2-[(3-aziridin-1-ylpropionyl)methyl]-2-ethylpropane-1,3-diyl bis(aziridine-1-propionate)

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:

comparable to guideline study with acceptable restrictions

Remarks:

purity of the test substance not specified

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-[(3-aziridin-1-ylpropionyl)methyl]-2-ethylpropane-1,3-diyl bis(aziridine-1-propionate)

EC Number:

257-765-0

EC Name:

2-[(3-aziridin-1-ylpropionyl)methyl]-2-ethylpropane-1,3-diyl bis(aziridine-1-propionate)

Cas Number:

52234-82-9

Molecular formula:

C21H35N3O6

IUPAC Name:

6-(aziridin-1-yl)-2-({[3-(aziridin-1-yl)propanoyl]oxy}methyl)-2-ethyl-4-oxohexyl 3-(aziridin-1-yl)propanoate

Specific details on test material used for the study:

Trimethylolpropane tris (3-azirinyl) propanoate (CAS# 52234-82-9)
(Paradox ID:A-11/08/91:01101)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: L.I.T. Rabbitry, Aptos, California
- Weight at study initiation: 2 - 3 kg
- Acclimatisation: several days

ENVIRONMENTAL CONDITIONS
- air-conditioned animal room

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): undiluted

Duration of treatment / exposure:

30 sec, 5 min, > 5 min (substance was not removed from the eye)

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

9 (in 3 rabbits the test material was washed off 30 sec after instillation, in 3 others the material was washed from the eye 5 min after Instillation and in the last 3, the compound was not washed from the eye.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): in 3 rabbits the test material was washed off 30 sec after instillation, in 3 others the material was washed from the eye 5 min after Instillation and in the last 3, the compound was not washed from the eye

SCORING SYSTEM: The grading system was taken from the Draize Test.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Reversibility:

not reversible

Remarks on result:

other: no information on scores available; corneal opacity occurred within 24 hours

Results 2

Irritation parameter:

iris score

Reversibility:

not reversible

Remarks on result:

other: no information on scores available; hemorrhaged irises; no reaction to light in 2 animals each in the 5-minute and no-wash group

Results 3

Irritation parameter:

conjunctivae score

Reversibility:

not reversible

Remarks on result:

other: no information on scores available; conjunctival swelling, redness, and discharge were still extremely pronounced on Day 7

Irritant / corrosive response data:

Moderate-to-severe lesions of the cornea, iris, and conjunctivae were seen in all rabbits treated with the test substance, regardless of wash treatment. Many corneal and iris reactions were difficult to score during the first few days due to extreme swelling of conjunctivae, resulting in closure of the eyelids. Generally, however, corneal opacity occurred within 24 hours. At 7 days after treatment, all 9 treated eyes had some degree of opacity over most or all of the corneal area. The density of these lesions ranged from translucent to opaque, with the worst cases appearing in the 5-minute wash group. Irises were also severely affected - two each in the 5-minute and no-wash groups showed no reaction to light. The remaining eyes in all groups had hemorrhaged irises. Conjunctival swelling, redness, and discharge were still extremely pronounced on Day 7.
The decision was made to sacrifice the rabbits on Day 7 since it appeared that healing, with a return to normal sight, was highly unlikely.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The test substance is considered to be a severe irritant to the rabbit eye.