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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:
from 27 august 2012 to 6 september 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 405) and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)

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): MK-0954 Free Acid
- Molecular formula (if other than submission substance): C22H23ClN6O
- Molecular weight (if other than submission substance): 422.91
- Structural formula attached as image file (if other than submission substance): see reference substance
- Physical state: white powder
- Analytical purity: not provided
- Lot/batch No.: not available
- Expiration date of the lot/batch: 24 april 2013
- Stability under storage conditions: stable
- Storage condition of test material: at room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Conditions
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle. Any variations to these conditions were maintained in the raw data and had no effect on the outcome of the study.

Accommodation
Animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
Acclimatization period was at least 5 days before start of treatment under laboratory conditions.

Diet
Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) and wooden sticks (Swedish aspen wood, Bioservices, Uden, The Netherlands) were available during the study period

Water
Free access to tap water.

Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures.
There were no findings that could interfere with the study.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
undiluted,
applied amount: approx. 0.1 ml volume or 65.6 - 66.0 mg
Duration of treatment / exposure:
Eyes unwashed
Observation period (in vivo):
Observation to 7 days in some cases
Number of animals or in vitro replicates:
3 male animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
-Washing: unwashed

SCORING SYSTEM:
after Draize, 1959

TOOL USED TO ASSESS SCORE: fluorescein (for 1-day reading)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: mean of data at 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: mean of data at 24, 48, 72 h
Score:
0
Max. score:
2
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: mean of data at 24, 48, 72 h
Score:
1.1
Max. score:
3
Reversibility:
fully reversible within: 3 d for two animals and 7 days for one animal
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: mean of data at 24, 48, 72 h
Score:
0.2
Max. score:
4
Reversibility:
fully reversible within: 3 d for two animals and 7 d for one animal

Any other information on results incl. tables

 

 

Cornea

 

Iris

 

Conjunctivae

 

 

Comments

Animal 

Time after dosing

 

Opacity

(0-4)

Area

(0-4)

Fluor area (%)2

 

 

(0-2)

 

Redness

(0-3)

Chemosis

(0-4)

Discharge

(0-3)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

3301

 1 hour

 

0

0

-

 

1

 

2

1

1

 

b

 

24 hours

 

0

0

0

 

0

 

2

0

1

 

-

 

48 hours

 

0

0

-

 

0

 

1

0

0

 

-

 

72 hours

 

0

0

-

 

0

 

1

0

0

 

-

 

 7 days

 

0

0

-

 

0

 

0

0

0

 

-

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

329

 1 hour

 

0

0

-

 

1

 

2

2

2

 

b

 

24 hours

 

0

0

0

 

0

 

2

1

1

 

-

 

48 hours

 

0

0

-

 

0

 

1

0

0

 

-

 

72 hours

 

0

0

-

 

0

 

0

0

0

 

-

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

331

 1 hour

 

0

0

-

 

1

 

2

2

1

 

b

 

24 hours

 

0

0

0

 

0

 

2

1

1

 

-

 

48 hours

 

0

0

-

 

0

 

1

0

0

 

-

 

72 hours

 

0

0

-

 

0

 

0

0

0

 

-

 

 

 

 

 

 

 

 

 

 

 

 

 

1 Sentinel, 2 Green staining after fluorescein treatment (percentage of total corneal area)

Comments: b Remnants of the test substance in the eye

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A reliable study, conducted according to OECD 405, and in compliance with GLP. Iridial irridial irritation grade 1 was observed in all animals. The study was terminated at 7 days, when the irritation of the conjunctivae completely resolved. Based on these results, the test substance does not need to be classified for eye irritation according to GHS.