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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
OS3600 undergoes rapid hydrolysis in aqueous to MPKO and the corresponding silanol. Silanols undergo continuous condensation reactions to produce higher molecular weight siloxanes which are considered biologically unavailable. Therefore, the observed toxicity is likely due to MPKO and their values are comparable. The study has been conducted according to OECD guidance under GLPs.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

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)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-pentanone oxime (methyl propyl ketoxime)
- Molecular formula (if other than submission substance): C5H11NO
- Molecular weight (if other than submission substance): 101.15
- Smiles notation (if other than submission substance): C\C(CCC)=N\O
- InChl (if other than submission substance): Mixture of all possible stereoisomers
- Structural formula attached as image file (if other than submission substance): see Fig.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan, France
- Age at study initiation: at least 6 weeks
- Weight at study initiation: at least 1.0 kg
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21.4
- Humidity (%): 42 - 70
- Air changes (per hr): 16
- Photoperiod (hrs dark / hrs light):12 hrs

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: one eye was untreated and served as the control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 ml
- Concentration : 100%

Duration of treatment / exposure:
lids held together for 1 sec
Observation period (in vivo):
24, 48, and 72 hour, 7 days, and 14 days after exposure
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done


SCORING SYSTEM: Draize


TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 47, and 72 hours
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, and 72 hour
Score:
0.5
Max. score:
0.7
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24, 48, and 72 hr
Score:
1.67
Max. score:
2.3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Remarks:
chemosis
Basis:
mean
Time point:
other: 24, 48, and 72 hr
Score:
ca. 1
Max. score:
1.3
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Instillation of the test substance resulted in effects on the cornea, iris and conjuctivae. The corneal injury consisted of opacity (maximum grade 1) and epithelial damage (maximum 50% of the corneal area) in two (of the three) animals. The corneal injury had resolved within 7 days. Iridial irritation grade 1 was observed and had resolved within 24 hours in one animal and within 72 hours in the remaining animals. The irritation of the conjunctivae consisted of redness, chemosis and discharge and had completely resolved within 72 hours in one animals and within 14 days in the other two animals.
Other effects:
No clinical signs of toxicity noted

Any other information on results incl. tables

The data matrix is included in the reporting format attached

Applicant's summary and conclusion

Interpretation of results:
Category II
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the read-across approach from the analogue substance MPKO, the test item was determined to be irritating to the eyes.
Executive summary:

An acute eye irritation/corrosion study was performed with the analogue substance MPKO in rabbit according to OECD Guideline 405 (GLP study). Single samples of 0.1 mL of test item were instilled into one eye of each of three rabbits. Observations were made 1, 24, 48 and 72 hours and 7 and 14 days after instillation. Instillation of the test substance resulted in effects on the cornea, iris and conjuctivae. The corneal injury consisted of opacity (maximum grade 1) and epithelial damage (maximum 50% of the corneal area) in two (of the three) animals. The corneal injury had resolved within 7 days. Iridial irritation grade 1 was observed and had resolved within 24 hours in one animal and within 72 hours in the remaining animals. The irritation of the conjunctivae consisted of redness, chemosis and discharge and had completely resolved within 72 hours in one animal and within 14 days in the other two animals. The mean 24 -72 h scores for each animal were determined to be as follows: Corneal opacity: 0, 1.0, 1.0; Iris: 0, 0.7, 0.7; Redness: 0,7, 2.3, 2.0; Chemosis: 0.3, 1.3, 1.3. Based on these results, the read-across approach was applied and the substance OS3600 was determined to be irritating to the eyes.