1,2-Ethanediamine, N1-(2-aminoethyl)-, 2-hydroxy-2-phenylethyl and stearyl derivs.

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 March 1991 to 25 March 1991.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2-({2-[(2-hydroxy-2-phenylethyl)({2-[(2-hydroxy-2-phenylethyl)amino]ethyl})amino]ethyl}(octadecyl)amino)-1-phenylethan-1-ol; 2-({2-[(2-hydroxy-2-phenylethyl)[2-(octadecylamino)ethyl]amino]ethyl}(octadecyl)amino)-1-phenylethan-1-ol; 2-({2-[(2-hydroxy-2-phenylethyl)amino]ethyl}[2-(octadecylamino)ethyl]amino)-1-phenylethan-1-ol; 2-{[2-({2-[bis(2-hydroxy-2-phenylethyl)amino]ethyl}(2-hydroxy-2-phenylethyl)amino)ethyl](octadecyl)amino}-1-phenylethan-1-ol

EC Number:

807-655-9

Cas Number:

1629160-48-0

Molecular formula:

Not available - UVCB substance

IUPAC Name:

2-({2-[(2-hydroxy-2-phenylethyl)({2-[(2-hydroxy-2-phenylethyl)amino]ethyl})amino]ethyl}(octadecyl)amino)-1-phenylethan-1-ol; 2-({2-[(2-hydroxy-2-phenylethyl)[2-(octadecylamino)ethyl]amino]ethyl}(octadecyl)amino)-1-phenylethan-1-ol; 2-({2-[(2-hydroxy-2-phenylethyl)amino]ethyl}[2-(octadecylamino)ethyl]amino)-1-phenylethan-1-ol; 2-{[2-({2-[bis(2-hydroxy-2-phenylethyl)amino]ethyl}(2-hydroxy-2-phenylethyl)amino)ethyl](octadecyl)amino}-1-phenylethan-1-ol

Test material form:

other: viscous-liquid

Details on test material:

- Test article: FAT 92267/A.
- Description: Beige, viscous-liquid.
- Batch number: EN 3.86
- Purity: Active ingredient is 81.1%
- Stability of the test article: Stable for months
- Storage conditions: At room temperature
- Safety precautions: Gloves, goggles and face mask were sufficient to assure personnel health and safety.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: EN 3.86

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature in the dark
- Stability under storage conditions: stable for months

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd., Wölferstrasse 4, CH-4414 Füllinsdorf.
- Age at study initiation: 14 weeks.
- Weight at study initiation: Male: 2.5 kg.
- Identification: By unique cage number and corresponding ear tag.
- Housing: Individually in a stainless steel cage equipped with an automatic cleaning and drinking system.
- Diet: Diet Pelleted standard Kliba 341, Batch 58/90 rabbit maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst), ad libitum.
- Water: Community tap water from Itingen, ad libitum.
- Acclimation period: Four days under laboratory conditions after veterinary examination.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 40-70
- Air changes (per hr): Air conditioned with 10-15 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light / 12 hours dark, music during the light period.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye remainded untreated and served as the reference control.

Amount / concentration applied:

0.1 ml of the (undiluted) test article was applied to the rabbit eye.

Duration of treatment / exposure:

One application

Observation period (in vivo):

The eye of the animal was examined for ocular irritation 1, 24, 48 and 72 hours and 7 days after administration.

Number of animals or in vitro replicates:

1 male

Details on study design:

- The eyes of the animal were examined once, one day prior to test article administration.
- Only those animal with no signs of ocular injury or irritation was used on the test.
- On test day 1, 0.1 ml of the (undiluted) test article was placed in the conjunctival sac of the left eye of the animal after gently pulling the lower lid away from the eyeball. The lid was then gently held together for about one second to prevent loss of the test article.

SCORING SYSTEM:
EVALUATION OF EYE REACTIONS
CORNEAL IRRITATION:
Opacity: degree of density (densest area used for assessment)
- No ulceration or opacity: 0
- Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible: 1 *
- Easily discernible translucent area, details of iris slightly obscured: 2 *
- Nacrous area, no details of iris visible, size of pupil barely discernible: 3 *
- Opaque cornea, iris not discernible through the opacity: 4 *

IRIDIC IRRITATION:
- Normal: 0
- Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia, or injection, any of these or combination thereof, iris still reacting to light (sluggish reaction is positive): 1 *
- No reaction to light, hemorrhage, gross destruction (any or al 1 of these): 2 *

CONJUNCTIVAL IRRITATION:
- Redness (refers to palpebral and bulbar conjunctivae, cornea and iris). Blood vessels normal 0
- Some blood vessels definitely hyperemic (injected) 1
- Diffuse, crimson color, individual vessels not easily discernible 2 *
- Diffuse beefy red 3 *

Chemosis: lids and/or nictitating membranes
- No swelling: 0
- Any swelling above normal (includes nictitating membranes): 1
- Obvious swelling with partial eversion of lids: 2 *
- Swelling with lids about half closed: 3 *
- Swelling with lids more than half closed: 4 *

The maximum scores are:
Cornea : 4
Conjunctival Redness : ** 3
Iris : 2
Conjunctival Chemosis : ** 4
Maximum attainable score : 13


TOOL USED TO ASSESS SCORE:
Eye examinations were made with a slit-lamp 30 SL/M (C. Zeiss AG, Zuerich / Switzerland) and a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel /Switzerland).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

IRRITATION
- FAT 92'267/A showed a primary Irritation score of: 3.00, when applied to the conjunctival sac of the rabbit eye.

CORROSION
- Slight diffuse corneal opacity was observed within 1 hour to 24 hours after test article application.

Other effects:

VIABILITY / MORTALITY AND CLINICAL SIGNS
No acute clinical signs were observed in the animal during the test and observation period, and no mortality occurred.

COLORATION
In the area of application no staining of the cornea and conjunctivae by pigment or coloring of the test article was observed.

BODY WEIGHTS
The body weight gain of the rabbit was within physiological limits.

Any other information on results incl. tables

INDIVIDUAL FINDINGS

hours/days after application

After 1 hour:

- Cornea: generally slight diffuse;

- Conjunctivae: generally severe erythema and edema;

- Nictitating membrane: generally reddened and swollen

- Sclera: blood vessels, generally slightly visible

- Discharge: lidhair, slightly wetted.

After 24 hours:

- Cornea: generally slight diffuse;

- Conjunctivae: generally slight erythema and edema;

- Nictitating membrane: generally reddened and swollen

- Sclera: blood vessels, generally clearly visible

After 48 hours:

- Conjunctivae: generally slight erythema and edema;

- Nictitating membrane: generally reddened and swollen

- Sclera: blood vessels, generally clearly visible

After 72 hours:

- Conjunctivae: generally slight erythema and edema;

- Nictitating membrane: generally reddened and swollen

- Sclera: blood vessels, generally clearly visible

After 7 days:

- Sclera: blood vessels, ventral visible

Individual eye scores

Time point	Corneal opacity	Iris	Conjunctiva
			Redness	Chemosis
After 24 hours	1	0	1	1
After 48 hours	0	0	1	1
After 72 hours	0	0	1	1

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 92267/A was not considered as not irritant to the rabbit eye.

Executive summary:

The primary eye irritation study was carried out to assess the possible irritation potential when a single dose of FAT 92267/A was placed in the conjunctival sac of a rabbit eye. The experiment was donne according to the OCED guideline 405. GLP methodology was follows during the test. One New Zaeland White rabbit was used. On test day 1, 0.1 ml of the (undiluted) test article was placed in the conjunctival sac of the left eye of the animal after gently pulling the lower lid away from the eyeball. The lid was then gently held together for about one second to prevent loss of the test article. The eye of the animal was examined for ocular irritation 1, 24, 48 and 72 hours and 7 days after administration. Under the conditions of this experiment, FAT 92267/A was found to cause a primary irritation score of 3.00, when applied to the conjunctival sac of the rabbit eye. Slight diffuse corneal opacity was observed within 1 hour to 24 hours after test article application. In the area of application no staining of the cornea and conjunctivae by pigemnt or coloring of the test article was observed. Under the conditions of the experiment, FAT 92267/A had to be classified as not irritant to the rabbit eye.