Bis(2-ethylhexyl) adipate

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

In Vitro Dermal Absorption of Di(2-ethylhexyl) adipate (DEHA) in a Roll-On Deodorant Using Human Skin

Author:

Zhou

Year:

2013

Bibliographic source:

Journal of Toxicology and Environmental Health,Part A: Current Issues, 76:3, 157-166

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-ethylhexyl) adipate

EC Number:

203-090-1

EC Name:

Bis(2-ethylhexyl) adipate

Cas Number:

103-23-1

Molecular formula:

C22H42O4

IUPAC Name:

bis(2-ethylhexyl) adipate

Details on test material:

- Name of test material (as cited in study report): DEHA
- Physical state: liquid
- Composition of test material, percentage of components: 1.56% of DEHA as part of a roll-on deodorant

Radiolabelling:

no

Test animals

Species:

human

Administration / exposure

Duration of exposure:

24h

Doses:

5mg total (7.8mg/cm²)
100mg total (156mg/cm²)

No. of animals per group:

4 skin samples per dose from four different individuals, tested in triplicate

Details on in vitro test system (if applicable):

SKIN PREPARATION
- Source of skin: General Hospital, Ottawa, Ontario, Canada
- Type of skin: Breast surgical waste skin samples
- Preparative technique: the skin was dermatomed and circular-punched (area 0.64cm²)
- Thickness of skin (in mm): 0.4-0.5mm
- Storage conditions: first skin was used fresh while the subsequent 3 samples were stored at -20°C
- Justification of species, anatomical site and preparative technique: storage at -20°C for up to 2 months does not change barrier function of human skin (Moody et al (2009))

PRINCIPLES OF ASSAY
- Diffusion cell: Bronaugh cell
- Receptor fluid: Hanks HEPES buffered balanced salt solution containing 4% bovine serum albumin
- Flow-through system: 1.5mL/h
- Test temperature: 32°C
- Occlusion: occlusive conditions
- Solubility od test substance in receptor fluid: not tested, but supposedly similar to water solubility of 3.2ng/mL
- Collection intervals: fractions were collected at 6h intervals
- Final sampling procedure: After 24 h the skin surface was wiped with a cotton swab that had been treated with 200 μl of 10% Radiacwash soap; this procedure was repeated with another two swabs that each had been soaked with 200 μl distilled water. All three swabs were placed in a glass vial
labeled as “Soap Skin Wash.” The skin disc was then removed from the cell and placed in another vial labeled as “Skin Depot.” Both the top and bottom chambers of the diffusion cell were then rinsed with 5 ml ethanol at a time, and collected and labeled as “Top-wash” and “Bottom-wash,” respectively. All samples were stored at −20◦C prior to chemical analysis.

Results and discussion

Absorption in different matrices:

Values given as average mass recovery (4 skin samples, triplicate measurements)
Skin Depot: 28% (low dose), 34% (high dose)
Soap skin wash: 52% (low dose), 21% (high dose)
Top wash: 0.5% (low dose), 0.4% (high dose)
Bottom wash: 0.08% (low dose), 0.01% (high dose)
Receiver Solution (sum over 24h): 0.04% (low dose), 0.002% (high dose)
DEHA amounts in the receiver solutions remained essentially constant among samples collected at any of the 6-h intervals.

Total recovery:

81% (low dose)
56% (high dose)
Low recovery might have been due to metabolism by esterases still active in the skin, but was not further investigated.

Percutaneous absorption

Dose:

5 and 100mg

Remarks on result:

other: 24h

Remarks:

2.2ng/cm²/h

Applicant's summary and conclusion

Executive summary:

Our results showed that the majority of applied DEHA mass remained in the Skin Depot and Soap Skin Wash. Together they accounted for the majority of mass recovered. A small percentage of the total mass approximately 0.5% was also found in the Top-wash and Bottom-wash solutions. The average percent mass recovery in the in vitro dermal absorption experiments was 81 and 56% for the low dose and high dose, respectively. Rather low solubility in receptor solution (app. 4 fold above the measured concentrations) might have influenced dermal penetration.