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Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2007-03-01 to 2007-03-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
Version / remarks:
adopted 13. April 2004
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: OECD Environmental Health and Safety Publications, Series on Testing and Assessment No. 28, Guidance Document for the Conduct of Skin Absorption Studies; Environment Directorate, Organisation for Economic Co-operation and Development; March 2004
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Guidance for Ind.; Nonsterile Semisolid Dosage Forms; Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Release Testing and In Vivo Bioequivalence Documen.; U.S. Dep. Health a. Hum. Serv., Food a. Drug Admin., May 1997
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(2-ethylhexyl) carbonate
EC Number:
238-925-9
EC Name:
Bis(2-ethylhexyl) carbonate
Cas Number:
14858-73-2
Molecular formula:
C17H34O3
IUPAC Name:
bis(2-ethylhexyl) carbonate
Test material form:
other: liquid
Radiolabelling:
no

Test animals

Species:
other: Skin membranes from female human abdominal origin from cosmetic surgery
Details on test animals or test system and environmental conditions:
IN VITRO TEST
Skin membranes from female human abdominal origin from cosmetic surgery were used. Split skin (approx. 500 µm) was prepared with a dermatome and comprises the stratum corneum, the epidermis and part of the dermis. With a punch (10 mm diameter) skin slices were produced for the use in the diffusion cell. The skin pieces were frozen between microscopical slides at

Administration / exposure

Vehicle:
other: Receptor fluid DMEM with 10 % FCS
Duration of exposure:
24 hours
Doses:
- Dose volume: 40.0 µL test substance (approx. 99.9%)
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: human female, abdominal origin from cosmetic surgery
- Ethical approval if human skin: no data
- Type of skin: stratum corneum, the epidermis and part of the dermis
- Preparative technique: Split skin (approx. 500 µm) was prepared with a dermatome
- Membrane integrity check: yes
- Storage conditions:


Results and discussion

Absorption in different matrices:
- Receptor fluid, receptor chamber, donor chamber (in vitro test system): No Bis(2-ethylhexyl) carbonate could be detected in the skin penetration samples up to a skin exposition time of 24 h.
- Skin preparation (in vitro test system): no data
- Stratum corneum (in vitro test system): (i.e tape strips) no data
Percutaneous absorption
Dose:
40.0 µL
Parameter:
percentage
Absorption:
0 %
Remarks on result:
other: 24 hours
Remarks:
No bis(2-ethylhexyl) carbonate could be detected in the skin penetration samples up to a skin exposition time of 24h.

Any other information on results incl. tables

The results of the in-study validation data show that the used method is able to quantify Bis(2-ethylhexyl) carbonate in cell culture medium with the respective precision and accuracy down to a concentration of 10.0 µg/mL for Bis(2-ethylhexyl) carbonate.

In all 60 samples the concentrations of Bis(2-ethylhexyl) carbonate was < 10.0 µg/mL. 6 skin samples were used and 10 medium samples were collected during a 24 -hour period each.

In conclusion it can be stated that no Bis(2-ethylhexyl) carbonate could be detected in the skin penetration samples up to a skin exposition time of 24 h.

Applicant's summary and conclusion

Conclusions:
No Bis(2-ethylhexyl) carbonate could be detected in the skin penetration samples up to a skin exposure time of 24 h. Therefore, Bis(2-ethylhexyl) carbonate is not expected to penetrate the human skin.
Executive summary:

The percutaneous absorption of Bis(2-ethylhexyl) carbonate (99.9 % a.i.) was assayed by using an in vitro method according to OECD Guideline 428, adopted 13. April. 2004. The penetration profile of the test item in human abdominal skin was analysed using an in vitro flow-through diffusion cell. A validated GC-MSD method was used to measure Bis(2-ethylhexyl) carbonate in cell culture medium (DMEM with 10% FCS). The results of the in-study validation data show that the used method is able to quantify Bis(2-ethylhexyl) carbonate in cell culture medium with the respective precision and accuracy down to a concentration of 10.0 µg/mL for Bis(2 -ethylhexyl) carbonate, corresponding to a detection limit of 0.025%. No Bis(2-ethylhexyl) carbonate could be detected in the skin penetration samples up to a skin exposure time of 24 h. Therefore, Bis(2-ethylhexyl) carbonate is not expected to penetrate the human skin.