Estimation of octanol-water partition coefficients and correlation with dermal absorption for several polyhalogenated aromatic hydrocarbons.
n-Octanol-Water partition coefficients (K(ow)) were experimentally estimated for: 2,3,7,8-tetrachloro-and 2,3,7,8-tetrabromodibenzo-p-dioxin; 2,3,7,8-tetrachloro-, 2,3,7,8-tetrabromo-, and 1,2,7,8-tetrabromodibenzofuran; 1,2,3,7,8-pentachloro-, 1,2,3,7,8-pentabromo-, 2,3,4,7,8-pentachloro-, and 2,3,4,7,8-pentabromodibenzofuran; 1,2,4,6,8,9-hexachlorodibenzofuran (HxCDF), and 3,4,3',4'-tetrachlorobiphenyl (3,4,3',4'-TCB). The method involved correlation of literature K(ow) with reverse-phase high-performance liquid chromatography (RP-HPLC) retention time for a series of 23 calibration standards and estimation of K(ow) for test compounds from measured RP-HPLC retention. Retention times for all standards and test chemicals were measured in duplicate on the same octadecasilane (C18) reverse-phase column with an isocratic 85:15 methanol:water mobile phase; solutes were detected by uv absorbance (254 nm). Literature log K(ow) values used for the calibration standards had been measured exclusively by the generator column method. Log K(ow) estimates for the test compounds in the present study ranged from 5.45 for 3,4,3',4'-TCB to 6.81 for HxCDF. K(ow) estimates were then plotted against laboratory data for the in vivo 3-day dermal absorption of single equimolar doses (200 pmol and 20 nmol, or approximately 1 nmol/kg and approximately 0.1 mumol/kg) of selected test compounds in male F344 rats. Strong inverse correlations were found between octanol-water partition coefficient estimates and single-dose dermal absorption for most of the compounds studied. In addition, RP-HPLC retention time itself appeared to be as equally suited as K(ow) to such correlations with dermal absorption. The structure-activity relationships suggested in this study were sought in order to explain observed differences in the dermal absorption of polyhalogenated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners differing in number, position, and/or type (Cl or Br) of halogen substituents. Moreover, these results should be of predictive value in the risk assessment of dermal exposure to polychlorinated dibenzo-p-dioxins, dibenzofurans, biphenyls, and their brominated analogues.
Jackson
J A
JA
ManTech Environmental Technology, Inc., Research Triangle Park, North Carolina 27709.
Diliberto
J J
JJ
Birnbaum
L S
LS
D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000493:pharmacokinetics; D002138:Calibration; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004147:Dioxins / Q000737:chemistry / Q000493:pharmacokinetics; D006846:Hydrocarbons, Halogenated / Q000737:chemistry* / Q000493:pharmacokinetics*; D007700:Kinetics; D008297:Male; D000442:Octanols / Q000737:chemistry; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000493:pharmacokinetics; D011083:Polycyclic Compounds / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D012869:Skin Absorption; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D001572:Benzofurans; D004147:Dioxins; D006846:Hydrocarbons, Halogenated; D000442:Octanols; D011083:Polycyclic Compounds; D014867:Water; D011078:Polychlorinated Biphenyls