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AX5-19 Subject Exposure Protocol Table AX5-3.1 (cont’d). Summary of Key Studies on Neurochemical Alterations Peak Blood Pb or [Pb] used Observed Effects Reference Rat Hippocampal neurons 2.5–50 µM Pb Cl 2 Pb has a blocking effect on the NMDA subtype of glutamate receptors. Alkondon et al. (1990) Rat Brain protein kinase C 10 −10 M Pb salts Stimulates brain protein kinase C and diacylglycerol-activated calcium. Markovac and Goldstein (1988b) Abbreviations GD—gestational day
AX5-20 Subject Exposure Protocol Rat PND 22 Rat PND 42–64 Rat PND 130–210 250 ppm Pb(Ac) 2 3–6 wks (electro) or 7-13 wks (immuno) 100, 250, or 500 ppm Pb(Ac) 2 in chow for 3-6 wks 0.2% Pb(Ac)2 in water Adult rat Water—0.1-1.0% Pb(Ac)2 from GD 16 to adult Adult rat 0.2% Pb(Ac) 2 in water Adult rat 0.2% Pb(Ac) 2 in water PND 0-21 Rat PND 90–130 Table AX5-3.2. Summary of Key Studies on Neurophysiological Assessments 750 ppm Pb(Ac) 2 chow from 50 days pre-mating to experimental use Rat 7–18 mo Water—0.2% Pb(Ac) 2 from GD 16 to experimental use Rat PND 13–140 750 ppm Pb(Ac) 2 chow from 50 days pre-mating to experimental use Peak Blood Pb or [Pb] used Observed Effects Reference 30.8 µg/dL Reduces midbrain dopamine impulse flow and decreases dopamine D1 receptor sensitivity in nucleus accumbens. Tavakoli-Nezhad and Pitts (2005) 54.0 µg/dL Decrease in number of spontaneously active midbrain dopamine neurons. Tavakoli-Nezhad et al. (2001) Review paper examining glutamatergic components contributing to impairments in synaptic plasticity. Lasley and Gilbert (2000) 75.4 µg/dL Deficits in synaptic plasticity in the dentate gyrus from early exposure. Gilbert et al. (1999a) 117.6 µg/dL Biphasic dose-dependent inhibition of hippocampal LTP. Gilbert et al. (1999b) 30.1 µg/dL Chronic Pb exposure significantly decreases range of synaptic plasticity. Zhao et al. (1999) 30.1 µg/dL Impairments in LTP and paired-pulse facilitation in the hippocampal DG. Ruan et al. (1998) 16.04 µg/100 mL NMDA-dependent forms of synaptic plasticity are more vulnerable than NMDA-independent potentiation or paired pulse-facilitation. Gutowski et al. (1998) — Impairs ability to maintain LTP over time in the dentate gyrus. Gilbert and Mack (1998) 28.5 µg/dL Paired-pulse stimulation of CA3 region shows inhibitory mechanisms. Gutowski et al. (1997) Adult rat Water—0.2% Pb(Ac)2 from PND 0–adult — Chronic Pb increases the threshold for LTP in dentate gyrus in vivo. Gilbert et al. (1996) Rat PND 4–30 Hippocampal neurons 1–100 µM Pb Cl2 Identified the nicotinic acetylcholine receptor as a target for Pb. Ishihara et al. (1995) Rat 750 ppm Pb(Ac) 2 chow from 50 days pre-mating to experimental use 16.2 µg/100 mL LTP and learning are impaired if exposed to Pb in the immature brain. Altmann et al. (1993) Abbreviations GD—gestational day
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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
Page 109 and 110: List of Tables (cont’d) AX5-6.3 G
Page 111 and 112: List of Tables (cont’d) AX5-9.3 S
Page 113 and 114: Principal Authors (cont’d) Author
Page 115 and 116: Principal Authors Authors, Contribu
Page 117 and 118: Principle Authors (cont’d) Author
Page 119 and 120: Technical Support Staff U.S. Enviro
Page 121 and 122: Members (cont’d) U.S. Environment
Page 123 and 124: ANP atrial natriuretic peptide AP a
Page 125 and 126: CCE Coordination Center for Effects
Page 127 and 128: DR drinking water DSA delayed spati
Page 129 and 130: FTII Fagan Test of Infant Intellige
Page 131 and 132: H3PO4 phosphoric acid HPRT hypoxant
Page 133 and 134: MATC maximum acceptable threshold c
Page 135 and 136: NOS nitric oxide synthase; not othe
Page 137 and 138: PPVT-R Peabody Picture Vocabulary T
Page 139 and 140: SOPR sperm-oocyte penetration rate
Page 141 and 142: vit C vitamin C vit E vitamin E VMA
Page 143 and 144: AX5-2 Table AX5-2.1. Effect of Lead
Page 145 and 146: AX5-4 Table AX5-2.1 (cont’d). Eff
Page 147 and 148: AX5-6 Table AX5-2.2. Lead, Erythroc
Page 149 and 150: AX5-8 Table AX5-2.2 (cont’d). Lea
Page 151 and 152: AX5-10 Table AX5-2.4. Lead Effects
Page 153 and 154: AX5-12 Table AX5-2.5. Lead Interact
Page 155 and 156: AX5-14 Table AX5-2.7. Lead, Erythro
Page 157 and 158: AX5-16 Subject Exposure Protocol Ra
Page 159: AX5-18 Subject Exposure Protocol Ra
Page 163 and 164: AX5-22 Subject Rat, female, 22 wks
Page 165 and 166: AX5-24 Subject Rat, F344, male Expo
Page 167 and 168: AX5-26 Subject Monkey, cynomolgus,
Page 169 and 170: AX5-28 Subject Rat, SD, male, PND 6
Page 171 and 172: AX5-30 Subject Monkey, cynomolgus,
Page 173 and 174: AX5-32 Subject Exposure Protocol Ta
Page 175 and 176: AX5-34 Table AX5-3.6 (cont’d). Ke
Page 177 and 178: AX5-36 Table AX5-3.6 (cont’d). Ke
Page 179 and 180: AX5-38 Citation Al-Hakkak et al. (1
Page 181 and 182: AX5-40 Citation Fox et al. (1997)
Page 183 and 184: AX5-42 Citation Pinon- Lataillade e
Page 185 and 186: AX5-44 Citation Wiebe et al. (1998)
Page 187 and 188: AX5-46 Citation Chowdhuri et al. (2
Page 189 and 190: 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)
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AX5-70 Reference Shelkovnikov and G
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AX5-72 Reference Fujiwara and Kaji
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AX5-74 Reference Fugiwara et al. (1
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AX5-76 Table AX5-6.1. Genotoxic/Car
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AX5-80 Table AX5-6.3 (cont’d). Ge
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AX5-86 Compound Table AX5-6.6. Geno
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AX5-96 Table AX5-6.10 (cont’d). G
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AX5-98 Table AX5-6.12. Genotoxic/Ca
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AX5-100 Table AX5-6.14. Genotoxic/C
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AX5-102 Compound Table AX5-6.16. Ge
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AX5-104 Table AX5-6.18. Genotoxic/C
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AX5-106 Table AX5-6.18 (cont’d).
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AX5-110 Compound Assay (Concentrati
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AX5-112 Table AX5-7.1. Light Micros
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AX5-114 Table AX5-7.2. Lead and Fre
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AX5-116 Table AX5-7.2 (cont’d). L
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AX5-118 Table AX5-7.4. Effect of Ch
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AX5-120 Table AX5-7.5 (cont’d). E
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AX5-122 Table AX5-8.1. Bone Growth
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AX5-124 Table AX5-8.1 (cont’d). B
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AX5-126 Table AX5-8.2. Regulation o
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AX5-128 Table AX5-8.2 (cont’d). R
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AX5-136 Table AX5-8.4. Bone Lead as
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AX5-142 Table AX5-8.5. Uptake of Le
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AX5-144 Table AX5-8.7. Effects of L
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ANNEX TABLES AX5-9 AX5-146
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AX5-148 Nature of Exposure Table AX
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AX5-150 Table AX5-9.2. Effect of Le
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AX5-152 Species Strain/Gender Age M
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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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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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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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SOPR sperm-oocyte penetration rate
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vit C vitamin C vit E vitamin E VMA
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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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AX6-30 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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AX6-166 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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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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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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SOPR sperm-oocyte penetration rate
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vit C vitamin C vit E vitamin E VMA
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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
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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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