Fatty acids, coco, 2-sulfoethyl esters, sodium salts

Endpoint summary

Description of key information

There is no information available on absorption, metabolism and distribution of Coco fatty acids 2-sulfoethyl ester, sodium salt (sodium cocoyl isethionate) CAS No 61789-32-0, there is however an in-vitro hydrolysis and metabolism study,  Unilever in vitro hydrolysis AE100086.  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.

Coco fatty acids 2-sulfoethyl ester, sodium salt (sodium cocoyl isethionate) CAS No 61789-32-0 has a similar carbon chain distribution to Sodium [14C]lauryl isethionate (Fatty acids, C12-18 and C18-unstaurated, 2-sulfoethyl esters, sodium salt CAS No 85408-62-4),  however it has a lower proportion of C16 and C18 which should make it more easily hydrolyzed.   Full justification for this read across is provided in section 13.

There is also Toxicokinetic data on the Sodium [14C]lauryl isethionate (Fatty acids, C12-18 and C18-unstaurated, 2-sulfoethyl esters, sodium salt CAS No 85408-62-4), Unilever Toxicokinetics PCW741191.  This study is also 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.

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

There is no information available on absorption, metabolism and distribution of Coco fatty acids 2-sulfoethyl ester, sodium salt (sodium cocoyl isethionate) CAS No 61789-32-0, there is however an in-vitro hydrolysis and metabolism study, 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.

 

This information is directly applicable also to Coco fatty acids 2-sulfoethyl ester, sodium salt (sodium cocoyl isethionate) CAS No 61789-32-0, which has an overlapping carbon chain distribution, but with a significantly lower proportion of the less easily metabolized C16 and C18 fatty acid (see the read across document in Section 13 for details). Therefore the Coco fatty acids 2-sulfoethyl ester, sodium salt would be expected to be very rapidly hydrolyzed and metabolized, more rapidly and completely than the Sodium lauryl isethionate. This would give the same primary metabolites of fatty acid predominantly lauric acid (which as a fatty acid would be further rapidly oxidized to be excreted as CO₂) and sodium isethionate. This strongly supports the use of read across to Coco fatty acids 2-sulfoethyl ester, sodium salt from both the Sodium lauryl isethionate (Fatty acids, C12-18 and C18-unsaturated, 2-sulfoethyl esters, sodium salt CAS No 85408-62-4) and from the sodium 2-hydroxyethanesulfonate CAS No 1562-00-1 (sodium isethionate), the common metabolite from both substances, that could have potential toxicity.