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Thomas G Preuss - One of the best experts on this subject based on the ideXlab platform.
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a toxicokinetic and toxicodynamic modeling approach using myriophyllum spicatum to predict effects caused by short term exposure to a sulfonylurea
Environmental Toxicology and Chemistry, 2016Co-Authors: Simon Heine, Frederik Schild, Walter Schmitt, Ralph Krebber, Gerhard Gorlitz, Thomas G PreussAbstract:Toxicokinetic and toxicodynamic models are a promising tool to address the effects of time-variable chemical exposure. While standard toxicity tests rely, in most cases, on static concentrations, these chemical exposure patterns are unlikely to appear in the field, where time-variable exposure of chemicals is typical. In this study, we integrated toxicodynamic processes into an existing model that includes Toxicokinetics and growth of the aquatic plant Myriophyllum spicatum, to predict the impact on plant growth of two iofensulfuron short-term exposure patterns. To establish a method that can be used with standard data from risk assessments, toxicodynamics of iofensulfuron are based on effect data from a 14-day standard toxicity test using static concentrations. Modelling showed that the toxicokinetic and toxicodynamic growth model of M. spicatum can be successfully used to predict effects of short-term iofensulfuron exposure by using effect data from a standard toxicity test. A general approach is presented, in which time-variable chemical exposures can be evaluated more realistically without conducting additional toxicity studies. This article is protected by copyright. All rights reserved
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Demographic Toxicokinetic–Toxicodynamic Modeling of Lethal Effects
2016Co-Authors: André Gergs, Faten Gabsi, Armin Zenker, Thomas G PreussAbstract:The aquatic effect assessment of chemicals is largely based on standardized measures of toxicity determined in short-term laboratory tests which are designed to reduce variability. For this purpose, uniform individuals of a species are kept under environmental and chemical exposure conditions which are as constant as possible. In nature, exposure often appears to be pulsed, effects might last longer than a few days, sensitivity might vary among different sized organisms and populations are usually size or age structured and are subject to demographic processes. To overcome this discrepancy, we tested toxicokinetic–toxicodynamic models of different complexities, including body size scaling approaches, for their ability to represent lethal effects observed for Daphnia magna exposed to triphenyltin. The consequences of the different toxicokinetic and toxicodynamic assumptions for population level responses to pulsed exposure are tested by means of an individual based model and are evaluated by confronting model predictions with population data for various pulsed exposure scenarios. We provide an example where increased model complexity reduces the uncertainty in model outputs. Furthermore, our results emphasize the importance of considering population demography in Toxicokinetics and toxicodynamics for understanding and predicting potential chemical impacts at higher levels of biological organization
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A toxicokinetic and toxicodynamic modeling approach using Myriophyllum spicatum to predict effects caused by short‐term exposure to a sulfonylurea
Environmental toxicology and chemistry, 2015Co-Authors: Simon Heine, Frederik Schild, Walter Schmitt, Ralph Krebber, Gerhard Gorlitz, Thomas G PreussAbstract:Toxicokinetic and toxicodynamic models are a promising tool to address the effects of time-variable chemical exposure. While standard toxicity tests rely, in most cases, on static concentrations, these chemical exposure patterns are unlikely to appear in the field, where time-variable exposure of chemicals is typical. In this study, we integrated toxicodynamic processes into an existing model that includes Toxicokinetics and growth of the aquatic plant Myriophyllum spicatum, to predict the impact on plant growth of two iofensulfuron short-term exposure patterns. To establish a method that can be used with standard data from risk assessments, toxicodynamics of iofensulfuron are based on effect data from a 14-day standard toxicity test using static concentrations. Modelling showed that the toxicokinetic and toxicodynamic growth model of M. spicatum can be successfully used to predict effects of short-term iofensulfuron exposure by using effect data from a standard toxicity test. A general approach is presented, in which time-variable chemical exposures can be evaluated more realistically without conducting additional toxicity studies. This article is protected by copyright. All rights reserved
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The advantage of a toxicokinetic model of the honey bee colony in the context of the risk assessment of plant protection products
Julius-Kühn-Archiv, 2015Co-Authors: Kerstin Hörig, Walter Schmitt, Christian Maus, Alexander Nikolakis, Hans-toni Ratte, Martina Roß-nickoll, Thomas G PreussAbstract:Within the current discussions about risk assessment of plant protection products regarding honey bees, one of the most important aspects is how to link pesticide exposure on field and landscape scale to potential effects within the colony. A dynamic toxicokinetic model may help to improve the evaluation of dose rates individuals are exposed to through various compartments of the colony, which may result from the application of plant protection products in the field. In addition, it may help to interpret the significance of ecotoxicological test results, especially from lower-tier studies, in the risk assessment and help to refine the exposure assessment and risk evaluation. Linking it to a realistic population model and a landscape-based foraging model would give an improved insight into the dynamics in a honey bee colony under exposure of plant protection products Keywords: modelling, Toxicokinetics, risk assessment, exposure
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Body size-dependent Toxicokinetics and toxicodynamics could explain intra- and interspecies variability in sensitivity.
Environmental pollution (Barking Essex : 1987), 2015Co-Authors: André Gergs, Devdutt Kulkarni, Thomas G PreussAbstract:Ecological risk assessment of chemicals aims at quantifying the likelihood of adverse effects posed to non-target populations and the communities they constitute, often based on lethal concentration estimates for standard test species. There may, however, be intra- and interspecific differences in responses to chemical exposure. Here with the help of a toxicokinetic-toxicodynamic model, we explored whether differential body sizes might explain the observed variability in sensitivity between species and between life-stages of each individual species, for three model organisms, Daphnia magna, Chaoborus crystallinus and Mesocyclops leuckarti. While body size-dependent Toxicokinetics could be used to predict intraspecies variation in sensitivity, our results also suggest that changes in both toxicokinetic and toxicodynamic parameters might be needed to describe differential species sensitivity. Accounting for biological traits, like body size, in mechanistic effect models will allow more accurate predictions of chemical effects in size structured populations, ultimately providing mechanistic explanations for species sensitivity distributions.
Frédéric Y. Bois - One of the best experts on this subject based on the ideXlab platform.
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Occupational exposure to cobalt : a population toxicokinetic modeling approach validated by field results challenges the Biological Exposure Index for urinary cobalt
Journal of Occupational and Environmental Hygiene, 2010Co-Authors: Aurélie Martin, Frédéric Y. Bois, Francis Pierre, Pascal WildAbstract:This study modeled the urinary Toxicokinetics of cobalt exposure based on 507 urine samples from 16 workers, followed up for 1 week, and 108 related atmospheric cobalt measurements to determine an optimal urinary cobalt sampling strategy at work and a corresponding urinary exposure threshold (UET). These data have been used to calibrate a population toxicokinetic model, taking into account both the measurement uncertainty and intra- and interindividual variability. Using the calibrated model, urinary sampling sensitivity and specificity performance in detecting exposure above the 20 micro g/m3 threshold limit value - time-weighted average (TLV-TWA) has been applied to identify an optimal urine sampling time. The UET value is obtained by minimizing misclassification rates in workplace exposures below or above the TLV. Total atmospheric cobalt concentrations are in the 5-144 micro g/m3 range, and total urinary cobalt concentrations are 0.5-88 micro g/g creatinine. A two-compartment toxicokinetic model best described urinary elimination. Terminal elimination half-time from the central compartment is 10.0 hr (95% confidence interval [8.3-12.3]). The optimal urinary sampling time has been identified as 3 hr before the end of shift at the end of workweek. If we assume that misclassification errors are of equal cost, the UET associated with the TLV of 20 micro g/m3 is 5 micro g/L, which is lower than the ACGIH-recommended biological exposure index of 15 micro g/L.
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Occupational Exposure to Cobalt: A Population Toxicokinetic Modeling Approach Validated by Field Results Challenges the Biological Exposure Index for Urinary Cobalt
Journal of occupational and environmental hygiene, 2009Co-Authors: Aurélie Martin, Frédéric Y. Bois, Francis Pierre, Pascal WildAbstract:This study modeled the urinary Toxicokinetics of cobalt exposure based on 507 urine samples from 16 workers, followed up for 1 week, and 108 related atmospheric cobalt measurements to determine an optimal urinary cobalt sampling strategy at work and a corresponding urinary exposure threshold (UET). These data have been used to calibrate a population toxicokinetic model, taking into account both the measurement uncertainty and intra- and interindividual variability. Using the calibrated model, urinary sampling sensitivity and specificity performance in detecting exposure above the 20 μg/m3 threshold limit value – time-weighted average (TLV-TWA) has been applied to identify an optimal urine sampling time. The UET value is obtained by minimizing misclassification rates in workplace exposures below or above the TLV. Total atmospheric cobalt concentrations are in the 5–144 μg/m3 range, and total urinary cobalt concentrations are 0.5–88 μg/g creatinine. A two-compartment toxicokinetic model best described urina...
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Benzene Toxicokinetics in humans
Advances in Environmental Control Technology: Health and Toxicology, 2007Co-Authors: Frédéric Y. BoisAbstract:Publisher Summary This chapter discusses the toxicokinetic effects of benzene in humans. Benzene is a human carcinogen, and chronic exposure to benzene at high levels in the workplace leads to the bone marrow depression and aplastic anemia. It also acts as an agent of acute myelogenous leukemia and some of its variants. Humans are more susceptible to the leukemogenic potential of benzene than most animal species. At very high concentrations, it induces acute toxicity to the central nervous system. The liver is the major organ involved in benzene metabolism and the bone marrow is the target site for benzene toxicity. Hepatic metabolites are carried via the bloodstream to the bone marrow, where they accumulate and undergo further transformations. In situ bone marrow metabolism also contributes to benzene toxicity. Ring opening of benzene oxide leads to trans, trans-muconaldehyde. Muconaldehyde is cytotoxic and involved in benzene toxicity. The chapter discusses several models that further describe the Toxicokinetics of benzene in humans.
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Toxicokinetics of inhaled trichloroethylene and tetrachloroethylene in humans at 1 ppm : emprirical results and comparisons with previous studies
Toxicological Sciences, 2007Co-Authors: Weihsueh A. Chiu, Sandrine Micallef, Aart C. Monster, Frédéric Y. BoisAbstract:Trichloroethylene (TRI) and tetrachloroethylene (TETRA) are solvents that have been widely used in a variety of industries, and both are widespread environmental contaminants. In order to provide a better basis for understanding their Toxicokinetics at environmental exposures, seven human volunteers were exposed by inhalation to 1 ppm of TRI or TETRA for 6 h, with biological samples collected for analysis during exposure and up to 6-days postexposure. Concentrations of TRI, TETRA, free trichloroethanol (TCOH), total TCOH (free TCOH plus glucuronidated TCOH), and trichloroacetic acid (TCA) were determined in blood and urine; TRI and TETRA concentrations were measured in alveolar breath. Toxicokinetic time courses and empirical analyses of classical toxicokinetic parameters were compared with those reported in previous human volunteer studies, most of which involved exposures that were at least 10-fold higher. Qualitatively, TRI and TETRA Toxicokinetics were consistent with previous human studies. Quantitatively, alveolar retention and clearance by exhalation were similar to those found previously but blood and urine data suggest a number of possible toxicokinetic differences. For TRI, data from the current study support lower apparent blood-air partition coefficients, greater apparent metabolic clearance, less TCA production, and greater glucuronidation of TCOH as compared to previous studies. For TETRA, the current data suggest TCA formation that is similar or slightly lower than that of previous studies. Variability and uncertainty in empirical estimates of total TETRA metabolism are substantial, with confidence intervals among different studies substantially overlapping. Relative contributions to observed differences from concentration-dependent Toxicokinetics and interindividual and interoccasion variability remain to be determined.
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Physiologically based pharmacokinetic modeling of inhalation exposure of humans to dichloromethane during moderate to heavy exercise
Toxicological Sciences, 2001Co-Authors: Fredrik Jonsson, Frédéric Y. Bois, Gunnar JohansonAbstract:Dichloromethane (methylene chloride, DCM) is metabolized via two pathways in humans: mixed-function oxidases (MFO) and glutathione-S-transferase (GST). Most likely, the carcinogenicity for DCM is related to metabolic activation of DCM via the GST pathway. However, as the two pathways are competing, the metabolic capacity for the MFO pathway in vivo is also of interest in risk assessment for DCM. Past estimates of MFO metabolism are based on the in vitro activity of tissue samples. The aim of the present study was to develop a population model for DCM in order to gain more knowledge on the variability of DCM inhalation Toxicokinetics in humans, with main emphasis on the MFO metabolic pathway. This was done by merging published in vitro data on DCM metabolism and partitioning with inhalation toxicokinetic data (Astrand ef at, 1975, Scand. J. Work.Environ. Health 1, 78-94) from five human volunteers, using the MCMC technique within a population PBPK model. Our results indicate that the metabolic capacity for the MFO pathway in humans is slightly larger than previously estimated from four human liver samples. Furthermore, the interindividual variability of the MFO pathway in vivo is smaller among our five subjects than indicated by the in vitro samples. We also derive a Bayesian estimate of the population distribution of the MFO metabolism (median maximum metabolic rate 28, 95% confidence interval 12-66 mu mol/min) that is a compromise between the information from the in vitro data and the toxicokinetic information present in the experimental data.
Simon Heine - One of the best experts on this subject based on the ideXlab platform.
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a toxicokinetic and toxicodynamic modeling approach using myriophyllum spicatum to predict effects caused by short term exposure to a sulfonylurea
Environmental Toxicology and Chemistry, 2016Co-Authors: Simon Heine, Frederik Schild, Walter Schmitt, Ralph Krebber, Gerhard Gorlitz, Thomas G PreussAbstract:Toxicokinetic and toxicodynamic models are a promising tool to address the effects of time-variable chemical exposure. While standard toxicity tests rely, in most cases, on static concentrations, these chemical exposure patterns are unlikely to appear in the field, where time-variable exposure of chemicals is typical. In this study, we integrated toxicodynamic processes into an existing model that includes Toxicokinetics and growth of the aquatic plant Myriophyllum spicatum, to predict the impact on plant growth of two iofensulfuron short-term exposure patterns. To establish a method that can be used with standard data from risk assessments, toxicodynamics of iofensulfuron are based on effect data from a 14-day standard toxicity test using static concentrations. Modelling showed that the toxicokinetic and toxicodynamic growth model of M. spicatum can be successfully used to predict effects of short-term iofensulfuron exposure by using effect data from a standard toxicity test. A general approach is presented, in which time-variable chemical exposures can be evaluated more realistically without conducting additional toxicity studies. This article is protected by copyright. All rights reserved
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A toxicokinetic and toxicodynamic modeling approach using Myriophyllum spicatum to predict effects caused by short‐term exposure to a sulfonylurea
Environmental toxicology and chemistry, 2015Co-Authors: Simon Heine, Frederik Schild, Walter Schmitt, Ralph Krebber, Gerhard Gorlitz, Thomas G PreussAbstract:Toxicokinetic and toxicodynamic models are a promising tool to address the effects of time-variable chemical exposure. While standard toxicity tests rely, in most cases, on static concentrations, these chemical exposure patterns are unlikely to appear in the field, where time-variable exposure of chemicals is typical. In this study, we integrated toxicodynamic processes into an existing model that includes Toxicokinetics and growth of the aquatic plant Myriophyllum spicatum, to predict the impact on plant growth of two iofensulfuron short-term exposure patterns. To establish a method that can be used with standard data from risk assessments, toxicodynamics of iofensulfuron are based on effect data from a 14-day standard toxicity test using static concentrations. Modelling showed that the toxicokinetic and toxicodynamic growth model of M. spicatum can be successfully used to predict effects of short-term iofensulfuron exposure by using effect data from a standard toxicity test. A general approach is presented, in which time-variable chemical exposures can be evaluated more realistically without conducting additional toxicity studies. This article is protected by copyright. All rights reserved
Gerhard Gorlitz - One of the best experts on this subject based on the ideXlab platform.
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a toxicokinetic and toxicodynamic modeling approach using myriophyllum spicatum to predict effects caused by short term exposure to a sulfonylurea
Environmental Toxicology and Chemistry, 2016Co-Authors: Simon Heine, Frederik Schild, Walter Schmitt, Ralph Krebber, Gerhard Gorlitz, Thomas G PreussAbstract:Toxicokinetic and toxicodynamic models are a promising tool to address the effects of time-variable chemical exposure. While standard toxicity tests rely, in most cases, on static concentrations, these chemical exposure patterns are unlikely to appear in the field, where time-variable exposure of chemicals is typical. In this study, we integrated toxicodynamic processes into an existing model that includes Toxicokinetics and growth of the aquatic plant Myriophyllum spicatum, to predict the impact on plant growth of two iofensulfuron short-term exposure patterns. To establish a method that can be used with standard data from risk assessments, toxicodynamics of iofensulfuron are based on effect data from a 14-day standard toxicity test using static concentrations. Modelling showed that the toxicokinetic and toxicodynamic growth model of M. spicatum can be successfully used to predict effects of short-term iofensulfuron exposure by using effect data from a standard toxicity test. A general approach is presented, in which time-variable chemical exposures can be evaluated more realistically without conducting additional toxicity studies. This article is protected by copyright. All rights reserved
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A toxicokinetic and toxicodynamic modeling approach using Myriophyllum spicatum to predict effects caused by short‐term exposure to a sulfonylurea
Environmental toxicology and chemistry, 2015Co-Authors: Simon Heine, Frederik Schild, Walter Schmitt, Ralph Krebber, Gerhard Gorlitz, Thomas G PreussAbstract:Toxicokinetic and toxicodynamic models are a promising tool to address the effects of time-variable chemical exposure. While standard toxicity tests rely, in most cases, on static concentrations, these chemical exposure patterns are unlikely to appear in the field, where time-variable exposure of chemicals is typical. In this study, we integrated toxicodynamic processes into an existing model that includes Toxicokinetics and growth of the aquatic plant Myriophyllum spicatum, to predict the impact on plant growth of two iofensulfuron short-term exposure patterns. To establish a method that can be used with standard data from risk assessments, toxicodynamics of iofensulfuron are based on effect data from a 14-day standard toxicity test using static concentrations. Modelling showed that the toxicokinetic and toxicodynamic growth model of M. spicatum can be successfully used to predict effects of short-term iofensulfuron exposure by using effect data from a standard toxicity test. A general approach is presented, in which time-variable chemical exposures can be evaluated more realistically without conducting additional toxicity studies. This article is protected by copyright. All rights reserved
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Mechanistic modelling of toxicokinetic processes within Myriophyllum spicatum.
Chemosphere, 2014Co-Authors: S. Heine, Walter Schmitt, Gerhard Gorlitz, Andreas Schäffer, H. Buresová, Gertie Arts, Thomas G PreussAbstract:Effects of chemicals are, in most cases, caused by internal concentrations within organisms which rely on uptake and elimination kinetics. These processes might be key components for assessing the effects of time-variable exposure of chemicals which regularly occur in aquatic systems. However, the knowledge of toxicokinetic patterns caused by time-variable exposure is limited, and gaining such information is complex. In this work, a previously developed mechanistic growth model of Myriophyllum spicatum is coupled with a newly developed toxicokinetic part, providing a model that is able to predict uptake and elimination of chemicals, as well as distribution processes between plant compartments (leaves, stems, roots) of M. spicatum. It is shown, that toxicokinetic patterns, at least for most of the investigated chemicals, can be calculated in agreement with experimental observations, by only calibrating two chemical- specific parameters, the cuticular permeability and a plant/water partition coefficient. Through the model-based determination of the cuticular permeabilities of Isoproturon, Iofensulfuron, Fluridone, Imazamox and Penoxsulam, their toxicokinetic pattern can be described with the model approach. For the use of the model for predicting Toxicokinetics of other chemicals, where experimental data is not available, equations are presented that are based on the log (Poct/wat) of a chemical and estimate parameters that are necessary to run the model. In general, a method is presented to analyze time-variable exposure of chemicals more in detail without conducting time and labour intensive experiments.
Walter Schmitt - One of the best experts on this subject based on the ideXlab platform.
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a toxicokinetic and toxicodynamic modeling approach using myriophyllum spicatum to predict effects caused by short term exposure to a sulfonylurea
Environmental Toxicology and Chemistry, 2016Co-Authors: Simon Heine, Frederik Schild, Walter Schmitt, Ralph Krebber, Gerhard Gorlitz, Thomas G PreussAbstract:Toxicokinetic and toxicodynamic models are a promising tool to address the effects of time-variable chemical exposure. While standard toxicity tests rely, in most cases, on static concentrations, these chemical exposure patterns are unlikely to appear in the field, where time-variable exposure of chemicals is typical. In this study, we integrated toxicodynamic processes into an existing model that includes Toxicokinetics and growth of the aquatic plant Myriophyllum spicatum, to predict the impact on plant growth of two iofensulfuron short-term exposure patterns. To establish a method that can be used with standard data from risk assessments, toxicodynamics of iofensulfuron are based on effect data from a 14-day standard toxicity test using static concentrations. Modelling showed that the toxicokinetic and toxicodynamic growth model of M. spicatum can be successfully used to predict effects of short-term iofensulfuron exposure by using effect data from a standard toxicity test. A general approach is presented, in which time-variable chemical exposures can be evaluated more realistically without conducting additional toxicity studies. This article is protected by copyright. All rights reserved
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A toxicokinetic and toxicodynamic modeling approach using Myriophyllum spicatum to predict effects caused by short‐term exposure to a sulfonylurea
Environmental toxicology and chemistry, 2015Co-Authors: Simon Heine, Frederik Schild, Walter Schmitt, Ralph Krebber, Gerhard Gorlitz, Thomas G PreussAbstract:Toxicokinetic and toxicodynamic models are a promising tool to address the effects of time-variable chemical exposure. While standard toxicity tests rely, in most cases, on static concentrations, these chemical exposure patterns are unlikely to appear in the field, where time-variable exposure of chemicals is typical. In this study, we integrated toxicodynamic processes into an existing model that includes Toxicokinetics and growth of the aquatic plant Myriophyllum spicatum, to predict the impact on plant growth of two iofensulfuron short-term exposure patterns. To establish a method that can be used with standard data from risk assessments, toxicodynamics of iofensulfuron are based on effect data from a 14-day standard toxicity test using static concentrations. Modelling showed that the toxicokinetic and toxicodynamic growth model of M. spicatum can be successfully used to predict effects of short-term iofensulfuron exposure by using effect data from a standard toxicity test. A general approach is presented, in which time-variable chemical exposures can be evaluated more realistically without conducting additional toxicity studies. This article is protected by copyright. All rights reserved
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The advantage of a toxicokinetic model of the honey bee colony in the context of the risk assessment of plant protection products
Julius-Kühn-Archiv, 2015Co-Authors: Kerstin Hörig, Walter Schmitt, Christian Maus, Alexander Nikolakis, Hans-toni Ratte, Martina Roß-nickoll, Thomas G PreussAbstract:Within the current discussions about risk assessment of plant protection products regarding honey bees, one of the most important aspects is how to link pesticide exposure on field and landscape scale to potential effects within the colony. A dynamic toxicokinetic model may help to improve the evaluation of dose rates individuals are exposed to through various compartments of the colony, which may result from the application of plant protection products in the field. In addition, it may help to interpret the significance of ecotoxicological test results, especially from lower-tier studies, in the risk assessment and help to refine the exposure assessment and risk evaluation. Linking it to a realistic population model and a landscape-based foraging model would give an improved insight into the dynamics in a honey bee colony under exposure of plant protection products Keywords: modelling, Toxicokinetics, risk assessment, exposure
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Mechanistic modelling of toxicokinetic processes within Myriophyllum spicatum.
Chemosphere, 2014Co-Authors: S. Heine, Walter Schmitt, Gerhard Gorlitz, Andreas Schäffer, H. Buresová, Gertie Arts, Thomas G PreussAbstract:Effects of chemicals are, in most cases, caused by internal concentrations within organisms which rely on uptake and elimination kinetics. These processes might be key components for assessing the effects of time-variable exposure of chemicals which regularly occur in aquatic systems. However, the knowledge of toxicokinetic patterns caused by time-variable exposure is limited, and gaining such information is complex. In this work, a previously developed mechanistic growth model of Myriophyllum spicatum is coupled with a newly developed toxicokinetic part, providing a model that is able to predict uptake and elimination of chemicals, as well as distribution processes between plant compartments (leaves, stems, roots) of M. spicatum. It is shown, that toxicokinetic patterns, at least for most of the investigated chemicals, can be calculated in agreement with experimental observations, by only calibrating two chemical- specific parameters, the cuticular permeability and a plant/water partition coefficient. Through the model-based determination of the cuticular permeabilities of Isoproturon, Iofensulfuron, Fluridone, Imazamox and Penoxsulam, their toxicokinetic pattern can be described with the model approach. For the use of the model for predicting Toxicokinetics of other chemicals, where experimental data is not available, equations are presented that are based on the log (Poct/wat) of a chemical and estimate parameters that are necessary to run the model. In general, a method is presented to analyze time-variable exposure of chemicals more in detail without conducting time and labour intensive experiments.
