3,3'-(methylimino)bispropiononitrile

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Range-Finding Toxicity data List V

Author:

Smyth Jr H.F., Carpenter C.P., Weil C.S., Pozzani U.C.

Year:

1954

Bibliographic source:

AMA Arch. Ind. Hyg. Occup. Med. 10, 61-68 (1954)

Reference 2

Reference Type:

publication

Title:

Chemical burns of the rabbit cornea

Author:

Carpenter C.P., Smyth H.F.

Year:

1946

Bibliographic source:

American Journal of Ophthalmology, Vol. 29, Issue 11, p1363–1372

Materials and methods

Principles of method if other than guideline:

The potential of the test substance to cause eye injury was assessed. The degree of corneal necrosis from various volumes and concentrations of the chemical was reported.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

3,3'-(methylimino)bispropiononitrile

EC Number:

216-305-9

EC Name:

3,3'-(methylimino)bispropiononitrile

Cas Number:

1555-58-4

Molecular formula:

C7H11N3

IUPAC Name:

3-[(2-cyanoethyl)(methyl)amino]propanenitrile

Test material form:

liquid

Specific details on test material used for the study:

- Name as used in publication: N-Methyl-3,3'-iminodipropionitrile

Test animals / tissue source

Species:

rabbit

Strain:

other: normal albino rabbits, not further specified.

Details on test animals or tissues and environmental conditions:

Rabbits were selected on the bases of absence of grossly visible staining by a 5% aqueous solution of fluorescein sodium, flushed with distilled water 20 seconds after application.

Test system

Vehicle:

other: undiluted

Controls:

not specified

Amount / concentration applied:

Depending on effects ranging between 0.5 mL undiluted to 0.005 mL of a 1% solution in water of propylene glycol.

Duration of treatment / exposure:

Substance was not washed out

Observation period (in vivo):

18-24 hours

Number of animals or in vitro replicates:

Usually 5 eyes were exposed

Details on study design:

The eye injury test in rabbits reports the degree of corneal necrosis from various volumes and concentrations of chemical. Different amounts of the undiluted or dilured test material is apllied to the center of the cornea while the lids are retracted. About 1 minute later, the lids were released. The exposed eyes were were examined in strong daylight., then stained with fluorescein, and the injury scored.Eye injury was translated into a numerical score. The individual numerical scored of each eye treated with a given volume or concentration of a chemical were added together and then divided by the number of eyes to obtain the score of the injury caused by the treatment. A score of 5.0 was representative of severe injury, corresponding to necrosis, visible only after staining and covering about three fourth of the surface of the cornea; or a more severe necrosis covering a smaller area.System for numerical scoring of injury to the rabbit eye 24 hours after apllication:- Symptom visible before fluorescein staining-- Cornea dull: 2 points-- Cornea opaque, less than half of area: 4 points-- Cornea opaque, more than half of area: 6 points-- Iritis, slight internal congestion: 1 point-- Iritis, marked internal congestion: 2 points-Symptom visible after fluorescein staining (If necrosis is diffuse assign points corresponding to half observed area)-- Necrosis on less than 5% of cornea: 1 point-- Necrosis on 5 to 12 % 2 points-- Necrosis on 13 to 37 % 3 points-- Necrosis on 38 to 62 % 4 points-- Necrosis on 63 to 87 % 5 points-- Necrosis on 88 to 100 % 6 pointsGrades of injury employed for rating the relative damage produced by chemicals in the eye:1: 0.5 mL undiluted gives injury of 0 to 1.0 points2: 0.5 mL undiluted gives injury of 1.0 to 5.0 points3: 0.1 mL undiluted gives injury of up to 5.0 points (0.5 mL gives over 5.0)4: 0.02 mL undiluted gives injury of up to 5.0 points (0.1 mL gives over 5.0)5: 0.005 mL undiluted gives injury of up to 5.0 points (0.02 mL gives over 5.0)6: Excess of 40 % solution gives injury of up to 5.0 point (0.005 mL gives over 5.0)7: Excess of 15 % solution gives injury of up to 5.0 point (40% gives over 5.0)8: Excess of 5 % solution gives injury of up to 5.0 point (15% gives over 5.0)9: Excess of 1 % solution gives injury of up to 5.0 point (5% gives over 5.0)10: Excess of 1 % solution gives injury of over 5.0 point.

Results and discussion

In vivo

Results

Irritation parameter:

other: Grade

Basis:

mean

Time point:

other: 18 to 24 hours

Score:

2

Max. score:

10

Reversibility:

not specified

Remarks on result:

other: 0.5 mL undiluted test substance gives injury of over 1.0 up to 5 points

Irritant / corrosive response data:

Based on the applied system for numerical scoring of injury to the rabbit eye 24 hours after apllication, 0.5 mL of the undiluted test substance gave a score between 1 and 5.

Applicant's summary and conclusion

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria