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See detailDevelopment and evaluation of a harmonized whole body physiologically based pharmacokinetic (PBPK) model for flutamide in rats and its extrapolation to humans.
Sharma, Raju Prasad; Kumar, Vikas; Schuhmacher, Marta et al

in Environmental research (2020), 182

By their definition, inadvertent exposure to endocrine disrupting compounds (EDCs) intervenes with the endocrine signalling system, even at low dose. On the one hand, some EDCs are used as important ... [more ▼]

By their definition, inadvertent exposure to endocrine disrupting compounds (EDCs) intervenes with the endocrine signalling system, even at low dose. On the one hand, some EDCs are used as important pharmaceutical drugs that one would not want to dismiss. On the other hand, these pharmaceutical drugs are having off-target effects and increasingly significant exposure to the general population with unwanted health implications. Flutamide, one of the top pharmaceutical products marketed all over the world for the treatment of prostate cancer, is also a pollutant. Its therapeutic action mainly depends on targeting the androgen receptors and inhibiting the androgen action that is essential for growth and survival of prostate tissue. Currently flutamide is of concern with respect to its categorization as an endocrine disruptor. In this work we have developed a physiologically based pharmacokinetic (PBPK) model of flutamide that could serve as a standard tool for its human risk assessment. First we built the model for rat (where many parameters have been measured). The rat PBPK model was extrapolated to human where the re-parameterization involved human-specific physiology, metabolic kinetics derived from in-vitro studies, and the partition coefficient same as the rat model. We have harmonized the model by integrating different sets of in-vitro, in-vivo and physiological data into a PBPK model. Then the model was used to simulate different exposure scenarios and the results were compared against the observed data. Both uncertainty and sensitivity analysis was done. Since this new whole-body PBPK model can predict flutamide concentrations not only in plasma but also in various organs, the model may have clinical applications in efficacy and safety assessment of flutamide. The model can also be used for reverse dosimetry in the context of interpreting the available biomonitoring data to estimate the degree to which the population is currently being exposed, and a tool for the pharmaceutical companies to validate the estimated Permitted Daily Exposure (PDE) for flutamide. [less ▲]

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See detailEnergy saving in WWTP: Daily benchmarking under uncertainty and data availability limitations
Torregrossa, Dario; Schutz, George; Cornelissen, Alex et al

in Environmental Research (2016)

Efficient management of Waste Water Treatment Plants (WWTPs) can produce significant environmental and economic benefits. Energy benchmarking can be used to compare WWTPs, identify targets and use these ... [more ▼]

Efficient management of Waste Water Treatment Plants (WWTPs) can produce significant environmental and economic benefits. Energy benchmarking can be used to compare WWTPs, identify targets and use these to improve their performance. Different authors have performed benchmark analysis on monthly or yearly basis but their approaches suffer from a time lag between an event, its detection, interpretation and potential actions. The availability of on-line measurement data on many WWTPs should theoretically enable the decrease of the management response time by daily benchmarking. Unfortunately this approach is often impossible because of limited data availability. This paper proposes a methodology to perform a daily benchmark analysis under database limitations. The methodology has been applied to the Energy Online System (EOS) developed in the frame work of the project “INNERS” (INNovative Energy Recovery Strategies in the urban water cycle). EOS calculates a set of Key Performance Indicators (KPIs) for the evaluation of energy and process performances. In EOS, the energy KPIs take in consideration the pollutant load in order to enable the comparison between different plants. For example, EOS does not analyse the energy consumption but the energy consumption on pollutant load. This approach enables the comparison of performances for plants with different loads or for a single plant under different load conditions. The energy consumption is measured by on-line sensors, while the pollutant load is measured in the laboratory approximately every 14 days. Consequently, the unavailability of the water quality parameters is the limiting factor in calculating energy KPIs. In this paper, in order to overcome this limitation, the authors have developed a methodology to estimate the required parameters and manage the uncertainty in the estimation. By coupling the parameter estimation with an interval based benchmark approach, the authors propose an effective, fast and reproducible way to manage infrequent inlet measurements. Its use enables benchmarking on a daily basis and prepares the ground for further investigation. [less ▲]

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