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
Study period:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(see below)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
yes
Remarks:
(see below)
Principles of method if other than guideline:
The animal room and temperature ranges were outside the allowed ranges on more than one occasion during the study. On day 3 the bodyweight for animal number R1004 was taken prior to written approval from the Study Director. These deviations were not considered to have any impact on the validity of the study.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsor's identification: AS305BD
Description: dark brown, viscous liquid
Lot number: TS07002
Analytical purity: 100%
Storage conditions: room temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Myrtle's Rabbitry, Thompson Stattion, Tennessee
- Age at study initiation: approximately 11-14 weeks of age
- Weight at study initiation: 2.5-3.3 kg prior to dosing
- Housing: suspended stainless steel cages
- Diet (e.g. ad libitum): PMI Certified Rabbit Chow #5322 (PMI Nutrition International)
- Water (e.g. ad libitum): municipal tap water ad libitum
- Acclimation period: minimum of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23 ºC
- Humidity (%): 21-63
- Air changes (per hr): 10-15 per hour
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Each of two rabbits (one animal dosed initially, followed by one additional animal) received a 0.1 mL dose of the test article in the conjunctival sac of the right eye. Following installation, the eyelids were gently held together for approximately one second in order to limit test material loss. The contralateral eye of each animal remained untreated and served as a control.
Duration of treatment / exposure:
Test and control eyes were examined for signs of irritation at 1, 24, 48, 72 hours and up to 28 days following dosing according to the Ocular Grading system (see attached Appendix 2). The study was terminated prior to resolution of the ocular irritation.
Observation period (in vivo):
28 Days
Number of animals or in vitro replicates:
Two rabbits (one animal dosed initially, followed by one additional animal)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 hours
Score:
2
Reversibility:
not fully reversible within: 28 Days
Remarks on result:
other: 1 of 2 animals reversed by day 14; remaining animal did not reverse at 28 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 hours
Score:
1
Reversibility:
fully reversible within: Day 14
Remarks on result:
other: one animal reversed by day 10.
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24-72 hours
Score:
2.83
Reversibility:
fully reversible within: 21 Days
Remarks on result:
other: one animals reversed by day 14
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-72 hours
Score:
2.17
Reversibility:
fully reversible within: 21 days
Remarks on result:
other: one animal reversed by day 10, the other one by day 21
Irritant / corrosive response data:
Exposure to the test article produced conjunctivitis (redness, swelling, and discharge), iritis, and corneal opacity in 2/2 test eyes at the 1-hour scoring interval. The conjunctival irritation resolved completely in 1/2 test eyes by the day 14 scoring interval and in the remaining test eye by the day 21 scoring interval. The iritis resolved completely in 1/2 test eyes by the day 10 scoring interval and in the remaining test eye by the day 14 scoring interval. The corneal opacity resolved completely in 1/2 test eyes by the day 14 scoring interval and did not resolve in the remaining test eye by study termination (day 28).
Other effects:
Additional findings included neovascularization and hair loss in both animals during the study.

Any other information on results incl. tables

The mean irritation scores at each interval were as follows:

Scoring interval Corneal opacity Iritis Conjunctival redness Conjunctival chemosis
24 hours 1.50 1.00 2.50 2.50
48 hours 2.00 1.00 3.00 2.00
72 hours 2.50 1.00 3.00 2.00
24-72 hours mean 2.00 1.00 2.83 2.17

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Based on the results of this study, the mean 24 hour Draize eye irritation score for AS305BD was 50/110.
Executive summary:

In line with OCED Guideline 405, the potential irritant and/or corrosive effects of AS305BD was evaluated in the eyes of New Zealnd white rabbits. Each of two rabbits received a dose of 0.1 mL of the test material in the conjunctival sac of the right eye and test and control eyes were observed for 28 days after treatment.

Exposure to the test material produced conjunctivitis (redness, swelling and discharge), iritis and corneal opacity in 2/2 test eyes at the 1 hour scoring interval. The conjunctival irritation resolved completely by the 21 day scoring interval. The iritis resolved completely by the day 14 scoring interval. The corneal opacity did not resolve by study termination.

Based on the results of this study, the mean 24 hour Draize eye irritation score for AS305BD was 50/110 and the test material should be classified as 'irreversible effects on the eye'.