Registration Dossier

Administrative data

Endpoint:
dermal absorption
Type of information:
experimental study
Adequacy of study:
supporting study
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.
Cross-reference
Reason / purpose:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1974
Report Date:
1974
Reference Type:
publication
Title:
Unnamed
Year:
1975

Materials and methods

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. Also, 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 Lauryl 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 lauryl 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 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

Type of coverage:
open
Vehicle:
water
Duration of exposure:
15 minutes

Further groups of rats were exposed using Silflo silicone cups for up to 12 hours
Doses:
0.5mL (4.9mg Igepon A in 0.5mL aqueous solution)
No. of animals per group:
3
Control animals:
no
Details on study design:
VEHICLE
- Justification for use and choice of vehicle (if other than water): not applicable

TEST SITE
- Type of cover / wrap if used: non-occlusive protective patch
- Time intervals for shavings or clipplings: not applicable


REMOVAL OF TEST SUBSTANCE
- Removal of protecting device: no data
- Time after start of exposure: 15 minutes or 12 hours

ANALYSIS
- Method type(s) for identification no data
- Liquid scintillation counting results (cpm) converted to dpm as follows: no data
- Validation of analytical procedure: no data
- Limits of detection and quantification: 1.5 x 10exp3 dpm/day in urine, 5 x 10exp3 dpm/day in faeces, 1 x 10exp4 dpm/day in expired CO2 and for most tissues 1 x 10exp3 dpm/gm
Details on in vitro test system (if applicable):
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

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Absorption in different matrices:
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

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
Conversion factor human vs. animal skin:
no data

Any other information on results incl. tables

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 thein vitrorat 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 thein vitrohuman 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. 

Applicant's summary and conclusion

Conclusions:
From these experiments it can be seen that SLI can be absorbed through skin at a low to moderate rate. 
Executive summary:

The dermal absorption of SLI was determined through various methods, both in vivo and in vitro:

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 thein vitrorat 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 thein vitrohuman 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.