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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Permeability of commercial solvents through living human skin
Author:
Ursin C, Hansen CM, Van Dyk JW, Jensen PA, Christensen IJ, Ebbehoej J
Year:
1995
Bibliographic source:
Am Ind Hyg Assoc J, 56:651-660

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Evaluation of the absorption
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test compound Dimethylsulfoxyde
CAS no.: 67-68-5
Source: Research Industris, Salt Lake City, Utah
Batch : no data
Purity : no data
Radiolabelling:
no

Test animals

Species:
human
Sex:
female
Details on test animals and environmental conditions:
The human skin was removed from healthy females during plastic surgery of the breast. During thinning, most of the dermal tissue was removed from the epidermis using a Downs-Watson dermatome. The thickness of this unstretched "split skin" was about 1 to 2 mm. Split skin samples were stored in the above Dulbecco's medium until used for permeation measurements (<= 10 days).

Administration / exposure

Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Duration of exposure:
0.16, 0.33, 0.5, 1.0, 1.33, and 2 hr
Doses:
0.5 ml of DMSO
No. of animals per group:
Females: 3
Details on study design:
Permeation measurements were made using a Franz Diffusion Cell, a two-chamber cell with a water jacket and magnetic stirrer in the collection cell. The area of exposed skin in the cell was 0.64 cm². The skin was stretched (area increase of about 3 fold) onto the cell giving a final thickness of about 300 to 600 µm. Water temperature was 37°C, which gave a skin temperature of about 34°. The receptor fluid was isotonic, nourished, saline solution (Dulbecco's medium with gentamycin [50 µg/mL]). A special cap prevented pressure build-up in the challenge half cell, containing solvent.

In all cases [3H] water was run for two hours before the test solvent in order to calibrate the relative permeability of the skin samples and to detect defective (leaky) specimens. [3H] Water permeation was measured by removing 0.5 mL samples from the collection chamber at times of 0.16, 0.33, 0.5, 1.0, 1.33, and 2 hr. The [3H] water was then removed and replaced with the challenge chemical. Its permeation rate was measured by removing 0.5 mL samples at times of 0.16, 0.33, 0.5 (or 0.66), 1.0, 2.0, 4.0, and 6.0 hr. In all the above cases fresh receptor fluid was added to replace the amount used for analysis.
DMSO was analyzed by high pressure liquid chromatography and the detection limits was 0.05 ppm.

Permeability tests and viability tests were not run on the same specimen but were always measured on the same piece of surgically removed skin. Viability tests were started either at the same time or after the permeation tests were started. If the test showed the skin was not viable, all the permeation results for that piece of skin were discarded. Skin viability was determined by measuring the ability of the skin cells to engage in DNA synthesis as measured by their ability to incorporate BrdUrd (5-bromo-2'deoxyuridine), a DNA precursor.
The viability test also was run on skin that had been exposed to solvent for 2 hr (but not used for permeability tests). The results give some insight into how the solvent affects the viability of the skin.

Results and discussion

Any other information on results incl. tables

Summary of Data for the Permeability Constants of DMSO through Living Human Skin (Effect of Normalization; Effect of Skin Specimen on Variability; Deviation of steady state region from Linearity).
        

 

Permeability Constant

% Error in slope

Skin Donor#

Un-Normalized

Normalized

 

 

 

 

 

4

136

174

9,4

4

198

323

10,7

4

179

51

9

5

217

427

1

5

138

254

10,7

7

112

127

25,7

7

208

171

33,7

7

220

270

35,9

 

 

 

 

Mean±Std. Dev.

176 ± 42

224 ± 118

 

Applicant's summary and conclusion

Executive summary:

The steady-state rate of permeation of commercial solvents was measured through living human skin. The skin was removed from healthy females during plastic surgery of the breast. The samples were thinned by removing the dermal tissue from the epidermis and then stretched to a thickness of 300 to 600 µm. The permeability rate of DMSO was reported to be 176 g/m2.hour compared to a permeability rate for water of 24 g/m2.hour indicating that DMSO is readily absorbed through the skin. For comparison, N-methyl-2-pyrrolidone, dimethylformamide and methylethylketone present a permeability rate of 171, 98 and 53 g/m2.hour, respectively.