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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 428 (Skin Absorption: In Vitro Method)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Lead oxide
- Supplier: EBRC Consulting GmbH, Zeppelinstrasse 8, D-30175 Hannover, Germany
- Substance type: Solid
- Physical state: Yellowish powder
- Analytical purity: 99.8%
- Batch No.: 210213
- Stability under test conditions: 2 years
- Storage condition of test material: Ambient temperature in the dark
Radiolabelling:
no

Test animals

Species:
human

Administration / exposure

Type of coverage:
open
Vehicle:
other: 1% hydroxypropylmethyl cellulose in water
Duration of exposure:
6 hours, with an additional 18 hour monitoring period
Doses:
- Nominal doses: 0, 100, and 1000 µg/cm2
- Actual doses: 0, 111, and 1033 µg/cm2
Details on study design:
Test preparations (7.6 µL) were applied over the surface of the stratum corneum of exposed skin. At 6 hours post-exposure, skin was washed with a 2% soap solution and then dried with tissue swabs. At 24 hours post-exposure, each diffusion cell was disconnected and the underside of the skin was rinsed with receptor fluid. The skin was removed and the donor and receptor chambers were transferred into separate pots of receptor fluid and test items were extracted for 30 minutes. The skin was dried and the stratum corneum was removed with 25 successive tape strips, which were pooled into vials. Throughout the study, receptor fluid was collected in four fractions (0-6 hours, 6-12 hours, 12-18 hours, and 18-24 hours). All samples were analyzed for lead concentration by Harwell Scientifics using ICP-MS.
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: 40-year-old patient undergoing routine surgery
- Ethical approval if human skin: Informed consent received
- Type of skin: A single, full-thickness human breast skin sample
- Preparative technique: Split-thickness membranes prepared by pinning the skin, with the stratum corneum up, onto a raised corkboard and cutting at a setting of 200-400 um depth using a Zimmer electric dermatome.
- Thickness of skin: Split-thickness skin samples were 390-400 um thick
- Membrane integrity check: Assessed by penetration of tritiated water (250 µL) applied to skin surface with the donor chamber occluded. All skin samples with a tritiated water permeability coefficient (kp) less than 0.0025 cm/hour were accepted into the study.
- Storage conditions: Full-thickness skins were dried and stored at -20 degrees C. Split-thickness skins were used immediately after being cut.

PRINCIPLES OF ASSAY
- Diffusion cell: Automated flow-through diffusion cell apparatus (Scott/Dick, University of Newcastle-upon-Tyne, United Kingdom)
- Receptor fluid: Phosphate buffered saline containing 5% bovine serum albumin, Streptomycin, and Penicillin G, pH 7.4
- Flow-through system: Flow-through cells were connected to multi-channel peristaltic pumps from their afferent ports. The receptor chamber volume was 0.25 mL and the peristaltic pumps maintained a flow-rate of 1.5 mL/hour.
- Test temperature: 32 degrees C
- Occlusion: None; the chambers were left open to the atmosphere.
- Other: Surface area of exposed skin within diffusion cells was 0.64 cm2.

Results and discussion

Absorption in different matrices:
For the 111 µg/cm2 dose: 95.63% of the applied lead was removed during the wash at 6 hours post-exposure. At 24 hours post-exposure, 99.51% of the applied dose was not absorbed. The absorbed dose into the receptor fluid was <0.01% (5 ng/cm2) of the applied dose and the dermal delivery (absorbed dose plus the amount in the skin itself) was 0.13% (148 ng/cm2) of the applied dose.

For the 1033 ug/cm2 dose: 96.10% of the applied lead was removed during the wash at 6 hours post-exposure. At 24 hours post-exposure, 98.28% of the applied dose was not absorbed. The absorbed dose was < 0.01% (10 ng/cm2) of the applied dose and the dermal delivery was 0.05% (479 ng/cm2) of the applied dose.
Percutaneous absorptionopen allclose all
Dose:
111 ug/cm2
Parameter:
percentage
Absorption:
ca. 0.13 %
Remarks on result:
other: 24 hours
Dose:
1033 ug/cm2
Parameter:
percentage
Absorption:
ca. 0.05 %
Remarks on result:
other: 24 hours

Applicant's summary and conclusion

Conclusions:
The authors concluded that the apparent decrease in absorption as a function of dose may be attributable to the considerable background from endogenous lead in the donor skin restricting the reliability of the absorption factor at the low dose.
Executive summary:

This study assessed the in vitro absorption of lead oxide in human skin samples at 0, 111, and 1033 µg/cm2 concentrations over 24 hours. For the 111 µg/cm^2 dose, 95.63% of the applied lead was removed during the wash at 6 hours post-exposure. At 24 hours post-exposure, 99.51% of the applied dose was not absorbed. The absorbed dose into the receptor fluid was <0.01% (5 ng/cm^2) and the dermal delivery was 0.13% (148 mg/cm^2) of the applied dose. For the 1033 µg/cm^2 dose, 96.10% of the applied lead was removed during the wash at 6 hours post-exposure. At 24 hours post-exposure, 98.28% of the applied dose was not absorbed. The absorbed dose was <0.01% (10 ng/cm^2) and the dermal delivery was 0.05% (479 ng/cm^2) of the applied dose. The authors concluded that the apparent decrease in absorption as a function of dose may be attributable to the considerable background from endogenous lead in the donor skin restricting the reliability of the absorption factor at the low dose.