2-[2-[4-[(2-cyanoethyl)ethylamino]-o-tolyl]vinyl]-1,3,3-trimethyl-3H-indolium dihydrogen phosphate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1981

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-(2-{4-[(2-cyanoethyl)(methyl)amino]phenyl}vinyl)-1,3,3-trimethyl-3H-indolium dihydrogen phosphate

Cas Number:

72208-21-0

Molecular formula:

C23H28N3O4P

IUPAC Name:

2-(2-{4-[(2-cyanoethyl)(methyl)amino]phenyl}vinyl)-1,3,3-trimethyl-3H-indolium dihydrogen phosphate

Test material form:

solid: particulate/powder

Details on test material:

Basic Red 14

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hacking & Churchill ltd., Huntingdon, UK
- Weight at study initiation: 3.5 kg
- Accommodation: individual cages
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 25 °C
- Humidity: 40 - 60 %
- Photoperiod: 12 hours light and 12 hours dark

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye used as control

Amount / concentration applied:

0.1 g test substance.

Duration of treatment / exposure:

24 hours.

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3 males.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: yes, with physiological solution of NaCl.
- Time after start of exposure: 24 hours.

SCORING SYSTEM: Draize scale for ocular lesions (1944)
Cornea
Degree of opacity (most dense area used)
0 no opacity
1 scattered or diffuse areas, details of iris clearly visible
2 easily discernible translucent area, details of iris slightly obscured
3 opalescent areas, no details of iris visible, size of pupil barely discernible
4 opaque cornea, iris invisible

Area of cornea involved:
1 one quarter or less but not zero
2 greater than one quarter, but less than half
3 greater than half, but less than three quarters
4 greater than three quarters, up to whole area


Iris
0 normal
1 folds above normal, congestion, swelling, circumcorneal injection (any of all of these or combination of any thereof), iris still reacting to light (sluggish reaction is positive)
2 no reaction to light, hemorrhage, gross detsruction (any or all of these)


Conjuctivae
Redness (refers to palpebral and bulbar conjuctivae, excluding cornea and iris)
0 vessels normal
1 vessels definitely injected above normal
2 more diffuse, deeper crimson red, individual vessels not easily discernible
3 diffuse beefy red

Chemosis:
0 no swelling
1 any swelling above normal (includes nictitating membranes)
2 obvious swelling with partial eversion of lids
3 swelling with lids about half closed
4 swelling with lids more than half closed

Discharge:
0 no discharge
1 any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2 discharge with moistening of the lids and hairs just adjacent to lids
3 discharge with moistening of the lids and hairs, and considerable area around the eye

TOOL USED TO ASSESS SCORE: one drop of 1 % fluorescein applied in the eye, then rinse with physiological NaCl solution and examination under UV light.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 7 d

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 21 d

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 d

Remarks on result:

no indication of irritation

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance instillation led to slight irritant effectss which were reversible within 21 days and did not lead to classification according to GHS

Executive summary:

Method

Eye irritation study was conducted in 3 male rabbits by instillation of 0.1 g of test material into one eye (the other eye serves as control). After 24 hours, rinse of eye was done with physiological NaCl solution. Observation and scoring were carried out at 1h, 24 h, 48 h, 72 h, 7 d and 21 d after application, based on the Draize scale (1944).

Result

Animals were observed for corneal opacity, iritis, conjuctival redness and chemosis. A score was associated to each animal at each time point. Evaluation was done averaging over results at 24, 48 and 72 hours and considering reversibility within 21 days. All responses were fully reversible within 21 days.