18 results on '"OTTON, S. VICTORIA"'
Search Results
2. In vitro biotransformation rates in fish liver S9: Effect of dosing techniques.
- Author
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Lee, Yung‐Shan, Lee, Danny H.Y., Delafoulhouze, Maximilien, Otton, S. Victoria, Moore, Margo M., Kennedy, Chris J., and Gobas, Frank A.P.C.
- Subjects
FISH research ,BIOTRANSFORMATION (Metabolism) ,BIOCONCENTRATION ,CHEMICALS ,ORGANIC compounds ,POLYCYCLIC aromatic hydrocarbons ,ENVIRONMENTAL toxicology research - Abstract
In vitro biotransformation assays are currently being explored to improve estimates of bioconcentration factors of potentially bioaccumulative organic chemicals in fish. The present study compares thin-film and solvent-delivery dosing techniques as well as single versus multiple chemical dosing for measuring biotransformation rates of selected polycyclic aromatic hydrocarbons in rainbow trout ( Oncorhynchus mykiss) liver S9. The findings show that biotransformation rates of very hydrophobic substances can be accurately measured in thin-film sorbent-dosing assays from concentration-time profiles in the incubation medium but not from those in the sorbent phase because of low chemical film-to-incubation-medium mass-transfer rates at the incubation temperature of 13.5 °C required for trout liver assays. Biotransformation rates determined by thin-film dosing were greater than those determined by solvent-delivery dosing for chrysene (octanol-water partition coefficient [ K
OW ] = 105.60 ) and benzo[ a]pyrene ( KOW = 106.04 ), whereas there were no statistical differences in pyrene ( KOW = 105.18 ) biotransformation rates between the 2 methods. In sorbent delivery-based assays, simultaneous multiple-chemical dosing produced biotransformation rates that were not statistically different from those measured in single-chemical dosing experiments for pyrene and benzo[ a]pyrene but not for chrysene. In solvent-delivery experiments, multiple-chemical dosing produced biotransformation rates that were much smaller than those in single-chemical dosing experiments for all test chemicals. While thin-film sorbent-phase and solvent delivery-based dosing methods are both suitable methods for measuring biotransformation rates of substances of intermediate hydrophobicity, thin-film sorbent-phase dosing may be more suitable for superhydrophobic chemicals. Environ Toxicol Chem 2014;33:1885-1893. © 2014 SETAC [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
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3. Relationship between biodegradation and sorption of phthalate esters and their metabolites in natural sediments.
- Author
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Kickham, Peter, Otton, S. Victoria, Moore, Margo M., Ikonomou, Michael G., and Gobas, Frank A.P.C.
- Subjects
- *
BIODEGRADATION , *PHTHALATE esters , *METABOLITES , *SOIL biology , *ECOLOGICAL risk assessment , *TOXICOLOGICAL interactions , *ENVIRONMENTAL toxicology ,ENVIRONMENTAL aspects - Abstract
Regulatory evaluations of commercial chemicals in Canada, the United States, the European Union, and other countries aim to identify biodegradation rates of chemicals in natural soils and sediments. However, commonly used biodegradation testing methods are limited in their capacity to determine biodegradation rates under natural environmental conditions. As a result, widely varying biodegradation rates have been reported for many very hydrophobic substances. This variability causes difficulties in regulatory evaluations, potentially leading to chemical misclassification. In the present study, the authors developed a model of the relationship between biodegradation, sorption, and hydrophobicity, and tested the model in experiments that measured the biodegradation rates of a range of di-phthalate esters (DPEs) and mono-phthalate esters (MPEs) in natural sediments. The results indicate that DPEs and MPEs have the inherent capacity to be quickly degraded by microbes in sediments at a common rate, but that DPE biodegradation rates in natural sediments decrease with increasing phthalate ester sorption to sediments. The results show that inherently biodegradable substances that are subject to a high degree of sorption can be expected to exhibit long half-lives in natural sediments. The model provides a potential methodology for assessing biodegradation rates in natural sediments from inherent biodegradation rates measured in screening tests by accounting for chemical sorption. The present study indicates that a reduced rate of biodegradation is due to a reduced fraction of freely dissolved chemical concentration in the interstitial water, and that the environmental significance of sorption-reduced biodegradation rates needs to be viewed in the context of risk in chemical evaluations. Environ. Toxicol. Chem. 2012; 31: 1730-1737. © 2012 SETAC [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
4. Measuring In Vitro Biotransformation Rates of Super Hydrophobic Chemicals in Rat Liver 59 Fractions Using Thin-Film Sorbent-Phase Dosing.
- Author
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Yung-Shan Lee, Otton, S. Victoria, Campbell, David A., Moore, Margo M., Kennedy, Chris J., and Gobas, Frank A. P. C.
- Subjects
- *
BIOTRANSFORMATION (Metabolism) , *HYDROPHOBIC compounds , *PHYSIOLOGICAL effects of chemicals , *BIOACCUMULATION , *DOSE-response relationship in biochemistry , *TISSUE analysis , *ANIMAL models in research - Abstract
Methods for rapid and cost-effective assessment of the biotransformation potential of very hydrophobic and potentially bioaccumulative chemicals in mammals are urgently needed for the ongoing global evaluation of the environmental behavior of commercial chemicals. We developed and tested a novel solvent-free, thin-film sorbent-phase in vitro dosing system to measure the in vitro biotransformation rates of very hydrophobic chemicals in male Sprague-Dawley rat liver S9 homogenates and compared the rates to those measured by conventional solvent-delivery dosing. The thin-film sorbent-phase dosing system using ethylene vinyl acetate coated vials was developed to eliminate the incomplete dissolution of very hydrophobic substances in largely aqueous liver homogenates, to determine biotransformation rates at low substrate concentrations, to measure the unbound fraction of substrate in solution, and to simplify chemical analysis by avoiding the difficult extraction of test chemicals from complex biological matrices. Biotransformation rates using sorbent-phase dosing were 2-fold greater than those measured using solvent-delivery dosing. Unbound concentrations of very hydrophobic test chemicals were found to decline with increasing S9 and protein concentrations, causing measured biotransformation rates to be independent of S9 or protein concentrations. The results emphasize the importance of specifying both protein content and unbound substrate fraction in the measurement and reporting of in vitro biotransformation rates of very hydrophobic substances, which can be achieved in a thin-film sorbent-phase dosing system. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
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5. ASSESSING EXPOSURE OF SEDIMENT BIOTA TO ORGANIC CONTAMINANTS BY THIN-FILM SOLID PHASE EXTRACTION.
- Author
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MELOCHE, LIZANNE M., DEBRUYN, ADRIAN M. H., OTTON, S. VICTORIA, IKONOMOU, MICHAEL G., and GOBAS, FRANK A. P. C.
- Subjects
COASTAL organisms ,BIOAVAILABILITY ,CONTAMINATED sediments ,THIN films ,SOLID phase extraction ,EXTRACTION techniques ,PARTITION coefficient (Chemistry) ,BIOACCUMULATION ,MACOMA baltica - Abstract
Differences in bioavailability among sediments are a source of variability and uncertainty in sediment quality assessment. We present three sets of studies designed to test a thin-film solid phase extraction technique for characterizing the bioavailability of organic chemicals in sediments. Laboratory studies with spiked natural sediments reveal highly reproducible thin-film extractions for chemicals with octanol-water partition coefficients between 10
4.5 and 108.5 , with 95% equilibration times between 1 and 600 h. Studies with field-collected sediments illustrate that method detection limits are sufficiently low for field application at contaminated sites. Bioaccumulation studies with clams (Macoma balthica) show excellent correlations between thin-film and animal tissue concentrations. We conclude that thin-film extraction provides an ecologically relevant, fugacity-based measure of chemical exposure that can be expected to improve sediment quality assessments. [ABSTRACT FROM AUTHOR]- Published
- 2009
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6. Biodegradation of mono-alkyl phthalate esters in natural sediments
- Author
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Otton, S. Victoria, Sura, Srinivas, Blair, Joel, Ikonomou, Michael G., and Gobas, Frank A.P.C.
- Subjects
- *
PHTHALATE esters , *METABOLITES , *BIODEGRADATION , *SEDIMENTS , *CHEMICAL kinetics , *POLYVINYL chloride , *MICROBIOLOGY - Abstract
Mono-alkyl phthalate esters (MPEs) are primary metabolites of di-alkyl phthalate esters (DPEs), a family of industrial chemicals widely used in the production of soft polyvinyl chloride and a large range of other products. To better understand the long term fate of DPEs in the environment, we measured the biodegradation kinetics of eight MPEs (-ethyl, -n-butyl, -benzyl, -i-hexyl, -2-ethyl-hexyl, -n-octyl, -i-nonyl, and -i-decyl monoesters) in marine and freshwater sediments collected from three locations in the Greater Vancouver area. After a lag period in which no apparent biodegradation occurred, all MPEs tested showed degradation rates in both marine and freshwater sediments at 22°C with half-lives ranging between 16 and 39h. Half-lives increased approximately 8-fold in incubations performed at 5°C. Biodegradation rates did not differ between marine and freshwater sediments. Half-lives did not show a relationship with increasing alkyl chain length. We conclude that MPEs can be quickly degraded in natural sediments and that the similarity in MPE degradation kinetics among sediment types suggests a wide occurrence of nonspecific esterases in microorganisms from various locations, as has been reported previously. [Copyright &y& Elsevier]
- Published
- 2008
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7. Drug metabolism and interactions in abuse liability assessment.
- Author
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Sellers, Edward M., Otton, S. Victoria, and Busto, Usoa E.
- Subjects
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DRUG metabolism , *DRUG abuse , *PRODUCT liability of drugs , *DRUG use testing - Abstract
The interpretation of acute abuse liability studies and drug interaction studies would be importantly strengthened by the routine inclusion of drug concentration measurements at appropriate sampling times. Reliance on mean kinetic data misrepresents the variation in drug kinetics and fails to take experimental advantage of the natural differences in the population which may represent the extremes of abuse risk. Pharmacokinetic-pharmacodynamic studies to better understand the relationship of plasma drug concentration, drug concentration in the receptor biophase and specific drug reinforced behaviour will ensure proper study design and yield useful theoretic information. Multi- and poly-drug abuse (including heavy smoking and heavy ethanol use) are very common. Such patterns of use can have quite large effects on drug kinetics. Because of the potentially large qualitative and quantitative differences in drug metabolism and kinetics between pre-clinical species and the human, data should be gathered at the earliest possible time with respect to human metabolic rates, patterns, and identification of inhibitors. The availability of human liver microsomes facilitates such studies. [ABSTRACT FROM AUTHOR]
- Published
- 1991
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8. CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone.
- Author
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Otton, S Victoria, Schadel, Mordecai, Cheung, Siu Wah, Kaplan, Howard L, Busto, Usoa E, and Sellers, Edward M
- Published
- 1993
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9. Inhibition by fluoxetine of cytochrome P450 2D6 activity.
- Author
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Otton, S Victoria, Wu, Dafang, Joffe, Russell T, Cheung, Siu Wah, and Sellers, Edward M
- Published
- 1993
- Full Text
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10. Imipramine demethylation and hydroxylation: Impact of the sparteine oxidation phenotype.
- Author
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Brøsen, Kim, Otton, S Victoria, and Gram, Lars F
- Published
- 1986
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11. Comparison of three CYP2D6 probe substrates and genotype in Ghanaians, Chinese and Caucasians.
- Author
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Droll, Kurt, Bruce-Mensah, Kofi, Otton, S Victoria, Gaedigk, Andrea, Sellers, Edward M., and Tyndale, Rachel F.
- Published
- 1998
12. CYP2D6 Inhibition in Patients Treated With Sertraline.
- Author
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Sproule, Beth A., Otton, S. Victoria, Cheung, Siu W., Zhong, X. Howard, Romach, Myroslava K., and Sellers, Edward M.
- Published
- 1997
- Full Text
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13. Pharmacokinetics of Dextromethorphan and Metabolites in Humans.
- Author
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Schadel, Mordecai, Wu, Dafang, Otton, S. Victoria, Kalow, Werner, and Sellers, Edward M.
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- 1995
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14. Cytochrome P450 2D6 and Treatment of Codeine Dependence.
- Author
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Romach, Myroslava K., Otton, S. Victoria, Somer, Gail, Tyndale, Rachel F., and Sellers, Edward M.
- Published
- 2000
- Full Text
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15. In vitro to in vivo extrapolation of biotransformation rates for assessing bioaccumulation of hydrophobic organic chemicals in mammals.
- Author
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Lee YS, Lo JC, Otton SV, Moore MM, Kennedy CJ, and Gobas FAPC
- Subjects
- Animals, Benzo(a)pyrene metabolism, Biotransformation, Chrysenes metabolism, Hydrophobic and Hydrophilic Interactions, Kinetics, Liver metabolism, Mammals metabolism, Organic Chemicals chemistry, Models, Theoretical, Organic Chemicals metabolism
- Abstract
Incorporating biotransformation in bioaccumulation assessments of hydrophobic chemicals in both aquatic and terrestrial organisms in a simple, rapid, and cost-effective manner is urgently needed to improve bioaccumulation assessments of potentially bioaccumulative substances. One approach to estimate whole-animal biotransformation rate constants is to combine in vitro measurements of hepatic biotransformation kinetics with in vitro to in vivo extrapolation (IVIVE) and bioaccumulation modeling. An established IVIVE modeling approach exists for pharmaceuticals (referred to in the present study as IVIVE-Ph) and has recently been adapted for chemical bioaccumulation assessments in fish. The present study proposes and tests an alternative IVIVE-B technique to support bioaccumulation assessment of hydrophobic chemicals with a log octanol-water partition coefficient (K
OW ) ≥ 4 in mammals. The IVIVE-B approach requires fewer physiological and physiochemical parameters than the IVIVE-Ph approach and does not involve interconversions between clearance and rate constants in the extrapolation. Using in vitro depletion rates, the results show that the IVIVE-B and IVIVE-Ph models yield similar estimates of rat whole-organism biotransformation rate constants for hypothetical chemicals with log KOW ≥ 4. The IVIVE-B approach generated in vivo biotransformation rate constants and biomagnification factors (BMFs) for benzo[a]pyrene that are within the range of empirical observations. The proposed IVIVE-B technique may be a useful tool for assessing BMFs of hydrophobic organic chemicals in mammals. Environ Toxicol Chem 2017;36:1934-1946. © 2016 SETAC., (© 2016 SETAC.)- Published
- 2017
- Full Text
- View/download PDF
16. Chemical activity-based environmental risk analysis of the plasticizer di-ethylhexyl phthalate and its main metabolite mono-ethylhexyl phthalate.
- Author
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Gobas FAPC, Otton SV, Tupper-Ring LF, Crawford MA, Clark KE, and Ikonomou MG
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- Animals, Aquatic Organisms drug effects, Aquatic Organisms growth & development, Aquatic Organisms metabolism, Biotransformation, Chromatography, High Pressure Liquid, Diethylhexyl Phthalate metabolism, Diethylhexyl Phthalate toxicity, Environmental Pollutants metabolism, Environmental Pollutants toxicity, Geologic Sediments analysis, Geologic Sediments chemistry, Lethal Dose 50, Plants drug effects, Plants metabolism, Plasticizers metabolism, Plasticizers toxicity, Soil Pollutants analysis, Soil Pollutants metabolism, Soil Pollutants toxicity, Tandem Mass Spectrometry, Temperature, Toxicity Tests, Water Pollutants, Chemical analysis, Water Pollutants, Chemical metabolism, Water Pollutants, Chemical toxicity, Diethylhexyl Phthalate analysis, Environmental Pollutants analysis, Plasticizers analysis, Risk Assessment
- Abstract
The present study applies a chemical activity-based approach to: 1) evaluate environmental concentrations of di-ethylhexyl phthalate (DEHP; n = 23 651) and its metabolite mono-ethylhexyl phthalate (MEHP; n = 1232) in 16 environmental media from 1174 studies in the United States, Canada, Europe, and Asia, and in vivo toxicity data from 934 studies in 20 species, as well as in vitro biological activity data from the US Environmental Protection Agency's Toxicity Forecaster and other sources; and 2) conduct a comprehensive environmental risk analysis. The results show that the mean chemical activities of DEHP and MEHP in abiotic environmental samples from locations around the globe are 0.001 and 10
-8 , respectively. This indicates that DEHP has reached on average 0.1% of saturation in the abiotic environment. The mean chemical activity of DEHP in biological samples is on average 100-fold lower than that in abiotic samples, likely because of biotransformation of DEHP in biota. Biological responses in both in vivo and in vitro tests occur at chemical activities between 0.01 to 1 for DEHP and between approximately 10-6 and 10-2 for MEHP, suggesting a greater potency of MEHP compared with DEHP. Chemical activities of both DEHP and MEHP in biota samples were less than those causing biological responses in the in vitro bioassays, without exception. A small fraction of chemical activities of DEHP in abiotic environmental samples (i.e., 4-8%) and none (0%) for MEHP were within the range of chemical activities associated with observed toxicological responses in the in vivo tests. The present study illustrates the chemical activity approach for conducting risk analyses. Environ Toxicol Chem 2017;36:1483-1492. © 2016 SETAC., (© 2016 SETAC.)- Published
- 2017
- Full Text
- View/download PDF
17. Concentration dependence of biotransformation in fish liver S9: Optimizing substrate concentrations to estimate hepatic clearance for bioaccumulation assessment.
- Author
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Lo JC, Allard GN, Otton SV, Campbell DA, and Gobas FA
- Subjects
- Animals, Anthracenes analysis, Anthracenes metabolism, Benzo(a)pyrene analysis, Benzo(a)pyrene metabolism, Biotransformation, Chrysenes analysis, Chrysenes metabolism, Hydrophobic and Hydrophilic Interactions, Kinetics, Liver Extracts metabolism, Environmental Pollutants analysis, Environmental Pollutants metabolism, Liver metabolism, Models, Biological, Oncorhynchus mykiss metabolism
- Abstract
In vitro bioassays to estimate biotransformation rate constants of contaminants in fish are currently being investigated to improve bioaccumulation assessments of hydrophobic contaminants. The present study investigates the relationship between chemical substrate concentration and in vitro biotransformation rate of 4 environmental contaminants (9-methylanthracene, pyrene, chrysene, and benzo[a]pyrene) in rainbow trout (Oncorhynchus mykiss) liver S9 fractions and methods to determine maximum first-order biotransformation rate constants. Substrate depletion experiments using a series of initial substrate concentrations showed that in vitro biotransformation rates exhibit strong concentration dependence, consistent with a Michaelis-Menten kinetic model. The results indicate that depletion rate constants measured at initial substrate concentrations of 1 μM (a current convention) could underestimate the in vitro biotransformation potential and may cause bioconcentration factors to be overestimated if in vitro biotransformation rates are used to assess bioconcentration factors in fish. Depletion rate constants measured using thin-film sorbent dosing experiments were not statistically different from the maximum depletion rate constants derived using a series of solvent delivery-based depletion experiments for 3 of the 4 test chemicals. Multiple solvent delivery-based depletion experiments at a range of initial concentrations are recommended for determining the concentration dependence of in vitro biotransformation rates in fish liver fractions, whereas a single sorbent phase dosing experiment may be able to provide reasonable approximations of maximum depletion rates of very hydrophobic substances., (© 2015 SETAC.)
- Published
- 2015
- Full Text
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18. Measuring in vitro biotransformation rates of super hydrophobic chemicals in rat liver s9 fractions using thin-film sorbent-phase dosing.
- Author
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Lee YS, Otton SV, Campbell DA, Moore MM, Kennedy CJ, and Gobas FA
- Subjects
- Adsorption, Animals, Biotransformation, Kinetics, Male, Models, Biological, Rats, Rats, Sprague-Dawley, Solvents chemistry, Subcellular Fractions metabolism, Time Factors, Environmental Monitoring methods, Hydrophobic and Hydrophilic Interactions, Liver metabolism, Organic Chemicals metabolism
- Abstract
Methods for rapid and cost-effective assessment of the biotransformation potential of very hydrophobic and potentially bioaccumulative chemicals in mammals are urgently needed for the ongoing global evaluation of the environmental behavior of commercial chemicals. We developed and tested a novel solvent-free, thin-film sorbent-phase in vitro dosing system to measure the in vitro biotransformation rates of very hydrophobic chemicals in male Sprague-Dawley rat liver S9 homogenates and compared the rates to those measured by conventional solvent-delivery dosing. The thin-film sorbent-phase dosing system using ethylene vinyl acetate coated vials was developed to eliminate the incomplete dissolution of very hydrophobic substances in largely aqueous liver homogenates, to determine biotransformation rates at low substrate concentrations, to measure the unbound fraction of substrate in solution, and to simplify chemical analysis by avoiding the difficult extraction of test chemicals from complex biological matrices. Biotransformation rates using sorbent-phase dosing were 2-fold greater than those measured using solvent-delivery dosing. Unbound concentrations of very hydrophobic test chemicals were found to decline with increasing S9 and protein concentrations, causing measured biotransformation rates to be independent of S9 or protein concentrations. The results emphasize the importance of specifying both protein content and unbound substrate fraction in the measurement and reporting of in vitro biotransformation rates of very hydrophobic substances, which can be achieved in a thin-film sorbent-phase dosing system.
- Published
- 2012
- Full Text
- View/download PDF
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