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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Link to relevant study record(s)

Description of key information

Due to lack of quantitative data, absorption rates of 100% are indicated for all three routes. This basically indicates that, although the absorption is probably low, there is no significant difference taking into account in the comparison of absorption via dermal and inhalation routes compared to the oral route by which the hazard evaluations are done. Especially for the absorption via dermal route this possibly represents an overly conservative approach.Available studies do not indicate a concern for bioaccumulation.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
Absorption rate - dermal (%):
Absorption rate - inhalation (%):

Additional information

Scope of the group of Polyamine (PPA):

(See also Category approach justification for polyamines)

Polyamines are substances that basically contain multiple (2 or more) 1,3-diamine propane (DP) groups linked to a fatty amine. These can be linearly linked based on two DP and fatty amine (triamine structure: alkyl dipropylene triamine) or 3 DP with a fatty amine (tetramine structure: alkyl tripropylene tetramine), or in a branched form of two DP and a fatty amine (dipropylene triamine, branched).


Production starts from the fatty amine that is reacted with equimolar amounts acrylonitrile and then hydrogenated, resulting to a diamine. Subsequent additions with acrylonitrile result to linear triamine and then tetramines. However, reactions are not complete, and consequently tetramines also contain for a large part triamines and some diamines, and the triamines can contain a considerable amount of diamines and some tetramines. Consequently, there is some overlap between these substances. Further purification can be obtained by distillation.

Branched triamines (Y-triamine) are produced from the single reaction of primary fatty amine with 2 equivalents of acrylonitrile and subsequent hydrogenation.


The common structures of the polyamines can be represented as:

 Linear triamine: R – NH – [CH2]3– NH - [CH2]3– NH2

 Triamine, branched: R – N [– [CH2]3– NH - [CH2]3– NH2]2and

  Linear tetramine: R – NH – [CH2]3– NH - [CH2]3– NH - [CH2]3– NH2

respectively, where the R is an alkyl chain ranging from 10 (Decane) to 18 (Octadecane), depending on the source of the fatty amine. For alkyl chain lengths, largely the following ranges are implied in this group:


Alkyl chain






50-75 %



> 70 %







At first glance the PPA group seems to consist of two substructures, for which the similarity needs to be ascertained in order to obtain confidence for cross reading within the whole group. Structurally, both are very similar: a linear alkyl chain and a primary amine at the end, with 2 or 3 secondary amines in between. Consequently, they share the same chemical reactivity and their physico-chemical properties are very similar from which a comparable toxicological profile can be expected.

Within a specific structure, the variability of the alkyl chain length is considered to have a possible modifying activity, which is related to modification of the physiological properties of the molecule by the increase or shortening of the apolar alkyl chain part. This is suspected to influence aspects related to bioavailability, but not aspects of chemical reactivity and route of metabolisation, aspects that influence specific mechanisms of toxicity such as sensitisation and genotoxicity. For these reasons, many of the studies can best be performed on the substance with the shortest chain length within the sub-category, as this is considered to result to the lowest NOAEL or most likely able to show specific effects. The data obtained so far indicate that the length of the alkyl chain determines more the level of toxicity then the number of propylene groups. Within the group, results from the shortest chain length can be considered a worst-case approach for the longer chain lengths.


Specifically for Oleyl dipropylene triamine, the cross-reading toC16-18, C18-unsaturated (Tallow) dipropylene triamine is most relevant. The two substances are structurally very similar. The ratio between the C16, C18 and C18:1 (C18-unsaturated) alkyl chains in the Oleyl and Tallow dipropylene triamine products show an overlap in alkyl chain of about 50%:

- Oley: C18:1 = 85.5%; C18 = 12.4 %; C16: 7,1%

- Tallow: C18:1 = 26.5%; C18 = 38.3 %; C16: 35.2%

The higher level of unsaturation in Oleyl based products has never shown to have an important effect. This is in agreement with the expectation that these structures do not undergo an important level of metabolism, and if metabolism occurs in the limited amount of absorbed material, the resulting alkyl chains will fit in the physiological pool of these natural alkyl chains. Further, the relatively somewhat sorter chain lengths of C16 would make it slightly more bioavailable, in agreement to the notion that shorter alkyl chains represent a more conservative evaluation.

Consequently, the data on Tallow (C16-18, C18-unsaturated-alkyl) dipropylene triamine can be used for the read-across to Oleyl dipropylene triamine


Toxicological profile:

The acute oral toxicity of Olyl dipropylene triamine indicates a LD50 between 300 and 2000 mg/kgbw with a LD50 cut-off of 500 mg/kgbw. Other polyamines show comparable results where those with on average shorter alkyl chains show a somewhat higher toxicity compared to those with longer alkyl chain lengths. The number of propylene groups (dipropylenetriamine or tripropylenetetramine) does not seem to be of influence.

Potential exposure to PPA is mainly dermal. As the active substance is corrosive to the skin, dermal irritation/corrosion is a major concern when dealing with PPA formulations. Effects following dermal exposures will be characterized by local corrosive effects that are related to duration, quantity and concentration of the substance, rather than by systemic toxicity due to dermal uptake.

As tallow triporpylene tetramine and oleyl tripropylene tetramine represent the substances with the highest number of propylene groups and longest alkyl chain-length in this group, 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, and further in vivo testing would not be ethical. Also following oral dosing ulcerations in gastro-intestinal system are observed at the higher dose levels indicating corrosive properties for these compounds.

Dermal corrosion of polyamines is a property that is common in all fatty acid structures with free primary amines: The primary fatty amines are generally corrosive, and the branched alkyl dipropylene triamines are even very corrosive in in vivo studies in rabbits.

As the substance is corrosive to skin, there is no need for in vivo skin sensitisation study. However, the molecular structure of the polyamines does not contain toxicophores indicating a concern for sensitization. Polyamines show further low dermal penetration, and no reactivity and protein binding (processes needed for haptenisation). Data available from sensitisation studies on structurally related branched triamine (Dodecyl dipropylene triamine, branched) and primary amines, do in general not indicate a concern for sensitisation.


For the evaluation of repeated dose toxicity of Oleyl dipropylene triamine, cross-reading is done from a 90-day oral toxicity study in rats (OECD 408) with Tallow dipropylene triamine. The NOAEL was determined at 2.5 mg/kg bw/day, based on effects observed at 10 mg/kg bw/day. At this level changes in blood were confined to a higher inorganic phosphate level, and marginally higher neutrophil counts. Also at 10 mg/kg bw/day, adverse histopathological findings were observed in the jejunum/ileum (minimally to slight foamy macrophages in lamina propria), mesenteric lymph nodes (general minimal to moderate foamy macrophages, accompanied by incidental cases of granulomas with central necrosis, lymphoid hyperplasia, sinus ectasia), liver (granulomatous lesion with central necrosis in 2 males) and bone marrow (minimal myeloid hyperplasia in 7/40 animals).


Supportive information comes from read-across to Coco dipropylenetriamine, a structural identical substance with on average a shorter alkyl chain length. A combined repeated dose/reproduction toxicity screening (OECD 422) study on Coco dipropylenetriamine indicated LOAEL of 10 mg/kgbw/day based on foamy macrophage infiltration in the ileum and jejunum and foamy macrophage foci found in the mesenteric lymph nodes observed at this dose level. This study further showed severe toxicity at 100 mg/kg, causing the early termination of this dose group on day 9 of the study. Ulceration of the stomach was considered to be the most likely cause of death/moribundity for these animals.

A similar study with Tallow tripropylenetetramine showed similar toxicity but at levels that were 3 times higher.


The most significant treatment-related changes in all studies performed on polyamines are effects on the small intestine and mesenteric lymph nodes. A relatively strong inflammatory reaction is also observed at high dose levels. These effects in the gastro-intestinal tract have consistently been observed with these polyamines, and are considered local effects related to the corrosive nature of the substances.

A mode of action has not been established but it is possible to suspect the known corrosivity to be at least partially involved. It is indicative that the observed effects are local and they are by some interpreted as phospholipidosis, something commonly observed following treatment with cationic amphiphilic material, including marketed pharmaceuticals, and considered to be non-adverse. When taking into consideration the relatively strong corrosive effects of this substance, and for substances belonging to the same group of chemicals, and the route of administration, it cannot be excluded that the overall toxicity reflects a point-of-first-contact effect. In that respect, considering that macrophages in the mesenteric lymph nodes are a local, porte d’entrée related effect due to the route of application, and not a systemic effect per se, the level of 2.5 mg/kg bw/day could also be argued to represent a NOAEL for local effects, and that the NOAEL for systemic effects is higher.


Available data therefore results to classification for STOT-RE category 2, with phrase H373: May cause damage to organs through prolonged or repeated exposure (based on mortality). Affected organs: Gastro intestinal system. These effects are specific for the oral route.


No reproductive toxicity was observed at any dose level in an OECD 422 study with Coco dipropylene triamine. A reproduction/developmental NOAEL of 30 mg/kg/day was determined, based on termination of the 100 mg/kg dose group between study days 6-9 due to severe toxicity and mortality.

No adverse effects on reproductive organs were identified in the 90 day study in rats Tallow dipropylene triamine. Additionally, no treatment-related changes in the estrous cycle length or sperm were apparent.

A prenatal developmental toxicity study resulted to a maternal NOAEL for Tallow dipropylene triamine of 30 mg/kg. Based on the observation of pale adrenals, and signs of retarded skeletal ossification seen at 60 and 120 mg/kg, a developmental NOAEL of 30 mg/kg was selected. This study also includes endpoints that are relevant to assessing an effect on fertility. No effects on pre/post implantation rate, late/early resorptions, corpora lutea or number of live fetuses were seen in this study.

Other available studies on comparable polyamines include an OECD 422 study on Tallow tripropylenetetramine and a full two-generation study and developmental toxicity studies in rat and rabbit on a structurally related dodecane dipropylene branched triamine have also shown no indication of concern for reproductive or developmental toxicity.

In addition, there is no consumer exposure to Oleyl dipropylene triamine, and manufacture and use are highly controlled, limiting the possibility of exposures.


Oleyl dipropylenetriamine is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay, and based on read-across from Tallow dipropylene triamine, is not clastogenic in human lymphocytes, and not mutagenic in the TK mutation test with L5178Y mouse lymphoma cells. Also studies on other polyamines indicate no concerns for genotoxicity. Furthermore, polyamines do not react with DNA or react to protein.


Toxicokinetics, metabolism and distribution:

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 cytoplasmic membrane, leading to lyses of the cell content and consequently the death of the cell.

The very high water solubility can be explained by the fact that the terminal amine groups are completely protonated under environmental conditions. The water solubility of polyamines is strongly influenced by pH.

The polyamines are all corrosive to skin. This is probably related to their structure causing disruption of cytoplasmic membranes. Toxicity following dermal exposure is characterised by local tissue damage, rather than the result of percutaneously absorbed material. A dermal absorption study [IRI report No.: 204648, 2003, The In vitro percutaneous absorption of [14C]-N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine through human skin] performed on a structurally related dodecyl branched dipropylene triamine for 24 hours, resulted in a complete 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. Further toxicokinetic studies with substance indicated that oral absorption is about 2-5%, considerably higher than the indicated dermal absorption, and that there is no significant entero-hepatic circulation.

Due to lack of quantitative data, absorption rates of 100% are indicated for all three routes. This basically indicates that, although the absorption is probably low, there is no significant difference taking into account in the comparison of absorption via dermal and inhalation routes compared to the oral route by which the hazard evaluations are done. Especially for the dermal route this approach therefore represents a worst case situation. Available studies do not indicate a concern for bioaccumulation.


Physical-chemical properties of tallow dipropylenetriamine indicate a low likelihood for exposure via inhalation, being a viscus liquid at room temperature with a mp 17 °C, a boiling point > 300 °C and low vapour pressure (4.7 x 10-5 Pa at 20°C for the coco dipropylene triamine, with the shortest average alkyl chain length representing the highest vapour pressure for the group of polyamines).


These polyamine substances are almost completely protonated under ambient conditions and will therefore not easily transported over biological membranes. Due to the cationic surface-active PPA adsorb strongly onto organic material which could be a limiting factor for intestinal uptake.