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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Project Publications: Colorado State University: Toxicologic Interaction Studies in Chemical Mixtures Using Physiologically Based Pharmacokinetics/Pharmacodynamics (PB-PK/PD) Coupled with Statistical/Mathematical Modeling

Superfund Research Program

Toxicologic Interaction Studies in Chemical Mixtures Using Physiologically Based Pharmacokinetics/Pharmacodynamics (PB-PK/PD) Coupled with Statistical/Mathematical Modeling

Project Leader: Raymond S H. Yang
Grant Number: P42ES005949
Funding Period: 1995 - 2000

Project-Specific Links

Publications

2003

  • Andersen ME, Ou YC, Yang RH, Conolly RB, Thomas RS, Gustafson DL, Long ME, Dobrev ID, Chubb LS, Xu Y, Lapidot SA. 2003. Stochastic simulation of hepatic preneoplastic foci development for four chlorobenzene congeners in a medium-term bioassay. Toxicol Sci 73(2):301-314. PMID:12700395
  • Bae D, Handa RJ, Yang RH, Campain JA. 2003. Gene expression patterns as potential molecular biomarkers for malignant transformation in human keratinocytes treated with MNNG, arsenic, or a metal mixture. Toxicol Sci 74(1):32-42. PMID:12773770

2002

  • Andersen ME, Yang RH, French CT, Chubb LS, Dennison JE. 2002. Molecular circuits, biological switches, and nonlinear dose-response relationships. Environ Health Perspect 110(suppl.6):971-978. PMID:12634127
  • Bae D, Hanneman WH, Yang RH, Campain JA. 2002. Characterization of gene expression changes associated with MNNG, arsenic, or metal mixture treatment in human keratinocytes: application of cDNA microarray technology. Environ Health Perspect 110(suppl.6):931-941. PMID:12634122
  • Dobrev ID, Andersen ME, Yang RH. 2002. In silico toxicology: simulating interaction thresholds for human exposure to mixtures of trichloroethylene, tetrachloroethylene, and 1,1,1-trichloroethane. Environ Health Perspect 110(10):1031-1039. PMID:12361929
  • Klein MT, Hou G, Quann RJ, Wei W, Liao KH, Yang RH, Campain JA, Mazurek MA, Broadbelt LJ. 2002. BioMOL: a computer-assisted biological modeling tool for complex chemical mixtures and biological processes at the molecular level. Environ Health Perspect 110(suppl.6):1025-1029. PMID:12634134
  • Suk WA, Olden K, Yang RH. 2002. Chemical mixtures research: significance and future perspectives. Environ Health Perspect 110(suppl.6):891-892. PMID:12634115

2001

  • Bae D, Gennings C, Carter, Jr. WH, Yang RH, Campain JA. 2001. Toxicological interactions among arsenic, cadmium, chromium, and lead in human keratinocytes. Toxicol Sci 63(1):132-142. PMID:11509753
  • Dobrev ID, Andersen ME, Yang RH. 2001. Assessing interaction thresholds for trichloroethylene in combination with tetrachloroethylene and 1,1,1-trichloroethane using gas uptake studies and PBPK modeling. Arch Toxicol 75(3):134-144. PMID:11409535
  • Liao KH, Gustafson DL, Fox MH, Chubb LS, Reardon KF, Yang RH. 2001. A biologically based model of growth and senescence of Syrian Hamster Embryo (SHE) cells after exposure to arsenic. Environ Health Perspect 109(12):1207-1213. PMID:11748027
  • Ou YC, Conolly RB, Thomas RS, Xu Y, Andersen ME, Chubb LS, Pitot HC, Yang RH. 2001. A clonal growth model: time-course simulations of liver foci growth following penta- or hexachlorobenzene treatment in a medium-term bioassay. Cancer Res 61(5):1879-1889. PMID:11280742
  • Pott WA, Benjamin SA, Yang RH. 2001. Pharmacokinetics, metabolism, and carcinogenicity of arsenic. Rev Environ Contam Toxicol 169:165-214. PMID:11330077

2000

  • Gustafson DL, Long ME, Thomas RS, Benjamin SA, Yang RH. 2000. Comparative hepatocarcinogenicity of hexachlorobenzene, pentachlorobenzene, 1,2,4,5-tetrachlorobenzene, and 1,4-dichlorobenzene: application of a medium-term liver focus bioassay and molecular and cellular indices. Toxicol Sci 53(2):245-252. PMID:10696772
  • Thomas RS, Conolly RB, Gustafson DL, Long ME, Benjamin SA, Yang RH. 2000. A physiologically based pharmacodynamic analysis of hepatic foci within a medium-term liver bioassay using pentachlorobenzene as a promoter and diethylnitrosamine as an initiator. Toxicol Appl Pharmacol 166(2):128-137. PMID:10896854

1999

  • Benjamin SA, Yang RH, Tessari JD, Chubb LS, Brown MD, Dean CE, Keefe TJ. 1999. Lack of promotional effects of groundwater contaminant mixtures on the induction of preneoplastic foci in rat liver. Toxicology 137(3):137-149. PMID:10522494

1998

  • Gustafson DL, Coulson AL, Feng L, Pott WA, Thomas RS, Chubb LS, Saghir SA, Benjamin SA, Yang RH. 1998. Use of a medium-term liver focus bioassay to assess the hepatocarcinogenicity of 1,2,4,5-tetrachlorobenzene and 1,4-dichlorobenzene. Cancer Lett 129(1):39-44. PMID:9714333
  • Pott WA, Benjamin SA, Yang RH. 1998. Antagonistic interactions of arsenic-containing mixtures in a multiple organ carcinogenicity bioassay. Cancer Lett 133(2):185-190. PMID:10072168
  • Thomas RS, Gustafson DL, Pott WA, Long ME, Benjamin SA, Yang RH. 1998. Evidence for hepatocarcinogenic activity of pentachlorobenzene with intralobular variation in foci incidence. Carcinogenesis 19(10):1855-1862. PMID:9806169
  • Thomas RS, Gustafson DL, Ramsdell HS, El-Masri HA, Benjamin SA, Yang RH. 1998. Enhanced regional expression of glutathioneS-transferase P1-1 with colocalized AP-1 and CYP 1A2 induction in chlorobenzene-induced porphyria. Toxicol Appl Pharmacol 150(1):22-31. PMID:9630449
  • Yang RH. 1998. Some critical issues and concerns related to research advances on the toxicology of chemical mixtures. Environ Health Perspect 106(Suppl.6):1595. PMID:9703493
  • Yang RH, Thomas RS, El-Masri HA. 1998. Integrating computer modeling and mechanistic toxicology for the development of a predictive and alternative toxicology approach for chemicals and chemical mixtures. In: Proceedings of the Superfund Basic Research Program: A Decade of Improving Health through Multi-Disciplinary Research. Chapel Hill, NC.
  • Yang RH, Thomas RS, Gustafson DL, Campain JA, Benjamin SA, Verhaar HJ, Mumtaz MM. 1998. Approaches to developing alternative and predictive toxicology based on PBPK/PD and QSAR modeling. Environ Health Perspect 106(suppl.6):1385-1393. PMID:9860897

1997

  • El-Masri HA, Reardon KF, Yang RH. 1997. Integrated approaches for the analysis of toxicologic interactions of chemical mixtures. Crit Rev Toxicol 27(2):175-197. PMID:9099518
  • Saghir SA, Feng L, El-Masri HA, Benjamin SA, Yang RH. 1997. Toxicologic interactions involving three chemicals: Kepone, carbon tetrachloride, and 1,1,2,2-tetrachloroethane. Environ Health Perspect 36:151.
  • Smith TB, Reardon KF, Yang RH. 1997. Assessment of the carcinogenic potential of arsenic and arsenic-containing chemical mixtures using the Syrian Hamster Embryo (SHE) cell assay. Environ Health Perspect 36:89.
  • Verhaar HJ, Morroni JS, Reardon KF, Hays SM, Gaver DP, Carpenter RL, Yang RH. 1997. A proposed approach to study the toxicology of complex mixtures of petroleum products: The integrated use of QSAR, lumping analysis, and PBPK/PD modeling. Environ Health Perspect 105(supp.5):179-195. PMID:9114286
  • Yang RH. 1997. Some current approaches for studying combination toxicology in chemical mixtures. Food Chem Toxicol 34(11-12):1173-1174. PMID:9119313
  • Yang RH. 1997. Toxicologic Interactions of Chemical Mixtures. In: Comprehensive Toxicology, Vol. 1, General Principles, Toxicokinetics, and Mechanisms of Toxicity. Elsevier Science, Ltd., Oxford, United Kingdom. pp.189-203.

1996

  • Chubb LS, El-Masri HA, Saghir SA, Yang RH. 1996. A physiologically based pharmacokinetic model predicting liver dosimetry of kepone. Environ Health Perspect 30:252.
  • Constan AA, Benjamin SA, Tessari JD, Baker DC, Yang RH. 1996. Increased rate of apoptosis correlates with hepatocellular proliferation in Fischer-344 rats following long-term exposure to a mixture of groundwater contaminants. Toxicol Pathol 24(3):315-322. doi:10.1177/019262339602400307 PMID:8736387
  • El-Masri HA, Constan AA, Ramsdell HS, Yang RH. 1996. Physiologically based pharmacodynamic modeling of an interaction threshold between trichloroethylene and 1,1-dichloroethylene in Fischer 344 rats. Toxicol Appl Pharmacol 141(1):124-132. PMID:8917684
  • El-Masri HA, Thomas RS, Mumtaz MM, Andersen ME, Yang RH. 1996. A biologically based mathematical model of the effects of partial hepatectomy on cell cycle kinetics. Environ Health Perspect 30:131.
  • El-Masri HA, Thomas RS, Sabados G, Phillips JK, Constan AA, Benjamin SA, Mehendale HM, Yang RH, Andersen ME. 1996. Physiologically based pharmacokinetic/pharmacodynamic modeling of the toxicologic interaction between carbon tetrachloride and kepone. Arch Toxicol 70:704-713. PMID:8896716
  • Hwang IY, Reardon KF, Tessari JD, Yang RH. 1996. A gas-liquid system for enzyme kinetic studies of volatile organic chemicals: Determination of enzyme kinetic constants and partition coefficients of trichloroethylene. Drug Metab Dispos 24:377-382. PMID:8801050
  • Thomas RS, Bigelow PL, Keefe TJ, Yang RH. 1996. Variability in biological exposure indices using physiologically based pharmacokinetic modeling and Monte Carlo simulation. Am Ind Hyg Assoc J 57(1):23-32. PMID:8588550
  • Thomas RS, Lytle WE, Keefe TJ, Constan AA, Yang RH. 1996. Incorporating Monte Carlo simulation into physiologically based pharmacokinetic models using Advanced Continuous Simulation Language (ACSL): a computational method. Fundam Appl Toxicol 31(1):19-28. PMID:8998950
  • Thomas RS, Yang RH, Morgan DG, Moorman MP, Kermani HR, Sloane RA, O'Connor RW, Adkins, Jr. B, Gargas ML, Andersen ME. 1996. PBPK modeling/Monte Carlo simulation of methylene chloride kinetic changes in mice in relation to age and acute, subchronic, and chronic inhalation exposure. Environ Health Perspect 104(8):858-865. PMID:8875160
  • Yang RH. 1996. A comparison of quantitative, immunohistochemical markers for cell-cycle specific changes in F344 rats. Environ Health Perspect 30:130.
  • Yang RH. 1996. The application of computer modeling to health effects research. In: Proceedings of the Pacific Basin Conference on Hazardous Waste, November 4-8, 1996, Kuala Lumpur, Malaysia. East-West Center, Kuala Lumpur, Malaysia.
  • Yang RH. 1996. Toxicology of representative superfund mixtures. In: Proceedings of the 1996 Annual Meeting of the International Life Sciences Institute. Cancun, Mexico.

1995

  • El-Masri HA, Thomas RS, Benjamin SA, Yang RH. 1995. Physiologically based pharmacokinetic/pharmacodynamic modeling of chemical mixtures and possible applications in risk assessment. Toxicology 105(2-3):275-282. PMID:8571364
  • Veeramachaneni D, Palmer J, Amann RP. 1995. Infantile exposure of rabbits to a chemical mixture alters pituitary and testicular function as adults. J Androl 16(supp.):80.
  • Veeramachaneni D, Palmer J, Amann RP. 1995. Sexual dysfunction and abnormal acrosomes in rabbits following infantile exposure to a mixture of chemicals in drinking water. Biol Reprod 52:171.
  • Yang RH, El-Masri HA, Thomas RS, Constan AA. 1995. The use of physiologically based pharmacokinetic/pharmacodynamic dosimetry models for chemical mixtures. Toxicol Lett 82/83:497-504. PMID:8597101
  • Yang RH, El-Masri HA, Thomas RS, Constan AA, Tessari JD. 1995. The application of physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling for exploring risk assessment approaches of chemical mixtures. Toxicol Lett 79(1-3):193-200. PMID:7570656
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