N-(3-ammoniopropyl)-N-[C16-C18, C18 unsatured]alkylpropane-1,3-diaminium triacetate

Endpoint summary

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 anin vivoconfirmatory study. As experience (e.g. 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 (C₁₈tripropylene tetramine, CAS# 67228-83-5) was selected, as this has the largest alkyl chain.Oleyl tripropylene tetraamine(C₁₈tripropylene tetramine, CAS# 67228-83-5)was evaluated in anin vivodermal irritation/corrosion study in rabbits. Exposure of the skin of one animal for 4 hours with tripropylenetetraamine resulted to evidence of full thickness destruction of the skin, and hence no further animals were tested. It was concluded that Oleyl tripropylene tetraamine(C₁₈tripropylene tetramine, CAS# 67228-83-5)should be classified as skin corrosive (Category 1C).

Also available olderin vivostudies on Tallow tripropylene tetraamine (C_12-18tripropylene tetramine) results show corrosive properties to the skin. A study was performed to assess the irritancy potential of Tallow dipropylene triamine, branched (C_12-18dipropylene triamine, branched; the amine of the registered substance) to the skin of the New Zealand White rabbit. The method essentially followed OECD Test Guideline 404. Following a preliminary test, a single 3-min occluded application of the test material to the intact skin of three rabbits produced slight erythema immediately after patch removal. Necrotic lesions developed in all 3 animals after 3 days.

In the interest of animal welfare and to minimize any testing likely to produce severe responses in animals, it was decided not to perform furtherin vivocorrosion studies in rabbits to confirm the corrosive properties of the to be registeredN-(3-aminopropyl)-NN-(C16-18 evennumbered, 18 unsaturated)-alkylpropane-1,3-diamine acetate.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Justification for classification or non-classification

An in vivo dermal corrosion study with Tallow dipropylene triamine, branched resulted after three days to corrosion of the skin following 3 minutes exposure.

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 N-(3-aminopropyl)-NN-(C16-18 evennumbered, 18 unsaturated)-alkylpropane-1,3-diamine acetate should be classified as corrosive Cat.1B under GHS and Corrosive, R35 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 to confirm their corrosive properties. Corrosive to eyes is assumed for substances for which dermal corrosion has been established