Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
08 April - 04 May 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study. Full read-across justification report is attached in section 13.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Anydrous Sodium Perchlorate
- Substance type: Technical material
- Physical state: white powder
- Analytical purity: 98.21%
- Purity test date: 10/01/2008
- Lot/batch No.: GRL 0005/08
- Expiration date of the lot/batch: February 2010
- Storage condition of test material: Room temperature, keep hermetically closed. Store away from heat & ignition sources
- Other: Disposal - dilute with water

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Grimaud Freres Selection S.A.S., La Corbiere, Roussay, France
- Age at study initiation: 2 - 4 months
- Weight at study initiation: 3.0 ± 0.2 kg
- Housing: Individually in Pajon cages (50 x 57 x 75 cm)
- Diet: ad libitum 110C pelleted diet (SAFE, Augy, France).
- Water: ad libitum filtered by a FG Millipore membrane (0.22 micron)
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30 - 70%
- Air changes (per hr): approx. 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 08 April 2008 To: 04 May 2008

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
100 mg of the test item in its original form
Duration of treatment / exposure:
One application to one eye and there was no rinsing after administration. The other eye acted as control.
Observation period (in vivo):
up to 12 days
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
The test material was not removed after exposure


SCORING SYSTEM:

Conjunctival lesions and discharge
Chemosis (lids and/or nictitating membranes)
. no swelling ...............................................................................................................................0
. any swelling above normal (includes nictitating membranes) ...................................... ..1
. obvious swelling with partial eversion of lids......................................................................2
. swelling with lids about half-closed......................................................................................3
. swelling with lids more than half-closed .............................................................................4


Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)
. blood vessels normal ...............................................................................................................0
. a number of blood vessels definitely hyperemic (injected).................................................1
. diffuse, crimson colour, individual vessels not easily discernible ....................................2
. diffuse, beefy red........................................................................................................................3

Discharge
. absence of discharge .............................................................................................................. .0
. slight discharge (does not include small amounts normally found in
inner canthus) ..............................................................................................................................1
. discharge with moistening of lids and hairs adjacent to lids...............................................2
. discharge with moistening of lids and hairs on wide area around the eye........................3

Iris lesions
. normal ..........................................................................................................................................0
. markedly deepened rugae, congestion, swelling, moderate circum-corneal
hyperemia, or injection, any of these or combination of any thereof, iris still
reacting to light (sluggish reaction is positive) .......................................................................1
. no reaction to light, haemorrhage, gross destruction (any or all of these) ......................2

Corneal lesions
Degree of opacity (area most dense taken for reading)
. no ulceration or opacity..............................................................................................................0
. scattered or diffuse areas of opacity (other than slight dulling or 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

Area of opacity
. one quarter (or less) but not zero..............................................................................................1
. greater than one quarter but less than a half...........................................................................2
. greater than one half but less than three quarters..................................................................3
. greater than three quarters up to whole area. .........................................................................4

Any other lesions observed were noted.

TOOL USED TO ASSESS SCORE: UV lamp/ 0.5% sodium fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72h
Score:
2.4
Max. score:
4
Reversibility:
fully reversible within: 7-12 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 7-12 days
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
mean
Remarks:
2 rabbits
Time point:
other: 24-48-72h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72h
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
cornea opacity score
Remarks:
Opacity intensity
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72h
Score:
1.4
Max. score:
4
Reversibility:
fully reversible within: 72 hours/ 6 days
Irritation parameter:
cornea opacity score
Remarks:
Opacity area
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72h
Score:
1.6
Max. score:
4
Reversibility:
fully reversible within: 72 hours / 6 days
Irritant / corrosive response data:
Slight to marked chemosis was observed in all animals from day 1 until day 6, 9 or 11.
Slight to severe redness of the conjunctiva was noted in all animals from day 1 until day 6 (one animal) or 11 (two animals).
A clear to whitish purulent discharge was noted in all animals from day 1 until day 3 (two animals) or 4 (one animal).
An iritis was noted in 2/3 animals from day 1 until day 3 or 5 and on day 2 in 1/3 animals.
A slight or moderate corneal opacity was recorded in 2/3 animals on days 2 and 3. In the third animal, a slight to severe corneal opacity, which covered sometimes the whole area of the cornea, was noted from day 1 until day 5.
Brownish area on the third eyelid was observed in 1/3 animals from day 7 until day 11.
Mean scores calculated for each animal over 24, 48 and 72 hours were 2.0, 2.3 and 3.0 for chemosis, 2.3, 2.0 and 2.7 for redness of the conjunctiva, 0.7, 0.3 and 1.0 for iris lesions and 1.0, 1.0 and 2.3 for corneal opacity.

Any other information on results incl. tables

Table 1a: Individual ocular examinations and mean values of the scores recorded for each animal (24, 48 and 72 hours)

Rabbit Number

Region of Eye

Description of ocular reactions

Scores

Mean irritation score (1)

Interpretation

(+)

(-)

1 hour

Day 1

24 hours

Day 2

48 hours

Day 3

72 hours

Day 4

62

Conjunctivae

Chemosis

2

2

2

2

2.0

(+)

Redness

3

3

2

2

2.3

(-)

 

Discharge

1

2

1

0

1.0

 

 

Iris

 

1

1

1

0

0.7

(-)

 

Corneal opacity

Intensity

0

2

1

0

1.0

(-)

Area

0

1

1

0

0.7

 

 

Other

 

*

*

*

*

 

 

Fluorescein

 

/

U

U

U

 

 

 

73

Conjunctivae

Chemosis

2

3

2

2

2.3

(+)

Redness

2

2

2

2

2.0

(-)

 

Discharge

2

2

1

0

1.0

 

 

Iris

 

0

1

0

0

0.3

(-)

 

Corneal opacity

Intensity

0

2

1

0

1.0

(-)

Area

0

1

1

0

0.7

 

 

Other

 

*

*

*

*

 

 

Fluorescein

 

/

U

U

U

 

 

 

816

Conjunctivae

Chemosis

2

3

3

3

3.0

(+)

Redness

2

2

3

3

2.7

(+)

 

Discharge

2

S

S

S

(2)

 

 

Iris

 

1

1

1

1

1.0

(+)

 

Corneal opacity

Intensity

2

2

3

2

2.3

(+)

Area

2

4

4

2

3.3

 

 

Other

 

Su

*

*

*

 

 

Fluorescein

 

/

U

U

U

 

 

 

 

(1): mean of scores on days 2, 3 and 4       (2): not calculable

(+): irritant according to EEC criteria           U: fluorescein (batch No. L653 & P756)

(-): non-irritant according to EEC criteria     /: fluorescein not used

S: whitish purulent discharge Su: residual test item

*: none

Table 1b: Individual ocular examinations of the scores recorded for each animal (from Day 5 to Day 12)

Rabbit Number

Region of Eye

Description of ocular reactions

Scores

Day 5

Day 6

Day7

Day 8

Day 9

Day 10

Day 11

Day 12

62

Conjunctivae

Chemosis

1

1

0

-

-

-

-

-

Redness

1

1

0

-

-

-

-

-

 

Discharge

0

0

0

-

-

-

-

-

 

Iris

 

0

0

0

-

-

-

-

-

 

Corneal opacity

Intensity

0

0

0

-

-

-

-

-

Area

0

0

0

-

-

-

-

-

 

Other

 

*

*

*

-

-

-

-

-

Fluorescein

 

/

/

/

-

-

-

-

-

 

73

Conjunctivae

Chemosis

1

1

1

1

1

1

1

0

Redness

2

2

2

2

1

1

1

0

 

Discharge

0

0

0

0

0

0

0

0

 

Iris

 

0

0

0

0

0

0

0

0

 

Corneal opacity

Intensity

0

0

0

0

0

0

0

0

Area

0

0

0

0

0

0

0

0

 

Other

 

*

*

*

*

*

*

*

*

Fluorescein

 

/

/

/

/

/

/

/

/

 

816

Conjunctivae

Chemosis

2

1

1

1

1

0

0

0

Redness

2

2

1

1

1

1

1

0

 

Discharge

0

0

0

0

S

S

0

0

 

Iris

 

1

0

0

0

0

0

0

0

 

Corneal opacity

Intensity

1

0

0

0

0

0

0

0

Area

1

0

0

0

0

0

0

0

 

Other

 

*

*

ZB

ZB

ZB

ZB

ZB

*

Fluorescein

 

U

U

/

/

/

/

/

/

 

 *: none                                                                       ZB: brownish area on the third eyelid

U: fluorescein (batch No. P756)                                  -:  ocular examination not performed

/: fluorescein not used

Applicant's summary and conclusion

Interpretation of results:
other: Category 2
Remarks:
Criteria used for interpretation of results: other: Regulation (EC) No 1272/2008
Conclusions:
Under the experimental conditions of the study, the test item ANHYDROUS SODIUM PERCHLORATE (batch No. lot moyen du 10/01/08 test) was
irritant when administered by the ocular route to rabbits.
Executive summary:
The potential of the test item ANHYDROUS SODIUM PERCHLORATE (batch No. lot moyen du 10/01/08 test) to induce ocular irritation was evaluated in rabbits according to OECD (No. 405, 24th April 2002) and EC (2004/73/EC, B.5, 29th April 2004) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. Under the experimental conditions of the study, the test item ANHYDROUS SODIUM PERCHLORATE (batch No. lot moyen du 10/01/08 test) was irritant when administered by ocular route to rabbits and should be classified as Irritant, Category 2 under CLP (GHS).