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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 from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1994

Materials and methods

Principles of method if other than guideline:
In Vitro percutaneous absorption study was conducted to determine the dermal absorption of sodium arsenate (73As) in various donor vehicles (aqueous and solid) on the skin surface of female B6C3F1 mice under various conditions of exposure. Doses of 5, 50, 500 or 5000 ng were applied to the skin surface (area = 0.64 cm2) as the solid compound, in aqueous vehicle (100 and 250 µL) or in soil (23 mg/cm2). This experiment was conducted for 24 hours using previously clipped full-thickness dorsal skin in a flow-through system with HEPES-buffered Hanks' balanced salt solution as the receptor fluid. Dermal absorption was quantified by summing the amounts of arsenate-derived radioactivity using a gamma counter in the receptor fluid and skin following washing of the skin surface to remove unpenetrated compound.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Sodium arsenate (73As)
- Source: Los Alamos National Laboratory, USA
- Radiochemical purity (if radiolabelling): >99%
Radiolabelling:
yes

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
female

Administration / exposure

Vehicle:
water
Duration of exposure:
- 24 hours exposure for 5, 50, 500 or 5000 ng sodium arsenate (all vehicles)
- 1 hour exposure for 50 ng sodium arsenate (100 µL aqueous vehicle)
- 1 hour exposure for 50 ng sodium arsenate (100 µL aqueous vehicle) and receptor fluid perfused for additional 23 hours
Doses:
5, 50, 500 or 5000 ng
No. of animals per group:
Not applicable

Results and discussion

Percutaneous absorptionopen allclose all
Dose:
100 µL aqueous vehicle
Parameter:
percentage
Absorption:
62 %
Remarks on result:
other: 24 hours
Remarks:
maximum absorption (62% of the applied dose) was obtained from 100 µL aqueous vehicle and skin contained a higher level of the compound than the receptor fluid.
Dose:
Solid vehicle
Parameter:
percentage
Absorption:
< 0.3 %
Remarks on result:
other: 24 hours
Remarks:
Solid provided the least (<0.3% of the applied dose) absorption of the chemical, with the major portion (68%) of the absorbed dose residing within the skin
Conversion factor human vs. animal skin:
None

Any other information on results incl. tables

- Absorption of sodium arsenate increased linearly in all exposure vehicles, with a constant fraction of the dose being absorbed.

- In aqueous vehicle (100 µL), maximum absorption (62% of the applied dose) was obtained and the skin contained a higher level of the compound than the receptor fluid.
- Solid provided the least (<0.3% of the applied dose) absorption of the chemical, with the major portion (68%) of the absorbed dose residing within the skin

- Skin compartment contained higher percentages of the permeated dose than the receptor fluid in all cases with the highest value (> 89% of permeated dose) was obtained with 250 µL aqueous vehicle

- Short term (1 hour) dermal exposure to arsenate in water resulted in the passage of the chemical into the skin, which on further perfusion (23 hours) passed into receptor fluid

Table 1:Maximum permeation rates of sodium arsenate through mouse skin from different exposure vehicles

 

Vehicle

Applied dose (ng)

Permeation rate*

Water (100 µL)

5

10.1 (4.8)

50

9.1 (5.5)

500

11.5 (2.7)

Water (250 µL)

5

0.9 (0.3)

50

1.0 (0.1)

500

1.9 (0.8)

Solid

5

4.9 (3.6)

50

5.5 (2.7)

500

5.5 (2.9)

Percentage of applied dose/4 hours.

Values are mean ± SD of atleast five determinations

Applicant's summary and conclusion

Conclusions:
Under the test conditions, in vitro dermal absorption of sodium arsenate is greater in aqueous vehicle than soil in skin of B6C3F1mice
Executive summary:

In vitro percutaneous absorption study was conducted to determine the dermal absorption of sodium arsenate (73As) in various donor vehicles (aqueous and solid) on the skin surface of female B6C3F1 mice under various conditions of exposure. Doses of 5, 50, 500 or 5000 ng were applied to the skin surface (area = 0.64 cm2) as the solid compound, in aqueous vehicle (100 and 250 µL) or in soil (23 mg/cm2). This experiment was conducted for 24 hours using previously clipped full-thickness dorsal skin in a flow-through system with HEPES-buffered Hanks' balanced salt solution as the receptor fluid. Dermal absorption was quantified by summing the amounts of arsenate-derived radioactivity using a gamma counter in the receptor fluid and skin following washing of the skin surface to remove unpenetrated compound.

Absorption of sodium arsenate increased linearly in all exposure vehicles, with a constant fraction of the dose being absorbed. In 100 µL aqueous vehicle, maximum absorption (62% of the applied dose) was obtained and the skin contained a higher level of the compound than the receptor fluid. While, solid provided the least (<0.3% of the applied dose) absorption and the major portion (68%) of the absorbed dose residing within the skin.

 

Under the test conditions, In Vitro dermal absorption of sodium arsenate is greater in aqueous vehicle than soil in skin of B6C3F1mice