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Description of key information

Due to lack of quantitative data, absorption rates of 100% are indicated for all three routes. Available studies do not indicate a concern for bioaccumulation.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
Absorption rate - dermal (%):
Absorption rate - inhalation (%):

Additional information

Category Amidoamines/imidazolines (AAI):

Amidoamine/imidazolines are made from fatty acid and polyethyleneamines.

The manufacturing process is a one-step process with formation of amide and imidazoline structures. To promote imidazoline formation from the amide, the reaction mixture is heated to temperatures above 180ºC. The resulting product therefore is a mixture of the amide structure of the fatty acid and the polyethyleneamine and its imidazoline. Also is possible that two fatty acid molecules bind at each end of the polyethyleneamine resulting todi-substituted amine or imidazoline. This can be influenced by the ratio of fatty acids (FA) and ethyleneamines (EA) in the reaction.

The final product is a mixture of these substances, containing amine-, amide-, and imidazoline functional groups.


The members of this category can be characterised by their starting materials: the hydrophobic part from fatty acids and the hydrophilic part from the polyethyleneamines:


- Fatty acids (FA):

The difference in alkyl chain length distribution is limited among the members of this category. The sources are indicated as tall oil, vegetable oil, rape oil, C12-18 and C18-unsaturated fatty acids and tallow. All of these consist of predominantly C16 and C18 alkyl chain lengths.

The majority is derived from tall oil, basically consisting of C18 and some C16. Some of the substances refer to another source in their name as vegetable oil or tallow, but even then the actual composition could show the same chain length distribution as tall oil.

Upon harmonization of the use of names and CAS numbers within this category this has lead to some renaming and use of different CAS numbers compared to what was reported in earlier study reports for those substances.


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 with 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 metabolism, aspects that influence specific mechanisms of toxicity such as sensitisation and genotoxicity and are more related to the hydrophilic part. As the differences in chain lengths are only very minimal as all substances basically contain C16 and C18 alkyl chains, it seems justified from a toxicological point of view to consider the fatty acid part as similar for all AAI substances.


- Polyethyleneamines (EA):

The chain length of the polyethyleneamines used for the production of the various Amidoamines/imidazolines in this category can vary. In order of increasing EA length, ranging from DETA (diethylenetriamine), TETA (triethylenetetramine), TEPA (tetraethylenepentamine), PEHA (pentaethylenehexamine) and higher, generally denoted as polyethyleneamines (PolyEA). Although some products are derived from the use of basically one specific ethyleneamine, often a mixture of ethyleneamines of different lengths are used.

Upon the binding of the fatty acids with the amines of the EA, this results to a mixture of these substances, containing amine-, amide-, and imidazoline functional groups. These groups determine chemical reactivity and route of metabolism, and relate to toxicity.

All substances within the AAI group show the same reactive groups, show similar composition of amide, imidazoline, and some dimer structures of both, with the length of original EA amines used for production as biggest difference. The range of molecular weights among the AAI substance are very similar, with a range from about 100 to 600 (for Tall oil + DETA) up to 100 to 900 (for Tall oil + polyamines) in case of use of larger ethyleneamines. Other physico-chemical properties also show very little variation: They are all (somewhat viscous) liquids, with a melting point below -15 ºC or lower (generally < -30 ºC), a boiling point above 300 ºC, and a very low vapour pressure (1.7 x 10-7Pa at 25°C for Tall oil + DETA).

They are surface active with surface tension about 30-35 mN/m for aqueous concentrations above CMC. For DETA, TETA and HEPA based AAI, are the CMC resp. 99, 19 and 15 mg/L.

The Pow for Tall oil + DETA is 2.2, which representing the substance with relatively the smallest hydrophilic part and thus highest Pow value within the group of AAI substance.


The substance Fatty acids, C18 unsaturated, reaction product with ammonia-ethanolamine reaction by-products (AAI-AEA) differs from other substances in the AAI group that are based on fatty acids with polyamines, in that it contains a high amount of hydroxylated polyethylene amines, causing it to display more neutral OH groups, rather than basic primary amine groups. As toxicity is much related to the presence of free primary amine groups, it can be expected that in specifically in aspects of acute toxicity related to direct chemical interactions, this substance shows less effects compared to other AAI substances.


Toxicological profile

As indicated above, the substances within the group of AAI are all very much alike, and show the same reactive groups. The major difference is related to the length of the ethyleneamines used for the production. Available data from repeated dose studies performed on various representative substances over the group of AAI indicates that toxicity decreases with increasing length of EA groups. The level of formed imidazoline compared to imidazoline seems to be of no consequence for the toxicity. Data from study on a substance consisting of only Amidoamine and no imidazoline resulted to the same level 

The level of free EA can be of impact, but as EA are not much more toxic compared to the NOAELs obtained for these AAI products, it cannot have a large impact. Tall oil + ammonia-ethanolamine reaction by-products showing less free primary amines than the other AAI substances, indeed shows a lower acute toxicity.


All substances show similar acute oral toxicity, all with a LD50 > 2000 mg/kg bw. There is possibly a small tendency of decreased toxicity with increasing size of the EA. As expected, shows Tall oil + ammonia-ethanolamine reaction by-products (AAI-AEA) with a LD50 of 4000 mg/kg even a somewhat lower toxicity than the other AAI substances.

All AAI are corrosive to skin Cat. 1C, and sensitizing to skin. (The presence of some free EA in the products could also have some influence here). Only AAI-AEA is irritating rather than corrosive, which is expected to be related to its lower level of free primary amines.

Several AAI substances were tested for genotoxicity, and all that were tested were not mutagenic in bacterial mutagenicity study (Ames test), induced no chromosomal aberrations in human lymphocytes, and were not mutagenic in mouse lymphoma cells. This was also the case for AAI_AEA. AAI substances in general therefore need not be classified for genotoxicity.


Repeated dose studies (combined repeated dose/reproduction toxicity screening studies or standard 28-day studies) show the lowest NOAEL of 10 to 30 mg/kg bw/day for Tall oil diethylenetriamine imidazoline (AAI+DETA).

AAI-DETA was tested in a combined repeated dose/reproduction screening toxicity study according to OECD 422. The study report concludes to a parental NOAEL of 30 mg/kg/day based on the increased incidence and severity of foamy macrophage foci in the mesenteric lymph node at the end of treatment, and in males also after the after the recovery period. However, considering that the incidence and severity of macrophage as observed at 30 mg is somewhat higher than at 10 mg and the control group, the NOAEL could also have been set at 10 mg/kg bw.

OECD 422 studies on both AAI-TEPA and AAI-PolyEA (containing higher EA) show a NOAEL of 300 mg/kg bw/day in an (showing some small effects at this level, not considered toxicologically relevant). A 28-day study on Tall oil fatty acids, reaction products with polyethylenepolyamines (Amidoamine; i.e. without imidazoline formed) resulted to an overall NOAEL of 100 mg/kg/. Although the NOAEL in this study was set at 100 mg/kgbw, the only effect noted at the next higher level of 300 mg/kg was a small increase in ALAT and ASAT level. It can be argued whether the 300 mg/kgbw should be selected as the NAOEL for this study. The 28-day study with AAI-AEA show comparable results: The NOAEL resulted to 80 mg/kg bw (Corrected from 100 mg/kg dose for the analytical accuracy), but toxicity at next dose level of 300 mg/kg was very minimal (consisting only of a marginal increase observed in ALAT and a (local) treatment related effect in the stomach in one male), and it can be argued whether the 300 mg/kgbw should be selected as NAOEL in this study.

These results from the repeated dose studies on various AAI substances indicate that the level of toxicity is comparable among these substances, with TO+DETA showing the highest toxicity. Consequently, results from studies on TO + DETA can therefore be regarded as worst case assumption of the toxicity of the other AAI substances.

Also a 90-day study on AAI-DETA was performed applying the same dose levels as in the OECD 422 study of 0, 10, 30 and 100 mg/kg/day AAI-DETA. The results from this study are comparable to those obtained from the OECD 422 study: The first effect to occur is the presence of foamy macrophages in the lamina propria of the small intestines and mesenteric lymph nodes. The magnitude of these effects as observed at the lowest dose level of 10 mg/kg is also often also observed in control groups in general, and was also seen in the control group of the OECD 422 study performed before on the same substance. These effects are therefore not considered adverse. As no other effects were observed, this dose level is considered to represent the NOAEL. These effects are considered to represent a local, porte d’entrée related effect due to the route of application, rather than a systemic effect. Comparison of the NOAELs from the studies on AAI-DETA show that the threshold for toxicity does not change much upon increasing the duration of the study.

Other available data from the group of AAI substances, including 90-day studies in rat and dogs on a similar substance, indicate low toxicity.


No reproductive or developmental toxicity was observed in the OECD 422 screening studies with AAI-DETA, AAI-TEPA and AAI-PolyEA up to the highest doses tested.The prenatal developmental toxicity study (OECD 414) on AAI-DETA resulted to a maternal NOAEL of 50 mg/kg. The developmental NOAEL was at least 150 mg/kg. Also no developmental toxicity was observed in a OECD 414 study on a similar substance.

In conclusion, the available data show a total lack of effects observed in reproductive parameters from developmental toxicity and reproduction screening studies within the group of AAI, and no effects on reproductive organs observed in any of the available repeated dose studies.


In conclusion: It seems that lower EA results to higher toxicity, and that the forming of imidazoline itself does not play a significant role. For cross-reading between substances in AAI category in general use can be made of data from same or lower EA-length where available, where data of AAI-DETA represents the worst case, showing highest toxicity.


There is a low likelihood of exposure to the AAI, as its use is limited to industrial and professional users where following its corrosive/irritating and severe eye damaging properties will provide for sufficient protection measures to prevent exposure. The likelihood of exposures via inhalation is low considering the high boiling point (> 300 °C) and very low vapour pressure (1.7x10-7Pa at 25°C for AAI-DETA, representing highest vp in category of AAI) and use applications that do not involve the forming of aerosols, particles or droplets of an inhalable size.

In view of low potential of exposures in combination with an overall low level of toxicity where increased study duration does not change the threshold for effects, a total lack of effects observed in reproductive parameters from developmental toxicity and reproduction screening studies within the group of AAI, and no effects on reproductive organs observed in available repeated dose studies, further studies are not indicated.


Toxicokinetics, metabolism and distribution

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


No specific toxicokinetic, metabolism or distribution studies are identified for AAI substances..

Alkyl amidoamine/imidazolines are mainly protonated under environmental conditions. The protonated fraction will behave as salt in water. AAI are surface active and have a low solubility in the form of CMC. For DETA, TETA and HEPA based AAI, the observed CMC were resp. 99, 19 and 15 mg/L. The actual dissolved concentration in water will be extremely low as alkyl amidoamines/imidazolines will sorb strongly to sorbents. As a consequence, absorption from gastro-intestinal system is likely to be slow, but with lack of actual data, absorption of 100% is indicated as key value here.


At this stage no data are available on dermal absorption. Itis not expected to easily pass the skin in view of its ionised form at physiological conditions.Except for Tall oil + ammonia-ethanolamine reaction by-products (AAI-AEA), are all AAI corrosive to skin, and toxicity following dermal exposure is characterised by local tissue damage, rather than the result of percutaneously absorbed material.

Based on the corrosive properties, dermal absorption as a consequence of facilitated penetration through damaged skin can be anticipated.

Also for AAI-AEA dermal absorption is expected to be limited. The major component consists of tall oil imidazoline dimer (almost 50%) which has a molecular mass of 639, a LogPow of 13.05, and protonated secondary amines of the imidazoline rings at pH 7, and as such is not expected to be easily absorbed through the skin. (Failing the Lipinski rules for absorption: mol.mass below 500, LogPow less than 5)

Dependent on the solvent and concentration, up to 60% dermal absorption might be suggested as a worst case for assessment purposes (value taken from the existing EU risk assessment on primary alkylamines). Due to the lack of quantitative absorption data, 100% absorption is taken as a conservative approach.


Also for inhalation no data are available on absorption, and100% is proposed as worst case. With a vapour pressure of 8.4x10-8Pa at 25°C, the potential for inhalation is limited. Relevant (in view of possible systemic absorption) exposures are therefore only possible as aerosol. If any inhalation does occur, this can only be in the form of larger droplets, as the use does not include fine spraying. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route. Absorption via respiratory route is therefore also set at 100%.


Considering the only limited increase of toxic effects following longer duration of dosing observed between OECD 422 (females up to 45-days) and 90-days dosing study, the potential for bioaccumulation of Tall oil reaction products with AEP is considered to be low.