Research Topics
| Charles A TimchalkSummaryAffiliation: Pacific Northwest National Laboratory Country: USA Publications
Research Grants
| Collaborators
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Detail Information
Publications
An age-dependent physiologically based pharmacokinetic/pharmacodynamic model for the organophosphorus insecticide chlorpyrifos in the preweanling ratCharles Timchalk
Battelle Pacific Northwest Division, Center for Biological Monitoring and Modeling, Richland, Washington 99352, USA
Toxicol Sci 98:348-65. 2007..Hence, this model represents an important starting point for developing a computational model to assess the neurotoxic potential of environmentally relevant organophosphate exposures in infants and children...- Development of an integrated microanalytical system for analysis of lead in saliva and linkage to a physiologically based pharmacokinetic model describing lead saliva secretionC Timchalk
Pacific Northwest National Laboratory, Richland, WA 99352, USA
AIHAJ 62:295-302. 2001..These results are encouraging, suggesting that once fully developed the microanalytical system coupled with PBPK modeling can be used as important tools for real-time biomonitoring of Pb for both occupational and environmental exposures... - Age-dependent pharmacokinetic and pharmacodynamic response in preweanling rats following oral exposure to the organophosphorus insecticide chlorpyrifosC Timchalk
Battelle Pacific Northwest Division, Center for Biological Monitoring and Modeling, 902 Battelle Boulevard, Richland, WA 99352, USA
Toxicology 220:13-25. 2006..The results suggest that in the preweanling rat, CPF was rapidly absorbed and metabolized, and the extent of metabolism and ChE inhibition was age-dependent... - Disposition of lead (Pb) in saliva and blood of Sprague-Dawley rats following a single or repeated oral exposure to Pb-acetateC Timchalk
Pacific Northwest National Laboratory, 902 Battelle Boulevard, PO Box 999, Richland, WA 99352, USA
Toxicology 222:86-94. 2006..These results demonstrate a feasibility to rapidly detect Pb in saliva and suggest that saliva may correlate best with plasma Pb concentration... 
In vitro and in vivo evaluation of a novel ferrocyanide functionalized nanopourous silica decorporation agent for cesium in ratsCharles Timchalk
Pacific Northwest National Laboratory, 902 Battelle Blvd, PO Box 999, Richland, WA 99352, USA
Health Phys 99:420-9. 2010..The comparable response may be the result of the low (137)Cs chloride dose and high sorbent dosage that was utilized. Future studies are planned to optimize the performance of SAMMS in vivo over a broader range of doses and conditions...- Development of a non-invasive biomonitoring approach to determine exposure to the organophosphorus insecticide chlorpyrifos in rat salivaCharles Timchalk
Pacific Northwest National Laboratory, 902 Battelle, Blvd, Richland, WA 99352, USA
Toxicol Appl Pharmacol 219:217-25. 2007.... - Comparative pharmacokinetics of the organophosphorus insecticide chlorpyrifos and its major metabolites diethylphosphate, diethylthiophosphate and 3,5,6-trichloro-2-pyridinol in the ratCharles Timchalk
Pacific Northwest National Laboratory, 902 Battelle Blvd, PO Box 999, Richland, WA 99352, USA
Toxicology 237:145-57. 2007..These studies support the hypotheses that DEP, DETP and TCPy present in the environment can be readily absorbed and eliminated in the urine of rats and potentially humans... 
Development of a physiologically based pharmacokinetic and pharmacodynamic model to determine dosimetry and cholinesterase inhibition for a binary mixture of chlorpyrifos and diazinon in the ratC Timchalk
Center for Biological Monitoring and Modeling, Battelle, Pacific Northwest Division, Richland, WA 99352, USA
Neurotoxicology 29:428-43. 2008..It is anticipated that at low environmentally relevant binary doses, most likely to be encountered in occupational or environmental related exposures, that the pharmacokinetics are expected to be linear, and ChE inhibition dose-additive...- Nanotechnology-based electrochemical sensors for biomonitoring chemical exposuresRichard C Barry
aBiological Monitoring and Modeling Group, Pacific Northwest National Laboratory, Richland, Washington 99352, USA
J Expo Sci Environ Epidemiol 19:1-18. 2009..In addition, future considerations and opportunities for advancing the use of EC platforms for dosimetric studies are discussed... - Pharmacokinetic and pharmacodynamic interaction for a binary mixture of chlorpyrifos and diazinon in the ratC Timchalk
Center for Biological Monitoring and Modeling, Battelle, Pacific Northwest Division, Richland, WA 99352, USA
Toxicol Appl Pharmacol 205:31-42. 2005.... - A Physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for the organophosphate insecticide chlorpyrifos in rats and humansC Timchalk
Battelle Pacific Northwest Division, Chemical Dosimetry, PO Box 999, Richland, Washington 99352, USA
Toxicol Sci 66:34-53. 2002.... - Noninvasive biomonitoring approaches to determine dosimetry and risk following acute chemical exposure: analysis of lead or organophosphate insecticide in salivaCharles Timchalk
Pacific Northwest National Laboratory, MSIN P7 59, 902 Battelle Blvd, PO Box 999, Richland, WA 99352, USA
J Toxicol Environ Health A 67:635-50. 2004..In summary, it is envisioned that once fully developed, these monitoring and modeling approaches will be useful for evaluating acute exposure and health risk... - Monte Carlo analysis of the human chlorpyrifos-oxonase (PON1) polymorphism using a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) modelC Timchalk
Battelle Pacific Northwest Division, Chemical Dosimetry, 902 Battelle Blvd, P O Box 999, Richland, WA 99352, USA
Toxicol Lett 135:51-9. 2002..This suggests that at low environmentally relevant exposures other esterase detoxification pathways may compensate for lower CPF-oxonase activity... - Comparative inter-species pharmacokinetics of phenoxyacetic acid herbicides and related organic acids. evidence that the dog is not a relevant species for evaluation of human health riskCharles Timchalk
Battelle, Pacific Northwest Division, Center for Biological Monitoring and Modeling, 902 Battelle Boulevard, Richland, WA 99352, USA
Toxicology 200:1-19. 2004.... - Potential technology for studying dosimetry and response to airborne chemical and biological pollutantsC Timchalk
Pacific Northwest National Laboratory, Richland, Washington 99352, USA
Toxicol Ind Health 17:270-6. 2001..The ability of these 3-D models to resolve dosimetry at such a high level of detail will require new techniques to measure regional airflows and particulate deposition for model validation... - Application of magnetic resonance (MR) imaging for the development and validation of computational fluid dynamic (CFD) models of the rat respiratory systemKevin R Minard
Pacific Northwest National Laboratory, Richland, Washington 99352, USA
Inhal Toxicol 18:787-94. 2006..Results from these diverse studies highlight the potential utility of MR imaging not only for speeding CFD development but also possibly for model validation... - Physiologically based pharmacokinetic/pharmacodynamic model for the organophosphorus pesticide diazinonT S Poet
Center for Biological Monitoring and Modeling, Battelle, Pacific Northwest Division, PO Box 999 MSIN P7 59, Richland, WA 99352, USA
Neurotoxicology 25:1013-30. 2004..This model further confirms the usefulness of the model structure previously validated for chlorpyrifos and shows the potential utility of the model framework for other related organophosphate pesticides... - 3D 3He diffusion MRI as a local in vivo morphometric tool to evaluate emphysematous rat lungsR E Jacob
Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA 99352, USA
J Appl Physiol 105:1291-300. 2008..88 and R = 0.90, respectively, with P < 0.0001). It is concluded that (3)He MRI is a viable noninvasive morphometric tool for localized in vivo emphysema assessment... - In vitro rat hepatic and intestinal metabolism of the organophosphate pesticides chlorpyrifos and diazinonT S Poet
Battelle, Pacific Northwest Division, Chemical Dosimetry, P O Box 999, Richland, Washington 99352, USA
Toxicol Sci 72:193-200. 2003..These results suggest that intestinal metabolism may impact the metabolism of CPF and DZN, especially following low-dose oral exposures... - Comparison of chlorpyrifos-oxon and paraoxon acetylcholinesterase inhibition dynamics: potential role of a peripheral binding siteA A Kousba
Battelle, Pacific Northwest Division, Richland, Washington 99352, USA
Toxicol Sci 80:239-48. 2004..These results support the potential importance of a secondary peripheral binding site associated with AChE kinetics, particularly at low, environmentally relevant concentrations... - Effects of nicotine exposure on in vitro metabolism of chlorpyrifos in male Sprague-Dawley ratsS Lee
Pacific Northwest National Laboratory, Center for Biological Monitoring and Modeling, Richland, Washington 99352, USA
J Toxicol Environ Health A 72:74-82. 2009..Future in vivo experiments based on these results need to be conducted to ascertain the impact of in vivo nicotine exposures on CPF metabolism in rats... - Age-related brain cholinesterase inhibition kinetics following in vitro incubation with chlorpyrifos-oxon and diazinon-oxonAhmed A Kousba
Department of Pharmaceutical Property Assessments, TargeGen Inc, San Diego, California 92121, USA
Toxicol Sci 95:147-55. 2007..02 nM(-1)hr(-1). These results demonstrated an age- and OP-selective inhibition of rat brain ChE, which may be critically important in understanding the potential sensitivity of juveniles to specific OPs exposures... - T2-shortening of 3He gas by magnetic microspheresKevin R Minard
Pacific Northwest National Laboratory, P O Box 999, Richland, WA 99352, USA
J Magn Reson 173:90-6. 2005..Based on these findings the feasibility of imaging inhaled particulates in vivo with hyperpolarized 3He is examined and performance projections are formulated... - Detection of Cd, Pb, and Cu in non-pretreated natural waters and urine with thiol functionalized mesoporous silica and Nafion composite electrodesWassana Yantasee
Pacific Northwest National Laboratory, Richland, WA 99352, USA
Anal Chim Acta 620:55-63. 2008.... - Carbon nanotube-based electrochemical sensor for assay of salivary cholinesterase enzyme activity: an exposure biomarker of organophosphate pesticides and nerve agentsJun Wang
Pacific Northwest National Laboratory, Richland, Washington 99352, USA
Environ Sci Technol 42:2688-93. 2008..This new CNT-based electrochemical sensor thus provides a sensitive and quantitative tool for noninvasive biomonitoring of the exposure to organophosphate pesticides and nerve agents... - Toxicity of chlorpyrifos and chlorpyrifos oxon in a transgenic mouse model of the human paraoxonase (PON1) Q192R polymorphismToby B Cole
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195-7720, USA
Pharmacogenet Genomics 15:589-98. 2005..CONCLUSION: These results indicate that individuals expressing only the PON1Q192 allele would be more sensitive to the adverse effects of CPO or CPS exposure, especially if they are expressing a low level of plasma PON1Q192... - Direct detection of Pb in urine and Cd, Pb, Cu, and Ag in natural waters using electrochemical sensors immobilized with DMSA functionalized magnetic nanoparticlesWassana Yantasee
Pacific Northwest National Laboratory, Richland, WA 99352, USA
Analyst 133:348-55. 2008..3 for seven measurements of 30 ppb Pb), and Pb concentrations comparable to those measured by ICP-MS. The sensor could also simultaneously detect background levels (<1 ppb) of Cd, Pb, Cu, and Ag in river and seawater... 
Electrochemical sensors for the detection of lead and other toxic heavy metals: the next generation of personal exposure biomonitorsWassana Yantasee
Pacific Northwest National Laboratory, Richland, WA 99352, USA
Environ Health Perspect 115:1683-90. 2007..These improved and portable analytical sensor platforms will facilitate our ability to conduct biological monitoring programs to understand the relationship between chemical exposure assessment and disease outcomes...- The effect of route, vehicle, and divided doses on the pharmacokinetics of chlorpyrifos and its metabolite trichloropyridinol in neonatal Sprague-Dawley ratsMary Sue Marty
Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI 48674, USA
Toxicol Sci 100:360-73. 2007.... - Removal of heavy metals from aqueous systems with thiol functionalized superparamagnetic nanoparticlesWassana Yantasee
Pacific Northwest National Laboratory, Richland, Washington 99352, USA
Environ Sci Technol 41:5114-9. 2007..DMSA-Fe3O4 had a capacity of 227 mg of Hg/g, a 30-fold larger value than GT-73. The nanoparticles removed 99 wt% of 1 mg/L Pb within a minute, while it took over 10 and 120 min for Chelex-100 and GT-73 to remove 96% of Pb... - Characterization of the in vitro kinetic interaction of chlorpyrifos-oxon with rat salivary cholinesterase: a potential biomonitoring matrixA A Kousba
Battelle, Pacific Northwest Division, 902 Battelle Blvd, PO Box 999, Richland, WA 99352, USA
Toxicology 188:219-32. 2003..These results support the potential utility of saliva as a biomonitoring matrix for evaluating occupational and environmental exposure to CPF and other OP insecticides... - Microanalyzer for biomonitoring lead (Pb) in blood and urineWassana Yantasee
Pacific Northwest National Laboratory, Richland, WA 99352, USA
Anal Bioanal Chem 387:335-41. 2007..Since it is miniaturized, the microanalyzer is portable and field-deployable. Thus, it shows much promise as the next-generation analyzer for the biomonitoring of toxic metals... - A real-time method to evaluate the nasal deposition and clearance of acetone in the human volunteerKarla D Thrall
Biological Sciences Division, Battelle, Pacific Northwest Laboratory, Richland, WA 99352, USA
Inhal Toxicol 15:523-38. 2003..Breath-by-breath analyses of [(13)C]acetone concentrations indicate that between 40 and 75% of the compound is absorbed upon inhalation and nearly all of that absorbed is released back into the breath stream during exhalation... - Paraoxonase 1 (PON1) status and risk of insecticide exposureClement E Furlong
Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA 98195-7720, USA
J Biochem Mol Toxicol 19:182-3. 2005 - The acquisition and application of absorption, distribution, metabolism, and excretion (ADME) data in agricultural chemical safety assessmentsHugh A Barton
U.S. Environmental Protection Agency, National Centerfor Computational Toxicology, Research Triangle Park, North Carolina, USA
Crit Rev Toxicol 36:9-35. 2006..Subsequent tiers provide additional information in an iterative manner, depending on pharmacokinetic properties, toxicity study results, and the intended uses of the compound...
Research Grants
- Mixture Modeling: Pesticide Drug InteractionsCharles Timchalk; Fiscal Year: 2009..It is fully anticipated that this approach will facilitate the understanding of a variety of complex chemical interactions as it relates to the occupational health implications of working with insecticides. ..
- Non-Invasive Biomonitoring of PesticidesCharles Timchalk; Fiscal Year: 2007..Once this model system has been adequately validated it can readily be employed to assess worker exposure to insecticides under a wide range of occupational situations. ..
- Development of Selective Nanoporous Sorbents for Radionuclide DecorporationCharles Timchalk; Fiscal Year: 2006....
- Mixture Modeling: Pesticide Drug InteractionsCharles Timchalk; Fiscal Year: 2007..It is fully anticipated that this approach will facilitate the understanding of a variety of complex chemical interactions as it relates to the occupational health implications of working with insecticides. ..
- INNOVATIVE BIOMONITORING FOR LEAD IN SALIVACharles Timchalk; Fiscal Year: 2006..It is reasonable to speculate that once this model system has been adequately validated it can readily be employed to screen sensitive populations (e.g. children) that are at greatest risk from chronic Pb exposure. ..
- COMPLEX MIXTURE MODELING ORGANOPHOSPHATE PESTICIDESCharles Timchalk; Fiscal Year: 2003....
- Non-Invasive Biomonitoring of PesticidesCharles Timchalk; Fiscal Year: 2010..Once this model system has been adequately validated it can readily be employed to assess worker exposure to insecticides under a wide range of occupational situations. ..