Registration Dossier

Administrative data

Description of key information

Fatty acids, C18-unsatd., dimers, polymers with oleic acid and triethylenetetramine was not corrosive in an in vitro study using the EpiDerm™ skin model. Based on available evidence from other polyamidamine substances, the substance is considered to have the potential to cause skin irritation. Based on read-across to an in vivo eye irritation study using Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine, the substance is considered to be highly irritating to the eyes.

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/corrosion

The skin corrosion potential of Fatty acids, C18-unsatd., dimers, polymers with oleic acid and triethylenetetramine was investigated in an in vitro EpiDerm™ study, conducted in accordance with GLP, OECD Test Guideline 431 and EU Method B.40 (Dreher, 2012a). Duplicate EpiDermTMinserts were treated with the test article, distilled water (negative control) and 8N potassium hydroxide (positive control) for 3 minutes and 1 hour. At the end of the treatment period, the tissues were washed with phosphate buffered saline (PBS) and cell viability was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The skin corrosivity potential was assessed based on the remaining cell viability obtained after test material treatment at the two treatment times. Skin viability after three minutes or one hour of exposure to the test article was 72% and 52%, respectively. Skin viability after a three minute or one hour exposure to the positive control article was 24% and 12%, respectively, demonstrating appropriate performance of the assay. The test article was not corrosive to skin in the in vitro skin model: EpiDermTM.

The skin irritation potential of Fatty acids, C18-unsatd., dimers, polymers with oleic acid and triethylenetetramine was investigated in an in vitro EpiDerm™ study, conducted in accordance with GLP, OECD Test Guideline 439 and EU Method B.46 (Dreher, 2012b). In te study, EpiDerm™ SIT (EPI-200) inserts were treated with test article, negative control (phosphate buffered saline (PBS)) and positive control (5% w/v sodium dodecyl sulphate (SDS)) for 60 minutes. At the end of the treatment period, the tissues were washed with PBS and cell viability was assessed using the MTT assay. The skin irritation potential was assessed according to the remaining cell viability obtained after test article treatment. The group mean viabilities were: 69.5% for the test article, 100% for the negative control and 12.5 % for the positive control. Under the conditions of this study, the test article was not irritating to skin in the in vitro skin model EpiDerm™ SIT (EPI-200).

Skin irritancy effects have been reported in similar studies using the in vitro skin model: EpiDerm™, conducted in accordance with GLP and OECD Test Guideline 439 using the polyamidoamine substances: Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine and Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and tetraethylenepentamine respectively. (Dreher 2012c and d). In a study using Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine, the group mean viabilities were: 5.6% for the test article, 100% for the negative control and 10.7 % for the positive control and the test substance was identified as a skin irritant. Similarly, in a study using Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and tetraethylenepentamine , the group mean viabilities were: 7.5% for the test article, 100% for the negative control and 5.1 % for the positive control and the substance was also identified as a skin irritant. On the basis of these findings, polyamidoamine substances are considered to have the potential to cause skin irritation and should be classified accordingly.

Eye irritation

The potential for Fatty acids, C18-unsatd., dimers, polymers with oleic acid and triethylenetetramine to cause corrosion or severe irritation to the eyes was evaluated in excised bovine corneas using the bovine corneal opacity and permeability (BCOP) assay, according to OECD Test Guideline 437 and GLP. A volume of 750 µL test material was applied to three separate corneas, followed by a 10 minute incubation period at 32°C ± 1°C. Following incubation each cornea was washed with media containing phenol red, followed by media without phenol red. The opacities were then measured and the anterior chamber was emptied. To evaluate permeability, sodium fluorescein solution was added into the anterior chamber and the corneas were incubated in the vertical position for 1.5 hours ± 5 minutes. Following incubation the media in the posterior chamber was removed and three 350 µL aliquots of the media (per cornea) were analysed for optical density at 490 nm (OD490). The opacity and permeability measurements were used to calculate an In Vitro Irritancy Score (IVIS). The calculated IVIS for the test material was 37.63. As this was below the trigger value of 55.1, the test material was not considered to be corrosive or severely irritating to the eyes in vitro.

To further characterise the eye irritation potential of the substance, read-across to an in vivo eye irritation study using the polyamidoamine substance: Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine is considered appropriate based on structural and chemical considerations. Read-across is scientifically justified and also enables the REACH requirements to be adequately addressed, while avoiding unnecessary animal testing in accordance with EU Directive 86/609/EEC. The potential for Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine to cause eye irritation in vivo was investigated in an eye irritation study in the rabbit conducted according to OECD Test Guideline 405 and GLP (Dreher, 2013c). In the study, undiluted test article (0.1 mL) was instilled into one conjunctival sac of a New Zealand White rabbit on Day 1. Occular reactions were assessed for 21 days after treatment. Instillation of the test article produced easily discernible translucent areas of corneal opacity, iridial inflammation and severe conjuctival irritation. The effects on the cornea, iris and conjunctiva did not reverse within the 21 day observation period. The substance was therefore found to to be corrosive to the eye in rabbits. On this basis, Fatty acids, C18-unsatd., dimers, polymers with oleic acid and triethylenetetramine is also considered to be an eye irritant.


Justification for selection of skin irritation / corrosion endpoint:
Weight of evidence approach: Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine and Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and tetraethylenepentamine show irritation effects in skin irritation studies in vitro. On this basis the polyamidoamine substances are considered to have the potential to cause skin irritation.

Justification for selection of eye irritation endpoint:
Based on existing datasets and structural and chemical considerations, read-across from Fatty acids, C18-unsatd., dimers, polymers with oleic acid and triethylenetetramine to an in vivo eye irritation study using Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine is appropriate to meet the REACH Annex VII-IX data requirements. Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine was found to cause irreversible effects on the eye in an eye irritation study in the rabbit conducted according to OECD Test Guideline 405.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Skin irritation/corrosion

Fatty acids, C18-unsatd., dimers, polymers with oleic acid and triethylenetetramine was not corrosive to the skin in anin vitroskin study using the EpiDerm™ model. While the substance was not identified as a skin irritant in an in vitro study using the EpiDerm™ SIT (EPI-200) model, evidence from other similar studies conducted using polyaminoamide substances indicate that these substances have the potential to cause skin irritation. On this basis, it is considered appropriate to classify the substance as: Category 2, H315 “Causes skin irritation” according to Regulation (EC) No 1272/2008, and as Xi, R38 “Irritating to skin” according to Directive 67/548/EEC.

Eye irritation

Based on read-across to an in vivo eye irritation study (OECD Test Guideline 405) conducted using Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine, the substance: Fatty acids, C18-unsatd., dimers, polymers with oleic acid and triethylenetetramine is considered to be irritating to the eyes. On this basis, it is considered appropriate to classify the substance as Category 1, H318 “Causes serious eye damage” according to Regulation (EC) No 1272/2008 and Xi, R41 “Risk of serious damage to eyes” according to Directive 67/548/EEC.