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

Categories

Category name:

Amphoterics, glycinate

Justifications and discussions

Category definition:

Structurally, the amphoteric, glycinates are very similar: a linear alkyl chain and one carboxymethylated nitrogen at the end, with 1, 2 or 3 carboxymethylated 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. Appendix 2 displays the chemical profile for all the structures. The substances consist of the same functional groups and therefore are considered to have similar properties. Noteworthy is that the reactivity profile as indicated by QSAR Toolbox (v.3.4) is very similar for all structures, and basically indicate no specific concern.

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, metabolism/transformations, and specific mechanisms of toxicity e.g. sensitization and genotoxicity. For these reasons, many of the toxicological studies can best be performed on the substance with the shortest chain length, as this is considered to result to the lowest NOAEL or most likely able to show specific effects.

Category rationale:

Applicability domain (AD) of the category
The members of this Amphoteric, glycinate category have a close structural relationship and thus are sharing common functionalities. However, some structural borders need to be defined.
The borders of the category are determined by the length of the linear alkyl chain involved. The lower end of the category is set at an alkyl chain length of C8 . If the alkyl chain becomes very short (e.g. below C8), the general properties of an amphiphilic structure with surfactant properties may become compromised, leading to a difference in physico-chemical properties, and consequently in different environmental fate and physiological behaviour involving absorption and kinetics of the substance, despite otherwise close structural relationship. Also related to availability of data, the upper end of the category is set at alkyl chain lengths of C20. When chain lengths become larger, this is expected to lead to decreased bioavailability following extreme high predicted Pow values. Besides, it is known that large alkyl chains from C22 are initially broken down in microsomes (peroxisomes) rather than in mitochondria, which could possibly lead to an altered toxicity profile. The only further variation related to the alkyl chains relates to the possible level of unsaturation of the alkyl chains (indicated by iodine number) but experience from testing of many fatty acid derived groups of substances has shown that this is of very limited impact to the (eco) toxicological profile. The major impact of unsaturation is that it tends to lead to a more liquid aspect of the product (lower mp or viscosity) leading to specifically better skin contact, and in general slightly better bioavailability in a similar fashion as shorter chain lengths. This is of less importance for the Amphoteric, glycinate substances as they are all manufactured and handled as aqueous solutions only.