T J Shafer

Summary

Affiliation: U.S. Environmental Protection Agency
Country: USA

Publications

  1. ncbi request reprint Effects of pyrethroids on voltage-sensitive calcium channels: a critical evaluation of strengths, weaknesses, data needs, and relationship to assessment of cumulative neurotoxicity
    Timothy J Shafer
    Neurophysiological Toxicology Branch, Neurotoxicology Division, NHEERL, ORD, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Toxicol Appl Pharmacol 196:303-18. 2004
  2. ncbi request reprint Effects of prolonged exposure to nanomolar concentrations of methylmercury on voltage-sensitive sodium and calcium currents in PC12 cells
    Timothy J Shafer
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Brain Res Dev Brain Res 136:151-64. 2002
  3. doi request reprint Complete inhibition of spontaneous activity in neuronal networks in vitro by deltamethrin and permethrin
    T J Shafer
    Neurotoxicology Division, MD B105 05, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Neurotoxicology 29:203-12. 2008
  4. doi request reprint Accumulation of pyrethroid compounds in primary cultures from rat cortex
    Timothy J Shafer
    Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC, USA
    Toxicol In Vitro 24:2053-7. 2010
  5. ncbi request reprint Perturbation of voltage-sensitive Ca2+ channel function by volatile organic solvents
    Timothy J Shafer
    Neurotoxicology Division, MD B105 05, NHEERL, ORD, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    J Pharmacol Exp Ther 315:1109-18. 2005
  6. pmc Developmental neurotoxicity of pyrethroid insecticides: critical review and future research needs
    Timothy J Shafer
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA
    Environ Health Perspect 113:123-36. 2005
  7. ncbi request reprint Extracellular calcium is required for the polychlorinated biphenyl-induced increase of intracellular free calcium levels in cerebellar granule cell culture
    W R Mundy
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Toxicology 136:27-39. 1999
  8. ncbi request reprint Inositol 1,4,5-triphosphate receptor-sensitive Ca(2+) release, store-operated Ca(2+) entry, and cAMP responsive element binding protein phosphorylation in developing cortical cells following exposure to polychlorinated biphenyls
    J R Inglefield
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA
    J Pharmacol Exp Ther 297:762-73. 2001
  9. ncbi request reprint Accumulation of methylmercury or polychlorinated biphenyls in in vitro models of rat neuronal tissue
    C A Meacham
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory ORD, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Toxicol Appl Pharmacol 205:177-87. 2005
  10. ncbi request reprint Effects of Cd2+, Pb2+ and CH3Hg+ on high voltage-activated calcium currents in pheochromocytoma (PC12) cells: potency, reversibility, interactions with extracellular Ca2+ and mechanisms of block
    T J Shafer
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Toxicol Lett 99:207-21. 1998

Collaborators

Detail Information

Publications30

  1. ncbi request reprint Effects of pyrethroids on voltage-sensitive calcium channels: a critical evaluation of strengths, weaknesses, data needs, and relationship to assessment of cumulative neurotoxicity
    Timothy J Shafer
    Neurophysiological Toxicology Branch, Neurotoxicology Division, NHEERL, ORD, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Toxicol Appl Pharmacol 196:303-18. 2004
    ..However, at the present time, the data available neither support nor refute conclusively the hypothesis that effects on VSCC are important to the acute neurotoxicity of pyrethroids...
  2. ncbi request reprint Effects of prolonged exposure to nanomolar concentrations of methylmercury on voltage-sensitive sodium and calcium currents in PC12 cells
    Timothy J Shafer
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Brain Res Dev Brain Res 136:151-64. 2002
    ..These results demonstrate that prolonged exposure to low concentrations of CH(3)Hg(+) reduces cationic currents in differentiating PC12 cells, but that current reduction is not always associated with morphological alteration...
  3. doi request reprint Complete inhibition of spontaneous activity in neuronal networks in vitro by deltamethrin and permethrin
    T J Shafer
    Neurotoxicology Division, MD B105 05, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Neurotoxicology 29:203-12. 2008
    ..In spinal cord, DM caused a greater number of biphasic responses (29%) than PM (10%). These results demonstrate that both DM and PM inhibit activity of glutamatergic networks, but with different potencies...
  4. doi request reprint Accumulation of pyrethroid compounds in primary cultures from rat cortex
    Timothy J Shafer
    Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC, USA
    Toxicol In Vitro 24:2053-7. 2010
    ..This data will be useful for making comparisons between in vivo and in vitro studies regarding effective concentrations of pyrethroids...
  5. ncbi request reprint Perturbation of voltage-sensitive Ca2+ channel function by volatile organic solvents
    Timothy J Shafer
    Neurotoxicology Division, MD B105 05, NHEERL, ORD, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    J Pharmacol Exp Ther 315:1109-18. 2005
    ..These data demonstrate that VOCs perturb voltage-sensitive Ca2+ channel function in neurons, an effect that could contribute to the acute neurotoxicity of these compounds...
  6. pmc Developmental neurotoxicity of pyrethroid insecticides: critical review and future research needs
    Timothy J Shafer
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA
    Environ Health Perspect 113:123-36. 2005
    ..These studies should employ state-of-the-science methods to promote a greater understanding of the mode of action of pyrethroids in the developing nervous system...
  7. ncbi request reprint Extracellular calcium is required for the polychlorinated biphenyl-induced increase of intracellular free calcium levels in cerebellar granule cell culture
    W R Mundy
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Toxicology 136:27-39. 1999
    ....
  8. ncbi request reprint Inositol 1,4,5-triphosphate receptor-sensitive Ca(2+) release, store-operated Ca(2+) entry, and cAMP responsive element binding protein phosphorylation in developing cortical cells following exposure to polychlorinated biphenyls
    J R Inglefield
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA
    J Pharmacol Exp Ther 297:762-73. 2001
    ..These results indicate that Ca(2+) disturbances following PCB exposure are associated with 1) discrete alterations in IP(3) receptor-mediated signals and 2) activation of downstream events that impact developing cortical cells...
  9. ncbi request reprint Accumulation of methylmercury or polychlorinated biphenyls in in vitro models of rat neuronal tissue
    C A Meacham
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory ORD, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Toxicol Appl Pharmacol 205:177-87. 2005
    ....
  10. ncbi request reprint Effects of Cd2+, Pb2+ and CH3Hg+ on high voltage-activated calcium currents in pheochromocytoma (PC12) cells: potency, reversibility, interactions with extracellular Ca2+ and mechanisms of block
    T J Shafer
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Toxicol Lett 99:207-21. 1998
    ..These results characterize effects of Cd2+ on Ca2+ channels and demonstrate that Cd2+, Pb2+ and CH3Hg+ differ in their actions on Ca2+ channels...
  11. ncbi request reprint Effects of the chlorotriazine herbicide, cyanazine, on GABA(A) receptors in cortical tissue from rat brain
    T J Shafer
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Toxicology 142:57-68. 1999
    ....
  12. ncbi request reprint Polychlorinated biphenyl-stimulation of Ca(2+) oscillations in developing neocortical cells: a role for excitatory transmitters and L-type voltage-sensitive Ca(2+) channels
    J R Inglefield
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U S Environmental Protection Agency, Research Triangle Park, North Carolina, USA
    J Pharmacol Exp Ther 295:105-13. 2000
    ..These novel findings show the induction of network activity in an in vitro model by A1254 via activation of excitatory GABAergic and/or glutamatergic synaptic activity, depending on the stage of maturation...
  13. ncbi request reprint Volatile organic compounds inhibit human and rat neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes
    Ambuja S Bale
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Toxicol Appl Pharmacol 205:77-88. 2005
    ..This toxicodynamic information will help decrease the uncertainty associated with animal to human extrapolations in the risk assessment of VOCs...
  14. ncbi request reprint Neurotoxicological outcomes of perinatal heptachlor exposure in the rat
    V C Moser
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S EPA, Research Triangle Park, North Carolina 27711, USA
    Toxicol Sci 60:315-26. 2001
    ..Thus, perinatal exposure to heptachlor produced neurochemical and persistent neurobehavioral changes, including alterations in spatial learning and memory...
  15. ncbi request reprint Acute toluene exposure and rat visual function in proportion to momentary brain concentration
    William K Boyes
    Neurotoxicology Division, U S Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA
    Toxicol Sci 99:572-81. 2007
    ..In general, however, the neurophysiological deficits caused by acute toluene exposure could be described by estimates of the momentary concentration of toluene in the brain at the time of VEP evaluation...
  16. ncbi request reprint Approaches to extrapolating animal toxicity data on organic solvents to public health
    Philip J Bushnell
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Neurotoxicology 28:221-6. 2007
    ....
  17. ncbi request reprint Methylmercury effects on ion channels and electrical activity in neurons: future directions
    T J Shafer
    Neurotoxicology Division Division MD 74B, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Cell Mol Biol (Noisy-le-grand) 46:855-64. 2000
    ..Ultimately, it may be possible to develop biologically-based dose-response models of CH3Hg+ neurotoxicity which will be useful in assessing the risks of developmental neurotoxicity of this metal...
  18. ncbi request reprint Evaluating the NMDA-glutamate receptor as a site of action for toluene, in vivo
    Ambuja S Bale
    Neurotoxicology Division, MD B105 05, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA
    Toxicol Sci 98:159-66. 2007
    ..These data support the hypothesis that acute actions of toluene on pattern-elicited VEPs involve NMDA receptors...
  19. doi request reprint Neural progenitor cells as models for high-throughput screens of developmental neurotoxicity: state of the science
    Joseph M Breier
    The Curriculum in Toxicology, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Neurotoxicol Teratol 32:4-15. 2010
    ....
  20. ncbi request reprint Ontogeny of voltage-sensitive calcium channel alpha(1A) and alpha(1E) subunit expression and synaptic function in rat central nervous system
    Connie A Meacham
    Neurotoxicology Division, MD BIO5 5, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Brain Res Dev Brain Res 142:47-65. 2003
    ..Overall, the results suggest that expression of voltage-sensitive Ca(2+) channels during development is dynamic and is important in central nervous system development...
  21. ncbi request reprint Identification of calcium-dependent and -independent signaling pathways involved in polychlorinated biphenyl-induced cyclic AMP-responsive element-binding protein phosphorylation in developing cortical neurons
    J R Inglefield
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Neuroscience 115:559-73. 2002
    ..Furthermore, A1254-induced CREB phosphorylation occurs predominantly in neurons, is dependent on synaptic activity and mediated by Ca(2+)- and PKA-dependent pathways...
  22. ncbi request reprint Time and concentration dependent accumulation of [3H]-deltamethrin in Xenopus laevis oocytes
    Joshua A Harrill
    Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    Toxicol Lett 157:79-88. 2005
    ..5-fold at 0.0005 ppm to 4.1-fold at 5.0 ppm. These data suggest that media concentration does not accurately predict tissue dose at all times for a broad range of deltamethrin concentrations in X. laevis oocytes...
  23. doi request reprint Developmentally-regulated sodium channel subunits are differentially sensitive to alpha-cyano containing pyrethroids
    Connie A Meacham
    Neurotoxicology Division, NHEERL, ORD, U S Environmental Protection Agency, RTP, NC 27711, USA
    Toxicol Appl Pharmacol 231:273-81. 2008
    ..3/beta(3) than on Na(v)1.2/beta(1) channels. These data demonstrate a greater sensitivity of Na(v)1.3 vs Na(v)1.2 channels to deltamethrin and other cyano-containing pyrethroids, particularly in the presence of a beta subunit...
  24. doi request reprint Assessment of chemical effects on neurite outgrowth in PC12 cells using high content screening
    Nicholas M Radio
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U S Environmental Protections Agency, Research Triangle Park, North Carolina 27711, USA
    Toxicol Sci 105:106-18. 2008
    ..Further studies will examine the utility of other in vitro preparations for cell-based assays of neurite outgrowth...
  25. ncbi request reprint Role of NMDA, nicotinic, and GABA receptors in the steady-state visual-evoked potential in rats
    Ambuja S Bale
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
    Pharmacol Biochem Behav 82:635-45. 2005
    ..5 mg/kg, i.p.; n = 8-10 rats/dose) did not significantly alter either F1 or F2 amplitudes. Results indicate important roles for glutamate and nicotinic acetylcholine receptors in both F1 and F2, while GABA receptors contribute to F1...
  26. ncbi request reprint Concentration-dependent accumulation of [3H]-deltamethrin in sodium channel Nav1.2/beta1 expressing Xenopus laevis oocytes
    Jennifer A Watkins
    North Carolina State University, Raleigh, NC 27695, USA
    Toxicol In Vitro 21:1672-7. 2007
    ..51+/-0.07 ppm DLT. There was a significant difference in DLT accumulation between VSSC-transfected oocytes and non-transfected controls, where the transfected oocytes consistently had less accumulation...
  27. ncbi request reprint Toluene inhibits voltage-sensitive calcium channels expressed in pheochromocytoma cells
    Riddick Tillar
    Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA
    Neurochem Int 41:391-7. 2002
    ..These results show that dihydropyridine sensitive and insensitive calcium channels are inhibited by toluene and may represent important sites of action for this compound...
  28. ncbi request reprint Permethrin, but not deltamethrin, increases spontaneous glutamate release from hippocampal neurons in culture
    Douglas A Meyer
    Curriculum in Toxicology, University of North Carolina Chapel Hill, 27599, USA
    Neurotoxicology 27:594-603. 2006
    ..The data indicate that permethrin increases mEPSC frequency via an alteration in intracellular calcium dynamics at the presynaptic terminal...
  29. doi request reprint Pyrethroid modulation of spontaneous neuronal excitability and neurotransmission in hippocampal neurons in culture
    Douglas A Meyer
    Curriculum in Toxicology, University of North Carolina Chapel Hill, Chapel Hill, NC 27599, USA
    Neurotoxicology 29:213-25. 2008
    ..In the absence of GABA receptor antagonists, both DM and PM increased spontaneous spike rates. Altogether, these data demonstrate that DM and PM disrupt network activity in vitro, largely via a VGSC-dependent mechanism...
  30. doi request reprint Development of a high-throughput screening assay for chemical effects on proliferation and viability of immortalized human neural progenitor cells
    Joseph M Breier
    The Curriculum in Toxicology, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
    Toxicol Sci 105:119-33. 2008
    ..Further development of this approach as part of a strategy to screen compounds for potential effects on nervous system development is warranted...