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William J. Adams - One of the best experts on this subject based on the ideXlab platform.
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The Tissue Residue approach for toxicity assessment: Findings and critical reviews from a Society of Environmental Toxicology and Chemistry Pellston Workshop
Integrated environmental assessment and management, 2010Co-Authors: James P. Meador, William J. Adams, Lynn S. Mccarty, Beate I. Escher, Anne E. Mcelroy, Keith SappingtonAbstract:Over the past few years, the "critical body Residue" approach for assessing toxicity based on bioaccumulated chemicals has evolved into a more expansive consideration of Tissue Residues as the dose metric when defining dose-response relationships,evaluating mixtures, developing protective guidelines, and conducting risk assessments. Hence, scientists refer to "Tissue Residue approach for toxicity assessment" or "Tissue Residue-effects approach" (TRA) when addressing ecotoxicology issues pertaining to Tissue (or internal) concentrations. This introduction provides an overview of a SETAC Pellston Workshop held in 2007 to review the state of the science for using Tissue Residues as the dose metric in environmental toxicology. The key findings of the workshop are presented, along with recommendations for research to enhance understanding of toxic responses within and between species, and to advance the use of the TRA in assessment and management of chemicals in the environment.
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10th Anniversary Critical Review: The Tissue-Residue approach for toxicity assessment: concepts, issues, application, and recommendations.
Journal of environmental monitoring : JEM, 2008Co-Authors: James P. Meador, Lynn S. Mccarty, Beate I. Escher, William J. AdamsAbstract:The Tissue-Residue approach for toxicity assessment (TRA) is simply the use of Tissue concentrations as the dose metric for characterizing toxicant potency. There are several advantages to using Tissue Residues over exposure concentrations (e.g., water, sediment, and diet) to calculate toxicity metrics. These include a large reduction in toxic response variability among all species for a given compound, an improved ability to address mixture toxicity, an increased use of information on modes and mechanisms of toxic action, a likely reduction in the number of species needed to characterize toxicant potency, the potential to improve ecological risk assessments, and the generation of more scientifically defensible Tissue, water, and sediment toxicity guidelines or criteria. A keystone concept for the TRA is that the body/Tissue Residue reflects the target “dose” better than the traditional dose (e.g., water, air, soil/sediment, or diet) because the closer the dose surrogate is to the actual site of toxic action the less it is influenced by myriad modifying factors. Our goal for this review is to present the concepts and issues associated with the TRA and discuss some of the potential applications and expected improvements to the field of environmental toxicology that we believe will promote enhanced protection for species and ecosystems.
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Setting site-specific water-quality standards by using Tissue Residue criteria and bioaccumulation data. Part 1. Methodology
Environmental Toxicology and Chemistry, 2005Co-Authors: John Toll, Kevin V. Brix, David K. Deforest, Lucinda M. Tear, William J. AdamsAbstract:We have developed a method for determining site-specific water-quality standards (SSWQSs) for substances regulated based on Tissue Residues. The method uses a multisite regression model to solve for the conditional prior probability density function (PDF) on water concentration, given that Tissue concentration equals a Tissue Residue threshold. The method then uses site-specific water and Tissue concentration data to update the probabilities on a Monte Carlo sample of the prior PDF by using Bayesian Monte Carlo analysis. The resultant posterior PDF identifies the water concentration that, if met at the site, would provide a desired level of confidence of meeting the Tissue Residue threshold contingent on model assumptions. This allows for derivation of a SSWQS. The method is fully reproducible, statistically rigorous, and easily implemented. A useful property of the method is that the model is sensitive to the amount of site-specific data available, that is, a more conservative or protective number (water concentration) is derived when the data set is small or the variance is large. Likewise, as the site water concentration increases above the water-quality standard, more site-specific information is needed to demonstrate a safe concentration at the site. A companion paper demonstrates the method by using selenium as an example.
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Setting site-specific water-quality standards by using Tissue Residue thresholds and bioaccumulation data. Part 2. Calculating site-specific selenium water-quality standards for protecting fish and birds
Environmental Toxicology and Chemistry, 2005Co-Authors: Kevin V. Brix, David K. Deforest, John Toll, Lucinda M. Tear, William J. AdamsAbstract:In a companion paper, a method for deriving Tissue Residue-based site-specific water-quality standards (SSWQSs) was described. In this paper, the methodology is applied to selenium (Se) as an example. Models were developed to describe Se bioaccumulation in aquatic-dependent bird eggs and whole fish. A simple log-linear model best described Se accumulation in bird eggs (r2 = 0.50). For fish, separate hockey stick regressions were developed for lentic (r2 = 0.65) and lotic environments (r2 = 0.37). The low r2 value for the lotic fish model precludes its reliable use at this time. Corresponding Tissue Residue criteria (i.e., Tissue thresholds) for bird eggs and whole fish also were identified and example model predictions were made. The models were able to predict SSWQSs over a wide range of water-Tissue combinations that might be encountered in the environment. The models also were shown to be sensitive to variability in measured Tissue Residues with relatively small changes in variability (as characterized by the standard error) resulting in relatively large differences in SSWQSs.
James P. Meador - One of the best experts on this subject based on the ideXlab platform.
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The Tissue Residue approach for toxicity assessment: Findings and critical reviews from a Society of Environmental Toxicology and Chemistry Pellston Workshop
Integrated environmental assessment and management, 2010Co-Authors: James P. Meador, William J. Adams, Lynn S. Mccarty, Beate I. Escher, Anne E. Mcelroy, Keith SappingtonAbstract:Over the past few years, the "critical body Residue" approach for assessing toxicity based on bioaccumulated chemicals has evolved into a more expansive consideration of Tissue Residues as the dose metric when defining dose-response relationships,evaluating mixtures, developing protective guidelines, and conducting risk assessments. Hence, scientists refer to "Tissue Residue approach for toxicity assessment" or "Tissue Residue-effects approach" (TRA) when addressing ecotoxicology issues pertaining to Tissue (or internal) concentrations. This introduction provides an overview of a SETAC Pellston Workshop held in 2007 to review the state of the science for using Tissue Residues as the dose metric in environmental toxicology. The key findings of the workshop are presented, along with recommendations for research to enhance understanding of toxic responses within and between species, and to advance the use of the TRA in assessment and management of chemicals in the environment.
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A review of the Tissue Residue approach for organic and organometallic compounds in aquatic organisms.
Integrated environmental assessment and management, 2010Co-Authors: Anne E. Mcelroy, James P. Meador, Mace G. Barron, Nancy Beckvar, Susan Kane Driscoll, Tom F. Parkerton, Thomas G. Preuss, Jeffery A. SteevensAbstract:This paper reviews the Tissue Residue approach (TRA) for toxicity assessment as it applies to organic chemicals and some organometallic compounds (Sn, Hg, and Pb) in aquatic organisms. Specific emphasis was placed on evaluating key factors that influence interpretation of critical body Residue (CBR) toxicity metrics including data quality issues, lipid dynamics, choice of endpoints, processes that alter toxicokinetics and toxicodynamics, phototoxicity, species- and life stage-specific sensitivities, and biotransformation. The vast majority of data available on TRA is derived from laboratory studies of acute lethal responses to organic toxicants exhibiting baseline toxicity. Application of the TRA to various baseline toxicants as well as substances with specific modes of action via receptor-mediated processes, such as chlorinated aromatic hydrocarbons, pesticides, and organometallics is discussed, as is application of TRA concepts in field assessments of Tissue Residues. In contrast to media-based toxicity relationships, CBR values tend to be less variable and less influenced by factors that control bioavailability and bioaccumulation, and TRA can be used to infer mechanisms of toxic action, evaluate the toxicity of mixtures, and interpret field data on bioaccumulated toxicants. If Residue-effects data are not available, body Residues can be estimated, as has been done using the target lipid model for baseline toxicants, to derive critical values for risk assessment. One of the primary unresolved issues complicating TRA for organic chemicals is biotransformation. Further work on the influence of biotransformation, a better understanding of contaminant lipid interactions, and an explicit understanding of the time dependency of CBRs and receptor-mediated toxicity are all required to advance this field. Additional Residue-effects data on sublethal endpoints, early life stages, and a wider range of legacy and emergent contaminants will be needed to improve the ability to use TRA for organic and organometallic compounds. Integr Environ Assess Manag 2011;7:50–74. © 2010 SETAC
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Application of the Tissue Residue approach in ecological risk assessment.
Integrated environmental assessment and management, 2010Co-Authors: Keith Sappington, David R. Mount, Todd S. Bridges, Steven P. Bradbury, Russell J. Erickson, A. Jan Hendriks, Roman P. Lanno, James P. Meador, Mike H Salazar, Doug SpryAbstract:The objective of this work is to present a critical review of the application of the Tissue Residue approach (TRA) in ecological risk and/or impact assessment (ERA) of chemical stressors and environmental criteria development. A secondary goal is to develop a framework for integrating the TRA into ecological assessments along with traditional, exposure concentration-based assessment approaches. Although widely recognized for its toxicological appeal, the utility of the TRA in specific applications will depend on numerous factors, such as chemical properties, exposure characteristics, assessment type, availability of Tissue Residue-response data, and ability to quantify chemical exposure. Therefore, the decision to use the TRA should include an evaluation of the relative strengths, limitations, and uncertainties among exposure and Residue-based methods for characterizing toxicological effects. Furthermore, rather than supplanting exposure concentration-based toxicity assessments, the TRA can be highly effective for evaluating and reducing uncertainty when used in a complementary manner (e.g., when evaluating multiple lines of evidence in field studies). To address limitations with the available Tissue Residue-response data, approaches for extrapolating Residue-based toxicity data across species, Tissues, and exposure durations are discussed. Some of these approaches rely on predicted Residue-response relationships or toxicological models that have an implicit Residue-response basis (e.g., biotic ligand model). Because risk to an organism is a function of both its exposure potential and inherent sensitivity (i.e., on a Residue basis), bioaccumulation models will be required not only for translating Tissue Residue criteria into corresponding water and sediment criteria, but also for defining the most vulnerable species in an assemblage (i.e., highly exposed and highly sensitive species). Application of the TRA in ecological assessments and criteria development are summarized for bioaccumulative organic chemicals, TBT, and in situ bioassays using bivalve molluscs. Integr Environ Assess Manag 2011;7:116–140. © 2010 SETAC
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Crucial role of mechanisms and modes of toxic action for understanding Tissue Residue toxicity and internal effect concentrations of organic chemicals.
Integrated environmental assessment and management, 2010Co-Authors: Beate I. Escher, James P. Meador, Roman Ashauer, Scott D. Dyer, Joop L. M. Hermens, Jong-hyeon Lee, Heather A. Leslie, Philipp Mayer, Michael St. J. WarneAbstract:This article reviews the mechanistic basis of the Tissue Residue approach for toxicity assessment (TRA). The Tissue Residue approach implies that whole-body or organ concentrations (Residues) are a better dose metric for describing toxicity to aquatic organisms than is the aqueous concentration typically used in the external medium. Although the benefit of internal concentrations as dose metrics in ecotoxicology has long been recognized, the application of the Tissue Residue approach remains limited. The main factor responsible for this is the difficulty of measuring internal concentrations. We propose that environmental toxicology can advance if mechanistic considerations are implemented and toxicokinetics and toxicodynamics are explicitly addressed. The variability in ecotoxicological outcomes and species sensitivity is due in part to differences in toxicokinetics, which consist of several processes, including absorption, distribution, metabolism, and excretion (ADME), that influence internal concentrations. Using internal concentrations or Tissue Residues as the dose metric substantially reduces the variability in toxicity metrics among species and individuals exposed under varying conditions. Total internal concentrations are useful as dose metrics only if they represent a surrogate of the biologically effective dose, the concentration or dose at the target site. If there is no direct proportionality, we advise the implementation of comprehensive toxicokinetic models that include deriving the target dose. Depending on the mechanism of toxicity, the concentration at the target site may or may not be a sufficient descriptor of toxicity. The steady-state concentration of a baseline toxicant associated with the biological membrane is a good descriptor of the toxicodynamics of baseline toxicity. When assessing specific-acting and reactive mechanisms, additional parameters (e.g., reaction rate with the target site and regeneration of the target site) are needed for characterization. For specifically acting compounds, intrinsic potency depends on 1) affinity for, and 2) type of interaction with, a receptor or a target enzyme. These 2 parameters determine the selectivity for the toxic mechanism and the sensitivity, respectively. Implementation of mechanistic information in toxicokinetic–toxicodynamic (TK–TD) models may help explain timedelayed effects, toxicity after pulsed or fluctuating exposure, carryover toxicity after sequential pulses, and mixture toxicity.We believe that this mechanistic understanding of Tissue Residue toxicity will lead to improved environmental risk assessment.
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Advancing environmental toxicology through chemical dosimetry: External exposures versus Tissue Residues
Integrated environmental assessment and management, 2010Co-Authors: L. S. Mccarty, James P. Meador, P. F. Landrum, Samuel N. Luoma, A. A. Merten, B. K. Shephard, A. P. Van WezelAbstract:The Tissue Residue dose concept has been used, although in a limited manner, in environmental toxicology for more than 100 y. This review outlines the history of this approach and the technical background for organic chemicals and metals. Although the toxicity of both can be explained in Tissue Residue terms, the relationship between external exposure concentration, body and/or Tissues dose surrogates, and the effective internal dose at the sites of toxic action tends to be more complex for metals. Various issues and current limitations related to research and regulatory applications are also examined. It is clear that the Tissue Residue approach (TRA) should be an integral component in future efforts to enhance the generation, understanding, and utility of toxicity testing data, both in the laboratory and in the field. To accomplish these goals, several key areas need to be addressed: 1) development of a risk-based interpretive framework linking toxicology and ecology at multiple levels of biological organization and incorporating organism-based dose metrics; 2) a broadly applicable, generally accepted classification scheme for modes/mechanisms of toxic action with explicit consideration of Residue information to improve both single chemical and mixture toxicity data interpretation and regulatory risk assessment; 3) toxicity testing protocols updated to ensure collection of adequate Residue information, along with toxicokinetics and toxicodynamics information, based on explicitly defined toxicological models accompanied by toxicological model validation; 4) continued development of Residue-effect databases is needed ensure their ongoing utility; and 5) regulatory guidance incorporating Residue-based testing and interpretation approaches, essential in various jurisdictions. Integr Environ Assess Manag 2011;7:7–27. © 2010 SETAC
Ernest E Smith - One of the best experts on this subject based on the ideXlab platform.
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qualitative and quantitative drug Residue analyses florfenicol in white tailed deer odocoileus virginianus and supermarket meat by liquid chromatography tandem mass spectrometry
Journal of Chromatography B, 2016Co-Authors: Shanoy C Anderson, Seenivasan Subbiah, Angella Gentles, Galen P Austin, Paul Stonum, T A Brooks, C Brooks, Ernest E SmithAbstract:Abstract Chlortetracycline is (CTC) is a tetracycline antibiotic which is being in the white-tailed deer industry to improve production and animal health. In this paper, we present a method for determining chlortetracycline Residues in edible white-tailed deer Tissues, using liquid chromatography with heated electrospray ionization and mass spectrometry detection. The procedure involved extraction with EDTA-McIlvaine buffer at pH 4.0, followed by solid-phase extraction cleanup using a hydrophilic-lipophilic balance (HLB) cartridge. The liquid chromatography analysis was performed with heated electrospray ionization and mass spectrometry detection. The limit of quantification for the method was 2.7 ng/g and limit of detection was 0.8 ng/g. The recovery values were >78.5% for muscle, 65.1% for kidney, 63.1% for liver. Mean Tissue Residue concentration of chlortetracycline and it's epimer, 4-epi chlortetracycline (4-epi-CTC) at 10-day withdrawal period for kidney, liver, muscle was 122.8, 44.7 and 26.7 ng/g, respectively. Chlortetracycline Tissue Residue concentration at 45-day withdrawal period for kidney, liver, muscle was 19.2, 28.9 and 10.7 ng/g, respectively. Mean Tissue concentration of CTC was less than the established maximum residual limit (MRL) values for bovine Tissues. We have validated and successfully applied this method in the qualitative and quantification of chlortetracycline in white-tailed deer Tissue samples.
R Bammer - One of the best experts on this subject based on the ideXlab platform.
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Time-to-Maximum of the Tissue Residue Function Improves Diagnostic Performance for Detecting Distal Vessel Occlusions on CT Angiography.
AJNR. American journal of neuroradiology, 2021Co-Authors: S A Amukotuwa, K Zhou, I Page, P Brotchie, R BammerAbstract:Detecting intracranial distal arterial occlusions on CTA is challenging but increasingly relevant to clinical decision-making. Our purpose was to determine whether the use of CTP-derived time-to-maximum of the Tissue Residue function maps improves diagnostic performance for detecting these occlusions. Seventy consecutive patients with a distal arterial occlusion and 70 randomly selected controls who underwent multimodal CT with CTA and CTP for a suspected acute ischemic stroke were included in this retrospective study. Four readers with different levels of experience independently read the CTAs in 2 separate sessions, with and without time-to-maximum of the Tissue Residue function maps, recording the presence or absence of an occlusion, diagnostic confidence, and interpretation time. Accuracy for detecting distal occlusions was assessed using receiver operating characteristic analysis, and areas under curves were compared to assess whether accuracy improved with use of time-to-maximum of the Tissue Residue function. Changes in diagnostic confidence and interpretation time were assessed using the Wilcoxon signed rank test. Mean sensitivity for detecting occlusions on CTA increased from 70.7% to 90.4% with use of time-to-maximum of the Tissue Residue function maps. Diagnostic accuracy improved significantly for the 4 readers (P < .001), with areas under the receiver operating characteristic curves increasing by 0.186, 0.136, 0.114, and 0.121, respectively. Diagnostic confidence and speed also significantly increased. All assessed metrics of diagnostic performance for detecting distal arterial occlusions improved with the use of time-to-maximum of the Tissue Residue function maps, encouraging their use to aid in interpretation of CTA by both experienced and inexperienced readers. These findings show the added diagnostic value of including CTP in the acute stroke imaging protocol. © 2021 by American Journal of Neuroradiology.
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time to maximum of the Tissue Residue function improves diagnostic performance for detecting distal vessel occlusions on ct angiography
American Journal of Neuroradiology, 2021Co-Authors: S A Amukotuwa, K Zhou, I Page, P Brotchie, R BammerAbstract:BACKGROUND AND PURPOSE Detecting intracranial distal arterial occlusions on CTA is challenging but increasingly relevant to clinical decision-making. Our purpose was to determine whether the use of CTP-derived time-to-maximum of the Tissue Residue function maps improves diagnostic performance for detecting these occlusions. MATERIALS AND METHODS Seventy consecutive patients with a distal arterial occlusion and 70 randomly selected controls who underwent multimodal CT with CTA and CTP for a suspected acute ischemic stroke were included in this retrospective study. Four readers with different levels of experience independently read the CTAs in 2 separate sessions, with and without time-to-maximum of the Tissue Residue function maps, recording the presence or absence of an occlusion, diagnostic confidence, and interpretation time. Accuracy for detecting distal occlusions was assessed using receiver operating characteristic analysis, and areas under curves were compared to assess whether accuracy improved with use of time-to-maximum of the Tissue Residue function. Changes in diagnostic confidence and interpretation time were assessed using the Wilcoxon signed rank test. RESULTS Mean sensitivity for detecting occlusions on CTA increased from 70.7% to 90.4% with use of time-to-maximum of the Tissue Residue function maps. Diagnostic accuracy improved significantly for the 4 readers (P < .001), with areas under the receiver operating characteristic curves increasing by 0.186, 0.136, 0.114, and 0.121, respectively. Diagnostic confidence and speed also significantly increased. CONCLUSIONS All assessed metrics of diagnostic performance for detecting distal arterial occlusions improved with the use of time-to-maximum of the Tissue Residue function maps, encouraging their use to aid in interpretation of CTA by both experienced and inexperienced readers. These findings show the added diagnostic value of including CTP in the acute stroke imaging protocol.
Beate I. Escher - One of the best experts on this subject based on the ideXlab platform.
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The Tissue Residue approach for toxicity assessment: Findings and critical reviews from a Society of Environmental Toxicology and Chemistry Pellston Workshop
Integrated environmental assessment and management, 2010Co-Authors: James P. Meador, William J. Adams, Lynn S. Mccarty, Beate I. Escher, Anne E. Mcelroy, Keith SappingtonAbstract:Over the past few years, the "critical body Residue" approach for assessing toxicity based on bioaccumulated chemicals has evolved into a more expansive consideration of Tissue Residues as the dose metric when defining dose-response relationships,evaluating mixtures, developing protective guidelines, and conducting risk assessments. Hence, scientists refer to "Tissue Residue approach for toxicity assessment" or "Tissue Residue-effects approach" (TRA) when addressing ecotoxicology issues pertaining to Tissue (or internal) concentrations. This introduction provides an overview of a SETAC Pellston Workshop held in 2007 to review the state of the science for using Tissue Residues as the dose metric in environmental toxicology. The key findings of the workshop are presented, along with recommendations for research to enhance understanding of toxic responses within and between species, and to advance the use of the TRA in assessment and management of chemicals in the environment.
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Tissue Residue approach for chemical mixtures.
Integrated environmental assessment and management, 2010Co-Authors: Scott D. Dyer, Heather A. Leslie, Michael St. J. Warne, Joseph S. Meyer, Beate I. EscherAbstract:At the SETAC Pellston Workshop "The Tissue Residues Approach for Toxicity Assessment," held in June 2007, we discussed mixture toxicology in terms of the Tissue Residue approach (TRA). This article reviews the literature related to the TRA for mixtures of chemicals and recommends a practical, tiered approach that can be implemented in regulatory or risk assessment applications. As with the toxicity of individual chemicals, addressing mixture toxicity by means of the TRA has a number of significant advantages. Early work provided a theoretical basis and experimental data to support the use of TRA for mixtures; later work provided a field-based validation of the integration. However, subsequent development has been hindered by the lack of mixture toxicity data expressed in Tissue or preferably target-site concentrations. We recommend a framework for addressing the toxicology of mixtures that integrates the TRA and mixture toxicology in a 3-tier approach. Tier I uses concentration addition (CA) to estimate the toxicity of mixtures regardless of the mechanism of action of the components. However, the common approach that uses a bioaccumulation factor (BAF) to predict TR from the exposure-water concentration for organics must be modified slightly for metals because, unlike organics, the BAF for a metal changes as 1) the aqueous exposure concentration changes, and 2) the concentration of other metals changes. In addition, total Tissue Residues of a metal are not a good predictor of toxicity, because some organisms store high concentrations of metals internally in detoxified forms. In tier I, if the combination of measured concentrations in the mixture exceeds that predicted to produce adverse effects or above-reference levels, it is necessary to proceed to tier II. Tier II is a mixed model that employs CA and independent action to estimate mixture toxicity. Tiers I and II estimate the toxicity of mixtures to individual species. In tier III, the TRA is integrated with the multisubstance potentially affected fraction (ms-PAF) method to derive TR levels that are protective of a selected percentage of species in aquatic communities (e.g., hazardous concentration for 5% of the species [HC5]).
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Crucial role of mechanisms and modes of toxic action for understanding Tissue Residue toxicity and internal effect concentrations of organic chemicals.
Integrated environmental assessment and management, 2010Co-Authors: Beate I. Escher, James P. Meador, Roman Ashauer, Scott D. Dyer, Joop L. M. Hermens, Jong-hyeon Lee, Heather A. Leslie, Philipp Mayer, Michael St. J. WarneAbstract:This article reviews the mechanistic basis of the Tissue Residue approach for toxicity assessment (TRA). The Tissue Residue approach implies that whole-body or organ concentrations (Residues) are a better dose metric for describing toxicity to aquatic organisms than is the aqueous concentration typically used in the external medium. Although the benefit of internal concentrations as dose metrics in ecotoxicology has long been recognized, the application of the Tissue Residue approach remains limited. The main factor responsible for this is the difficulty of measuring internal concentrations. We propose that environmental toxicology can advance if mechanistic considerations are implemented and toxicokinetics and toxicodynamics are explicitly addressed. The variability in ecotoxicological outcomes and species sensitivity is due in part to differences in toxicokinetics, which consist of several processes, including absorption, distribution, metabolism, and excretion (ADME), that influence internal concentrations. Using internal concentrations or Tissue Residues as the dose metric substantially reduces the variability in toxicity metrics among species and individuals exposed under varying conditions. Total internal concentrations are useful as dose metrics only if they represent a surrogate of the biologically effective dose, the concentration or dose at the target site. If there is no direct proportionality, we advise the implementation of comprehensive toxicokinetic models that include deriving the target dose. Depending on the mechanism of toxicity, the concentration at the target site may or may not be a sufficient descriptor of toxicity. The steady-state concentration of a baseline toxicant associated with the biological membrane is a good descriptor of the toxicodynamics of baseline toxicity. When assessing specific-acting and reactive mechanisms, additional parameters (e.g., reaction rate with the target site and regeneration of the target site) are needed for characterization. For specifically acting compounds, intrinsic potency depends on 1) affinity for, and 2) type of interaction with, a receptor or a target enzyme. These 2 parameters determine the selectivity for the toxic mechanism and the sensitivity, respectively. Implementation of mechanistic information in toxicokinetic–toxicodynamic (TK–TD) models may help explain timedelayed effects, toxicity after pulsed or fluctuating exposure, carryover toxicity after sequential pulses, and mixture toxicity.We believe that this mechanistic understanding of Tissue Residue toxicity will lead to improved environmental risk assessment.
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10th Anniversary Critical Review: The Tissue-Residue approach for toxicity assessment: concepts, issues, application, and recommendations.
Journal of environmental monitoring : JEM, 2008Co-Authors: James P. Meador, Lynn S. Mccarty, Beate I. Escher, William J. AdamsAbstract:The Tissue-Residue approach for toxicity assessment (TRA) is simply the use of Tissue concentrations as the dose metric for characterizing toxicant potency. There are several advantages to using Tissue Residues over exposure concentrations (e.g., water, sediment, and diet) to calculate toxicity metrics. These include a large reduction in toxic response variability among all species for a given compound, an improved ability to address mixture toxicity, an increased use of information on modes and mechanisms of toxic action, a likely reduction in the number of species needed to characterize toxicant potency, the potential to improve ecological risk assessments, and the generation of more scientifically defensible Tissue, water, and sediment toxicity guidelines or criteria. A keystone concept for the TRA is that the body/Tissue Residue reflects the target “dose” better than the traditional dose (e.g., water, air, soil/sediment, or diet) because the closer the dose surrogate is to the actual site of toxic action the less it is influenced by myriad modifying factors. Our goal for this review is to present the concepts and issues associated with the TRA and discuss some of the potential applications and expected improvements to the field of environmental toxicology that we believe will promote enhanced protection for species and ecosystems.