Oleonitrile

Endpoint summary

Description of key information

Irrittating to skin (GHS Cat.2)

Non-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

Remarks:

in vivo study used for read across. Performed according to TG 404. Preformed pre-REACH.

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to OECD Guideline 404 and in compliance with GLP. Read-across from structural identical substance with on average a somewhat shorter aliphatic chain length.

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: HOECHST AG, Kastengrund, conventional breed
- Age at study initiation: about 3 -5 months
- Weight at study initiation: 2.2 - 2.7 kg
- Housing: fully air-conditioned rooms, individual cages.
- Diet (e.g. ad libitum): ad libitum (Altromin 2123, Altromin GmbH (Lage/Lippe))
- Water (e.g. ad libitum): ad libitum (deionised, chlorinated water)
- Acclimation period:
- min. 7 days
- daily observation during acclimation period



ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +-3 °C
- Humidity (%): 50 +-20 %
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL per patch
- Concentration (if solution): undiluted

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- % coverage: 100 %
0.5mL of the test substance was applied over the whole surface of a 2.5 x 2.5 cm cellulose patch on a piece of surgical plater (specially produced by Beiersdorf AG, Hamburg. The plaster was fixed to the prepared skinarea (ca. 25 cm2) and then covered with a semi-occlusive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with warm tap water


SCORING SYSTEM:

Erythema and eschar formation
No erythema.......................................................................................................................0
very slight erythema (barely perceptible)......................................................................1
well-defined erythema......................................................................................................2
moderate to severe erythema..........................................................................................3
severe erythema (beet redness) to slight eschar formation (lesion in depth).........4

Oedema
No oedema...................................................................................................................................0
very slight oedema (barely perceptible)..................................................................................1
slight oedema (edges of area well defined by definite raising)............................................2
moderate oedema (raised approximately 1mm)....................................................................3
severe oedema (raised more than 1mm and extending beyond area of exposure.........4

Irritation parameter:

erythema score

Remarks:

overall

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: 7 - 14 days

Remarks on result:

other: 4 hour exposure

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: 4 hour exposure

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: 4 hour exposure

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: 4 hour exposure

Irritation parameter:

edema score

Remarks:

overall

Basis:

mean

Remarks:

all animals

Time point:

24/48/72 h

Score:

1.1

Max. score:

2

Reversibility:

fully reversible within: 7 - 14 days

Remarks on result:

other: 4 hour exposure

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: 4 hour exposure

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: 4 hour exposure

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: 4 hour esposure

Irritant / corrosive response data:

After 4 hour exposure following irritative responses were observed: slight to moderate erythyma, slight edema, rough and dry skin surface fine scales

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance tallow nitrile proved to be irritating to skin and has to be labelled with R38 - irritating to skin.

Executive summary:

In a GLP compliant OECD TG 404 study, 0.5 mL the undiluted test material Tallow Nitrile, a yellowish liquid (purity approximately 99%), was applied semi-occlusively for 4 hours to the shaved skin of three New Zealand White Rabbits. The test substance was applied to a 2.5 cm²gauze patch. Examination of the treated skin was started approx. 30 minutes after patch removal and on days 2, 3 and 4. Additional observations were performed on days 7 and 14. Well-defined up to moderate erythema and slight edema were observed in all three animals. All signs of irritation were fully reversible between day 7 and day 14 post application. Average scores for erythema were 2.7 (for 24h, 48h and 72h) in all animals. Scores for oedema were 1.0, 1.3 and 1.0 for the same time points. Based on the study results, the test material Tallow Nitrile is considered to be irritating to skin.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

23-nov-2009 to 30-nov-2009

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study has been performed according to OECD and/or EC guidelines and according to GLP principles. It concerns an in vitro study with a human skin construct model. This study model has shown not to provide reliable results for certain fatty nitrile derivatives.

Qualifier:

according to guideline

Guideline:

other: OECD Draft Proposal for a New Guideline: In Vitro Skin Irritation: Reconstructed Human Epidermis (RhE) Test Method

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EU method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test )

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 µL

POSITIVE CONTROL
- Amount(s) applied (volume or weight with unit): 10 µl
- Concentration (if solution): 5% (aq) Sodium dodecyl sulphate

Duration of treatment / exposure:

Exposure: 15 minutes
Post incubation period: 42 hours

Details on study design:

TEST SITE
- Area of exposure: human epidermis model
- % coverage: 0.38 cm2

REMOVAL OF TEST SUBSTANCE
- Washing (if done): phosphate buffered saline
- Time after start of exposure: 15 minutes

POST INCUBATION PERIOD
- 42 hours

SCORING SYSTEM:
- After a 42-hour incubation period, determination of the cytotoxic (irritancy) effect was performed. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment. Cell viability was calculated for each tissue as a percentage of the mean of the negative control tissues.

Irritation / corrosion parameter:

other: other: Percentage viability

Value:

110

Remarks on result:

other:

Remarks:

Basis: other:. Time point: 15 minutes. (migrated information)

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The positive and negative control were within the historical control data.

It is concluded that this test is valid and that Oleylnitrile is non-irritant in the in vitro skin irritation test under the experimental conditions.

Executive summary:

In vitro skin irritation test with Oleylnitrile using a human skin model.

 

This report describes the ability of Oleylnitrile to induce skin irritation on a human three dimensional epidermal model (EPISKIN Standard model (EPISKIN-SM^TM)). The possible skin irritation potential of Oleylnitrile was tested through topical application for 15 minutes.

 

The study procedures described in this report were based on the most recent OECD and EC guidelines.

 

Batch S001149 of Oleylnitrile was a clear amber liquid with a purity of 101.1 w/w%. Oleylnitrile was applied undiluted (10 µl) directly on top of the skin tissue. After a 42 hour incubation period, determination of the cytotoxic (irritancy) effect was performed. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment.

 

Skin irritation is expressed as the remaining cell viability after exposure to the test substance. The relative mean tissue viability obtained after 15 minutes treatment with Oleylnitrile compared to the negative control tissues was 110%. Since the mean relative tissue viability for Oleylnitrile was above 50% after 15 minutes treatment Oleylnitrile is considered to be non-irritant.

 

The positive control had a mean cell viability after 15 minutes exposure of 16%. The absolute mean OD₅₇₀(optical density at 570 nm) of the negative control tissues met the criteria given by the OECD draft proposal for a new guideline. The standard deviation value of the percentage viability of three tissues treated identically was less than 18%, indicating that the test system functioned properly.

In conclusion, Oleylnitrile seems to be non-irritant in the in vitro skin irritation test under the experimental conditions described in this report. However, It concerns an in vitro study with a human skin construct model. This study model has shown not to provide reliable results for certain fatty nitrile derivatives by largely underestimating corrosive/irritating properties for these compounds.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Remarks:

in vivo according to TG 405. Study used as read-across. Study performed pre-REACH.

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Acceptable study performed according to guideline and under GLP. Read-across from structural identical substance with on average a somewhat shorter aliphatic chain length.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: ENKI-Konijnenfarm, Someren, the Netherlands,
- Age at study initiation: young
- Weight at study initiation: 2500-3500g
- Housing: individually in suspended, galvanized cages, fitted with wire-mesh floor and front.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 3
- Humidity (%): at least 40
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: The test was started on February 24, 1986 and completed on February 25, 1986.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

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

Duration of treatment / exposure:

24 h

Observation period (in vivo):

24 h

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done

SCORING SYSTEM:
CORNEA
Opacity: degree of density (area most dense taken for reading) No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured 2
Nacrous area, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through the opacity 4

IRIS
Normal 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection,
any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive) 1
No reaction to light, haemorrhage, gross destruction (any or all of these) 2

CONJUNCTIVAE
Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)
Blood vessels normal 0
Some blood vessels definitely hyperaemic (injected) 1
Diffuse, crimson colour, individual vessels not easily discernible 2
Diffuse beefy red 3
Chemosis: lids and/or nictating membranes
No swelling 0
Any swelling above normal (includes nictating membranes) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4


TOOL USED TO ASSESS SCORE: No data

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1 hr

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 1 hr

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 1 hr

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

2

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1 hr

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 1 hr

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 1 hr

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 1 hr

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 1 hr

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 1 hr

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 1 hr

Score:

1

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 1 hr

Score:

1

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 1 hr

Score:

1

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

3

Reversibility:

fully reversible

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1h

Score:

0.25

Max. score:

1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritant / corrosive response data:

After one hour, the eye effects observed in all (three) rabbits consisted of slight redness of the conjunctivae with slight swelling in two animals. After 24 hours, all eye effects had cleared completely.

Rabbit No	Cornea opacity	Iris	conjunctivae
after 1 hour			redness	chemosis
3593	0	0	1	0
3601	0	0	1	0
3606	0	0	1	0
after 24 hours
3593	0	0	0	0
3601	0	0	0	0
3606	0	0	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

On the basis of the results obtained it is concluded that the undiluted test substance Arneel T is not an eye irritant and not corrosive to the eyes.

Executive summary:

According to OECD 405 and EC B.5 an eye irritation was performed in New Zealand white rabbits. 0.1 ml of the undiluted test substance was instilled in one eye of each animal and the animals were observed after 1 and 24 hours. The test substance caused slight eye effects in all (three) rabbits. After 24 hours, all eye effects had cleared completely.On the basis of the results obtained it is concluded that the undiluted test substance Arneel T is not an eye irritant and not corrosive to the eyes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Oleylnitrile was non-irritant in thein vitro skin irritation test applying a human skin construct model (EPISKIN-SM). However, this study model has shown not to provide reliable results for various fatty nitrile derivatives by largely underestimating corrosive/irritating properties for these compounds. Consequently, this study has been disregarded for the evaluation of Oleylnitrile for dermal irritation.

In a GLP compliant OECD TG 404 study, Tallow Nitrile was applied semi-occlusively for 4 hours to the shaved skin of three New Zealand White Rabbits. Well-defined up to moderate erythema and slight edema were observed in all three animals. All signs of irritation were fully reversible between day 7 and day 14 post application. Average scores for erythema were 2.7 (for 24h, 48h and 72h) in all animals. Scores for oedema were 1.0, 1.3 and 1.0 for the same time points. Based on the study results, the test material Tallownitrile is considered to be irritating to skin.

 

The eye irritation properties of Tallownitril has been evaluated according to OECD 405 and EU 84/449/EEC B.5 guidelines. This study concluded that Tallownitrile is not irritating to the eyes.

Effects on skin irritation/corrosion: irritating

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

Available information indicates that alkylnitriles are irritating to the skin, but not irritating to the eyes.

Dermal irritation:

An adequate guideline study with Tallownitrile has shown the substance to be irritating to skin.

A similar study performed with Dodecanenitrile resulted to similar results showing that also Dodecanenitrile is considered to be irritating to skin. (GHS Cat.2).

Other available dermal irritation studies with other alkylnitriles also indicated dermal irritation but the actual scoring in those studies was not sufficient to reach a Cat.2 classification.

In view of the collective data on dermal irritation on the various alkylnitriles, the weight of evidence indicates that it is considered prudent to classify the alkylnitriles collectively as irritating to skin.

 

Eye irritation:

Although irritating to the skin, none of the in vivo eye irritation studies performed on the various alkyl nitriles, including Tallownitrile, indicated a concern for eye irritation.

 

Respiratory irritation:

There is no information on possible respiratory irritation. Based on the available information on skin and eye irritation, alkylnitriles are not expected to pose a great concern in this respect. Moreover, based on the very low vapour pressure and water solubility, respiratory irritation is not likely to occur.