Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000-2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes
Remarks:
Experimental Toxicology and Ecology, BASF Aktiengesellschaft, 67056 Ludwigshafen/Rhein, Germany

Test material

Constituent 1
Chemical structure
Reference substance name:
2,3-Dihydro-1,3-dioxo-1H-perylo[3,4-cd]pyridine-8,9-dicarboxylic acid potassim salt (1:2)
EC Number:
807-752-6
Cas Number:
1451734-05-6
Molecular formula:
C24H9NO6K2
IUPAC Name:
2,3-Dihydro-1,3-dioxo-1H-perylo[3,4-cd]pyridine-8,9-dicarboxylic acid potassim salt (1:2)
Details on test material:
It cannot be entirely excluded that the test material used was the mono potassium salt rather than the di potassium salt.
Specific details on test material used for the study:
It cannot be entirely excluded that the test material used was the mono potassium salt rather than the di potassium salt. However, based on the very similar properties of these compounds, the toxicological data presented is considered valid and suitable to describe the toxicological property of the di potassium salt even if generated with the mono salt.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan-Winkelmann GmbH, Borchen, GER
- Age at study initiation: About 5 - 6 months
- Weight at study initiation: 3.37 - 3.79 kg
- Housing: Single housing in stainless steel wire mesh cages with grating
- Diet: Kliba-Labordiaet, Provimi Kliba SA, Kaiseraugst, Switzerland (about 130 g/animal per day).
- Water: Tap water ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated left eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml bulk volume (about 18 mg of the comminuted test substance)
Duration of treatment / exposure:
applied in a single dose, washed out after 24 hours
Observation period (in vivo):
7 days
Readings: 1 h, 24 h, 48 h, 72 h and 7 d, 14d and 21 d after application
Number of animals or in vitro replicates:
2 males and 1 female
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the substance was washed out with tap water about 24 hours after application (before 24 hour reading).

SCORING SYSTEM: according to OECD 405
in addition, conjunctival discharge was assessed as follows:
0 = No discharge
1 = Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2 = Discharge with moistening of the lids and hairs just adjacent to lids
3 = Discharge with moistening of the lids and hairs, and considerable area around the eye.


TOOL USED TO ASSESS SCORE: not specified

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.4
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.2
Max. score:
2
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.4
Max. score:
4
Reversibility:
fully reversible within: 7 days

Any other information on results incl. tables

Cornea Iris Conjunctiva Symptoms
Readings Animal Opacity Area redness Swelling Discharge
1h 1 0 0 0 2 2 1
2 0 0 0 2 2 2
3 0 0 0 2 2 2
24 h 1 1 4 1 3 2 0
2 1 4 1 3 2 0 43
3 0 0 0 3 2 1
48 h 1 0 0 0 3 1 0
2 1 4 0 3 2 1 43
3 0 0 0 2 1 0
72 h 1 0 0 0 2 1 0
2 1 3 0 3 2 0 LC, 43
3 0 0 0 2 0 0
7 d 1 0 0 0 0 0 0 SD
2 0 0 0 0 0 0 44
3 0 0 0 0 0 0 SD
14 d 2 0 0 0 0 0 0 44
21 d 2 0 0 0 0 0 0
mean 1 0.3 0.3 2.7 1.3
2 1.0 0.3 3.0 2.0
3 0.0 0.0 2.3 1.0
mean 0.4 0.2 2.7 1.4

LC: Loss of corneal tissue

SD: Study discontinued because the animal was free of symptoms

43: Parts of the conjunctiva and nictitating membrane brown discolored by rests of the test substance.

44: Part of the nictitating membrane brown discolored by a single, point-like rest of the test substance.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Based on the average conjunctival redness scores the substance is considered to be irritating to the eye of the rabbit.
Executive summary:

The potential of the test substance to cause damage to the conjunctiva, iris or cornea was assessed in 3 White New Zealand rabbits, subjected to a single ocular application of 0.1 ml bulk volume (about 18 mg) of the test substance. About 24 hours after application the eye was rinsed with tap water. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application and then in weekly intervals until day 14. Moderate conjunctival redness, moderate swelling and slight to moderate discharge was observed in all animals on the day of application. However, severe conjunctival redness was noticed in all animals 1 day after application. 2 animals additionally showed moderate iritis and slight corneal opacity, whereas 1 animal also exhibited brown discolored parts of the conjunctiva and nictitating membrane by rests of the test substance. The ocular reactions were reversible in all animals within 7 days after application, the discoloration was reversible within 21 days. The average score (24 to 72 hours) for irritation was calculated to be 0.4 for corneal opacity, 0.2 for iris, 2.7 for conjunctival redness and 1.4 for chemosis. Considering the described ocular reactions as well as the average score for irritation, the test substance gives indication of an irritant property to the eye under the test conditions chosen.