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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:
2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been conducted according to GLP and valid methods, therefore it is considered to be adequate, reliable and relevant for classifcation.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted October 02, 2012
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Commision Regulation (EC) No. 440/2008
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxododecyl)amino]ethyl]ester, disodium salt
IUPAC Name:
Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxododecyl)amino]ethyl]ester, disodium salt
Test material form:
other: liquid

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 Toxiclogy GmbH & Co. KG, Branch Löhndorf, 24601 Löhndorf/Post Wankendorf, Germany
- Age at dosing: Approx. 4.5 – 7.5 months
- Weight at dosing: Animal no. 1,2 and 3 : 2.7 kg each
- 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 600mm (manufacturer: Dipl.Ing. W. EHRET GmbH, 16352 Schönwalde, Germany).
- Diet (e.g. ad libitum): Commercial diet , ssniff®K-H, ssniff Spezialdiäten GmbH, 59494 Soest, Germany, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: At least 20 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C (maximum range)
- Humidity (%): 30% - 70% (maximum range)
- Air changes (per hr): Not provided
- Photoperiod (hrs dark / hrs light): 12/12 (about 150 lux at approx. 1.50 m room height)

IN-LIFE DATES: From: February 4, 2013 To: February 22, 2013

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye, which remained untreated, served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL
- Concentration (if solution): undiluted (39.90% solid content)
Duration of treatment / exposure:
Single instillation into the conjunctival sac
Observation period (in vivo):
Observations were performed at 1 hour, 24, 48, 72 hours, 7, 14, and 21 days
Number of animals or in vitro replicates:
3 males and 3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, with physiol. saline
- Time after start of exposure: 24 h

SCORING SYSTEM:
The grades of ocular reaction (conjunctivae, cornea and iris) were recorded at each examination according to the following scheme:

Cornea
Opacity: degree of density (Readings taken from most dense area. The area of corneal opacity will be noted)
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 area, 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 reacting 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 conjuntivae, 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 nictating membranes)
Normal: 0
Some swelling above normal: 1
Obvious swelling, with partial eversion of lids: 2
Swelling with lids about half closed: 3
Swelling, with lids more than half closed: 4


TOOL USED TO ASSESS SCORE:
slit lamp: prior to the administration and 1 hour, 24, 48 and 72 hours after the instillation
fluorescein: 24 hours after administration the eyes were treated additionally with fluorescein before being examined to aid evaluation of the cornea for possible lesions

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.11
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
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:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
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
Remarks:
redness
Basis:
mean
Time point:
24/48/72 h
Score:
0.56
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.22
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
Under the present test conditions, a single instillation of 0.1 mL Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxododecyl)amino]ethyl]ester, disodium salt per animal into the conjunctival sac of the right eye of three rabbits caused following changes:
Corneal opacity (grade 1) was observed in animal no. one 24 hours after instillation.
Conjunctival redness was observed in all animals:
animal no. 1: 24 and 48 hours (grade 1) after instillation;
animal no. 2: 48 hours (grade 1) after instillation;
animal no. 3: 60 minutes (grade 2) and 24 and 48 hours (grade 1) after instillation.
Chemosis was observed in all animals:
animal no. 1: 60 minutes (grade 3) after instillation;
animal no. 2: 60 minutes (grade 2) and 24 hours (grade 1) after instillation;
animal no. 3: 24 hours (grade 1) after instillation.
The irises were not affected by instillation of the test item.
There were no systemic intolerance reactions.

Any other information on results incl. tables

Table 1. Examination of the treated eye

 

Animal no.: 1/2/3

Time after administration

Cornea opacity

Iris

Conjunctivae

Redness#

Chemosis##

Before dosing

0/0/0

0/0/0

0/0/0

0/0/0

60 minutes

0/0/0

0/0/0

0/0/2

3/2/0

24 hours

1/0/0

0/0/0

1/0/1

0/1/1

48 hours

0/0/0

0/0/0

1/1/1

0/0/0

72 hours

0/0/0

0/0/0

0/0/0

0/0/0

# refers to palpebral and bulbar conjunctivae; excluding cornea and iris

##swelling: refers to lids and/or nictating membrane

24 hours fluorescein test: all animals: no pathological findings

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Not irritating

Executive summary:

Under the present test conditions, a single instillation of 0.1 mL test item, containing 39.90% active ingredient, per animal into the conjunctival sac of the right eye of three rabbits caused following changes: corneal opacity (grade 1) in on animal 24 hours after instillation, conjunctival redness (grade 1) in all animals, chemosis in all animals up to 24 hours after instillation (grade 1 -3). The irises were not affected by instillation of the test item. Mean 24-72h scores were 0.11/4, 0.55/3 and 0.22/4 for cornea opacity, conjuctivae redness and chemosis, respectively.

All scores were reversible within 72 hours and fell below classification criteria, therefore the test item was not irritant for the eyes.