Application of multi-component Damage Assessment Model (MDAM) for the toxicity of metabolized PAH in Hyalella azteca.
Biotransformation and time-dependent toxicity of pyrene and fluorene, in the presence and absence of the biotransformation inhibitor 6-propylpiperonyl butyl diethylene glycol ether known as piperonyl butoxide (PBO), were investigated in Hyalella azteca. Toxicokinetics and biotransformation were determined in both short- and longterm experiments. For pyrene, the uptake rate coefficient (ku = 99 +/- 9 L kg(-1) h(-1)), elimination rate constant for parent compound (kep = 0.050 +/- 0.008 h(-1)), biotransformation rate constant (km = 0.016 +/- 0.003 h(-1)), and elimination rate constant for metabolites (kem = 0.021 +/- 0.007 h(-1)) were determined from a short-term study. For fluorene, ku (130 +/- 30 L kg(-1) h(-1)) and kep (1.7 +/- 0.2 h(-1)) were estimated based on km (0.015 +/- 0.002 h(-1)) and kem (0.011 +/- 0.002 h(-1)) determined from a long-term study. At steady state, the percent metabolites for pyrene and fluorene were 43% and 58%, respectively, determined from km/(km +/- kem). Time-dependent toxicity was determined as both lethal water concentration and lethal body residue in the presence and absence of PBO. Co-exposure to PBO decreased the median lethal residue (LBR50) for parent pyrene and shortened the median lethal time (LT50). Pyrene toxicity was explained by the body residues of parent pyrene and PBO, where the metabolites' contribution was negligible. Forfluorene, co-exposure to PBO increased the LBR50 for parent fluorene and shortened the LT50. Thus, fluorene metabolites contributed significantly to the toxicity. Using a multicomponent damage assessment model, the toxicodynamic parameters, damage accrual rate coefficient, and damage recovery rate constant for parent pyrene and parent fluorene were very similar and estimated to be from 0.009 to 0.020 micromol(-1) g h(-1) and from 0.003 to 0.013 h(-1), respectively, and the incipient LBR50 at the infinite time (LBR50(t = infinity)) was from 0.24 to 0.46 micromol g(-1), respectively. These values are similar to the reported LBR50(t = infinity) for other nonpolar narcotics such as pentachlorobenzene (PCBz, 0.38 +/- 0.13 micromol g(-1)) and dichlorophenylchloroethylene (DDE, 0.41 +/- 0.19 micromol g(-1)). For fluorene metabolites, these values were 0.10 +/- 0.03 micromol(-1) g h(-1), 0.034 +/- 0.021 h(-1), and 0.33 +/- 0.23 micromol g(-1), respectively. However, for pyrene metabolites, since toxicity of pyrene metabolites was negligible, the parameters could not be estimated.
Cooperative Institute for Limnology and Ecosystems Research, University of Michigan, Ann Arbor, Michigan 48105-1593, USA.
Jong-Hyeon
JH
Lee
Peter F
PF
Landrum
D033304:Amphipoda; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D004347:Drug Interactions; D007928:Lethal Dose 50; D008954:Models, Biological; D010882:Piperonyl Butoxide / Q000494:pharmacology; D011084:Polycyclic Aromatic Hydrocarbons / Q000493:pharmacokinetics* / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000493:pharmacokinetics / Q000633:toxicity
D011084:Polycyclic Aromatic Hydrocarbons; D014874:Water Pollutants, Chemical; D010882:Piperonyl Butoxide