Oleic acid, compound with (Z)-N-octadec-9-enylpropane-1,3-diamine (2:1)

Endpoint summary

Description of key information

Oleyl-diamine dioleate was found to be irritating to skin (although moderately)and severely irritating to eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 Jan 1986 - 11 Feb 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: 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: Abbaye de Bellefontaine (49122 Bégrolles en Mauges, France)
- Age at study initiation: not indicated
- Weight at study initiation: mean weigh 2.6 kg
- Housing: individually housed in polystyrene cages 0.35 x O.55 x 0.32 m.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 50 +/- 20%
- Air changes (per hr): not stated: The inconing, non recycled air, was filtered by an absolute filter.
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 28 Jan 1986 To: 11 Feb 1986

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: non-exposed left flank served as control

Amount / concentration applied:

0.5 mL on approx. 6 cm2 on right flank animal

Duration of treatment / exposure:

3 animals for 1 hour, and 3 additional animals for 4 hours.
Residual test substance was removed by means of a gauze saturated with sterile pyrogen-free water.

Observation period:

14 days

Number of animals:

3 per exposure duration of 1 hour and 4 hours

Details on study design:

A dose of 0.5 ml was applied to the clipped area 6 cm2 wide of the right flank of each animal. The treated area was then covered with a hydrophilic gauze patch to prevent loss of test substance. The test substance and the gauze patch were held in contact with the skin using a semi-occluslve patch adhesive tape.

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

(1 hour)

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Skin dryness was shown reversible by day 11

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

(1 hour)

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Skin dryness was shown reversible by day 13

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

(1 hour)

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Skin dryness was shown reversible by day 11

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

(1 hour)

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

(1 hour)

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

(1 hour)

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Basis:

animal #4

Remarks:

(4 hours)

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Skin dryness was shown reversible by day 11

Irritation parameter:

erythema score

Basis:

animal #5

Remarks:

(4 hours)

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: Skin dryness was shown reversible by day 11

Irritation parameter:

erythema score

Basis:

animal #6

Remarks:

(4 hours)

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 5 days

Remarks on result:

other: Skin dryness was shown fully reversible by day 12

Irritation parameter:

edema score

Basis:

animal #4

Remarks:

(4 hours)

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal #5

Remarks:

(4 hours)

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

animal #6

Remarks:

(4 hours)

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

See scoring table.
The reactions were a bit more marked during the observation period in the animals receiving the test substance during four hours than in those receiving the test substance during one hour.
The report concludes that the test substance INIPOL 002 was considered as irritant however the criteria to classify as skin irritatnt according to CLP regulation (2015) are not satisfied.

 Evaluation of skin reactions

		Observation time after exposure
		hours				days
	Animal no.	1 hr	24 hr	48 hr	72 hr	4	5	6	7	8	9	10	11	12	13
Erythema	01	0	2	2	2	2	2	1A	1A	0A	0A	0A	0	0	-
	02	1	3	3	3	3	3	2A	1A	0A	0A	0A	0A	0A	0
	03	0	1	1	1	1	1	1A	0A	0A	0A	0A	0	0	-
	04	2	2	3	4	4	4A	3A	2A	1A	0A	0A	0	0	-
	05	1	2	2	1	1	1	1A	0A	-	-	-	-	0	-
	06	2	2	2	1	1	1	0A	0A	0A	0A	0A	0A	0	-
Oedema	01	0	1	1	0	0	0	0	0	0	0	0	0	0	-
	02	0	2	2	1	1	1	0	0	0	0	0	0	0	0
	03	0	1	1	1	0	0	0	0	0	0	0	0	0	-
	04	2	3	3	4	4	4	3	2	1	0	0	0	0	-
	05	1	1	1	0	0	0	0	0	0	-	-	-	0	-
	06	0	1	1	0	0	0	0	0	0	0	0	0	0	-

A: Skin dryness

 - : Animals without dermal reaction were not recorded any more.

Animals no. 01, 02, 03: Contact duration 1 hour

Animals no. 04, 05, 06: Contact duration 4 hours

Interpretation of results:

other: not iclassified according to CLP Criteria

Conclusions:

The test substance was considered as irritant according to ECETOC but not according CLP criteria.

Executive summary:

The acute dermal irritation of the test substance INIPOL 002 was evaluated after application of 0.5 ml on the skin of six New-Zealand white rabbits divided into two groups of three animals. The test substance was removed after one hour in one group and after four hours in the other group by means of a gauze patch saturated with sterile pyrogen-free water.

 

One hour after removal of the gauze patch, the signs of dermal irritation were very weak in the animals receiving the test substance during one hour, and moderate in the other animals.

After 24 hours, the signs of irritation were similar and moderate in both groups. They were marked in one animal on day 3 and day 4.

On day 4 an erythema associated with a severe oedema was observed in one animal, as well as a moderate to severe erythema in one animal, a well defined erythema in one animal, a very slight erythema in three animals, and a very slight oedema in two animals.

Oedema lasted until day 8 in one animal.

The erythema noted on day 4 persisted on day 6, and then had disappeared on day 8 in three animals and on day 9 in the last two animals.

On day 9 only skin dryness was noted in 5/6 animals and over the days was observed in less animals, and completely cleared on day 13.

To sum up, the reactions were a bit more marked during the observation period in the animals receiving the test substance during four hours than in those receiving the test substance during one hour.

Under our experimental conditions, the test substance INIPOL 002 was considered as irritant.

ECETOC (Technical Report 66) evaluated this report and calculated the Primary Irritation Index for the three animals that were exposed for 4 hours:

PII = ( SUM Erythema 24/48/72hr + SUM Oedema 24/48/72hr)/ (3 x no. of animals) = 3.67

However the criteria to classify as skin irritant Cat. 2 according to CLP regulation (2015) are not satisfied.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

July - august 1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Old study,non GLP, not performed according to current guidelines. Limited reporting. No observations after 96 hours.

Qualifier:

according to guideline

Guideline:

other: Federal Hazardous Substances Act (Revised, Federal Register, Vol. 37, No. 244, December 19,1972)

Principles of method if other than guideline:

Comparable to OECD 404

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

No information

Type of coverage:

occlusive

Preparation of test site:

other: clipped and intact and abraded skin areas

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 ml (solid material was measured ,and dispensed while in the molten state and allowed to cool before application)

Duration of treatment / exposure:

4 hours

Observation period:

4 hrs after start application (at end of application), 24 and 48 hours.
The animals were retained until 96 hours after the initial application and observed for any delayed necrosis, but the data were not used in determining the Primary Irritation Index.

Number of animals:

6

Details on study design:

0.5 ml applied under a 1.5 by 1.5 inch 12-ply gauze patch which was secured in place by two 1/2 x 4 inch strips of adhesive tape in the form of an X.

The application sites were prepared by clipping the hair from the saddle area of the rabbits. The abraded areas were prepared by making minor epidermal incisions with a sterile 18-gauge needle. The abrasions were sufficiently deep to penetrate the epidermis but not to induce bleeding. After application of the patches, the trunk of each rabbit was wrapped with rubber dental damming which was secured with staples. The animals were immobilized in wooden restraining stocks for four hours.
At the end of the 4-hour exposure period, the patches were removed and any residual sample was gently sponged from the skin with a towel moistened with lukewarm tap water or an appropriate solvent.

Each test material was evaluated on a total of 12 sites, that is, six abraded and six intact sites. The Primary Irritation Index was calculated by adding the values for erythema or eschar formation, and edema at 4, 24 and 48 hours on intact and abraded sites (12 values) and divided by 6 to obtain an individual score for each rabbit. The combined average of the six individual scores is the Primary Irritation Index.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: Combined 4, 24 and 48 hours

Score:

5.3

Max. score:

8

Reversibility:

no data

Remarks:

No observations beyond 96 hours

Remarks on result:

other: Evaluated as corrosive

Irritant / corrosive response data:

Irritative effects at the 4-hour reading were confined to very slight or well-defined erythema at each intact site and five abraded sites.
At the 24-hour reading irritative effects included entire blanching of each site with peripheral erythema and slight to severe edema.
At the 48-hour reading irritative effects noted were blanching of five sites, coriaceousness of seven sites and slight to severe edema at each site.
Irritative effects at the 96-hour reading included entire coriaceousness of ten sites with fissuring, blanching of two sites and very slight to severe edema at each site. The Primary Irritation Index was found to be 5.3.

Primary irritation scores in rabbits following a 4-hour patch application of DUOMEEN T-DO

		Erythema-eschar				Edema
rabbit	Skin	4 hr	24 hr	48 hr	96 hr	4 hr	24 hr	48 hr	96 hr	Total	Avg.
67	Intact	2	4A	4B	4C	0	4	4	3	36	6
	Abraded	2	4A	4B	4C	0	4	4	3
68	Intact	1	4A	4B	4C	0	2	2	2	26	4.3
	Abraded	1	4A	4B	4C	0	2	2	2
69	Intact	1	4A	4D	4C	0	4	4	2	34	5.7
	Abraded	1	4A	4D	4C	0	4	4	2
70	Intact	1	4A	4B	4C	0	4	4	4	33	5.5
	Abraded	0	4A	4B	4C	0	4	4	4
71	Intact	1	4A	4A	4C	0	3	3	1	30	5
	Abraded	1	4A	4A	4C	0	3	3	1
72	Intact	1	4A	4B	4C	0	3	4	4	31	5.2
	Abraded	1	4A	4B	4C	0	3	3	3
									Total		5.3

A - Entire site blanched

B - Entire site coriaceous

C - Entire site coriaceous with fissuring

D - Entire site blanched with spotted necrosis

96-hour scores not used in calculating the Primary Irritation Index.

The ratio of tissue destruction observed on both intact and abraded skin sites is as follows:

Test Site	Evaluation of Skin Reaction	Ratio_Regarding_Six_Rabbits; Observation Time
		4 hour	24 hour	48 hour
Intact	Corrosive	0:6	6:6	6:6
Abraded	Corrosive	0:6	6:6	6:6

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

Corrosive based on coriaceousness with fissuring in ten sites, and blanching of two sites of the in total 12 sites evaluated (6 intact and 6 abraded skin sites). The PII was found to be 5.3 (out of maximal possible scoring of 8)

Executive summary:

Five-tenths milliliter of test material was applied and was applied under a 1.5 by 1.5 inch 12-ply gauze patch which was secured in place by two 1/2 x 4 inch strips of adhesive tape in the form of an X.

Each material was applied to an intact and abraded skin area on each of six albino rabbits. The application sites were prepared by clipping the hair from the saddle area of the rabbits. The abraded areas were prepared by making minor epidermal incisions with a sterile 18-gauge needle. The abrasions were sufficiently deep to penetrate the epidermis but not to induce bleeding. After application of the patches, the trunk of each rabbit was wrapped with rubber dental damming which was secured with staples. The animals were immobilized in wooden restraining stocks for four hours.

 

At the end of the 4-hour exposure period, the patches were removed and any residual sample was gently sponged from the skin with a towel moistened with lukewarm tap water or an appropriate solvent. The reactions were scored immediately after removal of the patches (4-hour reading), and at 24 and 48-hour intervals after application of the sample according to the scale reproduced in the tables accompanying this report. The animals were retained until 96 hours after the initial application and observed for any delayed necrosis, but the data were not used in determining the Primary Irritation Index.

 

Each test material was evaluated on a total of 12 sites, that is, six abraded and six intact sites. The Primary Irritation Index was calculated by adding the values for erythema or eschar formation, and edema at 4, 24 and 48 hours on intact and abraded sites (12 values) and divided by 6 to obtain an individual score for each rabbit. The combined average of the six individual scores is the Primary Irritation Index

 

Results: At the 48-hour reading irritative effects noted were blanching of five sites, coriaceousness of seven sites and slight to severe edema at each site.

Irritative effects at the 96-hour reading included entire coriaceousness of ten sites with fissuring, blanching of two sites and very slight to severe edema at each site. The Primary Irritation Index was found to be 5.3 (out of maximal possible scoring of 8).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

between 21 and 28 August 1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study compliant to GLP

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: Morton Commercial Rabbits, Stansted, Essex
- Age at study initiation: approximately 9 to 11 weeks of age
- Weight at study initiation: 2.1 to 2.3 kg
- Housing: individually housed in metal cages with perforated floors
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not indicated; The rabbits selected for the study were all acclimated to the laboratory environment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approximately 19°C
- Humidity (%): 30-70%.
- Air changes (per hr): Air exchange was maintained at approximately 19 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: between 21 and 28 August 1984

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

Eye were not flushed after installation.

Observation period (in vivo):

Observations post application at 1 hour and after 1, 2, 3, 4 and 7 days

Number of animals or in vitro replicates:

3

Details on study design:

The eyes of each animal were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage or conjunctival inflammation.
A 0.1 ml aliquot of EN 455 was placed into the lower everted lid of one eye of each animal.
The eyelids were then gently held together for one second before releasing. The contralateral eye remained untreated and served as a control.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

2

Reversibility:

fully reversible within: 3 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

The numerical scores awarded to the ocular reactions elicited by EN 455 are given in the table on ocular reactions.
All three animals gave a "positive" response.
Corneal opacities developed in all three animals.
Temporary iritis was seen in one animal.
A diffuse crimson red colouration of the conjunctivae was observed in all three animals and was accompanied by considerable swelling with partial eversion of the eyelids or with the eyelids about half-closed.
The eyes were normal seven days after instillation.
There were no other lesions.

Ocular reactions:

rabbit (sex)	Region of Eye		One hour	Day after instillation					Result Positive(+) Negative(-)
				1	2	3	4	7
960 (female)	Cornea		0	2	2	2	2	0	+
	Iris		0	0	0	0	0	0
	Conjunctivae	Redness	2	2	2	2	2	0
		Chemosis	2	3	2	2	2	0
961 (female)	Cornea		0	1	1	1	1	0	+
	Iris		0	0	0	0	0	0
	Conjunctivae	Redness	2	2	2	2	2	0
		Chemosis	2	2	2	2	1	0
978 (female)	Cornea		0	2	2	2	2	0	+
	Iris		0	1	1	0	0	0
	Conjunctivae	Redness	2	2	2	2	2	0
		Chemosis	2	3	2	2	2	0

 

Classification for GHS Cat.2 is fulfilled, as:

- at least 2 of the three animals show an mean (24, 48 and 72 hr) score for corneal opacity = 1 (all three animals),

- at least 2 of the three a mean conjunctival redness of = 2 (all three),

- at least 2 of the three a mean conjunctival chemosis of = 2 (all three)

Interpretation of results:

Category 2A (irritating to eyes) based on GHS criteria

Remarks:

Migrated information

Conclusions:

Oleyl diamine, dioleate was irritating in the in vivo eye irritation test in rabbits. The effects were fully reversible within 7 days. The study results indicate that the substance should be classified Cat.2 irritating to the eyes for GHS.

Executive summary:

The eye irritation potential of Oleyl diamine, dioleate was assessed in an in vivo eye irritation study in rabbits according to OECD 405, and in compliance with GLP.

A 0.1 ml aliquot of Oleyl diamine, dioleate was placed into the lower everted lid of one eye of each animal. The eyelids were then gently held together for one second before releasing. The contralateral eye remained untreated and served as a control.

Examination of the eyes was made after 1 hour and 1, 2, 3, 4, and 7, days after instillation. Observation of the eyes was aided by the use of a handheld torch.

 

Results:

All three animals gave a "positive" response.

Corneal opacities developed in all three animals.

Temporary iritis was seen in one animal.

A diffuse crimson red colouration of the conjunctivae was observed in all three animals and was accompanied by considerable swelling with partial eversion of the eyelids or with the eyelids about half-closed.

The eyes were normal seven days after instillation.

There were no other lesions.

 

According the GHS criteria, these results indicate that the substance should be classified Cat.2 for eye irritation.

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Dermal irritation:

There are two studies available on Oleyl-diamine dioleate, both according to OECD 404 guidelines and in compliance to GLP.

 

In one study the acute dermal irritation of Oleyl-diamine dioleate was evaluated after application of 0.5 ml on the skin of 2 groups of 3 NZW rabbits for 1 or 4 hours.

One hour after removal, the signs of dermal irritation were very weak in the animals receiving the test substance during one hour, and moderate in the other animals. During the further observation days, the reactions were a bit more marked during the observation period in the animals receiving the test substance during four hours than in those receiving the test substance during one hour only.

The severest reaction was seen in one animal in the 4-hour group, with a grade reaction of 3 to 4 for both erythema and oedema, and then gradually decreased and was completely resolved by day 9.

On day 9 only skin dryness was noted in 5/6 animals, and over the days was observed in less animals, and was completely cleared on day 13.

ECETOC evaluated the data and concluded to a Primary Irritation Index of 3.67 for the three animals that were exposed for 4 hours.

The substance was concluded to be irritating to the skin according to ECETOC calculation. However, in the light of the REACH guidance (2015), the criteria are not met to classify skin irritant Cat. 2 for GHS.

An additional available study evaluated the skin irritation potential of Oleyl-diamine dioleate, in rabbits. A 0.5 ml aliquot of Oleyl-diamine dioleate was applied under a 2.5 cm square gauze pad to one intact skin site on each of three animals under semi-occlusive dressing for four hours. At the end of the exposure period, the dressing and pad were removed and the treatment site was washed using distilled water to remove any residual test substance. Observations were done approximately 30 minutes after removal of the patches, and then daily until day 6.

Very slight erythema was observed in all three animals following removal of the bandages, and very slight erythema with slight oedema was seen in all three animals on Days 2 and 3. These reactions gradually ameliorated and the skins were normal by day 5 or 6.

As none of the mean scores for erythema or oedema during three consecutive days was 2.3 or higher, the substance does not need to be classified as skin irritant Cat. 2 for GHS.

 

Next to these two studies on Oleyl-diamine dioleate, there is a study available on Tallow-diamine dioleate. Cross-reading between the two substances is acceptable on the basis of similarities of structure with same functional groups, properties leading to common biological activity, and common metabolic degradation. Contrary to oleyl the tallow-alkyl chains also contain some C16-chains next to the C18-alkyl chains. The higher level of unsaturation in oleyl-alkyl chains can be considered a worst case representation compared to tallow, whereas the shorter chains in tallow-alkyl chains on their turn also can be considered to lead to higher irritation. Due to this very great similarity between these two substances, the available results from both substances should be considered in the evaluation of each of them.

 

An older study with Tallow-diamine dioleate resulted to clear irritation, but also indication of possible corrosive effects. However, no observations were performed after 96 hrs, and for these substances it knowns that they can result to severe inflammatory reactions that often interpreted as corrosive, but which show complete recovery upon extended observations. In view of this, it is noteworthy that for 4 of the 6 animals improvements were already seen at 96 hours compared to 48 hours.

Additionally, the report is of limited validity due to shortcomings in study design and reporting.

 

On overall the available data shows mixed results between no need for classification as irritant and possibly even corrosive. The most reliable study concludes to mild irritation without need to classify according to GHS classification, however, in a worst case approach, the subtance is classified Skin irritant Cat 2 and this is also considered as the best conclusion based on all available information about the category.

Also the available eye irritation study did not show corrosive effects.

 

Additional considerations:

- Definition of corrosion for classification:

A corrosive substance is a substance that produces destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, in at least 1 tested animal after exposure up to a 4-hour duration. Corrosive reactions are typified by ulcers, bleeding, bloody scabs and, by the end of observation at 14 days, by discoloration due to blanching of the skin, complete areas of alopecia and scars.

- No real fixed line between very severe irritation and corrosive effects:

 The definition indicates for corrosion effects as "ulcers, bleeding, bloody scabs" should be seen, and by end of 14 day observation "blanching of the skin and scars". However, 'bleeding ulcers' and 'bloody scabs' are rarely observed, and in case very severe reactions indicative for necrosis, the study will be terminated for humane reasons, rather than complete the full observation period.

The study on Tallow-diamine dioleate did not extend observations beyond day 4 because of the severity of the reactions and there is a possibility that recovery could have occurred when the observation was prolonged. However, based on the very severe reactions, the decision to terminate the study was correct in view of animal welfare.

- Decontamination of the skin.

These substances are rather sticky to the skin, and will not easily be washed off with pouring some water over it. This could play also a role in view of the observations that reactions can take a longer time to develop. Possibly, cleaning in the studies on Oleyl-diamine dioleate was more efficient. Consequently, it is possible that this difference of substance removal plays a role in the observed difference in severity of reactions.

- Number of animals.

Even in case of testing with three animals, if corrosive effects are observed in one animal, classification is appropriate. In one Oleyl-diamine dioleate study, there is at least one animal that shows severe reactions resulting to the highest scoring, which is the same as the scoring of all three animals in the study with Tallow-diamine dioleate. There were no clear signs of necrosis, although this observation might have been differently evaluated when the other two animals also showed these very severe reactions.

Eye irritation:

The eye irritation potential of Oleyl-diamine dioleate was assessed in an in vivo eye irritation study in rabbits according to OECD 405, and in compliance with GLP.

A 0.1 ml aliquot of Oleyl diamine, dioleate was placed into the lower everted lid of one eye of each animal. The eyelids were then gently held together for one second before releasing.

Corneal opacities developed in all three animals and temporary iritis was seen in one animal.

A diffuse crimson red colouration of the conjunctivae was observed in all three animals and was accompanied by considerable swelling with partial eversion of the eyelids or with the eyelids about half-closed. The eyes were normal seven days after instillation. There were no other lesions.

 

Respiratory irritation:

N Oleyl-diamine dioleate is a very viscous fluid with a vapour pressure less than 0.0015 Pa at 20°C (value based on read-across from shorter chain C12 -14-diamine, whereas Oleyl-diamine dioleate is a salt and based on a larger diamine). Also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur. Consequently, despite the irritant nature of the substance, respiratory irritation is not expected.

Justification for selection of skin irritation / corrosion endpoint:
Most reliable study

Justification for selection of eye irritation endpoint:
Only available study

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

It is proposed to follow a worst case approach scenario and classify for skin irritation. Consequently, GHS classification Cat.2 skin irritation is appropriate, with hazard statement H315: Causes skin irritation.

 

In view of the irritant properties, Oleyl-diamine dioleate should be classified Cat.2 for eye irritation according to GHS, with hazard statement H319: Causes serious eye irritation.

 

STOT-SE Cat.3 for respiratory irritation is not required. Exposure via the inhalation route will be unlikely to occur. Especially, in view of the mild irritant nature of the substance, respiratory irritation is not expected.