L-Aspartic acid, N,N'-1,2-ethanediylbis-

Endpoint summary

Additional information

N, N'-1,2-Ethanediylbis-L-aspartic acid (EDDS acid; EC No.439-840-1, CAS RN20846-91-7) is a white, fine powder (Gair et al. 2002) with a purity of at least 88% (w/w). Water (6-10%) and aspartic acid (0.1-1%) are the main impurities. It decomposes above 195°C (Gair et al. 2002), has a density of 1.59 g/cm³ (Gair et al. 2002), a vapour pressure of about 0.00017 Pa (Tremain, 2002), a log Pow of <-1.4 (Gair et al. 2002) and is of low-moderate water solubility (Gair et al. 2002).

Other properties of EDDS acid such as flammability, explosiveness, oxidizing potential, stability and flash point further indicate that the substance is not likely to present a hazard to human health.

 

Read-across

Read-across involves the use of endpoint information for one chemical (the source chemical) to predict the same endpoint for another chemical (the target chemical). This can be a valid approach if the substances are considered to be "similar" in some way – usually on the basis of structure or mode/mechanism of action. In principle, read-across can be used to predict physicochemical properties, environmental fate, mammalian toxicity, and ecotoxicity. For any of these endpoints, it may be performed in a qualitative or quantitative manner (ECHA, 2008; OECD, 2007).

 

As indicated above, structural similarity is a common basis for read-across, and the process is essentially an assessment of a Structure Activity Relationship (SAR). Endpoint information is read-across from a structural analogue, a source chemical whose physicochemical and/or (eco)toxicological properties are likely to be similar to the target chemical. A judgement on structural similarity may be based on the following:

a) a common functional group

b) a common precursor and/or breakdown product (metabolic pathway similarity).

 

Analogues can also be chosen on the basis of common mechanisms of action and similarities in chemical (or biochemical) reactivity. The main application of qualitative read-across is in hazard identification (ECHA, 2008; OECD, 2007).

In support of this dossier, physico-chemical properties from trisodium EDDS have been included. From a comparison of the chemical structures, the physico-chemical data, environmental fate and behaviour, and (eco)toxicity data available, it can be concluded that trisodium EDDS does have read-across value for filling data-gaps and improving the database on EDDS acid. Notably, they both decompose before boiling (at >190°C), have comparable densities, low vapour pressures, and low log Pow values (both < -1). The test data indicate, however, that the trisodium salt and acid differ in two (maybe related) physicochemical respects, pH and water solubility. Trisodium EDDS is highly water soluble and is a weak alkali (pH of 9.5 at 33% in solution) has been reported. Whereas EDDS itself is only of low-moderate water solubility, and is a weak acid (pH of 3.3-4). Such differences would seem to limit the relevance of use of data on the trisodium salt in the prediction of the likely local toxic effects of the EDDS acid (i.e. it would be inappropriate to assume the acid and trisodium salt exhibited a comparable skin irritancy or lung toxicity via inhalation exposure). However, the pH and solubility differences do not undermine the read-across value of the systemic toxicity profile seen in the oral studies as both the acid and trisodium salt will be converted to a common molecular entity in the highly acidic environment of the stomach. Also, these differences will not undermine the usefulness in predicting the results of environmental fate and behaviour and ecotoxicity tests.

In addition, data on ethylenediamine tetra-acetic acid (EDTA; CAS RN 60 -00 -4) and its simple salts has also been included in this dossier.

EDDS and EDTA are markedly similar in structure, both being multifunctional organic carboxylic acids. They are chemical isomers and thus have identical molecular formulae (C10-H16-N2-O8) and molecular weights (MW 292). They both contain a central ethylenediamine moiety, in a spatial environment filled by four carboxylic acid groups that surround the ethylenediamine bridge. The acid groups are going to hinder access to the central (ethylenediamine) moiety and its nitrogen atoms, and are likely to be the major influence on the biological reaction profile of the two molecules. One illustration of this similar reactivity is the significant chelating ability of both EDDS and EDTA, which is likely to influence their toxicity.

 

EDTA and EDDS also exhibit similar physicochemical properties e.g. low vapour pressure, fairly high water-solubility and very low log Pow.

 

The toxicity of both substances must be related to the reactivity of the functional groups, and the ease by which they find their cellular targets. With their shared most spatially accessible functional groups and the two molecules’ similar physical properties, similar environmental fate and behaviour and (eco)toxic potentials would be predicted. EDTA is a tertiary amine whilst EDDS is a secondary amine, and some toxicological differences are possible based on this. The steric hindrance of the nitrogen atoms in EDTA and EDDS by the four surrounding carboxylic acid groups is likely to minimise the impact of this particular structural difference.

 

Toxicity may also be due to metabolites. Thus, any metabolism of EDDS is likely to involve the carbon chains containing the carboxylic acid; breaking of C-N bonds to yield L-aspartic acid seems much more unlikely.