Bioenergetics- and Physiologically-Based Toxicokinetics/Toxicodynamics and Mode of Action of Arsenic Toxicity to Tilapia Oreochromis mossambicus
Date Issued
2005
Date
2005
Author(s)
Tsai, Jeng-Wei
DOI
en-US
Abstract
This dissertation proposes a physiologically and bioenergetics based algorithm to relate acute and chronic metal toxicities to the internal effect concentration (IEC) of arsenic (As) in tilapia Oreochromis mossambicus. The relationships among As exposure, uptake, accumulation, and toxicity to tilapia are investigated using toxicokinetic (TK) and toxicodynamic (TD) modeling. A 7-d exposure bioassay reveals that the organ-specific bioconcentration factor (BCF) values of tilapia are all above 1 (1.04 – 3.05), indicating that the tilapia is capable of accumulating waterborne As. The As acute toxicity is analyzed by determining the median external effect concentration (LC50) at different integration times, indicating that 96-h LC50 and LC50(∞) for tilapia are 28.68 (95% CI: 24.92-32.44) and 12.04 µg mL-1, respectively. To determine the mode of action (MOA) governing the As acute toxicity, this study assesses the proposed mechanistics base acute toxicity models, including the critical body residue (CBR) model, the critical area under the curve (CAUC) model, and the recently proposed damage assessment model (DAM). This study test the 3 toxicity models with observed data of tilapia exposed to As, to compare the observed and predicted LC50 and median internal effect concentration (CL,50). Result suggests that the DAM characterizes As acute toxicity well and indicates that the intrinsic MOA of As toxicity might act through the reversible reaction between As and specific receptors in target sites. A physiologically based toxicokinetic (PBTK) model is constructed to elucidate the major mechanisms, accounting for the organ-specific selected accumulation of As in tilapia and then utilize the model to predict the behavior of As in tilapia under different exposure scenarios. This study links kinetically DAM with IEC-based Hill equation model to derive dose-response relationships between equilibrium organ-specific As burdens and mortality effects. Organ-specific dose-response relationships suggest that the gill can be used as a surrogate to assess the As toxicity due to its higher sensibility to toxic effects. To assess As chronic toxicity to tilapia, a bioenergetics-based approach is presented to analyze effects and the MOA of growth inhibition when tilapia are chronically exposed to waterborne As. A 28-d growth bioassay is conducted to quantitatively determine the relationships between As exposures and the magnitudes of growth inhibition. A bioenergetics-based ontogenetic growth model is incorporated with the DEBtox theory to explore the MOA of As growth toxicity. Result shows that the specific growth rates are inversely proportional to As concentrations and are calculated to be 0.76 % d-1 in 0 µg mL-1, 0.54 % d-1 in 1 µg mL-1, 0.26 % d-1 in 2 µg mL-1, and 0.017 % d-1 in 4 µg mL-1, respectively. This study indicates that decreasing of feeding accounts for the As growth inhibition in the case of feeding ad libitum condition. The bioenergetics-based growth model also illustrates the growth trajectories of tilapia in the entire life cycle, suggesting that the maximum biomass of tilapia are 1100.82 g in uncontaminated water, 924.00 g in 1 µg mL-1, 421.51 g in 2 µg mL-1, and 352.13 g in 4 µg mL-1, respectively. The study shows that the proposed physiologically and bioenergetics-based assessment framework successfully links As exposure to TK and TD under varied exposure scenarios. This study also suggests that considering MOAs in ecotoxicology not only improves our understanding of the toxicities of chemicals but also is useful in setting up models and avoiding pitfalls in species- and site-specific environmental risk assessment. This study also supports the suggestion that replacing external concentrations by IECs is a first step toward a measurement for chemical toxicity and can be used to improve the construction of future environmental quality criteria programs, aimed at protecting and restoring the rapidly degrading aquacultural ecosystems.
Subjects
砷
生物能量
生態毒理學
內部有效濃度
作用模態
吳郭魚
毒理動力
毒理動態
Arsenic
Bioenergetics
Ecotoxicology
Internal effect concentration
Mode of action
Tilapia
Toxicokinetics
Toxicodynamics
Type
thesis
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