Amides, C18-unsatd., N-[2-(1-piperazinyl)ethyl]

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:

other: The study is not performed under GLP but there was inhouse QA. The study was performed similar to OECD 405 reporting was not done in full detai.CoA is not included.

Cross-reference

Reason / purpose for cross-reference:

reference to same 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)

Deviations:

no

GLP compliance:

no

Remarks:

but inhouse quality assurance authentication was performed

Test material

Test material information

Constituent 1

Reference substance name:

N-[2-(piperazin-1-yl)ethyl]C18-unsatured-alkylamide

EC Number:

629-767-5

Cas Number:

1228186-18-2

Molecular formula:

No molecular formula

IUPAC Name:

N-[2-(piperazin-1-yl)ethyl]C18-unsatured-alkylamide

Test material form:

liquid: viscous

Details on test material:

test substance: EN 422
Batch Number: BX PPL 2
The test material was in the form of a viscous brown liquid and was stored i n the dark under ambient conditions.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Cheshire Rabbit Farms Limited
- Age at study initiation: no data
- Weight at study initiation: 2.5-3.0 kg
- Housing: housed individually in cages with a grid floor beneath which was a peat moss filled tray.
- Diet (e.g. ad libitum): Ad libitum: Special Diet Services (S.D.S.) Rabbit Diet of satisfactory analysis
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 ± 2
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: each animal served as its own control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml

Duration of treatment / exposure:

24h after which the animals were sacrificed for humane reasons

Observation period (in vivo):

observations were done at 1 and 24h

Number of animals or in vitro replicates:

two males and one female

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing : eye not rinsed

SCORING SYSTEM:OECD: Acute Eye Irritation/Corrosion Test i n Rabbits Grades for Ocular Lesions
Cornea
No ulceration or opacity ........................................... 0
Scattered or diffuse areas of opacity ,
details of iris clearly visible .................... .... ........... I*
Easily discernible translucent areas of
opacity, details of iris slightly obscured ........................ 2*
Nacreous areas of opacity, no details of iris
visible, size of pupil barely discernible ......................... 3*
Complete corneal opacity, iris not discernible ...................... 4*
Ulceration, absence of a gross
patch of corneal epithelium ....................................... 4*

Iris
Normal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
Markedly deepened folds, congestion, swelling,
moderate circumcorneal injection (any of these or
combination of any thereof), iris still reacting
to light (sluggish reaction i s positive) .......................... l*
No reaction to light, haemorrhage, gross
destruction (any or all of these) ................................. 2*

Conjunctivae
Redness (refers to pal pebral and bul bar
conjunctivae excluding cornea and iris) :
Vessels normal ...................................................... 0
Some vessels definitely injected ..................................... 1
Diffuse crimson red, individual vessels
not easily discernible ........................................... 2*
Diffuse beefy red . . . . . . . . . . . . . . . . . . . . .... . . . . . . . . . . . . . . . . . . . . . . . . . . . 3*

Chemosis
No swelling ........................................................ 0
Any swelling above normal (including nictitating membrane) ........... 1
Obvious swelling with partial eversion of lids ....................... 2*
Swelling with lids about half closed ........ . ....... . ............. ... 3*
Swelling with lids more than half closed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4*
Ulceration or necrosis of palpebral and bulbar
conjunctivae ornictitating membrane ............................... 4*

Discharge
Mild ................... ... ........ ................ ...............1
Moderate ........................................................2
Severe ............................................................ 3

* F i gures indicate the grades considered positive.

TOOL USED TO ASSESS SCORE: standard illumination.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

other: For humane reasons the animal was killed after 24h

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

other: For humane reasons the animal was killed after 24h

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

other: For humane reasons the animal was killed after 24h

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

other: For humane reasons the animal was killed after 24h

Remarks on result:

other: Additionally: severe discharge

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

other: For humane reasons the animal was killed after 24h

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

other: For humane reasons the animal was killed after 24h

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

other: For humane reasons the animal was killed after 24h

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

other: For humane reasons the animal was killed after 24h

Remarks on result:

other: Additionally: severe discharge

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

other: For humane reasons the animal was killed after 24h

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

other: For humane reasons the animal was killed after 24h

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

other: For humane reasons the animal was killed after 24h

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

other: For humane reasons the animal was killed after 24h

Remarks on result:

other: Additionally: severe discharge

Irritant / corrosive response data:

Cornea and Iris
It was not possible to assess corneal reactions at 1h in any animal because o f intense conjunctival swelling. At 24 h positive corneal reactions (score1 and 2) were noted in all animals. Positive iridial responses (score 1) were noted in all eyes at 1 and 24 h.

Conjunctival
Moderate conjunctival redness (score 2) and severe chemosis (score 3-4) were noted in all eyes at 1 and 24 h. Severe discharge (score 3) was noted
in all eyes at 1 and 24h.

Other effects:

All animals were sacrificed after the 24h reading on humane grounds.

Any other information on results incl. tables

Eye irritation/corrosion test in rabbits.

Rabbit No/Sex	1 hour			24 hours
	1♂	2♀	3♂	1♂	2♀	3♂
Cornea	+	+	+	1	2	2
Iris	1	1	1	1	1	1
Conjunctivae:
redness	2	1	2	2	2	2
chemosis	4	3	4	4	4	4
discharge	3	3	3	3	3	3
Total	10	8	10	11	12	12

+ = unable to read due to intense swelling

Applicant's summary and conclusion

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The test substance elicited positive corneal, iridial and conjunctival responses in all eyes at 1 and 24h. Because of the severe nature of the responses and following a veterinary inspection the rabbits were humanely sacrificed following the 24h reading.

Executive summary:

The potential of the test substance to induce eye irritation was assessed in 3 rabbits according to a method similar to OECD guideline 405.

A statement that the report was audited by the Quality Assurance Unit of the testing laboratory was provided.

A single dose of 0.1ml of the testsubstance was instilled into one eye, the other eye was not treated and served as control.The eyes were not rinsed after administration of the test item. Ocular reactions were observed 1 hour and 24 hours later.

It was not possible to assess corneal reactions at 1 hour in any animal because of intense conjunctival swelling. At 24 hours corneal scores of 1 or 2 were noted in all animals. Positive iridial scores of 1 were noted in all animals at 1 and 24 hours. Moderate conjunctival redness (score 2) and severe chemosis (score 4) were noted in all rabbits at 1 and 24 hours. Severe discharge was also noted in all rabbits.

Due to the severe nature of the reactions observed, the rabbits were sacrificed after the 24 hour recording on humane grounds. The authors concluded that the test substance was severely irritating to the eye.