trisodium ({3-[(carboxylatomethyl)amino]propyl}{3-[(carboxylatomethyl)(C16-18, C18 unsat alkyl)amino]propyl}amino)acetate

Endpoint summary

Description of key information

No experimental data is available on the toxicokinetics, metabolism and distribution on any of the four substances within the amphoteric, glycinate substance group. The information in this chapter has therefore been derived based on the physicochemical properties and QSAR estimations of the substances. Exposure to the substance is unlikely by inhalation due to the low vapour pressure and its physical form. Ingestion is not a likely route of exposure and the use is limited to industrial and professional uses.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

Additional information

Toxicokinetics

Under physiological conditions all nitrogens are positively charged as they are proton acceptors. The carboxylic groups acts as proton donors and are protonated only at lower pH. This results in different overall charge of the molecule depending on the pH; at lower pH the net charge is positive and at neutral or higher pH the overall charge is negative. This gives a structure consisting of a charged part with the carboxymethylated nitrogens and an apolar tail. The apolar carbon chain could easily dissolve in membranes, whereas the polar head would stay in the outside. As a consequence, the whole molecule will not easily pass membrane structures.

 

All the substances have been tested in the ToxTracker screening tool in order to evaluate the genotoxic profiles of the substances. In this screening test, also the cytotoxicity is determined both with and without S9 liver fraction. None of the four tested substances showed increased cytotoxicity properties when the cells were exposed in presence of S9 rat liver extract. This indicates that the substances are not metabolically activated by S9 enzymes.

 

Oral absorption

No actual data on the toxicokinetic properties of the amphoteric, glycinates are available. Based on the results from the QSAR models, the absorption via the gastrointestinal tract is expected to diminish as the molecule size and charges increases. According to the Discoverystudio ADMET tool, only the smallest diamine based substance has some adsorption, where the others are predicted as having “very low absorption”. This is also in line with the information on adsorption given from the SwissADME toolbox “Boiled egg” chart, see the graphs in the Category justification document under IUCLID chapter 13. Due to no actual oral absorption data on any of the substances within the group, the default 50% is used in the risk assessment.

 

Absorption of inhaled compound

The substances are manufactured, marketed and handled as aqueous solutions. Together with the relatively low vapour pressure, inhalational exposure is considered to be very limited. As a worst case, absorption via the inhalational route is also considered to be 100%, although exposure to the substance via inhalation is unlikely based on the physical appearance of the substance.

 

Dermal absorption

The partition coefficients (Log Kow) are below 0 for all of the substances within the group, indicating that the substances are not sufficiently lipophilic to cross the stratum corneum. This is further supported by the fact that the water solubility is high for this group of substances. All this taken together and in combination with the high molecular weight, the dermal absorption is considered to be low. This is also indicated in the estimation of dermal absorption performed using EpiSuite (v.4.11), showing very low dermal absorption potential, which also decreases with molecular size within the group. But due to no relevant data on any of the substances within the group, the default 50% is used in the risk assessment.