Registration Dossier

Diss Factsheets

Toxicological information

Eye irritation

Currently viewing:

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other: GLP-compliant guideline study, available as unpublished report, Test itm purity less than 80%., fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Qualifier:
according to guideline
Guideline:
other: Japan MAFF Testing Guideline of 12 Nousan No. 8147, November 24, 2000
GLP compliance:
yes (incl. QA statement)
Remarks:
Experimental Toxicology and Ecology, BASF Aktiengesellschaft, 67056 Ludwigshafen/Rhein, Germany

Test material

Constituent 1
Reference substance name:
297132-04-8
EC Number:
608-403-9
Cas Number:
297132-04-8
IUPAC Name:
297132-04-8
Details on test material:
- Name of test material (as cited in study report): 4-(4-Acryloyloxy-butoxycarbonyloxy)-benzoic acid
- Degree of purity / content: 66.7 area %
- Physical state / appearance: Solid / white
- Homogeneity: The test substance was homogeneous by visual inspection.
- ph-value: of a 10% aqueous preparation: about 4
- Storage conditions: Room temperature, protected from humidity and Iight

- Molecular formula (if other than submission substance): C15H16O7
- Molecular weight (if other than submission substance): 308.2
- Smiles notation (if other than submission substance): C=CC(=O)OCCCCOC(=O)Oc1ccc(cc1)C(=O)O
- 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: Centre Lago S.A., 01540 Vonnas, France
- Age at study initiation: About 5 - 7 months
- Weight at study initiation: 3.07 - 3.58 kg
- Housing: Single housing in stainless steel wire mesh cages with grating, floor area: 3000 cm2
- Diet: Kliba-Labordiät (Kaninchen & Meerschweinchenhaltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland (about 130 g/animal per day)
- Water: Tap water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr): fully air-conditioned rooms.
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated left eye
Amount / concentration applied:
0.1 mL bulk volume (about 34 mg of the comminuted test substance)
Duration of treatment / exposure:
About 1 hour
Observation period (in vivo):
28 days
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: After application of the solid test substance the treated eye of the animal(s) was rinsed with 3 to 6 mL of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe.
- Time after start of exposure: About 1 hour

SCORING SYSTEM: The evaluation of eye irritation is performed according to the quoted guidelines. In addition to specific observations recommended by the regulatory authorities, evaluations were made of discharge from the eye and the area of cornea affected by the lesions.

TOOL USED TO ASSESS SCORE: Daylight tubes "Lumilux" (L 58W/860 PLUS ECO 25X1, Osram, Germany)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean 24-48-72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Basis:
animal: #2 and #3
Time point:
other: mean 24-48-72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1 and #2
Time point:
other: mean 24-48-72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean 24-48-72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean 24-48-72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean 24-48-72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean 24-48-72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean 24-48-72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean 24-48-72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean 24-48-72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
- Moderate conjunctival redness and conjunctival chemosis and moderate to severe discharge were observed in all animals 1 hour after application.
- Moderate or severe conjunctival redness were observed in all animals up to 72 hours and decreased to slight in two animals after 7 days.
- Moderate to marked conjunctival chemosis, noted in all animals after 24 hours, decreased to slight to moderate after 48 hours and to slight 72 hours after application.
- Moderate to severe discharge persisted in all animals up to 48 hours after application and decreased in two animals to slight after 72 hours.
- Slight corneal opacity noted in one animal after 24 and 48 hours increased to moderate 72 hours after application and decreased thereafter (day 7) to slight.
- Moderate iritis was observed in two animals 24 or 72 hours after application.
- Suppuration, contracted pupil, discharge of blood and injected scleral vessels, circular or in a circumscribed area were observed during the observation period.
- The ocular reactions were reversible in one animal within 7 days and in two animals within 14 days after application.

Any other information on results incl. tables

Table: Individual findings

Readings Animal Cornea Iris Coniunctiva Additional findings
Opacity Area of cornea involved Redness Chemosis Discharge
1 h 01 0 0 0 2 2 2 PC
02 0 0 0 2 2 2  
03 0 0 0 2 2 3 49
24 h 01 1 4 0 3 2 3 PC, DB, 48
02 0 0 1 3 2 2 48
03 0 0 0 2 3 3 49
48 h 01 1 4 0 3 2 2 S, PC, DB, 49
02 0 0 0 3 1 3 48
03 0 0 0 3 2 3 48
72 h 01 2 2 1 3 1 1 S, PC, 49
02 0 0 0 2 1 0 48
03 0 0 0 2 1 1 48
7 d 01 1 1 0 1 0 0 49
02 0 0 0 0 0 0 so
03 0 0 0 1 0 0 48
14 d 01 0 0 0 0 0 0  
03 0 0 0 0 0 0  
Mean 01 1.3   0.3 3.0 1.7    
02 0.0   0.3 2.7 1.3    
03 0.0   0.0 2.3 2.0    
Mean   0.4   0.2 2.7 1.7    

S = Suppuration

PC = Pupil contracted

DB = Discharge of blood

SD = Study discontinued because the animal was free of findings

48 = Soleral vesseis injected, circumscribed area

49 = Soleral vesseis injected, circular

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU