Hexanedioic acid, di-C16-18 (even numbered) alkyl esters

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

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

Data source

Reference

Reference Type:

publication

Title:

The percutaneous absorption of some anionic surfactants

Author:

Howes, D.

Year:

1975

Bibliographic source:

J. Soc. Cosmet. Chem. 26:47-63

Materials and methods

Principles of method if other than guideline:

In vitro penetration study of several fatty acids through rat skin.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Decanoic acid

EC Number:

206-376-4

EC Name:

Decanoic acid

Cas Number:

334-48-5

Molecular formula:

C10H20O2

IUPAC Name:

decanoic acid

Constituent 2

Reference substance name:

dodecanoic acid

IUPAC Name:

dodecanoic acid

Constituent 3

Reference substance name:

tetradecanoic acid

IUPAC Name:

tetradecanoic acid

Constituent 4

Reference substance name:

hexadecanoic acid

IUPAC Name:

hexadecanoic acid

Constituent 5

Reference substance name:

octadecanoic acid

IUPAC Name:

octadecanoic acid

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 100-120 g

Administration / exposure

Type of coverage:

open

Vehicle:

other: 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 in vitro test system (if applicable):

SKIN PREPARATION
- 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)).



PRINCIPLES OF ASSAY
- Diffusion cell: similar to those described by Ainsworth (J Soc Cosmet Chem 11:69 (1960)).
- Receptor fluid: saline
- Occlusion: no

Results and discussion

Percutaneous absorption

Percutaneous absorption 1

Dose:

61.22 µg C10:0/cm²

Parameter:

percentage

Absorption:

ca. 14 %

Remarks on result:

other: 24 h

Remarks:

8.6 ± 3.4 µg C10:0/cm² absorbed (n=3)

Percutaneous absorption 2

Dose:

66.33 µg C12:0/cm²

Parameter:

percentage

Absorption:

ca. 10.9 %

Remarks on result:

other: 24 h

Remarks:

7.2 ± 3.7 µg C12:0/cm² absorbed (n=3)

Percutaneous absorption 3

Dose:

76.53 µg C14:0/cm²

Parameter:

percentage

Absorption:

ca. 9 %

Remarks on result:

other: 24 h

Remarks:

6.9 ± 3.0 µg C14:0/cm² absorbed (n=3)

Percutaneous absorption 4

Dose:

86.73 µg C16:0/cm²

Parameter:

percentage

Absorption:

0.2 %

Remarks on result:

other: 24 h

Remarks:

0.2 ± 0.1 µg C16:0/cm² absorbed (n=3)

Percutaneous absorption 5

Dose:

91.84 µg C18:0/cm²

Parameter:

percentage

Absorption:

< 0.1 %

Remarks on result:

other: 24 h

Remarks:

< 0.1 µg C18:0/cm² absorbed (n=3)

Conversion factor human vs. animal skin:

no data

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. Some 7.5 µg of the C10:0, C12:0 and C14:0 soaps had penetrated per cm² at 24 h but the results were not significantly different for the three soaps. For the three soaps which penetrated the skin there was a lag time of 1 h before any measurable penetration occurred, but after this the rate of penetration steadily increased. 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 C10, C12, C14, C16 and C18 fatty acids (as sodium salt solutions) through rat skin decreases with increasing chain length. At 86.73 µg C16/cm² and 91.84 µg C18/cm², about 0.23% and less than 0.1% of the C16 and C18 soap solutions is absoberd after 24 h exposure, respectively.