Amides, C8-18 (even numbered) and C18 (unsaturated) alkyl, N-[3-(dimethylamino)propyl]

Endpoint summary

Description of key information

Skin:
Category 1 (Corrosive), in vitro skin corrosion test, OECD Guideline 431; GLP, RL1
Eye:
Category 1 (irreversible effects on the eye), OECD Guideline 405, GLP, RL2; read-across: Amides, C8-18 even numbered, N-[3-(dimethylamino)propyl]

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

For the assessment of the skin and eye irritating potential of Amides, C8-18, C18 unsatd, N-[3-(dimethylamino)propyl] the following studies are available:

- in vivo skin irritation study in rabbits similar to OECD Guideline 404 with the target substance Amides, C8-18, C18 unsatd, N-[3-(dimethylamino)propyl] (no data on GLP, RL3 due to insufficient documentation)

- in vitro skin corrosion test according to OECD Guideline 431 (GLP, RL1)

- in vivo eye irritation test in rabbits similar to OECD Guideline 405 with the target substance Amides, C8-18, C18 unsatd, N-[3-(dimethylamino)propyl] (no data on GLP, RL3 due to insufficient documentation)

- in vivo eye irritation test in rabbits according to OECD Guideline 405 with the closely related source substance Amides, C8-18, C18 unsatd, N-[3-(dimethylamino)propyl] (GLP, RL2)

A justification for read-across is given in IUCLID section 13.

 

Skin irritation

In the In Vitro Skin Corrosion: Human Skin Model Test according to OECD Guideline 431 (adopted 13 April 2004) and EU Method B.40: "Skin corrosion" (8 June 2000), the topical application of Amides, C8-18, C18 unsatd, N-[3-(dimethylamino)propyl] on the skin tissue for a 3 minutes and 1 hour exposure was performed, followed by immediate determination of the cytotoxic (corrosive) effect. Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) at the end of the treatment.

Skin corrosion is expressed as the remaining cell viability after exposure to the test substance. The relative mean tissue viability obtained after 3 minutes and 1 hour treatment with the test item compared to the negative control tissues was both 45%. Since the mean relative tissue viability for the test item was below 50% after 3 minutes treatment with the test item is considered to be corrosive.

The positive control had mean relative tissue viability after 3 minutes exposure of less than 30%. The negative control had a mean OD540 (optical density at 540 nm) higher than 0.8. The maximum inter tissue variability in viability between two tissues treated identically was less than 30% and the maximum difference in percentage between the mean viability of two tissues and one of the two tissues was less than 15%, indicating that the test system functioned properly.

It is concluded that this test is valid and that the test substance is corrosive in the in vitro skin corrosion test under the experimental conditions described.

 

In a supporting study the substance Amides, C8-18, C18 unsatd, N-[3-(dimethylamino)propyl] was tested for primary skin irritation similar to OECD guideline 404 with 5 rabbits. The contact time of the test item was reduced to 30 min. The following symptoms were observed after application:

Intense erythema, crust development, necrotic skin alteration, moderate edema, healing with scars.

Based on this results the undiluted product has to be classified as corrosive.

 

Eye irritation

In a primary eye irritation study according to OECD Guideline 405 and EU Method B.5, 0.1 g of Amides, C8-18 even numbered, N-[3-(dimethylamino)propyl] was instilled into the conjunctival sac of six White New Zealand rabbits. The eyes of three animals were rinsed 4 seconds after substance application. Animals then were observed for 72 hours. Irritation was scored by the method of Draize as stipulated by OECD Guideline 405.

In unrinsed eyes severe eye reactions were seen at the 60 minutes and the 24 hour scoring:

-- Cornea scores of 0 or 1

-- Iris scores of 1 or 2

-- Conjunctivae redness scores of 2 or 3

-- Conjunctivae chemosis scores of 3 or 4.

Due to the severe reactions these animals were killed after the 24 hour scoring.

In eyes rinsed 4 seconds p.a. the test substance induced

-- Cornea scores of 0

-- Iris scores of 0 or 1

-- Conjunctivae redness scores of 2 or 3

-- Conjunctivae chemosis scores of 2 or 3

The observation time did not extend beyond 72 hours, even though severe eye responses were still present at these times, therefore, the reversibility of the eye effects cannot be evaluated.

The test substance was judged to be irritating to the eye based on the effects of the rinsed eye (washed out 4 secondes p.a.) within 72 hours.

Whereas an evaluation of the animals with unwashed eyes was not possible because they were killed 24 h p.a. due to the severe eye reactions.

 

In a supporting study the eye irritation potential of Amides, C8-18, C18 unsatd, N-[3-(dimethylamino)propyl] was tested with 4 male white rabbits. Therefore 0.1 mL 1% test substance diluted in dest. water was applied to the eye without later washout. Reaction were recorded for 48 h. The following symptomes were observed:

No alteration on cornea and iris, moderate conjunctivia reaction. 1 and 6 hours after application 45 and 40% of the maximal possible reaction, respectively. No reaction after 48 h.

In result a solution of 1% test item in dest. water has to rated as irritant to eye.

Justification for selection of skin irritation / corrosion endpoint:
guideline study, GLP

Justification for selection of eye irritation endpoint:
read-across from guideline study, GLP

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

Based on the available data Amides, C8-18, C18 unsatd, N-[3-(dimethylamino)propyl] has to be classified as corrosive to the skin (Category 1) and causing irreversible effects on the eye (Category 1) and labelled with H314 (Causes severe skin burns and eye damage) according to regulation (EC) 1272/2008.