Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to Guideline study with acceptable restrictions (one dose measured [screening of numerous substances]).

Data source

Reference
Reference Type:
publication
Title:
Percutaneous absorption of explosives and related compounds: an empirical model of bioavailability of organic nitro compounds from soil
Author:
Reifenrath WG, Kammen HO, Palmer WG, Major MM, Leach GJ
Year:
2002
Bibliographic source:
Toxicol Appl Pharmacol 182: 160–168

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Deviations:
no
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
[14C(U)]-thiodiglycol, specific activity of 12.33 mCi/mmol in ethanol solution (9.94 mg/ml) (prepared by Wizard Laboratories); radiochemical purity was 96.6–99.2% by thin-layer chromatography.
Radiolabelling:
yes
Remarks:
14C

Test animals

Details on test animals and environmental conditions:
in vitro

Administration / exposure

Duration of exposure:
24 h
Doses:
10.2+-0.5 µg/cm²
Details on study design:
Acetone solutions of radiolabeled compound prepared so that a 5-µl volume would contain approximately 8 µg of compound.
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: female Yorkshire pigs, weighing 30 to 50 kg
- Type of skin: upper back
- Preparative technique: whole skin was harvested
- Thickness of skin (in mm): 0.5-0.9
- Membrane integrity check: no data

- Diffusion cell: low volume flow cell
- Solubility od test substance in receptor fluid: yes

Results and discussion

Percutaneous absorption
Dose:
10.2 µg/cm²
Parameter:
percentage
Absorption:
ca. 20 %
Remarks on result:
other: 24 h

Any other information on results incl. tables

Percent applied radioactive dose (mean of 5 replicates)

Evaporation: 30 +-11%

Skin decontamination: 17 +-6%

Epidermis: 24 +-11%

Dermis: 12 +-9%

Receptor fluid: 7 +-3%

Total recovery: 90 +-6%

Percutaneous absorption of 14C-radiolabeled thiodiglycol in acetone solution: 20 +-9% of applied dose (n=5 replicates; 10 µg/cm² compound).

Applicant's summary and conclusion

Conclusions:
In vitro experiments revealed a percutaneous absorption of 20%.
Executive summary:

Comparable to Guideline study with acceptable restrictions (one dose measured [screening of numerous substances]).

Percutaneous absorption was studied in diffusion cells using harvested pig skin of the back. After application of 10.2 µg/cm²

14C-labelled thiodiglycol in acetone solution radioactivity was measured in dermis, epidermis and receptor fluid after 24 h, but also in skin decontamination and evaporation. The total recovery was 90% (n=5 replicates). The following amounts of radioactivity were measured: evaporation 30 +-11%, skin decontamination 17 +-6%, epidermis: 24 +-11%, dermis: 12 +-9%, receptor fluid: 7 +-3%.

Conclusion: In vitro experiments revealed a percutaneous absorption of 20%.