Sodium 2-sulphonatoethyl laurate

Endpoint summary

Description of key information

A toxicokinetic study on the Sodium [14C]lauryl isethionate (Fatty acids, C12-18 and C18-unstaurated, 2-sulfoethyl esters, sodium salt CAS No 85408-62-4) is available, Unilever Toxicokinetics PCW741191.  This study is Klimisch 2 as it was not carried out to GLP or an OECD guideline, but the study is scientifically valid and a detailed report is available.  These studies include in vivo and in vitro dermal penetration studies in rats and in vitro studies in human epidermis.  There is also a study of the turnover of the test item (metabolism and excretion) when administered by subcutaneous and intraperitoneal injection in rats in vivo.

An in-vitro hydrolysis and metabolism study,  Unilever in vitro hydrolysis AE100086 is available.  In this study Sodium [14C]lauryl isethionate or sodium [14C]stearyl isethionate were incubated with various biological matrices, including gastric fluid simulant, intestinal fluid stimulant or porcine liver esterase enzyme.  After various time points samples were taken and analysed by radio-HPLC to monitor disappearance of the parent material and the formation of any 14C-labelled products of digestion in the samples.  The study is Klimisch 2 as although carried out to GLP, but there were no standard guidelines available to follow.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

50

Absorption rate - inhalation (%):

100

Additional information

An in-vitro hydrolysis and metabolism study on the Sodium [14C]lauryl isethionate (Fatty acids, C12-18 and C18-unstaurated, 2-sulfoethyl esters,

sodium salt CAS No 85408-62-4) is available, Unilever in vitro hydrolysis AE100086. In this study Sodium [14C]lauryl isethionate (C12) or sodium [14C]stearyl isethionate (C18) were incubated with various biological matrices, including gastric fluid simulant, intestinal fluid stimulant or porcine liver esterase enzyme.

In the hydrolysis study with Sodium [¹⁴C]lauryl isethionate it was found to degrade by approximately 30% in simulated gastric fluid, which was considered to be probably due to acid hydrolysis, producing a single major ¹⁴C labeled metabolite. In simulated intestinal fluid degradation was approximately 10% in 6 hours.

Degradation was almost complete in the presence of porcine liver esterase over 6 hour with apparently the same¹⁴C labeled metabolite being produced.

It was concluded that Sodium [¹⁴C]lauryl isethionate was shown to be unstable in conditions likely to be met in the stomach, small intestine and that when subsequently absorbed would probably be completely metabolized in the liver before entering the systemic bloodstream.

In the hydrolysis study withsodium [¹⁴C]stearyl isethionate, hydrolysis in the simulated gastric juice was 40% with 10% in simulated intestinal fluid. But degradation was only 20% with the porcine esterase after 6 hours. This indicates that sodium [¹⁴C]stearyl isethionate, would be more slowly metabolized than theSodium [¹⁴C]lauryl isethionate. This slower metabolism for thesodium [¹⁴C]stearyl isethionateis considered to be due to it having predominantly C18 fatty acid linked to the isethionate, rather than C12. The C18 fatty acid present in thesodium [¹⁴C]stearyl isethionatebeing expected to be more slowly metabolized than fatty acids with shorter carbon chains such as C12.

In the toxicokinetic studies the 12 hour in vivo rat dermal penetration study the penetration rate plateaued at 0.6µg/cm² /h indicating that the material remaining associated with the skin would have been available for absorption.  In the in-vitro dermal penetration study in rat skin penetration was not detected over the 24 hour period, but this was considered due to limitation in the experiment.

In the in vitro dermal penetration study with human skin over 48 hours 30µg/cm²penetrated with approximately 10% of the dose associated with the skin at the end of the experiment which was considered to have been bioavailable for absorption.

In the metabolism experiments the Sodium [¹⁴C]lauryl isethionate (Fatty acids, C12-18 and C18-unsaturated, 2-sulfoethyl esters, sodium salt CAS No 85408-62-4) was administered as aqueous solution either subcutaneously under the skin of the thorax or intraperitoneally. Both subcutaneous and intraperitoneal administration resulted in approximately 80% of the dosed radioactivity being recovered as [¹⁴CO2], indicating that breaking of the isethionate/laurate ester bond and oxidation of the resultant lauric acid is the major route of metabolism. This was being demonstrated by measuring the expired¹⁴CO₂in the first 24hours. The urinary and faecal routes of excretion were only minor. The other product produced by hydrolysis of the ester bond was sodium isethionate; from this study, it cannot be determined whether this metabolite was further metabolized nor its route of excretion.

From these experiments it can be seen that Sodium [¹⁴C] lauryl isethionatecan be absorbed through skin at a low to moderate rate. Once within the body, metabolism to sodium isethionate, lauric acid (and its subsequent oxidation) is extensive.

 

It is clear that Sodium lauryl isethionate (Fatty acids, C12-18 and C18-unsaturated, 2-sulfoethyl esters, sodium salt CAS No 85408-62-4) when administered via the oral route would be rapidly hydrolyzed in the stomach and gastrointestinal tract, and when absorbed completely metabolized in the liver the single radiolabelled metabolite being lauric acid, the other metabolite being sodium isethionate. The toxicokientic experiments showed that administration by routes that avoid the hydrolysis in the gastrointestinal tract, still resulted in rapid metabolism in the liver to lauric acid (which is subsequently further oxidized to be excreted as CO₂) and sodium isethionate.