Diarsenic trioxide

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:

other: Reasonably well-documented publication, conduct acc. to general scientific principles.

Data source

Reference

Reference Type:

publication

Title:

In vivo and in vitro percutaneous absortpion and skin decontamination of arsenic from water and soil

Author:

Wester et al.

Year:

1993

Bibliographic source:

Fundamental and applied toxicology 20, 336-340

Materials and methods

Principles of method if other than guideline:

In vivo (Rhesus monkey) and In vitro (human skin) percutaneous absorption of arsenic acid (73As radiolabelled) from soil and water for (comparative reasons) was investigated. This endpoint record focuses on the in vitro data in human skin, because of higher relevance for human health risk assessment. Further, the focus is on the absorption experiments conducted with aqueous solutions (worst-case, as compared to absorption from soil).

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Arsenic acid

EC Number:

231-901-9

EC Name:

Arsenic acid

Cas Number:

7778-39-4

IUPAC Name:

arsenic acid

Radiolabelling:

yes

Remarks:

73As

Administration / exposure

Vehicle:

water

Doses:

Water formulations were prepared for comparison to experiments on As absorption from soil. The water load on skin was 5 µL/cm2 skin area. This amount of water is a thin layer of water which covers the skin but does not run off the skin. It is similar to a thin layer of other dermatological doses (cream, ointment).
The low (trace) dose was 0.000024 µg/cm2. The high dose: gave an arsenic skin concentration of 2.1 µg/cm2.

Details on in vitro test system (if applicable):

Three separate donor skin sources with three replicates per each experiment were used. Small cells were of the flow-through design with a 1 cm2 surface area. Phosphate-buffered saline at a flow rate of 3.0 mL/hr (reservoir volume) served as receptor fluid. Human cadaver skin was dermatomed to 500 µm and stored refrigerated at 4°C in Eagle's minimum essential medium to preserve skin viability. The skin was used within 5 days.
73As in water formulation was applied with a micropipette to the surface of the skin. Standards for each formulation were made by dissolving 5 µL of formulation in 10 mL of scintillation cocktail. At the end of a 24 h period the system was stopped. The residual water remaining in the cells was collected and analyzed. The skin surface was washed once with liquid soap (50/50 water, v/v: Ivory Liquid, Procter & Gamble. Cincinnati, OH) and twice with 1 mL of distilled water, and the wash solutions were analyzed by scintillation counting. Cells were disassembled. Cell tops were rinsed three times with 1 mL of water. The inner surface of the skin was swabbed with cotton balls and counted. The skin itself was completely solubilized in Soluene 3540 (Packard lnstruments, Downders Grove, IL), and 1 M HCl was added to neutralize the homogenate. The receptor fluid samples from the permeation cells' residual fluid, the skin surface washes, the cotton balls, the glass apparatus, and the skin itself were assayed for 73As content by liquid scintillation counting.

Results and discussion

Percutaneous absorption

Key result

Time point:

24 h

Dose:

up to 2.1 µg/cm2

Parameter:

percentage

Absorption:

ca. 2 %

Remarks on result:

other: 24 h

Remarks:

in vitro, human skin; result accounts for ca. 1% absorbed As (found in receptor fluid) plus ca. 1% retained in the skin (potentially absorbable)

Any other information on results incl. tables

With water formulation, 0.93 ± 1.1 % of the applied dose accumulated in the receptor fluid and 0.98 ± 0.96% was in skin after surface wash. The soap and water wash accounted for 69.8 ± 16.4%. If in vitro percutaneous absorption is calculated as receptor fluid accumulation plus residual skin concentration (after soap and water wash) then the absorption in human skin is 1.9% from water. It appears from the text of the publication that these detailed results are for the low dose (0.000024 µg/cm2) application only.

However, in the discussion section of the publication, it is mentioned that for the high dose (2.1 µg/cm2), the absorption/penetration was 0.04 µg/cm2, that is also around 2%.