Fatty acids, C12-18 and C18-unsatd., 2-sulfoethyl esters, sodium salts

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1974-03-11 to 1974-03-11

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study not conducted according to GLP or OECD guidelines. However, the study is a well documented in a 20 page Unilever Research Report and the test item (Sodium Lauryl Isethionate) is identified.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1974

Report date:

1974

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1975

Materials and methods

Objective of study:

absorption

excretion

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Six experiments were conducted on radiolabelled sodium [14C] lauryl isethionate (SLI): two in vivo metabolism studies, two in vivo skin absorption studies and two in vitro skin absorption studies. The test item was applied as an aqueous solution to the skins of rats in vivo and the amounts penetrating the skin was measured. The turnover of the test item administered by subcutaneous and intraperitoneal injection in rats in vivo was also studied. Finally, the in vitro penetration of the test item through rat skin and human epidermis was also examined.

GLP compliance:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): Sodium Lauroyl Isethionate
- Molecular formula (if other than submission substance): Na.SO3-CH2-CH2-O-CO-(CH2)10-CH3
- Molecular weight (if other than submission substance): 344.419g/mol
- Smiles notation (if other than submission substance): [O-]S(=O)(CCOC(CCCCCCCCCCC)=O)=O.[Na+]
- InChl (if other than submission substance): no data
- Substance type: organic
- Physical state: aqueous solution
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Radiochemical purity (if radiolabelling): no data
- Specific activity (if radiolabelling): 36.8 X 10exp6 dpm/mL (1.7 uCi/mg)
- Locations of the label (if radiolabelling): 1st Carbon of Lauroyl chain
- Expiration date of radiochemical substance (if radiolabelling): no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

other: Colworth-Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Colworth
- Age at study initiation: no data
- Weight at study initiation: 120g
- Fasting period before study: no data
- Housing: no data
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data


IN-LIFE DATES: no data

Administration / exposure

Route of administration:

other: dermal, intraperitoneal, subcutaneous

Vehicle:

water

Details on exposure:

Dermal: Hair on backs clipped off 24 hours before topical applications made; 0.5mL over 10cm2 skin and massaged gently with a rounded glass rod for 1 minute whilst the rats were lightly anaesthetised with cyclopropane & left for total of 15 minutes. After the sample was removed, a non-occlusive protective patch was applied over the treated area. 6 animals

Further groups of rats were exposed using Silflo silicone cups for up to 12 hours.


Intraperitoneal: 0.5 or 1mL injected intraperitoneally; 3 animals


Subcutaneous: 1mL injected under skin of thorax; 3 animals

Duration and frequency of treatment / exposure:

Dermal: 15 minutes

Doses / concentrations

Remarks:

Doses / Concentrations:
25mM aqueous solution
Dermal: 0.5mL (4.9mg Igepon A in 0.5mL aqueous solution)
Intraperitoneal: 0.5 or 1mL
Subcutaneous: 1mL

No. of animals per sex per dose / concentration:

3 animals per route of exposure

Control animals:

no

Positive control reference chemical:

Not applicable

Details on study design:

- Dose selection rationale: no data
- Rationale for animal assignment (if not random): no data

Details on dosing and sampling:

ABSORPTION, METABOLITE CHARACTERISATION & EXCRETION STUDIES
- Tissues and body fluids sampled (delete / add / specify): urine, faeces, skin, carcass, protective patches, expired air
- Time and frequency of sampling: 24 hours after treatment
- From how many animals: (samples pooled or not) 3
- Method type(s) for identification: no data
- Limits of detection and quantification: 1.5 x 10exp3 dpm/day in urine, 5 x10exp3 dpm/day in faeces, 1 x 10exp4 dpm/day in expired C02 and for most tissues 1x 10exp3 dpm/gm

Statistics:

No data

Results and discussion

Preliminary studies:

Not applicable

Main ADME results

Main ADME results 1

Type:

absorption

Results:

SLI can be absorbed through skin at low-moderate rate. 2 in vivo rat topical studies showed the penetration rate reached a plateau of 0.6ug/cm2/hour after 3 hours which continued to the end of the experiment

Main ADME results 2

Type:

absorption

Results:

In two in vitro experiments, no penetration was measureable using rat skin. Over the 48 hour exposure period, 30µg/cm2 penetrated into the receptor solution, with approximately 10% of the dose associated with the skin at the end of the experiment

Main ADME results 3

Type:

metabolism

Results:

Both s.c. and i.p. administration resulted in ~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

Main ADME results 4

Type:

excretion

Results:

major fate is the breaking of isethionate/laurate ester bond and the laurate is oxidised thus 80% of the dose is expired as 14C02 during first 24h after dosing. The urinary and faecal route are only minor excretion routes for test item.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Not applicable

Details on distribution in tissues:

Not applicable

Details on excretion:

Not applicable

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Both s.c. and i.p. 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. The other product produced by hydrolysis of the ester bond would be sodium isethionate.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results metabolism to sodium isethionate and lauric acid (and its subsequent oxidation is extensive)
From these experiments it can be seen that SLI can 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. Major fate is the breaking of isethionate/laurate ester bond and the laurate is oxidised thus 80% of the dose is expired as 14C02 during first 24h after dosing. The urinary and faecal route are only minor excretion routes for test item.

Executive summary:

Six experiments were conducted on sodium lauryl isethionate (SLI): two in vivo metabolism studies, two in vivo skin absorption studies and two in vitro skin absorption studies. 

 

For the metabolism (turnover) experiments, 0.5ml or 1.0ml of a 25mM aqueous solution of SLI were administered either subcutaneously under the skin of the thorax or intraperitoneally. Bothand i.p. 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. The other product produced by hydrolysis of the ester bond would be sodium isethionate; from this study, it cannot be determined whether this metabolite was further metabolised nor its route of excretion.

 

Two in vivo rat topical experiments were carried out, one with 15 minutes exposure to 0.5ml of 25mM aqueous SLR spread over 10cm², end time point of 24 hours, and one with the same dose applied for 12 hours, end time point 12 hours. In the 15 minute exposure experiment, levels of parent/metabolites in excreta were below the limits of detection. In the 12 hour exposure experiment, the penetration rate reached a plateau of 0.6µg/cm²/hr after 3 hours, which continued until the end of the experiment. This indicated that material remaining associated with the skin at the end of the experiment would have been available for absorption.

 

In the in vitro rat skin absorption experiment, 0.25ml 25mM aqueous solution of SLI was applied to full thickness rat skin mounted in 2.5cm penetration cells. Over the 24 hour period of exposure, no penetration into the receptor solution was measurable, although 622µg were recovered from the skin itself. Extrapolating from the results of the in vivo 12 hour rat experiment, it would seem likely that the material in the skin would eventually penetrate, and that maybe something in the experimental design prevented detection of SLI in the receptor solution (too small aliquots being taken for scintillation counting is one possibility).

 

In the in vitro human skin absorption experiment, 0.25ml 25mM aqueous solution of SLI was applied to human epidermal membranes mounted in 1cm penetration cells. Over the 48 hour exposure period, 30µg/cm²penetrated into the receptor solution, with approximately 10% of the dose associated with the skin at the end of the experiment. The material remaining in the skin would have been bioavailable as indicated by the ever increasing rate of absorption over the 48hrs. 

 

From these experiments it can be seen that SLI can 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.