Carbonic acid, 4-nitrophenyl 5-thiazolylmethyl ester, hydrochloride (1:1)

Eye irritation

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

Test material information

Constituent 1

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-yl)methyl carbonate 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

Results

Results 1

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

Results 2

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

Results 3

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

Results 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)