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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Publication on percutaneous absorption of anionic surfactants (soaps) is presented due to presence in and potential release of fatty acids C16-18 from the registered substance due to metabolic activation and presence of small quantities within the UVCB.

The reported study was conducted with sodium salts of palmitic and stearic acid. Sodium soaps of long chain C16 and C18 fatty acids are considered structural analoguous with regard to dermal absorption taking into account the physico-chemical properties (surface active properties, logKow, water solubility) and the chemical structure of the test item (mainly potassium soap of iso branched long chain C17 fatty acid) and therefore the results of the source substance are considered relevant for risk assessment.
Cross-reference
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Publication on percutaneous absorption of anionic surfactants (soaps) is presented due to presence in and potential release of fatty acids C16-18 from the registered substance due to metabolic activation and presence of small quantities within the UVCB.
Qualifier:
no guideline followed
Principles of method if other than guideline:
In vitro penetration through rat skin
GLP compliance:
no
Specific details on test material used for the study:
Name of test material (as cited in study report): Sodium salts of Decanoic acid (C10:0), Dodecanoic acid (C12:0), Tetradecanoic acid (C14:0), Hexadecanoic acid (C16:0), Octadecanoic acid (C18:0)
Analytical purity: Pure biochemical grade
Specific activity (if radiolabelling): 14 mCi/mM
Locations of the label (if radiolabelling): 1-Alkyl position with 14C (1-14C)
Radiolabelling:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Weight at study initiation: 100-120 g
Type of coverage:
open
Vehicle:
water
Remarks:
The test materials were applied as soap solutions (sodium salts).
Duration of exposure:
24 h
Doses:
Nominal doses: 300 µg C10:0, 325 µg C12:0, 375 µg C14:0, 425 µg C16:0 and 450 µg C18:0/4.9 cm² skin- Dose volume: 0.051 ml/cm²
No. of animals per group:
not specified
Control animals:
no
Details on study design:
Source of skin: rat dorsal skin
Type of skin: full thickness skin
Preparative technique: Dorsal skin was clipped 24 h before cervical dislocation. The skin was excised and mounted in 2.5 cm penetration cells similar to those described by Ainsworth (J Soc Cosmet Chem 11:69 (1960)).
Assay: Diffusion cell, similar to those described by Ainsworth (J Soc Cosmet Chem 11:69 (1960))
Receptor fluid: saline
Signs and symptoms of toxicity:
no effects
Dermal irritation:
no effects
Key result
Time point:
24 h
Dose:
86.73 µg fatty acid C16:0/cm²
Parameter:
percentage
Absorption:
0.2 %
Key result
Time point:
24 h
Dose:
91.84 µg fatty acid C18:0/cm²
Parameter:
percentage
Absorption:
< 0.1 %

The results show no measurable penetration of the C18:0 soap through rat skin up to 24 h after application, but 0.2 µg/cm² of the C16:0 soap had penetrated at 24 h. At the end of the experiment,i .e. 24 h after application, between 60 and 70% of the applied [14C] soaps were rinsed from the skin and 30-40% was associated with the skin.

Conclusions:
The in vitro penetration of C16 and C18 fatty acids (as aqueous sodium salt solutions) through rat skin decreases with increasing chain length. At 86.73 µg fatty acide C16/cm² and 91.84 µg fatty acid C18/cm², about 0.2% and less than 0.1% of the C16 and C18 sodium soap solutions is absoberd after 24 h exposure, respectively.
Executive summary:

The in vitro penetration of C16 and C18 fatty acids (as aqueous sodium salt solutions) through rat skin decreases with increasing chain length. At 86.73 µg fatty acide C16/cm² and 91.84 µg fatty acid C18/cm², about 0.2% and less than 0.1% of the C16 and C18 sodium soap solutions is absoberd after 24 h exposure, respectively.

Data source

Reference
Reference Type:
publication
Title:
The percutaneous absorption of some anionic surfactants
Author:
D. Howes
Year:
1975
Bibliographic source:
J. Soc. Cosmet. Chem. 1975, 26, 47-63

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In vitro penetration through rat skin
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium palmitate
EC Number:
206-988-1
EC Name:
Sodium palmitate
Cas Number:
408-35-5
Molecular formula:
C16H32O2.Na
IUPAC Name:
sodium palmitate
Constituent 2
Chemical structure
Reference substance name:
Sodium stearate
EC Number:
212-490-5
EC Name:
Sodium stearate
Cas Number:
822-16-2
Molecular formula:
C18H36O2.Na
IUPAC Name:
sodium stearate
Test material form:
solid
Specific details on test material used for the study:
The reported study was conducted with sodium salts of palmitic and stearic acid. Sodium soaps of long chain C16 and C18 fatty acids are considered structural analoguous with regard to dermal absorption taking into account the physico-chemical properties (surface active properties, logKow, water solubility) and the chemical structure of the test item (mainly potassium soap of iso branched long chain C17 fatty acid) and therefore the results are considered relevant for risk assessment.


Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Weight at study initiation: 100-120 g

Administration / exposure

Type of coverage:
open
Vehicle:
water
Remarks:
The test materials were applied as soap solutions (sodium salts).
Duration of exposure:
24 h
Doses:
Nominal doses: 300 µg C10:0, 325 µg C12:0, 375 µg C14:0, 425 µg C16:0 and 450 µg C18:0/4.9 cm² skin- Dose volume: 0.051 ml/cm²
No. of animals per group:
not specified
Control animals:
no
Details on study design:
Source of skin: rat dorsal skin
Type of skin: full thickness skin
Preparative technique: Dorsal skin was clipped 24 h before cervical dislocation. The skin was excised and mounted in 2.5 cm penetration cells similar to those described by Ainsworth (J Soc Cosmet Chem 11:69 (1960)).
Assay: Diffusion cell, similar to those described by Ainsworth (J Soc Cosmet Chem 11:69 (1960))
Receptor fluid: saline

Results and discussion

Signs and symptoms of toxicity:
no effects
Dermal irritation:
no effects
Percutaneous absorptionopen allclose all
Key result
Time point:
24 h
Dose:
86.73 µg fatty acid C16:0/cm²
Parameter:
percentage
Absorption:
0.2 %
Key result
Time point:
24 h
Dose:
91.84 µg fatty acid C18:0/cm²
Parameter:
percentage
Absorption:
< 0.1 %

Any other information on results incl. tables

The results show no measurable penetration of the C18:0 soap through rat skin up to 24 h after application, but 0.2 µg/cm² of the C16:0 soap had penetrated at 24 h. At the end of the experiment,i .e. 24 h after application, between 60 and 70% of the applied [14C] soaps were rinsed from the skin and 30-40% was associated with the skin.

Applicant's summary and conclusion

Conclusions:
The in vitro penetration of C16 and C18 fatty acids (as aqueous sodium salt solutions) through rat skin decreases with increasing chain length. At 86.73 µg fatty acide C16/cm² and 91.84 µg fatty acid C18/cm², about 0.2% and less than 0.1% of the C16 and C18 sodium soap solutions is absoberd after 24 h exposure, respectively.
Executive summary:

The in vitro penetration of C16 and C18 fatty acids (as aqueous sodium salt solutions) through rat skin decreases with increasing chain length. At 86.73 µg fatty acide C16/cm² and 91.84 µg fatty acid C18/cm², about 0.2% and less than 0.1% of the C16 and C18 sodium soap solutions is absoberd after 24 h exposure, respectively.

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