N,N-dimethylacetamide

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to Guideline study with acceptable restrictions (no details about the test substance; skin temperature 34 °C [32 °C recommended]; 3 replicates but at least 4 recommended).

Data source

Reference

Reference Type:

publication

Title:

Permeability of commercial solvents through living human skin

Author:

Ursin C, Hansen CM, Van Dyk JW, Jensen PO, Christensen IJ, Ebbehoej J

Year:

1995

Bibliographic source:

Am Ind Hyg Assoc J 56: 651-660

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Deviations:

yes

Remarks:

No details about the test substance; skin temperature 34°C (instead of 32°C); 3 replicates instead of 4

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethylacetamide

EC Number:

204-826-4

EC Name:

N,N-dimethylacetamide

Cas Number:

127-19-5

Molecular formula:

C4H9NO

IUPAC Name:

N,N-dimethylacetamide

Test material form:

liquid

Specific details on test material used for the study:

- Name of test material: dimethylacetamide (DMAC)
- Composition of test material, percentage of components: highest available commercial quality
No further details available.

Radiolabelling:

no

Test animals

Species:

human

Sex:

female

Details on test animals or test system and environmental conditions:

Skin specimen of women were used; living skin was obtained during plastic surgery of the breast.

Administration / exposure

Type of coverage:

other: in vitro cell; cap prevented pressure build-up in the challenge half cell, containing the test substance

Vehicle:

unchanged (no vehicle)

Duration of exposure:

Sampling was performed 0.16, 0.33, 0.5 (or 0.66), 1, 2, 4, 6 h after application of the test substance (0.5 mL of the receptor fluid).

Doses:

Undiluted test substance was placed in the challenge half of the cell.

No. of animals per group:

3 measurements were conducted using the skin samples of the same donor.

Control animals:

yes

Remarks:

control for leakage of skin

Details on study design:

The exposed skin area was 0.64 cm².

Details on in vitro test system (if applicable):

SKIN PREPARATION
- Source of skin: skin obtained during plastic surgery of the breast
- Ethical approval if human skin: no data
- Type of skin: skin of the breast
- Preparative technique: dermal tissue removed from the epidermis using a Downs-Watson dermatome
- Thickness of skin in the cell: 300-600 µm
- Membrane integrity check: yes, relative permeability was tested with 3H water for 2 h.
- Viability test: Skin viability was detemined prior to experiments by assessing the ability of the skin cells to engage in DNA synthesis as measured by incorporation of BrdU.

PRINCIPLES OF ASSAY
- Diffusion cell: Franz diffusion cell
- Receptor fluid: isotonic, nourished, saline solution (Dulbecco's medium) with gentamycin (50 µg/mL)
- Solubility od test substance in receptor fluid: yes
- Static system: yes
- Test temperature: 37 °C of the bath resulting in 34 °C of the skin
- Occlusion and humidity: cap prevented pressure build-up in the challenge half cell.

Results and discussion

Signs and symptoms of toxicity:

not specified

Remarks:

(in vitro)

Dermal irritation:

not specified

Remarks:

(see freetext for cell viability at termination)

Absorption in different matrices:

not applicable, in vitro

Total recovery:

not applicable, in vitro

Percutaneous absorption

Remarks on result:

other: at steady state

Remarks:

Permeability constant: 107 ± 19 g/m²/h (mean ± SD, n = 3)

Conversion factor human vs. animal skin:

Human skin was used.

Any other information on results incl. tables

Prior to the permeability test, no leakage of skin and cell viability was given. Skin cell viability was checked after the permeability test (DNA synthesis as measured by incorporation of BrdU);

Result: no labelling of cells (not clearly discussed by the authors).

A normalization procedure was used to assess the effects of 3H-water on permeability: after normalisation the permeability constant was 217 ± 84 g/m²/h.

In in vitro skin absorption experiments, the skin of a female donor was used. Viability and skin integrity check was performed prior to experiments. In the diffusion cell the skin was exposed to undiluted test substance and 0.5 mL samples of receptor fluid were collected 0.16, 0.33, 0.5 (or 0.66), 1, 2, 4, 6 h after application of the test substance. Totally 3 trials were performed.

The authors calculated a permeability constant of 107 ± 19 g/m²/h (mean ± SD of 3 trials).