title: Modeling polycyclic aromatic hydrocarbon bioaccumulation and metabolism in time-variable early life-stage exposures.
abstract: Recent laboratory investigations into the bioaccumulation and toxicity of polycyclic aromatic hydrocarbons (PAH) have focused on low-level, time-variable exposures to early life-stage fish. Polycyclic aromatic hydrocarbon body-burden residues reported in these studies were lower than critical body-burden residues predicted by the target lipid model (TLM). To understand this discrepancy, a time-variable uptake and depuration model of PAH bioaccumulation was developed. Kinetic constants were fit using measured exposure and tissue concentrations. The resulting lipid-water partition coefficients (K(LW)) were uncorrelated with the octanol-water partition coefficient (K(OW))--a qualitatively unrealistic finding considering that numerous studies have reported a positive correlation between the two. Because PAHs are known to be metabolized, the comparison of K(LW) with K(OW) suggests that metabolism may be occurring in early life-stage fish. Therefore, the uptake and depuration model was modified to include metabolism while assuming linearity of K(LW) with K(OW). Calculated metabolism rates were positively correlated with K(OW)--a finding qualitatively similar to those of other studies. The present study provides a reasonable explanation for the discrepancy between the TLM predictions and the measured toxic effect levels. Given the time-variable exposure concentrations, the maximum measured body burdens used to relate to toxic effects may be underestimated. In addition, the maximum body burden of parent PAH plus metabolites may be a better measure in relating tissue concentrations to toxic effects. Incorporating these refinements in relating body burdens to toxic effects may result in a better comparison between TLM predictions and measured effect levels.
authors: HydroQual, 1200 Macarthur Boulevard, Mahwah, New Jersey 07430, USA. rmathew@hydroqual.com
authors: Rooni
authors: R
authors: Mathew
authors: Joy A
authors: JA
authors: McGrath
authors: Dominic M
authors: DM
authors: Di Toro
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D004781:Environmental Exposure; D005399:Fishes / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D007700:Kinetics; D016014:Linear Models; D008055:Lipids / Q000737:chemistry; D008954:Models, Biological; D000442:Octanols / Q000737:chemistry; D010063:Ovum / Q000187:drug effects; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity*; D015203:Reproducibility of Results; D015996:Survival Rate; D013997:Time Factors; D018675:Toxicity Tests; D014867:Water / Q000737:chemistry
chemical_list: D008055:Lipids; D000442:Octanols; D011084:Polycyclic Aromatic Hydrocarbons; D014867:Water