Use of<i>In Vitro</i>Absorption, Distribution, Metabolism, and Excretion (ADME) Data in Bioaccumulation Assessments for Fish

Nichols, John W.; Erhardt, Susan; Dyer, Scott D.; James, Margaret O.; Moore, Margo M.; Plotzke, Kathleen P.; Segner, Helmut; Schultz, Irvin R.; Thomas, Karluss; Vasiluk, Luba; Weisbrod, Anne V.

doi:10.1080/10807030701655897

Cited by 47 publications

(62 citation statements)

References 80 publications

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“…In line with established and current extrapolation protocols for in vitro fish metabolism models [2, 12–14, 19, 51–54], we calculated clearance rates for propranolol and diclofenac and compared them with human clearance rates derived from the literature (Table 3; modified from trout and human intrinsic hepatic clearance literature review [2]). The extrapolation factors of 120 x 10 6 hepatocytes g liver -1 and 50 mg microsomal protein g liver -1 used previously to convert literature values from human studies to mL h -1 g liver -1 [55, 56], for comparison to calculated trout clearance rates [2] were adopted in this study.…”

Section: Resultsmentioning

confidence: 99%

“…As in vitro studies with fish hepatic models can be used to support screening-level bioaccumulation assessment of contaminants [2, 13, 14, 19], the aims of the present study were as follows: (1) determine the metabolic competency of 3-D liver spheroids prepared from rainbow trout, a recommended regulatory fish species, towards selected environmentally relevant pharmaceuticals; (2) utilise this in vitro data to (a) make predictions on pharmaceutical metabolism in fish based on ‘read-across’ to human metabolism data and (b) calculate intrinsic clearance rates for liver spheroids to compare with values obtained from both fish and human in vitro studies.…”

Section: Introductionmentioning

confidence: 99%

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Pharmaceutical Metabolism in Fish: Using a 3-D Hepatic In Vitro Model to Assess Clearance

et al. 2017

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At high internal doses, pharmaceuticals have the potential for inducing biological/pharmacological effects in fish. One particular concern for the environment is their potential to bioaccumulate and reach pharmacological levels; the study of these implications for environmental risk assessment has therefore gained increasing attention. To avoid unnecessary testing on animals, in vitro methods for assessment of xenobiotic metabolism could aid in the ecotoxicological evaluation. Here we report the use of a 3-D in vitro liver organoid culture system (spheroids) derived from rainbow trout to measure the metabolism of seven pharmaceuticals using a substrate depletion assay. Of the pharmaceuticals tested, propranolol, diclofenac and phenylbutazone were metabolised by trout liver spheroids; atenolol, metoprolol, diazepam and carbamazepine were not. Substrate depletion kinetics data was used to estimate intrinsic hepatic clearance by this spheroid model, which was similar for diclofenac and approximately 5 fold higher for propranolol when compared to trout liver microsomal fraction (S9) data. These results suggest that liver spheroids could be used as a relevant and metabolically competent in vitro model with which to measure the biotransformation of pharmaceuticals in fish; and propranolol acts as a reproducible positive control.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmaceutical Metabolism in Fish: Using a 3-D Hepatic In Vitro Model to Assess Clearance

et al. 2017

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“…An important potential use of these methods is to predict metabolism impacts on chemical bioaccumulation by fish (Nichols et al, 2007(Nichols et al, , 2009. Computational models driven largely by log K OW -based relationships accurately predict the accumulation of many compounds, provided that they do not undergo substantial biotransformation (Arnot and Gobas, 2003).…”

Section: Supplement 53mentioning

confidence: 99%

“…Basic Protocol 1 describes isolation of the S9 fraction from trout liver, assessment of metabolic stability using a substrate depletion approach, and expression of the result as in vivo intrinsic clearance. Potential applications of these methods in the field of ecotoxicology include prediction of metabolic impacts on chemical accumulation by fish (Nichols et al, 2007(Nichols et al, , 2009), evaluation of emerging chemical contaminants (e.g., pharmaceuticals in municipal waste water), and improved interpretation of in vivo toxicity testing results.…”

Section: Introductionmentioning

confidence: 99%

Assessment of Metabolic Stability Using the Rainbow Trout (Oncorhynchus mykiss) Liver S9 Fraction

Johanning¹,

Hancock

Escher

et al. 2012

CP Toxicology

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Standard protocols are given for assessing metabolic stability in rainbow trout using the liver S9 fraction. These protocols describe the isolation of S9 fractions from trout livers, evaluation of metabolic stability using a substrate depletion approach, and expression of the result as in vivo intrinsic clearance. Additional guidance is provided on the care and handling of test animals, design and interpretation of preliminary studies, and development of analytical methods. Although initially developed to predict metabolism impacts on chemical accumulation by fish, these procedures can be used to support a broad range of scientific and risk assessment activities including evaluation of emerging chemical contaminants and improved interpretation of toxicity testing results. These protocols have been designed for rainbow trout and can be adapted to other species as long as species-specific considerations are modified accordingly (e.g., fish maintenance and incubation mixture temperature). Rainbow trout is a cold-water species. Protocols for other species (e.g., carp, a warm-water species) can be developed based on these procedures as long as the specific considerations are taken into account.

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“…Recently, interest has been renewed in approaches for the assessment of the bioaccumulation potential of chemicals, principally driven by the need to evaluate large numbers of chemicals as part of new chemical legislation, (e.g., Environment Canada DSL [Environment Canada ], REACH [ECHA 2007]). This renewed interest has led to a variety of research activities and advances in bioaccumulation science as exemplified by recent International Life Sciences Institute–Health and Environmental Sciences Institute (ILSI‐HESI) (Nichols et al ; Weisbrod et al ; HESI ; Burkhard, Cowan‐Ellsberry, et al ) and Society of Environmental Toxicology and Chemistry (SETAC) workshops (Klecka and Muir ). Although much of this increased activity has focused on bioaccumulation in aquatic systems, increased interest also has been expressed in bioaccumulation assessment in terrestrial systems (Gottardo et al ).…”

Section: Introductionmentioning

confidence: 99%

Review of laboratory‐based terrestrial bioaccumulation assessment approaches for organic chemicals: Current status and future possibilities

Hoke¹,

Huggett

Brasfield

et al. 2015

Integr Envir Assess & Manag

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In the last decade, interest has been renewed in approaches for the assessment of the bioaccumulation potential of chemicals, principally driven by the need to evaluate large numbers of chemicals as part of new chemical legislation, while reducing vertebrate test organism use called for in animal welfare legislation. This renewed interest has inspired research activities and advances in bioaccumulation science for neutral organic chemicals in aquatic environments. In January 2013, ILSI Health and Environmental Sciences Institute convened experts to identify the state of the science and existing shortcomings in terrestrial bioaccumulation assessment of neutral organic chemicals. Potential modifications to existing laboratory methods were identified, including areas in which new laboratory approaches or test methods could be developed to address terrestrial bioaccumulation. The utility of “non‐ecotoxicity” data (e.g., mammalian laboratory data) was also discussed. The highlights of the workshop discussions are presented along with potential modifications in laboratory approaches and new test guidelines that could be used for assessing the bioaccumulation of chemicals in terrestrial organisms. Integr Environ Assess Manag 2016;12:109–122. © 2015 The Authors. Integrated Environmental Assessment and Management Published by Wiley Periodicals, Inc. on behalf of SETAC.

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Use ofIn VitroAbsorption, Distribution, Metabolism, and Excretion (ADME) Data in Bioaccumulation Assessments for Fish

Cited by 47 publications

References 80 publications

Pharmaceutical Metabolism in Fish: Using a 3-D Hepatic In Vitro Model to Assess Clearance

Pharmaceutical Metabolism in Fish: Using a 3-D Hepatic In Vitro Model to Assess Clearance

Assessment of Metabolic Stability Using the Rainbow Trout (Oncorhynchus mykiss) Liver S9 Fraction

Review of laboratory‐based terrestrial bioaccumulation assessment approaches for organic chemicals: Current status and future possibilities

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