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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:
other: acceptable publication

Data source

Reference
Reference Type:
publication
Title:
In vitro Absorption of Some o-Phthalate Diesters Through Human and Rat Skin
Author:
Scott RC et al.
Year:
1987
Bibliographic source:
Environ. Health Perspect. 74: 223-227

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)

Test material

Constituent 1
Chemical structure
Reference substance name:
Dimethyl phthalate
EC Number:
205-011-6
EC Name:
Dimethyl phthalate
Cas Number:
131-11-3
Molecular formula:
C10H10O4
IUPAC Name:
1,2-dimethyl benzene-1,2-dicarboxylate
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): DMP
- Physical state: liquid
- Purity: 99% (as stated by supplier)
Radiolabelling:
no

Administration / exposure

Duration of exposure:
Rat: 8h
Human: 30h
Doses:
app. 0.5mL, undiluted - covering the whole surface of the membrane
Details on in vitro test system (if applicable):
SKIN PREPARATION - Human
- Source of skin: deceased donors, mostly female and 55 years or older
- Type of skin: Abdominal epidermal sheets
- Preparative technique: The subcutaneous fat was removed and the skin immersed in water at 60°C for 40 to 45 sec . The epidermis was peeled away from the dermis and the epidermal sheet floated onto water and then taken up onto aluminium foil.
- Membrane integrity check: Yes, via tritiated water, human membranes with values greater than 1.5 x 10-3 cm/hr were rejected
- Storage conditions: 4°C, for at most 7 days after preparation
- Justification of species, anatomical site and preparative technique:

SKIN PREPARATION - Rat
- Source of skin: Wistar rats
- Type of skin: dorsal
- Preparative technique: The dorsal skin was removed and placed in 2 M NaBr for up to 24 hr. After blotting the epidermis dry, it was peeled from the dermis and stored on aluminium foil
- Membrane integrity check: Yes, via tritiated water, rat membranes with values greater than 2.5 x 10-3 cm/hr were rejected
- Storage conditions: 4°C, for at most 7 days after preparation
- Justification of species, anatomical site and preparative technique: To different methods have been used for the preparatipn of the human and rat epidermal membranes. Human epidermal membranes can be prepared by either heat or NaBr separation . The membranes produced have the same permeability properties independent of the reparation technique.

PRINCIPLES OF ASSAY
- Receptor fluid: 50% ethanol in water
- Water solubility: 3.38 ml/L
- Static system: Samples were taken frequently from the receptor chamber and replaced by an equal volume of fresh receptor fluid.
- Test temperature: 30°C +/- 1°C
- Occlusion: No
- Reference substance(s):
- Other: At the end of the experiment, the test substance was washed off the donor surface, and the determination of the membrane integrity was repeated. Comparing this value to the initial integrity give an indication of irreversibel alterations in the barrier properties of the epidermal membrane caused by contact with the test substance.

Results and discussion

Any other information on results incl. tables

Following application to the skin, a lag phase followed by a linear phase of absorption was detected.

Human:

Lag phase: 0.1h

Steady state absorption: 3.95 +/- 0.64µg/cm²/h (14 samples)

Permeability constant: 0.0332 +/- 0.0054 µm/h (4 samples)

Rat:

Lag phase: 0.5h

Steady state absorption: 41.6 +/- 4.18 µg/cm²/h

Permeability constant: 0.345 +/- 0.0351 µm/h

Following contact to DMP, permeability of human skin was hardly altered (comparable to the effects of water). In contrast, a permeability was increased by a factor of 4.3 in rat skin, indicating some irreversible damage to the rat epidermal membrane.

Applicant's summary and conclusion