Sodium 3-(allyloxy)-2-hydroxypropanesulphonate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: expert statement

Adequacy of study:

key study

Study period:

April 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The statement is performend through an expert of toxicology referring to the available data.

Data source

Reference

Reference Type:

other: expert statement

Title:

Unnamed

Year:

2013

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Expert statement

Test material

Test material information

Constituent 1

Reference substance name:

Sodium 3-(allyloxy)-2-hydroxypropanesulphonate

EC Number:

258-004-5

EC Name:

Sodium 3-(allyloxy)-2-hydroxypropanesulphonate

Cas Number:

52556-42-0

Molecular formula:

C6H12O5S.Na

IUPAC Name:

sodium 2-hydroxy-3-(prop-2-en-1-yloxy)propane-1-sulfonate

additive 1

Reference substance name:

Sodium hydroxide

EC Number:

215-185-5

EC Name:

Sodium hydroxide

Cas Number:

1310-73-2

Molecular formula:

HNaO

IUPAC Name:

sodium hydroxide

impurity 1

Reference substance name:

3-(allyloxy)propane-1,2-diol

EC Number:

204-620-4

EC Name:

3-(allyloxy)propane-1,2-diol

Cas Number:

123-34-2

Molecular formula:

C6H12O3

IUPAC Name:

3-(allyloxy)propane-1,2-diol

impurity 2

Reference substance name:

disodium 2-hydroxy-3-(3-sulfonatopropoxy)propane-1-sulfonate

Molecular formula:

C6H12Na2O8S2

IUPAC Name:

disodium 2-hydroxy-3-(3-sulfonatopropoxy)propane-1-sulfonate

Test material form:

solid: particulate/powder

Details on test material:

light yellow powder

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

dermal 10 %; oral 100%; inhalative 10%

Main ADME results 2

Type:

distribution

Results:

no statement possible based on available data

Main ADME results 3

Type:

metabolism

Results:

the substance may be target of typical PhaseI and Phase II enzymes

Main ADME results 4

Type:

excretion

Results:

renal and fecal excretion seem possible, excretion by inhalation does not seem to be relevant

Any other information on results incl. tables

Data from in vitro or in vivo studies, which were designed to identify the toxicokinetic properties of the substance, are not available. This means, that absorption, distribution, metabolism and excretion (ADME) can only be derived from available physical-chemical data.

 

To estimate the toxicokinetic properties of the substance the following information was considered (cited from IUCLID5 data file, section 4):

 

Parameter	Value used for CSR
Molecular weight	218,20 g/Mol
Melting point	Decomposition > 170°C
Boiling point
Density	1.5013 g/cm3
Vapor pressure	0.000205 Pa (at 20 °C)
Partition coefficient n-octanol/water (log Pow)	-1.51 (> 0,04 < 0,09)
Water solubility	781.1 g/L (at 20 °C)
pH	12 (aqueous solution)
pKa	11.004
Particle size

 

Absorption:

 

Based on above data the substance may be absorbed through the skin, but the low log Pow and the highly ionisation (pKa: 11.0004) indicate only limited dermal penetration potential (criteria for 100%: molecular weight < 500 g/Mol, -1 > log P_ow< 4, see EUROPEAN COMMISSION HEALTH & CONSUMER PROTECTION DIRECTORATE-GENERAL: Guidance Document on Dermal AbsorptionSanco/222/2000 rev. 7 19 March 2004).

For exposure assessments a value of 10 % of absorption after dermal exposure may be appropriate. Due to the high pH and the impurity of Sodium hydroxide local effects to the skin are possible.

 

The uptake after direct inhalation of the substance may be of low relevance due to the fact that the substance is imported and placed on the market as aqueous solution.

Uptake by inhalation after evaporation of solvent is unlikely, the substance is a solid at room temperature and decomposes at elevated temperatures (above 170 °C) and has a very low vapour pressure.

 

The absorption after oral ingestion cannot be calculated due to lack of data; by default an absorption of 100 % may be appropriate, until specific data will be available, although such a high absorption is rather unlikely.

 

Distribution:

 

Due to the fact that the substance is hydrophilic no body compartment can be identified as target. It seems to be unlikely that the substance easily crosses blood-tissue-barriers. The high water solubility indicates a prevalence in aqueous organs like blood and in intercellular liquids.

Due to the low log Pow the substance has no potential for bioaccumulation.

 

Metabolism and Excretion:

  

Taking into account the structural elements of the formula it follows that Phase I and Phase II metabolic reactions can occur:

 

The terminal double bond is a typical target for Phase I reactions leading to an epoxide or diol.

The Hydroxyl-group is known for its typical reaction with Phase II Enzymes like sulfotransferases, acetyltransferases and for glucoronidation. The substance may also be subject to glutathione (GSH) conjugation.

 

All of these reactions will increase the high water solubility of the substance and improve urinary excretion, which may be the most relevant way of excretion for this substance.

 

But even without metabolic conversion, a renal excretion of the unchanged molecule is possible and likely.

 

Another relevant pathway for excretion may be by feces, especially for the fraction, which has not been absorbed in the gastrointestinal tract after oral uptake.

 

Excretion by exhalation does not seem to be relevant.

 

Applicant's summary and conclusion

Conclusions:

Based on the physicochemical data the toxicokinetic properties of Sodium 3-(allyloxy)-2-hydroxypropanesulphonate (HAPS)
are assesssed.

Executive summary:

Absorption: for the oral route, an absorption of 100% is assumed,

for the inhalative and dermal route no relevant absorption is estimated and 10% are assumed.

Distribution: no information

Metabolism and Excretion: Phase I and Phase II reactions may occur.

Renale and fecal excretion are the prominent excretion routes.