Dioleamide

Endpoint summary

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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

Conclusions:

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.

Executive summary:

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.

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

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:

Slight eye irritation wit iris scores of 0.3 to 1 and conjuctiva redness score between 1.3 and 2 and chemosis 1.3 (all average 24,48 ans 72 h) was observed in the test animals. All effects were reversible within 14 days. 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

Conclusions:

Conclusion:
Slight eye irritation wit iris scores of 0.3 to 1 and conjuctiva redness score between 1.3 and 2 and chemosis 1.3 (all average 24,48 ans 72 h) was observed in the test animals. All effects were reversible within 14 days. 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. 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.

Executive summary:

Conclusion:

In a rabbit eye irritation test following OECG TG 405 and GLP the souce substance revealed slight eye irritation wit iris scores of 0.3 to 1 and conjuctiva redness score between 1.3 and 2 and chemosis 1.3 (all average 24,48 ans 72 h) was observed in the test animals. All effects were reversible within 14 days. 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.

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. The results are considered relevant for the target substance that, due to its lower water solubility, is supposed to be equally or less avaialble in the ocular fluid and is expeced to cause a comparable or lower level of effect.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Testing results for the read across source substance and QSAR predictions for the target substance show consistently only mild skin or eye irritation potential that would not lead to a classification as irritating to skin or eyes.

The results with the source substance are considered relevant for the target substance, that due to its lower water solubility is supposed to be euqually or less avaialble in the ocular fluid or on the skin and is expeced to cause a comparable or lower level of effect.

Justification for classification or non-classification

Read-across (CAS 16260-09-6) experimental data suggests that CAS 72901-31-6 is not classifiable with regards to skin or eye irritation/corrosion.

Testing results for the read across source substance and QSAR predictions for the target substance show consistently only mild skin or eye irritation potential that would not lead to a classification as irritating to skin or eyes.

The results with the source substance are considered relevant for the target substance, that due to its lower water solubility is supposed to be equally or less available in the ocular fluid or on the skin and is expected to cause a comparable or lower level of effect.