N-(2-hydroxypropyl)oleamide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 February 2013 - 28 March 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Compliant to GLP and testing guidelines; adequate consistence between data, comments and conclusions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

N-(2-hydroxypropyl)oleamide

EC Number:

203-828-2

EC Name:

N-(2-hydroxypropyl)oleamide

Cas Number:

111-05-7

Molecular formula:

C21H41NO2

IUPAC Name:

N-(2-hydroxypropyl)oleamide

Test material form:

other: waxy solid

Details on test material:

- Name of test material: N-(2-hydroxypropyl) Oleamide
- Physical state: beige waxy solid
- Lot/batch No.: T22221 without solvent
- Analytical purity: 100% dry matter
- Storage condition: at room temperature.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: breeder: CEGAV, Argenvilliers, France
- Age at study initiation: 2 to 4 months old on the day of treatment
- Mean body weight at study initiation: 2833 g (range: 2715 g to 2990 g)
- Housing: the animals were individually housed in noryl cages
- Diet: 110 pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: 6 days (first animal) or 4 days (the two other animals) before the beginning of the study.

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): 12 h/12 h.

IN-LIFE DATES: 18 March 2013 to 28 March 2013.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated right eye served as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL/animal.

Duration of treatment / exposure:

Not applicable: single application not followed by rinsing.

Observation period (in vivo):

1, 24, 48 and 72 h; if relevant, daily until reversibility of reactions

Number of animals or in vitro replicates:

Three males.

Details on study design:

REMOVAL OF TEST SUBSTANCE: 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

- Discharge:
0 absence of discharge
1 slight discharge (does not include small amounts normally found in inner canthus)
2 discharge with moistening of lids and hairs adjacent to lids
3 discharge with moistening of lids and hairs on wide area around the eye

- 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

- Any other lesions observed were noted

TOOL USED TO ASSESS SCORE: UV lamp after instillation of 0.5% sodium fluorescein solution

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: 24, 28 and 72 h (mean)

Results 2

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: 24, 28 and 72 h (mean)

Results 3

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Remarks on result:

other: 24, 28 and 72 h (mean)

Results 4

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: day 3

Remarks on result:

other: 24, 28 and 72 h (mean)

Results 5

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

1

Reversibility:

fully reversible within: day 4

Remarks on result:

other: 24, 28 and 72 h (mean)

Results 6

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: day 4

Remarks on result:

other: 24, 28 and 72 h (mean)

Results 7

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: 24, 28 and 72 h (mean)

Results 8

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: 24, 28 and 72 h (mean)

Results 9

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: 24, 28 and 72 h (mean)

Results 10

Irritation parameter:

cornea opacity score

Remarks:

(intensity)

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: 24, 28 and 72 h (mean)

Results 11

Irritation parameter:

cornea opacity score

Remarks:

(intensity)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: 24, 28 and 72 h (mean)

Results 12

Irritation parameter:

cornea opacity score

Remarks:

(intensity)

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

other: 24, 28 and 72 h (mean)

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP Regulation

Conclusions:

The test item was non irritant when administered by ocular route to rabbits.
Therefore, the test item should not be classified as irritating to the eyes according to the criteria of CLP Regulation.

Executive summary:

The objective of this study was to evaluate the potential irritant properties of the test item for the eye following a single administration to rabbits.

Methods

The test item was first administered to a single male New Zealand White rabbit.

 

As mean value from grading at 24, 48 and 72 hours after instillation was < 2 for conjunctival edema (chemosis) or for conjunctival redness and/or < 1 for iris lesion or for corneal opacity, the test item was administered in the left eye of two other animals.

 

The test item was administered inthe conjunctival sac of the left eye. The right eye remained untreated and served as control.

A dosage-volume of 0.1 mL/animal was used.

The eyes were not rinsedbefore 24-hour reading.

Each animal was observed once a day for mortality and clinical signs. Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until the end of the observation period. The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal. Body weight was recorded on the day of treatment and at the end of the evaluation of ocular reactions.

On completion of the observation period, the animals were sacrificed then discarded without macroscopic post‑mortem examination.

 

Results

No unscheduled deaths occurred during the study and no clinical signs were noted in any animals.

The body weight of the animals was unaffected by the test item treatment.

No ocular reactions were observed in the right untreated control eye.

In the left treated eye, slight chemosis of the conjunctiva was noted in all animals on day 1 and it persisted on day 2 in 1/3 males.

Slight or moderate redness of the conjunctiva was observed in all animals on days 1 and 2. Then, slight redness of the conjunctiva persisted on day 3 in 2/3 animals.

No iris and corneal lesions were noted in any animals.

 

Mean scores calculated for each animal over 24, 48 and 72 hours were as follows:

.          chemosis : 0.0, 0.0 and 0.3 ; showing no significant eye irritation,

.          redness of the conjunctiva: 0.3, 0.7 and 1.0 ; showing no significant eye irritation,

.          iris lesions: 0.0, 0.0 and 0.0 ; showing no significant eye irritation,

.          corneal opacity: 0.0, 0.0 and 0.0 ; showing no significant eye irritation.

 

Conclusion

The test item was non‑irritant when administered by ocular route to rabbits.

 

Therefore, the test item should not be classified as irritating to the eyes according to the criteria of CLP Regulation.