Registration Dossier

Diss Factsheets

Toxicological information

Dermal absorption

Currently viewing:

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:
other: Well documented study report (GLP) which meets basic scientific principles

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Principles of method if other than guideline:
Absorption of [14C]-acrylic acid measured through human and mouse skin.
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Acrylic acid
EC Number:
201-177-9
EC Name:
Acrylic acid
Cas Number:
79-10-7
Molecular formula:
C3H4O2
IUPAC Name:
acrylic acid
Details on test material:
- Name of test material (as cited in study report): Acrylic acid
- Analytical purity: 99 %
- Supplier: Sigma Aldrich Chemical Co Ltd, Dorset, England

- Radiochemical purity (if radiolabelling): 98 %
- Specific activity (if radiolabelling): no data
- Locations of the label (if radiolabelling): no data
- Supplier: Sigma Aldrich Chemical Co Ltd, Dorset, England
Radiolabelling:
yes

Administration / exposure

Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: 1. Mouse: Female Crl:CD-1(ICR)BR mice, 6-8 weeks old.
2. Human: Human abdominal whole skin was obtained post mortem.
- Ethical approval if human skin: yes
- Type of skin: back
- Preparative technique:
1. Mouse: After killing, the backs of the mice were clipped carefully, ensuring that the skin was not damaged. The clipped area of skin was excised and, after removal of any subcutaneous fat, stored in foil at 4°C until required for use (<1 week).
2. Human: Human abdominal whole skin (dermis + epidermis) was obtained post mortem from subjects of varying age. Surplus fat was removed from the abdominal skin samples leaving the dermis and epidermis intact. The samples were stored at 4°C in foil until required for use (<1 week).
- Thickness of skin (in mm): no data
- Membrane integrity check: by measurement of their permeability to tritiated water
- Storage conditions: 4°C


PRINCIPLES OF ASSAY
- Diffusion cell: glass diffusion cell
- Receptor fluid: saline (0.9%)
- Static system: yes
- Test temperature: 30°C± 1°C
- Occlusion: yes

Results and discussion

Absorption in different matrices:
1) Absorption rates were influenced by the vehicle (acetone > water > phosphate buffer).
2) Absorption rates were proportional to the applied concentration in each vehicle.
3) The amount of acrylic acid in the skin membrane during the steady state absorption period was proportional to the steady state absorption rate (within each species).
4) Mouse skin was 3 times more permeable than human skin.
Percutaneous absorption
Remarks on result:
other:

Any other information on results incl. tables

Steady state absorption rates:

1. Absorption rates [in µg/cm2/hr] through human skin:

Solvent

Acetone

Water

Phosphate buffer

Concentration [%]

0.01

0.204 ± 0.136 *

0.037 ± 0.015 *

0.007 ± 0.003 *

0.1

3.18 ± 2.06 *

0.44 ± 0.165 *

0.047 ± 0.030 **

1.0

16.1 ± 2.66 *

5.16 ± 0.702 *

0.898 ± 0.787 **

4.0

99.9 ± 64.0 *

28.9 ± 6.25 *

7.23 ± 3.94 *

* (n=5); ** (n=4)

2. Absorption rates [in µg/cm2/hr] through mouse skin:

Solvent

Acetone

Water

Phosphate buffer

Concentration [%]

0.01

0.651 ± 0.144 *

0.101 ± 0.015 *

0.022 ± 0.003 *

0.1

6.93 ± 2.16 *

0.964 ± 0.113 *

0.191 ± 0.048 *

1.0

103 ± 15.4 *

15.0 ± 3.49 *

2.60 ± 1.17 *

4.0

201 ± 130 *

69.3 ± 12.5 *

12.4 ± 0.694 **

* (n=5); ** (n=4)

The calculated Damage Ratios showed that the vehicles (containing l% w/v acrylic acid) caused little, if any, change to the permeability characteristics of the membranes. Membranes which have been exposed only to water, in a similar manner, had Damage Ratios of between 0.8 -1.1 (Downes AM et al, 1967).

Different profiles of absorption were apparent from each vehicle. Four concentrations were studied (4%, 1%, 0.1% and 0.01% w/v acrylic acid and similar profiies were detected with each concentration in each vehicle. From the acetone vehicle there was a short period, a lag phase, following skin contact, before the steady state period of absorption. With the water vehicle there was a similar lag phase as seen from the acetone vehicle, but from the phosphate buffer vehicle a larger lag phase was apparent before the establishment of a steady state absorption phase. These patterns were seen with both the mouse and human skin, however, the lag phases were longer through human skin than mouse skin. The lag times through mouse skin from the acetone and water vehicles were 1-2 hours and 2-4 hours from the phosphate buffer vehicle. Through human skin the lag time values were 2-6 hours from the acetone and water vehicles and approximately 4-12 hours from the phosphate buffer vehicle.

It is apparent from the data that the steady state absorption rates were influenced by the applied concentration in the vehicle. The data also show that mouse skin is more permeable than human skin to acrylic acid. For both species the steady state absorption rates were highest from acetone > water > phosphate buffer.

In addition to profiles and rates of absorption measured, the amount of [14C]acrylic acid in the skin membrane during the steady state absorption period was detemined following the 1% applications of each vehicle.

Concentration in Skin after 1% Application:

 

Skin type

Solvent

Amount in skin [µg/cm2]

Acetone

49.1

Mouse

Water

26.8

Phosphate buffer

4.04

Acetone

95.8

Human

Water

58.1

Phosphate buffer

9.34

Interestingly, more acrylic acid was found in human skin than in mouse skin. This might not have been expected since absorption rates were higher through the mouse skin. However, within a species and hence membrane-type, there was a proportionality between the amount in the membrane and the absorption rate. This is not believed to be due to the much thicker epidermis and dermis present in human skin acting as the diffusion barrier but due to differences in the structure and composition of the principal diffusion barrier, the stratum corneum, in both species.

Applicant's summary and conclusion