusion

Interpretation of results:
other: not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
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.