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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:
weight of evidence
Study period:
02 Nov 2016 to 05 Dec 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
October 02, 2012
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
30 May 2008
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
August 1998
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nousan No. 8147
Version / remarks:
November 24, 2000
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: Ra-He 2014-054
- Test item No.: 15/0531-1
- Purity test date: 100% UVCB
- Homogeity: The test substance was homogeneous by visual inspection.
- Appearance: Solid / beige

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Remarks:
Hsdlf:NZW – (SPF)
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Envigo CRS (Switzerland) Limited
- Sex: female
- Age at study initiation: Approx. 4 months
- Weight at study initiation: 2.96 – 3.54 kg
- Housing: Animals were individually housed in stainless steel wire mesh cages with grating with shallow cage body; floor area: 4225 cm2.
- Enrichment: Wooden gnawing blocks (Type KNH E-041); Abedd ® Lab. and Vet. Service GmbH Vienna, Austria
- Diet: STANRAB (P) SQC; SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 30-70 %
- Air changes: Approx. 10
- Photoperiod: 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL bulk volume (about 28 mg of the comminuted test item).
Duration of treatment / exposure:
The test item was applied in a single dose to the conjunctival sac of the right eyelid.
Observation period (in vivo):
Approx. 1, 24, 48 and 72 h after application and then at weekly intervals maximally up to day 14.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: the treated eye of the animal(s) was rinsed with 3 to 6 mL of lukewarm tap water for 1 to 2 minutes using a syringe with a blunt probe.
- Time after start exposure period: about (but not less than) 1 hour after application of the test item

PROCEDURE
- Body weight determination: Just before application of the test item and after the last reading.
- Local anesthesia: One drop of local anesthetic eye drops in each eye.
- Analgesia: 1 hour before and 8 hours after application with buprenorphine (0.01 mg/kg s.c.) and thereafter in 12 hour intervals until local and/or systemic findings had nearly disappeared. Meloxicam (0.5 mg/kg s.c.) 8 hours after application and thereafter in 24 hours intervals until local and/or systemic findings had nearly disappeared.
- Mortality: A check for any dead or moribund animals was made at least once each day.

SCORING SYSTEM:
The evaluation of eye irritation was 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:
Reading reactions on cornea or iris were observed using a slit lamp. Additional findings like corneal lesions detected with the aid of fluorescein.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal: #1 and #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal: #1 and #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Additional findings like corneal lesions detected with the aid of fluorescein (grade 1 – 2) and injected scleral vessels in a circumscribed or circular area were noted in the animals within 7 days after application.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria