Enbucrilate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1973

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

OPHTHALMOLOGICAL TEST METHOD:
- Corneal tolerance: an intracorneal needle tract was made approx. in the middle of the stroma using a gauge 26 needle attached to a tuberculin syringe filled with the adhesive. A small amount of adhesive was deposited in the cornea as the needle was withdrawn.
- Subconjunctival tolerance: the adhesive was introduced subconctivally using a gauge 26 needle.
- Intraocular tolerance: the adhesive (0.1 cc) was injected into the anterior chamber through the limbus using a gauge 26 needle, carefully so as not to injure the iris, lens or corneal endothelium.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Enbucrilate

EC Number:

229-552-2

EC Name:

Enbucrilate

Cas Number:

6606-65-1

Molecular formula:

C8H11NO2

IUPAC Name:

butyl 2-cyanoprop-2-enoate

Test material form:

liquid

Details on test material:

- Histoacryl N (butyl 2-cyanoacrylate, CAS 6606-65-1),
- blue liquid,
- polymerization period 10 sec

Test animals / tissue source

Species:

rabbit

Strain:

not specified

Details on test animals or tissues and environmental conditions:

7 Albino rabbits weighing 1-2kg were used.
The animals were anesthetized with intravenous Nembutal Sodium and 0.5% proparacaine (Ophtetic) was applied topically.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Duration of treatment / exposure:

once

Observation period (in vivo):

8 w

Number of animals or in vitro replicates:

7

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: Intracorneal tolernace

Basis:

mean

Time point:

other: week 4

Score:

0

Reversibility:

other: no signs of inflammation

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

other: Subconjunctival tolerance

Basis:

mean

Time point:

other: week 4-8

Score:

0

Reversibility:

other: subsiding reaction

Remarks on result:

no indication of irritation

Any other information on results incl. tables

RESULTS

Intracorneal tolerance:

Clinical: Of the four eyes, three had minimal edema noted during the first week. One had moderate corneal edema. Aqueous flares were noted in two eyes. One developed neovascularization. Chemosis was noted in one, which subsided without treatment. On the second week, corneal edema subsided. Aqueous flares disappeared. No further neovascularization was noted. From the fourth to the eighth week, no significant change was noted.

Histologic picture: Presence of chronic inflammatory cells was noted in the first week specimen. There was necrosis noted around the site of injection on the second week specimen. The fourth and eighth week specimen showed no inflammation. Stromal cells below the needle tract were noted to be minimal in all 4 specimens.

Subconjunctival tolerance:

Clinical: Minimal congestion of the conjunctiva was noted at the site of injection from the first to the eighth week.

Histologic picture: Intense reaction to the adhesive was noted in the first and second week specimens. This reaction subsided from the 4th to the 8th week. Granulomatous type of reaction was noted in this specimen.

Intracameral tolerance:

Clinical: Of the three eyes, one developed moderately severe corneal edema, while the other two developed minimal corneal edema. In the eye which developed moderately severe corneal edema, the anterior chamber was not visible and the cornea became staphylomatous. One had neovascularization. Aqueous flare was noted in one.

Histologic picture: The three specimens presented the same histologic picture: presence of acute and chronic inflammatory cells; breaks in the Descemet's membrane; increased vascularity and edema of the iris; presence of synechia-anterior and posterior.

Histopathologic results

Site	week 1	week 2	week 4	week 8
intralamellar	- presence of chronic inflammatory cells- minimal stromal cells below needle tract	- necrosis around site of injection	- (-) inflammation	- mild vascularization- (-) inflammation
subconjunctival	- presence of plasma cells and lymphocytes- fibroblastic proliferation- thickening of conjunctiva near limbus	- increased vascularity- acute inflammation	- chronic inflammation- milder	- foreign body giant cells- granulomatous reaction
intracameral	- fibroblastic proliferation throughout cornea- acute and chronic inflammatory cells- break in Descemet's- posterior synechia- vascularization and edema of iris- inflammatory cells at angle	- presence of chronic inflammatory cells at angle- peripheral anterior synechia - detached Descemet's	- presence of chronic inflammatory cells- break in Descemet's- vascularization and edema of iris

Applicant's summary and conclusion

Interpretation of results:

other: well tolerated

Conclusions:

Butyl 2-cyanoacrylate when applied in small amounts is well tolerated by the rabbit intralamellarly and subconjunctivally.
There was considerable reaction (toxic) when it was placed intracameral, even with the use of 0.1 cc of adhesive.

Executive summary:

SUMMARY

Results of experimental studies on butyl 2-cyanoacrylate showed that it is well tolerated by the rabbit intralamellarly and subconjunctivally, but produces toxic reaction when placed intracamerally even in small amounts (0.1 cc).