Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Start of the experimental phase: November 26, 2009; Termination of the in-life phase: December 16, 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report date:
2014

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

1
Chemical structure
Reference substance name:
Sulphamidic acid
EC Number:
226-218-8
EC Name:
Sulphamidic acid
Cas Number:
5329-14-6
Molecular formula:
H3NO3S
IUPAC Name:
sulfamic acid
Details on test material:
- Name of test material (as cited in study report): SULFAMIC ACID (100%)
- Molecular formula (if other than submission substance):
- Molecular weight (if other than submission substance):
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type:
- Physical state: White crystalline powder
- Analytical purity:
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date:
- Lot/batch No.:
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions:
- Storage condition of test material: At room temperature
- Other:

Test animals / tissue source

Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: LPT Laboratory of Pharmacologyand Toxicology GmbH & Co. KG, branch Löhndorf, 24601 Löhndorf/Post Wankendorf Germany
- Age at study initiation: Approx. 7 - 9 months
- Weight at study initiation: 2.7 to 3.1 kg
- Housing: 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), 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.
- Diet (e.g. ad libitum): The food was available ad libitum before and after the exposure period.
- Water (e.g. ad libitum): Tap water was offered daily 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): 15 to 20 times
- Photoperiod (hrs dark / hrs light): Rooms were lit (150 lux at approx 1.5 m room height) and darkened on a 12-hour light/12-hour dark cycle.

IN-LIFE DATES
- From: December 01, 2009 To: December 16, 2009

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): 100 mg of the fine mortared test item were administered into one eye each of three animals.
The test item was placed into the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second in order to prevent loss of the material. The left eye, which remained untreated, served as a control.

- Concentration (if solution):

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of treatment / exposure:
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.
1 hour after instillation the eyes were rinsed with 20 mL NaCl solution.
Observation period (in vivo):
The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48, 72 hours and 4 to 9 days after the administration. The eye reactions were observed and registered.
Number of animals or in vitro replicates:
3 male animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): 1 hour after instillation the eyes were rinsed with 20 mL NaCl solution.
- Time after start of exposure: 1 hour

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 / biomicroscope / fluorescein
24 hours and 7 days after administration, fluorescein was applied to the eyes before being examined to aid evaluation of the cornea for possible lesions (Fluorescein SE Thilo drops (ALCON PHARMA GmbH, 79108 Freiburg, Germany)).
Fluorescein-Test:

DEGREE OF STAINING
no staining 0
scattered or diffuse colouration, details of iris clearly visible 1
easily discernible translucent area, details of iris slightly obscured 2
opalescent areas, details of iris not discernible, extent of pupil difficultly determinable 3
opaque cornea, iris not discernible through the opacity 4
INVOLVED AREA OF CORNEA
none 0
up to 1/4 of the surface 1
1/4 to 1/2 of the surface 2
1/2 to 3/4 of the surface 3
3/4 to whole surface. 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
7 d
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
7 d
Score:
1
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
7 d
Score:
1
Max. score:
2
Reversibility:
fully reversible
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
In addition, secretion was observed in all animals 60 minutes to 72 hours, in animal no. 1 until 5 days after instillation.
Brown discoloured eye lids were observed in all animals 60 minutes to 48 hours, in animal nos. 2 and 3 until 72 hours after instillation.
Other effects:
There were no systemic intolerance reactions.

Any other information on results incl. tables

Time after

administration

CORNEA

IRIS

CONJUCTIVAE

 

Opacity

 

Redness#

Chemosis##

Animal No. : 1 / 2 / 3

right eye: 100 mg Sulfamic Acid (100%)/animal

before dosing

0/0/0

0/0/0

0/0/0

0/0/0

60 minutes

1/2/2

1/2/2

1a,b/1a,b/1a,b

2/1/2

24 hours

1/2/2

1/2/2

2a,b/1a,b/2a,b

2/2/2

48 hours

1/2/2

1/2/2

2a,b/2a,b/2a,b

1/2/2

72 hours

1/4/4

1/2/2

2a/2a,b/2a,b

1/2/2

4 days

1/1/1

1/1/2

2a/2/1

1/1/1

5 days

1/1/1

1/1/1

2a/1/1

1/1/1

6 days

1/1/1

1/1/1

1/1/1

1/1/1

7 days

1/1/1

1/0/0

1/1/0

1/1/1

8 days

0/0/0

0/0/0

1/0/0

1/0/0

9 days

0/-/-

0/-/-

0/-/-

0/-/-

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

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

24hoursfluorescein test:

animal nos. 1 and 3:corneal staining (1/2 to 3/4 of the surface)

animal no. 2: corneal staining (3/4 to wholesurface)

7 days fluorescein test:

all animals: corneal staining (up to 1/4 of the surface)

a  secretion

b  eye lids brown discoloured

- no examination

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Remarks:
Criteria used for interpretation of results: other: EC-Commission directive 67/548/EEC and its subsequent amendments
Conclusions:
In a GLP guideline study conducted according to EC method B.5. and OECD guideline 405, sulfamic acid demonstrated irritation in the eye of rabbits which was fully reversible 9 days post treatment. According to the criteria laid down in the Globally Harmonized System of Classification and Labelling of Chemicals, sulfamic acid is considered to be irritating to eyes.