Reaction mass of heptachromium tricarbide and trichromium dicarbide

Dermal absorption

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Comparable to guideline study. The release of chromium from chromium carbide is very similar to the release from chromium metal and chromium(III) oxide and therefore the results obtained with these substances can readily be used in the assessment of the reaction mass of heptachromium tricarbide and trichromium dicarbide.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

In vitro percutaneous absorption of chromium powder an the effect of skin cleanser

Author:

Larese Filon F, D'Agostin F, Crosera M, Adami G, Bovenzi M. and Maina G

Year:

2008

Bibliographic source:

Toxicology in Vitro 22, 1562-1567

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Deviations:

yes

Remarks:

In some of the experiments the test substance was removed after 30 minutes

Principles of method if other than guideline:

In some of the experiments the donor solution (containing Cr) was removed after 30 minutes, the skin was cleansed with a detergent, and pure synthetic sweat solution was added instead of the donor solution.
To carry out the experiments, the authors used the experience and protocols employed during the European project EDETOX (evaluations and predictions of dermal absorption of toxic chemicals), funded by EU.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Chromium

EC Number:

231-157-5

EC Name:

Chromium

Cas Number:

7440-47-3

Molecular formula:

Cr

IUPAC Name:

chromium

Details on test material:

- Name of test material (as cited in study report): Chromium

- Substance type: metal
- Physical state: powder
- Analytical purity: 99.8% purity (metals basis)
Average particle size (APS) <10 µm
Manufacturer: Alfa Aesar (Karlsruhe, Germany)

Radiolabelling:

no

Administration / exposure

Details on in vitro test system (if applicable):

SKIN PREPARATION
- Source of skin: human (surgical waste: at least two donors for each experiment, male and female 45-71 years)
- Ethical approval if human skin: no data
- Type of skin: full thickness skin
- Preparative technique: Skin obtained as surgical waste. Prior to freezing, subcutaneous fat was removed and hair shaved.
- Thickness of skin (in mm): <1mm ; mean exposed skin area 3.92 cm2
- Membrane integrity check: Skin integry was checked before and after each experiment using electrical conductibility by means of a conductometer (Metrohm, 660 Conductometer, Herisau, Switzerland). The electrical conductance data (as µS) were converted to K[omega]cm-2. Cells with a resistance <3.95 ± 0.27 K[omega]cm-2were considered to be damaged.
- Storage conditions: Freezer -25 C for a period up to (but not exceeding) 4 months
- Justification of species, anatomical site and preparative technique: no data


PRINCIPLES OF ASSAY
- Diffusion cell: Franz diffusion cells
- Cr metal powder was suspended in a synthetic sweat solution with pH 4.5 (donor fluid)
- Receptor fluid: phosphate buffered saline (PBS) (pH 7.35)
- Solubility od test substance in receptor fluid: no data
- The chromium powder in synthetic sweat was added to the exposure chamber.
- Test temperature: 32 C
- Humidity: no data
- Occlusion: no data
- Reference substance(s): no data
- Other: At 24 h the dermal bathing solution was removed and Cr concentration in the receptor fluid was determined by electro-thermal atomic absorption spectrometry.
After the experiments the skin was stored in a freezer at -25 C. Before analysis, the skin membranes were dried for 24 h at room temperature. Then the exposed area was cut into sections, weighted and digested in 70% v/v HNO3.

In experiment 2, the donor suspension was removed after 30 minutes, the skin pieces were carefully cleaned using cleanser, and instead of the donor solution synthetic sweat (pH 4.5) was added. The experiment was stopped after 24 h, after which samples were analysed as described above.

Results and discussion

Absorption in different matrices:

The permeation study resulted in low concentrations of Cr in the receiving phase at 24 h. The mean concentration was 0.016 µg/cm2 (sd 0.005 µg/cm2). In the experiment containing cleansing after 30 minutes, no detectable amounts of Cr could be detected in the receiving cells.

The Cr amounts detected in the skin samples after the exposures were higher in skin exposed for 30 minutes and cleaned, than in those exposed for 24 h (5.46 ± 1.09 and 3.19 ± 1.48 µg/cm2, respectively; p<0.03 Mann-Whitney U-test)

Applicant's summary and conclusion

Conclusions:

An in vitro percutaneous absorption study showed that chromium applied as powder in an artificial sweat suspension at pH 4.5 can penetrate the skin, but the concentrations in the receiving phases are very low. Decontamination, done after 30 minutes of exposure, prevents the Cr skin permeation effectively. The amount of chromium found in the skin layers was higher in the samples exposed for 30 minutes and washed with cleanser, than in those exposed for 24 h. This indicates a rapid initial absorption and ready binding of Cr to proteins.

Executive summary:

An in vitro percutaneous absorption study showed that chromium applied as powder in an artificial sweat suspension at pH 4.5 can penetrate the skin, but the concentrations in the receiving phases are very low. Decontamination, done after 30 minutes of exposure, prevents the Cr skin permeation effectively.

The amount of chromium found in the skin layers was higher in the samples exposed for 30 minutes and washed with cleanser, than in those exposed for 24 h. This indicates a rapid initial absorption and ready binding of Cr to proteins. Decontamination, done after 30 minutes of exposure, prevents the Cr skin permeation effectively. The amount of chromium found in the skin layers was higher in the samples exposed for 30 minutes and washed with cleanser, than in those exposed for 24 h. This indicates a rapid initial absorption and ready binding of Cr to proteins.