Registration Dossier

Administrative data

Description of key information

Skin irritation (OECD 404): not irritating
Eye irritation (OECD 405): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Remarks:
In vivo study existed before In-vitro acceptance
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.
Justification for type of information:
In-vivo study existed prior to REACh registration and prior to the requirement for or acceptance of in-vitro data.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: The Broekman Institute, Someren, The Netherlands
- Age at study initiation: 13-15 weeks
- Weight at study initiation: 2.42-2.85 kg
- Housing: Individually in plastic cages with perforated floors.
- Diet (e.g. ad libitum): Standard laboratory animal diet (LK-01, pellet diameter 4 mm; 100 g per day), obtained from Hope Farms, Woerden.
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5-22.0
- Humidity (%): 60-80
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
other: untreated contralateral flank served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Test substance preparation: Approximately 5 g of test substance were scraped from the surface of the solid and transferred into a glass vial; before dose administration the test substance was heated to 60-70 °C, and 3 portions of 0.5 mL were transferred into aluminium vials using a plastic syringe. The portions of test substance were allowed to solidify in the vials. Each portion of test substance was spread on a 6 cm² patch of Metalline and applied to the animals as described below.

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL for moistening
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, 72 hours
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: 6 cm² of clipped area of 10 cm x 10 cm on the central back (right flank).
- Type of wrap if used: Test substance was spread on a 6 cm² patch of Metalline (Lohmann, FRG), mounted on permeable tape (Micropore, 3M, St. Paul, USA). Each portion of test substance was moistened with 0.5 mL of Milli-RO water (Millipore Corp., Bedford, Mass. USA). The patch containing the test substance was applied to the right flank of each animal, the left flank being covered with the same dressing without test substance. Finally, the animals were wrapped in flexible bandage (Coban, 3M, St. Paul, USA).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, remaining test substance was removed, using a tissue moistened with tap-water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritant / corrosive response data:
One hour after dosing the skin of 2 animals showed slight erythema which disappeared within the next 24 hours. Other dermal effects were not observed in any of the animals.
Other effects:
There were no signs of systemic intoxication observed.

Conclusion:

According to the criteria of EU Directive 67/845/EEC and Regulation (EC) No 1272/2008 the test substance does not have to be classified as irritating to the skin.

Interpretation of results:
not irritating
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: The Broekman Institute, Someren, The Netherlands
- Age at study initiation: 13-15 weeks
- Weight at study initiation: 2.67-3.04kg
- Housing: Individually in plastic cages with perforated floors.
- Diet (e.g. ad libitum): Standard laboratory animal diet (LK-01, pellet diameter 4 mm; 100 g per day), obtained from Hope Farms, Woerden.
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 60-80, with an occasional peak of 90%
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eyes served as controls
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 90±1 mg (equivalent to 0.1 mL)

Test substance preparation: Test substance was ground to a fine powder using a mortar and pestle. On the day of dose administration three portions of 90±1 mg of the powder were dispensed in glass containers with screw caps.

Test substance administration: On administration one of the portions of the test substance was instilled into the conjunctival sac of one of the eyes of each animal using a spatula. The lids were then held gently together for two seconds and released. The other eye remained untreated and served as control. Immediately after instillation the animals were observed and abnormalities were recorded.
Duration of treatment / exposure:
Not washed out
Observation period (in vivo):
100 minutes, 24, 48 and 72 hours, 7 and 14 days
Number of animals or in vitro replicates:
3 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: Solution of 2% fluorescein approximately 24 hours after instillation, immediately after scoring of corneal opacity and alterations of iris and conjunctivae. The procedure was repeated 3 days after dose administration.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: 20% of corneal area affected on day 1, fully reversible by day 3
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: 25% of area affected on day 1, fully reversible by day 3
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
other: 20% of corneal area affected on day 1, fully reversible by day 3
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Immediately after dosing all animals were observed to blink excessively, thereby removing some of the test substance from their treated eye. At the first observation time (100 min after instillation) hyperaemia of the blood vessels of the conjunctivae, affecting the eyelids and the scleral conjunctivae, was observed in all animals, as well as obvious swelling of the eyelids. Increased lacrimation was also observed in all animals at this time.

Treatment of the eyes with fluorescein 24 hours after treatment revealed 20-25% corneal epithelial damage, but other corneal effects were not observed. When fluorescein treatment was repeated 3 days after dosing the epithelial damage had disappeared. On day 1 injection of the capillaries in the iris was observed in all animals, as well as deepened rugae in 1/3 animals; in all animals the iris still reacted to light. In the animal with the deepened rugae the iris effects disappeared within the next 24 hours, while in the other 2 animals the injection of capillaries persisted for 48 to 72 hours. Slight conjunctival swelling persisted in all animals for 3 days, while slight redness was still observable on day 7. Fourteen days after dosing all adverse ocular effects had disappeared.
Other effects:
Signs of systemic intoxication were not observed.

Conclusion:

According to the criteria of EU Directive 67/548/EEC and Regulation (EC) No 1272/2008 the test substance does not have to be classified as irritating to the eyes.

Interpretation of results:
not irritating
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

The skin irritation potential of (Z)-N-octadec-9-enylhexadecan-1-amide (CAS 16260-09-6) was investigated in a GLP-compliant study performed according to OECD 404 (Thouin, 1986). The shaved skin of 3 female New Zealand White rabbits was exposed to test substance moistened with 0.5 mL water for 4 h under semi-occlusive conditions. The skin of the contralateral flank remained untreated and served as control. Evaluation of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h after removal of the dressing. At the 1 h reading time point, 2 animals showed slight erythema which was fully reversible within the following 24 h. No further dermal effects were observed in any of the animals at the remaining reading time points. The mean erythema and edema scores after 24, 48 and 72 h were 0 for each individual animal. Based on these results, the test substance was not considered to be irritating to skin.

Eye irritation

An eye irritation study performed in compliance with OECD 405 and GLP is available for (Z)-N-octadec-9-enylhexadecan-1-amide (CAS 16260-09-6) (Mulder, 1986). The undiluted test material (90 mg equivalent to ca. 0.1 mL) was placed into the conjunctival sac of one eye of 3 female New Zealand White rabbits each. The other eye remained untreated and served as control. The eyes were examined and scored 100 min, 24, 48 and 72 h as well as 7 and 14 days after test substance application. At the first observation time (100 min after instillation), hyperaemia of the blood vessels of the conjunctivae, affecting the eye lids and the scleral conjunctivae, was observed in all animals, as well as obvious swelling of the eyelids. Increased lacrimation was also observed in all animals at this time. Treatment of the eyes with fluorescein 24 h after substance installation revealed 20-25% corneal epithelial damage, which was fully reversible 3 days after treatment. At the 24 h reading time point, injection of the capillaries in the iris was observed in all animals, as well as deepened rugae in 1/3 animals; but in all animals the iris still reacted to light. In the animal with the deepened rugae, the iris effects disappeared within the next 24 h, while in the other 2 animals the injection of capillaries was still present at the 48 and 72 h reading time point. Slight conjunctival swelling persisted in all animals until 72 h after treatment, while slight redness was still observable on Day 7 of the observation period. Fourteen days after treatment, all adverse ocular effects had fully disappeared in the animals. The mean iris, conjunctivae and chemosis scores of the reading time points 24, 48 and 72 h were 0.3/0.7/1, 1.3/2/1.7 and 1.3/1.3/1.3 for the 3 individual animals, respectively. For cornea, the mean score was 0 in each individual animal at the 24, 48 and 72 h reading time points. Therefore, the test substance does not have to be considered as irritating to the eye.


Justification for selection of skin irritation / corrosion endpoint:
There is only one study available.

Justification for selection of eye irritation endpoint:
There is only one study available.

Justification for classification or non-classification

The available data on skin and eye irritation of (Z)-N-octadec-9-enylhexadecan-1-amide (CAS 16260-09-6) do not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC and are therefore conclusive but not sufficient for classification.