Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From February 20, 2006 to March 3, 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was performed according to OECD Guideline 405 and EU method B.5, with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Erythromycin A-9 Oxime (E) Hydrochloride.
- Physical state: white powder.
- Lot/batch No.: B5310059
- Storage condition of test material: at ambient temperature, in the dark.
- Other:
pH: 6.16 (1% solution in deionised water, w/v, determined with a pH-Meter WTW pH340)

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, D-94633 Sulzfeld.
- Age at study initiation:
- Weight at study initiation:
Animal No. 121: 2.4 kg
Animal No. 122: 2.2 kg
Animal No. 123: 2.2 kg

- Housing: Individual caging in metal wire cages, Ehret GmbH, D-79312 Emmendingen, type KK 016R, 79 cm x 59 cm bottom area, 38 height.
- Diet (e.g. ad libitum): Altromin 2123 maintenance diet for rabbits, rich in crude fiber, ad libitum. Analysis of the feed for ingredients and contmainants is performed randomly by Altromin, D-32791 Lage, Germany. Hay. briquettes (supplied by SSniff, D-59494 Soest) are offered additionally as a dietary supplement.
- Water (e.g. ad libitum): Tap water from an automatic watering system, ad libitum.
- Acclimation period: 19 days (animal No. 121) and 5 days (animals Nos. 122 and 123)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Average of 19 ºC (continous control and recording)
- Humidity (%): Average of 48.8% (continous control and recording)
- Photoperiod (hrs dark / hrs light): Artificial light from 6 a.m. to 6 p.m.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eyes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The weighed amounts of the individual doses were 53, 57 and 56 mg.

Duration of treatment / exposure:
72 hours
Observation period (in vivo):
Both eyes of the animals were examined within 24 hours before instillation and approximately 1, 24, 48 and 72 h.
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 72 hours

SCORING SYSTEM:
Grades for ocular lesions:

CORNEA
Opacity: degree of density (area most dense is taken for reading)
0 No ulceration or opacity
1 Scattered or diffuse areas of opacity (exept for slight dulling of normal lustre), details of iris clearly visible.
2 easily discernible translucent area, details of iris slightly obscured.
3 Nacreous area, no details of iris visible, size of pupil barely discernible.
4 Opaque cornea, iris not discernible through the opacity.

IRIS
0 Normal
1 Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection; any of these or combination of any thereof, iris still reacting to light (lsuggish reaction is positive)
2 No reaction to light, haemorrhage, gross destruction (any of all these together)

CONJUNTIVAE
Redness: (refers to the most sever effect of parpebral and bulbar conjuntivae in comparison to the control eye)
0 Blood vessels normal.
1 Some blood vessels definitely hyperaemic (injected)
2 Diffuse crimson colour, individual vessels not easily discernible.
3 Diffuse beefy red.

Chemosis: lids and/or nictating membranes.
0 No swelling.
1 Any swelling above normal (includes nintating membranes)
2 Obvious swelling with partial eversion of lids.
3 Swelling with lids about half closed.
4 Swelling with lids more than half closed.


TOOL USED TO ASSESS SCORE: otoscope lamp.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean 24 - 72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: mean 24 - 72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: mean 24 -72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: mean 24 - 72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: mean 24 - 72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean 24 - 72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
other: mean 24 - 72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: 1 h: discharge, any amount different from normal.
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
other: mean 24 - 72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 h
Remarks on result:
other: 1h: discharge with moistening of the lids and hairs just adjacent to the lids; 24 h: discharge, any amount dofferent from normal.
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
other: mean 24 - 72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: 1h: discharge, any amount different from normal.
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean 24 - 72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean 24 - 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean 24 - 72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
The untreated eyes ("control eyes") were normal at each observation time.
The eyes, trated with the test susbtance ("test eyes") were normal before the instillation.
After the instillation with the test substance, the following findings were made:
Corneae: not affected.
Irises: not affected.
Conjuntivae, redness: a score of "1" in all animals from 1 h p.a. onwards until a maximum of 48 h p. a.
Conjuntivae, chemosis: a score of "2" or "1" in 2/3 animals only 1 h p.a., a score of "4" in 1/3 animals 1 h p.a., afterwards decreasing and lasting until 48 h p.a.
Additional findings: Ocular discharge was noted in all animals from 1 h p.a. until a maximum of 24 p.a.
Other effects:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results, the test substance is not an eye irritant.
Executive summary:

Assessment of the possible irritating or corrosive effects of the pure test substance following a single administration into a conjunctival sac of rabbits was determinated according to OECD 405 Guideline and B.5 EU Method, with GLP. The approximate equivalent of 0.1 mL of the test substance was instilled into the conjunctival sac of one eye of each of 3 New Zealand White rabbits. No symtoms of systemic toxicity were observed in the animals during the test period and no mortality occurred. Based on the results, the test substance is not an eye irritant.