Silicic acid, aluminum magnesium sodium salt

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

study initiation date: 23rd March 2016, experimental phase: 11th April - 23rd May 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Version / remarks:

2004

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Silicon dioxide

EC Number:

231-545-4

EC Name:

Silicon dioxide

Cas Number:

7631-86-9

Molecular formula:

O2Si

IUPAC Name:

Silicon dioxide

Test material form:

solid: nanoform, no surface treatment

Details on test material:

Precipitated, Surface area / BET [m2/g]: 37, Purity >99.8 %

Specific details on test material used for the study:

Sylodent VP5 (SAS)

Supplier: Grace GmbH & Co. KG
Appearance: white paste
SAS content: 10% w/w

Radiolabelling:

no

Test animals

Species:

pig

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Back/flank skin from suckling pigs (aged 6 - 8 weeks) was obtained from a food source abattoir. Prior to them being scalded, samples of whole skin were excised from the trunk area of each animal and the samples clipped to remove excess hair. Skin membranes were cut from the clipped samples at a thickness setting of 400 µm using an electric dermatome.
Each membrane was given an identifying number and stored frozen, at approximately -20°C, on aluminium foil until required for use.

Administration / exposure

Type of coverage:

open

Vehicle:

other: oil in water emulsion (formula no. 659/001/003)

Duration of exposure:

24 h

Doses:

2 mg / cm² (= 200 µg SAS/cm²)

No. of animals per group:

6 skin membrances per test substance (from at least four different animals)

Control animals:

yes

Details on study design:

The application rates (2 mg/cm²) and exposure conditions (24 hour) used in this study were designed to simulate predicted normal human exposure to the test material.

Results and discussion

Signs and symptoms of toxicity:

no effects

Dermal irritation:

not examined

Absorption in different matrices:

There was no detectable penetration of SAS through dermatomed pig skin using both AF4 and ICP methods.

Any other information on results incl. tables

According to the analytical laboratory, due to the contamination of the receptor fluid with very small skin debris and very small oil aerosols that have diffused from the skin samples into the receptor medium, a clear signal for silica particles could not be obtained. The situation was not improved by washing the receptor fluid with organic solvents to remove the oil aerosols due to the fact that the contamination was much higher than expected. The pre-testing with a pure receptor fluid spiked with a very low concentration of nano SAS particles (Colloidal Silica) demonstrated that the method was capable of detecting extremely low mass concentrations of SAS. Even using the blind sample to define the background and subtract the background of skin debris and oil aerosols from the test results did not provide any meaningful results.

ICP data did not present any evidence that silica was present in the receptor fluid samples and there was no indication that SAS was present in the noise scattering.

Asymmetric flow field-flow fraction (AF4) and multi angle light scattering is a viable option for analysing SAS particles in liquid media such as skin penetration receptor fluids. This was demonstrated by the Fraunhofer Institute using spiked receptor fluids. Contamination by skin debris and oil aerosols from the test materials and the test skin appeared to be very high in concentration and no meaningful results using the AF4 method could be obtained without removing the contaminants e.g. by washing or filtering. Analysis by ICP did not provide any evidence for penetration of SAS through dermatomed pig skin.

There was no detectable penetration of SAS through dermatomed pig skin using both AF4 and ICP methods. Quantification of SAS by either method was not possible in the presence of the contaminants that were already present in the test system.

Applicant's summary and conclusion

Conclusions:

There was no detectable penetration of Syloid VP 5 (a SAS) through dermatomed pig skin using both AF4 and ICP methods. Quantification of SAS by either method was not possible in the presence of the contaminants that were already present in the test system.

Executive summary:

The purpose of this study was to investigate the in vitro percutaneous penetration of four synthetic amorphous silica (SAS) formulations prepared as ‘oil in water' (O/W) emulsions through pig dermatomed skin following a 24 hour exposure. Only the results of the examinations in Syloid VP 5 are documented here. An untreated control group and a group of skin samples treated with the ‘oil in water' emulsion were also included.