Octadecanoic acid, 12-hydroxy-, reaction products with decanoic acid and ethylenediamine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 28 september 2010 to 18 october 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

The relative humidity recorded in the animal room was sometimes outside of the target ranges specified in the study plan.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of Octadecanamide, 12-hydroxy-N-[2-[(1-oxodecyl)amino]ethyl]- and N,N'-ethane-1,2-diylbis(12-hydroxyoctadecan-1-amide) and Decanamide, N,N'-1,2-ethanediylbis-

EC Number:

907-495-0

Cas Number:

198028-14-7

Molecular formula:

C90H180N6O9

IUPAC Name:

Reaction mass of Octadecanamide, 12-hydroxy-N-[2-[(1-oxodecyl)amino]ethyl]- and N,N'-ethane-1,2-diylbis(12-hydroxyoctadecan-1-amide) and Decanamide, N,N'-1,2-ethanediylbis-

Test material form:

solid

Details on test material:

Chemical name : Reaction mass of N,N'-ethane-1,2-diylbis(12-hydroxyoctadecan-1-amide) and Octadecanamide, 12-hydroxy-N-[2-[(1-oxodecyl)amino]ethyl]- and Decanamide, N,N'-1,2-ethanediylbis-
Chemical registery number : EC 907-495-0 / CAS : 198028-14-7

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hypharm, La Corbière, Roussay, France (instead of CEGAV, Saint Mars d’Egrenne, France).
- Age at study initiation: 2 to 4 months
- Weight at study initiation: 2.7 ± 0.1 kg
- Housing: The animals were housed individually in Pajon cages (50 cm x 57 cm x 75 cm).
- Diet (e.g. ad libitum): ad libitum (SAFE, Villemoisson, Epinay-sur-Orge, France)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: no data

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
- Concentration (if solution): not applicable

Duration of treatment / exposure:

Not applicable: single application not followed by rinsing.

Observation period (in vivo):

5 days.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

SCORING SYSTEM: Draize scale

- Conjunctival chemosis (lids and/or nictitating membranes):
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

- Conjunctival redness (palpebral and bulbar conjunctivae, cornea and iris):
0 blood vessels normal
1 a number of blood vessels definitely hyperemic (injected)
2 diffuse, crimson colour, individual vessels not easily discernible
3 diffuse, beefy red

- Iris lesions
0 normal
1 markedly deepened rugae, congestion, swelling, moderate circum-corneal hyperemia,or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2 no reaction to light, haemorrhage, gross destruction (any or all of these)

- Cornea intensity of opacity (direct examination and, if necessary, with an UV lamp)
0 no ulceration or opacity
1 scattered or diffuse areas of opacity (other than slight dulling or normal lustre), details of iris clearly visible
2 easily discernible translucent area, details of iris slightly obscured
3 nacreous areas, no details of iris visible, size of pupil barely discernible
4 opaque cornea, iris not discernible through the opacity

- Cornea area of opacity (direct examination and, if necessary, with an UV lamp)
1 one quarter (or less) but not zero
2 greater than one quarter but less than a half
3 greater than one half but less than three quarters
4 greater than three quarters up to whole area


TOOL USED TO ASSESS SCORE: Fluorescein (batch No. S667)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible

Remarks:

within 2 days

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible

Remarks:

within 2 days

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible

Remarks:

within 4 days

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible

Remarks:

within 2 days

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Remarks:

within 4 days

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible

Remarks:

within 2 days

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

A slight or moderate chemosis (grade 1 or 2) and a moderate or severe redness of the conjunctiva (grade 2 or 3) were noted in all animals 1h after the application of the test substance.
A slight chemosis and redness of the conjunctiva (grade 1) persisted in one animal within 24hrs, whereas a slight chemosis (grade 1) and moderate then slight redness of the conjunctiva (grade 2 then 1) persisted until day 3 (72 hrs) in another one .

Iris lesions were noted 1h after the application in one animal and within 24hrs in another one.

A slight corneal opacity (grade 1) was recorded in one animal 24hrs after the treatment.

Mean scores calculated for each animal over 24, 48 and 72 hrs were 1.0, 0.3 and 0.0 for chemosis, 1.3, 0.3 and 0.0 for redness of the conjunctiva, 0.3, 0.0 and 0.0 for iris lesions and 0.3, 0.0 and 0.0 for corneal opacity.

Other effects:

A clear discharge was observed in all animals 1 hour after the application of the test substance. It persisted within 24hrs in one animal.
Residual test item was observed in all animals 1hr after the application of the test substance. In one animal, residues were still observed 48hrs after the start of the test.

Any other information on results incl. tables

Table 7.3.2/1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
60 min	0/0/0	1/1/0	3/3/2	2/2/1
24 h	1/0/0	1/0/0	2/1/0	1/1/0
48 h	0/0/0	0/0/0	1/0/0	1/0/0
72 h	0/0/0	0/0/0	1/0/0	1/0/0
Average 24h, 48h, 72h	0.3/0.0/0.0	0.3/0.0/0.0	1.3/0.3/0.0	1.0/0.3/0.0
Reversibility*)	c/-/-	c/-/-	c/c/c	c/c/c
Average time (day) for reversion	2/-/-	2/-/-	4/2/1	4/2/1

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

not eye irritating

Conclusions:

The substance is not classified according to Regulation (EC) No. 1272/2008 and its subsequent amendments on classification, labelling and packaging (CLP) of substances and mixtures.

Executive summary:

In an eye irritation study, the test substance was administered to New Zealand White rabbits according to OECD 405 guideline. The study was conducted in compliance with the principles of Good Laboratory Pratices.

0.1 g of the test substance was placed into the conjunctival sac of one eye of three rabbits without irrigation. The other eye remained untreated and was used for control purposes. Assessment of ocular damage/irritation was made approximately 1, 24, 48 and 72 hours following treatment according to the Draize scoring method.

A slight or moderate chemosis (grade 1 or 2) and a moderate or severe redness of the conjunctiva (grade 2 or 3) were noted in all animals 1 hour after the application of the test substance. A slight chemosis and redness of the conjunctiva (grade 1) persisted in one of them within 24 hours, whereas a slight chemosis (grade 1) and moderate then slight redness of the conjunctiva (grade 2 then 1) persisted until day 3 (72 hours) in another one. Iris lesions were noted 1 hour after the application in one animal and within 24 hours in another one. A slight corneal opacity (grade 1) was recorded in one animal 24 hours after the treatment.

Mean scores calculated for each animal over 24, 48 and 72 hours were 1.0, 0.3 and 0.0 for chemosis, 1.3, 0.3 and 0.0 for redness of the conjunctiva, 0.3, 0.0 and 0.0 for iris lesions and 0.3, 0.0 and 0.0 for corneal opacity.

It was concluded that the test item was slightly irritant when applied topically to eyes.