| 著作名稱： | Bayesian population physiologically-based pharmacokinetic model for robustness evaluation of withdrawal time in tilapia aquaculture administrated to florfenicol |
| 年度： | 2021 |
| 類別： |
期刊論文
Ecotoxicology and Environmental Safety
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| 摘要： | The antimicrobial residues of aquacultural production is a growing public concern, leading to reexamine the method for establishing robust withdrawal time and ensuring food safety. Our study aims to develop the optimizing population physiologically-based pharmacokinetic (PBPK) model for assessing florfenicol residues in the tilapia tissues, and for evaluating the robustness of the withdrawal time (WT). Fitting with published pharmacokinetic profiles that experimented under temperatures of 22 and 28 °C, a PBPK model was constructed by applying with the Bayesian Markov chain Monte Carol (MCMC) algorithm to estimate WTs under different physiological, environmental and dosing scenarios. Results show that the MCMC algorithm improves the estimates of uncertainty and variability of PBPK-related parameters, and optimizes the simulation of the PBPK model. It is noteworthy that posterior sets generated from temperature-associated datasets to be respectively used for simulating residues under corresponding temperature conditions. Simulating the residues under regulated regimen and overdosing scenarios for Taiwan, the estimated WTs were 12-16 days at 22 °C and 9-12 days at 28 °C, while for the USA, the estimated WTs were 14-18 and 11-14 days, respectively. Comparison with the regulated WT of 15 days, results indicate that the current WT has well robustness and resilience in the environment of higher temperatures. The optimal Bayesian population PBPK model provides effective analysis for determining WTs under scenario-specific conditions. It is a new insight into the increasing body of literature on developing the Bayesian-PBPK model and has practical implications for improving the regulation of food safety. |
| 關鍵字： | Florfenicol; Tilapia; Bayesian analysis; Markov chain Monte Carlo; Physiologically-based pharmacokinetic model |
| 著作名稱： | Epidemiology-based wastewater monitoring for ecological risks of anti-tuberculosis drugs mixture effects. |
| 年度： | 2023 |
| 類別： |
期刊論文
Science of the Total Environment
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| 摘要： | First-line anti-tuberculosis (TB) drugs are commonly used to treat TB worldwide, leading to more contaminated wastewater being widely discharged into aquatic environments. However, studies of mixture interactions of anti-TB drugs and their residues in aquatic environments are scarce. This study aimed to determine the toxic interactions of anti-TB drugs—isoniazid (INH), rifampicin (RMP), and ethambutol (EMB)—in binary and ternary mixtures on Daphnia magna and used the epidemiology of TB history to construct epidemiology-based wastewater monitoring for assessing the environmental release of residues and related ecological risks. The acute immobilization of median effect concentrations (EC50) was 25.6 mg L−1 for INH, 80.9 mg L−1 for RMP, and 188.8 mg L−1 for EMB, as toxic units (TUs) for assessing mixture toxicity. The ternary mixture exhibited the lowest TUs at 50 % effects with 1.12, followed by 1.28 for RMP + EMB, 1.54 for INH + RMP, and 1.93 for INH + EMB, indicating antagonistic interactions. Nevertheless, the combination index (CBI) was used to examine the mixture toxicity in response to immobilization, revealing that the ternary mixture of CBI ranged from 1.01 to 1.08, tending to have a nearly additive effect when suffering >50 % effect (at high concentration levels). The forecasted environmentally relevant concentrations of anti-TB drugs have been on downward trends with ng L−1 level from 2020 to 2030 in Kaohsiung, Taiwan. Although ecotoxicological risks from the wastewater treatment plant and receiving water in the field were slightly greater than the prediction from epidemiology-based wastewater monitoring, there were no risk concerns. Here, we achieved the establishment of evidence that anti-TB drug mixtures interaction and epidemiological-based monitoring support a systematic approach, resolving the absence of the mixture toxicity information for anti-TB mixture risk assessment in aquatic environments. |
| 關鍵字： | Anti-tuberculosis drugsMixture toxicityDaphnia magnaEpidemic modelsEcotoxicological risk |
| 著作名稱： | Wastewater monitoring based on an epidemiological method for assessing environmental mixture risks of anti-tuberculosis drugs |
| 年度： | 2023 |
| 類別： |
會議論文
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| 摘要： | The environmentally relevant concentration of antimicrobial agents can be monitored by surveying or predicting the infected population in communities. Our study proposed real-time environmental monitoring based on epidemiology for assessing environmental mixture risks of anti-tuberculosis (TB) drugs, isoniazid (INH), rifampicin (RMP), and ethambutol (EMB). The trends of environmentally relevant concentration are decreasing in 2020 – 2030. The EMB has the highest residues in the environmental releases, whereas the INH was the lowest. For the mixture toxicity threshold, the no-observed effect concentration (NOEC) of RMP+EMB and INH+RMP+EMB mixture exposure are not observed from daphnia (Daphnia magna) acute immobilization test, whereas the LOECs is 70 mg L-1 and 76.26 mg L-1, respectively. The NOEC was 26.25 mg L-1 and 112.5 mg L-1 to INH+RMP and INH+EMB, respectively, higher than the NOEC of individual anti-TB drugs, indicating the antagonistic effects of INH+RMP and INH+EMB. The approach of combination index was used to examine the mixture toxicity in response to levels of immobilization. RMP+EMP range from 1.27 – 1.33, showing moderate antagonism. Other binary mixtures are higher than the RMP+EMP that presented antagonism, and the ternary mixture tends to be a nearly additive effect when exposing high concentrations of anti-TB drugs. The predicted environmental concentration was used to calculate the environmental exposure risk of anti-TB drugs in individuals and mixtures would decrease from 2020 to 2030; risk quotients were lower than 1, indicating no environmental risk concerns. |
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| 著作名稱： | Occurrences and ecological risks of Tamiflu metabolites in treated wastewater in Taiwan |
| 年度： | 2022 |
| 類別： |
會議論文
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| 摘要： | Humans highly use antiviral drugs Tamiflu during the flu season. The excreted active Tamiflu metabolites pass through wastewater treatment then discharge into rivers, which has sparked environmental concern potential ecological risks. This study aims to assess ecological risks posed by Tamiflu metabolites, oseltamivir ethlester (OE), and oseltamivir carboxylate (OC) of treated water in wastewater treatment plants (WWTPs) in Kaohsiung, Taiwan. We collected wastewater from primary and tertiary WWTPs during the flu season to detect the presence concentration of Tamiflu metabolites throughout the processing system of wastewater treatment and determine the removal efficiency. There is 100% OC detection in the tertiary WWTP, whereas only one-third of the influent and effluent samples can be detected OC in the primary WWTP. Major metabolite product OE was detected in all process systems in both WWTPs. Both WWTPs have low removal efficiency for Tamiflu metabolites, especially for OE. Surprisingly, the performance of tertiary WWTP is not significantly better than primary WWTP for removing Tamiflu metabolites. There are no ecological risk concerns to Tamiflu metabolites through treated water and rivers, even though highly frequency detection in OC and low removal efficiency. |
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| 著作名稱： | Epidemiology based wastewater monitoring for ecological risk assessment of anti tuberculosis drugs mixture effects |
| 年度： | 2022 |
| 類別： |
會議論文
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| 摘要： | Real-time monitor environmentally relevant anti-infective drugs and precise predictions for the mixture toxicity for anti-infective drugs are still limited.
This study seeks to provide a practical methodology, epidemiology-based wastewater monitoring (EBWM), as early warning signals for assessing the mixture toxicity risks of anti-tuberculosis (TB) drugs in water environments. We incorporated a TB transmission dynamic model and per capita water uses to predict the environmentally relevant concentrations of anti-TB drugs, isoniazid (INH), rifampicin (RMP), and ethambutol (EMB) in Taiwans high TB incidence area. Using our model, the predicted TB cases and environmentally relevant concentration of anti-TB drugs were decreasing to 2025. The EMB has the highest residues in water environments (INH: 0.010 μg L-1; RMP: 0.024 μg L-1; EMB: 0.136 μg L-1). For mixture toxicity, we find the antagonistic effect among anti-TB drugs from daphnia (Daphnia magna) immobilization tests. There are no ecological risk concerns on the mixture toxicity of anti-TB drugs in water environments. The EBWM predicts environmentally anti-TB drugs in real-time that will be validated with the measured environmental residues of anti-TB drugs and removal efficiency of wastewater treatment plants from fieldwork data to enhance the predictive power in future work.
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