trisodium (2S)-2,6-bis(3-carboxylatopropanamido)hexanoate

Endpoint summary

Description of key information

Toxicokinetic assessment of Disuccinyl lysine sodium salt

Background

Disuccinyl lysine sodium salt is an organic mono costituent substance. Disuccinyl lysine sodium salt is manufactured bysuccinylation of amine groups of Lysineand is placed on the marketin liquid form.

 

No studies on toxicokinetics are available for Disuccinyl lysine sodium salt, and the available toxicity studies provide little information on absorption, distribution, metabolism and excretion of the substance. Therefore, the following assessment is primarily based on physicochemical properties, supported by some toxicological indications.

Physical/chemical properties

The physical/chemical properties that are of importance to assess the toxicokinetic behavior of Disuccinyl lysine sodium salt are:

- Water solubility: 1047 g/L

- Molecular weight range: 412.28 g/mol

- Log Kow is -2.94 at 20 °C and pH 7

- Vapour pressure – 0.184 Pa (20 °C)

 

Absorption

Oral

Disuccinyl lysine sodium salt is a hydrophilic substance (having high water solubility (1047 g/l) and a log Kow estimated to be -2.94), therefore, its absorption from an oral route of exposure via passive diffusion is potentially expected also due to the intermediate molecular weight (412.28). Nevertheless, no signs of systemic toxicity have been observed in the acute toxicity study available, an LD50 >5000 mg/kg bw has been determined.

Inhalation

Respiratory exposure to Disuccinyl lysine sodium salt is unlikely to occur on a large scale, due to the very low vapour pressure (0,000184 kPa) and therefore, low volatility of the substance. However, when exposure occurs as an aerosol, some respiratory exposure may be possible. Any inhaled Disuccinyl lysine sodium salt may be absorbed through the inhalation tract to the same extent and for the same reasons as for oral absorption.

Dermal

Considering the liquid state, medium molecular weight, and the low vapour pressure of Disuccinyl lysine sodium salt, it is likely that it will be absorbed to some extent following dermal route of exposure. Based on its log Know and its high water solubility (above 10,000 mg/l), Disuccinyl lysine sodium salt is expected not to be sufficiently lipophilic to cross the lipid rich barrier of the stratum corneum.

Dermal uptake for the substance is predicted to be low be low. This understanding is in agreement with the results of one GLP-compliant in vitro study assessing the potential of Disuccinyl lysine sodium salt to cause skin irritation in which no irritation potential has been determined for the substance.

Distribution

Based on it physico-chemical properties (low log Kow and high water solubility), Disuccinyl lysine sodium salt is likely to be distributed into extracellular space and to a lower extent into cells and adipose tissues.

Metabolism and excretion

No information on metabolism and excretion is available.

Conclusions

In the absence of studies specifically addressing the toxicokinetic properties of Disuccinyl lysine sodium salt, and based on the available data, it is anticipated that the adsorption of Disuccinyl lysine sodium salt mainly occurs via oral and inhalation routes, with limited potential for skin absorption. Based on the information on the physico-chemical properties of Disuccinyl lysine sodium salt, the substance is expected to be distributed into extracellular space and to a lower extent into cells and adipose tissues

For risk assessment, absorption by oral and inhalation route is conservatively estimated being 100%, whereas absorption by dermal route is estimated being only 10%.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

10