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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:
key study
Study period:
11 April - 19 August, 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to OECD and in accordance with GLP. The study material is well characterized

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
414-490-2
EC Name:
-
Cas Number:
154212-59-6
Molecular formula:
C11H9ClN2O5S
IUPAC Name:
4-nitrophenyl 1,3-thiazol-5-ylmethylcarbonate hydrochloride

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Seven adult males, 2- 3kg (10 - 15weeks) were allowed to acclimatise for 13 days before treatment. Six animals were used in the study.
100 - 130g/day of Certified High Fibre Rabbit Chow was provided and water was available ad libitum.
The temperature was maintained at 64 - 68°F.
The room was on a 12 hour daily light cycle.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: other: right eye of each animal was untreated
Amount / concentration applied:
0.05gram
Duration of treatment / exposure:
0.05g test material was placed in the conjunctival sac of the left eye by gently pulling the lower eye lid away from the eyeball. The upper and lower eyelid were held closed for about one second after treatment to prevent loss of material and then released. The right eye was left untreated to serve as the control.
Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment. Additional observations were performed on day 4, 7, 14 and 21. After the 24hr observation period was completed, the eyes of all rabbits were washed with lukewarm water.
Number of animals or in vitro replicates:
6 male rabbits
Details on study design:
Before treatment both eyes were checked for sign of ocular irritation or defect with the aid of a direct light source. Only animals free of ocular damage were used in the study.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 0-21 days
Score:
1.1
Max. score:
3
Reversibility:
not fully reversible within: 21 days, value at end of observation period 3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 0-21 days
Score:
3.7
Max. score:
4
Reversibility:
not fully reversible within: 21 days, value at end of observation period 4
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 0-21 days
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 21 days, value at end of observation period 4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 0-21 days
Score:
0
Max. score:
0
Reversibility:
fully reversible
Other effects:
Grade 4 corneal opacity with extreme (grade 4) conjunctival
irritation persisted in 2/6 animals at the 21-day scoring.
The opacity had cleared in the remaining 4 animals by day 21
and the conjunctival irritation had recovered or was
recovering as well.

Any other information on results incl. tables

Abbott-87439 hydrochloride caused severe occular damage in the eys of rabbits in these studies including severe chemosis in all rabbits and severe corneal opacity in 3 rabbits, with opaque corneas being observed in 2 of the rabbits including corneal ulceration in one of two rabbits on the final observation day (day 21).

Comments:
Severe corneal opacity and conjunctival irritation persisted
beyond 72 hours, therefore, the substance is labelled R41.

Maximum duration of any effect:

Conjunctiva/redness: 21 days

Conjunctiva/chemosis: 21 days

Cornea: 21 days

Applicant's summary and conclusion

Interpretation of results:
other: Severe ocular damage
Conclusions:
Severe occular damage was observed including severe chemosis in all rabbits. Severe corneal opacity in three rabbits was observed with opaque corneas in two of the rabbits. This includes corneal ulceration in one of the rabbits on the final day of observation (day 21)