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Description of key information

The LD50 of 766 mg/kg bw was established in acute oral toxicity study with rats. As the substance is corrosive to skin, the performance of studies by other routes of exposure is not indicated in accordance with Column 2 of REACH Annex VII.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
766 mg/kg bw

Additional information

Oral

Branched triamine C16 -18 (Y-tallow)was tested for acute oral toxicity by AcuteUp-and-Down Procedure (OECD 425) with some additional investigations. Following an initialrange finding study in which rats (2/sex dose) were dosed at 2000, 200 or 25 mg/kg bw, an up-and-down procedure was followed dosing 1 animal at a time to determine a more exact LD50. Then, based on the LD50 findings, 10 animals (5/sex) were given a dose of 80 mg/kg bw (maximum non-lethal dose, as at 320 and 200 mg 1 or 2 of the 10 dosed animals died) and haematological parameters were measured 2 and 7 days after dosing. The LD50 in rats is between 200 and 2000 mg/kg bw, 895 (CI 657-1219) mg/kg bw for males and 637 (CI 467-869) mg/kg bw for females, and766 mg/kg bw for males and females combined.No effects on haematology were observed after a single oral dose of 80 mg/kg bw.

 

Comparable othertriamines (alkyl dipropylenetriamine) and tetramines (alkyl tripropylenetatramine) show similar results, where those with on average shorter alkyl chains show a somewhat higher toxicity compared to those with longer alkyl chain lengths:

 

LD50 in mg/kg bw

Acute toxicity Triamines:

Coco

50-300

Cat.3; cut off 200

Tallow

300-2000

Cat.4; cut of 500

Oleyl

300-2000

Cat.4; cut of 500

Y12

261

Cat.3

YTallow

766

Cat.4

Acute toxicity Tetramines:

Tallow

300-2000

Cat.4; cut of 500

Oleyl

300-2000

Cat.4; cut of 1000

 

In conclusion, there is little effect of the actual number propylene amine groups between linear triamine, branched triamine or linear tetramine. With increasing length of the alkyl chain, the acute toxicity decreases.

 

Dermal

Acute dermal toxicity: Polyamines are corrosive to the skin. Testing for acute dermal toxicity is therefore not justified. Toxicity following dermal exposure is characterised by local tissue damage, rather than the result of percutaneously absorbed material.

The mode of action of for polyamines follows from its structure, consisting of an apolar fatty acid chain and a polar end of a primary amine linked to a secondary amine. The structure can disrupt the cytoplasmatic membrane, leading to lyses of the cell contentand consequently the death of the cell.

The polyamines are completely protonated under environmental conditions which causes them to strongly adsorb to organic matter. This all leads to a low dermal absorption as is shown by a dermal absorption study performed on astructurally related branched triamine N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine (branched triamine C12)for 24 hours, resulted in a dermal penetration of less than 0.01% whereas 0.92% of the applied dose did pass the stratum corneum but remained further fixed in the skin. For thebranched triamine C16 -18,a similar or even lower (because of higher alkyl chain lengths) dermal penetration can be expected.

 

Inhalation:

Acute inhalation toxicity: Physical-chemical properties of polyamines indicate a low likelihood for exposure via inhalation having a boiling point > 300 °C and a low vapour pressure (1.4 x 10-4 Pa at 25°C for thebranched triamine C12, with the shortest average alkyl chain length representing the highest vapour pressure for the group of branched polyamines).

Furthermore, the substance is classified as severe corrosive and no acute toxicity testing should normally be conducted.

Justification for classification or non-classification

According to the criteria in Directive 67/548/EEC, based on the LD50 of 766 mg/kg bw,Branched triamine C16 -18needs to be classified as Xn; R22 (Harmful if swallowed). According to EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 it needs to be classified as Category IV, H301 (Harmful if swallowed).

 

Acute dermal testing with these very corrosive materials is not justified. As a consequence no classification can be made for acute dermal toxicity. Effects will be characterised by local tissue damage. Systemic uptake via skin is very limited and absorption studies indicated that dermal absorption is at least a factor three lower than oral absorption. The very corrosive effects on skin in combination with the relatively low acute oral toxicity, make systemic effects from acute dermal exposures are unlikely.

 

Also for acute inhalation toxicity information for classification is lacking, and is testing not justified. Due to very low vapour pressure is the likelihood of exposure low. Condidering the relatively low systemic toxicity after acute oral dosing, suggest that inhalation of this very corrosive substance at levels at levels causing systemic effects is very unlikely.

 

Polyamines do not contain containing aliphatic, alicyclic and aromatic hydrocarbons and so do not indicate an immediate concern for aspiration hazard.

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