title: Coupling toxicokinetics and pharmacodynamics for predicting survival of abalone (Haliotis diversicolor supertexta) exposed to waterborne zinc.
abstract: We developed a mortality model, by coupling an acute toxicity model and a pharmacodynamic model, to predict survival of abalone (Haliotis diversicolor supertexta) exposed to waterborne zinc (Zn). We conducted a laboratory 14-day exposure experiment to obtain biokinetic parameters of depuration rate constant (k(2)) and bioconcentration factor (BCF). A one-compartment uptake-depuration model was used to fit the exposure data to estimate BCF and k(2) values. The acute toxicity model was developed based on the receptor theory and was verified with LC(50)(t) data obtained from a 7-day acute toxicity test. A highly significant correlation (r(2) = 0.98) was found between predictions and LC(50)(t) data for the acute toxicity model, indicating a successful description of 7-day LC(50)(t) data of Zn in abalone. The predicted time course of lethal body burden of Zn in abalone was compared with measured data, showing that the average percent error was 14.04 +/- 3.02%. A refined pharmacodynamic model was expressed as the Hill equation, which in terms of waterborne Zn and LC(50)(t) data was used to fit observed mortality percentages to determine the Hill coefficient (r(2) = 0.98). The proposed mortality model in terms of whole body burden and lethal body burden at site of action was then employed to predict the time-varying mortality of abalone exposed to various Zn concentrations in pond water. Our results demonstrate that 96-h LC(50) and incipient LC(50) for H. diversicolor supertexta exposed to Zn are 1.1 and 1.05 mg L(-1), respectively. Our predictions also demonstrate that equilibrium lethal body burden at site of action is about 198 microg g(-1), whereas the mortalities never reach 50% when H. diversicolor supertexta exposed to Zn is < or = 1 mg L(-1).
authors.affiliation: Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan 10617 Republic of China. cmliao@ccms.ntu.edu.tw
authors.forename: Chung-Min
authors.initials: CM
authors.lastname: Liao
authors.forename: Bo-Ching
authors.initials: BC
authors.lastname: Chen
authors.forename: Ming-Chao
authors.initials: MC
authors.lastname: Lin
authors.forename: Hsiao-Mei
authors.initials: HM
authors.lastname: Chiu
authors.forename: Yun-Hua
authors.initials: YH
authors.lastname: Chou
mesh_terms: D000818:Animals; D005544:Forecasting; D007700:Kinetics; D007928:Lethal Dose 50; D008962:Models, Theoretical; D008974:Mollusca; D013534:Survival; D014018:Tissue Distribution; D014873:Water Pollutants / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity*; D015032:Zinc / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D014873:Water Pollutants; D015032:Zinc