Registration Dossier

Administrative data

Description of key information

Available information indicates that polyamines are corrosive to skin.

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)

Additional information

(Full justification for cross-reading can be found in the document attached to Chapter 13 of this IUCLID: "Category approach justification for polyamine acetates 29 03

2012.pdf".)

All the comparable non-acetate polyamines are corrosive to the skin when tested in vivo to the skin. The in vitro skin corrosion study using reconstructed human epithelia has been proven to be an unsuitable test method for these substances, as it is not able to demonstrate the corrosive properties as are seen in in vivo rabbit studies. Although the acetate salt could have a possible influence the corrosive properties, the only limited effects on in vitro skin constructs indicate that this is not an important mechanism for the corrosive properties of these substances. Therefore, it is prudent to classify these substances as corrosive as well, rather than perform in vivo skin corrosion studies with these substances.

Overview available data on dermal corrosion for polyamines::

 

dipropylene triamine

Tripropylene tetramine

dipropylene triamine (branched)

Possitive control

Based on FA:

Coco

Tallow

Oleyl

Tallow

Oleyl

C12

Tallow

Skin corrosion –

Non-Cor.

Non-Cor.

Non-Cor.

not pos.

Non-Cor.

Corrosive

-

Corrosive

viabilityin vitro:3 min

58%

98%

95%

-95%

91%

43%

8-9%

1 hour

22%

96%

89%

-

85%

42%

6-9%

Skin corrosion –in vivo

-

-

-

Corr.1C

Corr.1C

Very Corr. (3 min)

Very Corr. (3 min)

 

(In vitro dermal corrosion: Results considered corrosive when viability is below 50% following 3 minutes, or below 15% following 1 hour exposure)

 

For the polyamines, the substance which was considered likely to have the least corrosive properties was selected for an in vivo confirmatory study. As experience (eg. from primary fatty amines, but also indicated by comparing cytotoxicity scores from genotoxicity studies with the various polyamines) indicate that corrosivity diminishes with increasing alkyl chain length, the substance Oleyl tripropylene tetraamine (C18dipropylene tetramine) was selected, as this has the largest alkyl chain.

Oleyl tripropylene tetraamine (C18dipropylene tetraamine)was evaluated in an in vivo dermal irritation/corrosion study in rabbits. Exposure of the skin of one animal for 4 hours with tripropylene tetraamine resulted to evidence of full thickness destruction of the skin, and hence no further animals were tested. It was concluded that Oleyl tripropylene tetraamine (C18dipropylene tetraamine) should be classified as skin corrosive (Category 1C).

Also available older in vivo studies on Tallow tripropylene tetraamine (C12-18tripropylene tetraamine) results show corrosive properties to the skin.

In the interest of animal welfare and to minimize any testing likely to produce severe responses in animals, it was decided not to perform further in vivo corrosion studies in rabbits to confirm the corrosive properties of (Z)-N-(3-aminopropyl)-N'-9-octadecenylpropane-

1,3-diamine acetate.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

As Oleyl tripropylene tetraamine (C18dipropylene tetraamine) represent the substances with the highest number of propylene groups and longest alkyl chain-length within the group of polyamines, they are expected within the group of polyamines to show the lowest corrosive properties. As in vivo skin corrosion studies indicate that these substances are corrosive, it is expected that all other substances in this group are corrosive to skin as well. The in vitro skin corrosion study using reconstructed human epithelia has been proven to be an unsuitable test method for these substances, as it is not able to demonstrate the corrosive properties as are seen in in vivo rabbit studies. Although the acetate salt could have a possible influence on the corrosive properties, the only limited effects on in vitro skin constructs indicate that this is not an important mechanism for the corrosive properties of these substances. Therefore, it is prudent to classify these substances as corrosive as well, rather than perform in vivo skin corrosion studies with these substances. Consequently, it is concluded that (Z)-N-(3-aminopropyl)-N'-9-octadecenylpropane-1,3-diamine acetate should also be classified as corrosive (Cat.1C) under GHS and Corrosive, R34 for DSD.

In the interest of animal welfare and to minimize any testing likely to produce severe responses in animals, it was decided not to perform further in vivo corrosion studies in rabbits on to confirm their corrosive properties. Corrosive to eyes is assumed for substances for which dermal corrosion has been established.