N-[3-(dimethylamino)propyl]docosanamide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-12-24 to 2008-12-31

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-[3-(dimethylamino)propyl]stearamide (C18) and N-[3-(dimethylamino)propyl]docosanamide (C22) 50:50 (w/w %)

IUPAC Name:

N-[3-(dimethylamino)propyl]stearamide (C18) and N-[3-(dimethylamino)propyl]docosanamide (C22) 50:50 (w/w %)

Details on test material:

- Name of test material:50:50 (w/w %) N-[3-(dimethylamino)propyl]stearamide (C18) and N-[3-(dimethylamino)propyl]docosanamide (C22).
- Physical state: solid
- Analytical purity: 99%

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 16 weeks
- Weight at study initiation: 2437 g
- Housing: Individually in stainless stell cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks 4642 were provided for gnawing.
- Diet (e.g. ad libitum): pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum
- Water (e.g. ad libitum): tap water from Füllinsdorf ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2008-12-24 To: 2008-12-31

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

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

Duration of treatment / exposure:

eye was rinsed after 24 hours but part of the test substance remained in eye

Observation period (in vivo):

48 hours

Number of animals or in vitro replicates:

1

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): lavage with approximately 20 mL physiological saline
- Time after start of exposure: 24 and 48 hours

SCORING SYSTEM: Commission Directive 2001/59/EC of August 06, 2001

TOOL USED TO ASSESS SCORE: hand-slit lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.5

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: animal was killed for ethical reasons after 48 h

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: animal was killed for ethical reasons after 48 h

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: animal was killed for ethical reasons after 48 h

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: animal was killed for ethical reasons after 48 h

Irritant / corrosive response data:

A slight opacity of the cornea affecting the whole area was noted in the treated femael at the 24-hour reading and progressed into moderate at the 48-hour evaluation. The light reflex was absent 24 to 48 hours after test item instillation. Moderate reddening and obvious swelling (chemiosis) of the conjunctivae were noted 1 hour after treatment which progressed into marked reddening and marked swelling at the 24- and 48-hour reading. The sclerae of the animal were moderately reddened at the 1-hour observation and were not assessable 24 to 48 hours after treatment due to swelling of the conjunctivae. Moderate ocular discharge was noted 1 to 48 hours after test item exposure. Blood was noted in the eye of the animal at the 48-hour evaluation.

Other effects:

The treated female showed uneven head and severe signs of pain during the examination of the eye at the 48-hour reading and was therefore sacrificed immediatly thereafter. The treated female showed a slight body weight loss (-0.6 %) between treatment and last observation day.

Any other information on results incl. tables

Table 1: Individual eye irritation scores of animal #1

Irritation parameter	Time point	Score
Corneal opacity	1 hour	0
Area of corneal opacity	1 hour	0
Iris score	1 hour	0
Conjunctivae score	1 hour	2
Chemosis score	1 hour	2
Sclera	1 hour	2
Corneal opacity	24 hour	2
Area of corneal opacity	24 hour	4
Iris score	24 hour	2
Conjunctivae score	24 hour	3
Chemosis score	24 hour	4
Corneal opacity	48 hour	3
Area of corneal opacity	48 hour	4
Iris score	48 hour	2
Conjunctivae score	48 hour	3
Chemosis score	48 hour	4

No staining produced by the test item of the treated eye was observed. White test item remnants were evident in eye or conjuncitval sac of the animal 1 -48 hours after treatment. No corrosion of the cornea was observed at any of the reading times.

The mean score for corneal opacity, iris, redness and chemiosis of the conjunctivae were not calculated because the animal was sacrificed for ethical reasons after the 48 -hour reading.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In this in vivo eye irritation test N-[3-(dimethylamino)propyl]stearamide (C18) and N-[3-(dimethylamino)propyl]docosanamide (C22) 50:50 (w/w %) produced irreversible effects to the eye and thus has to be classified as Category 1 (irreversible effects on eye) based on CLP, EU GHS (Regulation (EC) No 1272/2008).

Executive summary:

In a primary eye irritation study according to OECD 405, 0.1 g of N-[3-(dimethylamino)propyl]stearamide (C18) and N-[3-(dimethylamino)propyl]docosanamide (C22) 50:50 (w/w %) (99 %) was instilled into the conjunctival sac of the left eye of one young adult female New Zealand White rabbit for 48 hours. The animal then was observed for 48 hours.  The eye was washed with physiological saline at 24 and 48 hours. Irritation was scored by the method of Commission Directive 2001/59/EC of August 06, 2001.

A slight opacity of the cornea affecting the whole area was noted in the treated femael at the 24-hour reading and progressed into moderate at the 48-hour evaluation. The light reflex was absent 24 to 48 hours after test item instillation. Moderate reddening and obvious swelling (chemiosis) of the conjunctivae were noted 1 hour after treatment which progressed into marked reddening and marked swelling at the 24- and 48-hour reading. The sclerae of the animal were moderately reddened at the 1-hour observation and were not assessable 24 to 48 hours after treatment due to swelling of the conjunctivae. Moderate ocular discharge was noted 1 to 48 hours after test item exposure. Blood was noted in the eye of the animal at the 48-hour evaluation. The treated female showed uneven head and severe signs of pain during the examination of the eye at the 48-hour reading and was therefore sacrificed immediatly thereafter.

In this in vivo eye irritation test N-[3-(dimethylamino)propyl]stearamide (C18) and N-[3-(dimethylamino)propyl]docosanamide (C22) 50:50 (w/w %) is classified as Category 1 (irreversible effects on eye) based on CLP, EU GHS (Regulation (EC) No 1272/2008).