Methyl benzoate

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Study was performed according to scientific principles.

Data source

Reference

Reference Type:

publication

Title:

An experimentally based approach for predicting skin permeability of chemicals and drugs using a membrane-coated fiber array

Author:

Xia X-R, Baynes RE, Monteiro-Riviere NA, Riviere JE

Year:

2007

Bibliographic source:

Toxicology and Applied Pharmacology 221: 320-8

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

With a membrane-coated fiber (MCF) technique relative strengths of the molecular interactions (the partition coefficients) were investigated. A multiple MCF polymer membranes consisted of polydimethylsiloxane (PDMS) for lipophilic, CarboWax (Wax) for hydrogen bonding and polyacrylate (PA) for π*-electron interactions. With porcine skin, experimental skin permeability log (kp) was determined, which were compared with estimated skin permeability from an empirical approach.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methyl benzoate

EC Number:

202-259-7

EC Name:

Methyl benzoate

Cas Number:

93-58-3

Molecular formula:

C8H8O2

IUPAC Name:

methyl benzoate

Radiolabelling:

no

Test animals

Species:

pig

Strain:

other: Yorkshire

Sex:

female

Administration / exposure

Control animals:

no

Details on in vitro test system (if applicable):

SKIN PREPARATION
- Source of skin: porcine skin of weaning
- Type of skin: dorsal area
- Preparative technique: dermatomed
- Thickness of skin (in mm): 0.35
- Membrane integrity check: no data
- Storage conditions: no data
- Justification of species, anatomical site and preparative technique: no data

PRINCIPLES OF ASSAY
- Diffusion cell: two-compartment Teflon flow-through diffusion cell
- Receptor fluid: Krebs-Ringer bicarbonate buffer spiked with dextrose and bovine serum albumin (4.5 %)
- Solubility of test substance in receptor fluid: no data
- Static system: Brinkman circulator
- Flow-through system: 4.0 mL/h
- Test temperature: 37 °C
- Humidity: no data
- Occlusion: no data
- Reference substance(s): no data
- Other: pH was maintained between 7.3 and 7.5

Results and discussion

Percutaneous absorption

Remarks on result:

other: Under experimental conditions in vitro with porcine skin, methyl benzoate was metabolised. The skin permeability log(kp) was estimated from refined Potts and Guy models in USEPA Supplemental Guidance for Dermal Risk Assessment and was -2.16 cm/h.

Any other information on results incl. tables

Three sets of partition coefficients (logK) were measured with three MCFs (PDMS, PA and Wax) for Methyl benzoate and were 1.882, 2.015 and 1.561, respectively.

In the in vitro experiment with porcine skin, the receptor solution was formulated to mimic the microvascular circulation of the skin, composed of 4.5 % bovine serum albumin in a Krebs-Ringer bicarbonate buffer with dextrose (0.12 %). Since Methyl benzoate was metabolized under the experimental conditions, the skin permeability value log(kp) was not obtained. However, skin permeability log(kp) was estimated from refined Potts and Guy models in USEPA Supplemental Guidance for Dermal Risk Assessment and was -2.16 cm/h.

Applicant's summary and conclusion

Conclusions:

Methyl benzoate was metabolized under the experimental conditions in vitro, therefore the skin permeability value log(kp) was not obtained. The skin permeability log(kp) was estimated by empirical approach from refined Potts and Guy models in USEPA Supplemental Guidance for Dermal Risk Assessment and was -2.16 cm/h.

Executive summary:

The MCF array approach is used to stimulate the biological processes, where passive diffusion is the rate limiting transport mechanism. The partition coefficients were determined for Methyl benzoate by multiple MCF membranes. For example, logK through polydimethylsiloxane (PDMS), where lypophilic interactions were measured was 1.882, logK through polyacrylate (PA), where π*-electron interactions were measured was 2.015 and logK through CarboWax (Wax), where hydrogen bonding were measured was 1.561.

Under experimental conditions in vitro with porcine skin, methyl benzoate was metabolised, therefore the skin permeability coefficient log (kp) was not determined. Using the empirical approach from refined Potts and Guy models in USEPA Supplemental Guidance for Dermal Risk Assessment, the log(kp) was calculated to be -2.16 cm/h.