Melvin E Andersen

Summary

Affiliation: The Hamner Institutes for Health Sciences
Country: USA

Publications

  1. pmc Toxicity testing in the 21 century: defining new risk assessment approaches based on perturbation of intracellular toxicity pathways
    Sudin Bhattacharya
    Program in Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, United States of America
    PLoS ONE 6:e20887. 2011
  2. pmc The need for a new toxicity testing and risk analysis paradigm to implement REACH or any other large scale testing initiative
    Bas J Blaauboer
    Arch Toxicol 81:385-7. 2007
  3. pmc Can case study approaches speed implementation of the NRC report: "toxicity testing in the 21st century: a vision and a strategy?"
    Melvin E Andersen
    The Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 2137, USA
    ALTEX 28:175-82. 2011
  4. doi request reprint Toxicity testing in the 21st century: bringing the vision to life
    Melvin E Andersen
    Computational Biology Division, Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 107:324-30. 2009
  5. ncbi request reprint Formaldehyde: integrating dosimetry, cytotoxicity, and genomics to understand dose-dependent transitions for an endogenous compound
    Melvin E Andersen
    Program in Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 118:716-31. 2010
  6. ncbi request reprint Genomic signatures and dose-dependent transitions in nasal epithelial responses to inhaled formaldehyde in the rat
    Melvin E Andersen
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709 2137, USA
    Toxicol Sci 105:368-83. 2008
  7. doi request reprint Are highly lipophilic volatile compounds expected to bioaccumulate with repeated exposures?
    Melvin E Andersen
    Division of Computational Biology, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 2137, United States
    Toxicol Lett 179:85-92. 2008
  8. doi request reprint The vision of toxicity testing in the 21st century: moving from discussion to action
    Melvin E Andersen
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 117:17-24. 2010
  9. doi request reprint Evaluation of placental and lactational pharmacokinetics of PFOA and PFOS in the pregnant, lactating, fetal and neonatal rat using a physiologically based pharmacokinetic model
    Anne E Loccisano
    Center for Human Health Assessment, The Hamner Institutes for Health Sciences, 6 Davis Drive, P O Box 12137, Research Triangle Park, NC 27709, United States
    Reprod Toxicol 33:468-90. 2012
  10. doi request reprint Comparison and evaluation of pharmacokinetics of PFOA and PFOS in the adult rat using a physiologically based pharmacokinetic model
    Anne E Loccisano
    Center for Human Health Assessment, The Hamner Institutes for Health Sciences, 6 Davis Drive, P O Box 12137, Research Triangle Park, NC 27709, United States
    Reprod Toxicol 33:452-67. 2012

Detail Information

Publications127 found, 100 shown here

  1. pmc Toxicity testing in the 21 century: defining new risk assessment approaches based on perturbation of intracellular toxicity pathways
    Sudin Bhattacharya
    Program in Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, United States of America
    PLoS ONE 6:e20887. 2011
    ..In this vein, we also discuss how the proposed strategy for toxicity testing might be applied to the toxicity pathways associated with DNA damage and repair...
  2. pmc The need for a new toxicity testing and risk analysis paradigm to implement REACH or any other large scale testing initiative
    Bas J Blaauboer
    Arch Toxicol 81:385-7. 2007
  3. pmc Can case study approaches speed implementation of the NRC report: "toxicity testing in the 21st century: a vision and a strategy?"
    Melvin E Andersen
    The Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 2137, USA
    ALTEX 28:175-82. 2011
    ....
  4. doi request reprint Toxicity testing in the 21st century: bringing the vision to life
    Melvin E Andersen
    Computational Biology Division, Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 107:324-30. 2009
    ..The present paper, and invited commentaries on the report that will appear in Toxicological Sciences over the next year, are intended to initiate a dialog to identify challenges in implementing the vision and address obstacles to change...
  5. ncbi request reprint Formaldehyde: integrating dosimetry, cytotoxicity, and genomics to understand dose-dependent transitions for an endogenous compound
    Melvin E Andersen
    Program in Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 118:716-31. 2010
    ....
  6. ncbi request reprint Genomic signatures and dose-dependent transitions in nasal epithelial responses to inhaled formaldehyde in the rat
    Melvin E Andersen
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709 2137, USA
    Toxicol Sci 105:368-83. 2008
    ..7 and 6 ppm. Low concentrations primarily affect extracellular matrix or external plasma membrane portions of the epithelium...
  7. doi request reprint Are highly lipophilic volatile compounds expected to bioaccumulate with repeated exposures?
    Melvin E Andersen
    Division of Computational Biology, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 2137, United States
    Toxicol Lett 179:85-92. 2008
    ..Based on this definition, highly cleared VCs, such as D(5), would not be considered to bioaccumulate on repeat exposures...
  8. doi request reprint The vision of toxicity testing in the 21st century: moving from discussion to action
    Melvin E Andersen
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 117:17-24. 2010
    ....
  9. doi request reprint Evaluation of placental and lactational pharmacokinetics of PFOA and PFOS in the pregnant, lactating, fetal and neonatal rat using a physiologically based pharmacokinetic model
    Anne E Loccisano
    Center for Human Health Assessment, The Hamner Institutes for Health Sciences, 6 Davis Drive, P O Box 12137, Research Triangle Park, NC 27709, United States
    Reprod Toxicol 33:468-90. 2012
    ....
  10. doi request reprint Comparison and evaluation of pharmacokinetics of PFOA and PFOS in the adult rat using a physiologically based pharmacokinetic model
    Anne E Loccisano
    Center for Human Health Assessment, The Hamner Institutes for Health Sciences, 6 Davis Drive, P O Box 12137, Research Triangle Park, NC 27709, United States
    Reprod Toxicol 33:452-67. 2012
    ....
  11. pmc Nuclear factor erythroid-derived factor 2-related factor 2 regulates transcription of CCAAT/enhancer-binding protein β during adipogenesis
    Yongyong Hou
    Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA
    Free Radic Biol Med 52:462-72. 2012
    ....
  12. ncbi request reprint Derivation of an inhalation reference concentration based upon olfactory neuronal loss in male rats following subchronic acetaldehyde inhalation
    David C Dorman
    CIIT at The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, USA david
    Inhal Toxicol 20:245-56. 2008
    ..A model of acetaldehyde pharmacokinetics in the nose was used to derive an inhalation reference concentration (RfC) of 0.4 ppm, based on the no-observed-adverse-effect level (NOAEL) of 50 ppm for the nasal pathology seen in this study...
  13. pmc Deficiency in the nuclear factor E2-related factor 2 renders pancreatic β-cells vulnerable to arsenic-induced cell damage
    Bei Yang
    Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709, USA
    Toxicol Appl Pharmacol 264:315-23. 2012
    ....
  14. ncbi request reprint A method to integrate benchmark dose estimates with genomic data to assess the functional effects of chemical exposure
    Russell S Thomas
    The Hamner Institutes for Health Sciences, Division of Computational Biology, Research Triangle Park, North Carolina 27709 2137, USA
    Toxicol Sci 98:240-8. 2007
    ....
  15. pmc Divergent effects of sulforaphane on basal and glucose-stimulated insulin secretion in β-cells: role of reactive oxygen species and induction of endogenous antioxidants
    Jingqi Fu
    Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, Durham, North Carolina 27709, USA
    Pharm Res 30:2248-59. 2013
    ..Since reactive oxygen species (ROS) can function as signaling intermediates for glucose-stimulated insulin secretion (GSIS), we hypothesize that exogenously boosting cellular antioxidant capacity dampens signaling ROS and GSIS...
  16. doi request reprint Temporal concordance between apical and transcriptional points of departure for chemical risk assessment
    Russell S Thomas
    Hamner Institutes for Health Sciences, Research Triangle Park, NC, USA
    Toxicol Sci 134:180-94. 2013
    ..Based on our results, we propose a practical framework for application of transcriptomic data to chemical risk assessment. ..
  17. pmc Adipose deficiency of Nrf2 in ob/ob mice results in severe metabolic syndrome
    Peng Xue
    Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, USA
    Diabetes 62:845-54. 2013
    ..Our findings support a novel role for Nrf2 in regulating adipose development and function, by which Nrf2 controls the capacity of WAT expansion and insulin sensitivity and maintains glucose and lipid homeostasis...
  18. pmc Development of PBPK models for PFOA and PFOS for human pregnancy and lactation life stages
    Anne E Loccisano
    Center for Human Health Assessment, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, USA
    J Toxicol Environ Health A 76:25-57. 2013
    ..These models may help address concerns regarding possible adverse health effects due to PFOA/PFOS exposure in the fetus and infant and may be useful in comparing pharmacokinetics across life stages...
  19. doi request reprint Integration of dosimetry, exposure, and high-throughput screening data in chemical toxicity assessment
    Barbara A Wetmore
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709 2137, USA
    Toxicol Sci 125:157-74. 2012
    ..The incorporation of dosimetry and exposure provide necessary context for interpretation of in vitro toxicity screening data and are important considerations in determining chemical testing priorities...
  20. pmc Stochastic modeling of B lymphocyte terminal differentiation and its suppression by dioxin
    Qiang Zhang
    Division of Computational Biology, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA
    BMC Syst Biol 4:40. 2010
    ..This humoral immune response is suppressed by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other dioxin-like compounds, which belong to the family of aryl hydrocarbon receptor (AhR) agonists...
  21. ncbi request reprint Physiologically based pharmacokinetic modeling of fetal and neonatal manganese exposure in humans: describing manganese homeostasis during development
    Miyoung Yoon
    Center for Human Health Assessment, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 122:297-316. 2011
    ..This PBPK approach can assess expected Mn tissue concentration during early life and compares contributions of different Mn sources, such as breast or cow milk, formula, food, drinking water, and inhalation, with tissue concentration...
  22. doi request reprint Manganese tissue dosimetry in rats and monkeys: accounting for dietary and inhaled Mn with physiologically based pharmacokinetic modeling
    Andy Nong
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 108:22-34. 2009
    ..PBPK models that account for preferential Mn tissue accumulation from both oral and inhalation exposures will be essential to support tissue dosimetry-based human risk assessments for Mn...
  23. doi request reprint Analysis of manganese tracer kinetics and target tissue dosimetry in monkeys and humans with multi-route physiologically based pharmacokinetic models
    Jeffry D Schroeter
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709 2137, USA
    Toxicol Sci 120:481-98. 2011
    ....
  24. pmc Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: involvement of the adaptive antioxidant response
    Peng Xue
    The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA
    Biochem Biophys Res Commun 407:360-5. 2011
    ....
  25. pmc All-or-none suppression of B cell terminal differentiation by environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin
    Qiang Zhang
    Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, NC 27709, USA
    Toxicol Appl Pharmacol 268:17-26. 2013
    ..In conclusion, the present study revealed the mode and specific pathway mechanisms by which the environmental immunosuppressant TCDD suppresses B cell differentiation...
  26. ncbi request reprint Time dependencies in perfluorooctylacids disposition in rat and monkeys: a kinetic analysis
    Yu Mei Tan
    The Hamner Institutes for Health Sciences, Research Triangle Park, NC, USA
    Toxicol Lett 177:38-47. 2008
    ..Understanding these cross-species, cross-compound, and cross-gender difference is an important step in the future development of a human model for these compounds...
  27. doi request reprint Relative impact of incorporating pharmacokinetics on predicting in vivo hazard and mode of action from high-throughput in vitro toxicity assays
    Barbara A Wetmore
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709 2137, USA
    Toxicol Sci 132:327-46. 2013
    ....
  28. pmc Dose-dependent transitions in Nrf2-mediated adaptive response and related stress responses to hypochlorous acid in mouse macrophages
    Courtney G Woods
    Division of Computational Biology, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA
    Toxicol Appl Pharmacol 238:27-36. 2009
    ..These findings confirm an Nrf2-centric mechanism of action of HOCl in mouse macrophages and provide evidence of interactions between Nrf2, inflammatory, and other stress pathways...
  29. ncbi request reprint Bayesian estimation of pharmacokinetic and pharmacodynamic parameters in a mode-of-action-based cancer risk assessment for chloroform
    Kai H Liao
    Center for Human Health Assessment, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA
    Risk Anal 27:1535-51. 2007
    ..Based on liver and kidney dose metrics, the respective RfCs were 0.9 and 0.09 ppm; and the respective RfDs were 0.4 and 3 mg/kg/day...
  30. ncbi request reprint Pharmacokinetic modeling of manganese in the rat IV: Assessing factors that contribute to brain accumulation during inhalation exposure
    Andy Nong
    Division of Computational Biology Division, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709 2137, USA
    J Toxicol Environ Health A 71:413-26. 2008
    ..Once validated across test animals, these PBPK models will be useful in tissue-dose based risk assessment with manganese...
  31. pmc ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function
    Jingbo Pi
    Division of Translational Biology, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709, USA
    Toxicol Appl Pharmacol 244:77-83. 2010
    ..In addition, we summarized our recent findings that persistent oxidative stress due to absence of uncoupling protein 2 activates cellular adaptive response which is associated with impaired pancreatic beta-cell function...
  32. ncbi request reprint Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytes
    Yanyan Chen
    Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709, USA The First Affiliated Hospital, China Medical University, Shenyang 110001, China
    Toxicol Appl Pharmacol 273:435-41. 2013
    ..The inhibition of ARE signaling may be a potential underlying mechanism by which INH attenuates cellular antioxidant response contributing to various complications. ..
  33. ncbi request reprint Quantitative in vitro to in vivo extrapolation of cell-based toxicity assay results
    Miyoung Yoon
    Center for Human Health Assessment, The Hamner Institutes for Health Sciences, Research Triangle Park, Durham, NC 27709, USA
    Crit Rev Toxicol 42:633-52. 2012
    ..Examples of successful QIVIVE approaches are described ranging from a simple steady-state approach that is suitable for a high throughput environment to more complicated approaches requiring full PBPK models...
  34. doi request reprint Evaluation and prediction of pharmacokinetics of PFOA and PFOS in the monkey and human using a PBPK model
    Anne E Loccisano
    Center for Human Health Assessment, Hamner Institutes for Health Sciences, 6 Davis Drive, P O Box 12137, Research Triangle Park, NC 27709, United States
    Regul Toxicol Pharmacol 59:157-75. 2011
    ..It is envisioned that our PBPK model will be useful in supporting human health risk assessments for PFOA and PFOS by aiding in understanding of human pharmacokinetics...
  35. doi request reprint Application of transcriptional benchmark dose values in quantitative cancer and noncancer risk assessment
    Russell S Thomas
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 120:194-205. 2011
    ....
  36. pmc Low-level arsenic impairs glucose-stimulated insulin secretion in pancreatic beta cells: involvement of cellular adaptive response to oxidative stress
    Jingqi Fu
    Division of Translational Biology, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Environ Health Perspect 118:864-70. 2010
    ..Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a central transcription factor regulating cellular adaptive response to oxidative stress...
  37. ncbi request reprint A map of the PPARα transcription regulatory network for primary human hepatocytes
    Patrick D McMullen
    The Hamner Institutes for Health Sciences, Institute for Chemical Safety Sciences, 6 Davis Drive, PO Box 12137, Research Triangle Park, NC 27709, USA
    Chem Biol Interact 209:14-24. 2014
    ....
  38. pmc Association between arsenic suppression of adipogenesis and induction of CHOP10 via the endoplasmic reticulum stress response
    Yongyong Hou
    Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Environ Health Perspect 121:237-43. 2013
    ..However, the mechanisms for the diabetogenic effect of iAs are still largely unknown. White adipose tissue (WAT) actively stores and releases energy and maintains lipid and glucose homeostasis...
  39. ncbi request reprint Comparing respiratory-tract and hepatic exposure-dose relationships for metabolized inhaled vapors: a pharmacokinetic analysis
    Ramesh Sarangapani
    ICF Consulting, The K S Crump Group, Inc, Research Triangle Park, North Carolina, USA
    Inhal Toxicol 14:835-54. 2002
    ..The difference in dose-response relationships for metabolism in the respiratory tract versus systemic organs depends on blood/air and blood/tissue partition coefficients and on the degree of systemic extraction of the metabolized vapors...
  40. ncbi request reprint Evaluating placental transfer and tissue concentrations of manganese in the pregnant rat and fetuses after inhalation exposures with a PBPK model
    Miyoung Yoon
    The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 112:44-58. 2009
    ....
  41. doi request reprint Computational systems biology and dose-response modeling in relation to new directions in toxicity testing
    Qiang Zhang
    Division of Computational Biology, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina
    J Toxicol Environ Health B Crit Rev 13:253-76. 2010
    ..In parallel, dissemination of computational systems biology techniques and other analytical tools among practicing toxicologists and risk assessment professionals will help accelerate implementation of the new toxicity testing vision...
  42. pmc Incorporating new technologies into toxicity testing and risk assessment: moving from 21st century vision to a data-driven framework
    Russell S Thomas
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709
    Toxicol Sci 136:4-18. 2013
    ..The framework provides a risk-based and animal-sparing approach to evaluate chemical safety, drawing broadly from previous experience but incorporating technological advances to increase efficiency. ..
  43. doi request reprint Cross-species transcriptomic analysis of mouse and rat lung exposed to chloroprene
    Russell S Thomas
    The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA
    Toxicol Sci 131:629-40. 2013
    ....
  44. doi request reprint A dose response study to assess effects after dietary administration of diisononyl phthalate (DINP) in gestation and lactation on male rat sexual development
    Rebecca A Clewell
    The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA
    Reprod Toxicol 35:70-80. 2013
    ..DiNP did not alter AGD, nipple retention or reproductive tract malformations on PND 49. Global endpoint analysis showed no evidence of a rat "phthalate syndrome" on PND 49 with DiNP administration...
  45. doi request reprint Application of a multi-route physiologically based pharmacokinetic model for manganese to evaluate dose-dependent neurological effects in monkeys
    Jeffry D Schroeter
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, USA
    Toxicol Sci 129:432-46. 2012
    ..These results also provide strong evidence of a dose-dependent transition in the mode of action for the neurological effects of Mn that needs to be considered in risk assessments for this essential metal...
  46. ncbi request reprint A comprehensive statistical analysis of predicting in vivo hazard using high-throughput in vitro screening
    Russell S Thomas
    The Hamner Institutes for Health Sciences Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 128:398-417. 2012
    ..However, if viewed as a survey of potential molecular initiating events and interpreted as risk factors for toxicity, the assays may still be useful for chemical prioritization...
  47. doi request reprint Integrating pathway-based transcriptomic data into quantitative chemical risk assessment: a five chemical case study
    Russell S Thomas
    The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA
    Mutat Res 746:135-43. 2012
    ....
  48. pmc A deterministic map of Waddington's epigenetic landscape for cell fate specification
    Sudin Bhattacharya
    Division of Computational Biology, Program in Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA
    BMC Syst Biol 5:85. 2011
    ..However the question of whether the epigenetic landscape can be mapped out quantitatively to provide a predictive model of cellular differentiation remains largely unanswered...
  49. pmc A systems biology perspective on Nrf2-mediated antioxidant response
    Qiang Zhang
    Division of Computational Biology, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709, USA
    Toxicol Appl Pharmacol 244:84-97. 2010
    ..Our analysis highlights some possible adverse effects of these widely consumed antioxidants...
  50. doi request reprint Use of short-term transcriptional profiles to assess the long-term cancer-related safety of environmental and industrial chemicals
    Russell S Thomas
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 112:311-21. 2009
    ....
  51. ncbi request reprint Multi-dose-route, multi-species pharmacokinetic models for manganese and their use in risk assessment
    Melvin E Andersen
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709 2137, USA
    J Toxicol Environ Health A 73:217-34. 2010
    ..These models are organized to contribute to a tissue-dose based risk assessment of Mn that simultaneously considers ingestion and inhalation kinetics of Mn along with homeostatic control of Mn...
  52. pmc A bistable switch underlying B-cell differentiation and its disruption by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin
    Sudin Bhattacharya
    Division of Computational Biology, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 115:51-65. 2010
    ..Second, TCDD may also disrupt the maintenance of the immune response by depleting the pool of available plasma cells through dedifferentiation...
  53. doi request reprint Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening
    Daniel M Rotroff
    National Center for Computational Toxicology, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA
    Toxicol Sci 117:348-58. 2010
    ..Importantly, these tools are necessary to move beyond hazard rankings to estimates of possible in vivo responses based on in vitro screens...
  54. doi request reprint Assessing dose-dependent differences in DNA-damage, p53 response and genotoxicity for quercetin and curcumin
    Bin Sun
    The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA
    Toxicol In Vitro 27:1877-87. 2013
    ..Thus, even with two compounds sharing common chemistries, DNA-damage response patterns differed significantly in terms of dose and cell fate...
  55. doi request reprint In vitro intestinal and hepatic metabolism of Di(2-ethylhexyl) phthalate (DEHP) in human and rat
    Kyoungju Choi
    The Hamner Institutes for Health Sciences, RTP, NC 27709, United States
    Toxicol In Vitro 27:1451-7. 2013
    ..These species/organ differences in major metabolic pathway and CYP isoforms should be considered for appraisal of the potential adverse health effects of DEHP...
  56. doi request reprint Deriving an explicit hepatic clearance equation accounting for plasma protein binding and hepatocellular uptake
    Miyoung Yoon
    The Hamner Institutes for Health Sciences, Six Davis Drive, PO Box 12137, Research Triangle Park, NC 27709 2137, United States
    Toxicol In Vitro 27:11-5. 2013
    ..This expanded equation provides a tool to estimate hepatic clearance for a more diverse array of compounds...
  57. doi request reprint An analysis of N-acetylcysteine treatment for acetaminophen overdose using a systems model of drug-induced liver injury
    Jeffrey L Woodhead
    The Hamner University of North Carolina Institute for Drug Safety Sciences, The Hamner Institutes, Research Triangle Park, North Carolina, USA
    J Pharmacol Exp Ther 342:529-40. 2012
    ..The modeling also suggests that modification of the current treatment nomograms should be considered...
  58. doi request reprint In vitro to in vivo extrapolation and species response comparisons for drug-induced liver injury (DILI) using DILIsym™: a mechanistic, mathematical model of DILI
    Brett A Howell
    The Hamner UNC Institute for Drug Safety Sciences, The Hamner Institutes, Durham, NC 27709, USA
    J Pharmacokinet Pharmacodyn 39:527-41. 2012
    ..Differences in model sensitivity to the parameters were related to species differences, but the severity of DILI for each drug/species combination was also an important factor...
  59. ncbi request reprint Perfluoroalkyl acids and related chemistries--toxicokinetics and modes of action
    Melvin E Andersen
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 102:3-14. 2008
    ..This report summarizes the discourse that occurred during the symposium...
  60. ncbi request reprint Quantitative interpretation of human biomonitoring data
    Harvey J Clewell
    The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA
    Toxicol Appl Pharmacol 231:122-33. 2008
    ..These exposure distributions can be compared to regulatory exposure guidance values or no-effect levels in toxicity studies to put potential risks in context...
  61. ncbi request reprint Route-specific differences in distribution characteristics of octamethylcyclotetrasiloxane in rats: analysis using PBPK models
    Ramesh Sarangapani
    ICF Consulting, P O Box 14348, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 71:41-52. 2003
    ..This model-based analysis indicates that the pharmacokinetics of D(4) delivered by the inhalation or dermal routes is similar, and is different from the iv or oral delivery routes...
  62. ncbi request reprint Lactational transfer of manganese in rats: predicting manganese tissue concentration in the dam and pups from inhalation exposure with a pharmacokinetic model
    Miyoung Yoon
    Center for Human Health Assessment, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 112:23-43. 2009
    ....
  63. ncbi request reprint Use of a pharmacokinetic-driven computational fluid dynamics model to predict nasal extraction of hydrogen sulfide in rats and humans
    Jeffry D Schroeter
    CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709 2137, USA
    Toxicol Sci 94:359-67. 2006
    ....
  64. ncbi request reprint 3-chlorotyrosine and 3,5-dichlorotyrosine as biomarkers of respiratory tract exposure to chlorine gas
    Mark A Sochaski
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709 2137, USA
    J Anal Toxicol 32:99-105. 2008
    ..similar rates of formation for CY and dCY when exposed to chlorine gas based on a strong [CY] versus [dCY] correlation (slope = 1.001, r(2) = 0.912)...
  65. doi request reprint Disposition of diiosononyl phthalate and its effects on sexual development of the male fetus following repeated dosing in pregnant rats
    Rebecca A Clewell
    The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA
    Reprod Toxicol 35:56-69. 2013
    ..The no observed effect level (NOEL) for this study was 50 mg/kg/day based on increased MNGs and reduced testes testosterone concentration in the fetal rat...
  66. pmc Organotypic liver culture models: meeting current challenges in toxicity testing
    Edward L LeCluyse
    The Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, NC, USA
    Crit Rev Toxicol 42:501-48. 2012
    ..In the future, a balanced approach between sample throughput and biological relevance should provide better in vitro tools that are complementary with animal testing and assist in conducting more predictive human risk assessment...
  67. ncbi request reprint Physiologically based pharmacokinetic modeling of styrene and styrene oxide respiratory-tract dosimetry in rodents and humans
    Ramesh Sarangapani
    The K S Crump Group, Inc, Research Triangle Park, North Carolina, USA
    Inhal Toxicol 14:789-834. 2002
    ..Pharmacodynamic factors are also expected to contribute to species sensitivity, potentially augmenting pharmacokinetics-based differences...
  68. doi request reprint The future of toxicity testing
    Melvin E Andersen
    Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, USA
    J Toxicol Environ Health B Crit Rev 13:163-96. 2010
    ..In addition to the overview of the NRC vision, this study documents the reaction by a number of stakeholder groups since 2007, including the scientific, risk assessment, regulatory, and animal welfare communities...
  69. ncbi request reprint Activation of Nrf2-mediated oxidative stress response in macrophages by hypochlorous acid
    Jingbo Pi
    Division of Translational Biology, The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, USA
    Toxicol Appl Pharmacol 226:236-43. 2008
    ..Taken together, we provide direct evidence that HOCl activates Nrf2-mediated antioxidant response, which protects cells from oxidative damage...
  70. doi request reprint Genome-wide analysis of DNA methylation and gene expression changes in the mouse lung following subchronic arsenate exposure
    Frank Boellmann
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Toxicol Sci 117:404-17. 2010
    ....
  71. ncbi request reprint Physiologically based pharmacokinetic/toxicokinetic modeling
    Jerry L Campbell
    The Hamner Institutes for Health Sciences, Research Triangle Park, NC, USA
    Methods Mol Biol 929:439-99. 2012
    ....
  72. doi request reprint In vitro metabolism of di(2-ethylhexyl) phthalate (DEHP) by various tissues and cytochrome P450s of human and rat
    Kyoungju Choi
    The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709, United States
    Toxicol In Vitro 26:315-22. 2012
    ..Percent total normalized rates (%TNR) by CYP2C9(∗)1 in human liver microsomes (HLM) were 94%, 98% and 100%, respectively, for 5-OH MEHP, 5-Oxo MEHP, 5-carboxy MEPP, and 76% for PA production by CYP3A4...
  73. ncbi request reprint Quantitative analyses and transcriptomic profiling of circulating messenger RNAs as biomarkers of rat liver injury
    Barbara A Wetmore
    The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709 2137, USA
    Hepatology 51:2127-39. 2010
    ..Finally, gene expression microarray analysis of the plasma following DGAL and APAP treatment revealed chemical-specific profiles...
  74. ncbi request reprint Evaluating transport of manganese from olfactory mucosa to striatum by pharmacokinetic modeling
    Teresa L Leavens
    CIIT Centers for Health Research, Research Triangle Park, NC 27709, USA
    Toxicol Sci 97:265-78. 2007
    ..Only a small fraction of Mn tracer from the tract and tubercle was predicted to be delivered to the striatum, 3 and 0.1% following (54)MnHPO(4) or (54)MnCl(2) exposure, respectively...
  75. pmc Phase I to II cross-induction of xenobiotic metabolizing enzymes: a feedforward control mechanism for potential hormetic responses
    Qiang Zhang
    Division of Computational Biology, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709, USA
    Toxicol Appl Pharmacol 237:345-56. 2009
    ..Feedforward control, often operating in combination with negative feedback regulation in a homeostatic system, may be a general control theme responsible for steady-state hormesis...
  76. ncbi request reprint Application of pharmacokinetic data to the risk assessment of inhaled manganese
    David C Dorman
    CIIT Centers for Health Research CIIT, 6 Davis Drive, P O Box 12137, Research Triangle Park, NC 27709 2137, USA
    Neurotoxicology 27:752-64. 2006
    ..Environmental Protection Agency's current risk assessment for inhaled manganese, summarizes these contemporary pharmacokinetic studies, and considers how these data could inform future risk assessments of this metal following inhalation...
  77. ncbi request reprint On the incorporation of chemical-specific information in risk assessment
    Harvey J Clewell
    The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709, USA
    Toxicol Lett 180:100-9. 2008
    ....
  78. ncbi request reprint Identification of Nrf2-dependent airway epithelial adaptive response to proinflammatory oxidant-hypochlorous acid challenge by transcription profiling
    Lingxiang Zhu
    Division of Translational Biology, The Hamner Institutes for Health Sciences, 6 Davis Dr, Research Triangle Park, NC 27709, USA
    Am J Physiol Lung Cell Mol Physiol 294:L469-77. 2008
    ..By both methods, we conclude that Nrf2 directly protects airway epithelial cells from HOCl-induced toxicity...
  79. pmc Dose response relationship in anti-stress gene regulatory networks
    Qiang Zhang
    Division of Computational Biology, CIIT Centers for Health Research, Research Triangle Park, North Carolina, United States of America
    PLoS Comput Biol 3:e24. 2007
    ..This work would help biologists and especially toxicologists to better assess and predict the cellular impact brought about by biological stressors...
  80. ncbi request reprint Dose-response modeling in reproductive toxicology in the systems biology era
    Melvin E Andersen
    CIIT Centers for Health Research, Research Triangle Park, NC 27709 2137, USA
    Reprod Toxicol 19:327-37. 2005
    ..In addition to outlining a systems approach for dose-response research, this paper discusses initial stages of application of this strategy to examine inhibition of steroidogenesis in testes by phthalate esters...
  81. doi request reprint Assessing the relevance of in vitro measures of phthalate inhibition of steroidogenesis for in vivo response
    Rebecca A Clewell
    University of North Carolina, Chapel Hill, NC 27599, USA
    Toxicol In Vitro 24:327-34. 2010
    ..Based on these results, differences in the phthalates' ability to interfere with sexual development in vivo appears to be more associated with differential potency for testosterone inhibition than differences in tissue doses...
  82. doi request reprint Tissue exposures to free and glucuronidated monobutylyphthalate in the pregnant and fetal rat following exposure to di-n-butylphthalate: evaluation with a PBPK model
    Rebecca A Clewell
    The University of North Carolina, Chappell Hill, North Carolina 27599, USA
    Toxicol Sci 103:241-59. 2008
    ..Oxidative metabolism plays a significant role in elimination only at low doses (< 50 mg/kg DBP). Insights gained from modeling of the rat data will be used to support development of a human PBPK model for DBP...
  83. doi request reprint Kinetics of selected di-n-butyl phthalate metabolites and fetal testosterone following repeated and single administration in pregnant rats
    Rebecca A Clewell
    The University of North Carolina, Chapell Hill, NC 27599, USA
    Toxicology 255:80-90. 2009
    ..MBP kinetics in fetal testes allows direct comparison of active metabolite concentrations and testosterone response in the fetal testes...
  84. doi request reprint In utero exposure to chloroquine alters sexual development in the male fetal rat
    Rebecca A Clewell
    The University of North Carolina, Chapel Hill, NC 27599, USA
    Toxicol Appl Pharmacol 237:366-74. 2009
    ..This study indicates that CQ inhibits testosterone synthesis and normal testis development in the rat fetus at human relevant doses...
  85. pmc Regulatory role of KEAP1 and NRF2 in PPARγ expression and chemoresistance in human non-small-cell lung carcinoma cells
    Lijuan Zhan
    Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
    Free Radic Biol Med 53:758-68. 2012
    ....
  86. ncbi request reprint Incorporation of tissue reaction kinetics in a computational fluid dynamics model for nasal extraction of inhaled hydrogen sulfide in rats
    Jeffry D Schroeter
    CIIT Centers for Health Research, 6 Davis Drive, P O Box 12137, Research Triangle Park, North Carolina 27709 2137, USA
    Toxicol Sci 90:198-207. 2006
    ..The CFD model provides estimates of localized H2S flux to airway walls and can be used to calibrate lesion sites by dose...
  87. ncbi request reprint Kinetic and mechanistic data needs for a human phsiologically based pharmacokinetic (PBPK) model for acrylamide: pharmacokinetic model for acrylamide
    Melvin E Andersen
    CllT Centers for Health Research, Six Davis Drive, PO Box 12137, Research Triangle Park, NC 27709 2137, USA
    Adv Exp Med Biol 561:117-25. 2005
    ....
  88. ncbi request reprint Pharmacokinetic modeling of saturable, renal resorption of perfluoroalkylacids in monkeys--probing the determinants of long plasma half-lives
    Melvin E Andersen
    CIIT Centers for Health Research, Research Triangle Park, NC 27709 2137, United States
    Toxicology 227:156-64. 2006
    ..PFOS has longer half-life and had respective values of 13.6 mg/(h kg), 0.023 mg/L, and 0.025. PFOS appeared to have a higher transport capacity and lower affinity than PFOA. Human kinetics indicates even higher resorption efficiency...
  89. pmc Binary gene induction and protein expression in individual cells
    Qiang Zhang
    Division of Computational Biology, CIIT Centers for Health Research, Research Triangle Park, NC 27709, USA
    Theor Biol Med Model 3:18. 2006
    ..Support for each of these two mechanisms arises primarily from experimental studies measuring reporter proteins in individual cells, rather than from direct measurement of induction events at the gene template...
  90. ncbi request reprint New directions in incidence-dose modeling
    Melvin E Andersen
    CIIT Centers for Health Research, Six Davis Drive, PO Box 12137, Research Triangle Park, NC 27709 2137, USA
    Trends Biotechnol 23:122-7. 2005
    ..These interdisciplinary approaches should produce novel, quantitative ID models for biological responses and greatly improve the biological basis of safety and risk assessments...
  91. ncbi request reprint Reactive oxygen species as a signal in glucose-stimulated insulin secretion
    Jingbo Pi
    Endocrine Biology Program, The Hamner Institutes for Health Sciences, 6 Davis Dr, Research Triangle Park, NC 27709, USA
    Diabetes 56:1783-91. 2007
    ..Taken together, these findings suggest that H2O2 derived from glucose metabolism is one of the metabolic signals for insulin secretion, whereas oxidative stress may disturb its signaling function...
  92. ncbi request reprint Dose-incidence modeling: consequences of linking quantal measures of response to depletion of critical tissue targets
    Melvin E Andersen
    CIIT Centers for Health Research, Research Triangle Park, North Carolina 27709 2137, USA
    Toxicol Sci 89:331-7. 2006
    ..These conclusions are important for developing biologically based dose response (BBDR) models that link incidences of toxicity or other biological responses to measures of BED...
  93. ncbi request reprint Characterizing uncertainty and variability in physiologically based pharmacokinetic models: state of the science and needs for research and implementation
    Hugh A Barton
    US EPA, ORD, National Center for Computational Toxicology, Research Triangle Park, North Carolina 27711, USA
    Toxicol Sci 99:395-402. 2007
    ....
  94. ncbi request reprint Dose-response modeling of cytochrome p450 induction in rats by octamethylcyclotetrasiloxane
    Ramesh Sarangapani
    The K S Crump Group, ICF Consulting, P O Box 14348, Research Triangle Park, NC 27709, USA
    Toxicol Sci 67:159-72. 2002
    ....
  95. ncbi request reprint Ethyl acrylate risk assessment with a hybrid computational fluid dynamics and physiologically based nasal dosimetry model
    Lisa M Sweeney
    The Sapphire Group, Dayton, Ohio 45431, USA
    Toxicol Sci 79:394-403. 2004
    ..Thus, a chronic RfC based on maintaining GSH in the human nasal olfactory epithelium at levels equivalent to the rat NOEL would also provide an adequate margin of safety with respect to AA concentrations in nasal tissues...
  96. ncbi request reprint Stochastic simulation of hepatic preneoplastic foci development for four chlorobenzene congeners in a medium-term bioassay
    Ying C Ou
    Preclinical Development, Human Genome Sciences, Inc, Rockville, Maryland 20850, USA
    Toxicol Sci 73:301-14. 2003
    ..Together, these results indicate that examining effects of chemicals on regenerative responses following partial hepatectomy may be a means for understanding the carcinogenicity potential of chlorobenzene compounds...
  97. pmc In silico toxicology: simulating interaction thresholds for human exposure to mixtures of trichloroethylene, tetrachloroethylene, and 1,1,1-trichloroethane
    Ivan D Dobrev
    Quantitative and Computational Toxicology Group, Center for Environmental Toxicology and Technology, Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado 80523, USA
    Environ Health Perspect 110:1031-9. 2002
    ..Evaluation of metabolic interactions and their thresholds illustrates a unique application of PBPK modeling in risk assessment of occupational exposures to chemical mixtures...
  98. ncbi request reprint Application of a physiologically based pharmacokinetic model for isopropanol in the derivation of a reference dose and reference concentration
    P Robin Gentry
    The KS Crump Group, Inc, Ruston, Louisiana, USA
    Regul Toxicol Pharmacol 36:51-68. 2002
    ..All of the PBPK-derived RfD or RfC values for various endpoints were similar (within a factor of 3), regardless of route of exposure in the animal study...
  99. ncbi request reprint Characterization of the pharmacokinetics of gasoline using PBPK modeling with a complex mixtures chemical lumping approach
    James E Dennison
    Quantitative and Computational Toxicology Group, Center for Environmental Toxicology and Technology, Department of Environmental and Radiological Health Sciences, Colorado State University, Ft Collins, CO 80523, USA
    Inhal Toxicol 15:961-86. 2003
    ..The PBPK model analysis indicated that metabolism of individual components was inhibited up to 27% during the 6-h gas uptake experiments of gasoline exposures...
  100. pmc Application of biologically based computer modeling to simple or complex mixtures
    Kai H Liao
    Quantitative and Computational Toxicology Group, Center for Environmental Toxicology and Technology, Colorado State University, Fort Collins, Colorado, USA
    Environ Health Perspect 110:957-63. 2002
    ..We discuss the applications of reaction network modeling in the context of petroleum refining and its potential for elucidating toxic interactions with mixtures...
  101. ncbi request reprint Closed-chamber inhalation pharmacokinetic studies with hexamethyldisiloxane in the rat
    Ivan D Dobrev
    Quantitative and Computational Toxicology Group, Center for Environmental Toxicology and Technology, Department of Environmental Health, Colorado State University, Fort Collins, USA
    Inhal Toxicol 15:589-617. 2003
    ..This conclusion is likely to hold for any volatile lipophilic compound with low blood/air partitioning...