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Jing You - One of the best experts on this subject based on the ideXlab platform.

  • Enantioselective degradation and bioaccumulation of sediment-associated fipronil in Lumbriculus variegatus: Toxicokinetic analysis.
    The Science of the total environment, 2019
    Co-Authors: Shunhui Wang, Jing You
    Abstract:

    Abstract Enantioselective degradation and biotransformation are critical processes affecting the bioaccumulation and toxicity of chiral pesticides in the environment. In the present study, enantioselective uptake, biotransformation and elimination of a current use pesticide, fipronil in a benthic invertebrate, Lumbriculus variegatus were assessed using a sediment bioaccumulation test. Toxicokinetic models were constructed to quantitatively describe kinetic processes of fipronil enantiomers. The degradation of fipronil in sediment significantly affected chemical uptake, thus degradation kinetic model was incorporated into Toxicokinetic Modeling. It was shown that S-(+)-fipronil degraded faster than R-(−)-fipronil in sediment, with dissipation rate constants being 0.090 ± 0.008 and 0.023 ± 0.006 1/d, respectively. As a result, R-(−)-enantiomer preferentially accumulated in sediment over time. Similarly, higher concentrations of R-(−)-fipronil were detected in L. variegatus compared with S-(+)-fipronil. Toxicokinetic Modeling showed R-(−)-fipronil had larger uptake and elimination rate coefficients and apparent maximum reaction rate, but a smaller apparent half-saturation constant than S-(+)-fipronil. Preferential uptake of R-(−)-fipronil from sediment to L. variegatus was the main reason for greater R-(−)-fipronil concentrations in organism. Biotransformation of fipronil in L. variegatus was also enantioselective, yet it played fewer roles on enantioselective bioaccumulation than uptake. Overall, our findings highlight the importance of selective degradation, uptake and biotransformation of sediment-associated fipronil on its enantioselective bioaccumulation in benthic invertebrates, which helps to improve the accuracy for assessing aquatic toxicity of the chiral pesticide. Capsule Enantioselective bioaccumulation of sediment-associated fipronil in Lumbriculus variegatus was quantitatively explained by selective degradation, uptake, biotransformation and elimination parameters using a combination of degradation and Toxicokinetic Modeling.

  • Multi-compartmental Toxicokinetic Modeling of fipronil in tilapia: Accumulation, biotransformation and elimination.
    Journal of hazardous materials, 2018
    Co-Authors: Jing You, Wen-xiong Wang
    Abstract:

    Abstract Bioaccumulation and biotransformation are critical processes modifying toxicity of easily metabolizable chemicals to aquatic organisms. In this study, tissue-specific accumulation, biotransformation and elimination of a current-use pesticide fipronil in tilapia (Oreochromis niloticus) were quantified by combining in vivo measurements and a newly developed multi-compartmental Toxicokinetic model. Waterborne fipronil was taken up via gills and metabolized rapidly and solely to fipronil sulfone. Significant decrease of fipronil residues in liver and intestine during exposure period strongly suggested the induction of metabolism in these two organs. Significant transport of fipronil and fipronil sulfone in the liver-bile-intestine system implied that hepatobiliary excretion and enterohepatic re-absorption played important roles in fipronil metabolism and system circulation of the parent compound and the metabolite. The multi-compartmental model quantitatively described the highly dynamic inter-compartmental transport and rapid branchial clearance of fipronil in fish. Modeling results also suggested that uptake and biotransformation were the stronger driving forces for the inter-compartmental transport of fipronil in fish than the inherent partitioning capacity. Overall, our findings highlight the importance of biotransformation on internal disposition of fipronil in fish, which helps to improve aquatic toxicity assessment of this pesticide.

John W. Nichols - One of the best experts on this subject based on the ideXlab platform.

  • reliability of in vitro methods used to measure intrinsic clearance of hydrophobic organic chemicals by rainbow trout results of an international ring trial
    Toxicological Sciences, 2018
    Co-Authors: John W. Nichols, Kellie A. Fay, Mary Jo Bernhard, Ina Bischof, John W. Davis, Marlies Halder, Karla Johanning, Heike Laue, Diane L. Nabb, Christian Schlechtriem
    Abstract:

    In vitro assays are widely employed to obtain intrinsic clearance estimates used in Toxicokinetic Modeling efforts. However, the reliability of these methods is seldom reported. Here we describe the results of an international ring trial designed to evaluate two in vitro assays used to measure intrinsic clearance in rainbow trout. An important application of these assays is to predict the effect of biotransformation on chemical bioaccumulation. Six laboratories performed substrate depletion experiments with cyclohexyl salicylate, fenthion, 4-n-nonylphenol, deltamethrin, methoxychlor, and pyrene using cryopreserved hepatocytes and liver S9 fractions from trout. Variability within and among laboratories was characterized as the percent coefficient of variation (CV) in measured in vitro intrinsic clearance rates (CLIN VITRO, INT; ml/h/mg protein or 106 cells) for each chemical and test system. Mean intralaboratory CVs for each test chemical averaged 18.9% for hepatocytes and 14.1% for S9 fractions, whereas interlaboratory CVs (all chemicals and all tests) averaged 30.1% for hepatocytes and 22.4% for S9 fractions. When CLIN VITRO, INT values were extrapolated to in vivo intrinsic clearance estimates (CLIN VIVO, INT; l/d/kg fish), both assays yielded similar levels of activity (<4-fold difference for all chemicals). Hepatic clearance rates (CLH; l/d/kg fish) calculated using data from both assays exhibited even better agreement. These findings show that both assays are highly reliable and suggest that either may be used to inform chemical bioaccumulation assessments for fish. This study highlights several issues related to the demonstration of assay reliability and may provide a template for evaluating other in vitro biotransformation assays.

  • Reliability of In Vitro Methods Used to Measure Intrinsic Clearance of Hydrophobic Organic Chemicals by Rainbow Trout: Results of an International Ring Trial
    Toxicological sciences : an official journal of the Society of Toxicology, 2018
    Co-Authors: John W. Nichols, Kellie A. Fay, Mary Jo Bernhard, Ina Bischof, John W. Davis, Marlies Halder, Karla Johanning, Heike Laue, Diane L. Nabb
    Abstract:

    In vitro assays are widely employed to obtain intrinsic clearance estimates used in Toxicokinetic Modeling efforts. However, the reliability of these methods is seldom reported. Here we describe the results of an international ring trial designed to evaluate two in vitro assays used to measure intrinsic clearance in rainbow trout. An important application of these assays is to predict the effect of biotransformation on chemical bioaccumulation. Six laboratories performed substrate depletion experiments with cyclohexyl salicylate, fenthion, 4-n-nonylphenol, deltamethrin, methoxychlor, and pyrene using cryopreserved hepatocytes and liver S9 fractions from trout. Variability within and among laboratories was characterized as the percent coefficient of variation (CV) in measured in vitro intrinsic clearance rates (CLIN VITRO, INT; ml/h/mg protein or 106 cells) for each chemical and test system. Mean intralaboratory CVs for each test chemical averaged 18.9% for hepatocytes and 14.1% for S9 fractions, whereas interlaboratory CVs (all chemicals and all tests) averaged 30.1% for hepatocytes and 22.4% for S9 fractions. When CLIN VITRO, INT values were extrapolated to in vivo intrinsic clearance estimates (CLIN VIVO, INT; l/d/kg fish), both assays yielded similar levels of activity (

  • Physiologically-based Toxicokinetic Modeling of three waterborne chloroethanes in channel catfish, Ictalurus punctatus
    Aquatic Toxicology, 1993
    Co-Authors: John W. Nichols, James M. Mckim, Gregory J. Lien, Sharon L. Bertelsen, Alex D. Hoffman, Carol A. Gallinat
    Abstract:

    A physiologically-based Toxicokinetic model for fish was used to describe the uptake and disposition of three chlorinated ethanes in channel catfish (Ictalurus punctatus). Catfish were simultaneously exposed to 1,1,2,2-tetrachloroethane (TCE), pentachloroethane (PCE), and hexachloroethane (HCE) in fish respirometer-metabolism chambers to assess the kinetics of chemical accumulation in arterial blood and chemical extraction efficiency from inspired water. Chemical residues in tissues were measured at the end of each experiment. These data were used to evaluate the accuracy of model simulations and to form a basis for comparison with information collected previously from rainbow trout. TCE was at or near steady-state in catfish after 48 h. For PCE and HCE the time to steady-state appeared to be considerably longer than 48 h. Parameterized with in vitro chemical partitioning information, the model accurately simulated the accumulation of TCE in arterial blood and its uptake from inspired water, but consistently underestimated the uptake and accumulation of both PCE and HCE. The cause of these discrepancies was not conclusively determined; however, several possible sources of error were evaluated, including physiological and chemical partitioning inputs, and underlying Modeling assumptions. A comparison of data sets and Modeling efforts for rainbow trout and channel catfish suggests that gross similarities between the two species can be attributed to the comparability of relevant physiological and chemical partitioning parameters.

  • Physiologically based Toxicokinetic Modeling of three waterborne chloroethanes in rainbow trout (Oncorhynchus mykiss).
    Toxicology and applied pharmacology, 1991
    Co-Authors: John W. Nichols, James M. Mckim, Gregory J. Lien, Alex D. Hoffman, Sharon L. Bertelsen
    Abstract:

    A physiologically based Toxicokinetic model for fish was used to simulate the uptake and disposition of three waterborne chloroethanes in rainbow trout (Oncorhynchus mykiss). Trout were exposed to 1,1,2,2-tetrachloroethane, pentachloroethane, and hexachloroethane in fish respirometer-metabolism chambers to assess the kinetics of chemical accumulation in arterial blood and chemical extraction efficiency from inspired water. Chemical residues in tissues were measured at the end of each experiment. Trout exposed to tetrachloroethane were close to steady-state in 48 hr. Fish exposed to pentachloroethane were near steady-state in 264 hr. Extraction efficiency data showed that systemic (extrabranchial) elimination of both chemicals was small. Hexachloroethane continued to accumulate in fish exposed for 600 hr. Parameterized with chemical partitioning data obtained in vitro, the model accurately simulated the uptake of all three chloroethanes in blood and tissues and their extraction from inspired water. These results provide support for the basic model structure and the accuracy of physiological input parameters.

Sharon L. Bertelsen - One of the best experts on this subject based on the ideXlab platform.

  • Physiologically-based Toxicokinetic Modeling of three waterborne chloroethanes in channel catfish, Ictalurus punctatus
    Aquatic Toxicology, 1993
    Co-Authors: John W. Nichols, James M. Mckim, Gregory J. Lien, Sharon L. Bertelsen, Alex D. Hoffman, Carol A. Gallinat
    Abstract:

    A physiologically-based Toxicokinetic model for fish was used to describe the uptake and disposition of three chlorinated ethanes in channel catfish (Ictalurus punctatus). Catfish were simultaneously exposed to 1,1,2,2-tetrachloroethane (TCE), pentachloroethane (PCE), and hexachloroethane (HCE) in fish respirometer-metabolism chambers to assess the kinetics of chemical accumulation in arterial blood and chemical extraction efficiency from inspired water. Chemical residues in tissues were measured at the end of each experiment. These data were used to evaluate the accuracy of model simulations and to form a basis for comparison with information collected previously from rainbow trout. TCE was at or near steady-state in catfish after 48 h. For PCE and HCE the time to steady-state appeared to be considerably longer than 48 h. Parameterized with in vitro chemical partitioning information, the model accurately simulated the accumulation of TCE in arterial blood and its uptake from inspired water, but consistently underestimated the uptake and accumulation of both PCE and HCE. The cause of these discrepancies was not conclusively determined; however, several possible sources of error were evaluated, including physiological and chemical partitioning inputs, and underlying Modeling assumptions. A comparison of data sets and Modeling efforts for rainbow trout and channel catfish suggests that gross similarities between the two species can be attributed to the comparability of relevant physiological and chemical partitioning parameters.

  • Physiologically based Toxicokinetic Modeling of three waterborne chloroethanes in rainbow trout (Oncorhynchus mykiss).
    Toxicology and applied pharmacology, 1991
    Co-Authors: John W. Nichols, James M. Mckim, Gregory J. Lien, Alex D. Hoffman, Sharon L. Bertelsen
    Abstract:

    A physiologically based Toxicokinetic model for fish was used to simulate the uptake and disposition of three waterborne chloroethanes in rainbow trout (Oncorhynchus mykiss). Trout were exposed to 1,1,2,2-tetrachloroethane, pentachloroethane, and hexachloroethane in fish respirometer-metabolism chambers to assess the kinetics of chemical accumulation in arterial blood and chemical extraction efficiency from inspired water. Chemical residues in tissues were measured at the end of each experiment. Trout exposed to tetrachloroethane were close to steady-state in 48 hr. Fish exposed to pentachloroethane were near steady-state in 264 hr. Extraction efficiency data showed that systemic (extrabranchial) elimination of both chemicals was small. Hexachloroethane continued to accumulate in fish exposed for 600 hr. Parameterized with chemical partitioning data obtained in vitro, the model accurately simulated the uptake of all three chloroethanes in blood and tissues and their extraction from inspired water. These results provide support for the basic model structure and the accuracy of physiological input parameters.

Wen-xiong Wang - One of the best experts on this subject based on the ideXlab platform.

  • Multicompartmental Toxicokinetic Modeling of Discrete Dietary and Continuous Waterborne Uptake of Two Polycyclic Aromatic Hydrocarbons by Zebrafish Danio rerio.
    Environmental science & technology, 2019
    Co-Authors: Haotian Wang, Xinghui Xia, Ran Liu, Zixuan Wang, Xiaohan Lin, Derek C. G. Muir, Wen-xiong Wang
    Abstract:

    In the present study, we developed a multicompartmental Toxicokinetic model for two polycyclic aromatic hydrocarbons (phenanthrene and anthracene) in their deuterated form (PAHs-d10) in zebrafish c...

  • Multi-compartmental Toxicokinetic Modeling of fipronil in tilapia: Accumulation, biotransformation and elimination.
    Journal of hazardous materials, 2018
    Co-Authors: Jing You, Wen-xiong Wang
    Abstract:

    Abstract Bioaccumulation and biotransformation are critical processes modifying toxicity of easily metabolizable chemicals to aquatic organisms. In this study, tissue-specific accumulation, biotransformation and elimination of a current-use pesticide fipronil in tilapia (Oreochromis niloticus) were quantified by combining in vivo measurements and a newly developed multi-compartmental Toxicokinetic model. Waterborne fipronil was taken up via gills and metabolized rapidly and solely to fipronil sulfone. Significant decrease of fipronil residues in liver and intestine during exposure period strongly suggested the induction of metabolism in these two organs. Significant transport of fipronil and fipronil sulfone in the liver-bile-intestine system implied that hepatobiliary excretion and enterohepatic re-absorption played important roles in fipronil metabolism and system circulation of the parent compound and the metabolite. The multi-compartmental model quantitatively described the highly dynamic inter-compartmental transport and rapid branchial clearance of fipronil in fish. Modeling results also suggested that uptake and biotransformation were the stronger driving forces for the inter-compartmental transport of fipronil in fish than the inherent partitioning capacity. Overall, our findings highlight the importance of biotransformation on internal disposition of fipronil in fish, which helps to improve aquatic toxicity assessment of this pesticide.

Robert Tardif - One of the best experts on this subject based on the ideXlab platform.

  • ethanol Toxicokinetics resulting from inhalation exposure in human volunteers and Toxicokinetic Modeling
    Inhalation Toxicology, 2014
    Co-Authors: Josee Dumascampagna, Robert Tardif, Ginette Charesttardif, Sami Haddad
    Abstract:

    Uncertainty exists regarding the validity of a previously developed physiologically-based pharmacokinetic model (PBPK) for inhaled ethanol in humans to predict the blood levels of ethanol (BLE) at low level exposures (<1000 ppm). Thus, the objective of this study is to document the BLE resulting from low levels exposures in order to refine/validate this PBPK model. Human volunteers were exposed to ethanol vapors during 4 h at 5 different concentrations (125-1000 ppm), at rest, in an inhalation chamber. Blood and exhaled air were sampled. Also, the impact of light exercise (50 W) on the BLE was investigated. There is a linear relationship between the ethanol concentrations in inhaled air and (i) BLE (women: r²= 0.98/men: r²= 0.99), as well as (ii) ethanol concentrations in the exhaled air at end of exposure period (men: r²= 0.99/women: r²= 0.99). Furthermore, the exercise resulted in a net and significant increase of BLE (2-3 fold). Overall, the original model predictions overestimated the BLE for all low exposures performed in this study. To properly simulate the Toxicokinetic data, the model was refined by adding a description of an extra-hepatic biotransformation of high affinity and low capacity in the richly perfused tissues compartment. This is based on the observation that total clearance observed at low exposure levels was much greater than liver blood flow. The results of this study will facilitate the refinement of the risk assessment associated with chronic inhalation of low levels of ethanol in the general population and especially among workers.

  • evaluation of occupational exposure comparison of biological and environmental variabilities using physiologically based Toxicokinetic Modeling
    International Archives of Occupational and Environmental Health, 2013
    Co-Authors: Ginette Truchon, Robert Tardif, Ginette Charesttardif, A. Batz, P. O. Droz
    Abstract:

    Purpose Few studies compare the variabilities that characterize environmental (EM) and biological monitoring (BM) data. Indeed, comparing their respective variabilities can help to identify the best strategy for evaluating occupational exposure. The objective of this study is to quantify the biological variability associated with 18 bio-indicators currently used in work environments.

  • assessing exposure to chloroform in swimming pools using physiologically based Toxicokinetic Modeling
    Environment and Pollution, 2012
    Co-Authors: Cyril Catto, Robert Tardif, Ginette Charesttardif, Manuel J Rodriguez, Pavillon F A Savard
    Abstract:

    This work examines the use of physiologically based Toxicokinetic (PBTK) Modeling to assess exposure to the most abundant disinfection by-product (DBP), chloroform (TCM), to be found in indoor swimming pools. Real exposure scenarios including environmental (water and air levels) and biological (alveolar air or blood levels) data extracted from the literature were simulated. Predicted biological data matched up well with the reported actual levels, thereby confirming the reliability of this approach. Relative contributions of inhalation and dermal absorption to the total body burden were estimated and compared to the inconsistent results of reported studies. The PBTK simulations served to explain this inconsistency, suggesting that the prevalence of each pathway depends on environmental concentrations and on the ratio between air and water levels in particular. Likewise, comparisons between 24-h typical household and typical 1- or 2-h swimming pool exposure scenarios point to the preponderance of the latter.

  • The Effect of Workload on Biological Monitoring of Occupational Exposure to Toluene and N-Hexane: Contribution of Physiologically Based Toxicokinetic Modeling
    Journal of occupational and environmental hygiene, 2009
    Co-Authors: I. Sari-minodier, Ginette Truchon, Ginette Charest-tardif, Anick Bérubé, Robert Tardif
    Abstract:

    A physiologically based Toxicokinetic model was used to examine the impact of work load on the relationship between the airborne concentrations and exposure indicator levels of two industrial solvents, toluene and n-Hexane. The authors simulated occupational exposure (8 hr/day, 5 days/week) at different concentrations, notably 20 ppm and 50 ppm, which are the current threshold limit values recommended by ACGIH® for toluene and n-hexane, respectively. Different levels of physical activity, namely, rest, 25 W, and 50 W (for 12 hr followed by 12 hr at rest) were simulated to assess the impact of work load on the recommended biological exposure indices: toluene in blood prior to the last shift of the workweek, urinary o-cresol (a metabolite of toluene) at the end of the shift, and free (nonhydrolyzed) 2,5-hexanedione (a metabolite of n-hexane) at the end of the shift at the end of the workweek. In addition, urinary excretion of unchanged toluene was simulated. The predicted biological concentrations were comp...

  • Biological exposure indicators: quantification of biological variability using Toxicokinetic Modeling.
    Journal of occupational and environmental hygiene, 2006
    Co-Authors: Ginette Truchon, Robert Tardif, P. O. Droz, Ginette Charest-tardif, Guillaume Pierrehumbert
    Abstract:

    Compartmental and physiologically based Toxicokinetic Modeling coupled with Monte Carlo simulation were used to quantify the impact of biological variability (physiological, biochemical, and anatomic parameters) on the values of a series of bio-indicators of metal and organic industrial chemical exposures. A variability extent index and the main parameters affecting biological indicators were identified. Results show a large diversity in interindividual variability for the different categories of biological indicators examined. Measurement of the unchanged substance in blood, alveolar air, or urine is much less variable than the measurement of metabolites, both in blood and urine. In most cases, the alveolar flow and cardiac output were identified as the prime parameters determining biological variability, thus suggesting the importance of workload intensity on absorbed dose for inhaled chemicals.