In vitro dermal absorption of flame retardant chemicals.
Flame retardant chemicals may be used in furniture fabric in the future to reduce the flammability of the fabric. As a part of the process to evaluate the potential for exposure to these chemicals, this study examined the in vitro dermal absorption of two flame retardant chemicals. The chemicals were [14C]decabromodiphenyl oxide (DBDPO) and [14C]tris-(1,3-dichloro-2-propyl)phosphate (TDCP). 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 coefficient than DBDPO. The differences in the physico-chemical properties of these two chemicals most likely explains their dissimilar absorption through hairless mouse skin.
Hughes
M F
MF
US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711, USA. hughes.michaelf@epa.gov
Edwards
B C
BC
Mitchell
C T
CT
Bhooshan
B
B
D000279:Administration, Cutaneous; D000818:Animals; D001969:Bromobenzenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002247:Carbon Isotopes; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D005411:Flame Retardants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055768:Halogenated Diphenyl Ethers; D066298:In Vitro Techniques; D051379:Mice; D008812:Mice, Hairless; D008970:Molecular Weight; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; D012869:Skin Absorption
D001969:Bromobenzenes; D002247:Carbon Isotopes; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D009943:Organophosphorus Compounds; D010647:Phenyl Ethers; D011075:Polybrominated Biphenyls; C016805:tris(1,3-dichloro-2-propyl)phosphate; C010902:decabromobiphenyl ether