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AX5-101 Compound Table AX5-6.15. Genotoxic/Carcinogenic Effects of Lead—Epigenetic Effects and Mixture Interactions—Human Assay (Concentration and Exposure Time) Pb acetate Tyrosine aminotransferase expression and activity (0.3–10 µM for 24–48 h) PKC activity: 10 µM for 48 h Pb nitrate EROD/MROD activity (10–100 µM for 24 h) NAD(P)H: quinone oxidoreductase activity (10–100 µM for 24 h) Glutathione-S-transferase Ya activity (10–100 µM for 24 h) Pb nitrate NAD(P)H: quinone oxidoreductase activity (25 µM for 24 h) Glutathione-S-transferase Ya activity (25 µM for 24 h) Abbreviations Medium and Components DMEM—Dulbecco’s Minimal Essential Medium; FBS—Fetal Bovine Serum FCS—Fetal Calf Serum Cell Type and Culture Medium Co-exposure Effects Reference H4-IIE-C3— human hepatoma cells in DMEM + 2.5% FCS Hepa 1c1c7 wild type cells in DMEM + 10% FBS C12- AHRdeficient Hepa 1c1c7 cells in DMEM + 10% FBS Dexamethasone (0.1 µM for 16 h), or calcium chloride (10 µM) or genistein (100 µM to block PKC activity) TCDD (0.1 nM), 3-methyl cholanthrene (0.25 µM), betanaptflavone (10 µM), benzo(a)pyrene (1 µM) TCDD (0.1 nM), 3-methyl cholanthrene (0.25 µM), betanaptflavone (10 µM), benzo(a)pyrene (1 µM) Differences between the serum types are unclear as insufficient details are provided by authors to distinguish. Pb acetate inhibited glucocorticoid –induction of tyrosine aminotransferase in a time- and dose-dependent manner. Co-treatment with calcium reduced the effects of Pb. Co-treatment with genistein increased the effects of Pb. Pb acetate decreases PKC activity and its translocation from the cytosol to the particulate cellular fraction. Pb did not affect EROD/MROD activity. Pb reduced CYP1A1 induction by TCDD, 3-methyl cholanthrene, beta-naptflavone, benzo(a)pyrene. Pb increased NAD(P)H: quinone oxidoreductase activity Pb increased NAD(P)H: quinone oxidoreductase activity induction by TCDD, 3-methyl cholanthrene, beta-naptflavone, benzo(a)pyrene. 10 µM increased Glutathione-S-transferase Ya activity. 25 and 100 µM increased Glutathione-S-transferase Ya activity. Pb nitrate did not affect Glutathione-S-transferase Ya induction by TCDD, 3-methyl cholanthrene, beta-naptflavone, benzo(a)pyrene. Pb nitrate did not increase NAD(P)H: quinone oxidoreductase and Glutathione-S-transferase Ya activity Pb increased NAD(P)H: quinone oxidoreductase activity induction by TCDD, 3-methyl cholanthrene, beta-naptflavone, benzo(a)pyrene. Pb did not affect Glutathione-S-transferase Ya induction by TCDD, 3methyl cholanthrene, beta-naptflavone, benzo(a)pyrene. Tonner and Heiman (1997) Korashy and El-Kadi (2004) Korashy and El Kadi (2004)
AX5-102 Compound Table AX5-6.16. Genotoxic/Carcinogenic Effects of Lead—Epigenetic Effects and Mixture Interactions—DNA Repair—Human Assay (Concentration and Exposure Time) Pb acetate DNA strand breaks as nucleoid sedimentation (500 µM for 20–25 h) Abbreviations Medium and Components AMEM—Alpha Minimal Essential Medium; FBS—Fetal Bovine Serum Cell Type and Culture Medium Co-exposure Effects Reference HeLa Cells in AMEM + 5% FBS UV (5 J/m 2 ) Pb acetate alone did not induce single strand breaks. UV did induce strand breaks. Co-exposure of Pb and UV cause DNA strand breaks to persist longer suggesting an inhibition of repair. Hartwig et al. (1990)
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October 2006 EPA/600/R-05/144bF Air
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PREFACE National Ambient Air Qualit
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NCEA acknowledges the valuable cont
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Table of Contents Page PREFACE ....
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Authors, Contributors, and Reviewer
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Contributors and Reviewers (cont’
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Contributors and Reviewers (cont’
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Executive Direction U.S. Environmen
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Chair U.S. Environmental Protection
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Abbreviations and Acronyms αFGF α
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BLL blood lead level BLM biotic lig
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CRI chronic renal insufficiency CSF
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EPT macroinvertebrates from the Eph
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GRP78 glucose-regulated protein 78
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KABC Kaufman Assessment Battery for
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NADP nicotinamide adenine dinucleot
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Pb(Ac)2 lead acetate PbB blood lead
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RR RT RSEM RSUC RT ∑SEM SA7 SAB S
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TGF transforming growth factor TH t
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AX4. CHAPTER 4 ANNEX ANNEX TABLES A
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AX4-3 Table AX4-1 (cont’d). Analy
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AX4-5 Table AX4-2 (cont’d). Summa
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AX4-7 Table AX4-3. Bone Lead Measur
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AX4-9 Reference, Study Location, an
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AX4-11 Table AX4-4 (cont’d). Bone
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AX4-19 Reference, Study Location, a
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AX4-37 Table AX4-9 (cont’d). Lead
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AX4-39 Table AX4-11. Summary of Sel
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AX4-41 Table AX4-11 (cont’d). Sum
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AX-43 Table AX4-12 (cont’d). Summ
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Barltrop, D.; Meek, F. (1979) Effec
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Carroll, R. J.; Galindo, C. D. (199
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Flegal, A. R.; Smith, D. R. (1995)
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Gulson, B.; Mizon, K.; Smith, H.; E
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Khoury, G. A.; Diamond, G. L. (2003
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Morgan, W. D.; Ryde, S. J.; Jones,
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Pounds, J. G.; Leggett, R. W. (1998
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Skerfving, S. (1988) Biological mon
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U.S. Environmental Protection Agenc
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Air Quality Criteria for Lead Volum
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AQCD/Addendum and 1990 Supplement,
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Air Quality Criteria for Lead (Seco
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List of Tables AX4-1 Analytical Met
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List of Tables (cont’d) AX5-6.3 G
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List of Tables (cont’d) AX5-9.3 S
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Principal Authors (cont’d) Author
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Principal Authors Authors, Contribu
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Principle Authors (cont’d) Author
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Technical Support Staff U.S. Enviro
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Members (cont’d) U.S. Environment
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ANP atrial natriuretic peptide AP a
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CCE Coordination Center for Effects
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DR drinking water DSA delayed spati
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FTII Fagan Test of Infant Intellige
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H3PO4 phosphoric acid HPRT hypoxant
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MATC maximum acceptable threshold c
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NOS nitric oxide synthase; not othe
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PPVT-R Peabody Picture Vocabulary T
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SOPR sperm-oocyte penetration rate
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vit C vitamin C vit E vitamin E VMA
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AX5-2 Table AX5-2.1. Effect of Lead
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AX5-4 Table AX5-2.1 (cont’d). Eff
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AX5-6 Table AX5-2.2. Lead, Erythroc
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AX5-8 Table AX5-2.2 (cont’d). Lea
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AX5-10 Table AX5-2.4. Lead Effects
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AX5-12 Table AX5-2.5. Lead Interact
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AX5-14 Table AX5-2.7. Lead, Erythro
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AX5-16 Subject Exposure Protocol Ra
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AX5-22 Subject Rat, female, 22 wks
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AX5-24 Subject Rat, F344, male Expo
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AX5-26 Subject Monkey, cynomolgus,
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AX5-28 Subject Rat, SD, male, PND 6
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AX5-30 Subject Monkey, cynomolgus,
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AX5-32 Subject Exposure Protocol Ta
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AX5-34 Table AX5-3.6 (cont’d). Ke
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AX5-36 Table AX5-3.6 (cont’d). Ke
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AX5-38 Citation Al-Hakkak et al. (1
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AX5-40 Citation Fox et al. (1997)
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AX5-42 Citation Pinon- Lataillade e
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AX5-44 Citation Wiebe et al. (1998)
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AX5-46 Citation Chowdhuri et al. (2
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AX5-48 Citation Graca et al. (2004)
Page 191 and 192: AX5-50 Citation Marchlewicz et al.
Page 193 and 194: AX5-52 Table AX5-4.2 (cont’d). Ef
Page 195 and 196: AX5-54 Citation Sokol et al. (1985)
Page 197 and 198: AX5-56 Citation Table AX5-4.3 (cont
Page 199 and 200: AX5-58 Citation Priya et al. (2004)
Page 201 and 202: ANNEX TABLES AX5-5 AX5-60
Page 203 and 204: AX5-62 Table AX5-5.1 (cont’d). In
Page 205 and 206: AX5-64 Table AX5-5.1 (cont’d). In
Page 207 and 208: AX5-66 Reference Watts et al. (1995
Page 209 and 210: AX5-68 Reference Lai et al. (2002)
Page 211 and 212: AX5-70 Reference Shelkovnikov and G
Page 213 and 214: AX5-72 Reference Fujiwara and Kaji
Page 215 and 216: AX5-74 Reference Fugiwara et al. (1
Page 217 and 218: AX5-76 Table AX5-6.1. Genotoxic/Car
Page 221 and 222: AX5-80 Table AX5-6.3 (cont’d). Ge
Page 227 and 228: AX5-86 Compound Table AX5-6.6. Geno
Page 237 and 238: AX5-96 Table AX5-6.10 (cont’d). G
Page 239 and 240: AX5-98 Table AX5-6.12. Genotoxic/Ca
Page 241: AX5-100 Table AX5-6.14. Genotoxic/C
Page 245 and 246: AX5-104 Table AX5-6.18. Genotoxic/C
Page 247 and 248: AX5-106 Table AX5-6.18 (cont’d).
Page 249 and 250: AX5-108 Table AX5-6.19 (cont’d).
Page 251 and 252: AX5-110 Compound Assay (Concentrati
Page 253 and 254: AX5-112 Table AX5-7.1. Light Micros
Page 255 and 256: AX5-114 Table AX5-7.2. Lead and Fre
Page 257 and 258: AX5-116 Table AX5-7.2 (cont’d). L
Page 259 and 260: AX5-118 Table AX5-7.4. Effect of Ch
Page 261 and 262: AX5-120 Table AX5-7.5 (cont’d). E
Page 263 and 264: AX5-122 Table AX5-8.1. Bone Growth
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Page 267 and 268: AX5-126 Table AX5-8.2. Regulation o
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Page 289 and 290: AX5-148 Nature of Exposure Table AX
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AX5-152 Species Strain/Gender Age M
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AX5-154 Table AX5-9.5 (cont’d). E
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ANNEX TABLES AX5-10 AX5-156
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AX5-158 Table AX5-10.1 (cont’d).
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AX5-162 Table AX5-10.2. Biochemical
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AX5-166 Table AX5-10.4. Lead, Oxida
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AX5-180 Table AX5-10.7. Lead and In
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AX5-184 Table AX5-10.9. Lead, Calci
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AX5-188 Source Organ Species Table
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REFERENCES Abdollahi, M.; Dehpour,
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Bataineh, H.; Al-Hamood, M. H.; Elb
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Buchet, J.-P.; Roels, H. E.; Huberm
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Cline, H. T.; Witte, S.; Jones, K.
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Cory-Slechta, D. A.; McCoy, L.; Ric
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children's health: immune and respi
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Ferguson, C.; Kern, M.; Audesirk, G
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Fullmer, C. S. (1991) Intestinal ca
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Goyer, R. A.; Leonard, D. L.; Moore
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Hengstler, J. G.; Bolm-Audorff, U.;
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Jacquet, P.; Leonard, A.; Gerber, G
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Kim, K. A.; Chakraborti, T.; Goldst
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Laughlin, N. K.; Bowman, R. E.; Fra
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Maldonado-Vega, M.; Cerbón-Solórz
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Moorman, W. J.; Skaggs, S. R.; Clar
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O'Flaherty, E. J.; Inskip, M. J.; F
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Price, R. G.; Taylor, S. A.; Chiver
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Rodamilans, M.; Mtz.-Osaba, M. J.;
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Schlipkoter, H.-W.; Frieler, L. (19
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Skoczyńska, A.; Smolik, R.; Jeleń
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Tavakoli-Nezhad, M.; Pitts, D. K. (
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Valentino, M.; Governa, M.; Marchis
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Wetmur, J. G.; Lehnert, G.; Desnick
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Zhou, J.; Xu, Y.-H.; Chang, H.-F. (
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Air Quality Criteria for Lead Volum
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The purpose of this revised Lead AQ
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Air Quality Criteria for Lead (Seco
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List of Tables Number Page AX6-2.1
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List of Tables (cont’d) Number Pa
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ANOVA analysis of variance ANP atri
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CCD charge-coupled device CCE Coord
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DPPD N-N-diphenyl-p-phynylene-diami
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FTES free testosterone FTII Fagan T
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HPLC high-pressure liquid chromatog
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MAO monoamine oxidase MATC maximum
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NORs nucleolar organizing regions N
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ppm parts per million PPVT-R Peabod
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AX6-4 Table AX6-2.1 (cont’d). Pro
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AX6-10 Table AX6-2.2 (cont’d). Me
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AX6-12 Table AX6-2.3 (cont’d). Cr
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AX6-14 Table AX6-2.4. Effects of Le
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AX6-16 Table AX6-2.4 (cont’d). Ef
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AX6-24 Table AX6-2.8. Effects of Le
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AX6-28 Table AX6-2.10 (cont’d). R
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AX6-30 Table AX6-3.1. Neurobehavior
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AX6-32 Table AX6-3.1 (cont’d). Ne
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AX6-34 Table AX6-3.2 (cont’d). Sy
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AX6-36 Table AX6-3.3. Neurobehavior
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AX6-50 Table AX6-3.4 (cont’d). Me
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AX6-56 Table AX6-3.6. Evoked Potent
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AX6-58 Table AX6-3.6 (cont’d). Ev
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AX6-60 Table AX6-3.7 (cont’d). Po
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AX6-62 Table AX6-3.7 (cont’d). Po
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AX6-64 Table AX6-3.8 (cont’d). Oc
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AX6-66 Table AX6-3.9. Other Neurolo
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AX6-68 Table AX6-3.9 (cont’d). Ot
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AX6-70 Table AX6-4.1. Renal Effects
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AX6-72 Table AX6-4.1 (cont’d). Re
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AX6-104 Table AX6-4.3. Renal Effect
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AX6-130 Table AX6-5.1. Effects of L
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AX6-166 Table AX6-5.4. Cardiovascul
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AX6-170 Table AX6-6.1 (cont’d). P
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AX172 Table AX6-6.1 (cont’d). Pla
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AX6-174 Table AX6-6.2. Lead Exposur
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AX6-176 Table AX6-6.2 (cont’d). L
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AX6-186 Table AX6-7.2. Key Occupati
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AX6-188 Table AX6-7.2 (cont’d). K
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AX6-190 Table AX6-7.2 (cont’d). K
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AX6-192 Table AX6-7.3. Key Studies
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AX6-194 Table AX6-7.4. Other Studie
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AX6-196 Table AX6-7.4 (cont’d). O
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AX6-224 Table 6-9.2 (cont’d). Eff
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AX6-232 Table AX6-9.3 (cont’d.).
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AX6-258 Table AX6-9.10. Effects of
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REFERENCES Abbate, C.; Buceti, R.;
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Baghurst, P. A.; McMichael, A. J.;
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Bolla, K. I.; Schwartz, B. S.; Stew
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Chia, K. S.; Jeyaratnam, J.; Tan, C
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David, O. J.; Clark, J.; Hoffman, S
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Englyst, V.; Lundstrom, N. G.; Gerh
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Gennart, J. P.; Bernard, A.; Lauwer
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Haraguchi, T.; Ishizu, H.; Takehisa
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Jemal, A.; Graubard, B. I.; Devesa,
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Lanphear, B. P.; Howard, C.; Eberly
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Lundström, N.-G.; Nordberg, G.; En
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Muntner, P.; He, J.; Vupputuri, S.;
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Paksy, K.; Gáti, I.; Náray, M.; R
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Rhainds, M.; Levallois, P.; Dewaill
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Sargent, J. D.; Dalton, M. A.; O'Co
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Sheffet, A.; Thind, I.; Miller, A.
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Stevens, L. A.; Levey, A. S. (2005b
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Van Larebeke, N.; Koppen, G.; Nelen
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Winker, R.; Ponocny-Seliger, E.; R
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October 2006 EPA/600/R-05/144bF Air
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PREFACE National Ambient Air Qualit
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drafts of document materials were r
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Table of Contents PREFACE..........
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Table of Contents (cont’d) II-ix
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List of Tables (cont’d) AX7-2.3.1
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List of Figures (cont’d) Number P
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ANOVA analysis of variance ANP atri
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CCD charge-coupled device CCE Coord
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DPPD N-N-diphenyl-p-phynylene-diami
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FTES free testosterone FTII Fagan T
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HPLC high-pressure liquid chromatog
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MAO monoamine oxidase MATC maximum
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NORs nucleolar organizing regions N
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ppm parts per million PPVT-R Peabod
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Pb is ideally suited for this task.
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Concept For a given metal or metall
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(1979) observed that “the smaller
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Figure AX7-1.1.3. Illustration of p
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• Colorimetric • Electrochemica
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Figure AX7-1.1.5. Bulk lead versus
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diffraction lines and comparing the
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The major disadvantage of SIMS to s
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techniques can be useful in a study
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have included phosphoric acid (H3PO
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to 15 years after biosolid applicat
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thin films (DGT), and ICP technique
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completely extract targeted phases.
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epresents Eb. The precise energy re
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1974; Ruby et al., 1994). However,
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T1/2 = 14 × 10 9 year). The result
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floor) time-series data to evaluate
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contributions of dry deposition may
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Compared to their estimated 20th-ce
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thought to enter the plant via the
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soil was not allowed to equilibrate
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Lead concentrations in various tiss
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that the nematode may detoxify Pb v
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plasma levels of uric acid and crea
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effective use of glutathione metabo
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and oats (Avena sativa) had signifi
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other metals is inconsistent (Påhl
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Speciation and Form of Lead Recent
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organism responses to Pb. Section A
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Primary Producers Commonly reported
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solution and minimal translocation
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AX7.1.3.3 Recent Studies on the Eff
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AX7-66 Avian Species Reproduction J
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AX7-68 Avian Species American kestr
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Very little research has been done
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AX7-72 Mammalian Species Reproducti
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AX7-74 Mammalian Species No. of Dos
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AX7-80 Mammalia n Species No. of Do
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A literature search and review was
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Table AX7-1.3.6. Invertebrate Toxic
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The effects of Pb-chloride on the p
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Ecological Soil Screening Levels (E
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Since the movement and fate of Pb i
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Land Use and Industry Changes in la
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lakes in the United Kingdom the dis
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zinc; had very low pH; and were det
Page 855 and 856:
Sites Affected by Long-Range Lead T
Page 857 and 858:
iomass carbon. Because of this link
Page 859 and 860:
in an oak woodland site 3 km from a
Page 861 and 862:
the forested Lehstenbach catchment
Page 863 and 864:
there is little evidence that Pb ac
Page 865 and 866:
ecosystems. Just as in the terrestr
Page 867 and 868:
To develop chronic AWQC, acceptable
Page 869 and 870:
for the binding of free-metal ion a
Page 871 and 872:
partition in sediment between acid-
Page 873 and 874:
AX7.2.1.5 Metal Mixtures As discuss
Page 875 and 876:
varies from 4:1 in rural streams to
Page 877 and 878:
Organic compounds in surface waters
Page 879 and 880:
solution phase, complexation with c
Page 881 and 882:
The NAWQA dataset was chosen over o
Page 883 and 884:
Lead Distributions Generated from t
Page 885 and 886:
AX7-128 Figure AX7-2.2.3. Spatial d
Page 887 and 888:
AX7-130 Figure AX7-2.2.5. Spatial d
Page 889 and 890:
AX7-132 ` Figure AX7-2.2.7. Spatial
Page 891 and 892:
Figure AX7-2.2.8. Frequency distrib
Page 893 and 894:
Table AX7-2.2.4. Summary Statistics
Page 895 and 896:
Table AX7-2.2.5. Comparison of NCBP
Page 897 and 898:
AX7-140 Figure AX7-2.2.13. Spatial
Page 899 and 900:
calculations indicate that only a s
Page 901 and 902:
from municipal sewage, storm runoff
Page 903 and 904:
AX7.2.3 Aquatic Species Response/Mo
Page 905 and 906:
aquatic plants and insects and on t
Page 907 and 908:
designed to model uptake, MINTEQ pr
Page 909 and 910:
sequestering to organ tissues). The
Page 911 and 912:
AbdAllah and Moustafa (2002) studie
Page 913 and 914:
Summary of Detoxifiction Processes
Page 915 and 916:
1.1 µg/L Cd, 12 µg/L Cu, 55 µg/L
Page 917 and 918:
Studies have identified ALAD in fis
Page 919 and 920:
metals over nonessential metals. Th
Page 921 and 922:
In summary, relationships between a
Page 923 and 924:
potential toxic effects in other or
Page 925 and 926:
esulted in 91.7% survival (Horne an
Page 927 and 928:
carbon sources (including glucose),
Page 929 and 930:
separate concentration-effects mode
Page 931 and 932:
1994. mSQGQs are useful to risk ass
Page 933 and 934:
Algae The 1986 Lead AQCD (U.S. Envi
Page 935 and 936:
observed in Selenastrum capricornut
Page 937 and 938:
Nitrate uptake reported after 48, 7
Page 939 and 940:
1997). The most sensitive primary p
Page 941 and 942:
Freshwater Invertebrates Acute and
Page 943 and 944:
AX7-186 Amphipod (Hyalella azteca)
Page 945 and 946:
concentrations of
Page 947 and 948:
AX7-190 Freshwater Species Chemical
Page 949 and 950:
AX7-192 Species Chemical Frogs (Ran
Page 951 and 952:
studied using Spirodela polyrhiza,
Page 953 and 954:
However, in other cases multivariat
Page 955 and 956:
species was observed. Similar, sign
Page 957 and 958:
AX7-200 Table AX7-2.5.2. Essential
Page 959 and 960:
AX7-202 Table AX7-2.5.2 (cont’d).
Page 961 and 962:
variables, it does not imply causat
Page 963 and 964:
Poulton et al. (1995), the effects
Page 965 and 966:
metal levels. Furthermore, although
Page 967 and 968:
environment through bioaccumulation
Page 969 and 970:
Angle, C. R.; McIntire, M. S.; Colu
Page 971 and 972:
Black, M. C.; Ferrell, J. R.; Horni
Page 973 and 974:
Clements, W. H. (1994) Benthic inve
Page 975 and 976:
Ekenler, M.; Tabatabai, M. (2002) E
Page 977 and 978:
Getz, L. L.; Haney, A. W.; Larimore
Page 979 and 980:
Houlton, B. Z.; Driscoll, C. T.; Fa
Page 981 and 982:
Krüger, F.; Gröngröft, A. (2003)
Page 983 and 984:
Manceau, A.; Lanson, B.; Schlegel,
Page 985 and 986:
Niyogi, S.; Wood, C. M. (2003) Effe
Page 987 and 988:
Rand, G. M.; Wells, P. G.; McCarty,
Page 989 and 990:
Scherer, E.; McNicol, R. E. (1998)
Page 991 and 992:
Sturges, W. T.; Barrie, L. A. (1987
Page 993 and 994:
U.S. Environmental Protection Agenc
Page 995 and 996:
Zenk, M. H. (1996) Heavy metal deto
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