Registration Dossier

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: Used 14C-test article, appropriate controls for skin viability and published in the peer reviewed literature.

Data source

Reference
Reference Type:
publication
Title:
In vitro dermal absorption of flame retardant chemicals.
Author:
Hughes et al.
Year:
2001
Bibliographic source:
Food Chem Toxicol 39:1263–1270.

Materials and methods

Test guideline
Qualifier:
no guideline available
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes

Test animals

Species:
mouse
Strain:
SKH/HR1
Sex:
female

Administration / exposure

Type of coverage:
other: not applicable
Vehicle:
other: tetahydrofuran
Duration of exposure:
24 hr
Doses:
6, 30 60 nmol
No. of animals per group:
7 samples per dose
Control animals:
yes

Results and discussion

Signs and symptoms of toxicity:
not examined
Remarks:
not applicable
Dermal irritation:
not examined
Remarks:
not applicable
Percutaneous absorption
Dose:
6,30, 60 nmol
Parameter:
percentage
Absorption:
ca. 0.07 - 0.34 %
Remarks on result:
other: 24 hr
Remarks:
neglible movement through skin into receptor fluid

Applicant's summary and conclusion

Conclusions:
The skin is not a route leading to systemic exposure of DecaBDE.
Executive summary:

The in vitro dermal absorption of two flame retardant chemicals, [14C]decabromodiphenyl oxide (DBDPO) and [14C]tris-(1,3-dichloro-2-propyl)phosphate (TDCP) were studied. Skin from the adult hairless female mouse (SKH1) was removed and mounted in flow-through diffusion cells. The chemicals, at three dose levels (DBDPO: 6, 30 and 60 nmol; TDCP: 20, 100 and 200 pmol), were applied in a volatile vehicle (tetrahydrofuran for DBDPO; acetone for TDCP) to the skin. Fractions of receptor fluid, pumped below the skin, were collected over a 24-h period. The skin was washed with solvent (tetrahydrofuran for DBDPO; ethanol for TDCP) to remove unabsorbed chemical 24 h after application. The receptor fluid, skin wash and skin were analyzed for chemical-derived radioactivity. The skin from the high-dose group of both chemicals, and the receptor fluid from TDCP high-dose samples, were analyzed for parent compound and metabolites by HPLC. The 24-h cumulative percent of the dose of DBDPO in the receptor fluid was very low (0.07–0.34%). The applied dose of DBDPO detected in the skin ranged from 2 to 20%. The lowest dose of DBDPO had the highest percentage of the dose (20%) in the skin. The major portion of the applied dose was removed by washing the skin 24 h after application of DBDPO, and ranged from 77 to 92%. HPLC analysis of homogenate extract prepared from the high-dose of DBDPO-treated skin showed the presence of DBDPO and a minor unknown peak. TDCP was readily detected in the receptor fluid; 39–57% of the applied dose of TDCP was in the receptor fluid by 24 h. The solvent wash removed 11–25% of the dose from the skin and 28–35% remained in it. HPLC analysis of the skin homogenate extract and receptor fluid extract from the TDCP high-dose treated samples showed the presence of parent compound and a minor unknown peak. TDCP more readily penetrated hairless mouse skin and diffused into the receptor fluid than DBDPO. TDCP has a lower molecular weight and log octanol:water partition coefficent than DBDPO. The differences in the physico-chemical properties of these two chemicals most likely explains their dissimilar absorption through hairless mouse skin.