2-morpholinoethanesulphonic acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

expert statement

Type of information:

other: expert statement

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: expert statement based on physical/chemical and toxicology properties, no study on toxicokinetics available

Data source

Reference

Reference Type:

other: expert statement

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Principles of method if other than guideline:

Expert statement

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-morpholinoethanesulphonic acid

EC Number:

224-632-3

EC Name:

2-morpholinoethanesulphonic acid

Cas Number:

4432-31-9

Molecular formula:

C6H13NO4S

IUPAC Name:

2-morpholin-4-ylethanesulfonic acid

Test material form:

solid: particulate/powder

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Generally, oral absorption is favoured for molecular weights below 500 g/mol. The high water solubility of 185 g/L for the test substance enables it to dissolve in the gastrointestinal fluids. In combination with the low molecular weight of 195 g/mol the substance can possibly pass through aqueous pores or can be carried through the epithelial barrier by the bulk passage of water. The low log Pow value of the test substance indicates that passive diffusion is less likely. Taken together, the physiochemical properties indicate that the test substance becomes bioavailable following the oral route.

Due to the melting point of the substance above 70 °C, no availability as a vapour under standard environmental conditions is expected. Still the vapour pressure was determined and is very low. It was calculated to be 1.39*10-4 Pa at 25 °C. As the substance is a powder formation and inhalation of dusts might occur. Generally particles with an aerodynamic diameter below 100 μm have the potential to be inspired, below 50 μm may reach the thoracic region and those below 15 μm can pass into the alveolar region of the respiratory tract. The test substance consists of only ca. 31 % particles smaller or equal to 100 μm (ca. 7 % smaller than 15 μm and ca. 20 % below 50 μm). As demonstrated by the distribution of the particle size the inhalable amount of the test substance is low and less than 10 % of the substance’s particles might possess the ability to reach the alveolar region. Deposited substance can potentially passage through aqueous pores or be carried across membranes with the bulk passage of water, while passive diffusion is less likely due to the low log Pow determined for both substances.

As a powder, the substance is not readily taken up by the skin. However, once moistened on the skin surface, absorption is possible, due to the high water solubility determined for the test substance. The molecular weight of the substance neither favours nor excludes dermal uptake. Considering the low log Pow of -2.2 of the test substance, the substance is likely to be too lipophobic to cross the stratum corneum, resulting in low absorption.

Details on distribution in tissues:

As mentioned above, the physicochemical properties of the test substance favour systemic absorption following oral, inhalative and dermal uptake to a certain extent.

Direct transport through aqueous pores is likely to be an entry route to the systemic circulation. After being absorbed into the body, the substance is most likely not distributed into the interior part of cells due to the hydrophilic properties (log Pow -2.2) and in turn the extracellular concentration is expected to be higher than intracellular concentration.

The test substance does not have a bioaccumulative potential. The log Pow of the test substance indicates no bioaccumulation potential, as it is well below 3.

Details on excretion:

Most of the test substance will be excreted most likely in its unhydrolised but possibly metabolised forms.
The most prominent excretion pathway of the substance is via urine, as substances with a molecular weight below 300 g/mol and with high water solubility are prone for this pathway.
Scientific data also supports the excretion via urine as morpholine, a defining group of the substance, was observed to be excreted by this pathway (Sohn 1982). However, the extent of metabolized forms compared to non-metabolised forms varied depending on species (Sohn 1982).

Metabolite characterisation studies

Details on metabolites:

The genotoxicity studies with the test substance indicate no remarkable differences in regard to genotoxicity and cytotoxicity in the presence or absence of metabolic activation systems. Thus, no metabolic activation is expected. Generally it is likely that common protein interaction such as cytochrome P450 oxidases interaction during Phase I metabolism introduce a reactive or polar group in the substance. The oxidation and dehydrogenation are likely first steps of metabolic changes in the morpholine ring, followed by ring-opening.The involvement of cytochrome P450 is also supported by scientific data showing that the morpholine ring, the most defining group of the test substance, can be metabolized by cytochrome P450 starting with the C-N bond cleavage (Combourieu 2000). The resulting compounds might be further processed into polar compounds during the metabolism in Phase II.

Applicant's summary and conclusion

Conclusions:

Bioaccumulation of the test substance is not considered critical based on an expert statement.

Executive summary:

Based on physicochemical characteristics, particularly water solubility, molecular weight and octanol-water partition coefficient, systemic absorption following oral, inhalative and dermal uptake is favoured to a certain extent. Bioaccumulation of the test substance is not considered critical, as log Pow of the test substance indicates no bioaccumulation potential. Phase I and II metabolism within liver cells with involvement of cytochrome P450 is likely and excretion will presumably occur after renal passage via urine.