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Toxicological information

Dermal absorption

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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: The study reasonably well reported and adequately validated therefore results can be considered reliable 2.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1994

Materials and methods

Principles of method if other than guideline:
The partition coefficient (PC) of a chemical in skin is an indicator of the capacity for the chemical in the skin and may reflect the rate at which a chemical penetrates the skin and enters into systematic circulation. This method measures the skin:air PC for volatile organic chemicals.

Clipped whole-thickness skin was obtained from dorsal surface of 8- to 16- week-old male F-344 rats. After removal of the hypodermis, skin was cut into strips and placed on the side of a glass vial. An organic chemical vapor was introduced into a sealed sample vial (initial concentration before equilibrium was 203ppm) and a corresponding reference vial, which were equilibrated at 32oC. Headspace concentrations at equilibrium were used to determine the skin:air PC value.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Dibromomethane
EC Number:
200-824-2
EC Name:
Dibromomethane
Cas Number:
74-95-3
Molecular formula:
CH2Br2
IUPAC Name:
dibromomethane
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals or test system and environmental conditions:
Rats were group-housed (3/ cage) in clear plastic cages with wood chip bedding. Water and feed Purina Formula (No. 5008) were available ad libitum. the ambient temp was maintained at 22+/- 2oC and light was regulated on a 12-hour light /dark cycle (starting at 0600 hour).

Administration / exposure

Details on in vitro test system (if applicable):
Pieces of skin, either miced to 1-mm cubes or cut to 1x0.5-cm strips, were the best sizes to compare. Dorsal skin of a rat was clipped using an elecric clipper immediately after euthanasia with carbon dioxide. Afetr cooling the skin, the hypodermis was removed, the skin was cut into pieces with a razor blade, and the pieces were placed on the walls of scintillation vials (24.65 ml volume) without saline.

Results and discussion

Applicant's summary and conclusion

Conclusions:
Dibromomethane quickly enters the skin as shown by the high Skin:air PC value 68.3.
Executive summary:

The partition coefficient (PC) of a chemical in skin is an indicator of the capacity for the chemical in the skin and may reflect the rate at which a chemical penetrates the skin and enters into systematic circulation. In this simple method to measure the skin:air PC for volatile organic chemicals is presented.

  Important considerations in the development of this method for a skin:air PC were the effect of size and shape of skin sample, initial chemical concentration, and time to equilibrium in the skin. Clipped whole-thickness skin was obtained from dorsal surface of 8- to 16- week-old male F-344 rats. After removal of the hypodermis, skin was cut into strips and placed on the side of a glass vial.  An organic chemical vapor was introduced into a sealed sample vial (initial concentration before equilibrium was 203ppm) and a corresponding reference vial, which were equilibrated at 32oC. Headspace concentrations at equilibrium were used to determine the skin:air PC value.

 The skin:air PC values correlated with previously determined vapor permeability constants but correlated poorly with octanol/water PC values. 

 After incubating samples for various times, the equilibration time for dibromomethane is skin was determined to be 4 hours. There was no statistical between minced skin and stripes of skin. Dibromomethane quickly enters the skin as shown by the high Skin:air PC value 68.3.

This method provides screening technique for predicting skin penetration of volatile chemicals. Further studies, in which the stratum corneum and viable epidermis are separated, are needed to account for partitioning into these discrete physiological compartments.