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Toxicological information

Eye irritation

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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:
2009
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented, according to accepted guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
2 of the rabbits' body weights were less than 2 kg at study start, drinking water analysis was performed in September as opposed to August, and flurescein was used at one hour time point to examine the cornea
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Gluconic Acid
- Physical state: viscous liquid
- Analytical purity: 54.4%
- Lot/batch No.: S293E
- Expiration date of the lot/batch: 01 Aug 2014
- Storage condition of test material: Room temperature

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, La Corbiere, 49450 Roussay, France
- Weight at study initiation: 1.610 kg to 2.340 kg
- Housing: Individually housed in standard sized cages
- Diet (e.g. ad libitum): SDS/DIETEX STANRAB (P) SQC, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 to 21
- Humidity (%): 45 to 65
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 / 12


Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): Undiluted


Duration of treatment / exposure:
Single Exposure
Observation period (in vivo):
Up to 72 hours
Number of animals or in vitro replicates:
3
Details on study design:
One dose consisting of 0.1 mL (after instillation the eyelids were held closed for one second to prevent loss of dose). Ocular changes were assessed and recorded immediately, one hour after treatment, 24 hours, 48 and 72 hours after treatment. Signs of irritation persisted in one animal and observations to day 8 were taken.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM:
Ocular lesions were graded in accordance with OECD guideline No. 405

Ocular Reactions

Chemosis (Swelling refers to lids and/or nictitating membranes)
No swelling 0
Any swelling above normal (includes nictitating membranes) 1
Obvious swelling with partial eversion of the lids 2
Swelling with lids about half-closed 3
Swelling with lids more than half-closed 4

Lacrimation
No lacrimation 0
Slight lacrimation (slight secretions normally present at the medial angle should not be taken into account) 1
Lacrimation with the moistening of the eyelids and of fur around eyelids 2
Lacrimation with moistening of eyelids and of fur over large areas around eye 3

Redness (refers to palpebral and bulbar conjunctiva, not to cornea and iris)
Blood vessels normal 0
Some blood vessels definitely hyperaemic (injected) 1
Diffuse, crimson colour, individual vessels not easily discernible 2
Diffuse beefy red 3

Iris reactions
Normal 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperamia 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

Cornea reactions*
Opacity (degrees of density, most dense area is taken for reading)
No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight dulling of normallustre), details of iris clearly visible 1
Easily discernible translucent areas, 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

Area of cornea involved
A quarter (or less) but not zero 1
Greater than one quarter but less than half 2
Greater than half but less than three-quarters 3
Greater than three-quarters, up to whole area 4

* The zone with the most severe lesions only is described. The assessment of the area of cornea involved is described as an exponent of the
degree of opacification, on the result data sheet.


TOOL USED TO ASSESS SCORE: fluorescein
Corneal lesions seen after the instillation of fluorescein were graded using the following evaluation scale:

Grading
No epithelial damage 0
Superficial epithelial damage without loss of stromal substance (epithelial erosion) 1
Moderate ulcer with loss of stromal sustance 2
Deep ulcer (reaching Descemet0s membrane) 3
Perforating ulcer (with or without staphyloma) 4

Area
A quarter (or less) but not zero 1
Greater than one quarter but less than half 2
Greater than half but less than three-quarters 3
Greater than three-quarters, up to whole area 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: Average 24, 48, 72 hours
Score:
2.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
other: redness
Basis:
animal #1
Time point:
other: Average 24, 48, 72 hours
Score:
2.33
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: Average 24, 48, 72 hours
Score:
0.67
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: Average 24, 48, 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: Average 24, 48, 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
other: Redness
Basis:
animal #2
Time point:
other: Average 24, 48, 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: Average 24, 48, 72 hours
Score:
0
Max. score:
3
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: Average 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: Average 24, 48, 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
other: Redness
Basis:
animal #3
Time point:
other: Average 24, 48, 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: Average 24, 48, 72 hours
Score:
0.33
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: Average 24, 48, 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
The application of Gluconic Acid did not induce colouration of the eye and did not interfere with grading of lesions.

One hour after instillation, all animals had slight to moderate chemosis (score 1 to 2) and moderate to severe redness of the conjunctivae (score 2 to 3). Two animals also had lacrimation (score 1 to 2), lesions of iris (score 1) and one of them had corneal lesions (score 1) involving a quarter (or less) of the area (score 1).

24 hours after instillation, one animal had severe chemosis (score 3) with lacrimation (score 3) and severe redness of the conjunctivae (score 3), lesions of iris (score 1) and cornea (score 1) on an area greater than one quarter (score 2). The two other animals had slight chemosis (score 1), slight redness of conjunctivae (score 1) and one of them had also lacrimation (score 1) and lesions of iris (score 1).

48 hours after instillation, only one animal had signs, severe chemosis (score 3) with lacrimation (score 2) and severe redness of the conjunctivae (score 3), lesions of iris (score 1) and of cornea (score 2) involving a quarter (or less) of the area (score 1).

72 hours after instillation, only slight chemosis (score 1) and slight redness of the conjunctivae (score 1) persisted in Animal No. 20091235. No ocular lesion persisted in any animal at the end of the exposure period (i.e. at time 72 hours for two animals and on D8 for one animal).

Body weight of Animal Nos. 20091236 and 20091237 was slightly lower (respectively - 0.3% and - 0.4%) than their body weight, on D1. It was not considered as toxicologically relevant effect. Body weight gain of Animal No. 20091235 was normal.
Other effects:
No observations indicative of systemic toxicity or ill health were noted for any rabbits during the course of this study.

Applicant's summary and conclusion

Interpretation of results:
other: Not Classified
Remarks:
Criteria used for interpretation of results: other: CLP (EC 1278/2008)