Bis(2-ethylhexyl) carbonate

Dermal absorption

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Version / remarks:

adopted 13. April 2004

Deviations:

no

Test guideline 2

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

Test guideline 3

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

Test material information

Constituent 1

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.