Fatty acids, C18-unsatd., reaction products with diethylenetriamine, acetates

Endpoint summary

Description of key information

An acute dermal irritation study was conducted on the test item.
Acute dermal irritation: A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced moderate to severe erythema and moderate to severe oedema. Glossy skin and/or reduced regrowth of fur were noted at all treated skin sites at the 14-day observation.
An acute in-vivo eye irritation study showed corneal opacity and conjunctival irritation in all eyes which persisted to Day 21. Iritis cleared in two eyes by Day 7 and in one eye by Day 21. 

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

Introduction:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 17 July 1992) and Method B4 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

Method and results:

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced moderate to severe erythema and moderate to severe oedema.

Other skin reactions noted were light brown discolouration of the epidermis, blanching of the skin, haemorrhage of the dermal capillaries, loss of skin elasticity and flexibility and scabbing. Glossy skin and/or reduced regrowth of fur were noted at all treated skin sites at the 14-day observation.

3 -minute and 1 -hour semi-occluded applications of the test material to the intact skin of one rabbit produced no corrosive effects.

 

Conclusion:

The test material, PR 4659 SALT, produced a primary irritation index of 6.3 and was classified as a severe irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material produced positive criteria in 3/3 rabbits according to the EU labelling regulations and was classified as irritant to rabbit skin.

Eye Damage/Irritation:

Initially an in vitro Bovine Corneal Opacity and Permeability Test (BCOP - OECD Guideline No.437) was conducted on the substance to determine the potential for ocular irritation.

OECD Guideline No.437 defines a substance which produces an In Vitro score of ≥55.1 as a corrosive or severe irritant. An In Vitro score of ≤55.1 is not a corrosive or severe irritant and additional testing should be conducted for classification and labelling purposes.

The test substance produced an In Vitro scored of 5.73. Therefore, according to OECD Guideline No.437 the test substance is not a corrosive or severe irritant.

Based on this result, a subsequent in vivo study was conducted.

In-vivo Eye Irritation/Corrosion:

Objective:

To determine the irritant or corrosive effects of the test item, Fatty acids, C18 unsaturated, reaction products with diethylenetriamine, acetate salts. The study was designed to comply with the standards set forth in OECD Guidelines For Testing Chemicals, Number 405, adopted April 24, 2002, US EPA OPPTS Series 870.2400, fnal guideline, August 1998, and method B5 Acute Toxicity (Eye Irritation) of Commision Regulation (EC) No. 440/2008.

Method:

Three healthy New Zealand White rabbits (females), free from evidence of ocular irritation and corneal abnormalities, were dosed with Fatty acids, C18 unsaturated, reaction products with diethylenetriamine, acetate salts. The test article (0.1 ml) was placed into the conjunctival sac of one eye of each rabbit. The eyes were examined pretest and scored by the Draize technique at 1, 24, 48 and 72 hours and again on Days 7, 14 and 21. The control eyes were observed at the same time periods. Sodium fluorescein dye procedures were used at the 24 -hour observation interval up to Day 21. Observations for toxicity and pharmacological effects were recorded at each ocular observation period and mortality observations were performed daily. The mean total scores were calculated by adding the total score for each time period and dividing by the number of animals. The degree of irritation was determined according to Kay & Calandra and classified according to the Official Journal of the European Union, on Classification, Labeling and Packaging of substances and mixtures. Body weights were recorded pretest and at termination.

Summary:

Corneal opacity and conjunctival irritation, noted in three out of three eyes, persisted to Day 21. Iritis, noted in three out of three eyes, cleared in two eyes by Day 7 and in one eye by Day 21.

The control eyes appeared normal at all observation periods.

All animals gained weight.

Conclusions:

According to OECD and OPPTS the test item is corrosive.

According to Kay & Calandra, the test item is severely irritating.

According to EU CLP classification, the test item should be classified as, Category 1 - Irreversible effects on the eye.

Respiratory irritation:

Based on the irritant properties of the substance, it can be anticipated that respiratory irritation may occur if significant inhalation of the substance occured.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

The results from the dermal irritation study were evaluated according to the Classification, Labelling and Packaging Regulation (CLP).

The substance meets the criteria for classification as a Category 2 skin irritant (H315: Cause skin irritation). All three animals tested produced postive responses for irritation (mean values of ≥2.3 - ≤4 for erythema and oedema were obtained for each animal) according to the criteria for Category 2 irritants.

Effects (glossy skin and/or reduced regrowth of fur) also persisted to the end of the 14 day observation period.

The results from the in-vivo eye irritation/corrosin study were evaluated according to the Classification, Labelling and Packaging Regulation.

According to EU CLP classification, the test item should be classified as, Category 1 - Irreversible effects on the eye, as all three animals tested showed corneal opacity and conjunctival irritation that was not reversible or fully reversible and persisted until the day 21 observation.