EPA 600/8 77 017
                  December 1977
                  Special Series
Air Quality
Criteria for
    Office of Research and Development
    U.S. Environmental Protection Agency
          Washington, D.C. 20460

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                                            EPA-600/8-77-017
                                               December 1977
AIR  QUALITY  CRITERIA
                 FOR
               LEAD
U.S. ENVIRONMENTAL PROTECTION AGENCY
 OFFICE OF RESEARCH AND DEVELOPMENT
         WASHINGTON, D.C. 20460
    For sale by the Superintendent of Documents, U.S. Government
          Printing Office, Washington, D.C. 20402

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                              PREFACE
  This document has been prepared pursuant to Section 108(a)(2) of the Clean Air
Act, as amended, and the Administrator's action on March 31, 1976, of listing lead
as a criteria pollutant. Under the Act, the issuance of air quality criteria is a vital
step in a program of responsible technological, social, and political action to pro-
tect the public from the adverse effects of air pollution.
  These health and welfare criteria fulfill the regulatory purpose of serving as the
basis upon which the Administrator must promulgate national primary and second-
ary ambient air quality standards for lead under Section 109 of the Clean Air Act.
The proposed standards are being published concurrently with  the publication of
this criteria document.
  Although the  preparation of  a criteria  document requires  a comprehensive
review and evaluation of the current scientific knowledge regarding the air pollu-
tant in question, the document does not constitute a complete,  in-depth scientific
review. The references cited do not constitute a complete bibliography. The objec-
tive is to evaluate the scientific data base and to formulate criteria which may serve
as the basis for decisions regarding the promulgation of a national ambient air
quality standard for lead.
  In the case of  lead, as well as other air pollutants, adverse health effects are a
consequence of the total body burden resulting from exposure via all routes of in-
take. It is necessary, therefore, to evaluate  the relative contribution made by in-
halation and ingestion of atmospheric lead to the total body burden.
  The Agency is pleased to acknowledge the efforts and  contributions of all per-
sons' and groups who have participated as authors or reviewers to this document. In
the last analysis,  however, the Environmental Protection Agency is responsible for
its content.
                                     DOUGLAS M. COSTLE
                                     Administrator
                                     U.S. Environmental Protection Agency
                                    in

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                             ABSTRACT
  This document summarizes current knowledge about the relationships of air-
borne lead to man and his environment. The effects that have been observed to oc-
cur when  airborne lead has reached or exceeded specific levels for specific time
periods constitute the central criteria on which EPA will base a national ambient
air quality standard for lead.
  Although this document deals mainly with airborne lead, it also outlines other
environmental  routes of exposure. Primary  exposure to airborne lead occurs
directly via inhalation, and its sources are relatively easy to identify. Secondary ex-
posure may occur through ingestion of foods from crops contaminated by airborne
lead or, especially in children, through mouthing of nonfood items and materials so
contaminated. Exposures to nonairborne lead may also be direct and indirect, and
routes include ingestion of foods containing lead attributable to natural uptake and
to processing.
  In man, lead primarily affects red blood cells, the central and peripheral nervous
systems, soft  tissues such as liver  and kidney, and bone; the latter ultimately se-
questers 95 percent of the body's lead burden. Significant biological indices of ex-
posure to lead  include microgram quantities  of lead and  of erythrocyte pro-
toporphyrin (EP) per deciliter of blood (yug/dl). Adverse effects range from ele-
vated EP  and mild anemia at 20 to 40  /tig Pb/dl—through gastrointestinal, renal,
and hepatic pathologies—to severe neurobehavioral impairment at >80to 120 fj.g
Pb/dl, sometimes culminating  at  those  levels in convulsions and abrupt  death.
Preschool children and developing fetuses are the populations at greatest risk.
                                     IV

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              SCIENCE ADVISORY BOARD

           SUBCOMMITTEE ON SCIENTIFIC

     CRITERIA FOR ENVIRONMENTAL LEAD

  The substance of this document was review by a Subcommittee on Scientific Cri-
teria for Environmental Lead, Science Advisory Board, in public  session.

CHAIRMAN:
Dr.  Roger O. McClellan, Director of Inhalation Toxicology Research Institute,
     Lovelace Foundation, P.O. Box 5890, Albuquerque, New Mexico 87115
CONSULTANTS:
Dr.  J. Julian Chisolm, Jr., Senior Staff Pediatrician, Baltimore City Hospital,
     4940 Eastern Avenue, Baltimore, Maryland 21224, and Associate Professor
     of Pediatrics, Johns Hopkins University School of Medicine
Dr.  Paul B. Hammond, Professor of Environmental Health, Department of En-
     vironmental Health,  University of Cincinnati Medical Center, 3223 Eden
     Avenue, Cincinnati, Ohio 45267
Dr.  James G. Horsfall, Director Emeritus, Department of Plant Pathology and
     Botany, Connecticut Agriculture Experiment Station, New Haven, Connecti-
     cut 06504
MEMBERS:
Dr.  Samuel S. Epstein, Professor of Occupational and Environmental Medicine,
     School of Public Health, University of Illinois, P.O. Box  6998, Chicago, Il-
     linois 60680
Dr.  Edward  F. Ferrand, Assistant Commissioner for Sciences and  Technology,
     New York City Dept. for Air Resources, 51 Astor Place, New York,  New
     York 10003
Dr.  Sheldon K. Friedlander, Professor of Chemical Engineering and Environ-
     mental Health Engineering, W. M. Keck Laboratory, California Institute of
     Technology, Pasadena, California 91109
Dr.  Jennifer L. Kelsey, Associate  Professor  of Epidemiology, Yale University
     School of Medicine, Department of Epidemiology and Public Health, 60 Col-
     lege Street, New Haven, Connecticut 06504
Dr.  Ruth Levine,  Chairman, Graduate Division of Medicine  and Dentistry,
     Boston University College of Medicine, Boston, Massachusetts 02118
     Mailing address: 212  Crafts Road, Chestnut Hill, Brookline, Massachusetts
     02167
Dr.  Bailus Walker, Jr., Director, Environmental Health Administration, Depart-
     ment of Environmental Services, Government of the District of Columbia,
     801  North Capitol, NE, Washington,  D.C. 20002
STAFF OFFICER:
Mr.  Ernst Linde, Scientist  Administrator, Science Advisory Board, U.S. Environ-
     mental  Protection Agency, Crystal Mall Building 2,  1921  Jefferson Davis
     Highway, Arlington, Virginia 20460

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         CONTRIBUTORS  AND  REVIEWERS
Mr.  Gerald G. Akland, Environmental Monitoring and Support Laboratory, En-
     vironmental  Research  Center, U.S.  Environmental Protection  Agency,
     Research Triangle Park, North Carolina 27711
Dr.  C. Alex Alexander, Adjunct  Professor of Medicine and Chief of Hospital
     Medical Staff, School of Medicine, Wright State University, Dayton, Ohio
     45431
Dr.  A. P.  Altshuller, Director, Environmental Sciences  Research  Laboratory,
     Environmental Research Center,  U.S. Environmental Protection Agency,
     Research Triangle Park, North Carolina 27711
Dr.  Anna  Baetjer, Professor Emeritus of Environmental Medicine, Department
     of Environmental Medicine, School of Hygiene and Public Health, The Johns
     Hopkins University, 615 North Wolfe Street, Baltimore, Maryland 21205
Dr.  Donald Barltrop, Pediatrics Unit, St. Mary's Hospital Medical School, Lon-
     don W2 1PG, England
Ms.  Gayla  Benignus, Technical  Consultant,  Research Triangle Park, North
     Carolina 27709
Dr.  Irwin H.  Billick, Program Manager, Lead-Based Paint Poisoning Prevention
     Research, Division of Housing Research, Office of the Assistant Secretary for
     Policy Development  and Research,  Department  of Housing and  Urban
     Development, Washington, D.C. 20410
Dr.  Robert  P.  Botts,  Environmental Research  Laboratory,  Environmental
     Research Center, U.S.  Environmental Protection Agency,  200 SW 35th
     Street, CorvalHs, Oregon 97330
Dr.  Robert  Bornschein,  Department of  Environmental Health, College  of
     Medicine, University of Cincinnati, Cincinnati, Ohio 45267
Dr.  Ronald L. Bradow, Environmental Sciences Research Laboratory, Environ-
     mental Research Center, U.S. Environmental Protection Agency, Research
     Triangle Park, North Carolina 27711
Dr.  Kenneth  Bridbord, Director, Office of Extramural Coordination and Special
     Projects, National Institute for Occupational Safety and Health, 5600 Fishers
     Lane, Rockville, Maryland 20852
Dr.  Marijon  Bufalini, Environmental Sciences Research  Laboratory, Environ-
     mental Research Center, U.S. Environmental Protection Agency, Research
     Triangle Park, North Carolina 27711
Dr.  Robert  Burger,  Senior  Scientist, Research  Triangle Institute,  P.O.  Box
     12194, Research Triangle Park, North Carolina 27709
Dr.  John B. Clements, Environmental Monitoring and  Support Laboratory, En-
     vironmental Research  Center,  U.S.  Environmental  Protection Agency,
     Research Triangle Park, North Carolina 27711
Mr.  Stanton Coerr, Strategies and Air Standards Division, Office of Air Quality
     Planning and Standards, U.S. Environmental Protection Agency, Research
     Triangle Park, North Carolina 27711
                                    VI

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Ms.  Josephine S. Cooper, Strategies and Air Standards Division, Office of Air
     Quality  Planning and Standards, U.S. Environmental Protection  Agency,
     Research Triangle Park, North Carolina 27711
Mr.  Gunther F. Craun, Health Effects Research Laboratory, U.S. Environmental
     Protection Agency, Cincinnati, Ohio 45268
Dr.  Annemarie Crocetti, Professor of Epidemiology, New York Medical College,
     New York, New York 10029
Dr.  Terri Damstra, Office of Health Hazard  Assessment, National  Institute of
     Environmental Health Services, Research Triangle Park,  North Carolina
     27709
Dr.  Cliff Davidson, Graduate Research Assistant, California Institute of Tech-
     nology, Mail Stop 138-78, Pasadena, California 91109
Dr.  Ivan Diamond, Department of Neurology, School of Medicine, University of
     California, San Francisco, California 94143
Dr.  Michael Dowe,  Jaycor,  Incorporated, Research  Triangle Park, North
     Carolina 27709
Dr.  Ben B. Ewing, Professor and  Director, Institute  for Environmental Studies,
     University of Illinois, 408 S. Goodwin Avenue, Urbana, Illinois 61801
Dr.  Harold Furst,  Professor of Epidemiology,  New  York Medical College and
     New York City Health Department, New York, New York  10029
Mr.  Warren Galke,  Health Effects  Research  Laboratory,  Environmental
     Research Center, U.S. Environmental Protection Agency,  Research Triangle
     Park, North Carolina 27711
Dr.  J.H.B. Garner,  Health  Effects Research  Laboratory,  Environmental
     Research Center, U.S. Environmental Protection Agency,  Research Triangle
     Park, North Carolina 27711
Dr.  John T. Gatzy, Associate Professor of Pharmacology, School of Medicine,
     University of North  Carolina, Chapel Hill, North Carolina  27514
Dr.  Robert Goyer, Department of  Pathology, University of Western Ontario,
     London 72, Ontario, Canada
Dr.  Lester D. Grant, Associate Professor of Psychiatry, School of Medicine,
     University of North Carolina, Chapel Hill, North Carolina 27514
Mr.  Daniel Greathouse, Health Effects Research Laboratory,  U.S. Environmen-
     tal Protection Agency, Cincinnati, Ohio 45268
Dr.  Vic  Hasselblad,  Health Effects  Research  Laboratory,  Environmental
     Research Center, U.S. Environmental Protection Agency,  Research Triangle
     Park, North Carolina 27711
Dr.  Derek Hodgson, Professor, Department of Chemistry, C448 Kenan, Univer-
     sity of North Carolina, Chapel Hill, North Carolina 27514
Dr.  John Horn, Environmental Consultant, 758 Oxford Street, West, London,
     Ontario, Canada N6M1V2
Dr.  Robert J. M. Horton, Senior Research  Advisor, Health Effects Research
     Laboratory, Environmental Research Center, U.S. Environmental Protection
     Agency, Research Triangle Park, North Carolina 27711
Mr.  Allen  G.  Hoyt,  Health Effects  Research  Laboratory,  Environmental
     Research Center, U.S. Environmental Protection Agency,  Research Triangle
     Park, North Carolina 27711
Dr.  F. Gordon Hueter, Associate Director, Health Effects Research Laboratory,
     Environmental Research Center,  U.S. Environmental  Protection Agency,
     Research Triangle Park, North Carolina 27711
Dr.  Emmett S. Jacobs, Division Head, Additives and Environmental Studies, E.
     I.  du Pont  de  Nemours and  Company,  Inc., Petroleum  Laboratory,
     Wilmington, Delaware 19898
                                  vn

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Mr.  Gary L. Johnson, Industrial Environmental Research Laboratory, Environ-
     mental Research Center, U.S.  Environmental Protection Agency, Research
     Triangle Park, North Carolina  27711
Mr.  Robert Kellam, Strategies and  Air Standards Division, Office of Air Quality
     Planning and Standards, U.S.  Environmental Protection Agency, Research
     Triangle Park, North Carolina  27711
Dr.  Carole A. Kimmel, National Center for Toxicological Research, Jefferson,
     Arkansas 72079
Dr.  Robert R. Kinnison,  Environmental Monitoring and Support Laboratory,
     U.S. Environmental Protection Agency, P.O. Box 15027, Las Vegas, Nevada
     89114
Dr.  John H. Knelson,  Director, Health Effects Research Laboratory, Environ-
     mental Research Center, U.S.  Environmental Protection Agency, Research
     Triangle Park, North Carolina  27711
Dr.  Martin R. Krigman, Professor  of Pathology, School of Medicine, University
     of North Carolina, Chapel Hill, North Carolina 27514
Dr.  Robert E. Lee,  Deputy Director. Health Effects Research Laboratory, En-
     vironmental  Research  Center,  U.S.  Environmental Protection  Agency,
     Research Triangle Park, North Carolina 27711
Dr.  G.  J. Love,  Epidemiology Consultant, Research  Triangle  Park,  North
     Carolina 27709
Dr.  James MacNeill,  Pediatrician, Hillside  Medical Center,  El  Paso,  Texas
     79903
Dr.  Kathryn R. Mahaffey, Division of Nutrition. Food and Drug Administration,
     Department of  Health, Education, and Welfare, 1090 Tusculum Avenue,
     Cincinnati, Ohio 45226
Dr.  Alec E. Martin, Visiting Scientist, Office of Health Hazard Assessment, Na-
     tional Institute of Environmental Health Sciences, P.O. Box 12233, Research
     Triangle Park, North Carolina  27709
Dr.  Edward B. McCabe, 3225 Knollwood Way, Madison, Wisconsin 53713
Mr.  Gary D. McCutchen, Emission Standards and Engineering  Division,  Office
     of Air Quality Planning and Standards, U.S. Environmental Protection Agen-
     cy, Research Triangle Park, North Carolina 27711
Mr.  Thomas B. McMullen, Health  Effects Research  Laboratory, Environmental
     Research Center, U.S. Environmental Protection Agency, Research Triangle
     Park, North Carolina 27711
Mr.  Joseph Merenda, Office of Mobile Source Air Pollution Control, Office of
     Air and Waste Management, U.S. Environmental Protection Agency,  Wash-
     ington, D.C. 20460
Ms.  Margarita M. Morrison, Technical Information Specialist, Program Opera-
     tions Office, Health Effects Research Laboratory, Environmental Research
     Center, U.S.  Environmental Protection  Agency, Research  Triangle Park,
     North Carolina 27711
Dr.  Paul Mushak, Associate Professor of Pathology, School of Medicine, Univer-
     sity of North Carolina, Chapel Hill, North Carolina 27514
Dr.  D. F. Nataush, Professor of Chemistry, Colorado State University, Fort Col-
     lins, Colorado 80523
Dr.  John C. Nduaguba, Assistant  Professor of Medicine, School  of Medicine,
     Wright State University, Dayton, Ohio 45431
Dr.  Herbert L. Needleman, The Children's Hospital Medical Center, 300 Long-
     wood Avenue, Boston, Massachusetts 02115
Dr.  Stata Norton, Department of Pharmacology, University of Kansas Medical
     Center, Kansas City, Kansas 66110

                                   viii

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Mr.  John O'Connor, Strategies and Air Standards Division, Office of Air Quality
     Planning and Standards, U.S. Environmental Protection Agency, Research
     Triangle Park, North Carolina 27711
Dr.  Sergio  Piomelli, Professor  of Pediatrics  and  Director of  Pediatric
     Hematology, School of Medicine, New York University Medical Center, 550
     First Avenue, New York, New York 10016
Dr.  Herbert Posner, Office of Health Hazard Assessment, National Institute of
     Environmental Health Sciences,  Research Triangle Park, North Carolina
     27709
Dr.  Jerry Ptasnik, Director of Special Education, El Paso City Schools, El Paso,
     Texas 79903
Dr.  Michael J. Quigley,  Health  Effects  Consultant, Research  Triangle Park,
     North Carolina 27709
Dr.  Keturah Reinbold, Associate Research Biologist, Institute for Environmental
     Studies, University of Illinois, 405 S. Goodwin Avenue, Urbana, Illinois
     61801
Dr.  Lawrence  Reiter,  Health  Effects  Research  Laboratory,  Environmental
     Research Center, U.S. Environmental Protection Agency, Research Triangle
     Park, North Carolina  27711
Dr.  John  F. Rogers,  Assistant  Professor  of Medicine, School of Medicine,
     University of North Carolina, Chapel Hill, North Carolina 27514
Dr.  Gary L. Rolfe, Associate Professor of Forestry, Institute for Environmental
     Studies, University of Illinois, 408 S. Goodwin Avenue, Urbana, Illinois
     61801
Dr.  Donald Routh,  Professor  of Clinical  Psychology,  School of Medicine,
     University of North Carolina, Chapel Hill, North Carolina 27514
Mr.  Robert C. Ryans, Writer-Editor, Environmental Research Laboratory, U.S.
     Environmental Protection Agency, College Station Road, Athens, Georgia
     30605
Mr.  Edward A.  Schuck, Environmental Monitoring and Support Laboratory,
     U.S. Environmental Protection Agency, P.O. Box 15027, Las Vegas, Nevada
     89114
Dr.  R. K. Skogerboe,  Professor of Chemistry, Colorado State University, Fort
     Collins, Colorado 80523
Dr.  Cecil Slome, Professor of Epidemiology, School of Public Health, University
     of North Carolina, Chapel Hill, North Carolina 27514
Mr.  James  R. Smith,  Health  Effects Research  Laboratory,  Environmental
     Research Center, U.S. Environmental Protection Agency, Research Triangle
     Park, North Carolina 27711
Dr.  R. D. Snee,  Biostatistician, E. I. du Pont de Nemours and Company, Inc.,
     Petroleum Laboratory, Wilmington, Delaware 19898
Mr.  Andrew G. Stead, Statistician, Health Effects Research Laboratory, Environ-
     mental Research Center, U.S. Environmental Protection Agency, Research
     Triangle Park, North Carolina 27711
Mr.  Orin W. Stopinski, Health Effects Research  Laboratory,  Environmental
     Research Center, U.S. Environmental Protection Agency, Research Triangle
     Park, North Carolina 27711
Dr.  Richard J. Thompson, Environmental  Monitoring and Support Laboratory,
     Environmental Research Center, U.S. Environmental  Protection Agency,
     Research Triangle Park, North Carolina 27711
Ms.  Beverly E.  Tilton, Health  Effects Research  Laboratory,  Environmental
     Research Center, U.S. Environmental Protection Agency, Research Triangle
     Park, North Carolina 27711
                                    IX

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Mr.  Ian von  Lindern,  Environmental Engineer,  Department  of Health and
     Welfare, Division of the Environment, State of Idaho, 324 2nd Street, East,
     Twin Falls, Idaho 83301
Ms.  P. A. Warrick, Technical Consultant, School of Public Health, University of
     North Carolina, Chapel Hill, North Carolina 27541
Mr.  Tony  Yankel, Division of the Environment, Department of Health and
     Welfare, Statehouse, Boise, Idaho 83720
Dr.  R. L. Zielhuis, Universiteit von Amsterdam, Coronel Laboratorium, Eerste
     Constantijn Huygersstraat 20, Amsterdam, Netherlands
Dr.  R. L.  Zimdahl, Professor of Botany and Plant Pathology, Colorado State
     University, Fort Collins, Colorado 80523

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                           CONTENTS
                                                                   Pave
PREFACE  	      iii
ABSTRACT	      iv
SCIENTIFIC ADVISORY BOARD
 SUBCOMMITTEE ON SCIENTIFIC CRITERIA
 FOR ENVIRONMENTAL LEAD	      v
CONTRIBUTORS AND REVIEWERS	      vi
FIGURES	     xvi
TABLES	     xix
ABBREVIATIONS AND SYMBOLS	    xxiii
  1. SUMMARY AND CONCLUSIONS	    1-1
     1.1  Introduction	    1-1
           1.1.1  Potential Exposure to Environmental Lead	    1-1
           1.1.2  Sources of Environmental Lead	    1-2
           1.1.3  Monitoring of Environmental Lead	    1-3
     1.2 Effects of Lead on Man and His Environment	    1-4
           1.2.1  Effect of Lead on Man	    1-4
           1.2.2  Effects of Lead  on the  Ecosystem	    1-9
     1.3 Effects of Lead on Populations	   1-10
     1.4 Assessment of Risk from Human Exposure to Lead	   1-11
           1.4.1  Use of Blood-Lead Levels in Risk Assessment	   1-11
           1.4.2  Use of Biological and Adverse Health Effects of Lead in
                  Risk Assessment	   1-12
           1.4.3  Populations at Risk	   1-14
  2. INTRODUCTION	    2-1
  3. CHEMICAL AND PHYSICAL PROPERTIES	    3-1
     3.1  Elemental Lead	    3-1
     3.2 General Chemistry of Lead	    3-1
     3.3 Organometallic Chemistry of Lead	    3-2
     3.4 Complex Formation and Chelation	    3-2
     3.5 References for Chapter 3	    3-4
  4. SAMPLING AND ANALYTICAL  METHODS FOR LEAD	    4-1
     4.1  Introduction	    4-1
     4.2 Sampling	    4-2
          4.2.1  Sampler Site Selection  	    4-2
          4.2.2  Sampling Errors	    4-2
          4.2.3  Sampling for Airborne Paniculate Lead	    4-3
          4.2.4  Sampling for Vapor-Phase Organic Lead Compounds. .    4-4
          4.2.5  Sampling for Lead in Other Media	    4-4
          4.2.6  Source Sampling	    4-6
          4.2.7  Filter Selection  and Sample Preparation	    4-7
                                  XI

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                                                                     Page
    4.3  Analysis	    4-8
         4.3.1  Colorimetric Analysis	    4-8
         4.3.2  Atomic Absorption Analysis	    4-8
         4.3.3  Anodic Stripping Voltammetry	    4-9
         4.3.4  Emission Spectroscopy	    4-9
         4.3.5  Electron Microprobe 	   4-10
         4.3.6  X-Ray Fluorescence	   4-10
         4.3.7  Methods for Compound  Analysis	   4-11
    4.4  Conclusions	   4-11
    4.5  References for Chapter 4	   4-11
5.  SOURCES AND EMISSIONS	    5-1
    5.1  Natural Sources	    5-1
    5.2  Man-Made Sources	    5-1
         5.2.1  Production 	    5-1
         5.2.2  Utilization	    5-1
         5.2.3  Emissions	    5-2
    5.3  References for Chapter 5	    5-5
6.  TRANSFORMATION  AND TRANSPORT	    6-1
    6.1  Introduction	    6-1
    6.2  Physical  and Chemical Transformations in the Atmosphere ...    6-1
         6.2.1  Physical Transformations	    6-1
         6.2.2  Chemical  Transformations	    6-4
    6.3  Transport in Air	    6-8
         6.3.1  Distribution Mechanisms	    6-8
         6.3.2  Removal Mechanisms	   6-12
         6.3.3  Models	   6-19
    6.4  Transformation and Transport in Other Environmental Media   6-20
         6.4.1  Soils	   6-20
         6.4.2  Water	   6-21
         6.4.3  Plants	   6-23
    6.5  References for Chapter 6	   6-25
7. ENVIRONMENTAL  CONCENTRATIONS AND POTENTIAL
      EXPOSURES	    7-1
    7.1  Ambient Air Exposures	    7-1
         7.1.1  National Air Surveillance Network (NASN) Data	    7-1
         7.1.2 Airborne  Particle Size Distribution	    7-4
         7.1.3 Vertical Gradients of Lead in the Atmosphere	    7-4
    7.2  Mobile Source Exposures	    7-6
    7.3  Point Source Exposures	    7-7
    7.4  Dietary Exposures 	    7-9
         7.4.1  Food	    7-9
         7.4.2 Water	   7-11
    7.5  Occupational Exposures	   7-12
         7.5.1  Exposures in Lead Mining, Smelting, and Refining ....   7-12
         7.5.2 Exposures in Welding and Shipbreaking	   7-13
         7.5.3 Exposures in the Electric Storage  Battery Industry ....   7-13
         7.5.4 Exposures in the Printing Industry	   7-13
         7.5.5 Exposures in Alkyl  Lead Manufacture	   7-13
         7.5.6 Exposures in Other  Occupations	   7-13
         7.5.7 Exposures Resulting from Manmade Materials	   7-14
         7.5.8 Historical Changes	   7-14
    7.6 References for Chapter 7	   7-14
                                  xii

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 8.  EFFECTS OF LEAD ON ECOSYSTEMS	    8-1
     8.1  Effects on Domestic Animals, Wildlife, and Aquatic Organisms    8-1
          8.1.1  Domestic Animals	    8-1
          8.1.2  Wildlife	    8-3
          8.1.3  Aquatic Organisms	    8-5
     8.2  Effects on Plants	    8-8
          8.2.1  Routes of Plant Exposure  	    8-8
          8.2.2  Effects on Vascular Plants	   8-10
          8.2.3  Effects on Nonvascular Plants	   8-11
     8.3  Effects on Relationships Between Arthropods and Litter Decom-
           position 	   8-13
     8.4  References for Chapter 8	   8-13
 9.  QUANTITATIVE  EVALUATION OF LEAD AND  BIOCHEMI-
      CAL INDICES OF LEAD  EXPOSURE IN PHYSIOLOGICAL
      MEDIA 	    9-1
     9.1  General Sampling Procedures for  Lead in Biological Media...    9-1
     9.2  Blood Lead	    9-2
     9.3  Urine Lead	    9-3
     9.4  Soft-Tissue Lead	    9-3
     9.5  Hair Lead	    9-3
     9.6  Lead in Teeth and  Bone	    9-3
     9.7  Comparative  Studies of Methods  for Measurement of Lead in
           Biological Media	    9-4
     9.8  Measurements of Urinary  8-Aminolevulinic Acid (ALA-U) ...    9-4
     9.9  Measurements of 8-Aminolevulinic Acid Dehydratase (ALAD)    9-5
     9.10 Measurements of Free Erythrocyte Protoporphyrin (FEP)	    9-6
     9.11 References for Chapter 9	•	    9-6
10.  METABOLISM OF LEAD 	   10-1
    10.1  Introduction	   10-1
    10.2  Absorption	   10-1
         10.2.1  Respiratory Absorption	   10-1
         10.2.2  Gastrointestinal Absorption	   10-2
         10.2.3  Cutaneous Absorption	   10-5
    10.3  Distribution	   10-5
         10.3.1  Human Studies	   10-5
         10.3.2  Animal Studies	   10-6
    10.4  Elimination	   10-7
         10.4.1  Human Studies	   10-7
         10.4.2  Animal Studies	   10-7
    10.5  Alkyl  Lead Metabolism	   10-8
    10.6  Metabolic Considerations  in the  Identification of Susceptible
           Subgroups  in the Population	   10-8
    10.7  References for Chapter 10	   10-9
11.  BIOLOGICAL EFFECTS OF LEAD EXPOSURE	
    11.1  Introduction	
    11.2  Cellular and Subcellular Effects of Lead	
         11.2.1  Effects on Enzymes	
         11.2.2  Organellar and Cellular Effects	
         11.2.3  Effects of Lead on Chromosomes.
         11.2.4  Carcinogenesis	
    11.3  Clinical Lead Poisoning	
    11.4  Hematological Effects of Lead.
 -4
1-5
1-6
1-7
                                 Xlll

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     11.4.3  Effects of Lead on Heme Synthesis	
     11.4.4  Other Hematological Effects	  1
     11.4.5  Summary of Effects  of Lead  on  the Hematopoietic
              System	  1
11.5  Effects of Lead on Neurophysiology and Behavior	  1
         11.4.1  Anemia	   11-7
         11.4.2  Effects of Lead on Erythrocyte Morphology and Survival
                                                                    1-7
                                                                    1-8
                                                                    -13

                                                                    -13
                                                                    -14
         11.5.1  Human Studies	  1  -15
         11.5.2  Animal Studies	  11-26
   11.6  Effects of Lead on the Renal System	  11 -44
         11.6.1  Acute Effects	  11 -44
         11.6.2  Chronic Effects	  11 -44
   11.7  Reproduction and Development	  11 -45
         11.7.1  Human Studies	  11-46
         11.7.2  Animal Studies	  11 -48
   11.8  The Endocrine System	  11-51
   11.9  The Hepatic System	  11-52
   11.10 The Cardiovascular System	  11-52
   11.11 The Immunologic System	  11-53
   11.12 The Gastrointestinal System	  11 -54
   11.13 References for Chapter 11  	  11-54
12. ASSESSMENT OF LEAD EXPOSURES AND  ABSORPTION IN
      HUMAN  POPULATIONS	   12-1
   12.1  Introduction	   12-1
   12.2  Lead in Human  Populations	   12-1
         12.2.1  Statistical Descriptions and Implications	   12-1
         12.2.2 Geographic Variability  in Human Blood Lead Levels .   12-4
         12.2.3 Demographic Variables and Human Blood Lead Levels   12-6
   12.3  Relationships Between External Exposures and  Blood Lead
           Levels	  12-10
         12.3.1  Air Exposures	  12-10
         12.3.2 Soil and  Dust Exposures	  12-29
         12.3.3 Food and Water Exposures	  12-32
         12.3.4 Effects of Lead in the  Housing Environment:  Lead in
                  Paint	  12-33
         12.3.5 Secondary Exposure of Children From Parents'  Occupa-
                  tional Exposure	  12-36
         12.3.6 Miscellaneous Sources of Lead	  12-38
    12.4  Summary	  12-38
    12.5  References for Chapter 12	  12-39
13. EVALUATION OF HUMAN HEALTH RISKS FROM EXPOSURE
      TO LEAD AND ITS COMPOUNDS 	   13-1
    13.1  Introduction	   13-1
    13.2  Sources, Routes, and Mechanisms of Entry	   13-1
         13.2.1 Sources	   13-1
         13.2.2 Routes and Mechanisms of Entry	   13-2
    13.3  Evidence of Increased Blood Lead Levels in Humans Exposed to
           Environmental Lead	   13-2
         13.3.1 Relationships Between  Blood Lead Levels and Single-
                  Source Exposures	   13-2
         13.3.2 Multiple-Source Exposures	   13-3

                                 xiv

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                                                                   Page
          13.3.3  Effect of Host Factors on Blood Lead Levels	   13-3
          13.3.4  Summary of the Quantitative Relationship	   13-3
    13.4  Averaging-Time Considerations	   13-4
    13.5  Biological and Adverse Health Effects of Lead in Man	   13-4
          13.5.1  Assessment of Hematological Effects of Lead	   13-4
          13.5.2  Assessment of Neurobehavioral Effects of Lead	   13-6
          13.5.3  Effects of Lead on Reproduction and Development....   13-7
          13.5.4  Other Health Effects	!	   13-8
          13.5.5  Dose Effect/Response Relationships	   13-8
    13.6  Populations at Risk	  13-11
          13.6.1  Children as a Population at Risk	  13-11
          13.6.2  Pregnant Women  and the Conceptus as a Population at
                  Risk	  13-12
    13.7  Description of United States Population in Relation to Probable
            Lead Exposures	  13-13
    13.8  References for Chapter 13  	  13-14
APPENDICES
 A. GLOSSARY	   A-l
 B. PHYSICAL/CHEMICAL DATA FOR LEAD COMPOUNDS	   B-l
 C. ADDITIONAL STUDIES OF ENVIRONMENTAL CONCENTRA-
      TIONS OF LEAD	   C-l
 D. UNITS AND METRIC CONVERSION FACTORS	   D-l
 E. A REVIEW  OF THREE STUDIES ON THE EFFECTS OF LEAD
      SMELTER EMISSIONS IN EL PASO, TEXAS	   E-l
                                 xv

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                              FIGURES
                                                                        Page
4-1   Sequence of operations  involved in monitoring for lead in the en-
         vironment 	   4-2
5-1   Approximate flow of lead through  U.S. industry in 1975	   5-1
5-2   Location of major lead operations  in the United States, 1976	   5-3
6-1   Simplified  ecologic flow chart for lead showing  principal cycling
         pathways and compartments	   6-1
6-2   Effect of various driving conditions on the amount of lead exhausted   6-2
6-3   Effect of speed on size distribution of exhaust particles at  different
         road load cruise conditions and  using Indolene HO O fuel	   6-2
6-4   Cumulative mass distributions for lead aerosol in auto exhaust and at
         Pasadena, a receptor  sampling site 	   6-3
6-5   Differential mass distributions for  lead 1 m from a freeway and  at
         Pasadena sampling sites	   6-3
6-6   Cumulative mass distribution of lead particles by size	   6-4
6-7   Air-lead values as a function of traffic volume and distance from the
         highway	   6-9
6-8   Relationship of the diameter of the particles (mass) to distance from
         the highway	   6-9
6-9   Lead concentration profiles in the  oceans	   6-9
6-10  Midpoint collection location for atmospheric samples collected from
         R. V. Trident north of 30°N, 1970 through 1972	  6-10
6-11  The EFcrust values for atmospheric trace metals collected in the
         North Atlantic westerlies and at the South Pole	  6-10
6-12  Lead concentration profile in snow strata of northern Greenland . .  6-1 ]
6-13  World lead smelter and alkyl lead production since 1750 A.D. ...  6-11
6-14  2iopb jn Storbreen glacier ice,  1954-1966	  6-11
6-15  Predicted deposition velocity at indicated height for fi * = 20 cm/sec
         and zo  = 3.0 cm	  6-14
6-16  Predicted  deposition velocities at 1-m height for z0 =  3.0 cm ....  6-14
6-17  Predicted  deposition velocities at 1 m for /*» = 200 cm/sec	  6-14
6-18  Regression of percentage lead particulates  removed by dry deposi-
         tion with distance from roadway	  6-15
6-19  Comparison of size distribution of lead particulates collected at 20
         and 640 ft from an expressway north of Cincinnati, Ohio	  6-15
6-20  Atmospheric concentrations of lead and carbon monoxide as a func-
         tion of log of distance from edge of highway	  6-15
6-21  Atmospheric lead concentration at freeway site in Palo Alto, Califor-
         nia, on August 15,  1966	  6-16
6-22  Average lead in dry fallout as a function of distance from the freeway
          	  6-16
6-23  Fate of lead contributed  from automotive traffic in  Los Angeles
         Basin	  6-17
                                    xvi

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Number                                                                    Page
6-24  Contamination  of dust  by lead emissions from  two  secondary
         smelters	   6-17
6-25  Total deposition of lead on Teflon plates at various heights above the
         roof of  Keck Laboratories, California Institute of Technology,
         Pasadena	   6-19
6-26  Lead distribution between  filtrate  and suspended solids in stream
         water from urban and  rural compartments	   6-22
7-1   Seasonal patterns and trends in quarterly average urban lead con-
         centrations  	    7-3
7-2   Nationwide trends in regular, premium, and  unleaded gasoline sales,
         1960-1976	    7-4
7-3   Nationwide trends in lead content of regular and premium gasoline,
         1960-1976	    7-4
7-4   Annual ambient  air lead concentration near  a  smelter, by area,
         before the August 1974 and August 1975 surveys	    7-8
8-1   Simplified  ecologic  flow chart for  lead showing principal  cycling
         pathways and compartments	    8-1
8-2   Concentration  of lead  in three species of small mammals trapped
         beside major and minor roads and at arable and woodland sites    8-5
8-3   Mean  lead content in grouped insect  samples taken from low  and
         high lead emission areas for sucking, chewing, and predatory feed-
         ing types	    8-7
8-4   Mean lead levels in representative  organisms and sediments of the
         compartments of the drainage basin of the Saline Branch of the
         Vermilion River, Illinois	    8-7
8-5   Tree ring analysis of lead concentrations in  urban and rural trees .    8-9
11-1  Lead effects on heme biosynthesis 	   11-8
11-2  McCarthy general cognitive index scores as a function of degree of
         lead exposure	  11-21
11-3  Scores on McCarthy subscales as a function of degree of lead ex-
         posure 	  11-21
11-4  Peroneal nerve  conduction velocity  versus blood lead  level, Idaho,
         1974	  11-25
12-1  Estimated cumulative  distribution of blood  lead levels for popula-
         tions in which the geometric mean level is 15, 25, or 40 /ug/dl. .   12-2
12-2  Estimated cumulative  distribution of blood  lead levels for popula-
         tions having  a geometric mean blood lead level of  25  yug/dl, but
         geometric standard  deviations of  1.2, 1.3, or 1.5	   12-2
12-3  Geometric  means for blood lead values by race and age,  New York
         City, 1971	   12-9
12-4  Arithmetic mean of air lead  levels by traffic count,  Dallas, 1976. .  12-12
12-5  Blood  lead concentration and traffic density by sex and age,  Dallas,
         1976	  12-12
12-6  Monthly ambient air  lead  concentrations in Kellog,  Idaho, 1971
         through  1975	  12-16
12-7  Annual ambient air  lead concentration, by area, before the  August
         1974 and August  1975 surveys	  12-16
12-8  Blood  lead versus air lead for  urban male workers	  12-25
12-9  Cumulative distribution of lead levels  in dwelling units	  12-34
12-10 Cumulative distribution of lead levels by location  in dwelling, all
         ages	  12-35
12-11  Cumulative distribution of lead levels in dwelling units with unsound
         paint conditions	  12-35

                                   xvii

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12-12 Cumulative  frequency distribution of blood lead levels found  in
         Pittsburgh housing survey	  12-36
12-13 Correlation of children's blood lead levels with fractions of surfaces
         within a dwelling having lead concentrations > 2 mg Pb/cm2	  12-36
13-1  Dose-response curve for percent ALAD inhibition for adults and
         children as a function of blood  lead level	   13-9
13-2  Dose-response curve for ALA in  urine (ALA-U) as a function  of
         blood lead level	   13-9
13-3  Dose-response curve for FEP as a function of blood lead level..  . .   13-9
13-4  Dose-response curve for FEP as a function of blood lead level... .   13-9
13-5  Dose-response curve for FEP as a function of blood lead level....  13-10
13-6  EPA calculated dose-response curve for ALA-U (from  Azar et al.)  13-10
C-l   Locations of fixed  sampling stations in Kanawha River Valley ....   C-3
C-2   Air sampling sites for Southern Solano, California, study	   C-3
C-3   Omaha, Nebraska,  study: mean monthly composite atmospheric lead
         at industrial, commercial, mixed, and two residential sites	   C-4
C-4   Settleable paniculate lead  radial  distribution from Helena  Valley
         environmental pollution  study	   C-5
C-5   Annual average of settleable particulate lead at sites near Missouri
         lead mine and smelter	   C-6
C-6   Schematic  plan  of lead mine  and  smelter from Meza  Valley,
         Yugoslavia, study	   C-7
C-7   Soil transects by two streets: Curve A  =  low traffic volume (400
         veh/day); Curve B =  high traffic volume (14,000 veh/day)	   C-8
C-8   Surface soil  levels of lead in El Paso, Texas, and Dona  Ana County,
         New Mexico, 1972	   C-8
                                  xvin

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                               TABLES
Nwn her                                                                   Page
1-1    Blood lead levels versus lowest-observed-effects levels	   1-13
1 -2    Estimated  percentage of subjects with ALA-U exceeding 5 mg/1 for
         various  blood  lead levels	   1-14
1 -3    Estimated  percentage of children with EP exceeding specified cutoff
         points for various blood lead levels	   1-14
3-1    Properties  of elemental lead 	    3-1
3-2    Isotopes of lead 	    3-1
3-3    Properties  of major organolead compounds	    3-2
4-1    Daily food intake	    4-6
5-1    U.S. consumption of lead by product category	    5-2
5-2    Estimated  atmospheric lead emissions for the United States, 1975  .    5-3
6-1    Comparison of size distributions of lead-containing particles in ma-
         jor sampling area	    6-4
6-2    Results of  atmospheric sampling for organic and particulate lead.  .    6-5
6-3    Percentage of particulate versus vapor-phase lead in urban air sam-
         ples	    6-5
6-4    Analyses of five replicate samples taken in an underground parking
         garage	    6-5
6-5    Average composition of particulate lead compounds emitted in auto
         exhaust  	    6-6
6-6    Effects of aging on lead compounds in  samples of auto exhaust as
         determined by electron microprobe	    6-6
6-7    Concentration range and mean  EFcrust values for atmospheric trace
         metals collected over the Atlantic north of 30° N	  6-10
6-8    Lead aerosol production in the  northern hemisphere compared with
         lead  concentrations  in  Camp  Century,  Greenland, snow at
         different times	  6-11
6-9    Terminal velocities of spherical particles of unit density at ground
         level	  6-12
6-10   Summary of field data from Palo Alto, California	  6-17
6-11   Deposition  of lead at the Walker Branch Watershed, 1974	  6-17
6-12   Lead compounds identified  in roadside  soils  by  X-ray powder
         diffraction techniques	  6-21
7-1    Number of NASN urban stations whose data fall within selected an-
         nual average lead concentration intervals, 1966-1974	    7-2
7-2    Number of NASN nonurban stations whose data fall within selected
         annual average lead concentration intervals, 1966-1974	    7-2
7-3    Cumulative frequency distributions of quarterly  lead measurements
         at urban stations by year, 1970 through 1974	    7-2
7-4    Cumulative frequency distributions of quarterly  lead measurements
         at nonurban stations by year, 1970 through 1974	    7-2
7-5    NASN stations with annual average lead concentrations >  3.0 Atg/m3
         	    7-3

                                    xix

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Number                                                                    Page
7-6   Quarterly and annual size distributions of lead-bearing particles for
         six cities, 1970	    7-5
7-7   Lead in air on Main Street, Brattleboro, Vermont, September 12 and
         13,  1972	    7-5
7-8   Airborne lead concentrations at 5- and 20-ft elevations above street
         level	    7-6
7-9   Monthly average lead concentrations for 1975 Los Angeles catalyst
         study	    7-6
7-10  Lead dust on and near heavily traveled roadways	    7-7
7-11  Lead content in or on roadside soil and grass as a function of distance
         from traffic and grass depth in profile	    7-7
7-12  Lead dust in residential areas	    7-8
8-1   Accumulation of certain heavy metals from seawater by fish (Am-
         modytes and duped) and a puffin	    8-3
8-2   Summary of lead concentrations in bird organs and tissues from areas
         of high-lead and low-lead  environments	    8-4
8-3   Mean  lead concentrations in organs  and tissues of small mammals
         from indicated areas of environmental lead exposures	    8-6
8-4   Lead concentrations of insects at two distances from a high-traffic-
         volume road (interstate highway)	    8-6
8-5   Lead concentrations of predominant organisms from the rural, ur-
         ban, and combined compartments of the drainage basin of the
         Saline Branch of the Vermilion River, 111	    8-8
8-6   Summary of goldfish toxicity data	    8-8
8-7   Concentrations of selected heavy metals in fresh water and in fresh-
         water algal blooms	   8-12
10-1  Lead content of fresh, processed, and canned foodstuffs	   10-3
10-2  Effect  of different diets on lead absorption expressed as the ratio of
         mean retention for experimental and control subjects	   10-4
10-3  Percent absorption of different lead compounds relative to lead ace-
         tate 	   10-4
11-1  Enzymes affected by lead in animal studies	
11 -2  Enzymes affected by lead in human studies	
11 -3  Comparison of test results in lead and control groups	  1
11 -4  Summary of results of human studies on neurobehavioral effects at
         "moderate" blood lead levels	  1
11-5  Effects of lead exposure on locomotor activity in laboratory animals  1
1-2
1-2
-22

-27
-30
11-6  Lead exposure  and  resulting  blood  lead  levels in  experiments
         measuring locomotor activity in rats	  11-32
11 -7  Protocols used for the study of animal learning	  1
11 -8  Stage of learning	  1
11-9  In vivo effects of lead exposure on neurochemistry	  1
11-10 Statistics on the effect of lead on pregnancy	  1
-35
-37
-39
-46
-49
11-11 Reproductive performance of F, lead-toxic rats	  1
12-1  Analysis of variance for  the logarithms of blood lead values for
         selected studies	   12-3
12-2  Blood lead levels of remote populations	   12-4
12-3  Age and smoking-adjusted geometric mean blood leads in urban ver-
         sus suburban areas of three cities	   12-5
12-4  Blood lead concentrations in six urban and one rural population..   12-5
12-5  Mean blood  lead values for children in 14 intermediate-sized cities
         in  Illinois, 1971	   12-6

                                    xx

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 Number                                                                   Pa«f
 12-6  Blood lead levels (whole blood) in children in U.S. smelter and com-
         parison towns, 1975	   12-7
 12-7  Geometric mean and geometric standard deviations (in parentheses)
         of blood lead levels by age and study sector	   12-7
 12-8  Proportion of children with blood lead values between 50 and  99
         fig/dl, by age, Chicago, 1971-1975	   12-7
 12-9  Mean blood lead by age, sex, and G6PD status in 1559 urban black
         children	   12-8
 12-10 Geometric mean blood-lead levels in New York City lead screening
         program	   12-8
 12-11 Number of children's initial screens in New York City programs by
         race/ethnicity and  year, 1970-1977	   12-9
 12-12 Blood lead levels in military recruits, by race and place	   12-9
 12-13 Geometric mean blood lead levels in New York lead screening pro-
         gram, 1970-1976, for children  up to 72 months of age, by race and
         year	  12-10
 12-14 Mean blood lead levels for study and control groups, Houston....  12-11
 12-15 Arithmetic and geometric  mean  blood  lead levels for Los Angeles
         and Lancaster, California, by sex and age	  12-11
 12-16 Mean air  lead levels indoors and outdoors at two traffic densities,
         Dallas, Texas, 1976	  12-12
 12-17 Soil  lead levels by traffic density	  12-12
 12-18 Blood lead concentrations in relation to soil lead concentrations and
         traffic density	  12-13
 12-19 Blood lead levels in children aged 1 to  5 in Newark, New Jersey, in
         relation to distance of residence from a major roadway, 1971  ..  12-13
 12-20 Geometric mean blood lead levels by area compared with estimated
         air lead levels for 1- to  9-year-old  children living near Idaho
         smelter	  12-15
 12-21 Mean blood lead levels in  children living in  vicinity of a primary
         lead smelter, 1974 and 1975	  12-17
 12-22 Mean blood lead levels in selected Yugoslavian populations, by esti-
         mated weekly, time-weighted,  air lead exposure	  12-18
 12-23 Lead concentrations in air, dustfall, and blood, Omaha, Nebraska,
         study, 1970-1977	  12-19
 12-24 Geometric mean air and blood lead levels for five city-occupation
         groups	  12-21
 12-25 Geometric mean air and blood  lead values for 11 study populations  12-22
 12-26 Mean air and blood lead values for  five zones in Tokyo study  ....  12-22
 12-27 Length of time needed for mean blood lead values to reach specified
         levels at two exposure levels	  12-23
12-28 Estimated  blood lead to air lead  ratios  for four air lead concentra-
         tions 	  12-25
12-29 Yearly mean air and blood lead levels of black females in relation to
         distance of residence from a busy highway	  12-26
12-30 Blood and air  lead levels by sex  in Finnish population study	  12-27
12-31 Blood and air  lead data from clinical study	  12-28
12-32 Estimated  percentage of population exceeding a specific blood  lead
         level in relation to ambient air lead exposure	  12-28
12-33 Comparison of blood lead levels  in children with air lead levels for
         1974 and 1975	  12-29
12-34 Mean blood and soil  lead concentrations in English study	  12-30
12-35 Summary of soil lead/blood lead  relationships	  12-32

                                   xxi

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Number                                                                   Page
12-36 Blood lead levels of 771 persons in relation to lead content of drink-
        ing water, Boston, Massachusetts	  12-33
12-37 Results  of screening  and housing  inspection in childhood  lead
        poisoning control project by fiscal year	  12-36
12-38 Geometric mean blood lead levels of children by parental employ-
        ment 	  12-37
12-39 Geometric mean blood lead levels for children based on reported oc-
        cupation of father, history of pica, and distance of residence from
        smelter	  12-37
13-1  Sources of lead for human exposures	   13-2
13-2  Summary  of lowest observed effect levels	   13-8
13-3  Percentage of subjects with ALA-U exceeding 5 mg/1 for various
        blood lead levels	  13-10
13-4  Estimated percentages of children with EP exceeding cut-off points
        for various blood lead levels	  13-11
13-5  Population and percent distribution, urban and rural, by race, 1970
        census	  13-13
13-6  Number of births by race and size of population	  13-14
B-l   Physical properties of inorganic lead compounds	   B-l
B-2   Temperature variation of the vapor pressures of common lead com-
        pounds 	   B-2
C-l   Summary of monthly average lead concentrations found in seven-city
        study	   C-2
C-2   Seasonal   lead  concentrations  in  Birmingham,  Alabama,  area,
         1964-1965	   C-2
C-3   Lead data from Kanawha Valley Study	   C-3
C-4   Data on lead deposition in 77 midwestern cities	   C-3
C-5   Lead concentrations in air determined by analysis of suspended par-
        ticulate, Southern Solano County, California, March-May 1970.   C-4
C-6   Total lead and lead fallout determined by analysis  of dustfall sam-
        ples, Southern Solano County, California, June-September 1970   C-4
C-7   Lead concentrations in suspended paniculate air samples from El
        Paso, Texas, 1971	   C-5
C-8   Paniculate data summary from Helena Valley, Montana, environ-
        mental  pollution  study	   C-5
C-9   Peak deposition rates of lead measured in Southeast Missouri	   C-6
C-10  Atmospheric lead  concentrations  (24-hr)  in the Meza  Valley,
        Yugoslavia, November 1971 to August 1972	   C-7
C-l 1  Comparison of lead levels in the surroundings of two lead industry
        facilities and an urban control area	   C-7
C-l 2  Lead content of soil near 3-year-old Russian  smelter, E. Kazakhstan   C-8
C-l 3  Lead content of soil in vicinity of Russian lead plant in Kazakhstan   C-9
                                   xxu

-------
ABBREVIATIONS AND  SYMBOLS
A              Angstrom (10'10 meter)               FDA
AAS           Atomic absorption spectroscopy        59Fe
ALA           Delta-aminolevulinic acid             Fe2O3
ALAD         Delta-aminolevulinic acid             FEP
               dehydratase
ALAS          Delta-aminolevulinic acid             ft
               synthetase                           g
ALA-U        Delta-aminolevulinic acid in urine      GSH
8-ALA         Delta-aminolevulinic acid             G-6-PDH
APHA         American Public Health
               Association                         ha
ASTM         American Society for Testing and       5-HIAA
               Materials                           hr
ASV           Anodic stripping voltammetry         I ARC
b.p.            Boiling point
B.W.           Body weight                         ICRP
°C             Degrees Celsius (centigrade)
Ca             Calcium                             in
Cd             Cadmium                           i.p.
CDC           Center for Disease Control            K
               (Atlanta, Ga.)                       kcal
(Ch3)4Pb       Tetramethyl lead (also TML or        RCR
               Me4Pb)                             kg
(CH3)6Pb2      Hexamethyl lead                     km
(C2H5)4Pb      Tetraethyl lead (also TEL or           1
               Et4Pb)                              LC,
(C6H5)4Pb      Tetraphenyl lead
(C2H5)6Pb2     Hexaethyl lead
cm             Centimeter
CNS           Central nervous system
COj           Carbonate ion
CP             Coproporphyrin
CPG           Coproporphyrinogen                 Me3PbAc
CP-U          Coproporphyrin in urine              (Me3Pb)2S
Cu             Copper                             MeV
DA            Dopamine
dl              Deciliter                            MEPPs
DNA          Deoxyribonucleic acid                mg
EDTA         Ethylenediaminetetraacetate           Mg
EP             Erythrocyte protoporphyrin; also       min
               erythrocyte porphyrin                 MM ED
EPA           U.S. Environmental  Protection         ml
               Agency                             mo
°F             Degrees Fahrenheit                   m.p.
LC

m
M
                              50
Food and Drug Administration
Radioisotope of iron
Ferric oxide
Free erthythrocyte protoporphyrin;
also free erythrocyte porphyrin
Foot
Gram
Glutathione (reduced)
Glucose-6-phosphate
dehydrogenase
Hectare
5-Hydroxyindole acetic acid
Hour
International Agency for Research
on Cancer
International Radiological
Protection Commission
Inch
Intraperitoneal
Potassium
Kilocalorie
Respiratory control rate
Kilogram
Kilometer
Liter
Concentration lethal to 1 percent of
recipients
Concentration lethal to 50 percent
of recipients
Meter
Molar
Maximum
Trimethyl lead acetate
Trimethyl lead sulfide
Mega electronvolts (106
electronvolts)
Miniature end-plate potentials
Milligram
Magnesium
Minute
Mass median equivalent diameter
Milliliter
Month
Melting point
                       xxin

-------
MT
Na
NADH

NAS
NASN

NE
ng
Ni
r\m
NO3
NSF
NVS
P
Pb
204pb
Pb-t--1-
Pb-A
Pb-B
PbBr2
PbBrCl
PbBrCI-NH4CI

[Pb(C2H302)2.
2Pb(OH)2]
PbCl2
PbCO3
PbCrO4
PbF2
Pb(N03)2
PbO
PbOx
(PbO)2
Pb304
Pb(OCOCH3)2
Pb(OH)2
Pb(OH)Br
Pb(OH)Cl
Pb(OH)2CO3
PbO«PbSO4
Pb40(P04)2
Metric ton
Sodium
Reduced(hydrogenated)
nicotinamide adenine dinucleotide
National Academy of Sciences
National Air Surveillance
Networks
Norepinephrine
Nanogram
Nickel
Nanometer
Nitrate ion
National Science Foundation
Nonvolatile solids
Phosphorus
Lead
Isotope of Lead (210Pb, etc.)
Diavalent lead ion
Concentration of lead in air
Concentration of lead in blood
Lead bromide
Lead (II) bromochloride
Lead bromochloride-ammonium
chloride

Basic  lead (II) acetate
Lead chloride
Lead carbonate
Lead chromate
Lead fluoride
Lead nitrate
Lead oxide
Lead oxides
Lead oxide dimer
Lead (IV) oxide
Lead (II) acetate
Lead hydroxide
Lead  (II) hydroxybromide
Lead hydroxychloride
Basic lead carbonate
Basic lead sulfate
Lead  oxyphosphate
Pb(PO3)2      Lead metaphosphate
Pb3(PO4)2     Lead orthophosphate
Pb5(PO4)3OH  Lead hydroxqpmxqpqwzn
PbS           Lead sulfide
PbSO4        Lead sulfate
PBG          Porphobilinogen
pCi           Picocurie (1(H2 curie)
PIXE         Proton-induced X-ray emissions
pH            Log of the reciprocal of the
              hydrogen ion concentration
POJ          Phosphate ion
PP            Protoporphyrin
ppb           Part per billion
ppm          Part per million
PVC          Polyvinyl chloride
RBC          Red blood cell;erythrocyte
RNA         Ribonucleic acid
s.c.           Subcutaneous
scm           Standard cubic meter
sec            Second
SGOT        Serum glutamic oxaloacetic
              transaminase
SGPT         Serum glutamic pyruvic
              transaminase
SH            Sulfhydryl
SO2           Sulfur dioxide
SOf          Sulfate ion
85Sr           Radioisotope of strontium
STEL         Short-term exposure limit
TEL          Tetraethyl lead
TML         Tetramethyl lead
TVL          Threshold value limit
USPHS       U.S. Public Health Service
Zn            Zinc
ZnS          Zinc sulfide
ZPP          Erythrocyte zinc protoporphyrin
/Ltg            Microgram
//.I            Microliter
fj.m           Micrometer
>            Greater than
<            Less than
—            Approximately
                                              xxiv

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                       1. SUMMARY  AND CONCLUSIONS
1.1 INTRODUCTION
  The first portion of this document is devoted to
lead in the environment: its physical and chemical
properties; its  monitoring  and  measurement in
various environmental  media;  its environmental
sources, emissions, and concentrations; and its trans-
port and  transformation  within  the environment
(Chapters 3 through 7).
  Chapters 8 through  13 are concerned with the
effects of lead on ecosystems and, most  important,
on human  health. Among the questions  that have
been specifically addressed in this document are:

    1. What are the sources of lead in the environ-
       ment?
    2. What  are the routes and  mechanisms by
       which lead  from these  sources  enters the
       body?
    3. Once  lead enters  the body,  where  is it
       deposited?
    4. Once lead is in the body, what are its health
       effects?
    5. Are there groups within the population that
       are particularly vulnerable to lead?
    6. What is the magnitude of the risk in terms of
       the  number  of persons exposed  in various
       subgroups of the population?

  This document has been prepared to  reflect the
current  state  of knowledge  about  lead —
specifically, those  issues that are most relevant to
establishing the  objective  scientific data base that
will be used to recommend an air quality standard
for lead that will adequately safeguard  the  public
health.

1.1.1  Potential Exposure to Environmental Lead
  Lead is unique among the toxic heavy metals in
that it is relatively abundant in the earth's crust.
Because of its easy isolation  and  low melting point,
lead was among  the first metals to be used by man
thousands of years ago.  The environmental signifi-
cance of lead is a result  both of its utility and of its
abundance. World production exceeds  3.5  million
tons/year, a far larger quantity than the production
of any other toxic heavy metal.
  Lead is present in food, water, air, soil, dustfall,
paint, and other materials with  which the general
population comes in contact. Each of these repre-
sents a potential pathway for human lead exposure
via inhalation or ingestion. The actual lead content
in each  source may vary by several orders of mag-
nitude. Potential exposure patterns are further con-
founded  by  human  activity  patterns  and  by
differences between  indoor and outdoor  environ-
ments. The number and extent of variables involved
make it very difficult to determine the actual lead
intake of individuals in their normal environment.
  As a  result of centuries of the mining, smelting,
and use of lead  in human  activities, natural  back-
ground  concentrations are  difficult to determine.
Geochemical data  indicate that the concentrations
of lead in most surface materials in the United States
range from 10 to 30 ppm (/ug/g). Trace amounts of
lead occur naturally in air  and water as a result of
wind  and rain  erosion, and .in  air as a result of
volcanic dusts, forest fires, sea salt, and the decay of
radon. Natural background concentrations of air-
borne  lead have been estimated  to  approximate
0.0006 ij,g Pb/m3 of air (or 5 x  10-7 ^.g  Pb/g air).
Natural concentrations in fresh water have been esti-
mated to be about  0.5 yu,g/liter of water (about 5 x
10'4 /j.g Pb/g water) and in ocean water about 0.05
fj.g Pb/liter of  water (about 4.9  x 10-5  /ig Pb/g
water).  As a  consequence of  the extensive and
diverse uses of lead, present concentrations of lead
in air, soil, and water are  substantially higher than
these estimated background levels.  Nonurban lead
concentrations average 0.1 /Ag Pb/m3 of air (about 8
x 10'5 /j.g Pb/g air). Concentrations of airborne lead
in U.S. cities, at sites not conspicuously  influenced
by major sources, average 1  jug Pb/m3 of air (8 x 10'4
^g Pb/g air).  Expressed  on a  weight basis with
respect to the total  suspended particulate  (TSP) in
the air,  this amount is approximately equivalent to
104/*g Pb/g TSP.
  The shape of buildings in urban  areas may  cause
large horizontal and vertical variations in lead con-
                                                1-1

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centrations.  In  the absence of such structures, the
vertical gradient would usually be relatively small.
During periods of maximum traffic density on  free-
ways, airborne  concentrations of lead immediately
adjacent to the  freeways may reach 20 /ug/m3 for a
few hours. In the immediate vicinity of large station-
ary sources  having no air pollution controls,  con-
centrations of airborne lead may reach  300 /ng/m3
under unfavorable  meteorological  conditions.
Consequently, exposure via inhalation of airborne
inorganic lead particulates may vary by a factor of at
least  100, depending  on location and activity pat-
terns. The small number of indoor air lead studies
conducted have shown indoor concentrations to be
one-third or less the  level measured outdoors. In-
door  levels vary widely depending on type of struc-
ture,  air conditioning, wind, etc.
  Dust is a generic term and consequently  imprecise
when used to describe potential human exposure.
Dust  in the popular sense usually refers to solid par-
ticles that have settled on a surface and  that can be
readily redispersed in the atmosphere. In an aero-
metric sense, dust is solid particles suspended in the
atmosphere; consequently, it is an  integral part of
total  suspended particulates. In  an occupational
sense, dust may encompass even larger particles dis-
charged into the work environment by  mechanical
means. Dustfall is  a measure of the settled particu-
late,  or that  deposited in  or  on  the  collection
devices; thus dustfall  is more closely related to the
popular definition of dust. In this document, dustfall
is treated as a separate pathway for potential ex-
posure to lead via ingestion of these settled particles,
but only in a qualitative manner.
   Lead concentrations in dustfall vary widely with
the type and distribution of sources. The highest
values occur in  the immediate vicinity of sources and
diminish rapidly with distance.  Potential  exposure
to lead in dustfall depends on the total accumulation
of dust in  accessible  areas. The accumulation de-
pends on the deposition rate  and the frequency and
efficiency  with  which accessible  surfaces  are
cleaned. Lead accumulation  resulting from deposi-
tion from the air may be augmented in the homes of
lead  workers by transportation  of lead-containing
dusts from the workplace. The level of accumulated
lead  potentially available both  indoors  and  out-
doors clearly may vary by one to two orders of mag-
nitude.
   Concentrations of lead  in solution in  most urban
water supplies  are below 10 /u,g Pb/liter of water
(0.01 /j.g Pb/g water), but some values >50 /Ag/liter
(the U.S. Public Health Service standard for lead in
drinking water)  have been  reported.  Suspended
solids contain the major  fraction of lead  in  river
waters. Concentrations of lead in tap water may be
considerably higher  than those  in municipal sup-
plies. Lead  values as high as about  2000  /tg/liter
have been reported for homes with lead pipes and
lead-lined storage tanks.
  Sea spray, rainwater leaching, and flaking  paint
from older buildings can contribute significantly to
lead levels in adjacent soil. Direct ingestion  of the
soil or of re-entrained dust, as well  as ingestion of
the paint chips themselves, constitute an important
source of lead in areas where these conditions exist.
  The contribution of food to human exposure to
lead is highly variable and not well quantified. Esti-
mates of daily intake vary from about 100 to 350 ^ig
Pb/day. Recent studies in the Unitd  States estimate
the adults  ingest about   200  ^g  Pb/day in  food.
Beverages and foods that  are stored in lead-soldered
cans or stored or served in lead-glazed pottery have
been  identified as having high  lead  content. Pro-
cessed milk has been reported to contain more lead
than fresh  cow's milk — about  20  to  40  pig/liter
compared to about 5 to 10 /xg/liter,  respectively. If
these values are correct,  processed milk could be a
significant source of lead  exposure for infants.
  For adults, illicitly distilled whiskey and old auto-
mobile batteries used as home heating fuel represent
two nonindustrial sources of overt lead poisoning.
Of much greater  significance as a health problem,
however, are various sources of  occupational ex-
posure.
  Workers involved in uncontrolled (without pollu-
tion controls) mining, smelting,  and manufacturing
processes where lead is used, have the highest level
of potential exposure. Although occupational condi-
tions have generally been substantially improved, in
some cases  lead concentrations  in the  air  in work
places  have been  measured at  1000 jug/m3 or
greater. The major occupational exposure problems
occur  where adequate hygiene  programs have not
been implemented or where individuals fail to take
the recommended precautions. The major  route  of
occupational exposure is  the inhalation of dust and
fumes;  in  addition, dust transported  on  clothing
from the work place to the home or automobile may
be a significant pathway of exposure for workers and
their families.

1.1.2 Sources of Environmental Lead
  The mining, smelting, and use of lead in human
activities has significantly altered the natural distri-
bution of lead in the environment.  Contamination
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has occurred primarily in the vicinity of sources and
in densely populated areas.
   The lead  used  in gasoline antiknock  additives
represents a major fraction of the total U.S. lead
consumption, and  motor  vehicle  emissions  con-
stitute the major source of lead emissions to the at-
mosphere. In 1975, some 189,000 MT of lead (16
percent of total production) used in antiknock com-
pounds were converted  to 142,000 MT  of at-
mospheric emissions (88 percent of total lead emis-
sions). As a result of legislation setting a maximum
limit on the  lead content of gasoline, the production
and  use of alkyl lead additives has decreased in re-
cent years and will probably continue to do so.
   Based on  1975 estimates, combustion of waste oil
and  incineration of solid waste are the major contri-
butors of lead emissions from  stationary sources
(12,060 MT/year). This figure represents only that
portion of waste oil that is reprocessed and burned
in oil-fired  or coal-fired boilers and  municipal in-
cinerators.  Other stationary sources of lead emis-
sions include iron and steel production  in plants
with poor pollution controls, primary and secondary
smelting,  battery  manufacturing,  and  lead alkyl
manufacturing. Lead that  may  be emitted to the
environment from these operations includes that in
stack emissions and  fugitive dusts. Contamination
from the major stationary emitters may determine
environmental concentrations for a radius of several
kilometers around the  sources. Fugitive dusts may
result  in a high level of contamination in the  im-
mediate vicinity of small, uncontrolled battery re-
cycling operations.
   In terms of mass balance, lead from mobile and
industrial  sources is  transported  and  distributed
mainly via the atmosphere.  Certain waste disposal
operations that discharge large amounts of lead into
soil  and water result only in highly localized con-
tamination.  Lead is emitted to the atmosphere pri-
marily in  the form  of  inorganic  particulates;
however, small amounts of organic vapors have been
reported in the vicinity  of gasoline service stations,
garages, and  heavy  traffic areas.  These  organic
vapors undergo photochemical decomposition in the
atmosphere, but they may also be adsorbed on dust
particle surfaces.
  Based on the limited data available, it is estimated
that  75 percent of the particulate lead emitted from
automobiles is removed from the atmosphere in the
immediate vicinity of traffic sources.
  Particles smaller than those from mobile sources,
and emissions from tall  stacks will  remain airborne
longer and be transported over greater distances.
Submicron particles may reside in the atmosphere a
week or  more  before  they  are removed by  dry
deposition (diffusion and inertial mechanisms)  and
by precipitation. The tendency toward uniform ver-
tical and  horizontal distribution (mixing with con-
comitant distribution) increases  with an increase in
residence time.
  The chemistry of lead aerosols discharged into the
environment has not been studied as extensively as
the chemistry of some of the  other major air pollu-
tants. Much of the work on lead  particulate chemis-
try before 1973 was limited  to  elemental analyses
and did not include analyses of associated ions. In-
formation from  elemental analyses  is not  sufficient
to  permit a  thorough  examination  and  under-
standing of (1)  transformation and transport pro-
cesses that occur among the  environmental  media,
(2) mobility of lead in soils,  (3) uptake and distri-
bution of lead in plants, and  (4) the overall  impact
of lead pollution on human health  and ecosystems.
Information is needed on the chemical forms  and
interactions of lead and its tendency to form com-
pounds of low solubility with the  major anions. Only
a few studies have been conducted on the chemical
forms of lead in soil and plants. They show that the
principal lead form found in soils is sulfate, and the
principal form found in plants is phosphate.
  Lead  dissolved  from  primary lead sulfide  ore
tends to combine with carbonate or sulfate ions to
form relatively insoluble lead carbonate or lead sul-
fate, or to be absorbed by ferric  hydroxide. The
amount of lead that can remain in solution in water
is  a  function  of the concentration of other ions,
especially hydrogen ions.

1.1.3  Monitoring of Environmental Lead
  Lead has been monitored in air, water, soil, food,
and biological samples such as blood and  urine for
many years, but the accuracy of  the early  sampling
and  analytical  techniques  was  quite low. Conse-
quently, these earlier data can  be  used  only  in a
qualitative or semiquantitative  manner.  External
contamination has  been  the  major  problem in all
sampling procedures, particularly in  sampling  for
blood lead analyses. Sampling and analytical techni-
ques for  environmental lead have enjoyed con-
siderable improvement  and refinement in the past
few years. Some of the best methods,  however,  are
tedious  and expensive  and  are  available only in
relatively  specialized laboratories. Those analytical
techniques that are less sophisticated produce results
of limited value.  The  capability  now exists  for
achieving high precision in lead  monitoring; but in
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general  practice, precise and accurate  results are
difficult to obtain, particularly for biological  sam-
ples. Atomic absorption spectroscopy is the  most
successful analytical method used in recent years.
The primary problem  faced in environmental
monitoring — that is, sampling and analysis — is to
determine the type of monitoring procedures to be
used to accomplish specific objectives, and to estab-
lish and maintain adequate quality control.
  Ambient  air  monitoring  procedures designed
specifically for assessing population  exposure pat-
terns present particularly difficult problems.  Total
mass concentration, particle size distribution, and
chemical composition oi  lead aerosols all vary con-
siderably with space and  time. In using atmospheric
measurements to determine population exposures,
human activity patterns are a further complication.
Thus the relationship between measurements  of at-
mospheric  concentration of lead, duration  of ex-
posure, and incremental changes in blood lead  levels
is  not constant.  Although  measurements  of at-
mospheric lead levels are an essential ingredient in
population exposure assessment, other indices of ex-
posure such  as  blood  lead and free  erythrocyte
porphyrin (FEP) levels  are also essential  for the
characterization of human  population exposures.
   Blood lead may be measured by  several general
techniques that presently appear to be satisfactory in
the hands of qualified analysts who have a sophisti-
cated technical  appreciation of the many problems
associated with  measuring an element  that is both
present at trace levels and ubiquitously distributed
as  a contaminant.  Extensive  interlaboratory  com-
parisons have demonstrated the need for standardiz-
ing methodology, using reference standards, and ob-
taining  blood  lead  determinations from  those
laboratories  having  highly  skilled  personnel ac-
customed to handling a large number  of samples.
The present existence  of a number of regional and
national analytical proficiency testing programs will
help  improve  the  quality  of analysis and the
reliability of consequent clinical and epidemiologi-
cal data. Measurements of biological  indicators such
as erythrocyte porphyrin, 8-ALA, and 8-ALAD are
also a problem. A standardized  method exists for
urinary ALA,  and a program is underway  in the
United  States  to evaluate  standardizations of
methodology  for  determining  erythrocyte
porphyrin.
1.2 EFFECTS  OF LEAD ON MAN AND HIS
ENVIRONMENT
   In the summary material presented in the preced-
ing section, attention was directed  to  all the ex-
posure aspects of lead. The biological aspects of the
lead pollution problem are discussed in this section.
These aspects include not only the effects of lead  on
man, but also  its effects on a myriad of ecosystems
that support man and  contribute to his general
welfare.
1.2.1  Effects of Lead on Man
  The effects of lead on man are summarized in  se-
quential statements of present knowledge concern-
ing:
     1. Man's metabolism  of lead.
     2. Biological and adverse health effects in man.
     3. Effects of lead on populations.
    4. Risks man  incurs from exposure to lead.

1.2.1.1 METABOLISM
  Metabolism, as  discussed here,  encompasses the
physiological processes in man that relate to absorp-
tion, distribution,  excretion, and  net retention. It
can be discussed in terms of routes of lead exposure
and the  physiological distinctions existing within
certain segments of the population that modify these
processes. Special attention is focused on the factors
that may place the developing fetus and  the child in
a category of higher  risk than the adult.
  Nearly  all lead  exposures  result from inhalation
and ingestion. The quantities of lead absorbed via
these routes are determined by many factors such as
the physical and chemical  form of the lead, and the
nutritional status,  metabolic activity, and previous
exposure history of those exposed.
  Clinical studies on the  desposition of airborne
lead paniculate matter in the human  respiratory
tract suggest that 30 ±  10 percent of the ambient  air
lead particulates inhaled will be deposited. Of the
lead thus deposited  in the respiratory tract, it has
been estimated that as much as 50 percent or more is
absorbed and enters  the blood stream. This deposi-
tion may  vary considerably,  depending on particle
size and pattern of respiration. Part of the fraction
deposited  in  the  respiratory  tract, that portion
removed via the mucociliary escalator, is swallowed
and enters the gastrointestinal tract. Animal studies
suggest that the relative efficiency of lung clearance
mechanisms may be  impaired at high levels of air-
borne lead.
  In children, approximately 40 percent of the lead
taken  into  the  gastrointestinal tract is absorbed,
whereas the corresponding value for adults is about
10  percent. In one study  assessing  net  gastro-
intestinal  absorption, an  inverse  relationship  be-
                                                1-4

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tween  calcium  intake  and  lead absorption  was
shown. This relationship has also been demonstrated
in experimental  animals.
   In discussing the routes by which man may be ex-
posed to environmental lead, it is important to dis-
tinguish between primary and secondary exposure to
atmospheric lead. Primary exposure is direct, and
secondary is indirect. Primary exposure to airborne
lead consists of its direct inhalation, whereas sec-
ondary exposure to airborne  lead consists of inges-
tion of lead that is of atmospheric origin  (that is,
lead that is transported by the airborne route to the
ingested material).
   Lead may contaminate foodstuffs by atmospheric
fallout, with subsequent adsorption onto plant sur-
faces or absorption into plants. This contamination
may involve primary food  (plants consumed by
man) or  animal  food crops.  Soil lead taken  into
plants may come from atmospheric fallout or from
leaching from  natural as well  as industrial  sources.
The absorption of soil lead by plants, however,  is
thought to be relatively poor, although data on  lead
accumulation in  tree rings suggest that absorption
from soil may occur in at least some plants. In any
case, the contribution of air lead to food lead levels
is probably small on the basis of a nationwide food
distribution system;  but  adequate  quantification
does not yet exist to allow precise statements on this
point to be made. It is clear, however, that commer-
cial processing raises the lead content of food signifi-
cantly.
   Another important depot of lead in the environ-
ment is soil or dust. The ultimate source of this lead
varies from place to place; it can be dustfall from the
atmosphere (coming  from  either  stationary or
mobile sources), or it can be soil or dust into which
leaded paint has eroded. This exposure route  is
thought to be more important for children than for
adults. Studies have consistently shown associations
between soil or  dust lead levels and blood  lead
levels in children when such exposures exceed  1000
ppm. It is  thought that lead  reaches the children
through their normal mouthing behavior.  Lead  is
picked up on children's hands through their play and
is then transferred to their mouths by their custom-
ary  habit  of  putting their  hands, objects,  and
materials in their mouths. There is evidence demon-
strating a relationship between dust lead and lead on
fingers, but as yet there is no direct evidence linking
lead on fingers with lead in the blood. In children
with pica, however,  the importance  of this source
could be greatly magnified.
  It has been shown repeatedly that levels of lead in
blood increase when  oral  intake  increases, but
studies do not show a precise, quantitative expres-
sion of this relationship. Rather, a number of studies
show that, with sustained daily ingestion of 100 fj.g
of lead, the maximum increase in steady-state levels
of blood  lead ranges from 6 to  18 /ig/dl. These
variations  probably relate to nutritional  factors,
biological  variability,  unreported  sources of ex-
posure, differences in analytical techniques, or pre-
vious exposure history — or  to a  combination of
these factors.  Since children, particularly  infants,
absorb a larger percentage of lead than adults do,
the relative contribution of oral intake is undoubt-
edly greater for them. Because of higher metabolic
activity, children  also  inhale relatively more air-
borne lead than do adults. Therefore, the contribu-
tion  of airborne lead to total  lead  intake may be
greater in children than in adults, but one must keep
in mind that children also eat correspondingly more
on a body weight basis.
  A number of experimental animal  studies have
assessed the effects of nutrition and other factors on
gastrointestinal absorption  as reflected  by blood
lead  levels. It is clear  from these studies that the
status of essential nutrients such as calcium, iron,
phosphorus, fat, and protein is very  important.
  The absorption, distribution, and accumulation of
lead in man  is conveniently described by a three-
compartment  model. The first compartment, cir-
culating red blood cells, distributes lead to the other
two, soft tissues (primarily liver and  kidney) and
bone,  where  it accumulates.  This accumulation
begins in fetal  life as a result of transplacental trans-
fer.  In nonoccupationally exposed adults,  such
storage approaches 95  percent of the total  body
burden. The skeleton is a repository of lead that re-
flects the long-term cumulative exposure  of the in-
dividual; body fluids and soft tissues reflect more re-
cent exposure.
  Since the nonaccumulating  body  burden in soft
tissues has  a greater toxicological significance than
that  fraction  sequestered  in bone, the mobilizable
lead burden is a more important concept than total
body burden. In this connection, chelatable urinary
lead has been  shown to  provide  an index of the
mobile portion of the total body burden, as has the
lead level in blood, which is the more generally used
indicator of internal dose.
  There is a time  frame in which changes in ex-
posure register as  a perturbation in the blood lead
level. Clinical  studies show that (1) a controlled
daily intake results in a constant concentration of
blood  lead after  110 days, depending on the ex-
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posure setting, and (2) a single, acute, controlled ex-
posure yielded a blood lead half-life of about 2 days
compared to approximately 17 days in the case of
repeated exposures. Following cessation of exposure
after long exposure periods (e.g., years), however,
the half-life of blood lead can be expected to be sub-
stantially longer than  17 days.
  Fecal excretion represents  the  major route by
which  ingested lead  is eliminated from  the body.
Though excretion by  this route is  usually  much
greater than by urinary elimination,  the total fecal
lead content includes  unabsorbed lead as its major
component.

1.2.1.2  BIOLOGICAL  AND  ADVERSE
HEALTH EFFECTS OF  LEAD IN  MAN
  There are various  physiological levels and  ex-
posure ranges at which the effects of lead in man oc-
cur. Furthermore, lead  affects man at the  sub-
cellular, cellular, and organ system levels.
  Among subcellular components, both nuclei and
mitrochondria generally show the most pronounced
responses  to  cellular  invasion  by   lead.  The
mitochondria,  however,  are most vulnerable and
sustain  the  greatest functional  impairment.
Mitochondrial injury, both  in  terms of cellular
energetics and morphological  aberration, has been
shown in a number of experimental animals. In man,
the evidence for mitochondrial impairment has been
morphological rather  than  functional. Those sub-
cellular changes observed are primarily the develop-
ment of nuclear inclusion bodies in  kidney cells as
well as mitochondrial changes in renal tubular cells
in persons exposed occupationally.
  Any discussion  of the subcellular  effects of lead
must consider the question of chromosomal aberra-
tions and carcinogenesis.  At the present time,  no
conclusive statements can  be made about the induc-
tion of chromosomal damage by lead. The literature
on this issue either yields conflicting information or
describes  studies  that are  difficult to compare with
each other. Some experimental animal studies relate
the development of cancer to relatively high doses of
lead, but as  is true in the case of other suspected car-
cinogens, there are no data corroborating these find-
ings in man.
  Among the systemic and  organic effects of lead,
important  areas  are its hematologic, neurobe-
havioral,  and renal effects.  Attention must also be
given, however, to the effects  of lead on reproduc-
tion and  development as well  as  its  hepatic, en-
docrine, cardiovascular,  immunologic, and  gastro-
intestinal  effects.
  A number of significant effects of lead on  the
hematopoietic system in humans have been observed
in lead  poisoning. These effects are prominent in
clinical  lead poisoning but are still present to a
lesser degree in persons with a lower level of lead
exposure.
  Anemia is a clinical  feature of lead intoxication,
resulting from both increased erythrocyte destruc-
tion and  decreased  hemoglobin  synthesis.   In
children, a threshold blood lead level for produc-
tion of these symptoms of anemia is  approximately
40 fig Pb/dl, and the corresponding value for adults
appears to be 50 /ug Pb/dl.
  Hemoglobin synthesis is impaired by lead via in-
hibition of synthesis of the globin moiety and inhibi-
tion at several steps in the synthesis of heme. The
step most sensitive to  lead in the heme synthetic
pathway  is that mediated  by  the  enzyme
8-aminolevulinic acid  dehydratase  (8-ALAD),
which connects two units of  8-aminolevulinic acid
(8-ALA) to  form porphobilinogen. The result is an
increase in plasma level  and enhanced  urinary ex-
cretion  of 8-ALA. Also inhibited by lead is the in-
corporation of iron into protoporphyrin to form
heme,  the  prosthetic group  of hemoglobin. This
results  in  the  accumulation of  coproporphyrin,
which  is excreted in  the urine, and of protopor-
phyrin, which is  retained in  the erythrocytes. The
overall  effect of lead is a net decrease in heme syn-
thesis. (This also derepresses 8-ALA  synthetase, the
enzyme involved in the first step of heme synthesis.)
  Inhibition  of 8-ALAD occurs at  extremely  low
blood lead levels and has been shown to start at a
blood  lead  level as low as 10 jug/dl. Though  the
health-effect significance of  inhibition  at a blood
level of 10  /Ltg/dl is open to debate, the increased
urinary 8-ALA excretion that occurs with increasing
inhibition at 40 //.g/dl  is accepted as a measure of
probable  physiological impairment  in vivo. This
threshold  level  for urinary  8-ALA excretion  (40
/ng/dl)  appears  to be  true  for  both  adults  and
children.
  An increase in free  erythrocyte protoporphyrin
(FEP)  occurs at blood  lead  levels of 16 /ig/dl in
children. In adult females, this threshold is probably
similar. In adult males, the value is 20 to 25 ^tg/dl.
The precise threshold for coproporphyrin, while not
well established, is probably similar to that  for
8-ALA. Elevation  ot  free erythrocyte protopor-
phyrin has the  same implications  of physiological
impairment in vivo as urinary 8-ALA. To the extent
that the protoprophyrin elevation is a likely indica-
tor of the  impairment of mitochondrial function in
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erythroid tissue, it may be even more important. For
these reasons,  physicians who  participated in the
development of the  1975 statement by the Center for
Disease  Control and  the  American Academy of
Pediatrics reached  a consensus  that elevated' FEP
should be used  as an indicator of increased exposure
to lead.
  The effects of lead on the nervous system range
from acute intoxication and fatal encephalopathy to
subtle behavioral and electrophysiologic changes as-
sociated with   lower  level  exposures.  Changes
throughout the  range of effects are related to blood
lead levels.
  It would  appear  that surprisingly low levels of
blood  lead  may sometimes be  associated with the
most extreme effects of lead poisoning — servere, ir-
reversible brain damage as indexed by the occur-
rence of acute or chronic encephalopathy symptoms
and/or death. Though for most  adults such damage
does not occur  until blood  lead levels substantially
exceed 120 /ug/dl, some evidence suggests that acute
encephalopathy and death may occur in some adults
at blood lead levels slightly  below 100 /Ag/dl.  For
children, the effective blood levels for producing en-
cephalopathy or death are lower  than  for  adults,
with such effects being seen somewhat more often,
starting  at  approximately  100  /Ag/dl.  Again,
however,  evidence   exists  for  the  occurrence of
encephalopathy in a very few cases at lower levels,
down to about  80 /ig/dl.
  It should  be  noted that once  encephalopathy oc-
curs, death can  be a frequent outcome, regardless of
the level of medical intervention at the  time of the
acute crisis.  It is also crucial to cite the rapidity with
which acute encephalopathy or death can develop in
apparently asymptomatic individuals or in those ap-
parently only mildly affected  by elevated body bur-
dens of lead. It  is not unusual for rapid deterioration
to occur, with convulsions or coma suddenly appear-
ing and progressing to  death within 48 hr.
  This suggests that at high blood lead levels, even
when individuals are asymptomatic, rather severe
neural damage  can exist without overt manifesta-
tions. Studies show  that apparently asymptomatic
children with high blood lead levels of over 80 to
100 fjig/dl are permanently  impaired cognitively, as
are individuals  who  survive acute episodes of lead
encephalopathy. These studies tend to support the
hypothesis that  significant if albeit subtle changes in
neural function occur at what were once considered
tolerable blood lead levels.
  Other evidence tends to confirm rather  well that
some type of neural damage does exist in asympto-
 matic children, and not necessarily only at very high
 levels of blood lead. The body of studies on low- or
 moderate-level  lead  effects  on  neurobehavioral
 functions present overall an impressive array of data
 pointing to that conclusion. Several well-controlled
 studies find effects that are clearly statistically sig-
 nificant, and many others report nonsignificant but
 borderline effects. Since some of the effects at low
 levels of lead exposure discussed in this document
 are of a subtle nature, the findings  are not always
 striking in individual cases. Nevertheless, when the
 results of all of the studies on neurologic and be-
 havioral effects at subclinical  exposures are con-
 sidered in an overall perspective, a rather consistent
 pattern of impaired neural and  cognitive functions
 appears  to  be associated  with  blood  lead levels
 below those producing the overt  symptomatology of
 lead encephalopathy. The blood lead levels at which
 neurobehavioral  deficits  occur  in otherwise
 asymptomatic children appear to start at a range of
 50 to 60 /ug/dl, although some evidence tentatively
 suggests that such effects may occur at slightly lower
 levels for some children.
   Data obtained for the effects of lead on the ner-
 vous system in laboratory animals are also quite ex-
 tensive. Encephalopathy is produced by high-level
 perinatal exposure to lead; in different species, this
 occurs to varying degrees  as characterized by the
 relative  extent  of neuronal  degeneration and
 vasculopathy. It seems clear that the animal data
 support the contention that  the developing organism
 represents the population at greatest risk for central
 nervous system toxicity.
   There  is also good evidence  that perinatal ex-
 posure of laboratory animals to lead at moderate
 levels will produce delays in  both neurological and
 sexual  development. Since these effects have been
 demonstrated to occur  in  the  absence of either
 undernutrition  or  growth retardation, it  has been
 suggested that they may represent more or less direct
 effects of lead in the respective systems.
   In animal studies, locomotor activity has been the
 most commonly used behavioral index of lead tox-
 icity. Data  indicate that increased  locomotor ac-
 tivity in  young animals occurs only at moderately
 high exposure levels. It may be, in view of the levels,
that  the  changes in activity  currently reported in
 laboratory animals are more diagnostic of a  post-
 encephalopathic hyperactivity than  of subclinical
 effects. Interestingly, the reactivity changes seen in
older animals are associated with much lower blood
 lead levels.
  Finally, reports on the effects of lead exposures on
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the acquisition  and/or  performance  of  operant
responses indicate that perinatal exposure to moder-
ate or  low levels of lead may disrupt this type of
behavior. Thus at blood lead levels ranging from 30
to 80 /^.g/dl,  cognitive function appears  to be dis-
rupted in animals.
  Excessive lead exposure can result in acute as well
as chronic renal injury  in man.  The acute  renal
effects of lead are seen in persons dying of acute lead
poisoning  where   lead-induced   anemia and/or
encephalopathy may also be seen. These effects are
manifested by nonspecific degenerative changes in
renal tubular lining cells, cloudy swelling, and some
degree of cellular necrosis. In addition, nuclear  in-
clusion  bodies form in tubule cells, and there are
functional  and ultrastructural  changes in tubular
mitochondria.  Aminoaciduria,  glycosuria,  and
hyperphosphaturia  are noted, with  aminoaciduria
being a rather consistent feature of tubular damage
in children. These effects are usually reversible. It is
not possible at the present time to state what level of
lead in  blood is associated with aminoaciduria or
any of the other specific indices of acute renal injury.
   Prolonged  lead exposure in humans can result in
chronic lead  nephropathy. The pathology of these
chronic changes is different from that seen in acute
renal injury. It is characterized by the gradual onset
of  pronounced  arteriosclerotic changes, fibrosis,
glomerular atrophy, hyaline  degeneration, and
reduction in kidney size. This can be a progressive,
irreversible condition resulting in death from renal
failure.  A  threshold of  lead  exposure for  these
chronic changes cannot yet be stated, however, as a
result of the typical inaccessibility of data needed for
the accurate assessment of the preceding long-term
exposure history.
   Considerable evidence for the adverse effects of
lead on reproduction and development in man has
been  accumulating for  many  years.  Many of the
early data on the induction of abortions, stillbirths,
and neonatal deaths were for occupationally ex-
posed  pregnant women,  where such  effects were
demonstrated at high blood  lead  levels. Of more
pressing present interest are certain recent studies in
this area focusing on two aspects of the effects of low
to moderate lead exposure on reproduction: garheto-
toxicity and post-conception events.
   In  regard  to potential  lead effects on human
ovarian function, one study has shown that short-
term exposure at ambient air  levels of less than 7
/n,g/m3 may cause an increase in the anovular cycle
and disturbances  in the lutein phase. This study,
however, requires  confirmation before  conclusive
statements can  be made. Another recent report in-
volving occupational  exposure  similarly  suggests
that  moderately increased lead  absorption (blood
lead  mean  =  52.8 /ug/dl)  may  result in direct
testicular  impairment;  however, the design of this
study is  such that  this  observation  also  requires
verification.
  Thus, it is clear  that gametotoxic, embryotoxic,
and  teratogenic effects at a gross level can be in-
duced in laboratory animals with lead, but it should
be emphasized  that the production of such effects
probably  requires  acute, high  exposures.  Unfor-
tunately,  a  paucity of information  exists  on the
teratogenicity and developmental toxicity of chronic
low  or moderate lead exposures. Available data on
the subject do  suggest, however, that chronic low-
level lead exposure may induce postnatal develop-
mental delays in rats.
  Our present knowledge about the effects of lead in
man on the hepatic, cardiovascular,  immunologic,
and  endocrine  systems is fragmentary, rendering  it
difficult to make any  conclusive statements about
quantitative relationships. For example, effects of
lead on the endocrine system are not well defined at
present. Thyroid function in  man, however, has been
shown to  be decreased in occupational plumbism.
Also, effects of lead on pituitary and  adrenal func-
tion  in  man  have  been observed,  with decreased
secretion of pituitary gonadotrophic hormones being
noted but adrenal function effects being a less con-
sistent finding.
  The response of the hepatic system to lead has not
been well characterized in man; instead, much of the
literature  deals with hepatic effects  in experimental
animals.  Lead-poisoned animals show significantly
impaired drug-metabolizing activities, thus suggest-
ing an effect on the hepatic mixed-function oxidase
system. Since detoxification  in animals depends on
the  microsomal heme protein,  cytochrome  P450,
and  since  heme biosynthesis is impaired in  lead ex-
posure,  such an effect is a  logical  consequence of
lead poisoning.
  Of more direct interest in terms  of reproductive
efficiency  are the effects of lead exposure on preg-
nant women — not only on fetal health and develop-
ment, but also on maternal complications. Placental
transfer of lead  has been demonstrated both by fetal
tissue analysis and comparison of newborn umbilical
cord blood lead with maternal blood lead. One must
not only consider the resulting absorption of lead by
the fetus,  but also the  specific points  in embryonic
development at which exposure occurs. Fetal tissue
uptake of lead  occurs by the end  of the first tri-
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niester,  which  may  be  a  sensitive  period  in
embryonic development of the nervous system.
  Studies  comparing  umbilical  cord blood  lead
levels  in  newborns with simultaneously sampled
maternal blood show that the newborn and maternal
levels are closely correlated. The studies have also
shown that the newborns of mothers in an urban set-
ting are born with generally higher blood levels than
those of corresponding newborns from rural areas.
  That  the prenatal exposure of the fetus to  lead,
even in the absence of teratogenic effects, is of conse-
quence for adverse health effects is shown by studies
relating fetal levels to changes  in fetal heme syn-
thesis and to the incidence of premature births. Some
suggestions in the literature that heme biosynthesis
in a newborn may be affected require confirmation.
  In evaluating  maternal complications  related to
lead exposure, one must consider that pregnancy is a
physiological stress that may place the  pregnant
woman  at higher risk to lead exposure effects.  Both
iron and  calcium  deficiency  increase the suscep-
tibility  of  an  individual to lead toxicity.  Women
have an increased risk of both  deficiencies during
pregnancy  and postpartum.
  Some available but  unconfirmed  information in-
dicates that the risk  of premature rupture of the am-
niotic membrane may be higher in cases of elevated
exposure than in age-matched controls without such
exposure.
  The   literature leaves  little  doubt  about  the
deleterious  health effects of lead on reproduction,
but most reports do  not provide specific descriptions
of exposure levels  at  which specific reproductive
effects are  noted.  Maternal  blood  lead  levels of
approximately 30 /zg/dl  may be associated with  a
higher incidence  of premature  delivery and  pre-
mature  membrane rupture,  but  these observations
require confirmation. In adult males, levels of 50 to
80  jiig/dl  may  be  sufficient to  induce significant
spermatotoxic effects,  but this effect has not  been
conclusively demonstrated.
  Lead has not been shown to be  teratogenic in  man,
but  animal experiments have demonstrated that high
levels of lead that are still compatible with life in
sexually  mature  animals  interfere with  normal
reproduction;  these studies  include assessment  of
lead effects in both  parents.  Reduction in offspring
number, weight, and survival and an  increase in fetal
resorption  is a consistent finding in rats, mice, and
other  species over  a range  of high-level  lead ex-
posures. Effects on offspring have been shown to in-
volve the gametotoxic effect of lead on males as well
as females in a number of animal species.
   At lead  levels presently encountered in occupa-
tional exposure, no significant cardiovascular effects
are discernible. Clinical data for children suffering
from chronic lead poisoning resulting in death indi-
cate that extensive myocardial  damage occurs. It is
not clear that the associated morphological changes
are a specific response to lead intoxication. How-
ever, in many  instances where encephalopathy is
present, the electrocardiographic abnormalities dis-
appear  with chelation therapy.
   There are insufficient data pertaining to the effects
of elevated blood lead levels and the incidence of in-
fectious diseases in man to allow the derivation of a
dose-response  relationship.  Neither can  a dose-
response relationship be defined for the effects of
elevated blood  lead levels on the gastrointestinal
tract, even though colic is usally a consistent early
symptom  of  lead poisoning  in  adults  exposed
occupationally  and in infants and young children.
1.2.2 Effects of Lead on the Ecosystem
   As a  natural  constituent,  lead does not  usually
pose  a  threat to ecosystems. The redistribution of
naturally occurring lead in the environment, how-
ever, has now caused some concern that lead may
represent a potential threat to the ecosystem. For  ex-
ample, studies have shown a fivefold increase in lead
in tree rings during the last 50 years; this accumula-
tion may serve as a useful index of patterns of  en-
vironmental lead accumulation.
   There are also documented effects of  lead  on
domestic animals, wildlife, and aquatic  life.  Lead
poisoning in domestic  animals  produces  varying
degrees of  derangement  of the  central  nervous
system,  gastrointestinal  tract, muscular system, and
hematopoietic system.  As  is  true in man,  younger
animals appear to be more sensitive than older ones.
   Wildlife  are  exposed to a wide range  of lead
levels. Toxic effects from ingestion of lead shot have
long been recognized as a  major health problem in
waterfowl.  Several species of small mammals trap-
ped along roadways were tested for lead concentra-
tions. All but one of the  species living in habitats  ad-
jacent to  high-volume  traffic showed high con-
centrations of lead. This was especially true in urban
areas.
   Lead  toxicity in aquatic organisms has been  ob-
served  and studied  experimentally.  Symptoms of
chronic lead poisoning in fish include anemia, possi-
ble damage to the respiratory system, growth inhibi-
tion,  and retardation of sexual  maturity.
   There is  evidence that lead has both harmful and
beneficial effects on plants. Plants are exposed to
lead through the leaves, stems, bark, or roots, and
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the extent  of the effects depends on  the form,
amount, and  availability  of that  lead. The
morphology of the plant surface plays the major role
in determining the type and quantity of material  re-
tained by plants. Meteorological factors are also im-
portant in determining the fate of  lead that comes
into contact with  plants. Large deposits of inert  in-
soluble metal compounds on the leaves are probably
of little consequence to plants, as the most important
factor is the solubility of the metal. Thus, because in-
organic   lead  compounds  are generally   of  low
solubility, there is little incorporation and accumu-
lation within  the leaves of plants.
  The majority of studies reporting lead toxicity in
plants have been conducted with  plants grown in
artificial  nutrient culture. These studies have pro-
moted the concept that the effects of lead are depen-
dent on a variety of environmental factors, including
anions and cations within  the plant and in the growth
media, and  the physical and chemical characteristics
of the soil  itself.  As lead  interacts  with many
environmental factors, specific correlations between
lead effects and  lead concentrations are extemely
difficult to  predict.
1.3 EFFECTS OF LEAD ON POPULATIONS
   The frequency distribution of blood lead levels in
homogeneous human populations has almost invari-
ably been found to be lognormal. Most data sets of
homogeneous populations display a geometric stan-
dard  deviation (GSD) of 1.3 to  1.5.  This would
roughly correspond, for  example,  to an arithmetic
standard deviation  of 5.3 to 8.5 Atg/dl at  a mean
blood lead of 20  /xg/dl.
   From  the  lognormal distribution, given  a mean
blood lead  level and estimated GSD, it is possible to
predict the percentage of a population whose blood
lead levels exceed or fall below a specified value. It
is also possible to estimate the probable increase in
mean blood lead levels for a population exposed to a
specific increases in environmental lead. These two
procedures,  used together,  provide a  method by
which air quality  standards may be  chosen to protect
the health of the  population.
   Blood lead levels vary with geographic  location.
They are lowest in some remote populations, higher
in most rural settings, higher still in suburban areas,
and highest in inner-city areas. This gradient follows
the presumed lead exposure gradient. Blood  lead
values also vary by age, sex, and race, although in a
somewhat more complex fashion. Generally, young
children  have  the  highest  levels,  with  little
difference noted  between sexes at this age.  In older
segments of the population, after elimination of oc-
cupational  exposure in lead workers, males still
have a higher bLood lead than females. Only limited
published data are  available comparing the blood
levels of the various racial and ethnic groups of the
population. These data suggest  that urban blacks
have higher lead  levels than whites, with  levels  in
Puerto Ricans frequently being intermediate.
  Results of the numerous studies of environmental
lead exposures of man  have indicated strongly that
man does indeed have cumulative uptake from each
source to which he  is exposed. Equally important,
these studies have shown that the blood lead level
represents a summation of the absorption from each
of these sources.
  Data for the two most widespread environmental
sources  of lead other  than food permit  summary
statements  concerning  their  quantitative  relation-
ship with blood lead levels: air and soil/dust. Blood
lead levels were  found to  increase with  rising air
lead concentrations. The relationships were found  to
be either log-linear or  log-log.  Evaluation of the
equations at various commonly  observed air lead
levels revealed that the  ratio between changes  in
blood and changes in air lead varied generally be-
tween 1  and 2 and that it was not constant over the
range of air exposures. This implies that an increase
of 1 /ug/m3 of air lead results in an average increase
of 1  to 2 /jig/dl in blood lead levels. Suggestive evi-
dence indicates that children may have higher  ratios
than adults and that males may  have higher  ratios
than females.
  One of the most extensive data sets on blood lead
in children comes from a study by the U.S. Depart-
ment of  Housing  and Urban Development on the
blood  lead  values of  approximately   180,000
children in New York City. These data covered the
period March  1970 through December 1976. A pre-
liminary analysis  of these important research find-
ings was presented to the Subcommittee on Lead  of
EPA's Science Advisory Board  in October  1977.
The following patterns appear  to be indicated  by
these data:
     1. There  is a definite difference in blood lead
       values for racial and ethnic groups, blacks
       having higher mean lead levels,  and His-
       panics and whites having lower levels.
     2. Analysis shows that the mean blood lead
       level  is related to race and  ethnicity, age,
       and year of sampling. This age dependence is
       similar for all years: The 1 - to 12-month-old
       group  has the lowest levels,  arid  generally
       the maximum is found in 2- to 4-year-olds.
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     3.  There was  a consistent decrease of  mean
        blood lead  levels  over the course of  the
        study. This decrease was coincident with a
        reduction in lead levels in gasoline  in  the
        New  York City area.
     4.  There appears to be a likely corresponding
        decrease in  the air lead. However, it should
        be  pointed  out  that air lead data for New
        York City are sparse and that it would be un-
        wise  to assume that the  air  lead  level as
        measured at a single location would be  the
        same for all locations. Because of the height
        of  the sampler,  it  is also questionable
        whether the air lead level would represent
        the level to  which the population is exposed.
   Consistent relationships between blood lead levels
and exposure  to  lead-containing  soil   have  been
shown.  Also,  children exposed  to higher  con-
centrations of soil  and house dust lead have been
shown to have elevated concentrations  of lead on
their hands.  The intermediate link, from elevated
hand levels of lead  to elevated blood levels, has  not
yet  been  established.  Quantitatively,  blood  lead
levels have been  shown to increase 3 to 6 percent
given a doubling of the soil or dust lead content.
   Significant water  lead exposures in this country
have only occurred  in places having a soft water sup-
ply  and using  leaded pipes. Such exposures  have
been shown to  be associated with  significant eleva-
tions of blood lead. They have also been linked to
cases of mental retardation.
   Exposure to  leaded paint still constitutes a very
serious problem for American children in urban set-
tings. Although new regulations of the lead content
of paint should alleviate the problem in new hous-
ing, the poorly enforced  regulation and  lack of
regulation  of the past have left a  heavy burden of
lead exposures. Most of the studies on lead poison-
ing in children have assumed  an  association with
leaded paint. It is very difficult in these studies to
measure the  actual  amount of exposure. There is
nevertheless incontrovertible evidence that the con-
tribution from this source is very significant for cer-
tain segments of the population.
   Food lead exposures are thought to be a source of
a significant portion of blood lead.  Precise quantita-
tive estimates of the relationship between food and
blood lead are not  available,  however. Similarly,
precise quantitative estimates are not available for
the relative contributions of different sources to the
total amount  of lead in the diet. It is clear, however,
that probably the largest proportion of dietary lead
is derived from food processing (e.g., from solder in
 the seams of cans), and some is also derived from
 lead in the air and the soil.
 1.4  ASSESSMENT OF RISK  FROM  HUMAN
 EXPOSURE TO LEAD
   Of the estimated 160,000 metric tons of lead emit-
 ted into the atmosphere in 1975, the combustion of
 gasoline additives and waste oil accounted  for 95
 percent of the total. Once lead is introduced into the
 air,  it  is subject to a variety  of processes, including
 dry deposition, precipitation, and resuspension.
   Other uses of lead result in other avenues of ex-
 posure: (1) Lead in paint makes lead available by in-
 gestion; (2)  lead  in plumbing for potable water
 where the water  is soft  (low pH) permits leaching
 and  makes lead available by ingestion; (3) lead in
 the diet, introduced by  processing,  packaging, and
 raw  food  stock,  also  makes lead available  by in-
 gestion.  It is  therefore important  to realize  that
 human exposure to lead is the summation of all these
 complex and individual  sources.
   The factors that govern the quantitative aspects of
 inhalation and ingestion of lead have been pointed
 out,  and attention has been given to the fact that in-
 gestion includes both food and  nonfood  materials.
 In the case of children, the nonfood  material has
 especially important implications. Thus the total in-
 ternal  dose is a function  of all external sources with
 which  the body comes into contact. The relative sig-
 nificance of any given exposure source depends on
 the specific exposure circumstances  and certain at-
 tributes of the  population at  risk.

 1.4.1  Use  of Blood Lead Levels in Risk Assess-
 ment
  The  evidence for increased blood  lead levels, the
 usual  accepted indicator of lead  exposure,  has
 evolved  from  studies of both  single-source  and
 multiple-source exposures. Studies of single sources
 of air lead have included both epidemiological and
 clinical investigations. Clinical  data uniformly
 demonstrate and quantify the actual transfer of lead
 in air to blood. The epidemiological data are not as
 definitive,  but  they are  more relevant to the real
 world  and  clearly support such a relationship.
  Studies  concerned  with dust  and soil  lead ex-
 posures may   be  considered jointly, since  most
 studies have not attempted to isolate their relative
 contributions.  Strong evidence exists to  show that
 these  sources  can  be  significant  determinants of
 blood  lead levels.  Furthermore, investigations in-
volving children exposed to lead-contaminated dust
have demonstrated lead  on  the children's hands.
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providing strong inferential  evidence for  an oral
route of entry.
  Lead-based paint is associated with overt clinical
intoxication and widespread excess absorption in
children. Screening  programs in all major  urban
areas have sought to abate this severe public health
problem,  but  only  with  limited  success.  These
children  represent a particularly  high risk  group
with respect to  the incremental lead  exposure attri-
butable to direct inhalation of atmospheric lead as
well as with respect to the ingestion of dust con-
taminated by lead from the atmosphere.
  Studies centered  around  primary lead smelters
and  secondary  industrial sources in urban settings
have consistently and independently demonstrated a
relationship between blood  lead levels  and these
mixed sources.  Most characteristics that mediate the
relationship between blood lead level and lead ex-
posure have been examined in several studies.  Age is
certainly a significant  factor in  determining  blood
lead levels, particularly in children under 6 years of
age. With regard to sex differences, there appear to
be none  among children, whereas in adults,  males
generally exhibit higher levels than females. Though
one  study  has  reported that black  children have
higher lead  levels than white children, the overall
data are too sparse to establish a conclusive relation-
ship. Socioeconomic variables such  as income  and
education, as well as general health status, have not
been examined  in these studies.
  A number of summary statements may be made
about  the quantitative relationships pertaining to
blood lead. The weight of evidence indicates  that
blood lead  levels follow a log-normal distribution
with a geometric standard deviation  of about  1.3 to
1.5. The log-normal  distribution possesses  prop-
erties that make it of value in arriving at acceptable
maximal exposures, since it makes it possible to esti-
mate a proportion of a population whose blood lead
levels exceed any specified level.
  The increase  in blood lead level resulting from an
increase  in air lead  concentration is not constant in
magnitude  over the range of air lead levels com-
monly found in the environment. The relationship is
dependent on many factors, including rate of current
exposure and the history of past exposure.  The ob-
served ratios vary from air  lead level to  air lead
level; they are generally between 1 and 2. Evidence
suggests  that the ratios for children may be  higher
than those of adults; also it suggests that ratios for
males may be higher than those  for females.
  There  is general agreement that blood lead levels
begin to  increase when soil levels are 500 to 1000
ppm. Mean percent increases in blood  lead levels,
given a twofold increase in soil lead levels, ranged
from 3 to 6; this is remarkably consistent given the
divergence of the populations studied.
  One of the most important aspects of risk assess-
ment is the  evaluation of effects of long-term, low-
level, or  intermittent exposures.  In such circum-
stances, blood  lead levels do not  always correlate
well with the exposure history. In one clinical study
of lead exposure by inhalation, an  average air level
of 3.2 jug/m3 over a period of about 7 weeks was re-
lated to a significant rise in blood lead after about 7
weeks. When exposed to clean air, the blood lead
levels  of  these  same subjects returned  to pre-ex-
posure levels.

1.4.2 Use  of  Biological and Adverse Health
Effects of Lead in Risk Assessment
  Lead is  not  conclusively  known  to have  any
biological  effect on  man that can be considered
beneficial.  Therefore, any of the biological and ad-
verse health effects on man at this time must be con-
sidered  from   a  medical   point of  view  that
acknowledges  the  absence  of  any health
benefit/health cost ratio.
  Earlier discussion considered the biological and
adverse health effects of lead  across the entire range
of lead exposures. In risk assessment, the primary
focus is on those biological and adverse physiologi-
cal effects that  relate  to the general population.
  Though  the  literature dealing  with the health
effects of lead  embraces virtually all of the major
organ systems in man, hematological and neurologi-
cal effects are  of prime concern  These effects are
summarized in  Table 1-1. It  should be  pointed out
that Table  1-1 is  a  lowest-observed-effects  level
tabulation; i.e., it lists the lowest blood lead levels at
which particular effects have been credibly reported
for given subpopulations. Four hematological effects
are  considered: anemia, inhibition of  the enzyme
8-ALAD, urinary 8-ALA excretion, and elevation
of free erythrocyte porphyrin (FEP).
  Anemia is found in children with and without con-
comitant  iron  deficiency.  Increased  lead intake
prompts a more severe anemia. This is of special im-
portance in children 1 to 6 years old of lower socio-
economic status, since this group also has a high inci-
dence of iron deficiency.
  The literature relating blood  lead  levels  to  a
statistically  significant  reduction  in  hemoglobin
points to a threshold  level of 40 jug/dl for children
and  a corresponding  value of 50 jig/dl for adults.
The question of a low-threshold  or  no-threshold
                                                1-12

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   TABLE 1-1. BLOOD LEAD LEVELS VERSUS LOWEST-
            OBSERVED-EFFECTS LEVELS
Lowest level
for observed
effects, ng Pb/dl
whole blood
10
15 to 20

20 to 25

40

40
40

50
50 to 60

50 to 60

80 to 100

100 to 120

Observed effect
ALAD inhibition
Free erythrocyte
porphyrin elevation
Free erythrocyte
porphyrin elevation
Increased urinary
ALA excretion
Anemia
Coproporphynn
elevation
Anemia
Cognitive (CMS)
deficits
Peripheral
neuropathies
Encephalopathy
symptoms
Encephalopathy
symptoms
Population group
Children and adults
Adult females
and children
Adult males

Children and adults

Children
Adults and children

Adults
Children

Adults and children

Children

Adults

level for the inhibitory effect of lead on the enzyme
8-ALAD is overshadowed by the larger issue of the
health significance of this observation. In any event,
a value of 10/xg/dl blood lead appears to represent a
threshold  level. Elevation of urinary 8-ALA levels,
however,  appears to  be  considered an  index  of
physiological impairment, and the threshold level of
this  effect is approximately  that  for anemia  in
children (i.e., 40  /u,g/dl). This value seems to apply
for both children and adults.
  Elevation of erythrocyte  porphyrin  is  better ac-
cepted as an indicator of physiological  impairment.
On the basis of a number of studies, threshold values
of blood lead at which erythrocyte protoporphyrin is
elevated appear to be  15  to 20  /itg/dl  for children
and  adult females and 20  to 25  /Ag/dl for adult
males.
  The hematological effects  described above are the
earliest  physiological impairments encountered as a
function of increasing lead exposures as indexed  by
blood lead elevations; as such, those effects may  be
considered to represent critical  effects of lead ex-
posure.  Although it may be argued that certain of the
initial hematological effects  (such as ALAD inhibi-
tion)  constitute  relatively  mild,  nondebilitating
symptoms at low blood lead levels, they nevertheless
signal  the onset  of steadily  intensifying  adverse
effects as blood lead elevations increase. Eventually,
the hematological effects reach such magnitude that
they  are of clear-cut  medical significance as indica-
tors of undue lead exposure.
   Of even greater concern than early symptoms of
 lead exposures (i.e., hematological impairments) are
 the neurologic effects of lead that begin to  be en-
 countered as the hematological deficits reach clini-
 cal  magnitudes. Children  are  most  clearly  the
 population at  risk  for neurologic  effects.  The
 neurologic effects, including both peripheral  neuro-
 pathies and signs of CNS damage, are first encoun-
 tered for some children as blood lead levels reach 50
 to  60 /ig/dl;  and  they very rapidly  intensify in
 severity as a function of increasing blood lead eleva-
 tions. Of great medical concern is the very steep up-
 ward  rise in  the  risk for  permanent,  severe
 neurological damage or  death as blood lead eleva-
 tions approach and  exceed 80  to  100 /u,g/dl  in
 children.  Inner city  children are  of particular con-
 cern with  respect to the manifestation of lead-in-
 duced neurologic deficits, as documented by the evi-
 dence discussed in Section 11.5.
   Some evidence has  recently  been advanced that
 suggests  that  long-term  neurobehavioral  deficits
 may also be induced by in utero exposures of human
 fetuses to lead,  as indicated by the  apparent  higher
 incidence  of  postnatal mental retardation among
 children born of mothers experiencing elevated lead
 exposure before or during pregnancy. Thus women
 of childbearing age may be another group at special
 risk by virtue of the potential in utero exposures of
 fetuses. However, the paucity of information  on ex-
 act exposures experienced by these mothers and the
 lack of other confirmatory studies do not allow firm
 statements to be made  about  probable  threshold
 lead exposure levels for pregnant women that may
 induce  later neurobehavioral  deficits in  their
 children.
   It is even more difficult to speak of risk-to-health
 assessment in terms of threshold levels for effects of
 lead on reproduction, since  the  relevant data  are
 sparse. However, in no other aspect of health effects
 is the potential for deleterious health effects of lead
 as inherently great as in the area of reproduction and
 development.  In particular, lead crosses the placen-
 tal barrier, placing the human  fetus at direct risk.
 And such  exposure  begins at a stage of gestation
 when neural  embryonic  development is beginning.
 Placental  transfer, coupled with the  fact that an
 effective blood-brain barrier is not present in human
 fetus, means  that there is effectively a direct path
 from maternal lead  exposure to  the fetal nervous
 system.
  Available  information suggests  that  there are
several possible consequences to the newborn arising
from lead exposure. Premature birth is suggested as
                                               1-13

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being associated with elevated blood lead levels in
women, and some impairment in the heme biosyn-
thetic pathway may exist in the newborn children of
mothers having elevated blood lead levels.
  Much  of the discussion  above has  dealt  with
relationships between blood lead levels and various
biological effects of lead. This discussion was pri-
marily concerned with threshold levels  at which
health effects of lead are first observed  in different
population groups. Of additional interest is the pro-
portion of a population exhibiting a health effect at a
given  blood lead  level  (i.e.,  the  dose-response
curve). Three different assessments of dose-response
relationships for hematological  effects have  been
carried out and  published. These effects are the in-
hibition of ALAD, elevation of ALA-U, and eleva-
tion of EP levels in the blood. As noted elsewhere in
this summary, some question exists concerning the
relevance of ALAD inhibition to human health. The
other two hematological effects are relevant. Table
1-2 shows ALA-U data from two studies,  one  pub-
lished and  one done by EPA (see Chapter 13).

TABLE 1-2. ESTIMATED PERCENTAGE OF SUBJECTS WITH
 ALA-U EXCEEDING 5 mg/liter FOR VARIOUS BLOOD LEAD
                     LEVELS
Blood tead
level, /xg/dl
10
20
30
40
50
60
70
Zielhuis
estimate, %
0
0
6
24
48
76
96
Azar et al
estimate. %
2
6
16
31
50
69
84
Published studies (see Chapter 13) of dose-response
relationships also exist for erythrocyte  proto-
porphyrin and are presented in Table 1-3.

 TABLE 1-3. ESTIMATED PERCENTAGE OF CHILDREN WITH
 EP EXCEEDING SPECIFIED CUTOFF POINTS FOR VARIOUS
               BLOOD LEAD LEVELS
Blood lead
level, /ig/dl
10
20
30
40
50
60
70
80
Zielhuis
estimate,3 %
0
6
22
37
49
-
—
-
Roels et al
estimate,11 %
3
27
73
100
-
-
-
--
Piomelli
estimate,0 %
9
11
48
80
-
—
—
-
  aEP >EP ot children with blood lead levels <20 jig/dl
  bEP >82^g/dl cells
  CEP >33».g/dl
1.4.3 Populations at Risk
  The concept of  "special risk" is  defined as a
population segment exhibiting characteristics asso-
ciated significantly higher probability of developing
a condition, illness, or other abnormal status as a
result  of exposure to  a given  toxic  agent. With
respect to lead, two such segments of human popula-
tions are currently definable: preschool children and
unborn fetuses, with pregnant women  as the recip-
ient  population of concern.

1.4.3.1  PRESCHOOL CHILDREN
  There is an impressive body of data that indicates
that  children are inherently more susceptible to lead
by virtue of physiology and that they have a different
relationship to exposure sources. These physiologi-
cal factors include: (1) greater lead intake on a per-
unit-body-weight basis;  (2)  greater net respiratory
intake as well as greater net absorption and retention
of lead entering the gastrointestinal tract; (3) rapid
growth, which reduces the margin of safety against a
variety of stresses, including nutritional deficiency;
(4) certain incompletely developed defense mechan-
isms in very young children, such as the blood-brain
barrier in newborns; and (5) different partitioning of
lead in the bones of children compared to that of
adults, with only 60 to 65 percent of the lead body
burden occurring in bone, and that fraction proba-
bly being more labile than in adults.
  An important aspect of the dietary habits of very
young children in connection with lead exposure is
their normal mouthing activity, such as thumb-suck-
ing  or  tasting  of nonfood objects.  Such behavior
poses a risk of increased contact with dust and soil
contaminated  with  lead. Clinical evidence also  ex-
ists  to indicate children are at special  risk for lead
effects.  Thresholds for  anemia  and  erythrocyte
protoporphyrin  elevation are lower for children,
and  a number of neurological effects appear at lower
levels of lead  in children than in adults.
1.4.3.2 PREGNANT WOMEN
  Considerable evidence  indicates that pregnant
women are a population segment at risk with respect
to lead mainly because of increased risk to the fetus
and  maternal  complications. Lead crosses the  pla-
cental barrier and  does so at an  early  stage in
embryonic development. Although quantitative  ex-
pressions of this risk cannot be stated, certainly the
potential for damage exists.
  Pregnancy  places  a  physiological  stress on a
woman in terms of nutritional states that lead to iron
and  calcium  deficiency, in consequence of which
                                                1-14

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bone lead may be mobilized and the hematopoietic
system may be placed  at higher risk to lead ex-
posure. In addition, data suggest that elevated blood
lead levels  in pregnant women may result in in-
creased  incidence of premature membrane rupture,
placing  the  mother  as  well  as her newborn  in  a
special risk category.
1.4.3.3  UNITED  STATES  POPULATION IN
RELATION  TO  PROBABLE  LEAD  EX-
POSURES
  With the exception of those living  in areas  with
primary lead smelters, most populations exposed to
lead live in urban areas.  Residents of the central city
are at the highest risk in these urban  areas.  There-
fore, for other than point stationary  sources of  lead,
it is the urban population that is at risk, and  in par-
ticular, central city  residents. Blacks and Hispanics
are probably subject to greater exposure to airborne
lead because higher proportions of these segments of
the population live in urban areas.  In  the United
States in 1970, 149 million persons were reported to
live in, urban areas, and 64 million in  the central
cities.  These  figures  include  about   12  million
children under 5 years of age, with approximately 5
million of these children living in central-city areas.
There are  an estimated 600,000  children  in  the
United States with blood lead values greater than 40
/ng/dl. These values do not result from exposure to
airborne  lead alone; they also include exposure to
leaded paint and lead  in food. In view of the narrow
margin of safety from  currently  observed urban
blood lead levels, children exposed to an additional
increment of lead from the air would be at great risk
for adverse health effects.

  Of the  roughly  3 million U.S.  pregnancies  per
year, inner-city women are estimated to  account for
500,000. In view of available data, these women and
their unborn children are also at high risk.
                                               1-15

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                                   2. INTRODUCTION
   According to Section 108 of the Clean Air Act of
 1970, as amended in June 1974, a criteria document
 for a specific pollutant or class of pollutants shall
      . .  . accurately reflect the latest scientific
      knowledge useful in indicating the kind
      and extent of all identifiable effects on
      public health or welfare which may be ex-
      pected from  the  presence of such pollu-
      tant in the ambient air, in varying quan-
      tities.
   Air quality criteria are of necessity based  on pre-
 sently available scientific data, which in turn reflect
 the sophistication of the technology used in  obtain-
 ing those data as well as the magnitude of the experi-
 mental efforts expended. Thus air quality criteria for
 atmospheric pollutants are a scientific expression of
 current knowledge and uncertainties.  Specifically,
 air quality criteria are expressions of the scientific
 knowledge of the relationships between various con-
 centrations — averaged  over  a suitable  time
 period — of pollutants in the same atmosphere and
 their  adverse effects upon public health and the  en-
 vironment. Criteria are issued to  help make deci-
 sions about the need for control of a pollutant and
 about the  development of  air quality standards
 governing  the  pollutant.  Air  quality  criteria  are
 descriptive; that is, they describe the effects that have
 been  observed  to occur as a result of external  ex-
 posure at specific levels of a  pollutant. In contrast,
 air quality standards  are prescriptive;  that is, they
 prescribe  what a  political jurisdiction has  deter-
 mined to be the maximum permissible exposure for a
given time in a specified geographic area.
   In the case of criteria for pollutants that appear in
the atmosphere only in the gas phase (and thus  re-
 main  airborne), the sources, levels, and  effects of ex-
posure must be considered only as they affect  the
human population through inhalation of or external
contact with that pollutant.
   Lead, however,  is found in the atmosphere pri-
marily as inorganic particulate, with only a small
fraction normally occurring as vapor-phase organic
lead.  Consequently, inhalation and contact are but
two of the routes by which  human  populations may
be exposed to lead. Some particulate lead may  re-
main suspended in the air and enter the human body
only by inhalation, but other  lead-containing parti-
cles will be deposited on vegetation, surface waters,
 dust, soil, pavements, interior and exterior surfaces
 of housing — in fact, on any surface in contact with
 the air. Thus criteria for lead must be developed that
 will take into account all  principal routes of ex-
 posure of the human population.
   This criteria document sets forth what is  known
 about the effects of lead contamination in the en-
 vironment on human  health and welfare. This re-
 quires that  the  relationship between levels  of ex-
 posure to lead,  via all routes and averaged  over a
 suitable time period, and the biological responses to
 those levels be carefully assessed. Assessment of ex-
 posure must take into consideration the temporal
 and spatial distribution of lead and its various forms
 in the environment.
   This document focuses primarily on lead as found
 in its various forms in the ambient atmosphere; in
 order to assess its effects on human health, however,
 the distribution and biological availability of  lead in
 other environmental  media have been  considered.
 The rationale  for  structuring the document  was
 based  primarily on the two major questions of ex-
 posure and response. The first portion of the docu-
 ment  is devoted to lead in the environment — physi-
 cal and chemical properties; the monitoring of  lead
 in various media; sources, emissions, and concentra-
 tions  of lead; and the transport and transformation
 of lead within environmental media. The latter sec-
 tion is devoted to biological responses and effects on
 human  health and ecosystems. An  effort has been
 made to limit the document to a highly objective
 analysis of the scientific data  base. The scientific
 literature  has been reviewed through March 1977.
 The references cited  do not constitute  a complete
 bibliography but they are hoped  to be sufficient to
 reflect the current state of knowledge on those issues
 most relevant to the  establishment of an air quality
 standard for  lead.
  The status of control technology for lead has not
 been treated.  For information on the subject, the
 reader is referred to appropriate control technology
 documentation  published  by  the  Office of  Air
 Quality Planning and Standards (OAQPS), EPA.
The subject of adequate margin of safety stipulated
 in Section 108 of the  Clean Air Act  also  is  not
treated  here; this topic will  be considered in depth
by EPA's  Office of Air Quality Planning and Stan-
dards in documentation prepared as a  part  of the
process of establishing an air quality standard.
                                                2-1

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               3.  CHEMICAL  AND  PHYSICAL  PROPERTIES
3.1 ELEMENTAL LEAD
   Lead is a gray-white metal of bright luster that,
because of its easy isolation  and low melting point
(327.4°C), was among the first  of the metals to be
placed in the service of man.  Lead was used as early
as 2000 B.C. by the Phoenicians, who traveled as far
as Spain and England to mine it. Its most abundant
ore is galena, in which lead is present as the sulfide
(PbS), and from which metallic lead is readily ob-
tained by roasting. The metal is  soft, malleable, and
ductile; it is a poor electrical conductor,  and  it is
highly impervious to  corrosion. This  unique com-
bination of physical properties has led to its use in
piping and roofing, and  in containers for  corrosive
liquids. By the time of the Roman Empire, it was al-
ready  in wide  use in aqueducts and public water
systems, as well as in cooking and storage  utensils.
   Lead is unique among the toxic heavy  metals in
that it is relatively abundant in  the earth's  crust; its
abundance is estimated1  to be more than 100 times
that of cadmium  and  mercury,  two other  systemic
metallic poisons.  The great  environmental signifi-
cance of lead is the result both of its utility and of its
abundance; lead is produced  in far larger quantities
than any other  toxic  heavy metal, with world pro-
duction exceeding 3.5 million tons per year.2  The
properties of elemental lead (Pb) are summarized in
Table 3-1.
     TABLE 3-1. PROPERTIES OF ELEMENTAL LEAD
Property
Atomic weight
Atomic number
Oxidation states
Density
Melting point
Boiling point
Covalent radius (tetrahedral)
Ionic radii
Resistivity
Description
207.19
82
+2, +4
11.35g/cm3at20°C
327 4°C
1744°C
1 .44 A
1.21 A (+2), 0.78 A (+4)
21 .9 x 10"6 ohm/cm
  There are eight isotopes of lead; Four are stable
and four are radioactive. The average abundances of
the stable isotopes and the decay  characteristics of
the radioactive isotopes are listed in Table 3-2. The
stable isotopic compositions of naturally occurring
lead ores  are not identical, but rather show varia-
tions reflecting geological evolution.3 There  is no
radioactive progenitor for  204Pb. However, 206Pb,
207Pb, and 2()8Pb  are  produced by the radioactive
decay of 2™U, 2-1sU, and "2Th, respectively.  Thus
the observed isotopic ratios depend on the U/Pb and
Th/Pb ratios  of  the source from  which the ore is
derived  and  the  age  of  the ore  deposit.  The
2()hPb/204Pb isotopic ratio, for example, varies from
approximately 16.5 to 21, depending on the source.4
           TABLE 3-2.  ISOTOPES OF LEAD
Isotope
204pb
206Pb
207pb
208pb
210pb
210pb
211Pb
211Pb
212Pb
212pb
214pb
214pb
Average
abundance °°
1 4
263
208
51 5
—
—
—
—
—
—
—
—
Decay mode
Stable
Stable
Stable
Stable
P
a
0
a
ii
a
0
(V
Energy MeV
_
„_
	
_
0017
0047
1 4
082
0.36
024
072
035
Half-life
Stable
Stable
Stable
Stable
22 yr
22 yr
36 1 mm
36 1 mm
106hr
106hr
26 8 mm
268 mm
3.2 GENERAL CHEMISTRY OF LEAD
  Lead is the heaviest element in Group IVB of the
periodic  table; this is the  group that also contains
carbon, silicon,  germanium, and  tin.  Unlike  the
chemistry of carbon, however, the inorganic chemis-
try of lead is dominated by the divalent ( + 2) oxida-
tion state rather than the tetravalent ( +4) oxidation
state.  This important  chemical feature  is a direct
result of the fact that  the strengths of single bonds
between  the  Group  IV  atoms  and  other  atoms
generally  decrease as the  atomic number of  the
Group IV atom increases.5 Thus, the average energy
of a C-H  bond is 100 kcal/mole, and it is this factor
that stabilizes CH4  relative to CHr For lead, the Pb-
H energy is only approximately 65 kcal/mole, and
this is too  small to compensate for the Pb(II) —-
Pb(IV) promotional energy. It is this same feature,
of course, that explains the marked difference in  the
                                                3-1

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tendencies to catenation shown  by these elements.
Though C-C bonds are present in  literally millions
of compounds, lead  is not known to form any cate-
nated inorganic compounds.

  A listing of the solubilities and physical properties
of the more common compounds of lead is given in
Appendix B.  As can be discerned  from those data,
most inorganic lead  salts are sparingly soluble (e.g.,
PbF,,  PbCI,)  or  virtually  insoluble  (PbSO4,
PbCrO4) in water; the  notable exceptions are lead
nitrate, Pb(NO,)2, and lead acetate, Pb(OCOCH_,).,.
Inorganic lead  (II)  salts are generally relatively
high-melting-point solids with correspondingly low
vapor  pressures  at room temperatures. The vapor
pressures of the most commonly encountered lead
salts are also tabulated  in Appendix B. The decay of
lead salts in the atmosphere  is discussed in Section
6.2.2.

3.3 ORGANOMETALLIC  CHEMISTRY  OF
LEAD
  The  properties of organolead compounds (i.e.,
compounds containing bonds between lead and car-
bon) are entirely different from  those  of the  in-
organic compounds  of lead. The Pb-C bond energy
is approximately 130 kcal/mole,6 or twice the Pb-H
value  cited  above. Consequently,  the organic
chemistry  of lead is dominated by the tetravalent
( +4) oxidation state. An important property of most
organolead compounds is that they undergo photo-
lysis when exposed to light. The physical properties
of some of  the more important organolead com-
pounds are summarized  in Table 3-3.
                       TABLE 3-3. PROPERTIES OF MAJOR ORGANOLEAD COMPOUNDS
Compound
Tetramethyl lead
Tetraethy! lead
Tetraphenyl lead
Hexamethyl lead
Hexaethyl lead
aAt 13 mm pressure
At 2 mm pressure
Formula
iCH3)4Pb
(C2H5)4Pb
(C6H5)4Pb
(CH3)6Pb2
(C2H5)6Pb2


Appearance
Colorless liquid
Colorless liquid
White solid
Pale oil
Yellow oil


m p C
-275
-130
223
38
36


rjp C
110
82a
Decomposes
Decomposes
100b


  Because  of their  use as  antiknock  agents in
gasoline and other  fuels, the  most  important
organolead  compounds  are  the tetraalkyl com-
pounds tetraethyl lead (TEL) and tetramethyl lead
(TML). As would be  expected for such nonpolar
compounds, TEL and  TML are insoluble in water
but soluble in hydrocarbon  solvents (e.g., gasoline).
These  two  compounds are manufactured in  ex-
tremely large quantities (Chapter 5) by the reaction
of the alkyl chloride with lead-sodium alloy7
 4NaPb + 4C2H5C1 -*(C\Hs)4Pb + 3Pb + 4NaCl
The methyl compound, TML, is also  manufactured
by a Grignard process involving the electrolysis of
lead pellets in methylmagnesium chloride:7
2CH.,MgCl  +  2CH,Cl  +  Pb  —  (CH3)4Pb +
                    2MgCl2
  These lead compounds are removed from auto or
other  internal  combustion  engines  by  a  process
called lead  scavenging, in  which they react in the
combustion chamber with halogenated hydrocarbon
additives (notably ethylene dibromide and ethylene
dichloride)  to  form  lead  halides,  usually bro-
mochlorolead.  Such  inorganic  compounds  ap-
parently originate  as vapors  in  the combustion
chamber of  an  automobile engine.  During their
passage through the  exhaust system,  however, they
condense  to form  small  spherical  particles with
diameters  on  the  order  of  a  tew  tenths  of a
micrometer; they also condense or absorb onto  the
surfaces of co-entrained particles derived from  the
intake air or from corrosion of the exhaust  system.
Consequently, lead halides emitted from automobile
exhaust are present as vapors, as pure solid particles,
and as a coating on the surface of particulate sub-
strates. Mobile source emissions are discussed in
detail in  Chapter 6 (Section 6.2.2.1).
  Several hundred other organolead  compounds
have been synthesized, and the properties of many of
them  are  reported by Shapiro and Frey.7 Some of
these  are used in the  commercial preparation of
organomercury compounds used as fungicides, and
their  use  as catalysts and stabilizers in  industrial
processes has been investigated extensively.

3.4 COMPLEX  FORMATION AND  CHELA-
TION
  The bonding in organometallic derivatives of lead
is principally covalent  rather than ionic because of
the small difference in the electronegativities of lead
(1.8) and carbon (2.6).  As is the case in virtually all
metal  complexes,  however,  the  bonding is of  the
donor-acceptor type, in which  both electrons in  the
bonding  orbital originate from the carbon atom.
  The donor atoms in a metal  complex could, of
                                               3-2

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course, be almost any basic  atom or molecule; the
only requirement is that  a donor, usually called a
ligand, must have a pair  of  electrons available for
bond formation. In general, the metal atom occupies
a centra) position in the complex, as exemplified by
the lead atom  in  tetramethyl  lead  (a), which  is
                                   CH,
                       Pb
          H3C
                        CH-
                       (a)
tetrahedrally surrounded by four methyl groups. In
these simple organolead  compounds,  the  lead is
usually present as Pb(IV), and the complexes  are
relatively inert. These simple ligands, which bind to
metal at only a single site, are called monodentate
ligands.  Some  ligands,  however, can bind  to  the
metal atom by more than  one donor atom, so as to
form  a heterocyclic ring  structure. Rings of this
general type are called chelate rings, and the donor
molecules which form them are called  polydentate
(as opposed to  monodendate)  ligands or chelating
agents. In the chemistry  of lead, chelation normally
involves Pb(ll), leading to kinetically  quite labile
(although highly stable)  complexes that are usually
six-coordinate.  A wide  variety of biologically sig-
nificant chelates with ligands, such as amino acids,
peptides, nucleotides, and  similar macromolecules,
are known. The simplest  structure of this type is with
the amino acid, glycine, as represented in (b) for a
1:2 (metal: ligand) complex.
                    The importance of chelating agents in the present
                 context is their widespread  use in the treatment of
                 lead and other metal poisoning.
                    Since Pb(II) is  a relatively soft (or class b) metal
                 ion,8 it forms strong bonds to soft donor atoms like
                 the sulfur atoms in the cysteine residues of proteins
                 and enzymes;  it also coordinates strongly with the
                 imidazole groups of histidine residues and with the
                 carboxyl  groups  of  glutamic  and  aspartic  acid
                 residues.  In living systems, therefore, lead atoms
                 bind to these  peptide residues in proteins, thereby
                 preventing the proteins from carrying out their func-
                 tions by changing the tertiary structure of the protein
                 or by blocking the approach  by a substrate to the ac-
                 tive site of  the protein.  The role of the chelating
                 agents is to compete with the peptides for the metal
                 by forming stable chelate complexes that can then be
                 transported  from  the  protein and eventually  ex-
                 creted  by the body.  For simple thermodynamic
                 reasons (see Appendix B),  chelate complexes  are
                 much more stable than monodentate metal complex-
                 es, and it is  this enhanced stability that is the basis
                 for their ability to compete favorably with proteins
                 and other ligands  for the metal ions. The chelating
                 agents  most commonly  used for the treatment  of
                                                  O
                                                   I
                                                O-C-CH.
                                                      O
                                                      I    CD
                                                CH2-C-O
                                                         N-CH2-CH2-N
                                                                      \
                                                0-C-CH
                           O
                                                 CH2-C-0
                                                                            O
                                                                      EDTA
      O
 C-
 I
CH.
                •O.
                 •NH,
                      Pb
                            .NH,
                         \
 CH,
•C
  \\
    o
                      H2O
                       (b)
            (c)


       CH,

HS	C	CH-
                                                                  CH3   NH2
                                                     PENICILLAMINE

                                                             (d)
                                                                          • O
                                                                          'OH
                                               3-3

-------
lead poisoning are ethylenediaminetetraacetate ions
(EDTA) (c), D-penicillamine (d), and their deriva-
tives. EDTA is known to act as a hexadentate ligand
toward metals.9  Recent X-ray  diffraction studies
have demonstrated that D-penicillamine is a triden-
tate ligand (binding  through  S,  N, and O) toward
cobalt,10 chromium," and  lead,12 but monodentate
toward mercury.13'15
  It should be noted that both the stoichiometry and
structures  of metal chelate depend on pH, and that
different structures may occur in crystals from  those
manifest in solution. It will suffice to state, however,
that several  ligands can  be found that are capable of
sufficiently strong chelation with lead present in the
body under  physiological conditions to  enable their
use in the  effective treatment  of lead poisoning.

3.5 REFERENCES FOR CHAPTER 3
   I.  Moeller, T Inorganic Chemistry. John Wiley and Sons,
      Inc., New York  1953  966 p.
  2.  Dyrssen, D  The changing chemistry ot the oceans. Ambio.
      /(I) 21-25, 1972.
  3.  Russell, R  and R  Farquhar  Lead  Isotopes in Geology.
      Interscience. New York. 1960
  4  Doe, B  Lead Isotopes  Spnnger-Verlag, New York. 1970.
      p. 3-80
  5 Cotton.  F  A   and  G  Wilkinson,  Advanced Inorganic
     Chemistry. John Wiley and Sons. Inc , New York.  1972
  6  Shaw.C F. Ill, and A  L Allred. Nonbonded interactions
      in organometallic compounds  ot Group  IV  B
      Organometalhc Chem  Rev, A 50 95. 1970
 7.  Shapiro, H. and F. W. Frey. The Organic Compounds of
    Lead. Interscience Publishers, John Wiley and Sons, Inc.,
    New York, 1968, 486 p.
 8.  Basolo, F  and R G Pearson  Mechanisms of Inorganic
    Reactions. J. Wiley and Sons, Inc., New York. 1967  p.
    23-25, I 13-119
 9  Richards, S., B. Pedersen, J. Silvenon, and J. L. Hoard.
    Stereochemistry of ethylenediaminetetraacetate complex-
    es. Inorg. Chem. 3:27-33, Jan.  1964.
10  de Meester, P and D J  Hodgson  Model for the binding
    of D-penicillamme to metal ions in living systems: Syn-
    thesis and  structure of  L-histidinyl-D-penicil-
    laminatocobalt (III)  monohydrate. [CO(L-his) (D-
    pen)] H20. J. Arn Chem. Soc 99(1)-101 -104.  1977

I 1  de Meester, P and D  J Hodgson. Synthesis and  X-ray
    structure  of  L-histidmyl-D-penicillaminatocobalt  (III)
    and  L-histidmyl-D-penicillaminatochromium (III). J
    Chem. Soc. Chem  Commun. 280, 1976.
12  Freeman, H  C , G. N. Stevens, and I. F. Taylor, Jr.  Metal
    binding in chelation therapy. The crystal structure of D-
    penicillammatolead (II). J  Chem Soc Chem Commun.
    70:366-367, 1974.
13  Wong, Y  S.P C Chieh.andA J. Carty The  interaction
    of organomercury pollutants with biologically important
    sites. Can  j. Chem  51 2597,  1973.
14  Wong, Y  S, P C  Chieh, and A  J. Carty.  Binding of
    methylmercury by ammo-acids. X-ray structure of  D, L-
    penicillaminatomethylmercury (II). J. Chem. Soc. Chem.
    Commun 741, 1973.
15  Carty. A J. and N J  Taylor. Binding of inorganic mercury
    at biological sites  J Chem. Soc. Chem  Commun. 214,
    1976
                                                     3-4

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     4.  SAMPLING AND  ANALYTICAL METHODS  FOR  LEAD
4.1  INTRODUCTION
  Monitoring for lead in the environment, which in-
cludes sampling and measurement, is a demanding
task that requires careful attention. Lead is receiving
careful  scrutiny as a pollutant, and the  accurate
assessment of its impact on the environment is con-
tingent on the acquisition of valid monitoring data.
Furthermore, the movement  and accumulation  of
lead  in ecosystems occur via complex pathways and
compartments. In addition, many difficulties are in-
herent in the identification and tracing of lead in  its
various forms in the environment.  Airborne lead
originates from  manmade sources,  primarily the
automobile, and  is extracted from the  atmosphere  by
animals, vegetation, soil, and water.  Knowledge  of
the concentrations of lead in these  various media
and the movement of lead between and among them
is critical for controlling  lead pollution  and for
mitigating the adverse effects of lead in the environ-
ment on people.
  Sampling and  analytical  methods for monitoring
lead  have been  devised for almost every  purpose.
Some methods  are too tedious or  expensive for
general  use; others are relatively easily applied but
produce results  of limited utility  or questionable
validity; and  others  are  appropriate for use  in
monitoring lead  in certain systems but not in others.
The monitoring  of environmental lead can be car-
ried out with almost any precision deemed necess-
ary,  but actually  obtaining precise  and  accurate
results is not  a  trivial task in many instances. (See
Chapter 9 for  a discussion of the  difficulties  in
reproducing blood  lead  analyses.)  The  primary
problem  is  that  of  determining what  types  of
monitoring procedures are  necessary  to realize
societal objectives for protecting human health on a
practical basis.  The objective of this chapter is  to
review the status of the monitoring procedures avail-
able. Another serious  problem is the present lack  of
instrumentation for the continuous analysis of aero-
sol.
  Monitoring for lead involves an operational  se-
quence, based on  the scientific method,  as shown
schematically in Figure 4-1. The type of data to be
collected must be defined clearly on the basis of the
question(s) to be answered. The required accuracy of
the data must be determined and assured by means
of a quality assurance strategy for all aspects of the
monitoring operation. Similarly,  the sampling
strategy must be based on the type of data needed
and yet take into account requirements imposed  by
the analytical methods to be  used. The selection and
application of the analytical  methods are in turn in-
fluenced  by the kind of data needed,  the types of
samples collected, the analytical capabilities availa-
ble, and  other  factors. Ultimately, analysis of the
data obtained determines whether the sequence has
reached a satisfactory conclusion or if modifications
of any particular segments of the sequence  are re-
quired. Although there are  numerous technical
sources  of information  concerning sampling
strategy,  sampling  methods, sample  preparation,
and analyses, only a few of the most noteworthy are
cited here.  These include the National  Academy of
Sciences report  on lead,1 Stern's three-volume com-
pendium  on air pollution,2  the Geological  Survey
review of lead in the environment,3 and the National
Science Foundation  publication,  "Monitoring for
Lead in the Environment."4
  In succeeding sections, the specific operations in-
volved in monitoring are discussed. Site selection is
treated succinctly because of the dearth of criteria in
the literature  and  the necessity  for  establishing
specific site criteria for each sampling requirement.
Much  remains to be done toward  establishing cri-
teria for location of samplers. The various samplers
used to collect lead data are  described. Methods for
collecting dustfall, water, soil, and vegetation  sam-
ples are  reviewed  along  with  current sampling
methods specific for  mobile  and stationary sources.
The processing of samples for analysis is critical and
influences  the  selection  of filter  materials  and
characteristics. This is an area of monitoring that is
receiving  much attention  because  of the inter-
ferences that have been encountered.
  The  analytical section is  lengthy because of the
                                                4-1

-------
           FORMULATE HYPOTHESIS OR
      DELINEATE QUESTIONS TO BE ANSWERED
          DEFINE TYPE OF DATA NEEDED
        AND QUALITY ASSURANCE REQUIRED
PLAN SAMPLING STRATEGY
SELECT
SITE
CHOOSE
COLLECTION
METHODS
i
DETERMINE
SAMPLE
STORAGE AND
TRANSPORT
REQUIREMENTS
•
                OBTAIN SAMPLES
               ANALYZE SAMPLES
   PREPARE
   SAMPLE
MEASURE
  LEAD
  MAKE
 QUALITY
ASSURANCE
  CHECKS
            ANALYZE/INTERPRET DATA
     HYPOTHESIS CONFIRMED'

      QUESTIONS ANSWERED?
                                 NO
                              YES (END)
Figure 4-1. Sequence of operations involved in monitoring for
lead in the environment.

large variety of methods applied  to lead analysis.
Analysis is the most advanced area of monitoring
operations, and if used properly, analytical methods
are already available that are capable  of providing
all the required data.

4.2 SAMPLING
  The purpose of sampling is to obtain lead-contain-
ing particles, adsorbed gases, liquids, and solid sam-
ples  that will provide  a measure of the nature and
concentration  of  lead at  various  points  in  the
environment. Sampling encompasses not only  the
method of sample collection, but also  the selection
of sampling sites and procedures applicable to  the
processing of samples.

4.2.1  Sampler She Selection
  The location of sample collection devices  has im-
portant and pervasive  effects on the data obtained.
In monitoring ambient air for lead, the proximity to
the sampler of mobile and  stationary  sources is of
prime importance. Also of importance are the height
of the sampler intake above the ground  and the local
topography, climate, and lead level in  the soil. Ott5
has enumerated the problems and difficulties  en-
countered  in  comparing  data obtained  from  air
monitoring stations in different cities.
  General guidelines  for  locating ambient  air
samplers include the following:
    1. Samplers should be a uniform height above
       the ground, although  to  assess the risk to
       children, some samplers should also be lo-
       cated at  a child's height (2 to 3 ft).
    2. Sampler inlets should  be  at least  3 m from
       any obstruction.
    3. Samplers should be located in  areas free of
       local  source influence and  convection  or
       eddy currents.
Most  existing sampler sites do not meet  these  cri-
teria,  and  information  on sampler location is  not
usually  provided  with  data.5  The  number  of
monitoring sites in an air monitoring network should
be related  to geography, population, and sources.6
Since  there is no suitable, continuous method  for
measuring  lead in air, the sampling period and fre-
quency are also important in  the overall sampling
strategy.  It should be noted, however,  that it is  not
possible to discuss sampling plans outside the con-
text of a  particular objective (e.g., characterization
of rural or urban background levels, assessment of
health hazards to people, determination  of source
effects, or  delineation  of transport mechanisms).4
The treatment  of sampling in detail is outside  the
scope of this  discussion, but reference  should  be
made to the available sources.6-7

4.2.2  Sampling Errors
  The fidelity with which a sample reflects the quan-
tity and nature of lead in any medium being sampled
is basic to the obtaining of valid data and therefore
to an understanding  of the  phenomena  being in-
vestigated. In Section 4.2.1, the  importance of  site
selection for collecting samples of airborne lead  was
noted. In Section 4.2.6.2, the problems of dilution of
samples from mobile sources  are noted. A general
sampling error associated with sampling of airborne
particulates is discussed here.
  Most ambient sample  collections  are obtained
nonisokinetically; that is, as the air is drawn into the
sampler inlet, the speed and direction of the air are
changed. The inertial characteristic of  suspended
particulates bring about losses of larger  particles
both by drift from the sampled air stream and by im-
paction on the surface  of the sampler inlet. It  has
been shown that appreciable errors may result from
nonisokinetic sampling, primarily because of the  loss
of large particles (those with diameters exceeding 10
                                                 4-2

-------
    ).8 Generally, it is not possible to estimate the er-
ror under any specified conditions. But such errors
may be minimized by avoiding eddy formation, tur-
bulence, divergence or convergence, and changes in
direction of the sampled air stream.

4.2.3 Sampling for Airborne Particulate Lead
  Airborne lead is primarily carried by particulates
or aerosols, but in smaller concentrations, it may oc-
cur  in the form of organic gases.  Samplers range
from the widely used high-volume filter sampler to a
variety of other collectors that employ filters, im-
pactors,  and impingers.
4.2.3.1 HIGH-VOLUME SAMPLER
  The most widely used method for  sampling air-
borne particulates in the 0.1- to  lO-^m range is the
high-volume air sampler,9-10 which is routinely used
in the National  Air Surveillance  Networks.  The
method requires a vacuum cleaner type of air blower
that  draws air through a filter at rates as high as 2
m3/min. Since the normal sampling  period is 24 hr,
particulates from a sample volume of about 2000 m3
are collected. Because the air flow varies with filter
type and the degree of filter loading, it is necessary
at least to measure  initial and  final  air flows. Gross
particulate loading is determined  by carefully
weighing the filter  before and after sample  collec-
tion. The lead content is then determined by one of
the analytical methods described  m the following.
  Commercial  high-volume samplers  in which the
filter is  held in a horizontal  plane and protected
from dustfall by a housing are available.9 An 8- by
10-in.  glass fiber  filter is usually recommended.
Problems with filter selection are discussed in a sub-
sequent section.
  High-volume  samplers  are  inexpensive, easy to
operate,  and in widespread use. A measure of their
precision and ease of operation can be deduced from
the observation that an interlaboratory relative stan-
dard deviation for  total particulate collection has
been reported  of 3.7 percent over  the range 80 to
125  /*g/m3. The disadvantages of the  high-volume
sampler  include the lack of separation of particu-
lates by size, the interferences by impurities in the
filters with some analytical procedures, and the par-
ticle  fracturing  that  occurs on  impact,  which
precludes subsequent determination of size distri-
bution.9  In addition,  high-volume samplers  are
usually operated nonisokinetically; this results in an
underestimation of the airborne concentration of
large particles.'' If there is appreciable mass  in par-
ticles with  aerodynamic  diameters  greater  than
 about  10 /^m,  this  effect  may be  important.
 Isokinetic impactor  measurements run  in  Los
 Angeles  have  indicated  that  the  mass  median
 equivalent diameters  are apparently  larger  than
 those  measured  under nonisokinetic conditions.12
 This topic is also discussed in Section 6.3.2.1.
   An  interlaboratory  comparison program being
 conducted in Europe has compared total particulate
 results from  high- and  low-volume  samplers.13
 Based on the low-volume sampler data, the preci-
 sion  of total particulate  collection of the  high-
 volume sampler  is estimated at  ±  0.5 ju,g/m3. Of
 course, such comparisons apply only to the particu-
 lar conditions and  methodology  of  sampling  and
 analysis used  in that study.

 4.2.3.2 D1CHOTOMOUS SAMPLER
   The size distribution of airborne particulates can
 be determined by  using multistage impactors  and
 impingers or  by analyzing unfractionated samples.
 Such information is desirable for monitoring sources
 of a  pollutant as  well  as for  assessing potential
 effects of the pollutant on human health. The above
 techniques are expensive to use on a large scale and
 generally  require  extended  sampling  periods.
 Measurements14 have indicated that airborne partic-
 ulates usually have a bimodal size distribution and
 also that there is a distinct difference in the effects of
 small and large particles on humans.15
   A dichotomous sampler  for particulates has been
 designed to collect and fractionate samples into two
 size ranges.l(l The dichotomous sampler uses virtual
 impaction to avoid the particle bounce errors fre-
 quently encountered with cascade  impactors.17 Vir-
 tual impaction involves the separation  of particles
 into separate air streams by inertial means.16 In the
 apparatus, the largest  portion of  the air stream  is
 pulled through an annular path so that it changes
 direction, while a small air flow is maintained  in a
 straight path.  The inertia of the larger  particulates
 tends  to keep them in the straight path while the
 smaller particles are diverted with the main  stream.
 Two stages of virtual  impaction have been  used to
 obtain better fractionation. Membrane filters in the
 two air paths collect  the  respective  samples.  The
 particle diameter demarcation of the two fractions is
 normally  between  2.0  and  3.5  /urn  in  various
 designs.  Commercial  dichotomous  samplers  are
 available, but  they are  considerably more expensive
 than high-volume samplers.
  Tests of a prototype dichotomous sampler in St.
Louis indicated16 that  80 percent of the particulate
lead was contained in  particles  less than  2  fj,m in
                                                4-3

-------
diameter, whereas only 20 percent was found to be
in larger particles. Other tests to evaluate the perfor-
mance ofdichotomous samplers are under way.18

4.2.3.3  TAPE SAMPLER
  Though  dustfall  and high-volume collectors
usually  require 24 hr sampling periods to obtain a
sufficient analytical sample, there may be a need in
source and transport studies to monitor airborne
particulates for  shorter  time  intervals.  The  tape
sampler draws air through a spot on a filter tape that
advances automatically at preset intervals (e.g., ev-
ery 2 hr).9  At a  sampling rate of about 0.56 m3/hr
(20 ft3/hr) for a 2-hr interval and with a 2.54-cm
(1-in.) spot diameter, it  is  possible to analyze the
collected sample for lead  using anodic  stripping
voltammetry analysis.19 Atmospheric  con-
centrations of lead ranging  from 0.1  to 2.0 /tig/m3
were  measured at monitoring  stations in Chicago
and Washington using tape samplers.19 Diurnal cy-
cles  in airborne  lead concentrations were obtained
that  correlate with manmade sources of lead.

4.2.3.4  IMPACTORS AND IMPINGERS
  Impactors  are multistage paniculate  collection
devices designed to provide a number of size frac-
tions.  The modified Andersen cascade  impactor
used  in the  National Air  Surveillance Networks
(NASN) is described here.20 Others are described in
standard texts.2-21
  The cascade impactor fractionates particles in a
series of five  or six collection stages.20 Particles pass
through a  series  of jets, 400  per stage, that are
progressively smaller. Under each series  of jets is a
collection plate.  The size fraction of particles col-
lected at  each stage depends  on  the air velocity,
geometry, and previous  stages. The last  stage con-
sists of a filter. Air is pumped through the impactor
at 0.14 to 0.17 m3/min by means of an air pump on
the downstream side. Aluminum foil is used as the
collector, and the size  fraction  is determined  by
weighing before  and after  a 24-hr  sample is col-
lected.  Five  fractions are usually  obtained: < 1.1,
1.1 to 2.0, 2.0 to 3.3, 3.3 to 7, and > 7  fj.m.
  Results obtained by the NASN22 indicate that lead
particulates typically have mass median diameters in
the range of 0.25 to 1.43 fj.m. Analysis  by optical
emission spectrography indicated that for particles
less than 0.5  (j.m  in diameter, the lead content was 2
to 4 percent. A cascade impactor has also been ap-
plied to multielement size characterization of urban
aerosols.23
  A size-selective particle  sampler  using cyclones
has also been described,24 and  a ten-fraction-size
sample can be obtained with the Lundgren impac-
ted
  Impingers  collect atmospheric  aerosols by  im-
pingement onto a surface submerged in a liquid.2-9
Impactors are sometimes called dry impingers. As in
impactors,  impingement  relies  on the inertial
characteristics of the particle for collection on a sur-
face.  High collection  efficiencies for  particles as
small as 0.1 yum may be obtained in wet impingers.2
4.2.4 Sampling  for Vapor-Phase Organic  Lead
Compounds
  In determining the total quantity of lead in the at-
mosphere, air is drawn through a membrane or glass
filter for  collecting  particulate  lead  and  then
through a suitable reagent or absorber for collection
of gaseous compounds that pass through the filter.26
Since the normal filter used has a nominal 0.45-fim
pore size, analysis by this method will include  any
material that passes through these pores, although it
is considered to be primarily organic lead. Organic
lead may be  collected on iodine crystals, adsorbed
on  activated charcoal,  or  absorbed  in  an  iodine
monochloride solution.4 Reviews of the procedures
are available.27-28
  The procedures using iodine monochloride have
been described and are claimed to be effective.26 In
one experiment, two bubblers containing the solu-
tion were placed  in series  in the sampling  train.
Head levels  corresponding to about 2.0 /n,g/m3 of
organic  lead were obtained in  the first bubbler,
whereas the second gave a blank response, indicating
that the collection efficiency of the first bubbler  was
essentially  100 percent and  that the method is quan-
titative. Analyses  were accomplished  with atomic
absorption spectrometry after chelation of the lead
and extraction into an organic solvent. It should be
noted, however, that  the detection sensitivity  was
low and that the  use of bubblers limits the sample
volume.

4.2.5 Sampling for Lead in Other Media
  In some respects, sampling for lead in water, soil,
dustfall, or vegetation  can  be easier than sampling
for airborne lead. However, the sampling conditions
may be equally as complex and  have  a  first-order
impact on the measurements.

4.2.5.1  WATER
  Heavy metals may be distributed in water as ions,
as chemical  complexes, or as species  adsorbed on
suspended  matter.4 Methods for  sampling   and
                                                4-4

-------
analysis of lead in water have been extensively de-
scribed.29-30 Sample containers may be either glass
or plastic. The dynamics of the water body should be
considered, and defined procedures and precautions
should  be followed.4 A variety of procedures,  each
associated  with particular  objectives,  exists  (e.g.,
separation of dissolved and suspended  lead  and
preservation of water samples to retain their original
state).
  Analysis of lead in water is typically accomplished
with atomic absorption and  emission spectroscopy,
although analytical  methods for  other media are
also applicable. The natural lead content of lakes
and rivers lies in the range of 1 to 10 /ug/liter,  with
an average value of 6.6 jug/liter for North American
rivers.1 Thus, it is  commonly found  necessary to
concentrate the  sample by chelating and extracting
the lead or by  evaporating the water.3 Techniques
for water analysis have been reviewed recently by
Fisherman and Erdman.31
4.2.5.2 SOIL
  Lead in soil samples collected from nearly 1000
locations around the United  States ranges from less
than 10 to about 700 ppm, with a mean concentra-
tion of  16 ppm.3 Deposition of lead on soil from the
atmosphere results in extreme vertical concentration
gradients, since  lead is relatively immobile in soil.4
It has  been  estimated that an  average  of 1 ^g
Pb/cm2- year from rainout or washout or  both, and
0.2 jitg Pb/cm2« year from  dust accumulates at or
near the soil surface.32 Horizontal gradients of lead
concentrations in soil occur as the result of natural
and manmade  sources.  The lead content of soil
decreases  rapidly with  distance from  emission
sources; for example, reductions of 75 percent are
observed in moving from  8 to 32 m from a high-
way.33 This point is discussed in detail in Chapter 6.
  Soil sampling is  not complex.4 Vegetation  and
large  objects  should  be  avoided,  and  a repre-
sentative site should be selected. The  vertical in-
tegrity of the sample should be preserved and noted.
The sample should be air-dried and stored in sealed
containers. The sampling should be planned to ob-
tain results representative of the conditions being in-
vestigated.  Most of the analytical procedures used
for  airborne particulates are applicable to soils, but
the  results may not  be comparable.  Many tech-
niques, including optical emission spectrography, X-
ray spectrography,  atomic  absorption,  and  the
electron microprobe have  been used for  soil lead
analysis.3 X-ray diffraction has been used to analyze
soil samples for lead emitted by automobiles.34
4.2.5.3  DUSTFALL
  All particles suspended in air are affected by grav-
itational settling.  The settling velocities of larger
particles (^5 to  10 pm) are such that they will be
transported shorter distances than the smaller parti-
cles (< 1 /j.m), which have nearly negligible settling
velocities.  Thus dustfall collections can be used to
monitor the dispersion of paniculate lead from a
specific source. The collections are made by placing
open containers at appropriate sites free of overhead
obstructions.9-10 Using buckets to measure dustfall
can lead to inaccurate data; wind eddies created by
the walls of the bucket may greatly affect deposition.
The dustfall surface should be smooth and flat, pre-
senting  as little disturbance to the wind as possible.
These points are discussed by Patterson.35
  Dustfall  is generally reported in units of grams per
square  meter per  month  (g/m2-mo) and  may be
analyzed by the methods described for particulates
collected on filters.9 The "ASTM Standard Method
for Collection and Analysis of Dustfall" provides
detailed procedures.36 One  comparison  of  lead
quantities collected by dustfall and by filtration in-
dicated  consistently that the lead content of particu-
lates collected  by filtration  in  the high-volume
sampler was higher than in dustfall.37 This is a result
primarily of the low settling velocities of the smaller
particles, which make up a significant fraction of the
total particulate.
4.2.5.4  VEGETATION
  Lead  analysis of plant  tissues has been less exten-
sive than studies in other media. Lead deposited on
leaf surfaces by   fallout  can  be  removed  and
analyzed.38 Lead in plants  is usually observed to be
less than 1  ^tg/g  dry weight, although levels as  high
as 31 uglg  have been cited.1 Plants can absorb solu-
ble lead from soils, but most soil lead is in forms not
available to plants.1 Leafy portions of plants often
exhibit higher concentrations of lead, but in general,
at least  50  percent of this  lead can be removed by
washing.' Since the presence of lead inside the plants
may manifest different effects than that on the plant
surface, attempts should be made to differentiate be-
tween these two conditions.
  Little mention  appears  in  the literature of
methods for the field sampling of plant life for
environmental studies. The standard methods and
procedures usually are focused  on statistical sam-
pling for determination of nutrient elements in food
crops.
  Plant  tissue collection and  treatment  have been
reviewed by Skogerboe  et  al.4  Sampling of plant
                                                4-5

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materials is generally carried out by random selec-
tion  of the indigenous species  representative of a
given area of interest. Where the entire plant is not
collected, emphasis is usually placed on the portion
of the plant consumed by herbivores or harvested for
market. In developing sampling plans, there should
be close  coordination  between  plant and animal
sampling groups, especially where foodchains are in-
volved.
  Before analysis, a decision must be made  as to
whether or not the plant material should be washed
to remove surface contamination from fallout and
soil particles. If the plants are sampled in a study of
total lead contamination, or if they serve as animal
food  sources, washing should  be  avoided. If the
effect of lead on  plant processes is being studied, or
if the plant is a source of human food, the plant sam-
ples  should be washed. In either case, the decision
must be made at the time of sampling,  as washing
cannot be effectively used after the plant materials
have  dried.  Neither can fresh  plant  samples be
stored for any length of time in a tightly closed con-
tainer before washing, because molds and enzymatic
action may affect the distribution of lead on and in
the plant tissues.  Freshly picked leaves stored  in
sealed polyethylene bags  at  room temperature
generally mold in a  few days. Storage time may be
increased to approximately 2 weeks by refrigeration.
  Methods reported in the literature for removing
surface contamination  vary considerably,  ranging
from mechanical wiping with a camel-hair brush to
leaching in mineral acids or EDTA. Removal of sur-
face  contamination with minimum leaching of con-
stituents  from  leaf  tissue  can generally  be  ac-
complished by using  dilute solutions of selected syn-
thetic detergents followed by rinsing in deionized
water.
  After collection, plant samples should be  dried as
rapidly  as  possible to   minimize  chemical  and
biological changes. Samples that are to be stored for
extended periods of  time or  to be ground should be
oven-dried  for  at least  4  hr  at 70°C to arrest
enzymatic  reactions and render the plant  tissue
amenable to  the grinding process. Storage in sealed
containers is always  advisable.

4.2.5.5 FOODSTUFFS
  In 1972, lead was  included in  the Food and Drug
Administration  Market  Basket  Survey,  which in-
volves nationwide sampling of  foods representing
the average diet  of an 18-year-old male (i.e., the in-
dividual  who on a statistical basis eats the greatest
quantity  of  food).39 Various food items from  the
different food classes are purchased in local markets
and made up into meals in the proportion that each
food item  is ingested; they are then cooked or other-
wise prepared as they would be consumed. Foods are
grouped into 12 food classes,  then composited and
analyzed chemically. The quantities represented in
the Total  Diet Survey and the percentages of these
foods grouped in the diet are presented in Table 4-1.
          TABLE 4-1. DAILY FOOD INTAKE39
Food consumption

I
II

III

IV
V
VI
VII
VIII
IX
X

XI
XII


Food group
Dairy products
Meat, fish, and
poultry
Gram and cereal
products
Potatoes
Leafy vegetables
Legume vegetables
Root vegetables
Garden fruits
Fruits
Oils, fats, and
shortening
Sugar and adjuncts
Beverages
(including water)
Total
Avg
g'day
consumed
756

290

369
204
59
74
34
88
217

52
82

697
2922
%of
total
diet
26.1

9.9

126
7.0
2.0
2.5
1 2
30
7.4

1 8
28

249
	
4.2.6 Source Sampling
  Sources of lead have been well identified and in-
clude automobiles, smelters  (lead  and other non-
ferrous metals), coal-burning facilities, battery
manufacturing plants, chemical processing plants,
and facilities for scrap processing and welding and
soldering  operations. An important secondary
source is fugitive dust from mining operations and
from soils  contaminated  with automotive  emis-
sions.34 A  complete discussion  of  sources of lead
emissions is given in Chapter 5. The following sec-
tions discuss the sampling of stationary and mobile
sources, which require different sampling methods.

4.2.6.1  STATIONARY SOURCES
  Sampling of stationary sources for lead  requires
the use of a sampling  train at the source to sample
the effluent  stream. Both particulates and vapors
must be collected by the sampling train, and often a
probe is inserted directly into the stack or exhaust
stream. In the tentative ASTM method for sampling
for  atmospheric  lead,  air  is  pulled through a
0.45-fj.m membrane filter and  an activated carbon
adsorption tube.40 In a study of manual methods for
                                                4-6

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 measuring emission concentrations of lead and other
 toxic materials,41 use of a filter, a system of im-
 pingers, a metering system, and a pump was recom-
 mended.  The  recommended solution  in the im-
 pingers was nitric acid.  More  recently, impinger
 solutions containing iodine monochloride have been
 shown to be effective.26
   Since lead in stack emissions may be present in a
 variety of physical and chemical forms, source sam-
 pling trains must be designed to trap and  retain both
 gaseous and paniculate lead.

 4.2.6.2 MOBILE SOURCES
   A variety of procedures has been used to obtain
 samples  of auto exhaust  aerosols for   subsequent
 analysis for lead  compounds.
   In one such procedure, a large horizontal air dilu-
 tion tube was designed to segregate fine combustion-
 derived aerosols  from larger lead particles ablated
 from  combustion chamber and exhaust deposit.42 In
 this procedure, hot exhaust was ducted into a 56-cm-
 diameter, 12-m-long, air dilution tunnel  and mixed
 with filtered ambient air in a 20-m-diameter mixing
 baffle in a concurrent flow arrangement. Total ex-
 haust and dilution air flow rate was 28 to 36 m3/min,
 which produced a residence time of about 5  sec in
 the tunnel.  At  the downstream end of the tunnel,
 samples of the aerosol were obtained by means of
 isokinetic probes facing upstream, using filters or
 cascade impactors. Properly designed air dilution
 tubes of this type have very  few  aerosol  losses for
 particles smaller than about 2 /u,m, the size that can
 be respired into human lungs.43
  Air-diluted aerosols from cyclic auto  emissions
 tests have been accumulated  in a large plastic bag.
 Filtration or impaction of aerosols from the bag
 samples produces  samples suitable  for  lead
 analysis.44 Because of the rather  lengthy residence
 time,  the bag technique may  result in the measure-
 ment  of anomalously large aerosol sizes  because of
 condensation of  low-vapor-pressure  organic  sub-
 stances onto the lead particles. This effect may be
offset, however, by fallout processes that  apply pri-
marily to larger particles (see above).
  A low-residence-time sampling  system has  been
 used that is  based on proportional sampling of raw
exhaust, followed by  air dilution and filtration or
 impaction.45'46 A  relatively large sample  of aerosol
constituents can be obtained  because of the  high
sampling rates of the raw exhaust. Since  a constant
proportion of the sample flow to the total exhaust
flow must  be maintained, this technique may be
limited by  the  response time of the equipment to
operating cycle phases that cause relatively small
transients in the exhaust flow rate.
   Most research on aerosol emissions in recent years
has used various configurations of the horizontal air
dilution tunnel.42 Several polyvinyl chloride dilu-
tion tunnels have been used with good success.43-47'48
These 46-cm-diameter tunnels of varying  lengths
have  been  limited by exhaust temperatures to total
flows above approximately  11  m3/min. Buildup of
electrostatic charge on  the walls of these plastic
systems can cause abnormally high wall  losses, but
these can be avoided  by  wrapping the tunnel  with a
grounded conductive cable at  about  30-cm inter-
vals.47 Similar tunnels have been used in which a
centrifugal fan located upstream is used rather than
a  positive  displacement  pump   located
downstream.43 This geometry produces a slight posi-
tive pressure in the tunnel and expedites  transfer of
the aerosol to holding chambers for studies of aero-
sol growth. Since the total exhaust plus dilution air
flow is not held constant in this system, there may be
slight sample disproportionation. However, these
errors can  be minimized by maintaining a very high
dilution air/exhaust flow ratio.43
   There have also been a number of studies per-
formed using total filtration of the exhaust stream to
arrive at material balances for lead using  rather low
back-pressure metal  filters.45'49'51 The cylindrical
filtration unit used in these studies is better than 99
percent effective  in retaining lead particles.51 Sup-
porting data for lead balances generally confirm this
conclusion.52
   Thus a wide variety of sampling and total exhaust
filtration procedures have been used  to measure the
mass  emissions of  lead compounds from  auto-
mobiles. Each  has its appropriate area  of  appli-
cation, depending on the objectives  of the various
research program carried out. The air dilution tun-
nel technique is most convenient, is compatible with
the usual  gas  emission measurements,  and  has
therefore been most commonly used.
4.2.7  Filter Selection and Sample Preparation
   In sampling  for  lead  particulates, air  is drawn
through filter materials such as fiber glass, asbestos,
cellulosic  paper,  or porous  plastics.2-4  These
materials include trace elements that can interfere in
the subsequent analysis.53'55 If the sample is  large,
then the effects of these trace elements are negligi-
ble, but this is not always the case.56  When samples
are prepared for analysis, reduction  of the mass of
filter  material  is  often  accomplished by ashing,
either chemically or in an oven.4  The nature of the
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filter  determines the  ashing  technique.  In  other
methods of analysis — X-ray fluorescence, for ex-
ample— analysis can be performed directly on the
filter if the filter material is suitable.16 Because the
nature and performance of filter materials are still
under investigation, general criteria for their selec-
tion cannot be given.4  A general review of filter
materials is available.57
  The main advantages of glass-fiber filters are their
low pressure  drop and high particle collection effi-
ciency at high flow rates. The  main disadvantage is
the variable  lead  content.  In  one investigation of
Nuclepore filters, examples were given in which the
analysis of samples and blanks showed results that
did not differ sufficiently to allow use  of the data.4
Others have  shown that the variability of residual
impurities in  some glass filters  makes their use inad-
visable in  most cases,54-55  and they  place a high
priority on the standardization of a suitable filter for
high-volume  samples.56 Other investigations have
indicated, however, that glass-fiber filters are avail-
able now that  do not present a  lead interference
problem.58 The collection efficiencies of filters, and
also of impactors, have been shown to  be dominant
factors in the quality of the derived data.59 The rela-
tive effectiveness of dry ashing (either at  low tem-
peratures  in  an  oxygen plasma  or at high  tem-
peratures) and of wet ashing by acid dissolution is a
subject of current  concern. Either technique will
give good results if employed properly.4'55

4.3 ANALYSIS
  A variety of useful analytical procedures is avail-
able for determination of lead in the environmental
samples. The choice of the best method in a given
situation depends on the nature of the data required,
the type of sample being analyzed, the skill  of the
analysts, and the equipment available. For general
determination of elemental lead, atomic absorption
spectroscopy is coming into wider use. However, if
multielement analysis is required, and if the equip-
ment  is available,  X-ray   fluorescence  has  been
shown  to be capable of rapid,  inexpensive
analyses.16 Other analytical methods have specific
advantages that  call  for  their continued  use  in
special  studies.  Only those analytical techniques
receiving current use in lead analysis are described
in the following. More complete reviews are availa-
ble in the literature.3'4*29

4.3.1  Colorimetric Analysis
  Colorimetric or spectrophotometric analysis for
lead using dithizone (diphenylthiocarbazone) as the
reagent has been  used for many years.60'62 This
method is the primary one recommended in a Na-
tional Academy of Sciences report on lead,1 and it is
the basis of the tentative method of testing for lead in
the atmosphere by the American Society for Testing
and Materials.40 Because of its history, it has served
as a reference by  which other methods have been
tested.
  Dithizone is an organic compound that reacts with
lead salts to form an intensely colored chelated com-
plex.  This complex  has an absorption  maximum,
with a known extinction coefficient, at a wavelength
of 510 nm, which is the basis of the measurement.
Standards can be prepared for calibration purposes
by adding known quantities of lead to  reagents.
  The procedures for  the Colorimetric dithizone
analysis require  a  skilled  analyst if reliable results
are to be obtained. The method has been analyzed,4
and the procedures  are given in the literature.4'40
The  American Society for Testing  and Materials
conducted a  collaborative test  of  the dithizone
method63  and concluded that  the ASTM dithizone
procedure gave  satisfactory precision  in the deter-
mination of paniculate lead in the atmosphere.
  The Colorimetric dithizone method has the advan-
tage of acceptability by professional organizations.
In addition, the required apparatus is simple and
relatively  inexpensive,  the absorption is linearly re-
lated to the lead  concentration, the method  requires
only a few micrograms of lead in the sample, large
samples  can  be used, and  interferences can  be
removed.4 Realization of these advantages depends
on  meticulous  attention to  the  procedures  and
reagents.  This requires  a relatively  lengthy pro-
cedure and thus a  high cost per sample.

4.3.2  Atomic Absorption Analysis
  Atomic absorption (AA) spectroscopy is the more
generally  accepted method for the measurement of
lead in environmental sampling.4 A  variety of lead
studies  using  AA  analysis  have  been re-
ported. 26,55,58,64,65
  In AA,  the lead determination is made by measur-
ing the resonance absorption of lead  atoms. The at-
tenuation  of the light beam passing through the sam-
ple is logarithmically related to the concentration of
the atoms being measured. The  lead  atoms in  the
sample must be  vaporized either in a precisely con-
trolled flame or in a nonflame medium. The sample
solution enters the flame through a  nebulizer. The
lead absorption  wavelengths  are precisely  at 217.0
nm and 283.3 nm. These wavelengths are produced
in a hollow cathode  lamp containing lead. The light
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beam, after passing through the flame, is separated
in a  monochromator and  detected with  a  photo-
multiplier. AA requires frequent use of calibration
standards to obtain precision and accuracy. Typical
precision is 1 to 5 percent. Several hundred samples
can be analyzed in an 8-hr day if sample preparation
procedures are simple.
  In  an  analysis using  AA  and high-volume
samplers, atmospheric concentrations of lead were
found to be 0.63 ± 0.30 ng/scm at the South  Pole.64
Lead analyses of 995 paniculate samples from the
NASN were accomplished  by  AA to an indicated
precision of 11  percent, with a 0.15 jug/m3 detection
limit.58
  Atomic absorption requires as much care as other
techniques to  obtain highly precise data.  Back-
ground absorption,  chemical  interferences,  back-
ground light losses, and other factors can cause er-
rors. A major problem with AA is that it has become
so popular that untrained operators are using it in
many laboratories. But for  general purposes, AA is
the most readily applicable of any of the analytical
methods.
  Techniques  for  AA are  still evolving, and  im-
proved performance involving  nonflame atomiza-
tion systems, electrode-less discharge  lamps, and
other equipment refinements and  technique
developments are to be expected.4
4.3.3 Anodic Stripping Voltammetry
  Electroanalytical methods of microanalysis based
on  electrochemical  phenomena are  found in a
variety of  forms.66'67 They are characterized by a
high degree of  sensitivity, selectivity, and accuracy
derived from   the  relationships between current,
charge, potential,  and time for electrodes in solu-
tions. The electrochemistry of lead is based pri-
marily on the plumbous ion, which behaves reversi-
bly in ionic solutions and has a reduction potential
near -0.4 volt versus a standard calomel electrode.4
Voltammetry,  the  electrometric  method with
greatest sensitivity for lead, is discussed here. Other
methods are described in the references  cited  above.
  Anodic stripping voltammetry  (ASV) describes
the process by which the component of interest, lead,
is selectively deposited on an electrode by reduction
in order to concentrate the component.66 The work-
ing electrode may be a mercury film  on a wax-
impregnated graphite electrode. After all of the lead
in solution is  reduced  onto  the  electrode,  the
analysis involves a stripping process.  In this, the lead
is oxidized by means of a linearly variable voltage
that is applied to the electrode. The voltammogram,
a plot of current versus voltage, shows a peak corres-
ponding to the oxidation of the lead. The area of the
peak corresponds to the quantity of lead ions avail-
able at the stripping voltage.
  ASV was  applied to the analysis of lead in  2-hr
samples obtained with a spot tape sampler.19 Be-
tween 80 ng and  2.4 jug of lead was present in the
samples. The average standard deviation obtained in
the lead measurements was 5.9 percent.  A detailed
procedure for sample preparation  and analysis has
been published.19
  Voltammetry was also used in analysis of panicu-
late lead collected by an impactor from the ambient
atmosphere.68 Lead concentrations found were in
the 600- to 3000-ng/m3 range.
  Current practice with  commercially  available
ASV equipment allows lead  determination at the 1
ppb level with routine 5- to 10-percent relative  pre-
cision.4  Extension to 0.1-ppb  levels  is attainable
with modified techniques.
  Differential ASV6"3 and differential-pulsed  ASV70
are reported to  give  improved sensitivity and  to
facilitate more rapid analysis, thus lowering the cost.

4.3.4 Emission Spectroscopy
  Optical  emission  spectroscopy has  been used to
determine the lead  content of soils, rocks,  and
minerals at the 5- to  10-ppm  level with a relative
standard deviation of 5 to  10 percent;62 this method
has also been applied to the analysis of a  large num-
ber of air samples.58-71 The primary  advantage of
this method  is that  it allows simultaneous analysis
for a large number of elements in a small sample of
the material.
  Emission spectroscopy essentially consists of ob-
serving the optical emission  spectra of material ex-
cited in a  spark,  arc, or flame. The wavelength and
intensity of the characteristic emission wavelengths
of the elements provide both qualitative and quan-
titative data  on composition. Before 1960, the emis-
sion spectrometer was the most common  instrument
in trace-detection laboratories.72

  When used for a single element such as lead, emis-
sion spectroscopy is at a disadvantage because of the
expense of  the   equipment,  the  required  special
operator training, and the use of photographic film
in the detection process.4 In  a study of environmen-
tal  contamination by  automotive lead, sampling
times were much  reduced  by using  a sampling tech-
nique in which lead-free porous graphite was  used
both as the  filter medium and  the electrode in the
spectrometer.70'73 Lead concentrations of 1 to  10
                                                4-9

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     3 could be detected after a half hour flow at
800 to 1200 ml/min through the filter.
  Scott et al. analyzed composited particulate sam-
ples obtained with high-volume samplers for about
24 elements, including lead, using a direct-reading
emission  spectrometer.74 Over  1000  samples  col-
lected by the NASN in 1970 were analyzed. Careful
consideration of accuracy and precision led to the
conclusion that optical emission spectrometry is a
rapid and practical technique for analysis of particu-
lates.

4.3.5  Electron  Microprobe
  When an  intense electron beam is incident on a
material, it produces, among other forms of radia-
tion, X rays whose wavelengths depend on the ele-
ments present in the material and whose intensity de-
pends on the relative quantities of these elements.
This X-radiation  is the basis of the electron micro-
probe method of analysis.  An electron beam  that
gives a spot size as small as 0.2 /j.m is  possible. The
microprobe  is  often  incorporated in a  scanning
electron microscope that allows precise location of
the beam. Under  ideal  conditions, the analysis is
quantitative, with an accuracy of 1 to 3 percent. The
mass of the analyzed  element  may be in the 10'14 to
10-'6g range.75
  Ter  Haar  and  Bayard76 applied  the  electron
microprobe method to the analysis of the composi-
tion of airborne lead-containing particles.  Particles
collected  on membrane  filters were  mounted on
special substrates and  analyzed  for lead com-
pounds.76  The analysis was based  on  the  ratios of
elemental  X-ray intensities. From an environmental
monitoring viewpoint, the ability  to determine the
composition of  complex lead particulates with  high
precision was demonstrated. The percentage com-
position of lead compounds in the sample ranged
from a low of 0.1 percent to a high of over 37  per-
cent.
  Electron microprobe analysis is  not a widely ap-
plicable monitoring method.  It requires expensive
equipment, complex sample preparation, and a high-
ly trained operator. The method is unique, however,
in providing composition information on individual
lead particles, thus permitting the  study of dynamic
chemical  changes  and perhaps allowing  improved
source identification.

4.3.6  X-Ray Fluorescence
  X-ray fluorescent emissions that characterize the
elemental content of a sample occur when atoms are
irradiated at sufficient energy to remove an inner-
shell  electron.4  This fluorescence  allows
simultaneous identification of a range of elements,
including lead. For example, 22 elements were iden-
tified and  quantitatively analyzed  in particulate
samples from dichotomous samplers without inter-
mediate sample preparation.16 This  analytical
method is identical to that described for the electron
microprobe in  the  preceding section  but utilizes
different excitation sources.
  X-ray fluorescence requires a high-energy irradia-
tion  source. X-ray tubes,16'23 electron beams,75 and
radioactive isotope sources77 have been used exten-
sively.78-79  To  reduce  background,  secondary
fluorescers have been employed.16 The fluorescent
X-ray  emission from the sample  may be analyzed
with a  crystal monochromator and detected  with
scintillation, with proportional counters,4 or  with
low-temperature  semiconductor  detectors  that
discriminate the energy of the fluorescence. The lat-
ter technique requires a very low  level  of excita-
tion.16
  X-ray emission induced  by charged-particle ex-
citation (proton-induced X-ray emission, or PIXE)
offers an attractive alternative to the more common
techniques.80-82  Recognition  of  the potential  of
heavy-particle bombardment for  excitation occur-
red  in  1970, and  an interference-free  sensitivity
down to the picogram  range  was demonstrated.80
The  excellent capability of accelerator beams for X-
ray  emission analysis  is  partially due  to  the
relatively low background radiation associated with
the  excitation. The  main  contribution  is
Bremsstrahlung from secondary electron  emission.
The  high particle fluxes obtainable from accelera-
tors  also contribute  to the sensitivity of the PIXE
method. Literature reviews83'86 on approaches to X-
ray elemental analysis agree that protons of a few
MeV energy provide a  preferred  combination for
high sensitivity analyses  under conditions less sub-
ject to matrix interference effects. As a result of this
premise, a  system designed for routine analysis has
been described,81 and papers involving the use of
PIXE   for  aerosol  analysis have recently  ap-
peared.81-82
  Advantages of X-ray fluorescence methods in-
clude the ability to detect a variety of elements, the
ability to analyze with little or no sample prepara-
tion, and the availability of automated  analytical
equipment.  Disadvantages include the need for low
blank  filters, expensive equipment, liquid  nitrogen
(e.g.,  for  energy-dispersive  models,  and highly
trained analysts. The detectability level for lead  is
about  20 ng/cm2 of filter area, which is well below
                                               4-10

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the quantity obtained  in  normal sampling periods
with the dichotomous sampler.16

4.3.7  Methods for Compound Analysis
   Colorimetry, atomic absorption, and anodic strip-
ping voltammetry are restricted to measurement of
total  lead and thus cannot identify the various com-
pounds of lead.  The electron microprobe and other
X-ray fluorescence  methods provide approximate
data on  compounds on the basis of the ratios  of ele-
ments present.76  Gas  chromatography  using  the
electron capture detector  has been demonstrated to
be useful for organic lead compounds.28 Powder X-
ray diffraction techniques have been  applied to the
identification of lead compounds in soil.34

4.4 CONCLUSIONS
   To monitor lead aerosol in air, sampling with the
high-volume sampler and  analysis by atomic absorp-
tion spectrometry have emerged as the  most widely
used method. Sampling in this way does not provide
for fractionation of the particles according to size,
nor  does  it allow  determination  of  the  gaseous
(organic)  concentrations; these  capabilities may
prove important for  special studies. The size  distri-
bution of lead aerosol is  important in considering
questions  regarding  exposure by  inhalation; sam-
pling  with   cascade impactors or  dichotomous
samplers is necessary to such evaluations. To deter-
mine  gaseous lead, it is necessary to back the filter
with chemical scrubbers or a crystalline iodine trap.
   X-ray  fluorescence  and  optical  emission
spectroscopy are applicable to multielement analysis
and are  convenient to apply to  the measurement of
lead in such studies. Because of the many environ-
mental variables  implicit in site monitoring,  the
development of useful biological monitoring techni-
ques may  be of more direct utility.

4.5 REFERENCES FOR CHAPTER 4
   1.  Lead: Airborne Lead in Perspective. National Academy of
     Sciences, Washington, D  C. 1972 330 p.
  2.  Stern,  A. C. (ed.). Air Pollution. 2nd ed. Academic Press,
     New York, 1968
  3.  Lovering, T. G (ed.). Lead in the Environment Geologi-
    cal Survey Professional  Paper  957. U.S. Government
     Printing Office, Washington, D C  1976. 90 p
  4 Skogerboe, R. K., A. M. Hartley, R. S.  Vogel, and S. R
     Koirtyohann. Monitoring  for lead in the environment. In.
    Lead in the Environment. (W. R  Boggs, ed ) Report to
    NSF® RANN. U.S. Government Printing Office, Washing-
    ton,  D.C. 1977 (In  press.)
  5. Ott, W R. Development of criteria for siting air monitor-
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                                                      4-13

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                           5.  SOURCES  AND EMISSIONS
 5.1  NATURAL SOURCES
   Lead  enters  the  biosphere from  lead-bearing
 minerals in the lithosphere through both natural and
 human-mediated processes. Measurements of sur-
 face materials taken at 8-in. depths in the continen-
 tal United States1 show a median lead concentration
 of 15  ppm. Ninety-five percent of these measure-
 ments show 30 ppm of lead or less, with a maximum
 sample concentration of 700 ppm. In natural pro-
 cesses, lead is first incorporated in soil in the active
 soil zone, from which it may be absorbed by plants,
 leached into  surface  waters,  or  eroded  into
 windborne dusts.2-5 In addition, minute amounts of
 radioactive 2l°Pb reach the atmosphere through the
 decay of radon gas released from the earth.6
   Because  lead  has been used for centuries, it is
 difficult to determine the  range of natural  back-
 ground levels. Calculations of natural  contributions
 using geochemical  information,  however, indicate
 that natural  sources contribute  a relatively  small
 amount of lead to the environment. For example, if
 the typical 25 to 40 /xg/m3 or rural airborne particu-
 late matter were derived from surface materials con-
 taining 15, and rarely more than 30, ppm  lead  as
 cited  above,  then the natural  contribution to air-
 borne  lead would  range  from 0.0004  to  0.0012
 Mg/m3. In fact,  levels as  low  as 0.0012 to 0.029
 Mg/m3 have been measured at  a site in California's
 White  Mountains.7 In contrast,  however,  annual
 average lead concentrations in urban suspended par-
 ticulate matter8 range as high as 6 /tg/m3. Clearly,
 therefore, most of this urban paniculate  lead stems
 from man-made sources.

 5.2 MAN-MADE SOURCES
 5.2.1  Production
  Lead occupies an important  position in the U.S.
economy,  ranking  fourth  among the nonferrous
metals in tonnage used.  The  patterns of its flow
through industry are identified in Figure 5-I.9 Ap-
proximately 85 percent of the primary lead pro-
duced in this country is from native mines,10 where it
is often associated with minor amounts of zinc, cad-
 mium,  copper, bismuth, gold, silver, and other
 minerals.10 Missouri ore deposits account for about
 80 percent of the domestic production.
 Figure 5-1. Approximate (low of lead through U.S. industry in
 1975, metric tons."
5.2.2 Utilization
  The reported uses of lead, listed by major product
categories in Table 5-1," stood at nearly 1.2 million
MT  in  1975,  with an estimated  consumption  for
1976of 1.35 million MT.12
  Certain products,  especially  batteries, cables,
plumbing, weights, and ballast, contain lead that is
economically recoverable  as  secondary lead. This
reserve of lead in use is estimated at 3.8 million MT,
of which  about 0.6  million MT  is recovered  an-
nually. Lead in pigments, gasoline additives, am-
munition, foil, solder, and steel products is widely
dispersed and therefore is largely unrecoverable.
                                                5-1

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                      TABLE 5-1. U.S. CONSUMPTION OF LEAD BY PRODUCT CATEGORY11
                                              (MT/yr)
Product category
Storage batteries
Gasoline antiknock
additives
Pigments and ceramics
Ammunition
Solder
Cable coverings
Caulking lead
Pipe and sheet lead
Type metal
Brass and bronze
Bearing metals
Weight ballast
Other
Total

1971
616,581
(679,803)a
239,666
(264,240)
73,701
(81,567)
79,423
(87,567)
63,502
(70013)
47,998
(52,920)
27.204
(29,993)
41,523
(45,781)
18.876
(20.812)
18,180
(20,044)
14,771
(16,285)
15,830
(17,453)
41,128
(45,345)
1,298,383
(1,431,514)
1972
661,740
(729,592)
252,454
(278,340)
80,917
(89,214)
76,822
(84,699)
64,659
(71,289)
41,659
(45,930)
20,392
(22,483)
37,592
(41,447)
18,089
(19,944)
17,963
(19,805)
14,435
(15.915)
19,321
(21,302)
43,803
(48,294)
1,349,846
(1,488,254)
1973
697,888
(769,447)
248,890
(274,410)
98,651
(108.766)
73,091
(81 ,479)
65,095
(71,770)
39,006
(43,005)
18,192
(20,057)
40,529
(44,685)
19,883
(21,922)
20,621
(22,735)
14,201
(15,657)
18,909
(20,848)
42,110
(46,428)
1,397,876
(1,541,209)
1974
772,656
(851,881)
227,847
(251,210)
105.405
(116,213)
78,991
(87,090)
60,116
(66,280)
39,387
(43,426)
17,903
(19,739)
34,238
(37,749)
18,608
(20,516)
20,172
(22,240)
13,250
(14,609)
19,426
(21,418)
42,680
(47,056)
1,450,679
(1,599,427)
1975
634,368
(699,414)
189,369
(208,786)
71,718
(79.072)
68,098
(75,081)
52,01 1
(57,344)
20,044
(22,099)
12,966
(14,296)
35,456
(39,092)
14,703
(16,211)
12,157
(13,404)
11,051
(12,184)
18,156
(20,018)
36,368
(40,097)
1,176,465
(1,297,098)
5.2.3  Emissions
  Lead or its compounds may enter the environment
at any step during its mining, smelting, processing,
use, or disposal. Recent estimates of the dispersal of
lead emissions  into  the environment by principal
sources indicate that the atmosphere is the major in-
itial recipient. Estimated lead emissions to the at-
mosphere in 1975 are shown in Table 5-2.
  Mobile and stationary sources of lead emissions,
although found throughout the nation, tend to be
concentrated in  areas of high population density,
with the exception of smelters. Figure 5-2 shows the
approximate locations of major lead mines, primary
smelters, alkyl  lead  plants, and manufacturers of
lead storage batteries.13

5.2.3.1 MOBILE SOURCES
  The largest source, by far, of lead emissions to the
atmosphere is the exhaust of motor vehicles powered
by gasoline  that contains  lead  additives.14 These
mobile-source emissions collectively constitute an
estimated 88 percent of total lead emissions (Table
5-2).9  Other mobile sources,  including aviation
usage of leaded gasoline and diesel and jet fuel com-
bustion,  contribute insignificant lead emissions  to
the atmosphere.
  Lead particulates emitted in  automotive exhaust
may be divided  into two size classes. Particles in-
itially formed by condensation of lead compounds in
the combustion  gases are quite small in size (well
under  0.1 fim  in  diameter). Particles in this size
category  that become  airborne  can remain sus-
pended in the atmosphere for long periods and thus
can travel substantial  distances from the  original
sources. Larger particles are also formed as a result
of agglomeration of smaller condensation particles.
                                                 5-2

-------
                 TABLE 5-2. ESTIMATED ATMOSPHERIC LEAD EMISSIONS FOR THE UNITED STATES, 19759."
                 Source  category
                                    Annual emissions,
                                        MT/yr
                                                                                       Emissions as percentage of
                                                                                                        Total
            Mobile subtotal
              Gasoline combustion

            Stationary subtotal
                                                                  142,000
                                       142,000

                                        19,225
                                                                                     100
100

100
                                                                             88.1
Waste oil combustion
Solid waste incineration
Coal combustion
Oil combustion
Gray iron production
Iron and steel production
Secondary lead smelting
Primary copper smelting
Ore crushing and grinding
Primary lead smelting
Other metallurgical
Lead alkyl manufacture
Type metal
Portland cement production
Pigments
Miscellaneous
Total
10,430
1,630
400
100
1 ,079
844
755
619
493
400
272
1,014
436
313
112
328
161,225
54.3
85
21
05
5.6
44
39
3.2
25
2 1
1 4
53
2.3
1 6
0.6
1 7
	
65
10
0.2
01
0.7
0.5
0.4
0.4
0.3
0.2
0.2
06
0.3
02
0.1
02
100
  a Inventory does not include emissions from exhausting workroom air, burning of lead-painted surfaces, welding of lead-painted steel structures, or weathering of painted
surfaces
              0
                                  O  LEAD SMELTING AND REFINING PLANTS (7),
                                       PRIMARY PRODUCTION FOR 1976 = 652, 877 MT
                                                                                   LEAD MINES (25 LARGEST!,
                                                                                     PRODUCTION = > 95% OF DOMESTIC OUTPUT
                                                     _ TETRAMETHYL AND TETRAETHYL LEAD PLANTS (5)
                                                IT

          STORAGE BATTERY MANUFACTURERS (> 188)


Figure 5-2. Location of major toad operations in the United States, 1976.13


                                  5-3

-------
These  larger  particles,  which  may  be  tens  of
micrometers or larger in diameter, behave in the at-
mosphere like the larger lead particulates  emitted
from most stationary sources and fall to the ground
in the vicinity of the traffic producing them. The dis-
tribution of  lead exhaust particles  between  the
smaller and larger size ranges appears to depend on
a number of factors, including the particular driving
pattern in which the vehicle is used and its past driv-
ing history (Chapter 6). But as an overall average, it
has been estimated15 that during the lifetime of the
vehicle, approximately 35 percent of  the lead  con-
tained  in the gasoline burned  by the vehicle will  be
emitted as  fine particulate, and approximately 40
percent will be emitted as coarse particulate. The re-
mainder  of the lead consumed in gasoline combus-
tion is  deposited  in the engine and exhaust system.
Engine deposits are, in part, gradually  transferred to
the lubricating oil  and removed  from  the vehicle
when the oil  is changed. Moreover, some oils and
lubricants contain lead naphthenate as a detergent.
The fate of spent oil and its lead content is of con-
siderable importance. A measure of its significance
is reflected in the waste oil combustion values in Ta-
ble 5-2.  In addition, some of the lead deposited in
the exhaust system gradually flakes off, is emitted in
the exhaust as extremely large particles,  and rapidly
falls into the streets and roads where it is incorpor-
ated into the dust and washed into sewers or onto ad-
jacent  soil.
  The  use of lead additives in gasoline, which was
increasing in total volume for  many  years, is now
decreasing as cars designed to use lead-free gasoline
constitute a growing portion of the total  automotive
population (see Section 7.1.1). Regulations promul-
gated by EPA16 that limit the average  concentration
of lead  additives in  gasoline will  contribute  to a
further reduction in future automotive lead emis-
sions.

5.2.3.2 STATIONARY SOURCES
  As shown in Table 5-2 (based on 1975 emission
estimates9), solid waste incineration and  combustion
of waste oil are  the principal contributors of lead
emissions from  stationary sources, accounting for
two-thirds  of  stationary  source  emissions.  The
manufacture  of  consumer products  such  as  lead
glass,  storage  batteries,  and  lead  additives for
gasoline  also contributes significantly to stationary
source lead emissions. Since  1970, the  quantity of
lead emitted from the metallurgical industry has
decreased somewhat because of the application of
control equipment and the closing of several plants,
particularly in the zinc and pyrometallurgical indus-
tries.
  A new locus for lead emissions emerged in the
mid-sixties, however,  with  the opening of  the
"Viburnum Trend" or "New Lead  Belt"  in south-
eastern Missouri. The presence of seven mines and
two accompanying lead smelters in this area makes it
the largest  lead-producing district in the world and
has moved  the United States into first place among
the world's lead-producing nations. An  extensive
study to assess the impact of the expanding lead in-
dustry in Missouri and to stimulate new emission
control technology has been initiated.17
  Although some  contamination of soil and  water
occurs as a result of such mechanisms as leaching
from mine and smelter wastes, quantitative estimates
of the extent of this contamination are not available.
Spillage of ore concentrates from open trucks and
railroad cars,  however, is known to contribute sig-
nificantly   to  contamination  along  transportation
routes. For example, along two routes used by ore
trucks in southeastern Missouri, lead levels in leaf
litter  ranged from 2000 to 5000 ^ig/g  at the road-
way, declining to a fairly constant 100 to  200 p.gl%
beyond about 400 ft from the roadway.'7
  Another  possible  source of  land  or  water con-
tamination  is  the disposal  of particulate  lead col-
lected by air pollution control  systems. The poten-
tial for impact on soil and water systems of the dis-
posal of dusts  collected by these control systems has
not been quantified.
  The lead-containing  particles emitted from sta-
tionary sources occur in various sizes. Those emitted
from  uncontrolled  stationary sources generally in-
clude particles larger than 1- to 2-/nm mass mean
diameter, and therefore tend to settle out near the
source.  These large-particle  emissions  add  con-
siderable lead  to the dust, soil, water, and vegetation
in the neighborhood of the source (see Section 7.2).
Uncontrolled  sources also  contribute  substantial
quantities  of smaller-diameter  particles to the at-
mosphere,  where long-range transport may occur.
When controls are applied to stationary sources, the
total  mass  of the emissions is reduced significantly.
But the number of particles being emitted may not
be affected greatly if most of the particles emitted
are small, because  current  particulate control
methods are usually more effective in removing the
larger-diameter particles. The smaller-diameter
particles (below 2 ^m) may be far greater in number
than  the larger, more massive particles;  and with
diminishing size, an increasing proportion is likely
to escape collection. Generally, control methods are
                                                 5-4

-------
applied to emissions from stacks, vents, and other
process outlets.  But  lead-containing particles may
also be emitted  as fugitive dusts in the  larger size
range  (>2-^m  diameter)  from less  controllable
sources such as windows and doors, conveyors, and
waste piles. Available emission inventories  do not
include emissions from the exhaust of workroom air,
burning  of  lead-painted  surfaces, weathering  of
lead-painted surfaces,  etc. The magnitude of emis-
sions from these sources is unknown.
53  REFERENCES FOR CHAPTER 5
   1. Shacklette, H T , J. C. Hamilton, J.  G. Boerngen, and J.
     M. Bowles. Elemental Composition of Surficial Materials
     in  the  Conterminous United  States  U S. Geological
     Survey.  Washington, DC. Professional Paper  574-D.
      1971  74 p.
   2. Chamberlain, A C. Interception and  retention of radioac-
     tive  aerosols  by vegetation  Atmos  Environ  457-77,
      1970.
   3. Chow, T. J. and C  C Patterson. The occurrence and sig-
     nificance of lead isotopes in pelagic sediments. Geochim.
     Cosmochim. Acta  (London) 26263-308,1962.
   4. Lead: Airborne Lead in Perspective. National Academy of
     Sciences. Washington, D  C. 1972 330 p
   5. Patterson, C C. Contaminated and natural  lead  environ-
     ments of man. Arch. Environ  Health II  334-360, 1965
   6. Burton, W.  M  and  N  G  Stewart. Use  of long-lived
     natural  radio-activity as an atmospheric tracer  Nature
      / 56:584-589, I960
   7. Chow, T. J., J  L  Earl, and C  B Snyder.  Lead aerosol
     baseline  Concentration at White Mountain and Laguna
     Mountain, California. Science.  /7S(4059).401-402, 1972.
   8.  Akland.G.G Air Quality Data for Metals,  1970 through
      1974, from the  National Air Surveillance Network US
    Environmental  Protection  Agency, Research  Triangle
    Park, N.C , Pub No. EPA 600/4-76-401. 1976
 9  Control Techniques for Lead Air Emissions (Draft final
    report.) Office of Air Quality Planning and Standards, U.S
    Environmental  Protection  Agency, Research  Triangle
    Park, N.C EPA Contract No. 68-02-1375. 1976. 424 p.
10.  Mineral  Facts  and  Problems.  U.S.  Bureau of  Mines
    Bulletin 667, U.S  Department of Interior, Washington,
    DC. 1975. p 1243
11.  Lead  Industry  in May 1976. Mineral  Industry  Surveys.
    U S.  Department of Interior, Bureau of Mines, Washing-
    ton, D.C August 1976. Cited in: Control Techniques for
    Lead  Air Emissions. (Draft final  report ) Office of Air
    Quality Planning and Standards, U  S Environmental Pro-
    tection Agency, Research Triangle  Park, N  C. EPA Con-
    tract No. 68-02-1375. 1976. 424 p
12  Commodity Data Summaries, 1977. U.S  Department of
    The Interior, Bureau of Mines, Washington, D. C. January
    1977.
13  Commodity Files, 1976. U.S. Dept  of Interior, Bureau of
    Mines, Washington, D.C  1976
14.  EPA's Position on the  Health Implications of Airborne
    Lead. U S Environmental Protection Agency, Washing-
    ton, D C  1973.  116 p
15.  Ter Haar, G  L., D. L Lenane, J N Hu, and M. Brandt.
    Composition, size, and control of automotive exhaust par-
    ticulates. J. Air Poll. Control Assoc 22(l):39-46, 1972.
16  Federal Register. Regulation of fuels and fuel additives.
    38(234) 33, 734-33, 741, Dec. 6. 1973.
17  Wixson, B G. and J. C. Jennett (eds ). An Interdisciplin-
    ary Investigation of Environmental  Pollution by Lead and
    Other Heavy Metals from Industrial Development  in the
    New Lead Belt ot Southeastern Missouri, (Interim report.)
    National Science Foundation, Research Applied to Na-
    tional Needs (RANN), Rolla and Columbia, Missouri, The
    University of Missouri  1974 480 p.
                                                       5-5

-------
                 6.  TRANSFORMATION  AND TRANSPORT
6.1 INTRODUCTION
   The circulation of lead in the environment (shown
conceptually in Figure 6-1) illustrates that lead
released into the atmosphere ca.n  be delivered to
man (animals)  via several  routes.  At present, it is
possible to obtain only qualitative or semiquantita-
tive estimates of the movement of lead within and
among  the  various environmental media.  This is
largely  because the  physical and chemical transfor-
mations occurring within the lead cycle are not well
understood. The purpose of this chapter is to sum-
marize the available data that reflect what is known
about the transformation and transport mechanisms
controlling the  distribution and fate  of lead in the
environment in  its various  chemical forms.  Primary
emphasis is placed on the atmosphere, since it serves
as the principal medium for transport of lead from
manmade sources.
Figure 6-1. Simplified ecologic flow chart for lead showing
principal cycling pathways and compartments.
62  PHYSICAL  AND CHEMICAL TRANS-
FORMATIONS IN THE ATMOSPHERE
  Although lead is introduced into the atmosphere
primarily in the particulate form, relatively small
amounts are also emitted in the vapor phase. Once
lead is  introduced  into the  atmosphere, important
physical and  chemical changes  occur  before its
transfer to other environmental media. The discus-
sion of these changes will be divided into mobile and
stationary source categories. This division  is some-
what arbitrary in   that the pollutants from  both
source categories are well mixed  in the atmosphere.
In those cases  in which one type of source predomi-
nates (e.g., freeways or smelters),  the approach
should be reasonably realistic.

6.2.1 Physical Transformations

6.2.1.1  SIZE  DISTRIBUTION  OF  PARTICLES
FROM  MOBILE SOURCES

  Automotive  exhaust is the primary  source of par-
ticulate lead introduced ubiquitously into the  at-
mosphere in urban areas. The size of the  particles
emitted may  range from  a few  hundredths  of a
micrometer in  diameter to several millimeters, de-
pending  on the opeuating  mode, age of exhaust
system,  fuel lead content, speed and load, accelera-
tion, deceleration,  engine condition, and other  fac-
tors.
  Numerous   environmental  processes, including
transformation, transport, deposition, and  mechan-
isms of impact, are prominently  influenced by the
particle sizes. It is significant, for example, that the
sizes of the particles directly affect the probability of
lead's being transported via the respiratory system.
Because of the importance of lead particle sizes in
relation to numerous environmental  questions, the
size  distributions  of those  particles  emitted from
automobiles have  been studied by many investiga-
tors.'-10
  Figure 6-2 shows the results of a series of variable
speed tests made by Hirschler and Gilbert4 on  an
auto after about 25,000  miles of deposit accumula-
                                               6-1

-------
tion in  the exhaust system.  The data  demonstrate
that smaller lead particles make up the largest frac-
tion of'those  exhausted, and  that there  is significant
exhaust system  accumulation  of lead  particles  in
both size  categories under city-driving conditions.
During  acceleration, release  of these accumulations
is quite rapidly induced, but the  increased emission
drops off during the  period  of constant highway
speed. The effect of speed on the  particle size distri-
bution shown in Figure 6-3, as  found by Ganley and
Springer,3 also demonstrates that the mean particle
sizes emitted decrease with  increasing speed.  The
results  of  these  two  studies  imply that although
larger lead particles are most likely to  be deposited
in  the exhaust system, the deposits  are released by
ablative processes  that cause  decreases  in particle
size. Figure 6-4 compares size distributions at recep-
tor sites in California with those typical of undiluted
auto exhaust. The smaller sizes at the receptor  sites
reflect the decrease in the mean size caused  by gra-
vitational settling  and other  scavenging processes
that occur during atmospheric  transport.  Figure 6-5
compares  differential mass  distributions  at the
California receptor sites with those at a freeway site.
These distributions  are generally bimodal, indicat-
ing that paniculate lead in the  atmosphere may  con-
sist of lead emitted by autos and lead that has been
deposited on surfaces  (soil) and re-entrained via at-
mospheric turbulence  (fugitive dust); or the bimodal
distribution  may  reflect  emission  patterns.  The
results of these studies generally indicate that more
than half of the lead particles are typically less  than
1 jum in diameter, but these estimates may be biased
by  the failure to  use isokinetic sampling  techniques
(see Section 4.2.3.1).
   Lee et al.9 measured the concentrations and size
distributions of  paniculate emissions from  auto-
mobile  exhaust and found that  95  percent of the
total paniculate  lead was in  particles with mass me-
dian equivalent  diameters (MMED) less than 0.5
/urn. All samples were taken at steady-cruise condi-
tions and thus do not represent the typical discharge
of particles under wide-open-throttle accelerations,
decelerations, and short-term cruise  and  idle condi-
tions typical of  urban traffic. The  varying  modes
result  in  the discharge of  much  larger particles.
Robinson and  Ludwig11  reported  MMED  of  0.25
/urn for urban and rural areas;  25 percent of the par-
ticles were smaller than  0.16  /xm,  and  25  percent
were  larger  than 0.43 ju,m (Table  6-1). Cholak  et
al.,12 Lee  et al.,13 and Flesch14 observed  similar
distributions; however, their data also  indicate that
these distributions change very little over distances.
                                 i       I    I
                           	TOTAL LEAD EXHAUSTED
                           	FINE PARTICLES. 0-5 urn _
                              AND UNCLASSIFIED LEAD
                           	COARSE PARTICLES. >5 urn
        636   640    645     650     655    660  663
Figure 6-2. Effect of various driving conditions on the amount
of lead exhausted.4
     1P
     08
     06
     05
     04
                   \   I
                   55 70 mph
                   I   I   I
               30  40  50  60  70  80     90

                PARTICLES WITH DIAMETER 
-------
   10.0

    8 0


    6.0
                            PASADENA Pb
                            (11/721
                            (2/74)
                 I   I   I    I   I
                 40
                  MASS IN PARTICLES < D , percent
                                 P
Figure 6-4. Cumulative mass distributions for lead aerosol in
auto exhaust and at Pasadena, a receptor sampling site. The
abscissa is a log-normal scale, and Dp is the aerodynamic,
unit density particle diameter.10
   £
   "i
  <] 04
        FREEWAY Pb
               -A
             X
         PASADENA Pb
                 ,
 p    001          01          10          10
 <
 li                MEAN DIAMETER (D I. micrometers
 EC                            P

Figure 6-5. Differential mass distributions for lead 1 m from a
freeway, May 1973, and at Pasadena sampling sites, Novem-
ber 1972 and February  1974. (The  abscissa  is the  mean
diameter, and the dashed lines assume that the smallest par-
ticle size is 0.01 fj.m and the largest 50 ^m. A log D_ =  inter-
val of log of aerodynamic particle diameter; mT = total mass
loading of lead in airborne particulates; Am  =  mass of lead
occurring in  a fraction, defined in terms of size, of the total
particulates; Am/my = fraction of mass occurring in a given
particle size  range.)10
lead  aerosol  size distributions  do  not  respond
noticeably to changes  in weather within a source
area during 24-hr sampling periods. The results of
their study suggest little modification of the charac-
teristics of the lead  aerosol size distribution as a
result of nonprecipitative atmospheric mechanisms
for equivalent particle radii larger than 0.2 /urn.
   Electron  microscope studies have  shown that
many of the  fine particles in exhaust emissions  are
nearly spherical  in  shape and  are electron-dense.
The coarser particles are much  more irregular, and
some are filamentous in outline. Particles collected
at a constant cruise speed of 30 mph were found to
be composed of a carbon core  or matrix, on  or in
which  were  distributed spherical or  crystalline
electron-dense   lead  particles  <0.1  /urn  in
diameter.3Jfl Electron  micrographs of the exhaust
particles have shown that although the particle  ag-
gregates of about 0.5 urn were stable, samples of  the
gas that  had  been  inhaled  showed  more
homogeneous aggregates  I to  2 micrometers  in
diameter than larger aggregates in the  exhaled gas.
A similar effect  was obtained  by drawing the  gas
through a humidifier.'7
6.2.1.2 SIZE DISTRIBUTION OF PARTICLES
FROM STATIONARY SOURCES
   High-temperature combustion and smelting pro-
cesses  generate  submicrometer-sized lead  particu-
late, whereas lead emissions from  material handling
and mechanical  attrition operations associated with
smelters consist of larger (> 1  ^m) dust particles.
Actual data on the size distribution of lead particles
emitted from stationary sources are limited.  Fugas et
al.,18 using a five-stage impactor, obtained  samples
in the  Meza  Valley (influenced by a lead  smelter)
and in the urban area of Zagreb. The results  are
shown in Figure 6-6. A considerable difference was
found in the size distribution of lead particles in  the
industrial (Meza Valley) versus the urban (Zagreb)
area. In the industrial area, only  10 percent of  the
lead particles had diameters  smaller  and  1  /urn,
whereas in the urban area,  75 percent were smaller
than 1 /Am. This  implies that the fugitive dust from
the mechanical  rather than  the  direct-smelting
operation is the primary emission.
   Lead emissions from stationary sources are proba-
bly affected by topographic influences  in a manner
similar to other  pollutants. Because of the moun-
tainous location  of half of the  six primary lead
smelters in the United States, however, and because
these three smelters are probably the largest single-
point emitters of lead, the topographic influence  on
transport and dispersion is important.
                                                 6-3

-------
  TABLE 6-1. COMPARISON OF SIZE DISTRIBUTIONS OF LEAD-CONTAINING PARTICLES IN MAJOR SAMPLING AREAS11

                                                      Distribution by particle size, ^m

                                      25%                      MMED3                     75%
Sample area
Chicago
Cincinnati
Philadelphia
Los Angeles
(DTN)
Pasadena
Vernon (rural)
San Francisco
Cherokee (rural)
Mojave (rural)
No of
samples
12
7
7
8

7
5
3
1
1
Avg
019(7)b
0 15(3)
014(3)
0.16(7)

018
0 17(4)
0 11
0.25
—
Range
0.10-029
0 09-0.24
0.09-0.25
0 10-0.22

0 05-0 25
0.12-022
006-013
—
—
Avg
0.30
0.23
024
026

024
024
025
0.31
027
Range
016-.64
0.16-028
019-031
0 19-0.29

008-032
0.18-032
015-031
—
—
Avg
0.40(10)
044
041
0.49(7)

0 48(6)
040
0.45(2)
0.71
034
Range
0.28-0.63
0 30-0 68
0.28-0 56
0.39-0 60

013-067
0 28-0.47
0 44-0.46
—
—
  MMED = mass median equivalent diameter
  Numbers in parentheses indicate number of samples available for a specific value when different from total number of samples
            I   1     I
           MEZA VALLEY
                                   ZAGREB

                                   SEP-OCT 1971
                                   JAN FEB 1972 _
                                   MAYJUL 1972 "
                                   AUG-SEP 1972
                                   JAN-FEB 1973

                                    I     I
                   MASS < DIAMETER, percent

Figure 6-6. Cumulative mass distribution of lead particles by
size.1*
  At least four general conclusions about lead from
mobile and stationary sources can be based on the
results of the above studies:
     1.  Lead is emitted  into  the  atmosphere prin-
        cipally  in the paniculate form.
     2.  The mass median equivalent diameters of the
        lead-bearing particles are typically less than
        1  jum,  and the size distributions are fairly
        uniform from area to  area.
     3.  The particle sizes in urban and  rural areas
        are  such that the  lead  can be transported
        over relatively large distances via typical at-
        mospheric convection and turbulence  pro-
        cesses.
     4.  The size distributions are such that signifi-
        cant fractions of the total atmospheric lead
        concentrations are within the respirable size
        range.
6.2.2  Chemical Transformations

6.2.2.1  MOBILE SOURCE EMISSIONS
  Tetraethyl  lead (TEL)  and  tetramethyl  lead
(TML), as well as the mixed-lead  alkyls,  are used
widely  as  additives  in  gasoline.  Although these
organic compounds are less volatile than  gasoline,
small amounts may escape to the  atmosphere  by
evaporation from fuel systems or storage  facilities.
TEL  and  TML  are  light-sensitive and  undergo
photochemical decomposition when they reach the
atmosphere.10-19 The lifetime of TML appears to be
longer than that of TEL. Exposure of dust to TEL,
both in the presence and absence  of water vapor,
results in sorption of organic lead  on dust particle
surfaces.20 Laveskog21 found  that  transient  peak
lead alkyl concentrations up to 5000 ^ig lead/m3 in
exhaust gas may  be reached in a cold-started, fully
choked, and poorly tuned vehicle.  If a  vehicle with
such emissions were to pass a sampling station on a
street where the lead alkyl level might typically be
0.02 to 0.04 /ix-g/m3 of air, a peak of about 0.5 /*g/m3
could be measured as the car passed  by. The data re-
ported by Laveskog were obtained with a procedure
that collected  very small (100 ml), short-time (10
min) air samples. The sensitivity reported was much
better than that reported by other investigators, who
have  not been able to duplicate his results.22 Har-
rison et al.22 found levels as high as 0.59 /*g/m3 (9.7
percent of total lead) at a busy gasoline service sta-
tion.
   Purdue et al.23 measured particulate and organic
lead in atmospheric samples. Some results are shown
in Tables 6-2 through 6-4. These data  demonstrate
that in all of the cities studied, particulate lead levels
are much higher  (an average of approximately 20
                                                 6-4

-------
times higher) than organic lead levels. The results
are entirely consistent with the studies of Huntzicker
et al.,'° who  report an organic component of 6 per-
cent of the total airborne lead in Pasadena for a 3-
day period in June 1974, and of Skogerboe,24 who
measured fractions in the range of 4 to  12 percent at
a site in Fort Collins, Colorado. It is  noteworthy,
however, that in  the underground  garage (Table
      TABLE 6-2. RESULTS OF ATMOSPHERIC SAMPLING
   6-4), total lead  concentrations  are  approximately
   five  times those  in the urban areas, and  the  per-
   centage of organic lead increases to  approximately
   17  percent.  Consequently, the  concentration  of
   organic lead in an  underground garage site is ten
   times that in the open  urban environment  (see Ta-
   bles  6-2 and 6-4), and the potential exposure level is
   similarly  magnified.
FOR ORGANIC AND PARTICIPATE LEAD23(M9/m3)
           Cincinnati
                            Denver
                                         Washington DC
                                                           St Louis
                                                                          Philadelphia
                                                                                           Chicago
Sample
       Organic  Particulate0   Organic   Particulate   Organic   Particulate   Organic   Particulate   Organic  Particulate  Organic  Particulate
1
2
3
4
5
6
7
8
9
10
Avg.
0.2
0.0
0.0
02
0.4
02
02
0.4
02
02
02
1 5
09
09
19
37
1 6
1 8
1 3
1 5
24
1 7
0.2
05d
14d
03
02
01
00
02
02
05d
02
23
1 8
1 6
1 7
1.0
18
22
1.8
20
—
1 8
00
0.2
01
03
01
0.1
01
02
04
0.2
0.2
1 4
1 4
1.5
10
1 1
0.8
1 7
1 2
08
16
1 2
05
02
04
02
03
0.2
03
04
0.4
1 3d
03
20
20
1 8
25
1 9
1.8
2.2
22
20
1.2
2.0
05
1 1d
0.2
0.4
0.8
04
0.0
03
01
01
03
1.3
1.7
29
24
1.1
1 1
1 7
2.1
18
23
1 8
02
04
0.2
16d
02
02
03
01
02
02
02
5.9
56
53
3.5
46
55
5.8
48
50
5.1
5.1
 aSample no represents order in which samples were taken Cities were not sampled concurrently
  All values are average of two determinations
 Determined by NASN method (6)
  Organic lead averages do not include these values because the replicate values for these samples were more than twice the standard deviation from the average
TABLE 6-3. PERCENTAGE  OF  PARTICULATE VERSUS
    VAPOR-PHASE LEAD IN URBAN AIR SAMPLES23
Total lead3
City
Cincinnati
Denver
Washington, D C
St Louis
Philadelphia
Chicago
Organic,
3
M9 m
02
02
02
03
03
02
Particulate
fj-q m
1 7
1 8
1 2
20
1 8
51
Particulate
°o of total
89
90
86
87
86
96
aAII values are averages of ten determinations

paniculate Pb x
100

TABLE  64. ANALYSES  OF FIVE REPLICATE SAMPLES
   TAKEN IN AN UNDERGROUND PARKING GARAGE23
Sample no
1
2
3
4
5
Average (X)
Relative standard
deviation (Srel)a
Organic
lead
fig'm3
1 9
1 9
1 9
1 8
22
19
79%
Organic
lead.
157
171
176
14.9
180
167
79%
Particulate
lead,
3
fig m
103
92
89
103
100
97
6.7%
Total
lead
f,gm3
122
11 1
108
12 1
122
11.6
52%
a- . Standard deviation
         Average
      As the lead alkyl compounds of gasoline are sub-
   jected to the elevated temperatures and pressure of
   combustion, they  are converted  to  lead  oxides,
   which function to inhibit engine knock. The lead ox-
   ides react with other additives in the fuel  and leave
   the combustion chambers in a variety of complex
   compounds. The results  of composition studies by
   Hirschler and  Gilbert,4 Ter Haar et al.,2 and  Ter
   Haar and Bayard25 are shown in Tables 6-5 and 6-6,
   respectively.
     Habibi et al.5 determined the composition of par-
   ticulate matter emitted from a test car operating on a
   typical driving cycle. The main conclusions  drawn
   from  the study were:
        1.  Composition of emitted exhaust particles is
           related  to particle size.
       2.  Very large particles greater than 200 /u,m
           have a composition similar to lead-contain-
           ing material deposited in the exhaust system,
           confirming  that they have been re-entrained
           or have flaked off from the exhaust system.
           These particles contain approximately 60 to
           65 percent lead salts, 30 to  35 percent ferric
           oxide (Fe2O3), and 2 to  3 percent soot and
           carbonaceous material. The major lead  salt
           is  lead bromochloride (PbBrCl), with large
           amounts  (15 to  17 percent) of lead oxide
                                                  6-5

-------
      TABLE 6-5. AVERAGE COMPOSITION OF PARTICULATE LEAD COMPOUNDS EMITTED IN AUTO EXHAUST8'2'4
                                                                         Compound, wt
                     Exhaust source
                                                      PbCI Br
                                                                 2PbCIBr
                                                                            2PbCI Rr
Car B
  City type cycle, fuel plus TEL motor mix only
  City type cycle, added sulfur0     .    ...
  City type cycle, added phosphorusd
  Constant speed, 60 mph, road load
  Full-throttle accelerations

Car M
  City type cycle, fuel plus TEL motor mix only...
  Constant speed, 60 mph, road load
  Full-throttle accelerations..              ..  ..
68
70
35
60
85


33
30
90
24
30
18
20
10


40
30
10
17
20
 5


 5
35
            2

           10
22
 5
                       20
  X-ray diffraction analyses made in situ on material deposited on glass slides mounted within the precipitator of the sampler
  In addition to the tabulated compounds, PbSO4 and PbO PbCI Br HjO occurred ocasionally in concentrations of 5 percent or less
 °Sullur content increased from 0 025 to 0 105 weight percent by addition of disulfide oil
  0 4 theory phosphorus added

 TABLE 6-6. EFFECTS OF AGING ON LEAD COMPOUNDS IN SAMPLES OF AUTO EXHAUST AS DETERMINED BY ELECTRON
                                               MICROPROBE25
                                                          Percentage of total particles sampled
                                       Black bag3
 Lead compound
                                                                     Eight-Mile Road
                                                18 hour
                                                                Near road
                                                                                 400yd
                                                                                                Rural site
PbCI2
PbBr2
PbBrCI
Pb(OH)CI
Pb(OH)Br
(PbO)2-PbCI2
(PbO)2-PbBr2
(PbO)2-PbBrCI
PbCO3
Pb3(P04)2
PbOx
(PbO)2-PbCO3
PbOPbS04
PbS04
10.4
55
320
77
22
52
1 1
314
1 2
—
2,2
1.0
—
0 1
83
0.5
120
72
0.1
56
01
16
138
—
21 2
296
0.1
—
11.2
40
44
4.0
20
28
07
2.0
15.6
0.2
120
379
1 0
22
10.5
07
06
8.8
1.1
56
03
0.6
14.6
03
250
21 3
4.6
60
5.4
01
1 6
4.0
—
1 5
_
10
302
—
20.5
27.5
50
32
  Sample collected directly from tailpipe in black bag to prevent irradiation of exhaust Analyzed immediately and again 18 hr later to determine effect of aging
  bState highway in Detroit carrying about 100,000 cars a day
  cSamples were taken 400 yd from a lightly traveled roadway
        (PbO) occurring as the 2 PbO-PbBrCl dou-
        ble salt. Lead sulfate and lead phosphate ac-
        count for 5 to 6 percent  of these  deposits.
        (These compositions resulted from  the com-
        bustion of low-sulfur  and  low-phosphorus
        fuel.)
     3. PbBrCI is the major lead salt in particles of 2
        to 10 micrometers equivalent diameter, with
        2 PbBrCI «NH4C1 present as a minor constit-
        uent.
     4. Submicrometer-sized  lead salts  are  pri-
        marily 2PbBrCl.NH4Cl.
     5. Lead-halogen molar ratios  in  particles  of
        less than  10 microns MMED  indicate  that
        much more halogen is  associated with these
        solids than the  amount expected  from the
        presence of 2PbBrCNNH4Cl,  as identified
        by X-ray  diffraction. This  is  particularly
        true for particles in the 2- to 0.5-micrometer
        size range.
     6.  There  is considerably more  soot and  car-
        bonaceous material  associated  with small
        particles than with coarse particles  re-
        entrained after having been  deposited after
        emission from the exhaust system. This car
        bonaceous material  accounts for  15 to  20
        percent of the finer particles.
     7.  Paniculate matter   emitted   under  typical
        driving conditions is rich in  carbonaceous-
        type material. There  is substantially less such
        material  emitted under continuous  hot
        operation.
     8.  Only  small quantities of 2PbBrCl-NH4Cl
        were found in samples collected at the tail-
                                                     6-6

-------
       pipe from the hot exhaust gas. Its formation
       therefore takes place primarily during cool-
       ing and mixing of exhaust with ambient air.
  Hirschler and Gilbert4 found similar  results and
speculated that higher gas temperature during full-
throttle operations reduced the tendency for the am-
monium-lead halide complexes to be present since
they are unstable at high temperatures.
  Based on the above  studies, it seems  quite clear
that the size distribution of lead particles emitted
from automobiles and the relative concentrations of
the complex compounds  in those particles  vary sig-
nificantly  with driving conditions, engine condition,
type of fuel, and age of exhaust system. Particles > 2
^m in the exhausted paniculate are  primarily lead
bromochloride. The very large particles,  a conse-
quence of deposits in the exhaust  system, are also
primarily  lead bromochloride.
  The fates of these lead compounds, once they are
introduced into the atmosphere from automobiles,
are not completely understood.  There is disagree-
ment  in the early  literature  concerning  the  loss of
halogens by these  lead compounds. Pierrard26 sug-
gested that  PbBrCl  undergoes  photochemical
decomposition with the formation of a  lead oxide
and the release of free  bromine and chlorine,  but
later suggested a hydrolytic conversion mechanism.
Ter Haar and  Bayard25 and Robbins and  Snitz27
confirm the loss of halogen from freshly  emitted Pb
salts,  but  they  do not support the photochemical
mechanism. Ter Haar and  Bayard25 suggest that
lead halides are eventually converted to lead car-
bonates and lead oxides. Pierrard26obtained data on
aged lead  aerosol that indicated that  the lead parti-
cle  surfaces  had  already been   converted to  a
relatively  insoluble form such as oxide, carbonate,
or basic halide; this would be consistent with a con-
version mechanism expected to release the less reac-
tive hydrogen halide rather than the  more reactive
molecular halogen. Dzubay and Stevens28 observed
a diurnal  variaton  in  the  bromine-to-lead con-
centration ratio in atmospheric paniculate  indica-
tive  of  the loss  of halogens during atmospheric
transport.  Ter Haar and Bayard25 studied the effects
of aging on automobile exhaust collected in a black
bag, using an electron probe. The results, shown in
Table 6-6, indicate that 75 percent of the bromine
and 30 to  40 percent of the chlorine associated with
the compounds contained in  the particulates were
lost in 18 hr; data presented suggest that  the pro-
portions ot lead  carbonates  ana  lead  oxides  in-
creased. Since these chemical reactions occurred in a
black bag, photolytic processes would not  likely be
responsible for the decrease in halides. At the very
least, therefore,  this experiment demonstrates  the
existence of nonphotolytic decomposition pathways
for lead halides in the atmosphere. Consequently,
the chemical composition of lead in the atmosphere
from automobile emissions almost certainly depends
to some extent on the age of the particles as well as
the presence of other pollutants with which the lead
compounds can react.
   The results of Lee et al.9 show that the percentage
of  water-soluble  paniculate lead  increased  when
diluted exhaust was irradiated by light in the wave-
length region of 3000 to 6000 A. This region is in the
near-ultraviolet and visible regions of the spectrum
and is available from direct sunlight. The percentage
of water-soluble lead in the diluted exhaust also was
increased by irradiation in  the presence of 0.5 ppm
SO2.  Irradiation significantly increased  the sulfate
concentration of  the particulates and was accom-
panied by a shift to smaller particle sizes. A shift of
nitrate-bearing particles to smaller sizes, with and
without addition of SO2, was also observed with  ir-
radiation.  The  amount  of nitrate  present was
decreased in the presence of SO2. The lead nitrate,
which is much more soluble in water than the other
lead salts present, cannot be totally responsible for
the increased water solubility  observed  if the NO3
concentrations decrease.
  The information available regarding the chemical
composition of lead particles emitted from  auto-
mobiles may be summarized as follows:
     1. Lead halogen compounds are  the principal
       forms emitted;  lead chlorobromide is  the
       most prominent of these.
    2. The particulates  undergo compositional
       changes during  transport  away  from  the
       source. These changes appear to consistently
       involve:
       a. Losses of halogens, the rate of which might
         be photochemically enhanced,  but which
         also occur in the absence of light.
       b. General increases in the water  solubilities
         of the particles with concomitant  shifts
         toward smaller mean particle sizes. These
         latter  changes are enhanced by the pres-
         ence of SO2, in which case the amounts of
         nitrate present decrease.
    3. Although several reports have suggested that
       the  lead halogen compounds are  converted
       to oxides and/or carbonates, the only specific
       examination of the composition after  aging
       was that of Ter Haar and Bayard.25 Unfor-
       tunately,  their experimental approach did
                                                6-7

-------
       not rely on a particularly definitive method
       of identification. Indeed, the electron micro-
       probe approach used can only be regarded as
       a crude qualitative tool for the identification
       of compounds; the simultaneous occurrences
       of other elements in lead-bearing particles
       and  the  general  morphological  charac-
       teristics of the particles can provide only cir-
       cumstantial indications  of  the compounds
       that are present. This is particularly true for
       lead-bearing particles because compounds of
       several other elements are also typically pre-
       sent. Habibi et al.,5 for example, have shown
       that the particles often include iron as well as
       lead  compounds. The percentage composi-
       tion data given in Table 6-6 should also be
       evaluated, taking into account  that they are
       number rather than mass percentages. Thus,
       although  lead  carbonate, for example, may
       comprise a relatively  high  number percen-
       tage of the total, its mass percentage may be
       quite different, depending on the  size distri-
       butions involved  and whether the particle
       compositions are size dependent.
  These general  conclusions and qualifications are
consistent with and supportive of the  results of the
study reported by Olson and  Skogerboe.29  They
determined that the principal form  of lead found in
lead-contaminated soils from  highway medians as
well as in street dusts was lead sulfate. Although this
study included evaluation  of 18 soil and/or dust
samples collected from different U.S. locations, sig-
nificant amounts of  the  lead  halogen compounds
were found in any case. The  conversion of lead
halides to other compounds appears  to  have been
quite complete for these aged lead aerosol deposits.
6.2.2.2 STATIONARY SOURCE  EMISSIONS
  Measurements  are  not available to confirm the
chemical form of lead  emissions  from  stationary
sources. Barltrop and Meek30 indicate the presence,
without reference to specific measurements, of lead
sulfide or lead chloride in the mining industry, lead
oxide in smelters, and lead carbonate and lead chro-
mate in pigments used in older paints.  Lead oxide is
the  principal  form of the  metal  used  in battery
manufacturing.
  The association of lead  sulfide  with  mining  is
clearly rational,  since this  is  the primary  mineral
form (galena). While lead  oxide may certainly be
derived from the smelting process, the amounts pro-
duced may be relatively small in comparison  to the
amounts of lead sulfide released as fugitive dust to
the atmosphere  around a smelter.  Moreover,  the
release of SO2 usually associated with lead smelting
operations, coupled  with the possible  interactions
between lead particles and SO2, imply that the com-
pounds  released may well undergo conversion to
other  forms.  Thus,  although  the   compounds
generally associated with stationary sources are not
particularly soluble, the possibility of conversion to
more soluble  compounds or accumulation  of the
particles in the lungs of exposed populations should
not be ignored.
6.3 TRANSPORT IN AIR
  The  mechanisms  of atmospheric  transport,
removal, and  resuspension of lead particulates in-
teract in a complex manner. The transport mechan-
isms are functions of the particle size  distribution,
particle morphology, meteorology,  and  local
topography.

6.3.1  Distribution Mechanisms
  The transport  and diffusion of gaseous and partic-
ulate materials in the atmosphere are consequences
of molecular  diffusion and the three-dimensional
motion field, the latter being the dominant factor. A
detailed treatment of these phenomena will be found
in many standard textbooks on meteorology. The
three-dimensional motion field can be assumed to be
composed of a mean wind (transport) vector and a
turbulent component.  The turbulent component is
analogous to molecular diffusion, but the coefficient
of  turbulent  eddy diffusion  is usually  of  much
greater  magnitude. The turbulent component tends
to spread the material vertically and laterally about
the mean horizontal transport  vector. Therefore,
assuming  a pollution  plume from a  local line or
point source, the  atmospheric motion serves to
dilute and transport the pollutants.
   Since lead emitted to the atmosphere is  primarily
in the inorganic paniculate form, its transport and
dispersion will depend primarily on particle size as
well as chemical stability, the height  of  injection,
and the intensity  and stability of the  atmospheric
motion  field.  Large particles injected at low eleva-
tions will  settle to  the  surface in the immediate
vicinity of the source, whereas the smaller particles
will be  transported over greater distances.
   A study by Daines  et al.31 related  atmospheric
lead to  traffic volume and distance from a highway.
They found the effect of traffic on lead content of the
air to be striking, but limited to a rather narrow zone
bordering primarily the lee side of the highway, as
shown in Figure 6-7. About 65 percent of the lead in
                                                6-8

-------
the air between  30 and 1750 ft from  the highway
consisted of particles under 2 /xm, and 85 percent
were under 4 /urn  in diameter. Figure 6-8 shows a
typical relationship of particle size to distance from
the highway. Cholak et al.'2and Schuck and Locke32
did similar studies with similar results. As shown in
Figures 6-4 and 6-5, Huntzicker et al.'° demon-
strated that the large particle mode (Dp >7 ^m) in
the freeway distribution is severly attenuated at the
Pasadena site.
                               TRAFFIC VOLUME,
                               vehicles/day

                                 O - 58,000
                                    47,000

                                 • - 44,000
                                 O - 19,800
                                     I
                    200      300      400

                  DISTANCE FROM HIGHWAY, feet
Figure 6-7. Air-lead values as a function of traffic volume and
distance from the highway.31
                 60         80         100

             % HAVING MEAN MASS DIAMETER LESS THAN
Figure 6-9. Relationship of the diameter  of the particles
(mass) to distance from the highway.31

  Knowledge of lead concentrations in the oceans
and glaciers provides some insight into the degrees
of atmospheric  mixing and long-range transport.
Tatsumato, Patterson, and Chow33'35  measured dis-
solved lead concentrations in sea water off the coast
of California, in the Central North Atlantic  (near
 Bermuda), and in the Mediterranean. The profiles
 obtained are shown in  Figure 6-9.  Surface con-
 centrations in  the Pacific were found  to be  higher
 than those of the Mediterranean or the Atlantic, and
 decreased abruptly to relatively constant levels with
 depth. The vertical  gradient was found to be much
 less in  the  Atlantic. Based  on  the  Pacific data,
 Tatsumato  and  Patterson33 estimated  an average
 surface lead concentration of 0.2 /^g/kg in the north-
 ern hemispheric oceans.  Chow  and  Patterson35
 revised this estimate downward to 0.07 /u-g/kg. There
 appears to be no difference between lead concentra-
 tions in deep water in the Atlantic and Pacific. These
 investigators calculated that industrial  lead  is cur-
 rently  being  added to the oceans at about 10 times
 the rate of introduction by natural weathering, with
 significant amounts  being removed  from the  at-
 mosphere by precipitation and  deposited directly
 into the ocean. Their data suggest considerable con-
 tamination of surface waters near shore, diminishing
 toward the open ocean.35 These investigators con-
 clude that lead  emissions from automobiles are the
 primary source of pollution of ocean surface  water.
                                                            4 6
                             O- ATLANTIC
                                (BERMUDA)

                             O- MEDITERRANEAN
                                40°39'N, 05°48'E

                             6- PACIFIC
                                29°13'N, 117°37'W
                                                                              J_
                   LEAD IN SEA WATER, M9/l<8
Figure 6-9. Lead concentration profiles in the oceans.33"35

  Duce, Taylor, Zoller,  and their  co-workers36'38
have  investigated trace-metal concentrations (in-
cluding lead) in the atmosphere in remote northern
and southern hemispheric sites. The natural sources
for such atmospheric trace metals include the oceans
and the weathering of the earth's crust, whereas the
manmade source  is paniculate pollution.  Enrich-
ment factors for concentrations relative to standard
values for the oceans and the crust were calculated
(Table 6-7); the mean crustal enrichment factors for
the North Atlantic and the South Pole are shown in
Figures 6-10 and 6-11. The  significance of the com-
                                                 6-9

-------
parison in Figure 6-11 is that 90 percent of the par-
ticulate pollutants in the global troposphere  are in-
jected  in the northern hemisphere.39 Since the resi-
dence  times  for particles in the  troposphere40 are
much less than the interhemispheric mixing time, it
is  unlikely that significant  amounts  of particulate
pollutants can migrate from the  North  Atlantic to
Antarctica via the troposphere; however this does
not rule out stratospheric transfer. In the case of
lead (and all other metals studied except vanadium),
the enrichment factors were very similar at the two
locations. This suggests (but does not prove) that the
atmospheric  concentrations  of these  metals may
originate primarily from natural  (rather than man-
made) sources.
 TABLE 6-7. CONCENTRATION RANGE AND MEAN EFcrust
 VALUES FOR ATMOSPHERIC TRACE METALS COLLECTED
         OVER THE ATLANTIC NORTH OF 30° N36
Element
Al
Se
Fe
Co
Mn
Cr
V
Zn
Cu
CO
Pb
Sb
Se
Concentration
range
ng scm
8-370
0 0008-0 01 1
3 4-220
0 006-0 09
0 05-5 4
0 07-1 1
006-14
03-27
012-10
0 003-0 62
010-64
0 05-0 64
0.09-0.40
EFcrust
qeom mean9
1 0
08
1 4
24
26
11
17
110
120
730
2,200
2,300
10,000
 aCalculated on the basis of the mean crustat abundances of Taylor ^f
          80 W      60
                      GREENLAND   •
                              •
                           NORTH ATLANTIC
                                 "AZORES
                  BERMUDA
                      .   •
 Figure 6-10. Midpoint collection  location for  atmospheric
 samples collected from R. V. Trident north of 30°N, 1970
 through 1972.36'38

   Murozumi et al.41 have presented supportive evi-
 dence. Their data show that long-range transport of
 lead aerosols emitted from automobiles  has signifi-
 cantly polluted  the  polar glaciers. They collected
Figure 6-11. The EFcrugt values for atmospheric trace metals
collected in the North Atlantic westerlies and at the South
Pole. The horizontal bars represent the geometric mean
enrichment factors,  and  the  vertical bars  represent the
geometric standard deviation of the mean enrichment fac-
tors. The EFcrust for lead at the South Pole is based on the
lowest lead concentration (0.2 mg/scm).36'38
samples of snow and  ice from  Greenland  and the
Antarctic. As shown in Figure 6-12, they found that
the concentration of lead varied inversely with the
geological age of the sample. The authors attribute
the gradient  increase  after 1750 to the  Industrial
Revolution  and  the enhanced  increase after  1940
to the increased  use of lead alkyls in gasoline. The
most  recent  levels fround in  the antarctic snows
were, however, less than those found in Greenland
by  a  factor  of 10 or more.  Before 1940, the  con-
centrations in the Antarctic were below the detect-
able level « 0.001 /xg/kg)  and have  risen to 0.2
Mg/kg in recent  snow. A graph of the world  lead
smelter and  lead  alkyl  production presented  by
Murozumi et al.41 is shown in Figure 6-13; support-
ing data are shown in  Table  6-8.
   The results and conclusions of Murozumi  et al.
 were criticized  by Mills,42  who suggested the  in-
 crease in the snow lead after 1940 could be due to
 aircraft  operating from  Thule  Air  Force  Base.
 Bryce-Smith43 countered Mills' argument by stating
 that  the  greatest amount  of  lead found  to   be
 deposited  in  the snow  was during  winter months
 when air traffic was lightest; there was no horizontal
 gradient between the air base and the collecting site;
 the collecting site was predominantly upwind from
 the air base; and, finally, the major increase in lead
 levels began about   20  years before the nearest
 operating base was established.
   Jaworowski44  found that  lead concentrations in
 two glaciers have increased by a factor of 10 during
 the last century. The concentrations in the most re-
                                                6-10

-------
                      AGE OF SAMPLES
Figure 6-12. Lead concentration profile in snow strata of
Northern Greenland.41
                                                            I         I         I          I
                                                           - O - LEAD SMELTED IN NORTHERN HEMISPHERE
                                                             D - LEAD SMELTED IN SOUTHERN HEMISPHERE
                                                             & - LEAD BURMED AS ALKYLS IN NORTHERN HEMISPHERE
Figure 6-13. World lead smelter and alkyl lead production
since 1750 A.D.41
 TABLE 6-8. LEAD AEROSOL PRODUCTION IN THE NORTHERN HEMISPHERE COMPARED WITH LEAD CONCENTRATIONS IN
                         CAMP CENTURY, GREENLAND, SNOW AT DIFFERENT TIMES41




Date
1753
1815
1933
1966


Lead
smelted
103 tons'yr
1
2
16
31
Fraction
converted
to
aerosols
%
2
2
16
006
Lead
aerosols
produced
from smelteries
103 tons'yr
2
4
8
2


Lead burned
as alkyls
103 tons yr
_
—
0-1
3
Fraction
converted
to
aerosols
%
	
—
40
40
Lead
aerosols
produced
from alkyls
103 tons'yr
	
—
4
100

Total lead
aerosols
produced
103 tons'yr
2
4
12a
102a

Lead
concentration
at Camp Century
M9 'kg snow
001
003
0.07
0.2
 aValues corrected
cent ice layers  were extremely  high (148 ^ug/kg).
Jaworowski et al.45 also  studied stable and radio-
active  pollutants from  ice samples  from Storbreen
glaciers in Norway. The mean stable lead concentra-
tion in Storbreen glacier ice in the 12th century was
2.13 /u,g/kg. The mean for more recent samples was
9.88 (tig/kg-  Around 1870, the  average lead  con-
centration in Norwegian glacier ice was 5.86 /ug/kg,
whereas that for glaciers in Poland was 5.0 /tig/kg. A
century later, the mean concentration in  the  Nor-
wegian glacier was  9.88  /Ltg/kg,  whereas the mean
concentration in  the  Polish  glacier reached  148
jtxg/kg. Jaworowski et  al.45 attributed the  large  in-
crease  of lead concentrations in the Polish glacier to
local sources.
  Jaworowski et al.45  also measured 210Pb in the
glacier ice. The values found in the Storbreen glacier
ice  are shown graphically in Figure  6-14. The high-
est  value was found in 1961.  A similar value was
found  in Polish glaciers and  in  the  Alps  the same
year.44 The values  and irregularities  observed in
2l°Pb concentrations in the investigations suggest
that part of the atmospheric 210Pb may have origi-
nated from  artificial sources  — nuclear explosions
in the Arctic,  or energy production in  fossil-fuel
power stations. Based on their findings, Jaworowski
et al.45 concluded that long-range transport of lead


                YEAR, AS DETERMINED BY DEPTH
         1966 65  64  63  62 61   60  59 58 67 56 65 54
Q
<
LU  0.1
           "1	1	1	1	1—I	\	1  Mill"
                 4  .5   6   7   8  9  10  11

                      DEPTH, meters
Figure  6-14.  210Pb In Storbreen, Norway, glacier Ice,
1954-1966.45
                                                 6-11

-------
pollutants in the atmosphere  is a reality, but the
authors suggest  that the rate  of contamination of
glacier ice correlates better with the total annual in-
put of coal burning to the energy system of the world
than with lead emissions from  automobiles.

6.3.2 Removal Mechanisms
  The principal mechanisms  for removal of in-
organic lead paniculate from the atmosphere are
dry  deposition  and precipitation.  Detailed  dis-
cussions of these processes will be found in standard
textbooks   by   Sutton,46  Pasquill,47  Fletcher,48
Junge,49 Green  and  Lane.50  and   Slade.51   The
removal efficiency of these processes varies signifi-
cantly, depending on physical  characteristics of the
suspended material, atmospheric conditions, and the
nature of the receiving surface.

6.3.2.1  DRY DEPOSITION
  Dry deposition removal processes include  sedi-
mentation, diffusion, and inertial mechanisms such
as impaction. Sedimentation, or settling of particles.
occurs when the mass of the particle  is large enough
to overcome  the  buoyancy force  and the lifting
forces of convective currents. Freely falling particles
of the size range found in suspended aerosols rapidly
attain their  terminal, or constant, velocity when the
aerodynamic drag  on the particle is equal to the
weight of the particle. The terminal velocity depends
on the particle size, its density, and gravitational ac-
celeration. When a particle is of a size comparable to
the mean free path of the gas  molecules, bombard-
ment by  the molecules results in  a  random  or
Brownian motion that is superimposed on its down-
ward motion. If a particle  is very small and its mo-
tion is observed for only a short period of time,  its
fall may be completely masked by the Brownian mo-
tion. Residence times  or, conversely, the rate  of
fallout of aerosols or dust  particles containing lead
in the atmosphere are then primarily a function  of
particle size. The shape of the suspended particles
also has a significant effect on the settling velocity.
Usually the settling velocity of  particles of various
geometrical forms is calculated  in terms of the set-
tling velocity  of spherical particles  of  the  same
volume. The aerodynamic particle size,  conven-
tionally used when  discussing airborne paniculate,
is defined as the size of a sphere of unit density that
has identical aerodynamic behavior to the particle in
question.  Particles  having the  same  aerodynamic
size may have differing shapes and dimensions.
   Airborne  particles are generally  divided  into
three  size  ranges:   Aitken  nuclei (particle radius
< 0.1  /urn), large nuclei  (particle  radius 0.1 to 1
/Jim), and giant nuclei (particle radius > 1 /urn). Ex-
tremely small particles (radius < 0.001 yum) tend to
coagulate rapidly to form  larger  (-— 0.05 to 0.5
/im), less mobile particles.50 Fletcher48 derived an
approximate equation  to  predict the rate at which
the concentration number, n, of particles of radius,
r, will decrease in a relatively uniform aerosol. For r
= 0.005 /u,m and n = 105/cm3 (typical in urban air),
the  time  required  for particle concentration to
decrease by one-half was  calculated to be 30 min.
For r = 0.1  /am and n = lO^/cm3, 50 percent reduc-
tion was calculated to  require 500 hr. The size dis-
tributions of large and giant nuclei are not signifi-
cantly affected by coagulation.
  Settling or terminal  velocities of spherical parti-
cles, as reported  by Green  and Lane50 and Israel and
Israel,52 are shown in Table 6-9.
    TABLE 6-9. TERMINAL VELOCITIES OF SPHERICAL
    PARTICLES OF UNIT DENSITY AT GROUND LEVEL
Particle radius
0.01
005
01
02
05
1 0
20
50
10.0
20.0
50.0
Terminal velocity cm 'sec
Israel and Israel Green and Lane
1.43X10'5 —
— 871X10'5
232x10-4 227x10-4
— 685x10-4
— 3.49 x10'3
1 32 x 1 0"2 1 29 x 1 0"2
— 5.00 x1Q-2
— 303x10"1
1.23x10° 1.20x10°
— 471
— 247
   Airborne particles are also removed from the at-
 mosphere by inertial mechanisms. In turbulent iner-
 tial  deposition,  turbulent wind fluctuations  per-
 pendicular to a horizontal surface impart sufficient
 inertia to propel the particles through the boundary
 layer and onto  the surface. This mechanism is im-
 portant for both smooth and rough surfaces. When
 the roughness elements on a surface protrude suffi-
 ciently  far into the  windstream, inertial  impaction
 may become important. The mean horizontal flow of
 the wind,  rather than  turbulent fluctuations, con-
 trols impaction. This mechanism occurs when parti-
 cles cannot follow the air streamlines as they pass
 around a roughness element. In this case, the mean
 windflow supplies the inertia that drives the parti-
 cles onto the surface.
   Inertial  mechanisms  are  dependent  on  at-
 mospheric conditions  and the characteristics of the
 surface. The small-scale surface structure may  be
 especially significant.  For example, small particles
                                                6-12

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are preferentially retained on leaf surfaces, where
they may be tightly retained by small hairs on the
leaf, by surface pores, and by tacky substances ex-
creted by the  leaves.  Impaction of submicrometer-
sized particles on leaf surfaces is possible at normal
wind speeds.53 Pine needles and  similarly shaped
surfaces appear to be aerodynamically attractive for
impaction  of  paniculate matter. Therefore, pine
trees near a surface source of lead paniculate pollu-
tion may increase the rate at which lead aerosols are
removed   from the   atmosphere.  Heichel  and
Hankin54 reported soil lead concentrations in front
of and within a roadside windbreak of pine trees as
being 50 percent and 100 percent higher, respec-
tively, than soil lead  concentrations at correspond-
ing distances in a nearby open field that bordered
the same side of the road.
  Particle  removal  rates from  the atmosphere are
usually described in  terms  of deposition velocity.
Historically, deposition velocities have been defined
as the ratio of deposition flux to the airborne con-
centration with units of length/time usually reported
as cm/sec.49 Sehmel and Hodgson55 have published a
model for the prediction of dry deposition velocities
based on this concept.
                    K  -  -
                    K"
                                 (6-1)
where K is the deposition velocity, N is the deposi-
tion flux, and  C is the airborne concentration  for
monodispersed particles measured 1  cm above  the
deposition surface.  The deposition  velocity,  K,
assumes  that particle deposition is described by a
one-dimensional, steady-state continuity  equation.
The basic assumptions in the model are that the flux
is constant with height, that a relationship for parti-
cle eddy diffusivity  can be determined,  that  the
effect of gravity can be described by the terminal set-
tling velocity,  that agglomeration does not occur,
and that particles are completely retained on  the
surface. The model was designed to predict deposi-
tion velocities  for simple surfaces. Actual removal
rates are non-steady-state processes  dependent  on
the delivery capability of the upper atmosphere and
the surface resistance. Based on the above assump-
tions, Sehmel and Hodgson55 write the equation  for
deposition flux as:
N=  -(
                     D)  — -v.C
                         dz
(6-2)
where vt is the absolute value of the terminal settling
velocity, e is the particle eddy diffusivity, D is the
Brownian diffusivity, C  is the airborne concentra-
tion, and  z is the reference height. For small parti-
cles, the sedimentation term (-v,C) is negligible so
that deposition velocity is a function  of the Brown-
ian and eddy diffusivity term only. For large parti-
cles,  the diffusivity  term  is  negligible,  and  the
deposition velocity is equal to the terminal velocity.
Incorporating the concepts of friction velocity:
             u.=  -!L_L_               (6-3)
                   K Im(z/z0)
where  k is von  Karman's constant,  u  is  the
windspeed,  z  is  height,  and z0 is the roughness
height. Roughness height  is defined as a measure of
the roughness of  a surface over which fluid is flow-
ing:
                   zo = H/30                (6-4)
where H  is  the  average  height  of surface   ir-
regularities. Sehmel and Hodgson55 developed pre-
diction  deposition  velocity curves for a  range of
roughness heights and friction velocities. Represen-
tative curves  are shown  in  Figures  6-15 through
6-17. Deposition  velocities are shown to be a func-
tion of particle diameter and  have  their smallest
values in the 0.1  to 1 /u,m particle  diameter range.
The mean diameter of lead-containing particles in
the atmosphere, remote from major sources, falls ap-
proximately in this range.  In the case of larger parti-
cles, both increased effective eddy diffusion  in sur-
face boundary layer (as a result of greater particle
inertia)  and increased gravitational  settling rates
tend to  increase the predicted deposition  velocities
above the minimum. The lower limit of the pre-
dicted deposition  velocities is the  sedimentation
velocity. For smaller  particles, deposition  velocities
increase  with decreasing particle diameters because
of  increased mass transfer, by  Brownian motion.
Deposition  velocities for 0.01-/urn  particles  are
relatively insensitive to changes in particle  diameter
at  elevated heights  above  10 cm. Deposition
velocities at 1 cm above  the ground  are extremely
large; consequently, in  the  0.01-jum  particle-
diameter range, the deposition velocities  are con-
trolled by atmospheric diffusion in the layers  im-
mediately above the canopy. As indicated by Sehmel
and Hodgson,55 the model should predict  reasona-
bly well the deposition velocities for simple surfaces,
assuming the wind direction is persistent over suffi-
cient distance. It  should not, however, be  expected
to predict deposition  velocities for a city because of
the complexity in the geometry of  the surface and
because of local wind conditions.
  Values of lead  deposition velocities found in  the
literature generally range from about 0.1  to  0.5
cm/sec.56 These values are based on total  lead flux
and total airborne concentrations, without regard to
                                                6-13

-------
particle sire. Since large particles may control lead
deposition in certain cases, it is necessary to examine
the entire size  distribution  of particles in order to
calculate  deposition  rates. Further, accurate
isokinetic measurements of large airborne particles
are required to relate airborne concentrations to
deposition. Davidson56 found a deposition velocity
of 0.29 cm/sec  in Pasadena, based on total flux  and
total airborne concentrations. Based on the fraction
of lead particles greater than  10 microns, however,
the deposition  velocity was 1.3  cm/sec. Huntzicker
et al.'°found a  deposition velocity of 1.80 cm/sec on
a Teflon  plate placed on  the  shoulder of a  Los
Angeles freeway.
 8 10
 E
 >  1
 z
 o
TYPICAL
 UPPER BOUND, UNSTABLE, L - -10 meters
 LOWER BOUND. STABLE. L =10 meters
                10 '          1           10
                 PARTICLE DIAMETER, micrometers
Figure 6-15. Predicted deposition velocity of particles at indi-
cated height for u. = 20 cm/sec and zo - 3.0 cm
                                          55
          i—r-ri .in]   ,	i|
         .UNSTABLE. L = -10 meters
        ..|  STABLE, L = 10 meters

          *  :/
        	   '..     u. .cm/sec
                 10         1          10
                PARTICLE DIAMETER, micrometers
 Figure 6-16. Predicted deposition velocities of particles at 1 -m
 height for zo =  3.0 cm.5'

   Johnson57 sampled particles with an instrumented
 aircraft flying at 300 m altitude in the vicinty of St.
 Louis, Missouri. Particles were collected by expos-
 ing a small (l.O- by 7.5-cm) glass slide covered with
 a thin layer of high-viscosity silicone oil to the free
 air stream outside the skin of the aircraft. Particles
 were counted and sized manually fr,om photographs.
 Samples were obtained upwind and downwind of St.
                                       >  10"
                                              ..--•-*
                                                    UNSTABLE. L = -10 meters
                                                       PARTICLE DIAMETER, micrometers
                                       Figure 6-17. Predicted deposition velocities of particles at 1 m
                                       for u. = 200 cm/sec.55
                                       Louis on each of 11 days during the  period July I
                                       through July 18, 1975. The results indicated typical
                                       number concentrations of airborne particles larger
                                       than  10 fj.m in diameter of 7,500 particles/m3 up-
                                       wind and  11,000 particles/m3 downwind. Particles
                                       larger than 30 /urn  in diameter were  found  in con-
                                       centrations of 200 particles/m3 upwind and 425 par-
                                       ticles/m3 downwind of the city. For the downwind
                                       particle number densities of > 10 /j.m and >30 yu,m
                                       particles, and with the assumed density of 2 g/m3, the
                                       mass concentrations would be about 0.01 ng/m3 and
                                       0.012 ng/m3, respectively. The results  reported indi-
                                       cate that particles >30 /j.m can be transported to
                                       altitudes of 300 m by convective currents; therefore,
                                       all large particles are not removed by  sedimentation
                                       in the immediate  vicinity  of sources.  Assuming a
                                       sedimentation velocity of 0.3 cm/sec  for a  10 ^m-
                                       diameter particle and an initial height of 300 m, the
                                       particle could remain airborne for approximately 27
                                       hr and be transported about 200 km with a uniform
                                       wind of 2 m/sec. This type of long distance transport
                                       has been observed by Gillette and Winchester15 over
                                       Lake Michigan. The actual concentrations observed
                                       are very small, however, and would contribute little
                                       to ambient air loading or dustfall accumulation in
                                       regions remote from the source.
                                         Lynam58 studied the atmospheric diffusion of car-
                                       bon monoxide and lead from  an expressway (1-75,
                                       north of Cincinnati, Ohio). The significant results
                                       are shown in Figures 6-18 through  6-20. Approx-
                                       imately 50 percent of the lead emitted  from the auto-
                                       mobile traffic was removed from the atmosphere by
                                                 6-14

-------
dry deposition within 640 ft of the edge of the road-
way (Figure 6-18). The size distribution of the lead
particles  was not significantly  altered between  20
and  640  ft (~6 and  —195 meters).  Wind  speeds
ranged from approximately 0.5 to 3.8 m/sec. Assum-
ing a mean  wind speed of 2 m/sec, the 50-percent
reduction within 640 ft would correspond to about
 1.5 min of travel time. The concentration of lead
decreased from about 7 /ng/m3 at 20 ft to about 1.5
ju,g/m3  at 640 ft, a decrease by a factor  of about 5.
The data were not sufficient to determine the rela-
tive efficiency of sedimentation versus impaction in
the total removal process; however,  Figures 6-19
and 6-20 indicate that the  removal mechanism was
not strictly  limited to sedimentation. Daines et al.,31
in their study of the relationship of atmospheric lead
to  traffic volume and distance from  a highway,
found a 50-percent reduction in lead between 10 and
 150 ft of the edge of the roadway.
 O   40
        I    I   I  I  I  I I  I
       - % LEAD REMOVED =
                             ii
                                    I   I   T
                                             I  I
40   60 80 100   150 200

      TRAVEL DISTANCE, feet
                                      400   600
Figure  6-18.  Regression of  percentage lead particulates
removed by dry deposition with distance from roadway.68
(Legend: — -  regression line; —= 95% confidence limits for
regression line;	=  95% confidence limits for single
value; R = correlation coefficient.)
  Smith59 investigated lead contamination of white
pine growing along an east-west section of Interstate
95 in Connecticut. He found that  lead contamina-
tion  decreased  regularly with  increasing distance
from the  road and was greatest on the sides of the
trees nearest the highway. Based on the much higher
concentration of lead deposited  on  the  needles
nearest the roadway, Smith concluded that pine trees
may serve as rather efficient air filters.

6.3.2.2 PRECIPITATION
  Precipitation,  or  wet  deposition, removal  pro-
cesses  include rainout and washout. Rainout occurs
     1 0

     08
                  I
                     I  I  I  I  I
          -O—  SAMPLING STATION
                20ft FROM EDGE
                OF EXPRESSWAY

          -D--  SAMPLING STATION
                640ft FROM EDGE
                OF EXPRESSWAY
           J	I
                   I  I  I  I  I  I   I
                                                                          j	I
J	I
       1  2   5  10  20      50   70     90  95  98 99
               Pb PARTICULATES 
-------
washout together  are  known  as wet  deposition.
Although data on  the  lead content of precipitation
are rather limited,  those that  do exist indicate a high
variability.  Lazrus et al.60 sampled precipitation at
32  U.S.  stations and found  a correlation between
gasoline use and lead concentration in  rainfall in
each area. Similarly, there is probably a correlation
between lead concentration in rainfall and distance
from large stationary point sources of lead emissions
in the vicinity of such  sources. The authors pointed
out that  at least twice as much lead is found in pre-
cipitation as  in  water supplies, inferring  the  exis-
tence of a process by  which  lead is depleted  after
precipitation  reaches the ground. Russian studies61
point to the insolubility of lead compounds in sur-
face waters  and  acknowledge  this  removal  by
natural sedimentation  and filtration.
  The intensity of rainfall appears to be negatively
correlated with the amount of lead washed out of the
atmosphere. Ter Haar et al.62 found that  showers
had lower concentrations than slow, even rainfall.
Data presented by  Jaworowski44 show that in recent
years, the lead content in rainwater ranged from 0 to
1858 Mg/liter.
  A laboratory  study in which simulated rainfall
was used to  determine the  efficiency  with which
automotive lead particulates could  be  washed out
indicated that the efficiency was less than 1  per-
cent.63
  Concentrations  of 210Pb in rainwater  have also
been reported by Jaworowski44 as highly variable (as
much  as two orders  of  magnitude in  the  same
locality) and not related to season or  amount of pre-
cipitation. Values  ranged  from 0.2  to  300
pCi/liter.44  High concentrations were found in  sam-
ples collected from northern continental  localities,
and low concentrations were found in samples  from
oceanic  and  Antarctic locations.  Jaworowski  sug-
gests that the differences might  be attributed in part
to artificial contamination by nuclear explosions.
6.3.2.3 FIELD STUDIES
  Atkins and Kruger64 conducted a field  sampling
program in Palo Alto, California, to determine the
effectiveness  of  sedimentation, impaction,  rainout,
and washout in  removing lead  contaminants  from
the  atmosphere.  Rainfall   in  the  area  averages
approximately 33  cm  (13 in)/year and occurs pri-
marily during the  late fall and winter months. Air-
borne  concentrations at a freeway site varied  from
0.3 jug/m3to a maximum of 19 /Ltg/m3in the fall and
winter seasons, and were a maximum  of 9.3 /u,g/m3 in
the spring.  During periods of  light  rainfall in the
spring, the maximum concentration  observed  was
7.4 jiig/m3. A typical daily concentration profile ob-
served is shown  in Figure 6-21.  More than 90 per-
cent of the lead pollutants reaching the surface dur-
ing the 1-year sampling period were collected in dry
fallout.  Dry  deposition as a  function of distance
from the freeway is shown in Figure 6-22.* Approx-
imately  1 percent of the total  dry fallout collected
near the expressway was  lead. Wet deposition (ap-
proximately 33  cm  or 13 in of rain per year) ac-
counted  for  5 to 10  percent of the lead  removal  at
the sampling sites. A  summary of the field  data  is
shown in Table  6-10.
         i   i   T  I  T  r   i   i
         O LEAD
         DTRAFFIC
         £ WIND
MID-  2   4
NIGHT
                   8   10 NOON  2   4

                      TIME OF DAY
6  8  10 MID-
        NIGHT
Figure 6-21. Atmospheric lead concentration at freeway site
in Palo Alto, California, on August 15,1966.63
  •3
  E
                                   i   i
                           I =STD DEV

                           X=90x1oV8-06L
                           (SEE FOOTNOTE IN TEXT)
                        I	I
  <   10 20   50 100 200  500 10002000 500010.000  50,000 100.000
                DISTANCE FROM FREEWAY (X). feet

Rgure 6-22. Average lead In dry fallout as a function of dis-
tance from the freeway.63
  "Figure 6-22 is a semi-log plot ot the three average lead values as a function of dis-
  tance trom the treeway The data appear to fall along a straight line, suggesting that
  the relationship between lead in tall out. I.  and distance from the freeway. X can
  he described by X = aeh'- where a and o are constants From the semi-plot, the ap-
  propriate values tor a and h are a = 9 0 x 10^ h = -8 06. if L is expressed in
  mg'fi2-wk and X is expressed in feet Therefore X = 90 x |04e'*ot'L- The area
  under this curve. Irom X, = SO ft to Xj = 26 900 ft should represent the total
  amount ot lead deposited m the Palo Alto area t
  value is 7 8^ g'ft The area under the curve i
  should represent the total amount ot lead tha
  assuming that the data can be extrapolated pas
  This indicated that an average ot 70 percent of
  mentation was removed within s miles ot the st urce
                           reach I-ft section of freeway This
                           m L = 0 95 mg/ft2-wk to L = 0
                             is removed by sedimentation.
                           26,900 ft This value is I I I g/ft
                           he lead that was removed by sedi-
                                                   6-16

-------
 TABLE 6-10. SUMMARY OF FIELD DATA FROM PALO ALTO,
                   CALIFORNIA64
Item
Lead in dry fallout:
Average, mg/ft -wk
Amount removed, mg/ft -yr
Lead in rainfall-
Average, mg/liter
Amount removed, mg/ft -yr
Average air concentration,
Aig/m3
Pb/total solids in air
Freeway3
(Bayshore)

092
49.4

0.181
325

7.30
0042
Resi-
dential

0.24
117

0.149
3.66

228
0018
Foot-
hills

0.153
8.3

0.035
0.92

1 90
0.016
Pb/nonvolatile solids
  in dry fallout
   0.0112   00102   0.0049
  Andren et al.65 evaluated the contribution of wet
and dry deposition of lead in a study of the Walker
Branch Watershed, Oak Ridge, Tennessee, during
the period June  1973 to July  1974. The mean pre-
cipitation in the  area is  approximately 130 cm/year
(51 in/year). The major atmospheric  emissions  in
the vicinity of Oak Ridge are derived primarily from
three coal-fired steam plants. A foundry and ferro-
alloy plant approximately 64.5 km (40 miles)  to
the west  were assumed to have  a minor impact
because of orographic barriers. Results reported for
the period January  through June of 1974 are pre-
sented in Table  6-11. Rainfall, or wet deposition,
contributed approximately 67 percent of the total
deposition for the period.
    TABLE 6-11. DEPOSITION OF LEAD AT THE WALKER
             BRANCH WATERSHED, 197465
                              _Lead deposition lg 'rial
  Period
                           Weta
                                             Dry
January
February
March
April
May
June
    Total
    Average
 34.1
  67
 21 6
 154
 26.5
 11 1
1154
 19.2
< 16,7
<  33
< 106
<  75
< 13.0
<  54
  565
   94
  aTotal deposition — 172 g/ha Wet deposition — 67 percent of total

  yuntzicker et al.10 estimated the flow of automo-
bile-emitted lead in the Los Angeles Basin based on
measurements  of particle  size, atmospheric con-
centrations, and surface deposition of lead at various
sites around the Basin. A flow diagram based  on the
study and modified  by Schuck  and   Morgan66  is
shown in Figure 6-23. Of the lead emitted from au-
tomobile exhaust in the Basin (estimated to be about
18 tons per day), the investigators calculated that
about 56 percent was deposited near the source (near
deposition), 12  percent was deposited in the Basin
                            but  in areas removed from the source (far deposi-
                            tion), and about 32 percent was transported out of
                            the  Basin by the wind.  The  values presented for
                            deposition and wind removal  were for dry weather
                            only (i.e., dry deposition only).
                                                              INPUT
                                                          23.7 metric tons Pb/day
b/day
EVAPORATION 1%
VAPOR 4%
^J» j \ AEROSOL 70%
REMOVAL
BY WIND
25%
*
ATMOSPHERE
75%
J
RETAINED IN CAR
25%
t
REMOVED
BY STREET
CLEANING 6%

SEWAGE
NEAR DEPOSITION
STREET LAND
8% 32%
RUNOFF 2% 1


0 64 metric

FAR
DEPOSITION
LAND
1
I'd
COASTAL WATERS
tons P b/day
                            Figure 6-23. Fate of lead contributed from automotive traffic
                            in Los Angeles Basin.65
                              Roberts et al.67 found an exponential decrease in
                            dustfall  with  distance  around  two  secondary
                            smelters (Figure 6-24). The authors concluded that
                            the high rate of fallout around the smelters origi-
                            nated from  episodal  large-particulate  emissions
                            from low-level fugitive sources rather than from the
                            stack. This being the case, sedimentation would  be
                            the principal removal process. The lead in dustfall
                            values decreased well over 90 percent within a dis-
                            tance of 300m.
                             ? 500
                             Q
                             <
SMELTER B
   1	1	1	1	
SMELTER A  Y « 6.100 2,560 log X
         R „ _0.81
         p<0001
         96 SAMPLES AT 16 SITES
         Y = 896 - 340 log X
         R =-0.63
         p <0 001
         34 SAMPLES AT 6 SITES
                                             200    300    400    500

                                             DISTANCE FROM STACK, meters
                                                                     600
                            Figure 6-24. Contamination of dust by lead emissions from
                            two secondary smelters. Solid and dashed lines are fitted
                            curves corresponding to the regression equations; dotted
                            lines  are an  extrapolated fit; U Indicates corresponding
                            values found In urban control areas.66
                                                 6-17

-------
  Studies such as those described above clearly indi-
cate that lead is  effectively removed from the at-
mosphere by dry  and  wet deposition processes, and
that atmospheric concentrations are significantly in-
fluenced by these removal  mechanisms even  in the
immediate  vicinity of  the  source.  The  rate  of
removal is highly dependent, however, on the size
distribution of the particles, the nature and charac-
teristics of the deposition  surfaces, airborne con-
centrations, and  atmospheric conditions including
stability, winds, and precipitation.  In dry weather,
the lead will be deposited on surfaces in the form of
dustfall  by sedimentation,  diffusion, or  inertial
mechanism, depending primarily on the size  of the
particles. Mass deposition  near the sources will  be
controlled primarily by sedimentation of large parti-
cles, whereas the  smaller particles will remain air-
borne  longer, be  transported further by the  wind,
and be removed primarily  by diffusion and inertial
mechanisms.
  The characteristics  of the surfaces on  which the
lead is deposited will  significantly  influence the
deposition and retention. Deposition will  be greater
in a wooded area than  on  paved surfaces  or short
grass.  Buildings also will influence the dry deposi-
tion, although there are few data available to quan-
tify the effect. In  areas with higher annual  rainfall,
removal by precipitation (wet deposition) becomes
more important and may be the  dominant process.
  All of these factors substantially influence poten-
tial human  lead-exposure  patterns — both inhala-
tion of airborne lead  and possible ingestion of dust
containing  lead. The dry deposition  removal
mechanisms deplete the airborne concentrations but
deposit the material in the form of dust. The factors
controlling  dry deposition then  become  extremely
important from the standpoint of potential exposure
patterns for dust, since they may strongly influence
temporal  and spatial variations. Because  of sedi-
mentation  of  large particles, dustfall  rates (mass)
will be highest immediately adjacent  to roadways
with dense  automobile  traffic and near  stationary
sources of all  types  where  lead may be  emitted.
These  rates will  diminish to a rather  low  value in
areas remote from sources and where the small par-
ticles are removed primarily by  diffusion and iner-
tial mechanisms.
  The accumulation on the deposition surfaces will
depend on  the rate of deposition  and the rate at
which  the material  is cleaned from the surfaces by
precipitation or by mechanical means such as street
sweeping or vacuuming. Dust entering buildings or
homes by air transport will usually be deposited on
flat surfaces such as floors or furniture. The same
physical  processes will control the rate  of deposi-
tion. The potential  exposure level, particularly for
young children, will depend on the accumulation,
which again will be influenced by the deposition rate
and the frequency and methods of cleaning. In oc-
cupational environments where fugitive  dust emis-
sions are high, accumulation will be rapid if surfaces
are not  frequently cleaned. Significant amounts of
this dust may be carried on clothing into the homes
of workers and contribute further to the total lead-
dust loading in the  home environment.
  Emission rates from automobile traffic and  from
stationary sources are highly variable in time, even
on an hourly basis. Since the residence time of large
particles in the atmosphere is on the same order or
less, the dustfall rates in the immediate vicinity of
sources  should  also  be highly  variable. This  is
reflected in airborne concentrations measured very
near the source.
  As a consequence of the number of variables in-
volved and of the temporal  and spatial variations
occurring, it is not possible to quantify human ex-
posure in uncontrolled cases without the use of per-
sonal monitors. Estimates of such exposure may vary
by an order of magnitude or greater. For a given
emission pattern, one  can  generally conclude that
potential exposure from lead in  dust  should  be
greatest  (1) in dry seasons, (2) in areas with sparse
vegetation, (3) within  a few hundred meters of the
sources,  (4) under conditions of stable atmospheres,
(5) during the morning  and afternoon traffic rush
hours in  the vicinity of freeways, and (6) during peak
production periods of stationary sources (usually
during the day).
6.3.2.4  RESUSPENSION
  The threshold stress,  which must  be exceeded
before a particle is  resuspended from a surface, is a
function of the particle properties, particle size, and
the surface properties. A particle of a given size and
density will resuspend more easily from a smooth
surface than from  an  irregular surface  such as an
asphalt road.  Particles on a dirt  road or other soil
surfaces may become attached to soil  particles and
behave quite differently from an inert free particle.
This process of weathering tends to reduce resuspen-
sion. Moisture, influenced by atmospheric variables
such  as wind,  precipitation, humidity, and  solar
radiation, may inhibit resuspension.
   Data in the literature  on resuspension show that
this process is not well understood, and hence resus-
pension  rates cannot yet  be predicted to any degree
                                               6-18

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 of accuracy. For example, Mishima68 indicates that
 reported resuspension factors* vary over  10 orders
 of magnitude from 10'2 to 10'11.  (The resuspension
 factor, in nr1, equals the airborne concentration, in
 ng/m3, divided by the ground  source concentration,
 in ng/m2.) It is useful, however, to  examine data
 from more  controlled resuspension experiments in
 order to obtain a qualitative idea of expected lead
 resuspension rates.
   Sehmel69 has examined  the resuspension of ZnS
 particles smaller than 25 microns  from an asphalt
 road surface. He found that when a car was driven
 across the recently applied tracer, 0.001  percent to
 1.0  percent  of the material was  resuspended.
 However, the fraction resuspended decreased by 2 to
 3 orders of magnitude when a 30-day period elapsed
 between application of  the  tracer  and  the  car
 passage.
   The fraction resuspended per vehicle passage in-
 creased as a function of vehicle speed and  was inde-
 pendent of  wind velocities for the test conditions.
 The fraction resuspended  per vehicle passage was
 greater for a drive through the tracer test  lane than
 on the adjacent lane and greater for a 3/4-ton truck
 than  for a  car.  These results suggest that resus-
 pension of lead from roadways may play a signifi-
 cant role in  the overall transport of lead away  from
 automotive  sources. This  may be  important  con-
 sidering the conclusions of Huntzicker et al.10that a
 considerable fraction of the emitted lead deposits
 directly on the roadways.
   In  another experiment, Sehmel and Lloyd70  ex-
 amined the resuspension of  10-/u.m  monodisperse
 uranine particles  from  a  smooth surface in  the
 laboratory. They found that the fraction of material
 resuspended per second varied from 10'6to 1Q-3  for
 wind speeds  of 16.5 to  18.3  m/sec. They  also
 measured  the resuspension of CaMo4 over sandy
 soil.70 The fraction of material resuspended per sec-
 ond ranged from 2 x 10-'°to 2.2 x 10-8for winds of
 1.3 to 20 m/sec.
   A limited amount of data on lead resuspension is
 also available. Figure 6-25 shows the deposition of
 lead found as a function of height above a roof sur-
 face.72 The lead was deposited on flat Teflon plates
 mounted at various heights. The greater depositions
 close to the roof are believed by the investigators to
 be due to resuspended roof dust.
  The environmental consequence  of salt particle
 resuspension from  roads  has been  reported  by
 Smith.73 Needles from white pine planted adjacent
to an interstate highway in Connecticut showed ex-
cessive sodium and calcium content resulting from
 airborne salt  resuspension from the  highway. The
 deposition of  airborne salt appears to be similar to
 that of lead from automobile exhaust.69
                  Pb DEPOSITION, ng/cm -day
 Figure  6-25. Total deposition of lead on Teflon plates at
 various heights above the roof of Keck Laboratories, Califor-
 nia Institute of Technology, Pasadena.71

   Baum et al.74 sampled airborne paniculate for a
 period of about 2 years at several locations in Port-
 land,  Oregon, using paraffin-coated  Mylar  films
 with four- and five-stage Lundgren impactors. Soil
 and dust samples, both surface and subsurface, were
 also taken at  the air-sampling sites. Samples were
 analyzed for lead and other  elements. Chemical ele-
 mental balance methods were used to calculate soil
 and dust burdens in the air.  The authors report that
 greater than 90 percent of the submicrometer-sized
 airborne particles were associated with automotive
 emissions. The larger particles  were reported to be
 contributed  about equally  by resuspended  street
 dust and direct emissions from  automobiles.
  These  data  suggest that  lead resuspension may
 play an important role  in the transport of lead. At
 present, however, it is not possible to reach quantita-
 tive conclusions about this  mechanism. Size distri-
 bution measurements of ambient lead presented here
 and elsewhere  in the literature represent airborne
data that have been influenced by the combined fac-
tors of atmospheric transport, deposition, and
 resuspension.

6.3.3  Models
  There is an extensive body  of literature  on at-
                                               6-19

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mospheric transport  and diffusion models.75"79 A
detailed discussion is beyond the scope of this docu-
ment. The mathematical models are  usually based
on the basic Gaussian plume model emanating from
the early work of Sutton46 and Pasquill47 and well
described by Gifford.76 Stern77 provided  an  ex-
cellent review of air quality modeling techniques for
both rural and  urban modeling situations. Experi-
mental data describing the pollutant concentrations
from point sources show that, in spite  of wide varia-
tions, these plumes exhibit a strong tendency toward
a Gaussian or normal distribution as a  statistical
average. In simple terms, parameters reflecting the
turbulent component define the horizontal and  ver-
tical dimensions of a pollutant cloud in  a vertical
plane perpendicular to the mean wind velocity.
  Cermack et al.80 have used the wind  tunnel to
model physically the atmospheric boundary layer
over  urban  areas  to determine the   pollutant
transport characteristics.

6.4 TRANSFORMATION AND TRANSPORT
IN OTHER ENVIRONMENTAL MEDIA

6.4.1  Soils
   Numerous  studies  have shown  significant  con-
tamination of soils by the emission  of lead from
mobile and stationary sources and through  the dis-
posal of waste products.  Excellent reviews of the
early literature, as well as reports on more recent
research, have been published by members of a joint
research staff from Colorado  State University and
the Universities of Missouri and Illinois.20-29 Many
of the studies of lead before 1973 were  limited to
analysis for  elemental lead  and  did not  include
analysis for associated ions. Such information is not
sufficient to  permit a thorough  examination  and
understanding of (1) transformation  and transport
processes that  occur among  the  environmental
media, (2) mobility of lead in soils, (3) uptake and
distribution of lead in plants, and (4) the overall im-
pact of lead on human health and ecosystems. Infor-
mation on the chemical forms of lead is needed.
   Soil  is a  complex matrix composed  of several
hundred different compounds, only a small  fraction
of which are lead. Most analytical techniques are not
capable of providing positive  identification of
specific compounds  unless separation methods are
used that do not alter the lead compounds. Recently,
nondestructive  separation/preconcentration  tech-
niques  have been developed and used by the  Col-
orado State University research group to determine
lead compounds in soil and plants.I0
  Lead contaminants are deposited on soil by dry
and wet deposition processes. Present understanding
of the  chemical reactions involving these particles
once they are deposited into or on the soil is in-
complete.81 Early work indicates that lead probably
reacts with soil anions, e.g., SO4=, PO4=, or CO3=,
or with some organic or clay complex.82 These reac-
tions would tend to make the Pb insoluble, thus in-
hibiting rapid mobility in the soil or plant as well as
microbial uptake. Direct evidence supporting these
reactions is limited. In a study by Lagerwerff and
Brower,83  lead was precipitated in  Na +-treated,
alkalized soils. The solubility of the precipitate in-
creased with decreasing pH  and concentration  of
NaCl.  Furthermore, absorption of soil lead by hy-
drous oxides of iron and manganese, and its conse-
quent immobilization, has been reported by Gadde
and Laitinen.84
  Studies have identified cation exchange capacity,
organic matter content, pH,soil type, and soil drain-
age as the important factors influencing the mobility
of lead in soils.85 Santillan-Medrano and Jurinak86
conducted  batch  equilibrium  studies  to  obtain
solubility data for lead and cadmium  in soil. Lead
solubility decreased in the soils as pH increased. The
lowest values were obtained  in calcareous soil.  In
noncalcareous soil, the solubility of lead appears to
be regulated by Pb(OH)2, Pb3(PO)4)2, Pb4O(PO4)2,
Pbs(PO4)3OH, and even PbCO3, depending on the
pH.
  The  creation   of organic  chelating  agents  by
biologic activity serves as one of the most effective
processes of metal mobilization or immobilization in
the soil. These  agents  are either plant products,
microbial metabolities, or humic compounds (humic
acids). The latter are capable of precipitating lead.
The amounts and types  of organic  matter  pre-
sent  appear  to  provide  an  important control
mechanism for the movement of heavy-metal ions in
soil systems. The association of lead and organic
matter, however, is not always empirically consis-
tent.87
   Olson  and Skogerboe29 preconcentrated  lead
compounds in roadside soil samples and used X-ray
powder diffraction techniques for  compound iden-
tification. The lead compounds in each soil fraction
examined are shown in Table 6-12. The most abun-
dant  lead  salt found was  the  relatively  insoluble
PbSo4. The authors note that generally 70 percent or
more of the total lead in the soils examined was con-
tained in the dense fractions and that the majority
(>50 percent) of this lead was present as sulfate.
The results indicate that oxides present in the soil
                                               6-20

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were  minor  constituents compared to  the  sulfate
concentrations.  Since  lead  bromochloride  com-
pounds are the principal constituents of fresh auto-
mobile exhaust emissions, conversion to lead sulfate
must  have occurred either in the atmosphere or in
the soil.  The  authors suggest that sulfuric  acid
formed from SO2 in the atmosphere or at the soil
interface may react with the lead paniculate to form
lead sulfate.  Reaction  with the sulfate ion  also may
occur in the soil in contact with groundwater.24 The
results of Lee et al.9 (Section 6.2.2.1) support these
general contentions.
  Data are limited regarding the chemical  composi-
tion of lead in soil contaminated by emissions from
stationary sources. Lead sulfide  and lead chloride
are thought to be the  major  constituents in soils in
the vicinity of mining  industries, and  lead oxide is
the chief one  in the vicinity of smelters. The presence
of lead sulfide as the primary compound in soils
along a mine-access road in  Missouri has been re-
ported, (Table 6-12). Analytical data confirming the
other compounds mentioned above are  not availa-
ble.

6.4.2 Water

6.4.2.1  INORGANIC
  The chemistry of lead in an aqueous solution is
highly complex because the element can be found in
a multiplicity  of forms. Hem and Durum have
reivewed the chemistry of lead in water in detail,88
and the aspects of aqueous lead  chemistry that are
germane to this document are discussed in Chapter
3.
  Natural concentrations  of lead  in  lead-ore
deposits do  not  normally  move  appreciably  in
ground or surface water. Any lead dissolved from
primary lead sulfide ore tends to combine  with car-
bonate or sulfate ions to (1) form insoluble lead car-
bonate or lead sulfate, or (2) be absorbed  by ferric
hydroxide.87 An outstanding characteristic  of lead is
its  tendency  to form compounds of low solubility
with the major anions of natural water. The hydrox-
ide, carbonate, sulfide, and more rarely the sulfate
may act as solubility controls. The amount of lead
that can remain in solution in water is a function of
the pH of the water and the  dissolved salt content.
Equilibrium  calculations  show  that the  total
solubility of  lead in hard water (pH >5.4) is about
30  jug/liter and about 500 /Ag/liter in soft water (pH
<5.4).89  Lead sulfate (PbSO4)  is  present in soft
water and limits the lead concentration in  solution.
Above pH 5.4, PbCO3 and Pb2 (OH)2CO3 limit the
 TABLE 6-12. LEAD COMPOUNDS IDENTIFIED IN ROADSIDE
 SOILS BY X-RAY POWDER DIFFRACTION TECHNIQUES
                                              :29
Location and
soil fraction
Fort Collins-
Magnetic
Nonmagnetic



Denver'
Magnetic
Nonmagnetic
Chicago
Magnetic
Nonmagnetic

Chicago
Magnetic
Nonmagnetic
Missouri
Magnetic
Nonmagnetic

Compounds
found

PbSO4
PbS04
PbO-PbSO4
PbO2
PbOb

PbSO4
PbSO4

PbSO4
PbO
PbSO4

PbSO4
PbSO4

None0
PbS
PbSO4
Estimated
concentrations3

Major
Major
Minor
Trace
Trace

Ma|or
Major

Major
Major
Minor

Major
Major



Major
Minor
 aMajor indicates the principal portion of lead present in the soil fraction indicated
and, therefore, the principal portion of the soil sample Minor refers to approx-
imately 1 to 10 percent of the lead in the respective fractions Trace quantities are
less than approximately 1 percent of the total in each fraction
 ^Assignment is based on the presence of only the most intense d-spacmg and is
therefore questionable
 GComplex d-spacmg pattern obtained with all intensities low, positive assign-
ment of any one compound or group of comoounds is questionable
concentration. The  carbonate  concentration  is in
turn dependent on the partial  pressure of CO2 as
well as the pH. Calculations by Hem and Durum88
show that  many  river  waters in the United  States
have lead concentrations near the solubility limits
imposed by their pH levels and contents of dissolved
CO2 species. Because the influence of changing tem-
perature and pH may be substantial, observed lead
concentrations  may  vary  significantly  from
theoretically calculated ones.
  Lazrus et al.60 calculated  that as much as 138
g/ha-mo of lead may be  deposited by rainfall in «ome
parts of the northeastern United States. Assuming an
average annual  rainfall runoff of 50 cm (~20 in),
the average concentration of  lead  in  the runoff
would have to be about 330 /ug/liter to remove the
lead at the rate of 138 g/ha-mo. Concentrations as
high as 330 /ig/liter could be stable in water  with pH
near 6.5 and  an alkalinity of about  25 ng  bicar-
bonate ion/liter of water. Water having these proper-
ties is  common in runoff areas  of New York State
and New England; hence,  the potential for high lead
concentrations exists  there.  In  other  areas,  the
average pH and alkalinity are so high that less than 1
/ig/liter of lead  could  be retained  in solutions at
equilibrium.87
                                                 6-21

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  A significant fraction of the lead carried by river
water may be in an undissolved state. This nonsolute
lead can consist of colloidal particles in suspension
or larger undissolved particles of lead carbonate,
oxide, hydroxide,  or other lead compounds incor-
porated in other  components  of paniculate  lead
from runoff, either as sorbed ions or surface coatings
on sediment mineral particles or carried as a part of
suspended living or nonliving organic  matter.87 A
laboratory study by Hem90 of sorption of lead by ca-
tion exchange indicated that a major part of the lead
in stream water may be adsorbed on suspended sedi-
ment. Figure 6-26  illustrates the distribution of lead
outputs between filtrate and solids in stream water
from  both  urban  and  rural  compartments, as re-
ported by Rolfe and Jennett.91 The majority of lead
output is associated with suspended solids in  both
urban and rural compartments  with very little dis-
solved in the filtrate. The ratio of lead in suspended
solids to lead in filtrate varies from 4:1 in the rural
compartment to 27:1 in the urban compartment.
              SUSPENDED SOLIDS

              FILTRATE
        6. Lead distribution between filtrate and suspended
solids In stream water from urban and rural compartments.90
  The concentration of lead usually reported repre-
sents a somewhat arbitrarily defined solute fraction,
separated from the nonsolute fraction by filtration.
Most  filtration techniques cannot be relied on to
remove all colloidal-sized particles. Upon acidifica-
tion of the filtered sample, which is usually done to
preserve it  before  analysis, the colloidal material
that passes through is dissolved and reported in that
form.  Usually  the  solids removed from a  surface
water  sample by filtration are not analyzed for lead.
But even the lead in rainfall can be mainly particu-
late, and thus it will be necessary to obtain more in-
formation  on the amounts of  lead transported in
nonsolute form87 before a valid estimate can be ob-
tained of the effectiveness of runoff in transporting
lead away from areas where it has been deposited by
atmospheric fallout and rain.
6.4.2.2 ORGANIC
  The organic components of soil-water system are
an extremely diverse group of compounds that in-
cludes carbohydrates,  amino  acids, phenolic and
quinonic compounds, organic  acids, nucleic  acids,
enzymes, porphyrins, and humic materials.87 In ad-
dition to the natural organic compounds present in
soils, streams and lakes contain organic sediments
and  suspended  solids that have  been derived from
municipal, agricultural, and industrial wastes. These
wastes include carbohydrates, proteins, nucleic
acids, enzymes, lipids, and many other organic com-
pounds found in living systems. In addition, oils,
plasticizers, polymers, and many other organic com-
pounds are discharged to natural waterways by man-
ufacturing and  chemical industries. The interaction
of lead with  these organic compounds is still not well
understood, but most of these organic materials can
confidently be expected to form complexes with lead
(and other metals), since they  all contain available
donor sites for complexation. A  discussion of metal
complexation is presented in Chapter 3 and Appen-
dix B.
  The presence of fulvic acid  (a constituent of soil
humic materials) in water has been shown to increase
the rate of  solution of lead sulfide 10 to 60 times
over that of a water solution at the same pH that did
not  contain fulvic acid.87-92 At  pH values near 7,
soluble lead-fulvic acid complexes were present in
solution. At initial pH values between 7.4 and about
9, the lead-fulvic complexes partially decomposed,
and lead hydroxide  and  carbonate were precipi-
tated. At initial  pH values of about  10, the lead-
fulvic acid complexes again increased. This increase
was attributed to dissociation of phenolic groups at
high pH  values, which increases  the  complexing
capacity of the fulvic acid. But it may also have been
due to the formation of soluble lead-hydroxyl com-
plexes.
  In summary, the complexing of lead by most of the
common sulfur-, phosphorus-, oxygen-,  and
nitrogen-containing ligands means that lead will ac-
cumulate in living and nonliving organic compo-
nents of soil-water and sediment-water systems. The
living and nonliving organic components are not in-
dependent of each other,  but they are constantly
interacting as the living components metabolize the
nonliving components of the  system and then die,
contributing their remains to the pool of nonliving
compounds in the system. The fate of heavy  metals
in this process has not been elucidated; but the sedi-
ment  in  a  contaminated surface-water body  will
serve as a large reservoir that  can provide lead and
other metals to the biota of the system even after
                                               6-22

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heavy-metal pollutants have ceased  to  be  in-
troduced. Most attention has been given to the heavy
metals dissolved in the water phase of surface water
rather than to the complexed metals in the sediment
phase, though  sediments probably contain a higher
amount of lead.87
  The biotransformation of lead to volatile tetra-
methyl lead constitutes one mechanism  by which
lead may leave sediment-water systems. The direct,
biological  methylation  of  certain  inorganic lead
compounds by lake  sediment  microorganisms has
been  reported.93'94 All  the  lake sediments tested
were able to transform trimethyl lead to tetramethyl
lead,93 but only some of the sediments were able to
transform  lead  nitrate  and  lead  chloride  into
tetramethyl lead. No biotransformation occurred
when the lake sediments were incubated with lead
oxide, lead hydroxide, lead bromide, lead cyanide,
or lead palmitate.93 Certain pure bacterial  isolates
(see  Chapter  8) from these  lake  sediments  were
shown to transform  trimethyl lead to tetramethyl
lead in the anaerobic incubation system used.93
  The conversion of the tri- to the tetramethyl lead
salt  was  subsequently postulated  to be chemical
rather than biological, proceeding via formation and
then  decomposition  of an organic sulfide inter-
mediate,  (Me3Pb)2S.95 Using a system containing no
sulfides, however, other workers showed the produc-
tion  by microorganisms  of Me4Pb from Me3Pb +
much  in excess of yields  expected  from  the
stoichiometry  of redistribution reactions of lead
alkyl compounds in aqueous solutions.94 Thus, the
alkylation appears to be direct and  biological.  The
alkylation of lead, unlike that of mercury, was not
mediated  by  methylcobalamin,  as shown when
equimolar  amounts of Me3PbOAc,  Me3PbCl,
Me2PbCl2, and Pb(NO3)2 were substituted  for  in-
organic mercury in an aqueous test system (~pH
7).95 Taylor and Hanna,96 however, have recently
demonstrated  that  prolonged  incubation  of
methylcobalamin with a fine suspension of lead ox-
ide (Pb3O4) in  an aqueous medium results in partial
demethylation  of  the  corrinoid.   This  chemical
demethylation of MeB12 by Pb3O4 was shown to be
highly pH dependent, with no demethylation occur-
ring at pH 7,  and 61 percent occurring at pH 2.
Tracer  studies  with  [ l4C]-methyl-labeled
methylcobalamin indicated that demethylation of
MeB|2 by Pb(IV)  was  accompanied by  a pro-
portional  volatilization of the label. These results
are  in agreement  with the  known instability of
monoalkyl lead compounds in aqueous media as de-
scribed by Wood.97
   The alkylation of lead, then, unlike that of merc-
 ury, does not appear  to result in nonvolatile, toxic
 organolead that could undergo biomagnification in
 the  food chain.  Volatile  TML generated  in  situ
 would be expected to escape from a body of water.
 The possible uptake of tetramethyl lead by aquatic
 organisms during its passage to the surface of a body
 of water is unknown.

 6.4.3 Plants
   Lead  is transferred from the atmosphere  to the
 soil  and vegetative compartments  of the environ-
 ment by dry and wet deposition. Considerable atten-
 tion has been devoted to determining the amount
 and  localization of lead in  roadside  and smelter
 areas, but little information is available regarding its
 chemistry and effects in those areas. Motto el al.98
 suggested that plant uptake is probably related bet-
 ter to soluble rather than total lead in soils. Wilson
 and  Cline" concluded that only 0.003 to 0.005 per-
 cent of total lead in soil is available for plant uptake.
 The soil solution is affected by all the reactions that
 occur as the constituents  are changed through addi-
 tion to  or  depletion from the soil. Ultimately, the
 composition of the soil solution is controlled  by the
 solubility of the various mineral phases in the soil.
 The long-term effects of lead in soils are  uncertain.
 Only recently has attention  been given  to  the
 solubility relationships of  PbSO4,  Pb3(PO4)2, and
 PbCO3  as possible controlling  mechanisms for the
 amount of lead in soils.44 If PbCO3 is involved as a
 reaction product, there is the possibility that soils of
 high pH, upon becoming acidic, could release lead
 at some future time.100 The question  of chemical
 identity of lead in plants is still  largely unanswered.
 Hamp and Ziegler101 have suggested that lead asso-
 ciated with plant surfaces in nature may be largely
 lead  phosphate.  Zimdahl,102 citing  studies con-
 ducted at Colorado State University and the Univer-
 sity of Illinois, reported  the identification of lead
 pyrophosphate in bean roots and  lead orthophos-
 phate in soybean root. The results of later solubility
 studies of the two compounds  suggested that lead
 pyrophosphate  should be  the  dominant  form  in
 plants.
  The process by which lead is taken up by plants,
 which may be passive,85-103 is favored under condi-
 tions of low soil  pH.104 MacLean et al.105 have sug-
gested that soil management practices such as the ad-
 dition of organic matter, lime,  and phosphate may
be appropriate in contaminated soils to reduce the
availability of lead for plant uptake. They found that
the concentration in oats and alfalfa varied inversely
                                               6-23

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with pH  and organic matter, and that addition of
phosphate reduced the uptake of lead; they sug-
gested that the pH effect  was due to repression of
lead solubility  at  the higher pH  values. John and
Van Laerhoven106 found little difference in uptake
by oats and  lettuce when lead was derived from
water-insoluble  lead carbonate as opposed to the
more water-soluble lead chloride or nitrate. Hence
the formation of lead carbonate as a result of liming
would not explain the pH effect.
  Work at the University of Illinois and at Colorado
State University, cited  by Zimdahl,102 has shown
that  uptake by several plant species is inversely pro-
portional to soil lead content and is greatest under
conditions of low pH and low phosphorus. The bind-
ing or exchange capacity of soils,  related to organic
content, is extremely important as a determinant of
lead  availability to plants.  Chelating  agents  can
modify the uptake and possibly  the  movement of
heavy metals by plants, but the relative importance
of natural chelating substances is hard to evaluate at
this time.102 Zimdahl,102 citing a  number of studies
regarding chelation of lead with  EDTA, concludes
that  the extent of lead movement  within the plant is
still  unresolved. He questions whether studies with
synthetic and highly ionized chelating agents such as
EDTA actually reflect what is happening in nature.
  In  a study  conducted  at  the  University  of  Il-
linois107 (cited by Zimdahl102), it was shown that the
roots of hydroponically grown corn acquired a sur-
face  lead  precipitate and  slowly  accumulated
crystalline lead in the cell walls. The surface precipi-
tate  formed quickly and independently of plant ac-
tivity. Two compounds were  postulated  but not
identified. The lead entering the root was concen-
trated in some but not all dictyosome vesicles. After
precipitation had  occurred in the dictyosome vesi-
cle, cell-wall precursors were added to the vesicle by
apposition of vesicles or by internal secretion. As the
lead-containing  crystals grew, more  cell-wall
material was added, so that the entire vesicle even-
tually moved to the periphery of  the cell to achieve
fusion with the cell wall. Lead deposits were thereby
concentrated  at  the  cell  wall  and  not within
mitochondria  or other organelles.102 Although this
sequence of events was observed in the  root tips,
deposits were  observed throughout the plant, and it
was  suggested that a similar process occurred in all
plant tissues.102
   The deposition of lead on  the leaf surfaces of
plants where the particles are often retained for long
time periods must also be considered.32,108,109 Sev-
eral studies have  shown that plants near  roadways
exhibit considerably higher levels of lead than those
farther  away. In most instances, the higher con-
centrations were due to lead particle  deposition on
plant surfaces.32 Studies have shown  that particles
deposited on plant surfaces are often very difficult to
remove completely by simple washing  techniques
considered characteristic  of the  treatment  that
would be  used  in a  household  kitchen.108.110."1
Leaves with hairy surfaces seem  able  to retain (and
attract) particles via  an  electrostatic mechanism.
Other types of leaves are covered with a cuticular
wax sufficiently sticky to preclude the removal of
particles. Thus rainfall does not serve as a particu-
larly effective means of removing the deposited par-
ticles.110 Animals or  humans consuming the leafy
portions of such plants can  certainly  be exposed to
higher than normal levels  of lead. Fortunately, a
major  fraction of lead emitted  by automobiles is
deposited inside a typical highway right-of-way, so
at least part of this problem is alleviated.
  The particle deposition on leaves has led some in-
vestigators to stipulate that lead may enter  plants
through the  leaves. This would typically require,
however, that the lead particles be dissolved by con-
stituents of the leaf surface  and/or converted to the
ionic form  via  contact with water. The  former
possibility  is  not considered likely, since cuticular
waxes are relatively inert chemically. Zimdahl  and
Arvik85 have  shown in a rather elegant set of experi-
ments that entry  of ionic lead through  plant leaves is
of minimal importance. By using the leaf cuticles of
several  types  of plants essentially as membranes,
they found that even high concentrations of lead  ions
would not pass  through the cuticles  into distilled
water on the  opposite side.
  The  results  of  the studies  discussed  above
generally indicate the following:
     1. The uptake of lead by plants from  soil is
       highly dependent on the chemical equilibria
       prevalent in the soil  in question. The uptake
       can probably  be controlled through treat-
       ment  of  the soil with materials (e.g., lime,
       phosphate fertilizers, etc.) that affect these
       chemical equilibria.
     2. Although uptake rates are enhanced at lower
       soil pH levels, the majority of  the lead taken
       up remains  in the plant roots; only smaller
       fractions are translocated to the shoots.
     3. Deposition and retention of lead particles on
       plant  surfaces can  serve as a route of animal
       or human exposure to automotive lead. Thus
       crops grown near sources of high  traffic
                                                6-24

-------
       should  probably  be considered  suspect
       unless  appropriate  safety  precautions  are
       taken.


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100.   Lindsay, W. L. Inorganic reactions of sewage wastes  with
     soils. In: Proceedings of the  Joint Conference on Recy-
     cling Municipal Sludges and Effluents on Land. National
                                                       6-27

-------
     Association  of State Universities and Land  Grant Col-
     leges, Washington. 1973. p. 91-96.
101.  Hamp, R.  and H.  Ziegler. Anreicherung  von Blei in
     Schliebzellen. Die Naturwissen.  7:236, 1974.
102.  Zimdahl, R. L. Entry and movement in vegetation of lead
     derived from air and soil sources. J. Air Pollut. Control
     Assoc  26(7):655-660, 1976.
103.  Arvik, J. H. and  R. L. Zimdahl. The influence of tem-
     perature, pH, and metabolic inhibitors on uptake of lead
     by plant roots J. Environ. Qual. (4):374-376, 1974.
104.  John, M. K. Lead availability related to soil properties
     and  extractable  lead.  J.  Environ.  Qual.  /(3):295-298,
     1972.

105.  MacLean, A. J., R. L.  Halstead, and B. J. Finn  Extrac-
     tabihty of  added lead  in  soils  and its concentration in
     plants. Can. J. Soil Sci. 49(3) 327-334, 1969.
106.  John, M. K. and C. Van Laerhoven. Lead uptake by let-
     tuce and oats as affected by lime, nitrogen, and sources of
     lead. J.  Environ. Qual  7(2):169-171, 1972.
107.  Malone, C., D. E. Koeppe, and R. J. Miller. Localization
     of  lead  accumulated  by  corn  plants  Plant  Physiol.
     54:388-394, 1974.
108.  Gange, P. J. and M. S. Joshi. Lead quantities in plants, soil
     and air near some major highways in Southern California.
     Hilgarda. 4/:l-30, 1971.
109.  Dedolph, R., G. Ter Haar, R. Holtzman, and H. Lucas.
     Sources of  lead in perennial rye grass and radishes. En-
     viron. Sci. Technol. 4(3):217-223, 1970.
110.  Arvik, J. H. and R. L. Zimdahl. Barriers to the foliar up-
     take of lead. J. Environ. Qual. J(4):369-373, 1974.
111.  Lagerwerff, J. V., W. H. Armiger, and A. W. Specht. Up-
     take of lead by alfalfa and corn from soil and air. Soil Sci.
     //5(6):455-460,  1973.
                                                          6-28

-------
                 7. ENVIRONMENTAL  CONCENTRATIONS
                         AND  POTENTIAL  EXPOSURES
7.1  AMBIENT AIR EXPOSURES
  Several  studies  on concentrations of lead in the
ambient air have been undertaken. These  studies
were generally intended to survey the levels and dis-
tributions of lead in the general air environment and
around sources. They usually were not designed in
conjunction with epidemiological studies of the con-
current effects of  lead on man or other organisms.
Yet that is the context in which these  studies  must
now be interpreted to shed the most light possible on
the  concentrations  likely to be encountered  in
various environmental settings.
  Measurements taken with high-volume samplers,
dust-fall buckets, and particle size fractionators are
included in these studies; however, with the excep-
tion of the NASN data  from 1970  through 1974,
quality control and interlaboratory comparability
are  unspecified.  The  effectiveness of some filter
media in collecting very small lead-containing parti-
cles has been questioned; this subject is discussed in
Chapter 4.  The studies show that:
    1.  Lead typically occurs in urban airborne sus-
       pended particles 0.5 /urn  or less in mass me-
       dian equivalent diameter at annual average
       concentrations ranging  from  <0.1  to  5
            3, with an overall  average of  1  to  2
    2.  Urban concentrations of lead have declined
       somewhat since 1970.
    3.  Suspended particles in rural air samples con-
       tain  lead  at  concentrations ranging  from
       <0.01 to 1 .4 /tig/m3' with an overall average
       of about 0.2 /u,g/m3.
    4.  Monthly average concentrations of lead in
       urban settleable particles range from 3 to 12
       mg/m2-mo.
    5.  Indoor  concentrations  of  lead  are  quite
       variable, but are generally one- to two-thirds
       the  concentrations of  adjacent  outdoor
       levels.
  A discussion of the NASN measurements follows.
Summaries of additional studies can be found in Ap-
pendix C.

7. 1 . 1  National Air Surveillance Network (NASN)
Data
  Since 1957, samples of suspended particulate mat-
ter collected  at some 300 urban and 30 nonurban
NASN sites have been analyzed for trace metals, in-
cluding lead.  Only data beginning  with  1966 are
summarized here,  however, because the procedure
used before 1 966 was found to recover only about 50
percent of the lead actually present. The emission
spectrographic  method  now  employed in  the
analysis has sufficient sensitivity to permit detection
of lead in all urban and most nonurban samples.
  Summaries of the  data  for urban and nonurban
NASN sites for 1966 through  1974 are presented in
Tables 7-1 and 7-2, which categorize the sites by
four  successive  annual  average  concentration
ranges. ' '2 The majority of the urban sites (9 1 percent
of the site-years) reported annual averages below 2.0
iUg/m3, and the majority of nonurban sites (86 per-
cent  of the site-years)  reported  annual  averages
below 0.2
  Samples  collected  by  the  NASN from   1970
through 1974 were combined for analysis into quar-
terly composites. Tables 7-3 and 7-4, respectively,
give the cumulative frequency distributions of urban
and nonurban quarterly composite values for  1970
through 1974.'
  Urban NASN sites for which annual average con-
centrations have been 3.0 ^ig/m3 or greater are listed
in Table 7-5. '-2 Highest concentrations for shorter
intervals (quarterly and 24-hr) have been  included,
where available, in  order to indicate the variation in
concentration  with averaging  time  and  potential
peak  exposure conditions.  A large number  of
Southern California cities are  included in the list
because of the heavy automobile traffic in these
areas. Both the annual average and maximum values
at Los Angeles County sites were consistently high,
                                               7-1

-------
TABLE 7-1. NUMBER Of NASN URBAN STATIONS WHOSE
DATA FALL WITHIN SELECTED ANNUAL AVERAGE LEAD
     CONCENTRATION INTERVALS, 1966-19741 2
  TABLE 7-2. NUMBER OF NASN NONURBAN STATIONS
WHOSE DATA FALL WITHIN SELECTED ANNUAL AVERAGE
    LEAD CONCENTRATION INTERVALS, 1966-1974L*
Concentration interval ^g'm3
Year < 0 5 0 5-0 99
1966
No. stations 9 40
Percent 9 42
1967-
No stations 4 37
Percent 3 32
1968-
No. stations 14 67
Percent 9 45
1969-
No. stations 5 46
Percent 2 25
1970-
No. stations 9 54
Percent 5 33
1971
No. stations — 23
Percent — 21
1972
No. stations 16 67
Percent 9 37
1973-
No stations 20 76
Percent 15 55
1974-
No stations 19 69
Percent 15 53
1966-1974-
No. stations 96 479
Total percent 8 38



Year
1970
1971
1972
1973
1974
aLD =

TABLE 7-3.
No
quarterly
composites
797
717
708
559
594
limit of detection
TABLE 74.
10-19 2 0-3 9 40-53 Total Year
1966
40 6 95
No. stations
42 6 - 10° Percent
63 9 — 113 1967
55 7 — 100 No. stations
Percent
54 10 1 146 196g
36 6 1 10° No stations
Percent
103 23 1 178
57 12 1 100 1969
No stations
80 15 1 159 Per°ent
50 9 1 100 197Q-1971-
No stations
64 21 1 109 Percent
58 19 1 100
84 12 1 180 No stations
47 7 0 100 PerC6nt
1973-
36 4 1 137 No. stations
26 3 1 100 Percent
1974
38 4 0 130 No. stations
29 3 0 100 Percent
1966-1974
562 104 6 1247 No. stations
45 8 1 100 Total percent
<003
1
5
1
5
10
29
9
39
3
19
24
15
Concentration interval.
003-0099 010-019
10 6
52 32
7 10
35 50
15 4
75 20
11 9
52 43
— 7
— 70
4 9
12 26
7 6
31 26
5 6
31 38
59 57
36 35
jxg'm3
0 20-0 45 Total
3 19
16 100
2 20
10 100
— 20
-- 100
1 21
5 100
3 10
30 100
11 34
33 100
1 23
4 100
2 16
12 100
23 163
14 100
CUMULATIVE FREQUENCY DISTRIBUTIONS OF QUARTERLY LEAD MEASUREMENTS
AT URBAN STATIONS BY YEAR, 1970 THROUGH 19741
(iug/m3)


Mm
LDa
LDa
LD<»
LDa
0.08


Percentile
10 30 50 70 90 95 99
0.47 075 105 1.37 201 2.59 414
0.42 0.71 1 01 1 .42 221 2 86 4.38
0.46 072 0.97 1.25 193 257 369
0,35 058 077 1.05 162 208 3.03
0.36 0.57 0.75 100 1.61 197 3.16



Max
5.83
631
6.88
5.83
4.09

Arithmetic
Std
Mean dev
1 19 0.80
1 .23 0 87
1 13 0.78
0 92 0.64
0.89 0 57

Geometric
Std
Mean dev
0 99 1 84
1 .00 1 89
0 93 1 .87
0.76 1.87
0.75 1 80

CUMULATIVE FREQUENCY DISTRIBUTIONS OF QUARTERLY LEAD MEASUREMENTS
AT NONURBAN STATIONS BY YEAR, 1970 THROUGH 19741

Year
1970
1971
1972
1973
1974
No
quarterly
composites
124
85
137
100
79

Mm
0003
0.003
0007
0015
0007
Percentile
10 30 50 70 90 95 99
0.003 0.003 0.003 0.003 0.267 0.383 0.628
0.003 0.003 0.003 0.003 0.127 0.204 0.783
0.007 0.007 0107 0.166 0.294 0392 0.950
0015 0.015 0058 0.132 0.233 0392 0.698
0.007 0053 0087 0.141 0221 0.317 0.496

Max
1.471
1.134
1.048
0939
0.534
Arithmetic
Std
Mean dev
0.088 0190
0.047 0.155
0.139 0169
0.110 0.149
0.111 0.111
Geometric
Std
Mean oev
0040 3.72
0008 4.80
0.090 2.59
0068 2.77
0.083 2.30
                                            7-2

-------
TABLE 7-5. NASN STATIONS WITH ANNUAL AVERAGE LEAD
           CONCENTRATIONS >
Maximum
Year and
station
1966
Phoenix, Ariz.
Burbank, Calif.
Los Angeles, Calif
Pasadena, Calif
1967-
Los Angeles, Calif
1968-
Burbank, Calif.
Glendale, Calif.
Long Beach, Calif
Los Angeles, Calif.
Pasadena, Calif.
1969-
Fairbanks, Alaska
Phoenix, Ariz.
Burbank, Calif
Glendale, Calif
Los Angeles, Calif.
San Juan, Puerto Rico
Dallas, Tex.
1970-
Burbank, Calif.
Glendale, Calif
Los Angeles, Calif.
San Juan, Puerto Rico
Dallas, Tex.
1971
Anaheim, Calif.
Burbank. Calif.
Santa Ana. Calif.
Los Angeles, Calif
1972
Burbank, Calif
Glendale, Calif
Los Angeles, Calif
San Juan, Puerto Rico
1973
Burbank, Calif
Average

32
3.7
36
3.6

3 1

4.4
30
3.3
39
35

3.2
3.1
3.5
3.1
4.6
3.8
30

49
3.5
45
3.7
3.2

3.3
5.3
35
46

3.2
3.5
3.1
50

4.0
Quarterly
composite

8.1
6.0
11.0
4.3

5.4

—
—
—
—
—

48
7 1
4.7
4.5
57
4.2
5.2

58
4.2
56
41
3.8

4.0
6,2
46
63

6.7
5.2
48
69

5-2
24-hr

	
—
—
—

—

14.0
75
12.0
100
8.3

__
	
__
__
—
—
—

	 	
	
—
—
—

^
	
	
—

	
—
—
—

—
apparently because of  location,  topography, and
meteorological  conditions that favor retention  of
pollutants in the air over the area.
  Ambient paniculate lead  data from NASN were
studied  for trends over the 10-year period from
1965 through 1974. Figure 7-1 shows the 10th. 50th,
and 90th percentiles for data from 92 NASN urban
sites.3 Urban lead concentrations as described by the
50th percentiles increased trom  1965 until 1971 and
then  declined  from  about  1.1   /ug/m3  to 0.84
      — about a 24-percent decrease, with most  of
this decline occurring between 1972 and  1973. The
other percentiles  exhibit a  similar pattern.  This
general pattern describes the trend for most of the
sites studied. Trends in the percentage of lead in the
total paniculate matter  measured also follow this
pattern, which indicates  that the trends in lead are
not just a result of general paniculate controls but
are a direct result  of decreases in lead emissions.
                                                      i
Figure 7-1. Seasonal patterns and trends in quarterly average
urban lead concentrations.3

  The seasonal  pattern  in  quarterly  composite
values (solid lines in Figure 7-1) shows that the high-
est  levels  of airborne  lead occurred  in the winter
quarters (first  and fourth) and  the lowest levels in
the summer quarters (second and third). In contrast,
automotive emissions of lead would be expected to
be  greater in  the summer  for  two  reasons:  (1)
gasoline usage is higher in the summer, and (2) lead
content  is raised in  summer gasolines to replace
some of the more volatile high-octane components
that cannot be used in summertime gasolines. Evi-
dently summertime meteorological conditions ex-
pedite the movement of these larger emissions more
quickly and widely through the  atmosphere on their
way to subsequent destinations in vegetation, crops,
soil, and water.
  Since  about  the 1970 model year,  automobiles
have been  built with lower-compression engines that
can use lower-octane  gasoline and thus gasoline with
lower lead  content.  As  a  result  of this  engine
modification,  practically all  cars built since 1970
are able to use regular gasoline instead of the more
leaded premium  fuels. Figures 7-2 and  7-3 show,
respectively, the percentage of the total market for
regular and premium gasolines and the trend in lead
content  of gasolines.4 The  results of the  engine
modifications  can be clearly  seen in the lower lead
content  in gasoline (both in  regular and  premium
grades) and in the subsequent  increase in regular
gasoline sales and decrease in premium sales. These
                                                7-3

-------
factors, coupled with the use of a modest amount of
low-lead and no-lead gasoline introduced at about
this same time, are identified as principally responsi-
ble for the observed decrease in ambient lead con-
centrations over this period. The increasing use of
unleaded gasoline resulting from  EPA regulations,
which is  reflected in Figure 7-2,  will lead to even
lower levels of atmospheric pollution in the future.
The effect of these changes is enough to override the
general increase in annual gasoline consumption of
about  5  percent typical  of recent years (except
1974). This increase in gasoline consumption proba-
bly does  not  proportionately  affect many urban
monitoring sites (which  are chiefly center-city  loca-
tions) because their neighborhoods are generally at
or near traffic saturation.  There may even be in-
stances of a reduction in vehicle miles traveled in
downtown  areas because of car pooling, improved
mass transit systems, and the loss of business activity
to suburban shopping centers.
          REGULAR GAS SALES {%)
      I-.--'f"
          PREMIUM GAS SALES <%l
                        UNLEADED GAS SALES (%)
                                         I  I
 Figure  7-2.  Nationwide  trends in  regular, premium, and
 unleaded gasoline sales, 1960-1976.4

  In addition to the NASN study, a number of other
 studies involving major cities and rural areas have
 been  undertaken. These  data  support the NASN
 results (see Appendix C).

 7.1.2 Airborne Particle Size Distribution
  In 1970, a cascade impactor network was estab-
 lished  by EPA in six cities (Cincinnati, Chicago,
 Denver, Philadelphia, St.  Louis, and Washington,
 D.C.) to collect particulates of different size ranges
 for subsequent analysis for lead and other metals.5
 The samples, collected once every 2 weeks for a full
    25 - „,
 a
 u-  20
 O
i  IT  n  i  i   rn  rn

.PREMIUM GAS LEAD CONTENT-
                                         i   r
                  REGULAR GAS LEAD CONTENT
                I  I  I   I  I  I   I  I  I   I  I
Figure 7-3. Nationwide trends in lead content of regular and
premium gasoline, 1960-1976.4
year,  were analyzed for size distribution.  Samples
from  each city were also composited quarterly and
analyzed for lead by optical emission spectroscopy.
  The average annual total  lead  concentration as
determined in this study ranged from a high quarter
of 3.2 /ug/m3  in  Chicago to a low quarter of 1.3
/Ltg/m3 in Washington, D.C. The average mass me-
dian diameter for lead particles ranged from 0.69
/am in St. Louis  to 0.42 
-------
       TABLE 7-6. QUARTERLY AND ANNUAL SIZE
 DISTRIBUTIONS OF LEAD-BEARING PARTICLES FOR SIX
                   CITIES. 1970S
 TABLE 7-7. LEAD IN AIR ON MAIN STREET, BRATTLEBORO,
        VERMONT, SEPTEMBER 12 and 13,1972"<«
City and Average
quarter concentration
of year ng'm'
Chicago, III.
1
2
3
4
Total year
Cincinnati, O. '
1
2
3
4
Total year
Denver, Colo •
1
2
3
4
Total year
Philadelphia, Penn
1
2
3
4
Total year
St Louis, Mo •
1
2
3
4
Total year
Washington, D C
1
2
3
4
Total year

29
35
35
29
32

1 0
2.2
1.9
2.1
18

20
1 1
1.4
3.0
1.8

1.5
1.2
1 8
1.9
16

1.9
1.6
1.8
1.8
1.8

1 3
1.0
1.3
1.8
1 3
Average
mass
median
diameter
^m

1.43
051
0.56
054
0.68

025
0.41
0.54
065
0.48

043
058
052
0.56
050

036
038
070
045
047

0.46
063
0.78
095
0.69

0.36
0.39
041
0.54
0.42
Percentage
of particles
- /Am

41
65
65
64
59

79
74
69
67
72

76
68
69
66
70

74
74
62
70
70

68
63
59
53
62

76
73
74
71
74
  Darrow and Schroeder6 measured lead concentra-
tions  at  eight heights above street  level in Brat-
tleboro, Vermont. The values found are shown in
Table 7-7. The average traffic flow was reported to
be 7500 cars per  day. The concentration  levels
shown in Table 7-7 are considerably higher than
those usually reported in other cities. The investiga-
tors attributed the higher values to greater collection
efficiency and lower sampling heights, but this was
not confirmed. The sampling times were short and
variable. General  conclusions regarding the  rela-
tionship of concentrations versus height  cannot be
drawn from these data.
Height
above
street, ft
1»
2
3
4
5C
7
8
30
Sampling times
836am
10 15am
8.94
—
822
—
715
—
—
—
10 20 a m
1200 noon
784
—
4.40
—
815
—
—
—
1 20 p m
300pm
3.85
531
—
756
—
—
—
—
3 25pm
4 25pm
—
1738
—
21.11
—
2.40
—
—
4 35 p m 9^12
1 02pm 9'13
—
—
—
—
—
—
301
4.25
                                                     a Average air lead value for 54 38 m^ air - 8 54 ng Pb/m^
                                                     b 1-, 2-, 3-, and 4-ft heights Average air lead values for 1353 m3 air = 801
                                                   Pb'm3
                                                     c5-,7- 8-, 30-ft heights Average air lead values tor 40 85m3 air =
  Edwards7  has  reported measurements made  in
downtown Fort Collins, Colo. Measurements were
made in a street canyon formed by two- and three-
story buildings (average  height,  9 m). With a 2.3
m/sec  wind  from  the Northeast  (street  running
north-south), lead concentrations along the east side
of the street canyon  ranged from 1 1.3 /u.g/m3at street
level to 4.0 jug/m3 at roof level. On the west side  of
the street, concentrations ranged from  0.9 /ig/m3  at
street level to 1 .3  /u,g/m3 at roof level. Values for two
additional sampling points above the rooftops on
each side of the street were 0.4 /ug/m3 (east side) and
0.9 jig/m3 (west  side).  Lead concentrations  2 to 5
blocks away  ranged from 0.1 to  0.3 /ig/m3. These
data reflect the wide variability that can be expected
in  urban traffic environments.  Under moderate
cross-wind conditions, concentrations within the
canyon  were  strikingly anisotropic, and street-level
concentrations along the upwind building faces were
substantially  higher than along the downwind face.
With different wind regimes, different building con-
figuration, and different stability conditions, the dis-
tribution  of  concentration  values would  also be
different.
  Barltrop and Strelow8 conducted an air sampling
program at a proposed nursery site under  an  ele-
vated motorway.  The  height of the  motorway was
9.3  m. Air samplers were operated at five to seven
sites from Monday  to  Friday, 8 a.m. to 6 p.m. for 1
year. The maximum individual value observed was
18  /itg/m3. The 12-month mean ranged  from 1.51
/ig/m3 to 1.35  /tg/m3, with standard deviations of
0.91 and  0.66, respectively. The authors reported
that the airborne concentrations were  independent
of height from ground  level up to 7 m.
  PedCo-Environmentaly measured lead concentra-
tions at  heights  of 5 and 20 ft at sites near streets in
                                                7-5

-------
Kansas City, Mo. and Cincinnati, O. The sampling
sites in Kansas City were described as unsheltered,
unbiased by localized pollution influences, and not
immediately surrounded by  large  buildings.  The
Cincinnati study area was located in a primarily resi-
dential area with one commercial  street. Samplers
were operated for 24-hr periods from  8 a.m. to 8
a.m.; but a few 12-hr samples were collected from 8
a.m. to 8 p.m. Data were obtained at Kansas City on
35 days and at Cincinnati on 33 days. The range and
average values reported are shown  in Table 7-8. In
all  cases except  two, the measured concentrations
were higher at 5  ft than  at 20 ft. Note  that the
difference between the east side and west side of the
streets was approximately the same  as the difference
between 5 and 20 ft in height.
 TABLE 7-8. AIRBORNE LEAD CONCENTRATIONS AT 5- AND
       20-FT ELEVATIONS ABOVE STREET LEVELS





East side of street
Location
Kansas City
Cincinnati
Range
08-40
0.1-46
20ft
1.7
09
5ft
20
1 4
Diff
03
05
Averages


West side of street
20ft
1 5
06
5ft
1 7
08
Diff
02
02
  These  data  reflect the strong influence  of  the
geometry  ot the boundary layer,  wind, and  at-
mospheric stability  conditions on the vertical gra-
dient of lead resulting from automobile emissions.
The varabihty of concentration with height is further
complicated by elevated  emissions (i.e.,  from
stacks). Concentrations  measured from sampling
stations on the roofs of buildings several stories high
may not  reflect  actual human  exposure  conditions,
but neither would a single sampling station located
at ground level  in a building  complex.  The height
variation  in concentration resulting from vertical
diffusion of automobile emissions  is likely  to  be
small compared to  temporal and spatial variations
resulting  from  surface  geometry,  wind, and  at-
mospheric conditions.
7.2 MOBILE SOURCE EXPOSURES
  Several major studies have been  undertaken to
determine the lead levels in the air and in  settled
dust near busy highways that  are far  from any  sta-
tionary lead source.  Among the most intensive of
these studies was the Los Angeles Catalyst Study of
 1974-1975, undertaken  by EPA to measure the im-
pact of the catalytic converter on air quality near a
major traffic lead source.10 ,
  Table  7-9 summarizes the  24-hr  ambient con-
centrations of lead  observed at two sites (A  and C)
on opposite sides  of a major freeway  during  the
calendar year 1975.  In addition  to  the monthly
average concentration  at each  site,  the monthly
average cross-freeway  difference in concentrations
(C-A) and ratio of concentrations (C/A) are shown
in the table. Finally, the percentage of hours in the
month when winds were from the directional sector
that is most favorable to the detection  of cross-free-
way differences is  shown in the righthand column.
The favorable wind direction interval  is approx-
imately 160° to 290° and was defined on the basis of
concentration of carbon monoxide, which is a tracer
for mobile-source pollutants.
 TABLE 7-9. MONTHLY AVERAGE LEAD CONCENTRATIONS
      FOR 1975 LOS ANGELES CATALYST STUDY"
Month
January
February
March
April
May
June
July
August
September
October
November
Site A
^g
-------
ranged from 0.21 to 0.59 /*g/m3, or 3.9 to 9.7 per-
cent of total airborne lead at that site.  At a less busy
service station, the  concentration  of organic  lead
was 0.07 /ug/m3, or 4.2 percent of total airborne lead
at that site.
  Data obtained  in  a  number of other  studies on
lead in dusts near roadways are summarized in Ta-
bles 7-10 and 7-11. The above data demonstrate that
abnormally high concentrations of lead are found in
the air and dust near major roadways, and that peo-
ple who live or work (e.g., traffic policemen, service
station and garage attendants) in these areas are ex-
posed to high lead concentrations.
  For  comparison, Table 7-12 summarizes lead  in
dusts from nominally residential urban areas. These
concentrations have a wider range  than those  in
traffic-oriented dust samples. They are higher in the
vicinity of an identified point source such as the El
Paso smelter, but the majority of the readings are
lower than those of the traffic-oriented samples.

7.3 POINT SOURCE EXPOSURES
  Several studies have  been undertaken to investig-
ate lead levels in  the vicinity of various point sources
of lead emission  such as  smelters or battery plants.
By far the most complete  and informative studies are
     TABLE 7-10. LEAD DUST ON AND NEAR HEAVILY
                TRAVELED ROADWAYS
                                        Concentration
      Sampling site
Washington, D C •
    Busy intersection
    Many sites

Chicago-
    Near expressway

Philadelphia-
    Near expressway

Brooklyn
    Near expressway

New York City-
    Near expressway
Detroit
    Street dust
Philadelphia
    Gutter (low exposure)
    Gutter (low exposure)
    Gutter (high exposure)
    Gutter (high exposure)
Miscellaneous U.S. Cities
    Highways and  tunnels

Netherlands-
    Heavily traveled roads
                            12820
                          (4000-8000)12


                             6600


                          (3000-8000)13


                           (900-4900)10


                             200015


                           (966-1213)16


                             1507
                           (270-2626)17
                             3262
                           (280-8201)1'


                         (10000-20000)18
                        TABLE 7-11. LEAD CONTENT IN OR ON ROADSIDE SOIL AND GRASS
                   AS A FUNCTION OF DISTANCE FROM TRAFFIC AND GRASS DEPTH IN PROFILE*
                                                                 Lead content ^.g/g dry weight
                   Site and distance
                    from road, m
            0-5 cm
           soil depth
          5-10 cm
         soil death
         10-15 cm
         soil tlpnth
          WestofU.S 1, near Plant
            Industry Station,
            Beltsville, Md.
              8
              16
              32

          West of southbound lanes,
            Washington-Baltimore Parkway,
            Bladensburg, Md
              8
              16
              32

          West of Interstate 29,
            Platte City, Mo
              8
              16
              32

          North of Seymour Road,
            Cincinnati, O •
              8
              16
              32
   68.2
   475
   263
   51.3
   30.0
   18.5
   21.3
   125
   7.5
   313
   260
   7.6
522
378
164
540
202
140
242
140
 61
150
101
 55
460
260
108
300
105
 60
112
104
 55
 29
 14
 10
416
104
 69
 98
 60
 38
 95
 66
 60
 11
  8.2
  6.1
 a Adapted from Lagerwerff and Specht (cited in Reference 20)
                                                  7-7

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    TABLE 7-12. LEAD DUST IN RESIDENTIAL AREAS
          Sampling site
                                Concentration.
                                  ng Ph/g
Philadelphia
   Classroom
   Playground
   Window frames
Boston and New York'
   House dust
Brattleboro, Vt
   In home
Birmingham, England
   In home
New York City
   Middle class
     residential
El Paso, Texas,
  Smeltertown
  dust at
   0-1 mile

   1-2 miles

   2-3 miles

    > 4 miles

Philadelphia
   Urban industrial

   Residential

   Suburban
                                 2000
                                 3000
                                 1750'7


                               (1000-2000)21


                                (500-900)6


                                 5000'4


                                (608-742)15
                                 36853
                               (2800-103750)22
                                  2726
                                (100-84000)22
                                  2234
                                (100-29386)22
                                  2151
                                (200-22700)22


                                  3855
                                (929-15680)23
                                  614
                                (293-1030)23
                                  830
                                (277-1517)23
those carried out by Yankel et al.24 and Landrigan et
al.25 in the  neighborhood of a smelter  in  Silver
Valley, Idaho.  Consequently,  the  data from these
studies will be described here in some detail. Other
studies carried out in Solano County, Calif.; Omaha,
Neb.;  El  Paso,  Tex.; Helena  Valley, Mont.;
Missouri; Helsinki, Finland; Meza River Valley,
Yugoslavia; and Ontario,  Canada, are summarized
in Appendix C. Their findings are in substantive
agreement with  those of the Idaho  study.
  Yankel  and   von Lindern24  defined five study
areas arranged  concentrically  around the smelter
and  two control areas. Area 1  consisted  of homes
within 1 mile of the smelter; Area 2, 1 to 2-1/2 miles
from smelter; Area 3,  2-1/2 to 6 miles; Area 4,  6 to
15 miles; and Area 5, 15 to 20 miles. Environmental
samples, including surface soil, house dust, paint,
grass, and garden vegetables were  collected at the
homes in each area, as were blood samples from the
resident children aged 1 to 9 years. The mean  lead
levels found in the ambient air, soil, and house dust
all  decreased  with  increasing distance from  the
smelter. As mentioned in Chapter  12, the blood lead
levels of  the  resident children followed a similar
pattern.
  Ambient air lead  levels were measured  by high-
volume samplers stationed throughout  the Silver
Valley. A highly significant relationship  between
distance from the smelter and ambient air lead con-
centration was found, and this relationship was used
to estimate the ambient air lead level for any loca-
tion in the study  area. The mean annual ambient air
lead levels  near  a smelter for two different years
(1974, 1975) are shown graphically in Figure 7-4.
Similar results were obtained for the lead content of
soil  and  house dust. As  noted in Chapter 12,  the
children's blood  lead levels correlate quite closely
with ambient air lead levels,  although  this  result
should not be interpreted as suggesting that  direct
inhalation of lead is the principal  exposure mechan-
ism  involved. One result of this  pivotal study was
that some specific emergency measures were taken in
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                      BY AREA (SEE TEXT)
 Figure 7-4. Annual ambient air lead concentration near a
 smelter, by area, before the August 1974 and August 1975 sur-
 veys.24 Area 1Is within 1 mite of smelter; Area 2 Is 1 to 1-1/2
 mile* from srneKer; Area 3, 2-1/2 to 6 mites; Area 4, 6 to 15
 mites; and Area 5,15 to 20 mites.
                                                  7-8

-------
 1974 (including  covering  contaminated  soil with
 clean soil and  reducing  smelter  emissions)  and
 brought about a decrease in blood lead levels that
 were measured a year later. The details of the blood
 lead levels and  their significance are presented in
 Chapter  12. The conclusion to be drawn from this
 study (and  from  the similar  studies referred to
 above) is that people who live in the vicinity of a ma-
jor industrial source of lead (e.g., a smelter) are ex-
 posed to abnormally high lead concentrations.
 7.4  DIETARY EXPOSURES
 7.4.1 Food
   The route  by which  most  people receive the
 largest portion of their daily lead intake is through
 foods, with estimates of the daily dietary lead intake
 for adult males ranging from 100 to 500 /u,g/day.26
 Only a fraction of this ingested lead is absorbed, as
 discussed in Chapter  10.
   The sources of the lead content of unprocessed
 vegetable foods have been noted earlier  (Section
 6.4.3). Studies of the lead associated  with crops
 (near highways) have shown that both lead taken up
 from soil  and aerosol lead delivered by deposition
 are  found with  the  edible portions  of common
 vegetable  crops. However,  there  is enormous
 variability in  the  amount  of lead associated with
 such crops and in the relative amounts of lead in and
 on the plants. Several factors are involved, the most
 prominent of which are: the plant species, the traffic
 density, the meteorological conditions, and the local
 soil  conditions.27'33  The  variability  induced  by
 differences in the above factors, coupled with the
 fact that many studies have neglected differentiation
 between  lead  on plants versus lead in the plants,
 makes it difficult to generalize. Data of Schuck and
 Locke29 suggest  that  in some cases (e.g.,  tomatoes
 and oranges), much of the surface lead is  readily
 removed by washing. But as noted in Section 6.4.3,
this is not universally true; in some cases much more
vigorous washing procedures are  required.
   In view of the wide variability of soil conditions
 (pH,  organic  matter, cation  exchange  capacity,
phosphorus  content,  etc.),  of  meteorology
 (especially wind conditions and rainfall), and of the
effects of species diversity on the  routes of lead ac-
cumulation, only crude general correlations between
air lead levels and food crop lead levels are possible.
This is influenced by the fact that the lead associated
with plants may be  derived from natural sources,
from automotive sources, and from other sources
such as manufacturing or combustion. One study in
Southern California reported that 60 to 70 percent
 of the lead associated with oat tops was directly at-
 tributable to automobile (aerosol) emissions, but it
 did  not distinguish between lead in the edible  por-
 tion (grain) and  lead on  the  hulls or chaff.27  This
 same study reported that lettuce grown in the Salinas
 Valley had 3 to 25 ppm lead (dry weight) associated
 with it, whereas  the soil lead content was only 10
 ppm. The lead content in the lettuce was reported to
 be 0.15  to  1.5 ppm  on a fresh  weight  basis.  The
 limited data accumulated were used to deduce that
 the excess lead was delivered to the lettuce by aerial
 emission from autos, and that  removal of lead from
 automobile  exhaust would reduce the lead content
 of the lettuce  by  as much as  80 percent.27 In other
 areas, the contribution would be smaller. Though
 these figures may be accurate, they  are based on
 some rather tenuous assumptions that are not  well
 supported by observation and very limited data. The
 estimates must thus  be considered   with caution.
 Moreover, one cannot extrapolate from lettuce or
 oats to all crops.
   The possible connection between  air  lead  and
 food lead may be underscored by comparisons be-
 tween leafy vegetables and food grains. Studies have
 shown that the edible portions of grains absorb very
 little air lead,32 whereas the leafy vegetables retain
 appreciable  quantities.27"29 An FDA survey34 shows
 that  grains  contain approximately 20 percent as
 much lead as the  leafy vegetables. It cannot be con-
 cluded, however, that 80 percent of the  lead in all
 leafy vegetables derives directly from air because
 the  difference  must also reflect  species-dependent
 differences in  uptake from  soil.
   An overall analysis of the data available supports
 the contention that plants grown near busy highways
 consistently  have more lead  in and on them than
 those in other areas. This difference is  typically very
 hard to detect  at distances greater than about 100 to
 200  m from the highway, thereby reflecting the fact
 that  large percentages of the  aerosol  lead fall out
 near roadways. It appears  reasonable to point out
 that  the vast majority of edible crops marketed in
 this country are grown at distances of more than 100
 to 200 m from the highway and that much of the
 aerosol lead can be removed  from association with
 the plants by  processing. Clearly there are  excep-
 tions that will  influence both sides of the question.
 For the present, however, the available data are not
 sufficient to  permit the quantitative estimate of the
contribution of automotive lead to foodstuffs on a
 national or even regional scale.
  The concentrations of lead  in various food items
are highly variable, and as  much variation is found
                                                7-9

-------
within specific food items as between different food
categories.  Schroeder and Balassa,35 in a study of
American foods, have found that the ranges are 0 to
1.5 mg/kg (ppm) for condiments, 0.2 to 2.5 mg/kg
for fish and other seafood, 0 to 3.7 mg/kg for meats
and eggs, 0 to 1.39 mg/kg for grains, and 0 to 1.3
mg/kg for vegetables. All of tht.se values  refer to
unprocessed foods. A British report36 on  lead in
foods describes  similar  ranges  for meat  and eggs,
grain  products (flour and bread), and vegetables;
but concentrations  up to 14 mg/kg were found in
condiments, and up to 18 mg/kg in certain shellfish.
  The amount of lead taken in with food varies from
person to person. It depends on (a) the total amount
of food eaten,  (b)  the history  of the food during
growth, (c) its opportunity to acquire intrinsic  lead
(absorbed from  soil  or water) and  extrinsic  lead
(deposited insecticides or contaminated dusts), and
(d) dietary habits (such as using fresh rather  than
canned foods). On a per-weight basis, the dietary in-
take of lead by children has been shown to be two or
three times that of adults. This additional dietary in-
take is especially significant when the lead added to
food by processing  and to water by plumbing (vide
infra) is considered. A 1974 FDA survey of heavy
metals in foods37 found  relatively high  lead  con-
centrations in metal-canned foods. In the adult food
category, canned foods  averaged 0.376 ppm lead,
and non-canned foods averaged 0.156 ppm  lead. In
the baby food   category,  canned  foods  (juices)
averaged 0.329 ppm lead, and foods in jars averaged
0.090 ppm. The report of the survey  concludes that
from the age of about 1 year on, canned foods com-
prise  11  to 12 percent of a person's diet, but  they
contribute about 30 percent of the average dietary
lead intake. In  a comparison made in the United
Kingdom,38 lead concentrations in  canned foods
were found to vary widely with the precise nature of
the food, but they averaged  about ten times greater
than those in fresh foods.
  The soldered seam of tin cans is evidently the ma-
jor source of this additional lead in canned foods,
and increasing  lead concentrations in samples of a
can's  contents taken progressively nearer the seam
have been found.39 Similarly, there is a correlation
between  increasing lead  concentrations in canned
products and the increasing ratio of the can's seam
length to volume. Of 256  metal-canned foods ex-
amined,  37 percent contained  200 /j.g  Pb/liter or
more; 12 percent contained 400 /ug Pb/liter or more.
These levels are markedly above the potable water
standard of 50 /u,g Pb/liter (0.05 mg/kg) established
by the U.S. Public Health Service.
  Canned pet foods have been found to contain 0.9
to 7.0  ppm  lead  (approximately 900  to  7.000
/xg/Iiter),40 and 18 products averaged 2.7 ppm (ap-
proximately 2700 /Ag/liter). Apart from the possible
toxic effects on pets, the products pose a hazard to
persons who may include them  in their own  diet.
  The  lead content in  milk is of special interest
because it is a major component of the diets of in-
fants and young children. The FDA survey37 found
lead concentrations in whole milk  ranging from 10
to 70 jitg/liter and averaging about 20 /xg/liter. In a
recent  study by Ziegler et al.,41 seven samples of
baby formula and three samples of whole cow's milk
were analyzed in duplicate. Mean concentrations of
lead were 18 Mg/kg  (range 15 to 20) in formula and
10 /ug/kg (range 7 to 15) in milk (1  /ug/kg is approx-
imately 1 /ig/liter). Lead  concentration in  infant
fruit juices ranged  from 23 to 327  /Mg/kg;  in five
varieties of strained fruits, it ranged from 13 to 131
/j.g/kg; and in seven varieties of strained vegetables,
lead concentration was  14 to 73 /xg/kg. Tolan and
Elton38 reported  30 ^g Pb/liter in fresh milk in
Great Britain and 50 /Mg Pb/liter in canned (evapor-
ated) milk. Michell and Aldous39  reported a com-
parable average fur fresh whole milk purchased in
New York State — 40 /j,g Pb/liter.  But their results
for evaporated  milk averaged 202 /ctg Pb/liter and
ranged as high as 820 /xg Pb/liter.
  Hankin et al.42 suggest an additional food-related
source of potential  lead exposure, again predomi-
nantly  affecting children.  The  colored portions of
wrappers from  bakery confections, candies,  gums,
and  frozen  confections have lead concentrations
ranging from  8 to  10,100 ppm. The higher con-
centrations are attributed to lead-containing inks.
No related illnesses were identified,  nor was con-
tamination  of the food  implied; but  the eating of
foods from such wrappers and the licking or chewing
of the wrappers were postulated as one more avenue
for an  additional increment to total lead exposure.
  The  presence of high lead concentrations in illicit
whiskey (moonshine), which is still popular in some
parts  of the  United States despite  the  repeal  of
prohibition, causes lead poisoning in adults. The ap-
parent  source of the lead is the soldered joints in the
distilling apparatus.
  Another potential source of dietary lead poisoning
is the use of inadequately glazed earthenware vessels
for food storage and cooking. An impressive exam-
ple of this danger involved the severe poisoning of a
physician's family  in  Idaho  and  stemmed from
drinking orange juice that had been stored in  an
earthenware pitcher.43 Similar cases, sometimes in-
                                               7-10

-------
 eluding  fatalities, have involved other  relatively
 acidic beverages such as fruit juices and soft drinks
 and have been documented by other workers.44-45
   Recent reports  on lead in European  wines46-47
 show concentrations typically averaging from 130 to
 190 /Mg/liter (0.13 to 0.19 ppm) and ranging as high
 as 299 ^tig/liter (0.299 ppm). Measurements of lead
 in domestic wines have  not been  undertaken; but if
 the European data are indicative, wines could con-
 tain lead concentrations comparable  to  processed
 foods previously discussed.

 7.4.2 Water
   The U.S. Public  Health Service's standards  for
 drinking water specify that lead should not exceed
 50 /xg/liter (0.05  ppm). The average  adult drinks
 about 1 liter of water per day. The presence of detec-
 table amounts of lead in untreated public water sup-
 plies was shown by Durum48 to be widespread, but
 only a few  samples contained amounts  above the 50
 jug/liter  standard. Durfor and  Becker49  analyzed
 untreated and treated  water for the  largest U.S.
 cities, and almost all pairs ot  samples showed a sub-
 stantial decrease in lead that was ascribable to treat-
 ment  provided.  A maximum lead concentration of
 62 jitg/liter was detected in finished water  from one
 of several wells used  in Salt Lake City to supplement
 their surface water supply. Some 95 percent of the
 water supplies sampled, however, had less  lead than
 10 /ug/liter in the treated water before entering the
 distribution system.  Eight of  the water  supplies dis-
 tributed water with a pH of less than 7, which could
 be corrosive to the distribution piping; most of these
 were in the Northwest.  A chemical analysis of 592
 interstate carrier water supplies in 1975 showed only
 0.3 percent to exceed the 50 /^g/liter standard.50
 These  samples were collected  after treatment but
 before distribution,  and they represent  both sus-
 pended and dissolved lead. Interstate carrier water
 supplies serve planes, trains, buses, and  vessels in  in-
 terstate commerce, and  they include almost all of
 the largest  U.S. water supplies.
  The presence of lead in drinking water may result
 from contamination of the water source or from the
 use of  lead  materials  in the water  distribution
 system. Although lead is a relatively minor constit-
 uent of the earth's crust, it is widely distributed in
 low concentrations in sedimentary rock and soils (as
 discussed in  Chapter 3), and naturally  occurring
deposits may be an important source of contamina-
tion in isolated instances. Industrial waste  may also
contribute to the lead content of water sources, but
this appears to be a local and not a widespread prob-
 lem.  The  extensive  use  of  lead compounds  as
 gasoline  additives  has  greatly increased  the
 availability of lead for solution in ground and sur-
 face waters. For example, in a study in east-central
 Illinois,51 the urban  portion  of an 86-square-mile
 watershed, which constituted 14 percent of the area,
 contributed about  75 percent of the  lead  in the
 drainage waters. The  principal source of this  lead is
 identified as automotive emissions. Detailed data re-
 ported for 1 month (June 1972) show that drainage
 waters from this urban portion contained an average
 total  lead concentration  of 69.5 /ig/liter,  including
 6.3  /ig/liter of  soluble lead. The rural portion
 yielded an  average of lead  concentration  of 7.4
 ^ig/liter of drainage water, including 2.1 /ig/liter  of
 soluble lead.
  The major source of lead contamination of drink-
 ing water is the  water supply system  itself.  Water
 that is corrosive can leach  considerable amounts  of
 lead from lead  plumbing and  lead compounds used
 to join pipe. Several widely adopted codes, such  as
 the ASA-A40 Code, Uniform  Plumbing Code, and
 BOCA Code, allow the use of lead pipe and list lead
 as an acceptable soldering material for joining pipes
 that convey water.  Lead pipe  is currently in  use  in
 many parts of  the  United  States for  water service
 lines and interior plumbing, particularly in older ur-
 ban areas.  In a community water supply  survey  of
 969 water systems conducted in nine geographically
 distributed areas of the United States in  1969 and
 1970, it was found  that  1.4 percent of all  tap water
 samples exceeded the 50 /u,g/liter standard.52 The
 maximum  concentration  found  was  640 /u.g/liter
 total lead. The occurrence of samples  exceeding the
 standard  was  more  prevalent in waters with  a
 relatively low pH and low specific conductance.  It
 was estimated that  2  percent of the survey popula-
 tion of 18.2 million was exposed to high lead levels
 at the tap.
  Hem and Durum53  discuss the solubility of those
 species of lead that may be present in drinking water
 and suggest that the solution of lead from environ-
 mental sources may be an important contribution  in
 certain areas, depending on the chemical  composi-
 tion of the runoff water. Above pH 8.0, the  solubility
 of lead  is  below  10 jug/liter, regardless of the
alkalinity of the water. In waters near pH 6.5  with a
 low alkalinity, however, the solubility of lead could
 approach  or exceed  100 /ug/iiter. Lazrus et al.54
 determined  the lead content of precipitation at 32
points in the United States for  a period of 6 months
 in 1966 and 1967.  They reported an average lead
concentration of 34 /tig/liter after filtering the sam-
                                               7-11

-------
pies. Samples of rainfall at Menlo Park, Calif., dur-
ing 1971 showed a wide range of lead  concentra-
tions, from  a  few  /tg/liter  to  more  than  100
jug/liter.53 Hem and Durum53 hypothesize that high-
er lead concentrations should  be anticipated  in
runoff water  and  impounded raw water  supplies in
the Northeast, certain urban areas of the South, and
along the  Pacific Coast because  of low  pH and
alkalinity in waters. However, in much of the rest of
the United States, lead fallout rates and the chemical
composition of the runott (pH  >8; alkalinity >100
mg/liter) would minimize the problem. Information
to test their hypothesis is limited at present. Of the
few surveys of  surface waters  that have been con-
ducted, most  were not done after periods of heavy
rainfall, and  the surveys that have been done have
measured dissolved rather than total lead. Durum48
measured  lead  at 700 lake and  river  sites in  the
United States. These measurements were primarily
single  samples  taken  at  times  of relatively low
stream  flows in   October  and  November  1970.
Detectable concentrations  of  dissolved lead (>1
/ug/liter) were found in 63 percent of the  samples,
but only  three samples contained more  than  50
ju.g/liter. A large  proportion of the samples for the
northeastern  and  southeastern  states contained lead
above the detection limit, and quite a few of the sam-
ples showed levels above 10 /Ag/liter, This regional
distribution ot lead in stream water is in accord with
the idea that  water composition in the eastern states
is more commonly favorable for solution of lead. A
substantial number  of samples from southern
California  were high  in lead,  and these influenced
the data from  the southwestern  states. Kopp and
Kroner55 presented data on dissolved lead in rivers
and  lakes  of the United  States. The  data were
gathered over a 5-year period (1962 to 1967) and
represent  more than  1500  samples. A detectable
concentration of dissolved lead was found in 305, or
19.3 percent of the samples;  the  observed values
ranged  from  2 to  140 /tig/liter.  The highest con-
centration  was  detected  on  the Ohio River  at
Evansville, Indiana. Twenty-seven of their  samples
exceeded  50  /^.g/liter. Observed mean observations
of >30 ^ig/liter  dissolved lead were found in the
following  river basins: Ohio, Lake  Erie, Upper
Mississippi, Missouri,  Lower Mississippi, and Col-
orado.
7.5 OCCUPATIONAL EXPOSURES
   The highest and most prolonged exposures to lead
are found among workers in the lead smelting, refin-
ing,  and manufacturing  industries.56 In the work
areas, the major route of lead exposure is by inhala-
tion  and ingestion of both lead-bearing dusts and
fumes. Airborne dusts settle out from the air onto
food, water, the workers' clothing, and other objects
and are then transferred to the mouth in  one fashion
or another.  Therefore,  good  housekeeping and,
above all, good ventilation have a strong impact on
exposure.  Exposure  levels have been found  to be
quite high in one factory and quite low in another
solely because of differences in ventilation engineer-
ing or housekeeping practices and worker education.

7.5.1 Exposures  in  Lead  Mining, Smelting, and
Refining
  The greatest potential for high-level exposure ex-
ists in  the process of lead  smelting and refining.56
The  most hazardous operations are those in which
molten lead and lead alloys are brought to high tem-
peratures, resulting in the vaporization of lead. This
is because condensed lead  vapor or fume has, to a
substantial degree, a small  (respirable) particle size
range. Thus although the total  air lead concentra-
tion  may be greater in the vicinity of ore-proportion-
ing bins than it is in the vicinity of a blast furnace in a
primary smelter, the amount  of particle mass in the
respirable size range may be  much greater near the
furnace.
  A  measure of the potential lead exposure in pri-
mary smelters was obtained in a study of three typi-
cal installations in Utah.56 Air  lead concentrations
near all major operations, as determined using per-
sonal monitors worn by the workers, were found to
vary from about 100 to more than 4000  /tig/m3. Ob-
viously, the hazard to these workers  would be ex-
tremely serious were it not for the fact that the use of
respirators is mandatory in these particular smelters.
  Although there  are no  comparable data tor ex-
posures in secondary smelters, which are found in or
near most large cities, the nature of their  operation is
similar to that  of primary smelters except that no
ore-processing is involved, since secondary smelters
depend on the local supply of lead scrap in the form
of discarded electric  storage batteries, cable casings,
pipes,  and other materials  for their supply of lead.
Consequently, the exposure  hazard  to  workers in
secondary smelters is probably similar to that found
in the primary smelter study.  Hundreds, perhaps
thousands, of the small scrap  dealers  that supply
these secondary smelters have their own neighbor-
hood or even backyard melting operations for ex-
tracting and  reclaiming lead. These operations can
contribute substantially  to  local  airborne  lead
levels.
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   High levels of atmospheric lead are also found in
 foundries in which molten lead is alloyed with other
 metals. Berg and Zenz57 found in one such operation
 that average concentrations of lead  in various work
 areas were 280 to 600 /xg/m3. These levels were sub-
 sequently reduced to 30 to 40 /ug/m3 with  the in-
 stallation of forced  ventilation  systems  to exhaust
 the work area atmospheres to the outside.
   Exposures for workers involved in lead  mining
 depend to  some extent on the solubility of the lead
 from the ores. The lead sulfide (PbS) in galena is in-
 soluble, and absorption  through the lung may be
 slight. It is not really known how readily  absorption
 takes place.  In  the  stomach, however,  some  lead
 sulfide  may be  converted  to slightly soluble  lead
 chloride, which  may then be absorbed in moderate
 amounts.

 7.5.2 Exposures in Welding and Shipbreaking
   When metals  that contain  lead or  are protected
 with a lead-containing coating (paint or plating) are
 heated in the process of welding or  cutting, copious
 quantities  of  lead particles  in the respirable size
 range are emitted into the air. Under conditions of
 poor ventilation, electric arc welding of zinc sili-
 cate-coated steel (determined to contain some 29 mg
 Pb/in2 of  coating)  produced  breathing-zone con-
 centrations of lead reaching 15,000 ftg/m^, far in ex-
 cess of 450 jug/m3, the current occupational short-
 term exposure limit  (STEL) in the United States.58
 Under good ventilation conditions,  a concentration
 of 140/xg/m3 was measured.59
   In a study of salvage workers using oxy-acetylene
 cutting  torches  on  lead-painted  structural steel
 under  conditions of good ventilation,  breathing-
 zone concentrations  of lead averaged 1200 /Ltg/m3
 and ranged as high as 2400 /ug/m3.60
 7.5.3 Exposures in the Electric Storage Battery In-
 dustry
  At  all stages  in battery  manufacture except  for
 final assembly and finishing, workers are exposed to
 high air lead concentrations, particularly  lead oxide
 dust. Air lead concentrations as high as 5400 //g/m3
 have been recorded in some studies.56 The hazard in
 plate casting, which is a molten-metal operation, is
 from the spillage of dross, resulting  in dusty floors.
 During  oxide  mixing, which  is probably the most
 hazardous  occupation, ventilation is needed when
the mix is loaded with lead oxide powder, and fre-
quent cleanup is  necessary to prevent the accumula-
tion of dust. In the pasting of the plates, whether by
hand  or machine, the danger again  is  from dust
 which accumulates as the paste dries. Also the form-
 ing and stacking processes are dusty, and ventilation
 is needed there also. The data cited are sufficiently
 alarming to suggest that respirators must be worn in
 most of these operations.

 7.5.4  Exposures in the Printing Industry
   In a printing establishment, the exposure to lead is
 probably in  direct proportion to the dispersion of
 lead oxide dust, secondary to the remelt operation.
 Brandt and Reichenbach6'  have  reported on a 1943
 study in which melting pots were located in a variety
 of places where used type  was discarded. The pots
 were maintained at temperatures ranging from 268°
 to 446°C.  The  highest air lead concentration
 recorded was  570 /xg/m3. Since this report  was
 published, working methods  and industrial hygiene
 conditions  have  changed  considerably;  but  a
 marginal degree of hazard still prevails. In 1960,
 Tsuchiya and Harashima62  found in several printing
 shops  in Japan lead levels of 30 to 360  jug/m3 at
 breathing level.

 7.5.5 Exposures in Alkyl  Lead Manufacture
   Workers  involved  in  the  manufacture of  both
 tetraethyl lead and tetramethyl lead, two alkyl lead
 compounds, are exposed to both  inorganic and alkyl
 lead. Some exposure also  occurs at the petroleum
 refineries where the  two compounds are blended
 into gasoline, but no exposure data are available on
 these blenders.
   The major potential hazard in the manufacturing
 of tetraethyl  lead and tetramethyl lead is from skin
 absorption, but this is guarded against by the use of
 protective clothing. Linch et  al.63 found a correla-
 tion between an index of organic plus inorganic air
 lead concentrations in a  plant and the rate of lead
 excretion in the urine  of the  workers. The average
 concentration of organic lead in the urine was 0.179
 mg/m3 for workers in the tetramethyl lead operation
 and  0.120 mg/m3 for workers in  the tetraethyl lead
 operation. The tetramethyl  lead reading was  proba-
 bly higher because the reaction between the organic
 reagent and  lead alloy takes place at a  somewhat
 higher temperature and pressure than that employed
 in tetraethyl lead production.
 7.5.6 Exposures in Other Occupations
   In both  the  rubber products industry and  the
 plastics industry there are potentially high exposure
 levels to lead. The potential hazard of the use  of lead
stearate as a  stabilizer in the manufacture of poly-
vinyl chloride was noted in the  1971 Annual Re-
                                               7-13

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port of the  British Chief Inspector of Factories.64
The Inspector stated  that the number of reported
cases of lead poisoning  in the plastics industry was
second only to that in  the lead smelting industry.
Scarlato et al.65 and Maljkovic66 have reported on
other individual cases of exposure. The source of the
problem is the dust that is generated when the lead
stearate is milled  and  mixed with the polyvinyl
chloride and the plasticizer.
  Sakurai et al.67 in a study of bioindicators of lead
exposure,  found ambient air concentrations averag-
ing 58 /xg/rn3 in the lead covering department of a
rubber hose  manufacturing plant. Unfortunately, no
ambient air  measurements were taken for the other
departments or the control group.
7.5.7  Exposures Resulting  from  Manmade
Materials
  At least two manmade materials in widespread use
are known to contain  lead: paint and  plastics.
  In 1974, the Consumer Product Safety Commis-
sion collected selected household paint samples and
analyzed  them  for lead content.68Analysis of 489
samples showed that  8  percent of oil-based  paints
and 1  percent  of water-based paints  contained
greater than 0.5 percent lead (5000 /jig Pb/g paint,
based on dried solids), which was the statutory limit
at the time of the study. The current statutory limit
for Federal construction is 0.06 percent. This limit is
equivalent to 600  /Ltg  Pb/g paint.68 Old paint that is
still on buildings  will continue to pose a potential
hazard for  some  time. It can become accessible
through flaking, even  though  painted over with non-
toxic paints.
  Lead in paint constitutes a potential health prob-
lem primarily  for children  with  pica  who  may
habitually ingest  1 to  3 g (or more) of paint per
week.68
  Plastics contain  a number of heavy metals that are
constituents  of organometallic  stabilizers   added
during manufacture. The most commonly used lead-
containing stabilizer  is dibasic lead stearate,  in
amounts ranging from 0.5 to  2.0 parts per 100 parts
of resin.69 This stabilizer is normally used in rigid
PVC products. Diffusion, or  leaching by solvents, is
estimated to be quite slow —  on the order of 10-'° to
10'12 cm2/sec at room temperature — but no defini-
tive information is available.
  Incineration  of lead-containing  plastics  may
become   an  increasingly  significant  source  of
localized  lead pollution. It has been estimated that
in the year  2000, for example, there could be ap-
proximately 2.54 times  109 kg of PVC plastic waste
to be disposed of annually, of which  about 0.59
times 109  kg  would  probably  be incinerated.70
Assuming that  lead  will be  emitted from the un-
controlled incineration of PVC's at the rate of 0.2 g
Pb/kg of waste71  (a  figure  applying  to  all  solid
waste),  about 1.2 times 10s kg  of lead  could be
released per year. This would be an increase of more
than fourteenfold over the estimate for  1975.  Since
the greater  part  of  the lead in  these  incinerated
plastic wastes will remain  in the ash,  electrostatic
precipitators can  substantially decrease the emitted
fraction (to an estimated 0.03 g/kg). But this process
only aggravates  the  difficulties  of  residual  solid
waste disposal with its attendant problems of fugi-
tive  dust and the potential contamination of soil,
surface  waters, and groundwaters through leaching
from landfill operations.
  Lead  is present in other products that  may con-
stitute sources of lead exposure when  used or dis-
posed of. Lead may  be found in color newsprint,
craft and hobby  materials,  toothpaste tubes,  cos-
metic products,  candle wicks,  pewter and  silver
hollowware,  painted  utensils,  and  decals  on
glassware. For example, lead  in the paint on handles
of kitchen utensils has been found by Hankin et al.72
to range from 0 to 9.7  percent (0 to 97,000 ppm).
More than  half the  paint  samples (13 of 21) ex-
ceeded the allowable limit for painted toys, which is
0.06 percent.
7.5.8 Historical Changes
  Perhaps the  most  impressive data on  the  mag-
nitude of environmental contamination by lead and
its increase  over  time are  to be  found in a small
group of recent  historical  studies that examined
levels of the  metal in polar snow and ice (Chapter 6).
Of particular interest was the 200-fold increase in
lead  levels over  several  centuries found  by
Murozumi et al.73 in the interior of northern Green-
land, and the 10-fold increase through the last cen-
tury of ice  layers reported  by Jaworowski74  in a
study of two Polish glaciers. These findings parallel
the results of a study by Ruhling and Tyler,75 which
indicated an approximate fourfold increase in lead
content  in Swedish  moss samples taken  from  the
period  1890 to the present. These historical records
reflect the increasing distribution of lead caused by
man.
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                                                7-14

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72.  Hankin, L., G H. Heichel, and R A  Botsford  Lead on          Geochim. Cosmochrm.  Acta.  (London).  3.?:1 247-1294,
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                  8.  EFFECTS  OF  LEAD  ON ECOSYSTEMS
  It has been substantiated  that lead is  a  natural
constituent of the environment, but natural, back-
ground  levels of lead in the environment are not
known with any degree of certainty. As  a  natural
constituent, lead does not usually pose a threat to the
organisms of natural and agroecosystems.  However,
the widespread use of lead in a variety of chemical
forms by man has redistributed the natural  lead in
the environment and has consequently increased the
exposure of the biotic components of ecosystems to
unprecedented  levels  of lead. Concern now exists
about the possible threat to these biotic components
because of their inherent value to ecosystem stability
and because of the ultimate impact that effects of the
ecosystem would have on  man. Figure  8-1  depicts
the environmental flow of lead and the possible ex-
posure  routes  for plants  and animals  in  the
ecosystem.1
                    V ATMOSPHERE <
                    :-. (LEAD AEROSOL:':
                    :•   AND    x
                    ::. ORGANIC LEADI::
Figure 8-1. Simplified ecologic flow chart for lead showing
principal cycling pathways and compartments.1
8.1  EFFECTS ON DOMESTIC ANIMALS,
WILDLIFE, AND AQUATIC ORGANISMS

8.1.1  Domestic Animals
  Lead poisoning, a frequent cause of accidental
death in domestic animals for many years,2 usually
results from the ingestion of lead or lead-containing
material. Substances that cause lead poisoning  in-
clude lead-based paints, used motor oil, discarded
oil filters, storage batteries, greases, putty, linoleum,
and old paint pails. Animals such as cattle, dogs, and
cats that have natural licking and chewing habits are
particularly  susceptible.  Horses  are  not  usually
poisoned in this manner because they  normally do
not lick discarded materials. Animals grazing in the
vicinity of smelters, mines, and  industrial  plants
from which lead fumes and/or dusts are being emit-
ted  or that are fed vegetation harvested from such
areas may also be  poisoned.  The possibility of
animals being poisoned from ingestion of roadside
pasture contaminated by  mobile sources is of con-
cern, but no case of this type has been reported in the
literature.3
  Breathing  of  lead  dusts  can  be another way
whereby animals are exposed to lead, but poisoning
of domestic and wild animals as a  result of lead  in-
halation has not been substantiated.
  Incidents of lead poisoning in cattle and  horses
caused by  emissions from stationary sources have
been reported from  Benecia, Calif.;3  Trail,  B.C.;2
Belleville,  Penn.;4  St. Paul, Minn.;5  and  south-
eastern Missouri.6 Deaths from lead  poisoning of
lambs and  sheep in Britain7 and  of horses,  sheep,
and  goats  in continental Europe  have  been  re-
ported.8-"
  Hammond and Aronson5 have estimated that  the
minimal cumulative lethal dose of lead for a cow is 6
to 7 mg/kg of body weight per day. They state that
this intake represents a concentration  of about 300
ppm in the total diet. In cattle that consumed lead-
contaminated hay and corn  silage grown in a field
adjacent to a smelter, fatal lead poisoning occurred
after approximately  2 months.  In  another study,12
                                               8-1

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cattle were fed  lead at the rate of 5 to 6 mg/kg per
day for a period of 2 years without the appearance of
visible clinical symptoms. A steer fed the same diet
for 33 months,  however, showed clinical symptoms
of lead poisoning culminating in death.13 The length
of time required for the appearance of overt clinical
symptoms of lead poisoning is  in  most instances
directly related to the amount consumed per unit of
time.
  Horses are more susceptible than cattle to poison-
ing from the chronic intake of lead. In the Trail,
B.C.,  study,2 horses grazing near  a lead  smelter
developed  overt symptoms of lead poisoning, but
cows in the same pasture were not clinically affected.
The minimal toxic dosage for a horse has been esti-
mated to be between 1.7 and 2.4 mg/kg body weight
daily,1 which is approximately 80 ppm dry weight in
forage.
  The reasons for the greater susceptibility of horses
are complex. An early symptom of lead poisoning in
the horse  is paralysis of the nerves of the pharynx
and larynx. This interferes with breathing, especially
on eAercise, and causes the animal  to breathe ster-
torously, or to roar. When severe, this paralysis can
produce suffocation and  death.  In addition,  the
faulty action of the epiglottis vwhich closes off the
lung during inhalation) permits inhalation of food,
which can result  in  suffocation  and death  or  in
severe pneumonia, which can also be fatal.
  Colts pastured  near the Trail,  B.C.,  smelter2
showed loss of weight, generalized  muscular weak-
ness, stiffness of joints, and harsh, dry coats. Distor-
tion of the limbs occurred, the joints became greatly
enlarged and  the  hocks  touched. The  laryngeal
paralysis usually associated with  lead poisoning did
not occur. Hupka9 noted the same symptoms in colts
that had grazed on pasture contaminated with flue
dust from a metal works. Autopsy  showed  that the
auricular cartilages were detached and loose  in the
joint. Also noted was an acute catarrhal pneumonia
of both  lobes of the lungs, with food particles in the
bronchi. Roaring typical of chronic lead poisoning
did not occur until quite late.
   The clinical picture described above  has come
under  close  scrutiny in  various  laboratory
studies.14*15 because of the lack  of consensus as to
whether it was the result of lead poisoning. Lead and
z-inc coexist in many ores, and both were present in
the two situations referred to above. Under these
conditions animals being reared in the area would be
exposed to both elements simultaneously. Studies by
Willoughby et  al.14 indicated that lameness, blind-
ness,  swelling  at the epiphy»eal ends of long bones,
or an increase in the amount of joint fluid in foals
resulted from the intake of zinc by itself and zinc and
lead together, but not from lead alone. Gunther,15 in
studies  based  on experimental exposure of colts,
reached similar conclusions.
  Horses  sometimes,  though infrequently, pull up
plants and eat roots and soil along with leaves. This
practice may be  a factor in increasing their lead in-
take'6 relative to that of cattle grazing  the same
pasture.
  Lead poisoning in all domestic animals produces
various degrees  of derangement of the central ner-
vous system, gastrointestinal tract, muscular system,
and hematopoietic system. Younger animals appear
to be more sensitive than older ones.13 Calves may
suddenly  begin to bellow and stagger about rolling
their  eyes,  frothing at the  mouth,  and crashing
blindly into objects. This phase may  last up to 2 hr,
after which  a sudden collapse occurs. In less severe
cases, depression, anorexia,  and colic may be ob-
served.  The animals  may  become  blind  and may
grind their teeth, move in a circle, push against ob-
jects, and lose their muscle coordination. Mature
cattle display fewer overt symptoms, although the
syndrome of  maniacal excitement  is not uncom-
mon.1
  Clinical symptoms  in  sheep consist  mainly  of
depression, anorexia, abdominal pain, and diarrhea.
Anemia  is  also commonly associated  with lead
poisoning in sheep.1 Pavlicevic11 notes that clinical
symptoms in lambs consist of paralysis of the ex-
tremities, pharynx, tongue,  and  larynx;  a rigidly
held neck; and an anemic mucous membrane. Lambs
may be poisoned through the mother's milk when the
ewe is on contaminated pasture. Sterility and abor-
tion in ewes have been observed as a result of lead
ingestion.1
  Toxic dosages of lead for domestic animals other
than horses  and cattle have not been calculated from
statistically reliable studies.
  The effects of  lead on  biological  processes in
animals generally include effects on the nervous and
hematopoietic systems and the kidney tissue. These
effects have been studied with various types of test
animals (primarily the rat)  at the  enzymatic, sub-
cellular, cellular, and tissue morphology levels; and
systemically at  the physiological  and biochemical
levels.
   The most sensitive indicator in rats is the decrease
of  the enzyme  8-aminolevulinic  acid  dehydrase
(ALAD)  that  regulates  heme synthesis.17  Lead
clearly affects test animals  at the  subcellular and
enzymatic levels of biological function.
                                                8-2

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8.1.2 Wildlife
  Lead has so permeated the environment that it is
now known to be a regularly occurring constituent of
all animal life. Birds and other wild animals are ex-
posed to a wide  range of lead levels.  Measurable
amounts of lead may be found in the tissues of these
animals, and lead poisonings have occurred.
  Toxic effects from the ingestion of spent lead shot
were lirst observed  in ducks in 1919 and have since
been recognized  as  a major health problem in both
aquatic and upland  species of waterfowl. It has been
estimated that thousands of ducks, geese, and swans
die  of lead poisoning each year.18 Lead  poisoning
from spent shot has also been reported in game birds
such as wild pheasants, mourning doves, and quail.19
The scope of the problem becomes readily apparent
when it is noted  that the majority of the birds die
after the hunting season is over; thus it is the breed-
ing stock that is lost. Spent shotgun pellets have been
removed from  the  gizzards  of birds with  lead
poisoning.20
  Pieces of lead metal when swallowed are normally
not harmful to humans or other mammals because
they pass through the digestive tract too rapidly to
lose more than a  minor portion of their surfaces to
digestive enzymes  and other  substances. But it
should be noted  that persons who  consistently eat
game often  have somewhat elevated  blood  lead
levels and high fecal lead  levels from swallowing
lead pellets. The gizzard of a  bird, however, is a
comminuting organ for food that operates by grind-
ing  up the food in a muscular sack containing small
stones that the bird has swallowed. Spent  shotgun
pellets lying in the sediment on the bottoms of lakes
are  picked  up by the bottom-feeding ducks in the
same manner as  pebbles. Because the shot are  soft,
they are ground  fine and made quite susceptible to
digestive action rather than just coming into super-
ficial contact with  the digestive  tract, as  in most
other animals.21  Lead released from the  gizzard is
absorbed by the lower digestive tract. One number-6
lead shot can furnish enough lead to  induce fatal
lead poisoning in a duck; but, the length of time a
pellet is retained in the gizzard depends partly on its
size and partly on the fiber content of the diet. A
high fiber diet is especially  conducive to  lead
poisoning. The number of shot required to poison a
bird also depends  on  the size of the bird itself. Six
number-6 shot are always fatal for mallards, and
four or five number-4 shot are generally fatal for
Canadian geese.22
  The  symptoms  generally  associated with  lead
poisoning in waterfowl are lethargy, anorexia, weak-
ness, flaccid paralysis, emaciation, anemia, greenish
diarrhea, impaction of the proventriculus, and dis-
tention of the gall bladder.22 Waterfowl appear to be
at least twice as sensitive to the biochemical effects
of lead as are man  and other mammals.23 Death ap-
pears  to  be  associated  with  the inhibition  of
8-aminolevulinic  acid  dehydrase  (ALAD)  by
lead.23'24 In instances where insufficient lead is in-
gested to cause death, sterility may result.1
  In an attempt to prevent the  deaths of waterfowl
through the ingestion of lead shot, the U.S. Fish and
Wildlife Service ordered the use of steel shot during
the 1976 hunting season in certain areas of the states
in the  Atlantic Flyway. Despite strong opposition
from the National Rifle Association and hunters, the
plan is to extend this  limitation to the Mississippi
Flyway during 1977.25
  Waterfowl mortality caused by the toxic effects of
lead mine wastes coupled with environmental stress
was  reported by Chupp and Dalke26 for the Coeur
d'Alene River Valley of Idaho. Because of their
feeding habits, feeding waterfowl  consumed  lead
from the sediments in the shallow areas of the river
along with metallic materials adhering to roots and
tubers of aquatic plants. Ingestion of plants contain-
ing lead can also  contribute to lead poisoning in
waterfowl.
  The  puffin  (Fratercula arctica), a  sea bird, is in
serious decline.  In studies to determine the cause,
Parslow et al.27 note the fact that puffins tend to con-
centrate lead  through  the  food chain (Table 8-1).
The authors were not able, however, to associate ob-
served  lead  concentrations with the decline of the
species.
                   TABLE 8-1. ACCUMULATION OF CERTAIN HEAVY METALS FROM SEAWATER
                              BY FISH (Ammodytes AND Clupea) AND A PUFFIN"
Metal levels, ppm wet weight

Metal
Mercury
Lead
Cadmium
Copper
Zinc

Seawater
0.00003
0.00003
000011
0.003
0.01

Fish
0.037
< 0.002
0309
1.74
53

Puffin
0.79
0.36
1 67
4.49
95
Approximate accumulation factors
Fish/
seawaler
1,230
<67
2,800
580
5,300
Puffin/
fish
21
>180
54
26
1.8
Puffin'
seawater
26,300
12,000
15,000
1,500
9,500
                                                8-3

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  Measurements of lead levels in pigeons28-29 and in
song birds30 indicate that urban birds have higher
lead levels than rural birds (Table 8-2). Bagley and
Locke19 analyzed 28 species of birds and noted the
concentration  of lead in  the livers and bone tissue.
Lead in the livers was an indication of acute  ex-
posure, and in the bone,  of chronic exposure. Liver
levels ranged from 0.3 to 5.0 ppm, and bone levels
ranged from 0.2 to 26.0 ppm. As might be expected,
the highest levels were found  in aquatic waterfowl;
however, ti.J osprey (Pandion haliaetus), a predator,
also showed h'°h bone levels. The bone lead  levels
are an indication of continued exposure to lead and
serve as an indication of normal levels rather than
adverse exposure.19
                       TABLE 8-2. SUMMARY OF LEAD CONCENTRATIONS IN BIRD ORGANS
                   AND TISSUES FROM AREAS OF HIGH-LEAD AND LOW-LEAD ENVIRONMENTS
                                            (ppm, dry weight)
Species and lead level3
                     Feathers
                                                           Lung
                                                                        Kidney
                                                                                     Bone0
                                                                                                 Muscle0
Red-winged
blackbird
Low(10)
High(4)
House sparrow
Low(16)
High(11)
Starling'
Low(11)
High(13)
Grackle
Low(10)
High(11)
Robin
Low(10)
High(IO)


265
668

270
1583

64
2251

36.0
81.4

253
79.7


2.1d
26d

23
26.2

13
6.0

1.4
102

32
245


5.8
1.2

06
12.0

40
161

2.5
121

24
105


04
41

09
69

2.8d
52d

23d
2.7d

2.2
10.3


21d
4.1d

3.5
33.9

3.6
98.5

35
135

73
250


6.9
9.1

169
130.4

128
2130

21.5
628

41 3
133.7


0.8=1
06d

09
2.1

08"
2.4d

0.8
1.4

1 Od
1 2d
  a High-lead and low-lead environments are urban and rural areas respectively high-lead area (or red-winged blackbirds is 10 m from an interstate highway Sample size in
parentheses
  k Femur
  c Pectoral
  ^ Differences between low- and high-lead environments not significant at the 0 05 level all others significant at least at the 0 05 level
   Studies  of  lead  exposure  and  effects  in wild
 animals other than  birds are infrequent. Braham3'
 studied  the  distribution  and  concentration  in  the
 California  sea lion  (Zalophus  californianus).  He
 noted that accumulation was occurring in the species
 but could detect no  adverse effects at the time of the
 study. The exposure of small mammals and selected
 invertebrates near  roadways  has  also  been
 studied.32'38 In general, gradients in body lead con-
 centrations declined with increasing  distance from
 the road. The body lead gradients usually were simi-
 lar in pattern to, though lower than, the soil level
 gradients; but interesting exceptions were observed
 in  some cases. No evidence of toxicity was observed
 in  any of these animals individually or in relation to
 population distributions.
   An analysis of lead concentrations in 3 species of
 small mammals from  11 sites in Huntingdonshire,
 Great Britian,32 showed that the lead concentrations
 in  the animals were  more closely associated with the
 type of food consumed than  with  nearness to  the
 highway  where  the  air  lead  concentrations were
 highest.
   One hundred and one mammals — 51 long-tailed
 field  mice (Apodemus  sylvalicus),  27  bank  voles
 (Clethrionomys  glariolus), and  23  field  moles
 (Microtus agrestis)—were trapped along road-
 sides.32 The concentration  of lead was significantly
 higher  in  Microtus than in  Clethrionomys  or
 Apodemus  (Figure  8-2).  The  marked differences
 among the lead  concentrations of the three species
 can be accounted for by species behavior and food
 consumed. Microtus eats  grass  as  its staple  food,
 whereas Apodemus feeds on grain,  seedlings, buds,
 fruit, hazel nuts, and animals such as snails and in-
 sects.  The range of food for  Clethrionomys encom-
 passes that of both the other species, but the habitat
 is restricted to  hedges  rather than the open field
 (Apodemus) or the roadside (Microtus). Differences
 in food and food contamination may therefore ac-
                                                  8-4

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count for the  differences in lead concentrations in
the three species.
                                - BANK VOLES
                                 (Clethnonomvs)
                               • - FIELD MICE
                                 iApodemus)
                               D-MEAN OF SPECIES
                     TYPE OF SITE
Figure 8-2. Concentration of lead In three species of small
mammal* trapped beside major and minor roads and at ara-
ble and woodland sites."
  In  a study  in central Illinois, samples  of small
mammals were obtained from a range of  environ-
ments including those within 10m of a high-traffic-
volume road ( > 12,000 vehicles/24hr), those within
5 m of medium-use roads (2000  to 6000 vehicles/24
hr), those within 5 m of low-use roads (<2000 vehi-
cles/24 hr), and those in urban areas (approximately
100,000 inhabitants).38
  All species  except  the  white-footed mouse
(Peromyscus  leucopus),  showed  higher  concentra-
tions  of  lead in habitats adjacent to  high-traffic-
volume situations, especially in  urban areas. Since
the home range of this species averages more than 50
m in diameter, even those individuals caught nearest
the highway were undoubtedly spending considera-
ble time much  further  removed  from  the  traffic
source, possibly accounting for the low lead levels in
these  animals.
  There was also a correlation between  habitat re-
quirements and  lead concentrations in small mam-
mals  captured  near high-traffic roadways. Species
requiring  dense  vegetation—the prairie  vole
(Microtus ochrogaster),  the  short-tailed  shrew
(Blarina brevicauda), the least shrew (Cryptotis par-
va),  and the  white harvest mouse (Reithrodontomys
megalotis) — had higher total body lead burdens and
higher  levels in selected tissues than  did  those
species such  as the white-footed mouse (Peromyscus
maniculatus)  and the house mouse (Mus musculus)
that extend their home ranges into cultivated fields.
There was also a correlation  between feeding habits
and  lead concentrations in body tissues. Insectivores
(the shrews)  had the  highest lead concentrations;
herbivores (voles) had intermediate concentrations;
and  granivores (deer mice, white-footed mice, and
house mice)  had the lowest concentrations, reflect-
ing the fact that lead concentrations in  seed  tissue
are usually extremely low « 1 ppm).
   It is highly doubtful that the very  low concentra-
tions of lead  in these mammals (Table 8-3) could be
having a  significant impact on  their   population
dynamics.
   Studies of  lead concentrations in insects in central
Illinois ecosystems have shown positive correlations
with lead emission levels, decreasing from areas ad-
jacent to heavily traveled  roads to areas remote
from roads (Table  8-4).39 There was also a strong
trend  of increasing  lead  content from  sucking to
chewing to predatory insects collected  near  high-
traffic roadways  (Figure 8-3). Chewing  insects pro-
bably ingested more lead from deposits on leaves
than did insects that suck liquids from the internal
vascular tissues of plants.  Data on predatory insects
that feed on  lead-containing herbivores suggest that
lead is selectively retained in the body, leading to
biological  concentration in this two-trophic (feed-
ing-level) system.39
   Definitive  studies  correlating  toxicity with  en-
vironmental  lead concentration have not been  done.
8.1.3 Aquatic Organisms
   Acute lead toxicity in aquatic organisms has been
observed and studied experimentally. Lead toxicity
in fish is partially related  to drainage from metallic
wastes into streams. Early experiments were carried
out  in  England  where contamination  of  natural
waters by lead mining caused the disappearance of
fish  from streams.1 Although the effect  of lead on
lower  forms  of life is not well documented,  it  ap-
pears to be less toxic than in higher forms.' '40
  Apparently, lead and other metals are irritating to
the skin of  many  freshwater fish  and cause  an
unusual reaction. The presence of metal in the water
around them causes a copious secretion of mucus
over the whole body surface,  particularly in the gill
                                                8-5

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TABLE 8-3. MEAN LEAD CONCENTRATIONS IN ORGANS AND TISSUES OF SMALL MAMMALS FROM
              INDICATED AREAS OF ENVIRONMENTAL LEAD EXPOSURE"
                              (ppm, dry weight)
Species and Total
exposure area body Gut Spleen
Blarina brevicauda'
High 18.4 24.0 4.5
Medium 6.7 7.0 3.6
Low 5.7 3.1 2.3
Microtus ochrogaster:
High 51 110 5.3
Medium 59 18.4 2.2
Low 1.9 2.8 2.4
Peromyscus maniculatus:
High 6.3 192 194
Medium 4.3 60 30
Low 3.3 4.5 65
Control0 3.1 43 37
Mus musculus:
High 68 186 12.1
Medium 6.0 8.8 3 1
Low 67 4.8 5.1
Control 2.0 2.7 2 1
fleirhrodontomys megatofis:
High 123 178 145
Medium 3.0 6.2 9.2
Low 2.7± 35 5.6
a Femur
6 Thigh
c Control areas are fields more than 50 m from a road
TABLE 8-4. LEAD CONCENTRATIONS OF INSECTS AT TWO
DISTANCES FROM A HIGH-TRAFFIC-VOLUME ROAD
(INTERSTATE HIGHWAY)"
(ppm)
Distance
0 to 7 m from 1 3 to 20 m from
Feeding type pavement pavement
Sucking 15.7 98
Chewing 27.3 104
Predatory 31 .0 20 0
Mean 24.7 134
area. Analysis of this mucus has revealed the pre-
sence of "considerable quantitities" of lead.41 The
mucus does not, however, prevent absorption of lead
into the fish. If the metal level is low, the process is
harmless because the excreted film is readily shed;
but if higher levels are present, the mucus blanket
generated may suffocate the animal before it can be
shed. The phenomenon has been observed only in
freshwater fish and is subject to modification by
water hardness, temperature, and other factors. It
should be emphasized that the process described
above is entirely external and unrelated to lead
levels in the body of the fish. In some cases of lead
poisoning in freshwater fish, mucus formation has
not been observed.
Liver Lung Kidney Bonea Muscle*3
4.6 16.9 12.4 67.1 97
2.0 56 5.8 199 5.7
10 78 39 12.2 5.4
1.6 2.8 81 16.6 82
12 1.8 7.6 23.2 3.0
10 1,3 2.8 4.6 2.0
3.5 6.4 7.9 24.6 6.8
1.7 24 9.0 8.0 7.4
1.8 6.1 30 6.4 18
1.1 15 1.8 5.7 21
2.9 2.8 8.1 19.2 5.9
1.6 34 6.6 210 3.9
1.6 1.7 3.1 235 3.4
1.9 34 3.4 9.3 3.8
4.7 20.9 — 109.5 275
11 42 2.1 — 4.4
23 4.7 48 18.4
Symptoms of chronic lead poisoning in fish in-
clude anemia, functional damage to the inner
organs, possible damage to the respiratory system,
growth inhibition, and retardation of sexual
maturity.1'42
A study in central Illinois43 of both urban and
rural tributaries of the Saline Branch of the Ver-
milion River showed that lead appears to be taken
up by aquatic organisms by means of external con-
tact rather than by ingestion. Lead concentrations in
aquatic organisms were found to be related to the
amount of contact with substrates, such as sediments
(Figure 8-4), that contain the highest lead con-
centrations in the streams. Thus species differences
in Concentrations are determined in part by habitat
preference and feeding habits.
Filtered water from the two streams had con-
centrations of lead varying from 0 to 15 mg/liter of
water (ppm), and suspended solids in the water con-
tained 15 to 200 ppm lead. The highest levels occur-
red in the urban stream. The upper 10 cm of sedi-
ments in the urban stream contained an average lead
concentration of 387.5 ppm, more than 10 times
greater than that in the rural stream. Fish in the
rural stream contained an average of 1.4 to 4.1 ppm
                                   8-6

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            I STD ERROR
            D LOW Pb EMISSIONS ARE A
            ED HIGH Pb EMISSIONS AREA
                      Q
                                    PREDATORY
                    INSECT FEEDING TYPES
Figure 8-3. Mean lead content in grouped insect samples
taken from low- and high-lead-emlsslon areas tor sucking,
chewing, and predatory feeding types.39
of lead in dry  tissue (Table 8-5).43 No fish were
found in the urban stream. Lead levels in the inver-
tebrates ranged  from about 5 to 20 ppm in the rural
stream  to more  than 350 ppm in the urban  stream.
These data  appear to be in agreement with relative
lead levels found in tubificid worms, clams, and fish
in the Illinois River.40
  Hardisty  et al.44 studied lead levels in estuarine
fish,  but were unable to determine any biological
effects of lead. Merlini and Pozzi45  studied lead ac-
cumulation by freshwater fish. Ionic lead (as Pb + + )
was concentrated threefold when the pH of the lake
water was lowered. Lead toxicity in fish was not re-
ported.
  Toxicity varies with pH, temperature, hardness,
and other water properties.40 The concentrations of
lead  injurious to fish and other aquatic and marine
life may be found in Water Quality  Criteria,  1972.46
The 96-hr LC50 value in soft water for rainbow trout
(Salmo gairdneri) has been reported to be 1 mg/liter.
Pickering and Henderson47 list the  soft  water LC50
values for  fathead minnows (Pimephales promelas)
and bluegills (Lepomis macrochirus) as being 5 to 7,
and 23.8 mg/liter, respectively.  In  hard water, the
LC50 values for  the last two species are  reported as
                                El??! URBAN COMPARTMENT

                                t^-J COMBINED COMPARTMENT

                                I  I MARGINAL COMPARTMENT

                                •B RURAL MAIN CHANNEL

                                   RURAL TRIBUTARIES
       SEDIMENTS     CLADOPHORACEAE
            TUBIFICIDAE       CHIRONOMIDAE
                                                                   SEDIMENTS AND ORGANISMS
Figure 8-4. Mean lead levels in representative organisms and
sediments of the compartments of the drainage basin of the
Saline Branch of the Vermilion River, III.43
being 482 and 442 mg/liter, respectively;47 whereas
for rainbow trout, Davies and  Everhard42 report
471 mg/liter. Detrimental effects on fish species oc-
cur at concentrations  as  low as  0.1  mg/liter.  In
studies of rainbow trout,  mortalities attributed to
lead occurred at the high test concentrations, which
in soft water were 95.2 ,ug  Pb/liter and in  hard
water, 3.24 mg/liter total lead or 0.064 mg/liter free
lead.42  Physical  abnormalities  occurred  between
11.9 and 6.0 jug  Pb/liter in soft water and between
0.12 and 0.36 mg/liter total lead (0.018 and 0.032
mg/liter free lead) in hard water. In Daphnia magna,
an effect on reproduction has been observed at 0.03
mg Pb/liter.48
  A study of long-term effects of lead exposure on
three generations  of  brook  trout (Salvelinus fon-
tinalis) indicated that all second generation trout ex-
posed to 235 and 474  /ug Pb/liter developed severe
spinal  deformities (scoliosis), and  34  percent of
those  exposed to 119 /u,g  Pb/liter  developed
scoliosis.  Of the  newly hatched  third generation
alevins  exposed  to 119 /u,g Pb/liter,  21  percent
developed  scoliosis. Analysis of residues in  eggs,
alevins, and juveniles indicated that accumulation of
lead occurred during these lite stages.49
  Weir and Hine50 utilized a conditioned avoidance
                                                  3-7

-------
Compartment and organism
Rural-
Plants
Cladophora
Potam'geton
lnvertebrc.,f s
Hirudinea
Oligochaeta
Tubificidae
Sphaeriidae
Lirceus fontinalis
Hexagenia limbata
Anisoptera
Chironomidae
Decapoda
Fish
Catostomus commersoni
(white sucker)
Etheostoma nigrum
(Johnny darter)
Ericymba buccata
(Silverjaw minnow)
Notropis umbratilus
(Redfm shiner)
Pimephales noiatus
(Bluntnose minnow)
Semot/'/us airomaculaws
(Creek chub)
Urban-
Plants
Claojphor i
invertebrates
Tub' cidae
Chironomidae
Decapoda
Combined.
Plants
E/odea
Cladophora
Invertebrates
Tubificidae
Chironomidae
Physa
Ps-'chodidae
Arithmetic Number of
mean samples


201
300

12.6
13.2
160
55
7.6
104
66
201
47


24

41

1 8

1 9

27

1 4


347

367
153
11


89.9
34.9

48.6
42.7
41.7
323


11
15

12
7
13
11
5
15
6
12
23


19

9

29

29

83

35


6

29
5
4


22
7

71
12
10
4
Standard
deviation


51
54

14.8
76
11 8
31
34
9.7
24
182
52


1.6

24

09

06

27

06


139

373
106



93.3
75

339
16.4
25.5
25.5
technique to assess the deleterious effects of four
metal ions, including lead, on goldfish. Behavioral
impairment  was  noted following  sublethal  con-
centrations of lead nitrate (Table 8-6). The lowest
concentration that gave significant impairment w
-------
hairs may make leaf surfaces sticky; thus, particulate
material can accumulate on the plant surface, partic-
ularly the leaves. However, particulate matter must
enter the internal plant tissues to affect the plant.56
Franke-5S suggests that the cutin is penetrable via in-
termolecular spaces and that cuticle has been shown
to be permeable to both organic and inorganic ions
and to undissociated molecules. The capability of an
ion to penetrate is determined by its charge, adsorb-
ability,  and radius.
  Vascular plants have  small surface  openings,
called stomata and lenticels, that function in gas ex-
change.  Stomata  are  also sites  of  exchange of
aqueous substances under certain conditions.58
Stomata occur in the epidermis of leaves and young
stems. Lenticels are found on older stems of woody
species.  Surrounding the stomatal pores are  guard
cells that open and close the pores through changes
in their  turgidity.  Gas  exchange, which takes place
through the stomata as the result of a concentration
gradient, is a passive phenomenon unlike the active
breathing of animals.
  Large deposits  of inert, insoluble  metal  com-
pounds  on  the  leaves are probably of little conse-
quence  to  a  plant. The  most  important  factor in
determining foliar penetration is the solubility of the
individual  metal.56-58 The insolubility of lead is un-
doubtedly  a major reason that little incorporation
and accumulation occur through the leaf surface.56
  Carlson et al.57 experimentally fumigated soybean
(Glycine max L.) with PbCl 2 aerosol particulate; no
intraplant movement was noted. Simulated rainfall
removed up to 95 percent of the topically applied
lead. Studies by Arvik and Zimdahl59'60  indicated
that only extremely small amounts of lead  could
penetrate  plant  cuticles,  even  after extended ex-
posure.  Increased  penetration  of some cuticles oc-
curred after the removal of waxes,  but penetration
seemed  more related to plant species than to cuticle
thickness. Oats (Avena sativa L.) and lettuce (Lactuca
sativa var.  Black-Seeded  Simpson) are two species,
according to Rabinowitz, whose leaves atmospheric
lead is capable of penetrating.61  The only conclusion
possible from current data is that airborne lead can
be taken up by the foliage of some plants, but only in
extremely small amounts.
  A recent report62 suggests that grasses and small
herbaceous plants in the field, as well as  pea plants
(Piswn  sativum L.) and pine tree seedlings (Pinus
sylvestris L.)  in  the  laboratory,  when  grown in
nutrient solution, release lead and zinc into the air.
It is questionable whether the  lead exuded  from
plant  leaves  adds appreciably  to the  atmospheric
 burden. The complexities of lead  movement from
 soil into plants make it unlikely that plants are capa-
 ble of exuding large amounts into the air.
   Particles containing lead,  in addition to chlorine
 and bromine, have been found embedded in the bark
 of both pine and elm trees growing near  highways.
 The  lead  content  of  the  particles on  the trees
 decreased over a 3-year period, and the particles on
 the bark of elm trees showed less lead than those on
 pine trees.63 No evidence exists to show that lead en-
 tered the trees through  the bark.
   Trees have  been  used as indicators of  increasing
 environmental  lead  concentrations  with  time.64
 Studies in central Illinois have shown a fivefold in-
 crease in lead in tree rings during the last 50 years
 (Figure 8-5). This graphically illustrates the increase
 in environmental lead uptake that  has occurred in
 that time. However, data reported by Holtzman on
 four hardwood trees in a rural suburban area and on
 one tree in a suburban area near Chicago  (tree ages
 were  100 to  120 years)  showed no  consistent  in-
 crease or decrease in lead in the tree rings.65
                              10-year AVERAGE,
                                1963- 1973
                              7.9ppmPb, RURAL
                              73.7 ppmPb, URBAN
                                 10-year AVERAGE,
                                    1910- 1920
                                 1.9ppmPb, RURAL
                                 2.7 ppm Pb, URBAN
Figure 8-5. Tree ring analysis of lead concentrations In urban
and rural trees.'3
8.2.1.2  ROOTS
  The root system is the major pathway of plant ex-
posure to lead, as lead in the soil may be absorbed by
the roots and  moved into the plant.60-66-77 But the
total lead content of the soil is only one of several in-
                                                8-9

-------
teracting factors  determining plant uptake. These
factors are not well understood, but uptake is known
to be influenced by plant species and by the availa-
ble lead pool  in soils.66-7u74 The pool of available
lead is determined by soil pH, soil organic and clay
fractions, and the cation exchange capacity as well as
other soil sorption characteristics.66'70-81 Absorption
of lead by plant roots is inversely related to cation
exchange capacity.74-79-80 The total lead in the soil in
relation to cation exchange capacity determines lead
availability.80 Roots take up minerals that are in the
soil solution;60-82 thus lead movement into roots is in
the form of ions from  the soil solution or from weak
sorption sites.60-66-74
   Baumhardt  and Welch70 have shown that the per-
centage of soluble lead in soil decreases with time as
sorption  occurs.  Soil phosphate60-75-77'78  and lim-
ing,60'75-83-84 as well as cadmium85 in soil, reduce the
uptake of lead by plant roots. Olson and Skoger-
boe86 have  identified the primary lead species in
their soil tests as lead sulfate (Chapter 6).  At pres-
ent, the capability of plants to take up this relatively
insoluble form is not understood.74  Jones  et al.87
have reported that lead uptake is enhanced by a defi-
ciency of sulfate in the soil. In this study, the lead in
rye grass tops  was higher than that in the roots when
the soil was deficient in sulfur.
   Once lead enters the plant from the soil solution,
most of it remains in the roots.60-66-72-77 Distribution
to other portions of the plant does occur, but it is
uneven and  variable among species.71-7277 Plant  age
and season of the year also  affect internal distribu-
tion.66-72 In all cases, the levels are quite low  because
of the small amounts of available lead in  the soil
solution.

 8.2.2  Effects on Vascular  Plants
   Lead is a normal  soil  constituent, but it has not
 been shown to be essential for plant growth.66-69 The
 response of plants to lead is therefore dependent on
 the extent to  which normal metabolic processes are
 disturbed.   Metabolic disturbances manifest them-
 selves as growth abnormalities (the visible symptoms
 of which  may  be  growth  stimulation,  stunting,
 yellowing or  purpling of leaves) or, in the  event of
 acute  toxicity,  senescence  and death.82 Metabolic
 disturbances are most likely to occur in response to
 high  available  lead  levels  and to highly  soluble
 forms of lead entering the plant.66-69
   Antonovics, Bradshaw, and Turner88 state  that
 lead uptake is constant with increasing levels of soil
 lead  until  a certain point is reached at which lead
 uptake becomes unrestricted and rises abruptly. Lit-
tle is known, however, about the mechanism of lead
uptake. Undoubtedly, lead in solution moves into
the plant through the root  hairs along with mineral
nutrients and is translocated to other areas of the
plant. The vascular tissue is the pathway of water in
the root, through the stem, into the petioles, and into
the leaf veins.89 After entering the root hairs, water
containing lead and nutrients must pass through the
root cortex  to reach the central  core of vascular
tissue.  Because the movement of water through the
cortex is from cell to cell with no specific pathway
such as vascular tissue, lead possibly may not pass
easily  through cell membranes. This may  explain
why plant roots show higher lead contents than other
plant organs. Malone et al.90 have shown  that some
of the lead that enters the root is concentrated in dic-
tyosome vesicles and subsequently moves  via the
vesicles to the cell wall, where fusion with  the cell
wall occurs.
  Lead has  been reported to have both a  beneficial
and an  inhibitory  effect  on  plant growth.66-69
Brewer69 cites studies in which lead nitrate resulted
in increased nitrification and increased plant growth
when added to the soil. However,  when lead nitrate
was added  to solution cultures, retardation of root
growth occurred. In neither  case was the  metabolic
action  of lead nitrate observed in the plants. The
chemical identity  of lead in plants is as  yet  not
known.60
  Most studies60-66-69 that describe growth inhibition
and plant toxicity caused  by lead compounds are
based  on visible growth responses resulting from
lead added to soils or to solution cultures and do not
deal with specific metabolic processes.
  The effects of lead compounds on such  plant pro-
cesses  as photosynthesis,60-91 ~93  mitosis,1-60-66 and
water  uptake92 have  been  reported.  Miles  et al.,91
using  isolated  chloroplasts from spinach  leaves,
found  that lead  salts inhibit photosynthetic electron
transport. Wong and Govindjee94 have  shown in
isolated  maize  chloroplasts that  lead salts affect
p*hotosystem I, inhibiting P700 photooxidation and
altering  the kinetics of re-reduction of P700.  In
laboratory studies, lead has been found  to have a
damaging  effect  on cell walls,  nuclei, and
mitochondria. Lead retarded cell proliferation but
permitted an increase in size.1 Spindle disturbances
and chromatid formation in  root tips of Allium cepa
induced by  lead nitrate  have been found to be  in-
distinguishable from those induced by colchicine.'
   Miller and Koeppe95 and Bittell  et al.96 studied
the effects  of lead  on  mitochondrial respiration.
Lead effects are related to the  phosphate status of
                                                 8-10

-------
the respiratory system as well as to the oxidation of
nicotinamide adenine diphosphonucleotide
monohydrogen (NADH). The  lead  levels used in
this study approximated  the  levels  found  near
heavily traveled highways. The form of lead used,
PbCl2, and the isolated mitochondria were not typi-
cal of field conditions, but lead in plants does associ-
ate with mitochondria  and   chloroplast
membranes.60-66'75
   The presence of lead in plants has also been shown
to have indirect effects on plant growth. For exam-
ple, absorption of phosphorus and manganese, two
essential elements for growth, is inhibited when lead
is present in the plant.97 Lead may also contribute to
copper deficiency in plants.98
   The majority of the studies reporting lead toxicity
have been conducted with plants grown in artificial
nutrient culture. As a  result of the studies, the con-
cept has emerged that the effects of lead, whether
stimulatory or inhibitory, depend on a variety of en-
vironmental factors, including associated anions and
cations within the plant  and in the growth  media,
and the physical and chemical characteristics of the
soil itself. Because lead  interacts with so many en-
vironmental factors, specific correlations between
lead effects and  lead concentrations are extremely
difficult to predict.60
   Lead toxicity  has not  been  observed  in plants
growing under field conditions.  This observation
may be explained by the fact that ambient lead con-
centrations in  the environment  have not been high
enough, except  under  unusual  conditions  (near
mines  and smelters) to cause a  toxic effect or a
decrease in crop yield.60
   In summary, the effects of lead on vascular plants
appear at this time to be minimal. The most impor-
tant effects may be those resulting from ingestion of
topical and internal plant lead by grazing animals
(the next trophic level). From the standpoint of eco-
nomic  consequences,  evidence developed  on  the
effects of lead in agroecosystems indicates that topi-
cal lead contamination of plants is more  likely to
have economic consequences than internal lead (see
Section 6.4.3).
8.2.3  Effects on Nonvascular Plants

8.2.3.1 MOSSES  AND LICHENS
  Mosses have been shown to have unique capacity
for sorbing heavy metal ions to their surfaces. Traces
of copper  and lead are sorbed  readily even in the
presence of other metal ions (calcium, magnesium,
potassium, sodium).99 These ions are sorbed through
the leaves  of the moss because m'osses have no root
 system  for uptake  of nutrients from soil or other
 substrates. Mosses also have neither epidermal cells
 nor  a  cuticle  (waxy  layer),  so  the internal
 parenchymal cells are readily exposed to substances
 from the air.99'100 Accumulation of heavy metal ions
 in mosses is generally from precipitation, which is a
 very  dilute solution of metals and water. The ac-
 cumulation occurs because of the chemical complex-
 es formed between these heavy metal ions  in pre-
 cipitation and negatively charged organic growth.l()l
   Lichens, like mosses, have no roots; therefore all
 minerals are absorbed through the cell membranes.
 Mechanisms similar to  those found  in mosses may
 also be responsible for the uptake of metal  ions by
 lichens. But lichen accumulation of lead is not as ex-
 tensive as that in mosses.101

 8.2.3.2  ALGAE
  Trollope and Evans,102 in a study of algal blooms
 in the Lower Swansea Valley, Wales, noted the sen-
 sitivity of algae to the heavy metal content of water.
 A marked difference was observed in the nature of
 algal  blooms found  in  three different  groups of
 waters at 12 different stations (Table 8-7). The algae
 most tolerant to high lead concentrations were: Coc-
 comyxa, Mougeotia, Tribonema, and Zygnema. Less
 tolerant were Microspora, Oscillatoria and Ulothrix,
 and the least tolerant were Cladophora, Oedogonium,
 and Spirogyra. All of these algae were subject to con-
 tamination from  run-off water and  dust  from  the
 zinc smelter. The concentrations of lead in the plants
 varied among genera and within a genus. The uptake
 of individual metals by  algal blooms appears to be
 regulated. Mean  metal  concentrations in  the three
 groups of algae are ordered Fe  >Zn  >Pb >Cu
 >Ni, whereas the mean metal concentrations in the
 aquatic bodies were ordered differently: Adjacent to
 the source, Zn >Pb >Fe >Ni >Cu; near, Zn >Ni
 >Pb  >Fe >Cu; distant (6 to 10km), Fe >Zn >Ni,
 Pb >Cu. Concentrations of metals in the algae were
 directly related to the concentrations in the water,
 with the algae in the most polluted waters having the
 highest  concentrations.  No experiments were con-
 ducted to determine whether the algae found in the
 least polluted waters would grow in more polluted
 ponds.
  Observations  in  the  New  Lead  Belt  of south-
 eastern Missouri103  have shown that relatively high
 concentrations of lead in stream bottom  sediments
 do not have much effect  on algal growth in these re-
 latively hard natural waters. Under these conditions,
the dissolved lead salts  are in  very low concentra-
tions and well below the limits of tolerance of most
                                               8-11

-------
TABLE 8-7. CONCENTRATIONS OF SELECTED HEAVY METALS IN FRESH WATER AND IN FRESHWATER ALGAL BLOOMS1"
Concentrations in fresh waters MC
Area of water
Water ad|acent to
zinc smelting waste
1


2

3

4
Mean
Water near zinc
smelting waste
5
6
7
Mean
Water distant from
zinc smelting waste
8


9
10
11
12
Mean
Cu


0-03


0-02

0-01

0-02
0-02


0-02
0-05
0-06
0-04


0-03


0-02
0-01
0-02
0-02
0-02
Fe


0-24


0-11

0-25

0-28
0-22


0-27
0-56
0-56
0-46


0-39


0-1
0-39
0-39
0-11
0-28
Ni


0-15


0-1

0-12

0-15
0-13


0-12
2-2
2-94
1-75


0-07


0-06
0-12
0-12
0-12
0-1
Pb


0-31


1-24

0-1

0-1
0-44


0-1
0-31
2-91
1-11


0-1


0-1
0-1
0-1
0-1
0-1
} 'ml
Zn


34-1


19-61

11-44

1-96
16-78


1-96
4-9
4-9
3-92


0-21


0-08
0-08
0-16
0-05
0-12
Algal bloom


Mougeotia
Tribonema a
Tribonema b
Tribonema c
Tribonema d
Coccomyxa
Zygnema

Mean


Oscillatoria
Ulothnx
Microspora
Mean


Cladophora a
Spirogyraa
Spirogyrab
Oedogonium
Cladophora b
Spirogyrac
Spirogyrad
Mean
Concentr
Cu


0-38
0-4
0-7
0-67
1-33
0-65
0-46

0-66


0-34
0-48
1-02
0-61


0-06
0-22
0-29
0-11
0-05
0-23
0-05
0-14
aliens in freshwater algal blooms ng mg
Fe


17-61
9-97
33-92
23-37
30-6
49-51
39-85

29-26


2-8
7-78
42-31
17-63


3-94
3-03
7-66
0-7
2-91
0-46
8-93
3-95
NI


0-24
0-16
0-26
0-29
0-24
0-15
0-7

0-29


1-07
0-3
0-11
0-49


0-03
0-13
0-12
0-07
0-1
0-09
0-03
0-08
Pb


6-19
5-45
4-94
3-68
14-19
3-23
2-6

5-75


0-58
2-38
2-16
1-70


0-23
0-4
0-11
0-06
0-09
0-13
0-04
0-15
Zn


44-94
19-93
17-61
21-11
17-44
19-05
45-89

26-57


1-88
3-56
9-26
4-89


0-89
1-59
1-92
0-12
0-97
1-09
0-32
0-98
algae, including the sensitive Cladophora. Extensive
blooms of Cladophora were observed in one stream
where bound lead associated with the filaments ex-
ceeded 5000 ppm. These results indicate that lead
chelated or bound to the cell envelopes apparently
had no major physiological effect on algae under the
existing  natural conditions.
8.2.3.3 BACTERIA
  The response of certain bacteria to lead has been
studied by Tornabene and Edwards.104'105 Micrococ-
cus luteus and Azotobacter sp., when grown in lead-
containing  media  under experimental conditions,
were able to take up substantial quantities  of lead
with no apparent effects on cell viability. Most of the
lead became associated with the cell membrane. Sev-
eral studies106-107 indicate that bacteria in lake sedi-
ments under anaerobic conditions react differently.
Methylation of mercury and arsenic by microorgan-
isms is  a  well-known  phenomenon,108-109 but the
methylation of lead is not. The first evidence for the
methylation of  lead was demonstrated experimen-
tally by Wong et al.110 Microorganisms in lake sedi-
ments were able to  transform certain inorganic and
organic lead compounds into a volatile tetramethyl
 lead (Me4Pb) when the sediment was enriched with
 nutrient broth and glucose to stimulate growth and
 growth occurred under anaerobic conditions. The
 Me4Pb lead production was greatly increased when
 inorganic lead nitrate or organic trimethyl lead ace-
 tate (Me3PbOAc) was added at 5  mg per liter  of
 sample. The biological methylation from  trimethyl
 lead (Me3Pb) to  Me4Pb appeared  to proceed quite
 readily. This conversion  was demonstrated using
 pure species of bacterial isolates from lake sediments
 without the sediments being present. They were able
 to  show that  Pseudomonas,  Alcaligenes,
 Acinetobacter, Flavobacterium,  and Aeromonas sp.
 growing  in a chemically  defined  medium  could
 transform lead nitrate, lead chloride, and  trimethyl
 lead acetate (Me^PbAc) into volatile tetramethyl
 lead (Me4Pb). None of the bacteria were able to con-
 vert  insoluble   lead to  Me4Pb. Schmidt  and
 Huber,107 however, have observed that Pb2+ can  be
 biologically alkylated and transformed to  Me4Pb
 (see Section 6.4.2.2).
  Generally, most naturally occurring bacteria can
tolerate lead without toxicity.104-110 However, there
is wide variation in effects. For example, lead has
been shown to stimulate growth of a bacterium iden-
                                               8-12

-------
 tified as Micrococcus flava Strevisan,"' producing an
 insoluble lead metabolite;  but lead has also  been
 shown to be widely inhibitory to aerobic activated
 sludge  bacteria,112 aerobic  river water  bacteria,113
 and marine sulfate-reducing  bacteria.114 These  re-
 ports seem to indicate that  lead  has a relatively
 casual  relationship with bacterial  cells, with  no
 specific inhibitory  role; but this should be viewed
 with caution.
   Previously, the presence of lead in estuarine  sedi-
 ments was mentioned.  The methylation of lead in
 this environment and its effects on the biota existing
 there have not been studied.
   Effects of the  addition of  1000 ppm of copper,
 nickel, lead, and zinc on carbon dioxide release dur-
 ing aerobic incubation of soil alone  and after treat-
 ment with straw were studied."5 Carbon dioxide re-
 lease during incubation from soils  without added
 straw was decreased by  all  metallic elements.  Car-
 bon djoxide  release  from  soil  plus  straw  was
 decreased by lead. The toxic effects of the high  con-
 centration   of  elements  on  the activity  of  the
 microorganisms attacking  organic  matter were
 believed to be caused by the ability  of the elements
 to compete with essential elements (manganese, iron,
 and zinc) for the active  sites (SH, NH2, =  NH) of
 enzymes.  Nickel  and lead  were slightly more in-
 hibitory than copper and zinc.1 IS
   Cole116 found that addition of lead to soil resulted
 in 75- and 50-percent decreases in net synthesis of
 amylase  and  a-glucosidase,  respectively.  The
 decrease in amylase synthesis was accompanied  by a
 decrease in the number  of lead-sensitive, amylase -
 producing  bacteria, whereas  recovery of synthesis
 (usually in 24 to 48 hr) was associated with an in-
 crease in the number of amylase-producing bacteria,
 presumably lead-resistant forms. The results indi-
 cated that lead is a potent but somewhat selective in-
 hibitor of enzyme synthesis in soil and that highly in-
 soluble  lead compounds such as PbS may be potent
 modifiers of soil biological activity.

 8.3 EFFECTS  ON  RELATIONSHIPS  BE-
 TWEEN  ARTHROPODS  AND  LITTER
 DECOMPOSITION
  A study117 of the impact of a  lead smelting com-
 plex in southeastern  Missouri  focused  on forest-
 floor litter arthropod fauna. Litter-arthropod food
 chains and  the  possible transfer  of lead through
 plant-herbivore-carnivore food chains were  studied
 as  a  means  of  detecting  perturbations  in  this
ecosystem.  Both  point  and  fugitive sources con-
tributed to  heavy metal levels in the study area.
 Lead, cadmium, zinc, and copper were the primary
 elements  studied.  Litter  mass,  heavy  metal and
 macronutrient  content (Ca, P, K, and Mg), cation
 exchange capacity, and pH were studied to charac-
 terize the arthropod  food  base. Arthropods were
 removed from  litter by Von Tullgren funnel extrac-
 tion.  The arthropods were taxonomically classified
 according  to   their  feeding  habits  or  levels:
 detritivore, fungivore, littergrazer,  omnivore, and
 predator. Level refers to the sequential location of a
 particular organism in the food chain or web.  Their
 population  density at each trophic  level, biomass,
 and heavy  metal  and macronutrient content was
 determined.
  Changes in litter decomposition and nutrient cy-
 cling  were reflected in the population dynamics of
 litter  arthropods and macronutrient pools. Reduced
 arthropod density, biomass, and richness (an esti-
 mate  of maximum diversity) were  observed. The
 macronutrients Ca, K, and Mg in the 01 and 02 litter
 layer  at a site 0.4 km from the smelter were signifi-
 cantly reduced. Two  litter layers or  horizons  are
 recognized by the  Soil Science Society of America.
 The 01, or surface layer, is that in which dead plant
 material still retains its original conformation. The
 02  layer is that layer in which the material  is frag-
 mented and no longer recognizable as to species or
 origin.
  Mean heavy-metal concentrations were greater in
 the undecomposed  02 litter layer collected  at 0.45
 and 0.8 km  from the smelter. The Pb concentration
 was 103,000 ppm; Zn was 4910 ppm;  Cu was 6080
 ppm;  and Cd was 179  ppm. At these sites, heavy-
 metal concentrations correlated with 02  litter layer
 accumulations.  A change  from the normal was also
 noted in the cation exchange capacity and pH of the
soil.
  In summary, the results of  this study117 indicate
 that the  dynamics of forest-nutrient  cycling pro-
cesses  are  seriously  disturbed  near  these  lead
smeltering complexes.

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9.  QUANTITATIVE  EVALUATION OF  LEAD AND  BIOCHEMICAL
   INDICES  OF  LEAD  EXPOSURE  IN  PHYSIOLOGICAL MEDIA
  In this  chapter, the state of the art regarding
measurement of lead  and biochemical  markers of
lead exposure is summarized, and the accuracy and
precision  of various methods of intra- and  inter-
laboratory comparison are examined. The relative
diagnostic merits of one type of measurement with
respect to another — blood lead versus urinary lead,
for example — are discussed  elsewhere in the  docu-
ment.

9.1 GENERAL  SAMPLING  PROCEDURES
FOR LEAD IN BIOLOGICAL MEDIA
  The occurrence of lead in physiological media of
interest  in this discussion is at the trace level, even
under conditions of marked exposure. Therefore, a
number of sample collection and handling precau-
tions are called for, both to  minimize loss of lead
from samples and to avoid  the contamination  of
samples by this ubiquitously  distributed element.
  Sample-gathering problems are of special concern
in blood lead screening  programs  in  which  great
numbers of samples must be  gathered, transported,
and processed in the shortest  possible time.1 Sample
collection details for blood lead and other biologi-
cal indicators of exposure have been reviewed  in the
clinical literature.2
  In blood studies it is often  desirable to use  capil-
lary blood by  finger  prick  instead  of venous
puncture,  especially  when young children are in-
volved. A number of studies have shown that capill-
ary and venous blood are essentially identical  in
lead content:  Mitchell et al.3  obtained a correlation
factor of 0.92.  However, it should be emphasized
that such results can be achieved only when extreme
care is used  in cleaning  the skin, and  when con-
tamination of capillary tubes and syringe is avoided.
  A number of workers have used filter paper discs
for blood sample collection as an alternative to han-
dling discrete blood volumes.  The paper for this
purpose must be selected for uniformity of manufac-
ture, low lead content, and uniform blood dispersal.
  In the methods of Cernik  and Sayers involving
lead workers,4-5 for example, whole blood obtained
by finger  prick  is spotted  onto Whatman No. 4
qualitative paper. Either 9.0-mm or 4.0-mm discs
are then punched out and analyzed by the Delves
cup microtechnique  or  the carbon-cup  flameless
atomic absorption procedure. These methods corre-
late well with blood obtained by venous puncture.
  Joselow and  Bogden6  have  employed  a micro-
method for routine mass screening of children using
a  paper  disc-in-Delves-cup technique.  Capillary
blood  is allowed to  drop onto an 8.2-cm  disc of
Schleicher and Schwell No.  903 filter paper so as to
form  a spot  somewhat larger than  1/4 in.  in
diameter, and discs of 1/4-in. diameter are punched
out directly  into  previously  conditioned  Delves
cups. A correlation coefficient  of 0.9 was obtained
when results of this method were compared with a
macroprocedure using venous  blood  and the pro-
cedure of Hessel.7
  Cook et al..**  in their  investigation  of capillary
blood  collected on  paper  and of blood volume
gathered by venous puncture, obtained a correlation
approaching 0.8.
  Puncture-site preparation is also  important  in
sampling.  Marcus et  al.1 report that a preliminary
cleaning with ethanolic citric acid solution followed
by a 70-percent ethanol rinse is  satisfactory, whereas
Cooke  et al.8 chose to employ a vigorous scrubbing
with low-lead  soap solution and  deionized water
rinsing.
  A second precaution with  finger-prick sampling is
the way in which the blood flow is expedited for
sampling.  Gravity flow or direct  uptake  (filter
paper)  is preferable to squeezing the finger tip, as
hard squeezing might dilute the blood drop with
tissue fluid.
  Further  precautions  include  the  use  of
polypropylene syringes9 with  needles of  stainless
steel and polypropylene hubs for puncture sampling.
  Urine-sample collection requires acid-washed
plastic  containers (and caps) and should include a
low-lead bacteriocide if samples are stored.
                                               9-1

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  Hard-  and soft-tissue gathering from  laboratory
animals or human sources entail surface debride-
ment of ambient lead encountered in the process of
sampling. Hair cleaning before analysis may be car-
ried out via the method of Hammer et al.;'° bone
and teeth may be given a quick rinse in EDTA solu-
tion.  With  soft tissue, the  outer  layer  may  be
removed  or a segment of underlying matter excised.
For organs of heterogeneous morphology such as
kidney, it may be more desirable to subject the sam-
ple to a  quick  rinse  in an ionic chelant, such as
EDTA, that  does  not penetrate beyond the  outer
membrane.
  Regardless of specific methodology employed, all
reagents  used in lead   determinations in biological
media should be certified for  low-lead content; and
samples should be stored in a manner that minimizes
lead contamination from air  or surfaces. Standard
lead solutions should be prepared frequently, either
from  stock  solutions  from  analytically  certified
sources or from the pure metal. Solution preparation
in glass  should be minimized, particularly  when
analysis is at the sub-part-per-million  level.
9.2 BLOOD LEAD
  The first generally accepted practice for measur-
ing lead  in  blood and other biological media in-
volved a  spectrophotometric technique based on the
binding of lead with a chromogenic agent to yield  a
chromophoric  product.  In  this  connection, the
classic ligating agent  has been  dithizone-1, 5-
diphenylthiocarbazone. The lead dithizonate is
measured spectrophotometrically at 510 nm.
  Two reliable variations of the spectrophotometric
technique when dealing with lead content of 1 to 10
ppm are  the USPHS and APHA procedures.
  The USPHS assay9 is a double-extraction, mixed-
color procedure having bismuth as the  chief inter-
ferent. Blood (and  urine) samples are  wet-ashed
using concentrated nitric  acid  certified as to low-
lead  content. After digest treatment  with hydrox-
ylamine  and sodium citrate, the pH is adjusted to  9
to 10, and cyanide ion is added. Formation and ex-
traction  of lead dithizonate  is carried out using  a
chloroform solution of dithizone. Lead is then re-ex-
tracted into dilute nitric acid (1:99 water), and the
aqueous  layer is treated with ammonia-cyanide solu-
tion  and  re-extracted with  dithizone-containing
chloroform.  The  organic  extracts are read  in  a
spectrophotometer at 510 nm. Although bismuth in-
terferes,  this element  is encountered infrequently in
biological media.
   The APHA   procedure"  varies from  that  de-
scribed  above  mainly  in  permitting  removal of
bismuth at pH 3.4 as the dithizonate.
  At  present, the colorimetric  method  has been
largely supplanted by two other techniques: atomic
absorption (AA)  spectrometry in all its variations
and anodic stripping voltammetry (ASV).
  Of these two analytical approaches, the more tech-
nically popular, by far, is AA spectrometry, which is
used for both macro- and micro-scale analyses. The
theoretical basis for AA and its instrumental design
are beyond  the scope  of this presentation; basic
reviews are  provided by Christian  and Feldman'2
and by L'Vov,'3 however.
  Macro-scale AA analysis involves direct aspira-
tion of suitably treated lead-containing samples into
a flame for lead-atom generation  and excitation.
Micro-AA, which is being used more widely as ac-
cessories and instrument refinements become com-
mercially available, is of two types: flame and flame-
less,  with  the latter employing  thermoelectric
systems in lieu of a flame.
  Of  the flame microtechniques for A A analysis of
blood samples,  the most  widely  used  is  Delves
cup procedure14 in which small volumes of blood,
10 to 100 ft\, are placed in lead-free nickel cruci-
bles. After the organic matrix is destroyed, the cups
are inserted into a flame. The overall configuration
of the system permits the optical path to be max-
imally occupied by the lead atom population origi-
nally present in  the  sample.  Destruction  of the
organic matrix in blood may be either partial, using
hydrogen peroxide, or total, with pre-ignition of the
organic matter caused by placing the cups near the
flame.15
  Increasing use is being made of flameless AA, par-
ticularly  the  heated  graphite furnace  accessory,
whereby volumes of blood are reduced to — 1 fi\,
and also whereby in-situ destruction of organic mat-
ter may be achieved.
  The electrochemical technique known as ASV16 is
also*  coming  into  common  use in a  number of
laboratories, particularly for blood and urine lead
analysis. As developed by Matson and Roe,16 the
technique involves concentrating  an  ion such as
divalent lead on  a negative electrode during a pre-
determined plating time (5 to 60 min) followed by
polarity reversal and  increase for short periods to
yield a discrete current peak that is proportional to
ion concentration.
   Also in  current  use are  X-ray  fluorescence
spectrometry and neutron-activation analysis, two
sophisticated  instrumental  methods  for trace
analysis. The considerable expense of the equipment
                                                9-2

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and  the  amount of  operator  expertise  involved
rather  limit their  use to  that  of  regional service
facilities  or central laboratories. The two methods
have a distinct advantage, however, in that they per-
mit multiple-element analysis, a feature that will be
of increasing importance as more is unveiled about
the complex interactions of lead with other metals in
man and other organisms.

9.3 URINE LEAD
  Precautions  to be taken for urine sample collec-
tion were noted earlier. Because of the considerable
amount of ionic  matter in urine, it is usually necess-
ary to manipulate  urine samples  in various ways
before analysis.
  All  of the  methods employed  for blood  lead
analysis as described  above may also be applied to
assessment  of urine  lead  levels.  Care,  however,
should be exercised in the analysis of urine samples
from  patients  undergoing chelation therapy,  with
special attention to how a specific procedure will ac-
commodate or be interfered with by lead excreted as
a complex, e.g., lead-EDTA. Prior ashing of urine
samples will minimize complications in this regard,
but partial degradation or no prior treatment might
necessitate co-analysis of lead in the complex form
for standards.

9.4 SOFT-TISSUE LEAD
   Because of the nature of this medium, it is usually
necessary either to ash or to solubilize tissue  sam-
ples. Wet-ashing is rapid and  avoids lead loss via
volatilization, but it requires use of corrosive acids
and procedural care to  avoid contamination  of
reagents and  other problems.  Dry ashing, on the
other  hand, is simple and  uses no contaminating
reagents. The drawbacks  are mainly those of lead
volatilization and retention of the element in refrac-
tory residues. Newer techniques of  ashing include
(1) low-temperature  ashing,  in which  dry samples
are mineralized in an evacuated  chamber that  is
bathed in an energy-rich plasma via r-f discharge in
an  oxygen  stream, and (2)  use of the combustion
bomb, in which samples are heated in acid an at ele-
vated temperature in  a sealed inert vessel.
  A newer method of tissue handling, solubilization,
entails the treatment of samples with quaternary am -
monium  compounds and analysis of aliquots, chiefly
by AAspectrometry.17
  The bulk of the current literature centers on the
use of atomic absorption spectrometry as the method
of choice for assessing lead levels in soft tissue.
9.5 HAIR LEAD
  An attractive feature of the clinical use of hair-
lead  levels  is  its  noninvasive  nature  and  the
feasibility of assembling a rough time frame for lead
exposure by isolating discrete segments of the total
hair length.
  A serious drawback in hair analysis, however, is
the level of contamination by ambient air lead, lead
in hair preparations, etc., as discussed by Hammer et
al.'°Hair measurements without prior treatment of
the sample include both exogenous and endogenous
sources. Examples of the former are dyes, shampoos,
sweat, and  dust.  Pre-analysis  hair washing  with
detergent and EDTA removes most of the externally
found lead; but  there is still no  definitive way to
determine whether any cleaning technique removes
the contamination portion of lead and leaves the in-
ternal lead content undisturbed.
  Hair is usually  wet-ashed before analysis, and the
digest is diluted and  analyzed by AA spectrometry.
Because relatively high levels of lead are encoun-
tered in hair, small sample sizes can be used when a
sensitive procedure  such as AA spectrometry is
employed.
9.6 LEAD IN TEETH AND BONE
  The biochemical significance of lead levels in
teeth  and bone is  discussed elsewhere. From  an
analytical standpoint, bone samples are usually ob-
tained from experimental animal studies. Bone sam-
ples must first be debrided of muscle and connective
tissue and chemically rid of surface lead contamina-
tion by rinsing with EDTA or other chelant solution.

   Bone  and  teeth  are  usually  wet-  or dry-ashed
before analysis, and the relative merits of these
mineralizing  procedures are as noted above with soft
tissue assays.  Because of the high mineral content of
bone  and teeth,  care  must  be  taken to  avoid
spectrochemical interference by calcium, phosphate,
etc. The relatively high levels of lead in these two
hard tissues, however, permit dilution of the samples
for testing. Because the effect of the high  mineral
content on analytical signals is probably sufficient to
preclude the use of simple aqueous lead standards, it
is advisable  to employ workup solutions  of bone
samples that  have first been analyzed for lead con-
tent and to which known amounts of lead from a
stock solution are then added. Matrix standards pre-
pared in this fashion are assumed to reflect the  in-
fluence of mineral content on all of the samples.
                                                9-3

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9.7 COMPARATIVE STUDIES OF METHODS
FOR MEASUREMENT OF LEAD IN BIOLOGI-
CAL MEDIA
  In an interlaboratory study of the USPHS  col-
orimetric  method  for  lead in blood and  urine,
Keenan et al.18 reported the results from 10 partici-
pating laboratories. For blood, a mean lead value of
26 ± 0.82 figld\ was obtained; spiked samples gave
virtually  identical  correspondence  among  the
groups. Urine  samples  with lead added gave  values
from the reporting  groups with a mean of 679 ± 5.5
  Microscale AA techniques for whole-blood lead
have been found to show good correspondence with
results  obtained using conventional  flame pro-
cedures.19-20
  Matson21 has reported good correlations for lead
levels in blood and urine when comparing ASV with
a colorimetric  and  an AA procedure.  Similarly,
Horiuchi et al.22 saw little difference in lead levels
for blood and urine when contrasting ASV. A A, and
polarography.
  Interlaboratory studies  of various  methods for
lead analysis of biological media have yielded some-
what disappointing results.23'25 In a recent study in-
volving 66 laboratories throughout Europe, blood
and urine determination variance was observed to be
unacceptably high.25
  Presently, the  Center for Disease Control (CDC)
is carrying on a monthly proficiency testing program
for  blood  lead involving approximately  200
laboratories.  Results are  made  available through
monthly reports for  analysis of bovine blood sam-
ples.26 The criterion  used by CDC for assessing un-
satisfactory performance is: greater than 1 5 percent
relative deviation at levels of 40 /ug/dl or above and
greater than 6 /ug/dl  at lower levels.
  In a recent CDC report (Survey 1 977I)27 covering
 130  laboratories for testing  and 26 reference
 laboratories using three bovine blood samples (cows
 fed lead acetate), 72 percent of the tested laborato-
 ries were within the acceptable  range for a sample
 having a mean of 16.6 /iig/dl. The acceptable percen-
 tage  was  lower,  interestingly,  at higher  sample
 means of 48.2  and 54.6 /^.g/dl (64  and 67 percent,
 respectively). When  results were  tabulated as a func-
 tion of method, the Delves cup A A  spectrometric
 and ASV methods furnished the smallest coefficients
 of variation.
   A number of  other proficiency programs are pre-
 sently operating in the United States, and the results
 of these have been included, along with the Euro-
 pean program,  in a recently published monograph
by Pierce et al.2 These same authors describe  the
state of the art critically and offer some recommen-
dations for  improving the quality  of blood lead
analyses:
     1.  Every  laboratory should  have established
       quality-control  procedures.
     2.  Control procedures should include replicate
       analyses, recovery of known  additions or
       spikes, participation in interlaboratory tests,
       and analyses of known materials.
     3.  Testing samples that the  analysts  analyze
       blind should be used to minimize bias.
  It  has been suggested28 that the acceptable agree-
ments  in  blood lead levels found  when a single
laboratory employs different techniques  compared
with the wide variance found when  different
laboratories employ  different methods on portions
of common  blood  samples relate  primarily to pre-
paration and state  of the blood samples before and
during distribution and  subsequent analysis. The
results of Grimes  and  coworkers29 bear this out
because  a large  number of carefully  controlled
blood samples analyzed by their laboratories, using
the paper disc technique, provided results that com-
pared  well with those of other laboratories using
other instrumentation with the disc technique.

9.8  MEASUREMENT  OF  URINARY
 8-AMINOLEVULINIC ACID (ALA-U)
  Some comments regarding sample collection for
ALA-U  are necessary. ALA is stable in acidified
urine (pH 1 to 5), so that acetic or hydrochloric acid
addition is satisfactory at the time of sample collec-
tion. If samples are stored  in the dark at 4°C, the
ALA content remains relatively constant for several
months.30
   ALA-U measurement usually entails  the classic
 method  of  Mauzerall and  Granick.31  In  this ap-
 proach,  ALA-U is condensed with  a /3-dicarbonyl
 compound such as acetylacetone or ethyl acetoace-
 tate to yield a substituted pyrrole derivative; this in-
 termediate  is  then  caused  to react  with  Ehrlich
 reagent (p-dimethylaminobenzaldehyde) to yield an
 intense ionic  chromophore. This procedure is not
 specific  for ALA-U, however, since  aminoacetone
 interferes. Though the significance of such inter-
 ference  is marginal  when  ALA-U  levels  are
 markedly elevated, it becomes very important when
 only slight elevations of ALA-U are  being measured.
   First,  urine samples are chromatographed on ion-
 exchange resin columns  (Dowex-2), the  ALA-U
 being  co-eluted with  urea  using water as eluent.
 Eluate transfer to a Dowex-50 column is followed
                                                 9-4

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by sequential elution with water to remove the urea
and then with acetate solution to permit removal of
the ALA-U. Treatment with acetylacetone and heat-
ing to effect  complete  condensation is followed by
treatment of  sample aliquots with modified Ehrlich
reagent  (p-dimethylaminobenzaldehyde in per-
chloric/acetic acid). The resulting chromophoric salt
is allowed to achieve  maximum intensity (ca.  15
min)  after which the sample is read in a spectro-
photometer at  553 nm. The detection  limit is  3
yLtmoles/liter  urine, and chromophore stability  is
limited to about 15 min.
  A number of modifications to the above basic ap-
proach have been reported. Several reports attempt
to take  into  account  the interference posed  by
aminoacetone.  The quantitative corrections to be
used  are described  by  the authors of  these re-
ports.32'33
  The initial  isolation of porphobilinogen is omitted
(in cases where porphyria is not  suspected)  in the
modification  of Williams and Few,34 in which a cor-
relation  of 0.99 was observed  with the  reference
technique using samples from 39 lead workers. Doss
and Schmidt3-'' report that use of commercially avail-
able dual ion-exchange columns offers results that
compare favorably with the Mauzerall and Granick
method.31
  The assay has been automated with good corres-
pondence of results  to  the manual method  in the
laboratories of Grisler et al.36 and Lauweryset al.37
  In another  variation of the ALA-U procedure, the
method of Schlenker et al.38 removes aminoacetone
which interferes with the assay. In the procedure of
MacGee et al.,39 urinary and blood ALA  is  deter-
mined by gas-liquid  chromatography,  a  highly
specific technique.
9.9  MEASUREMENT  OF  8-AMINO-
LEVULINIC ACID DEHYDRATASE (ALA-D)
  Located  in  erythrocytes.  8-aminolevulinic acid
dehydratase (ALA-D) catalyzes  the conversion of
ALA to porphobilinogen in the  heme biosynthetic
pathway. Its inhibition by heavy metals such as lead
indicates that  it is  a  sulfhydryl  enzyme  and also
forms the biochemical basis for assessing its activity
in lead-exposed organisms.

  Blood  collection  requires the  use  of  low-lead
tubes containing  anticoagulant, whereas  for
micromeasurement, blood  is  collected in  a
heparinized microhematocrit tube.40 Obviously, use
of strong chelants, such as EDTA, as anticoagulants
 is not advisable because competition for lead may
 reactivate the lead-inhibited enzyme.
   Minimal time lapse should occur between collec-
 tion and enzyme assay—no more than 24 hr if sam-
 ples of heparinized blood are held at 4°C.
   The chemical basis for measuring enzyme activity
 involves spectral  measurement of the  amount  of
 porphobilinogen generated from ALA, the porpho-
 bilinogen being condensed  with p-dimethyl-
 aminobenzaldehyde  to yield a chromophore that is
 measured at  553 nm. Mercury (II) is employed  to
 minimize the interference  effect of sulfhydryl en-
 tities present in the medium.
   The micromethod of Granick and co-workers40
 requires only 5 fj.\ of whole blood and appears to be
 of value in a screening program. Enzyme incubation
 is done at 37°C for about 60 min; ALA of the highest
 possible purity is necessary as a substrate.
   Termination of the reaction (enzyme  activity)  is
 done via trichloroacetic acid.
   The activity of the enzyme may  be calculated  in
 two ways:40'41
 Activity =  AODS53(sample-tissue control)

           X  138V(L0"nMo1 PBG/ml RBC/hr
                  HC1

        =  AOD^tfto'-t^x^
           x 131.48 nMol PBG/ml RBC/min
   In  the European standardized method for  ALA
 determination42 aimed specificially at enzyme levels
 in blood corresponding to low levels of exposure  to
 environmental lead, incubation  of the  enzyme  in
 three aliquots of blood (0.2 ml cooled to 4°C) is car-
 ried out  in the presence of excess 8-aminolevulinic
 acid. An aliquot  blank  is also carried through the
 procedure. Hemolysis of the cells and  incubation
 with substrate is followed by quenching with mer-
 curic  chloride-trichloroacetic  acid solution.
 Centrifugation  and treatment  with modified
 Ehrlich's reagent is followed at 5 min by absorbance
 measurement. Blood samples are preferably run
 within 3 hr and in no case after 24 hr when held  at
 4°C.

  In a study by Granick et al.43 the activity of ALA-
 D before  and after  treatment with dithiothreotol
 (DTT) is determined. The DTT (added in vitro, 20
 mM) provides  -SH groups  and  reactivates the
 enzyme completely at all concentrations of blood
 lead. Because DTT-reactivated ALA-D yields total
enzyme activity, variation in  levels of the unacti-
vated enzyme may be normalized by determination
of the rates of both activities. Hence a person having
                                               9-5

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a high ALA-D for genetic reasons at a given blood
level of lead will  have relatively high activity for
both activated and nonactivated enzyme, and the ac-
tivity ratio will depend less on genetic factors than
on  lead  inhibition.  Consequently,  correlation is
markedly  improved.  This study also shows that in-
hibition by lead  is of the noncompetitive type.
9.10  MEASUREMENT OF FREE ERYTHRO-
CYTE PROTOPORPHYRIN (FEP)
  Another reaction that lead inhibits in the human
heme biosynthetic pathway is heme formation. As a
result of blocking this reaction, porphyrins, particu-
larly protoporphyrin  IX  (actually zinc-pro-
toporphyrin),  accumulate   in  the  erythrocytes.
Measurement of protoporphyrin IX specifically, or
all  erythrocyte  prophyrins  together,  is generally
referred to as the free erythrocyte  protoporphyrin
(FEP) test.
  The spectrochemical properties of FEP that form
the basis for its measurement include its lability to
light and strong acids, its metal coordinating ability,
its possession of an absorption spectrum in the Soret
band region, and its marked intensity of fluores-
cence.  Spectral methods used,  however, must take
into account the fact that copro- and uroporphyrin
provide considerable interference in FEP measure-
ment. Although both absorption spectrophotometric
and fluorometric methods may be employed for FEP
assessment,44'46 fluorometric  techniques carried out
on  a microscale are more frequently used because of
the  relatively  cumbersome  nature  of absorption
spectrometry in terms of time and materials. These
microfluorometric techniques, in particular, provide
a rapid,  relatively  accurate means  of  screening
pediatric  populations.
   In the microtechnique of Granick et al.47, several
microliters of whole blood are  placed in 1-ml test
tubes that also serve  as fluorometric cuvettes. Addi-
tion of ethyl acetate/glacial acetic acid (2:1) is then
rapidly followed by treatment  with 0.5N HC1 and
vigorous shaking. The acidic phase (bottom layer)
contains the bulk of the porphyrins. The cuvettes are
scanned over the range 560 to 680 nm, using excita-
tion at 400 nm. The ratio of the two-band maxima at
605 and 655 nm is measured for each sample with  a
ratio of 2:1 indicating only FEP. Any lesser value in-
dicates copro- and/or uroporphyrins. In  the  latter
case, an extraction with 0.05N HC1 on analysis of a
second  sample removes copro- and uroporphyrin.
   The technique of Piomelli,48 using 20 fi\ of blood
added to a 5-percent Celite suspension in saline, uses
essentially the same  initial extraction procedures as
those noted above, but it is varied to employ 1.5N
HC1  to  generate  the  fluorescing  acid  layer.
Measurement is at 610 nm and excitation at 405 nm
with coproporphyrin employed as the standard.
  Observing that FEP is actually the zinc  complex
(ZPP),  Lamola  and  coworkers49  have  devised  a
rather rapid and sensitive fluorometric procedure in
which  20 fji\ of  whole  blood  is worked  up in  a
detergent-phosphate buffer solution  (dimethyl-
dodecylamine oxide) and fluorescence measured at
594 nm with excitation at 424 nm.
  In the procedure of Chisolm  and Brown,50 which
has been evaluated as a selected method by Schwartz
and Piomelli, 20-^1 blood volumes are treated with
ethyl acetate/acetic acid solution (3:1) and agitated
for  30 sec. After centrifugation, the layers are ex-
tracted  with 3N HC1, and  the acid  layer is diluted
with more 3N HC1. The acid extracts are analyzed
spectrofluorometrically   with coproporphyrin em-
ployed as the quantitating standard.
  A portable hematofluorometer that utilizes front-
face optics, internal  standards, and  built-in com-
putational  capabilities permits the  assessment  of
erythrocyte zinc protoporphyrin  (ZPP). As
developed by Bell  laboratories51 and subsequently
made available commercially,52 the apparatus per-
mits the analysis  of a drop of blood applied to a
cover slip directly  from  finger pricking. The ZPP
level (/jig ZPP/dl  blood) is automatically calculated
and displayed on  a digital readout.
  A number of micromethods for FEP analysis have
been critically evaluated  by Hanna et al. ": Double
extraction  with   ethyl acetate/acetic  acid-HCl,48
single extraction with ethanol, single extraction with
acetone,54 and direct solubilization with detergent
buffer.49 Of these, the ethyl acetate and ethanol pro-
cedures were satisfactory; the complete extraction of
FEP makes the former the technique of choice when
an absolute value rather than technical simplicity is
of primary concern.

9..11  REFERENCES FOR CHAPTER 9

  1   Marcus, M..M  Hollander, R E. Lucas, and N. C. Pfeiffer.
     Micro-scale  blood  lead determinations  in  screening
     Evaluation of factors  affecting results. Clin. Chem.
     27(4)533-536, 1975
  2  Pierce, J O.,S  R. Koirtyohann, T E Clevenger, and F. E
     Lichte. The  Determination of Lead  in Blood. Interna-
     tional Lead Zinc Research Organization, Inc., New York.
     1976
  3  Mitchell, D  G , K M. Aldous, and  F. J. Ryan. Mass
     screening for lead poisoning. Capillary blood sampling
     and automated Delves-cup atomic-absorption analysis
     NY State J  Med  74:1599-1603, Aug 1974
                                                 9-6

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 4.  Cernik, A. A and M. P H Sayers. Determination of lead
     in capillary blood using a paper punched disc atomic ab-
     sorption technique. Applications to the supervision of lead
     workers Brit. J. Ind. Med. 28 392-398, 1971.
 5   Cernik, A. A  Determination of blood  lead using a 4.0 mm
     paper punched  disc carbon cup sampling technique Brit.
     J. Ind. Med. J/:239-244, 1974.
 6.  Joselow, M   M. and J.  D  Bogden. A simplified micro
     method for collection and determination of lead  in blood
     using a paper disk-m-Delves cup technique. At  Absorp.
     Newsletter // 99-101,  1972
 1.  Hessel, D W. A simple and rapid quantitative determina-
     tion of lead in blood At. Absorp. Newsletter. 755, 1968.
 8.  Cooke, R. E , K. L. Glynn, W  W Ullmann, N Lurie, and
     M. Lepow. Comparative  study of a micro-scale test for
     lead in  blood, for use in mass screening programs. Clin.
     Chem. 20(5)582-585, 1974.
 9   Lead Airborne Lead in Perspective. National Academy of
     Sciences, Washington, D.C  1972.
 10  Hammer, D. I. J F. Finklea. R. H Hendncks, C. M. Shy.
     and R.  J  M   Horton   Trace-metal  concentrations  in
     human  hair  In: Helena Valley,  Montana, Area Environ-
     mental  Pollution Study  US  Environmental Protection
     Agency, Research  Triangle Park, N.C  Pub No. AP-91
     1972 p 125-134.
 11.  Methods  for Determining Lead in Air and Biological
     Materials.  American  Public  Health   Association, New
     York. 1955. 69 p
 12.  Christian, G  D and F  J. Feldman  Atomic Absorption
     Spectroscopy Applications in Agriculture, Biology and
     Medicine. Wiley-Interscience, New  York.  1970.
 13.  L'Vov, B.  V   Atomic  Absorption   Spectrochemical
     Analysis. J. H  Dixon (tr.). American  Elsevier Publishing
     Co., New York. 1971.
 14   Delves, H  T  A micro-sampling  method for the  rapid
     determination  of lead  in blood  by  atomic-absorption
     spectrophotometry.  Analyst (London) 95.431-438, May
     1970.
 15.  Ediger, R. D  and R  L. Coleman A modified Delves cup
     atomic absorption procedure for the determination of lead
     in blood. At  Abs. Newsletter. //(2)-33-36, 1972
 16   Matson, W.  R  and D. K  Roe.  Trace metal analyses of
     natural  media by anodic stripping voltammetry. Anal. In-
     strum. 4 19-22,  1966
 17.  Murthy, L.,E. E. Menden, P. M Eller,andH G. Petering.
     Atomic absorption  determination of zinc, copper, cad-
     mium  and  lead  in  tissues  solubilized by  aqueous
     tetramethylammonium  hydroxide.   Anal.  Biochem
     53(2)-365-372,  1973.
 18.  Keenan,R G., D. H. Byers, B  E Saltzman, and F L. Hy-
     slop. The  "USPHS" method for determining  lead in air
     and in  biological  materials.  J.  Am.  Ind. Hyg  Assoc
     24(5)-481-491,  1963
 19.  Kubasik.N P , M. T. VoJosm, and M.  H. Murray. Carbon
     rod atomizer applied to measurement of lead in whole
     blood  by atomic  absorption  spectrophotometry.  Clin.
     Chem. ;«(5).4IO-412, 1972.
20.  Hicks, J. M., A  N.  Gutierrez, and B. E  Worthy. Evalua-
     tion of the Delves micro system  for blood lead  analysis
     Clin. Chem. /9(3):322-325, 1973.
21.  Matson, W.  R  Rapid  sub-nanogram  simultaneous
     analyses. Trace  Substances  in Environ   Health.
     IV.396-406, 1970.
22.  Honuchi, K., S  Horiguchi, F. Takoda, and K Teramoto.
    A polarographic method for the determination of a small
    amount of  lead  in biological materials. Osaka Med. J
    14 113-118, 1968.
23  Keppler, J. F , M.  E Maxfield, W  D. Moss, G  Tietjen,
    and  A  L. Linch   Interlaboratory  evaluation  of  the
    reliability of blood lead analyses  J  Am. Ind. Hyg. Assoc.
    3/-412-429, 1970.
24.  Donovan,  D  T ,  V. M.  Vought,  and A.  B.  Rakow.
    Laboratories  which  conduct  lead  analysis on biologic
    specimens  Arch. Environ. Health. 23(2):\ 11-113, 1971.
25.  Berlin, A , P  Del Castilho. and J. Smeets. European inter
    comparison  programmes.  In:  Environmental  Health
    Aspects of Lead  Commission of  the  European Com-
    munities, Centre  for  Information  and Documentation,
    Luxembourg. May  1973. p.  1033-1049.
26.  Blood  Lead  Proficiency Testing.  U S.  Department  of
    Health, Education, and Welfare, Center for Disease Con-
    trol, Atlanta. Ga. 1975.
27.  Blood  Lead Proficiency Testing  Program  U.S.  Depart-
    ment of Health, Education,  and Welfare, Center for Dis-
    ease Control, Atlanta, Ga.  Monthly  Report  for March,
    1977
28.  Lead  Environmental Health Criteria 3.  World  Health
    Organization and the United  Nations Environment Pro-
    gramme, Geneva  1977 p. 59-65.
29.  Grimes, H., M. P  H. Sayers, A A. Cernik, A. Berlin, P.
    Recht, and  J. Smeets  Note on  the  Lead Exposure  of
    Children Determinations Carried Out  on  Behalf of the
    Commission in Western Ireland. Commission of the Euro-
    pean Communities, Luxembourg. Report  No  VF-1491.
    1975. p 7
30.  Haeger-Aronsen, B.  Studies on urinary excretion of 8-
    aminolevulinic acid and other haem precursors in  lead
    workers and lead-intoxicated rabbits. Scand J Clin Lab
    Invest  /2(Suppl. 47)—1-128, 1960.
31  Mauzerall.  D^ and S  Granick. The occurrence and deter-
    mination of 8-ammolevulinic acid and porphobilinogen in
    urine. J Bio7Chem. 2/9(1 H35-446, 1956.
32.  Marver, H. S., D. P Tschudy, M. G  Perlroth, A Colline,
    and G  Hunter, Jr  The determination of aminoketones in
    biological fluids. Anal. Biochem  74:53-60, 1966.
33  Urata,  G. and S. Granick Biosynthesis of 8-aminoketones
    and  the  metabolism of aminoacetone. J. Biol  Chem.
    238(2):81 1-820,  1963.
34.  Williams, M. K. and J. D. Few. A simplified procedure for
    the  determination of  urinary  8-aminolevulnic acid.
    Brit. J. Ind Med. 24-294-296, Oct.  1967
35.  Doss, M. and A. Schmidt Quantitative determination of
    8-aminolevulinic acid and porphobilinogen in urine with
    ready-made ion-exchange chromatographic columns.  Z.
    Klin, Chem. Klin, Biochem  9:99-102, 1971
36.  Grisler, R.. M. Genchi, and M. Perini. Determination of
    urinary 8-aminolevulinic acid by  continuous flux and se-
    quential automatic analyzers  Med. Lav 60-678-686, Nov
    1969.
37.  Lauwerys, R., R. Delbroeck, and M. D. Vens. Automated
    analysis of 8-aminolevulinic acid in  urine. Clin. Chim.
    Acta. 40:443-447, 1972.
38  Schlenker,  F. S., N. A  Taylor,  and B. P. Kiehn. The
    chromatographic separation, determination, and daily ex-
    cretion  of  urinary porphobilinogen,  aminoacetone, and
    delta-aminolevulinic  acid.  Am   J.  Clin.  Pathol.
    42:349-354, 1964.
                                                         9-7

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39. MacGee, J.. S. M Roda, S. V. Elias, A. Lington, M. W.
    Tabor, and  P  B  Hammond  Determination of delta-
    amtnolevulinic acid in blood plasma and urine by gas-
    liquid chromatography. Biochem. Med. /7:31-44, 1977.
40. Granick, J  L., S. Sassa. S. Granick, R. D. Levere, and A.
    Kappas. Studies  of  lead poisoning. I  Microanalysis of
    erythrocyte protoporphyrm levels  by spectrofluorometry
    in the detection  of chronic lead  intoxication  in  the
    subclinical range  Biochem  Med  8:135-148,1973
41. Weissberg,  J. B., F.  Lipschutz,  and  F.  A.  Oski.  8-
    ammolevulinic  acid  dehydratase  activity in  circulatory
    blood cells: A sensitive laboratory test for the detection of
    childhood  led poisoning.  New Eng.  J. Med.
    284(1 IV565-569, 1971
42 Berlin.  A.  and K H.  Schaller. European standardized
    method for  the  determination of 8-aminolevulmic acid
    dehydratese  activity  in blood  Z. Klin.  Chem  Klin.
    Biochem / 2.389-390. 1974
43. Granick, J. L , S  Sassa. S  Granick. R  D. Levere, and A.
    Kappas Studies in lead poisoning. II  Correlation between
    the ratio of  activated  and inactivated 8-ammolevulinic
    acid dehydratase of whole blood and the blood lead level.
    Biochem Med. 8-149-159  1973
44 Wranne, L  Free erythrocytes copro- and  protoporphyrin:
    A methodological and clinical study  Acta Pediatrica.
    49(Suppl  I24V1-78. 1960
45. HeiSmeyer.  L  Uber die erythropoetischen  porphyrien.
    Wien Med  Wochschr. //6-12-17,  1966
46 Langer. E E., R. G Hainmg, R F  Labbe, P Jacoby. E F
    Crosby, and  C  A  Finch. Erythrocyte  protoporphyrin.
    Blood. 40-\ 12-128.  1972
47 Granick. S  . S Sassa, J  L  Granick. R  D Levere, and A
    Kappas  Assays  for  porphynns,   8-aminolevulinic-acid
    dehydratase,  and porphyrmogen synthetase in microliter
    samples of whole blood Applications to metabolic defects
    involving the heme pathway Proc. Natl. Acad. Sci , U.S.A.
    69.2381-2385, 1972.
48. Piomelli, S.  A  micro-method for  free  erythrocyte
    porphyrins: The FEP test. J Lab. Clm. Med. S/.932-940,
    1973.
49. Lamola,  A.  A., M. Joselow, and T. Yamane  Zinc pro-
    toporphyrin (ZPP).  A  simple,  sensitive,  fluorometric
    screening test   for  lead  poisoning.  Clin.  Chem.
    2/(l).93-97, 1975.
50  Chisolm, J J , Jr., and D.  H Brown.  Micro-scale photo-
    fluorometnc  determination  of "free  erythrocyte
    porphyrin"  (protoporphyrin  IX).   Clin.   Chem.
    2/(ll):1669-l682, 1975.
51. Blumberg, W  E , J Eismger, A. A. Lamola, and D. M.
    Zuckerman  The  hematofluorometer.  Clin.  Chem.
    2J(2):270-274, 1974.
52  Matson,  W. R.,  R  M. Griffin, T.  J  Sapienza,  J  M
    Shiavone, and  A. J Reed   A Critical Evaluation of the
    Technical and Operational  Utility of Zinc Protoporphyrin
    (Z.nP), Erythrocyte Protoporphyrin (EP) and Blood Lead
    (BL) in Pediatric Screenings for Lead Insult Paper pre-
    sented at  Region  IV  DHEW  CDC Conference  on
    Pediatric Lead Poisoning Control Projects.  Atlanta, Ga
    February 1976.
53  Hanna.T L.D  W Dietzler. C H  Smith. S  Gupta, and
    H S  Zarkowsky  Erythrocyte  porphyrin  analysis in  the
    detection of lead poisoning in children: Evaluation of four
    micro methods. Clin Chem. 22  161-168,1976.
54. Chisholm, J. j .  C  W. Hastings, and  D  K  K Chenng.
    Micro-photo fluorometric  assay for  protoporphyrin in
    acidified acetone extracts of whole blood  Biochem. Med
    9:1 13, 1974.
                                                        9-8

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                            10.  METABOLISM  OF  LEAD
 10.1  INTRODUCTION
  The metabolism of lead in man may be defined as
the physiological processes relating to  absorption,
distribution,  translocation, and  net retention. The
metabolism of  lead  in  man  is  discussed  in this
chapter in terms of routes of exposure and of the
physiological  distinctions, existing within  popula-
tion  classes,  that  modify metabolic  processes.
especially with reference to children versus adults.
  Most of the material discussed in the following
pages addresses the dietary habits  of adults in the
United States. For children, however, there are die-
tary habits that are distinct from those of adults and
that have implications for differences in exposure
between adults and children.
  For example, in assessing the indirect contribution
of airborne lead to diet, one must consider the hand-
to-mouth activity of young children, i.e., sucking of
dirty fingers in contact with environmental dust and
dirt; retrieving foodstuffs, such as lollipops, that fall
into dirt; and a host of other childhood activities by
which airborne lead may contribute to the intake of
lead by children but not by adults.
  In  this chapter, the physiological processes that
control the uptake of lead by man (absorption) will
be  discussed  first.  Then  the movement of  lead
through the body into its depot tissues (distribution)
and  its eventual elimination  (excretion)  will be
treated.

10.2  ABSORPTION
  The quantities of lead absorbed from environmen-
tal sources are determined not only by the amount
ingested or inhaled but also by the particle size and
chemical species involved.
  Absorption  depends also on specific host  factors
such, as age, nutrition, and physiological status. In
addition,  the  total  quantity ingested in food and
water varies greatly from individual to  individual,
and  the total quantity inhaled depends on the size
and weight of the individual and  on the energy ex-
pended in day-to-day activity.
 10.2.1 Respiratory Absorption
   The International Radiological  Protection Com-
 mission (IRPC) Task Group on Lung Dynamics'
 developed a model designed to predict the percen-
 tage of inhaled aerosols that would be deposited and
 retained in the lungs. This model predicted that ap-
 proximately 35  percent  of the  lead  inhaled in
 general ambient air would be deposited in the air-
 ways. Since the aerodynamic diameter of lead parti-
 cles is generally in the range of 0.1   to 1.0  /nm,
 deposition would occur predominantly in the deeper
 regions of the  lung. Emissions  from stationary
 sources frequently include a significant proportion
 of  larger  particles that, when inhaled, would be
 deposited  primarily  in the nasopharynx.  Because
 these particles usually fall out of  the air rather
 quickly, exposure to these larger particles is limited
 primarily to the near vicinity of the emission source.
 The deposition within the respiratory tract of very
 small particles (<0.1  /xm) apparently occurs chiefly
 by diffusion,2 and rates or sites cannot be predicted.
 The IRPC model predicts a total airway deposition
 of 40 to 50 percent for 0.5 /^im particles, but a study
 in human  volunteers indicated only 6 to 16 percent
 desposition, depending on  the rate and depth of
 respiration.3 Chemical composition also affects up-
 take as does the aging of the aerosol (Chapter 6).
 This  illustrates the difficulty in  choosing  the ap-
 propriate   chemical  composition4 for  studies on
 deposition.
  Airway clearance of lead aerosols as predicted by
 the IRPC  lung model' is even more tenuous than are
 predictions regarding  deposition. The  model  indi-
 cates that  the absorption  or  clearance of  lead
 deposited  in the airways would vary greatly depend-
 ing on the solubility and on the inherent toxicity of
 the particles  to  the   clearance  mechanism  (lung
 macrophages and cilia).

 10.2.1.1 HUMAN STUDIES
  Actual studies on the fractional deposition of par-
ticles in the respiratory tract of man have not  been
extensive, especially in the case of lead. Using an air
                                                10-1

-------
lead level of  150 /^g/m3,  Kehoe5-"7  studied  the
deposition of combusted tetraethyl lead  in human
volunteers. The  source  of lead  was combusted
tetraethyl lead,  which produced lead (III) oxide
(Pb2O3) in the air. Subjects breathed air containing
1 50 /u,g/m3 lead; the smaller particles averaged 0.05
fj.m in  diameter and the larger  ones  averaged  0.9
/Am  in  diameter, as  viewed  under  the electron
microscope.  This represents a  mass median
equivalent diameter of approximately 0.26 and  2.9
/urn, respectively.8 Thirty-six percent of the smaller
particles and 46 percent of the larger particles were
deposited.
  Nozaki9 reported that when lead fumes  generated
in a high-frequency induction furnace were inhaled
at a concentration of 10,000 /oig/m3 deposition was
related to respiration  rate and particle size. At 10
respirations  per minute, the  deposition  decreased
from 63 to 42 percent as the particle  size  was
reduced from 1.0 to 0.05 ;u,m. At 30 respirations per
minute, deposition rates were  about halved.  The
results, which  are similar to those  of Kehoe,5-7  are
fairly consistent  with  the IRPC  lung deposition
model.1
  These data suggest that a 30 ±  10-percent deposi-
tion  rate can be expected in individuals  breathing
ambient air and that deposition may vary considera-
bly, depending on the particle size and the frequency
of respiration.
  The  rate of lung clearance  has  been studied by
means of gamma-ray lung scans following  inhalation
of 212Pb, but the relevance of the results to  the rate of
clearance of the chemical and physical forms of lead
usually  inhaled by man is  highly  questionable.10
These studies involved the absorption of 212Pb atoms
on  carrier aerosol particles; however, desorption
under these  artificial circumstances may  be  totally
unlike the clearance rate for ambient air lead parti-
cles.
  Kehoe5-7 reported a substantial increase in fecal
excretion when  large-particle lead oxide aerosols
were inhaled for many weeks at  105 Atg/m3; the in-
crease probably resulted from the swallowing of par-
ticles trapped  in the nasopharynx.  When  air with  a
similar lead concentration in small particles was in-
haled,  only a small rise in fecal  lead excretion  was
observed.
  In a recent study, Chamberlain et al.'' found a 35-
percent rate of deposition, at a respiration rate of 15
per minute, when subjects inhaled  automobile  ex-
haust  fumes  containing  radioactively labeled
tetraethyl lead  (203Pb).  This  compares  favorably
with Nozaki's previous findings.9 These  authors"
calculated that under conditions of chronic airborne
lead exposure roughly 50 percent of the deposited
lead is absorbed. Although alveolar  macrophages
ingest particles deposited in  the  lungs, these  cells
may be damaged by  inorganic lead compounds.12
Such damage has been demonstrated in rats and
guinea pigs. It  is possible, then,  that lung defense
mechanisms may be impaired when air contains high
lead concentrations.

10.2.1.2  ANIMAL STUDIES
  Animal studies by Bingham et  al.13 have demon-
strated a pronounced reduction  in the number of
lung macrophages resulting from  inhalation of lead
oxide at both  10 and 150 /xg/m3.  Similar results
have been  reported by others.12'14-15 This  suggests
that the lung clearance mechanism may function less
effectively  when  air lead concentrations are high.
Thus, Pott  and  Brockhaus16 reported that  large
doses of lead bromide solution or lead  oxide suspen-
sion administered intratracheally  to rats (1.5 mg of
lead oxide per  dose on 8 successive days) were re-
tained  by the body as completely as were  intra-
venous doses. At one-third the dose, however, reten-
tion via the intratracheal route was significantly less.
  Randall  and his coworkers17 exposed 4  baboons
to aerosolized lead (Pb3O4) of varying particle size
(mass median diameters of 5.9,  3.2,  and  2.0 /u.m,
respectively).  The  air lead concentrations varied
from approximately  1 to  4  /u,g/m3.  The exposure
period lasted 4 weeks,  and  blood sampling  con-
tinued for  6 weeks. The  rate of absorption of lead
into blood was faster and reached a higher  level for
coarse (mean diameter =  1.6 /tm) particles than for
fine (mean diameter = 0.8 /urn).

10.2.2 Gastrointestinal Absorption

10.2.2.1  HUMAN STUDIES
  It must be noted at the outset that the absorption
of lead from food varies with the physical form of
dietary intake. For example, the literature indicates
that the percent absorption of lead from beverages is
about five to eight times greater than that from solid
food.18-20 Kehoe5-7 concluded from long-term bal-
ance studies that approximately 10 percent of the in-
take of lead from food and beverages was absorbed
from the gastrointestinal  tract since this was the
amount excreted in the  urine. This estimate,  how-
ever, disregarded the urinary lead that might have
come from inhalation, as well as the lead excreted in
feces after absorption from the gastrointestinal tract.
  Rabinowitz et al.,21 however, obtained similar
                                                10-2

-------
results using orally administered 204Pb incorporated
into the diet.
  Alexander et al.22 studied the absorption of lead
from the gastrointestinal tract in 8 infants and young
children aged 3 months to 8.5 years and concluded
that 53 percent of ingested lead was absorbed.  Ab-
sorption and retention were consistent within the age
range studied. This study, however, has been criti-
cized  because the values varied greatly.
  In a recent study, Ziegler et al.23 showed that a
greater percentage of intake lead was absorbed  and
retained by infants than by older subjects. In this re-
port,  2 separate series of investigations were con-
ducted. In the first, 3 to 8 balance studies were per-
formed with 9 infants each. In the second, each of 6
infants consumed randomly allocated diets provid-
ing low, intermediate,  and moderate amounts of
lead.  When  intakes of lead exceeded 5 /u,g/kg/day,
which is a reasonable level given typical dietary pat-
terns, net absorption averaged  42 percent and reten-
tion averaged 32 percent of intake. It should also be
noted that there was an inverse relationship between
calcium intake and blood lead level.
  These  results  are  in general  agreement with
animal studies and to some extent  corroborate the
findings of Alexander et al.22The study of Ziegler et
al.23 appears to be much better designed than that of
Alexander et al.22
  Ingested  or dietary  lead  is often thought of as
reaching a subject via a distinctly different route of
exposure than inhaled lead. Inhalation of lead may
be regarded  as direct exposure to airborne lead.
Some portion of dietary lead may also be attributed
to exposure to airborne lead, but indirect rather than
direct, with lead reaching food either by deposition
onto aerial edibles or by fallout onto soil and subse-
quent  absorption  by root crops.  (Internal  trans-
location of lead between roots and aerial parts is ap-
parently small.) In addition, variable fractions of in-
haled lead are  ingested after deposition in the air-
ways; they are  cleared by retrograde movement to
the pharynx,  where the particles are then swallowed.

  Section 7.4.1  cites lead concentrations typically
found  in various foods,  but no research has been
brought to light that clearly partitions the origins of
food lead.  There would seem to be three principal
candidates: (1)  deposition of airborne lead (on pri-
mary food  crops and on animal feed crops); (2)  ab-
sorption of soil lead (much of this lead is often  the
historical accumulation of airborne  fallout); and (3)
lead  acquired  in  the  processing  and  canning  of
foods.

  Based on  the contrasts between  fresh and pro-
cessed  foods  (excluding frozen foods), it would  ap-
pear that  processing and  canning of certain foods
regularly doubles or triples their average lead con-
centrations (Table 10-1).
               TABLE 10-1. LEAD CONTENT OF FRESH, PROCESSED, AND CANNED FOODSTUFFS24
Food
Fresh produce
Carrots
Lettuce
Potatoes
Avg.
Processed foods
White flour
Cornmeal
Rice
Cereal
Sugar
Avg
Processed meats
Hot dogs
Hamburger
Avg
Fresh meats
Beef
Chicken
Liver
Avg.
Lead
concentration (ppm)
0.205
0130
0.050
0128
0052
0.143
0104
0107
0.031
0.087
0.446
0.578
0512
0120
0191
0.150
0154
Food
Canned vegetables
Beets
Beans
Peas
Tomatoes
Avg
Canned juices
Tomato
Vegetable
Orange
Fruit
Avg
Canned fruits
Peaches
Pineapple
Applesauce
Avg
Lead
concentration (ppm)
0.381
0.318
0.425
0710
0.458
0338
0.215
0135
0251
0235
0417
0.402
0.320
0380
                                                10-3

-------
  The data on lead in foods are not comprehensive
enough  to permit  construction of a  spectrum of
levels ranging from fresh to canned  and charac-
terization of the resulting lead exposure. It  must
suffice to state at this point that some fraction of die-
tary lead probably is indirectly of airborne origin.

 10.2.2.2 THE RELATIONSHIP OF  ORAL IN-
 TAKE TO BLOOD LEAD LEVELS
   It has been demonstrated repeatedly that blood
 lead levels increase when the oral intake of lead in-
 creases,  but a  quantitative expression of this
 relationship has not been determined. Studies from
 various parts of the world, as noted below, have
 shown that the increase  in the blood lead for each
 !00 /tig of lead ingested daily ranges from less than 6
 to more than  18 /xg/dl.
   It is important to point out that the high end of this
 range was gathered using subject groups whose die-
 tary intake may be of questionable relevance to the
 general population. Tepper and  Levin25  employed
 adult females in their study while Coulston et al.26
 used  an adult prison population. These findings are
 not only in contrast to those from earlier U.S. studies
 but also  to the results of a  number  of European
 studies based on the general population.27 The Euro-
 pean  data are more consistent with a contribution of
 about 6  /Ltg/dl to the blood  lead level per 100 /u,g
 daily oral intake of lead; a similar level is reported
 by Kehoe.5-7
   Children,  particularly infants, absorb  a  larger
 percentage of lead than do adults. Consequently, the
 contribution of dietary  lead to  blood lead levels
 probably is less for  adults, but definitive data are not
 available.

 10.2.2.3 ANIMAL STUDIES
   The absorption of lead from food and changes in
 absorption with age have been investigated in many
 animal  studies;  the usual values found  ranged be-
 tween 5  and 10 percent. However, Kostial et al.28
 demonstrated that 5- to 7-day-old rats absorb at
 least  55 percent of single oral tracer doses of 203Pb,
 and Forbes and Reina29 reported that  in rats the
 gastrointestinal  absorption of tracer doses of 2l2Pb,
 85Sr,  and 59Fe  was high  prior to  weaning  but
 decreased rapidly thereafter. The absorption rate for
 lead  was 83 percent at  16 days; it then decreased
 gradually to 74 percent on the day of weaning (22
 days) and rapidly thereafter to about  16 percent at
 89 days. Although there may be some question about
 the applicability of these data, they  are consistent
 with results reported from studies of young children.
  Kello  and Kostial30  have shown that milk  in-
creases lead absorption in 6-week-old  rats.  Fasting
enhances lead  absorption in mice.20  Low  dietary
levels of calcium, iron,  zinc, copper, selenium, and
vitamin  D  have been  reported to enhance lead
absorption.31'32 It has also been demonstrated that
rats on an iron-deficient diet accumulate more lead
in their bodies than do rats on an iron-sufficient
diet.33 Table 10-2 presents  the data of Barltrop34
relating to the effects of various nutritional factors
on lead absorption as reflected  in blood lead levels.
It should be noted that these studies are short term
studies obtained over a period  of 48 hr.

   TABLE 10-2. EFFECT OF DIFFERENT DIETS ON LEAD
   ABSORPTION EXPRESSED AS THE RATIO OF MEAN
    RETENTION FOR EXPERIMENTAL AND CONTROL
                   SUBJECTS34
                         Ratio of mean retention of lead
                            (experimental  control)
Diet
Low protein
High protein
Low fat
High fat
Low minerals
High minerals
Low fiber
High fiber
Low vitamins
High vitamins
Blood
5.1
4
1
96
17.7
02
1
1
1
1
Kidneys
25
37
1
76
11 9
0.2
1
1
1
1
Femur
2.8
26
1
48
13.7
01
1
1
1
1
Liver
2.2
1
1
42
8.8
01
1
1
1
1
   The absorption of lead in paint chips has received
attention because of the risk for young children who
tend to  ingest  this material. Recent data from rat
studies  indicate  that lead  chromate  and  lead
naphthenate incorporated into dried paint films are
substantially available for absorption, although the
absorption rate is 30 to 50 percent what it is for lead
naphthenate in oil or for lead nitrate  in aqueous
solution.35-56 The absorption of lead as a function of
chemical form  is shown in Table 10-3.37

  TABLE 10-3. PERCENTAGE ABSORPTION OF DIFFERENT
    LEAD COMPOUNDS RELATIVE TO LEAD ACETATE37
    Lead compound
                                        Absorption, %
 Control (no lead)
 Metallic lead (180 to 250 ^m)
 Lead chromate
 Lead octoate
 Lead naphthenate
 Lead sulfide
 Lead thallate
 Lead carbonate (basic)
  4
 14
 44
 62
 64
 67
121
164
                                                10-4

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 10.2.3 Cutaneous Absorption
   Absorption through the skin is of importance only
 in the case of organic compounds of lead, particu-
 larly the lead  alkyls and  lead  naphthenates.38-39
 Soon after tetraethyl lead was introduced into com-
 mercial  use, Eldridge39 reported  that  it was ab-
 sorbed through  the skin with great facility in both
 dogs and guinea pigs. The presence of gasoline has
 been said to delay the penetration of tetraethyl lead
 through  the skin,40 although it has no effect on its
 uptake by the lungs.41 In rats, five cutaneous or sub-
 cutaneous applications on alternate days of lead ace-
 tate or lead naphthenate produced, compared  with
 unexposed animals, a decrease in ALAD in liver, a
 decrease in liver and body weight,  and  distribution
 of lead in assayed body tissues.  Lead content was
 highest in kidney.  Lead naphthenate was considered
 by the investigators to be more toxic than lead ace-
 tate because of more pronounced skin  reactions,
 higher lead accumulation in brain, and the occur-
 rence of a paralytic syndrome before death in two
 animals.42
  The rate of absorption of tetraethyl lead and in-
 organic compounds through the skin was studied by
 Lang and Kunze.43 They applied solutions of  lead
 acetate,  lead  orthoarsenate,  lead oleate,  and
 tetraethyl lead to  the bare skin of a number of rats
 and measured the amount of lead  in  the kidney as an
 index of absorption. In all cases, the amount of lead
 in the kidney was greater than in controls; tetraethyl
 lead produced the  greatest difference. If the skin was
 traumatized before the lead solutions were applied,
 there was a  threefold or fourfold increase in renal
 lead  concentration. It  is  likely that   absorption
 through unabraded skin by various lead  compounds
 is primarily  dependent  on  their  relative  lipid
 solubilities.
  Because  of the  difficulty, particularly in tetra-
 ethyl-lead-contaminated atmospheres, in  attempting
 to separate cutaneous exposure from respiratory ex-
 posure, the role of cutaneous lead absorption in rela-
 tion to blood lead levels is still unclear.

 10.3 DISTRIBUTION
  When a single dose of lead enters the body, it is
 distributed initially in  accordance with the rate of
delivery of blood to the various organs and systems.
The  material  is then redistributed to organs  and
 systems in proportion  to their respective affinities
for lead. When daily ingestion is consistent for an
extended period, a nearly steady state is achieved
with  respect  to intercompartmental distribution.
The  steady-state condition will be disturbed, how-
 ever, whenever short-term high levels of lead intake
 are superimposed on such a long-term ingestion pat-
 tern.

 10.3.1  Human Studies
   Autopsy  data  have shown that lead  becomes
 localized and accumulates in  bone. This accumula-
 tion begins in fetal life,44-45  since lead is readily
 transferred  across the placenta. The concentration
 of lead in the blood of newborn children is similar to
 that of their  mothers,46-47 and  the distribution  of
 lead in fetal tissue is similar to that of adults.45
   The total content of lead in the body may exceed
 200 mg in men aged 60 to 70 years, but in women it
 is somewhat  lower.  Calculations by  several  in-
 vestigators48 show that in nonoccupationally ex-
 posed  adults  94 to 95  percent  of the  total  body
 burden is in the bones.44-49-50 These reports not only
 reaffirm the affinity of bone for lead, but also pro-
 vide evidence that  the  concentrations  of lead  in
 bones  increase at least until middle age (50 to 60
 years old).48-51 On the contrary, neither soft tissues
 nor  blood show  age-related changes in lead con-
 centration after age 20.52-53 Thus, it seems that the
 skeleton is a repository  that reflects the long-term
 accumulative exposure to lead, whereas body fluids
 and soft tissues equilibrate rather rapidly and reflect
 only recent exposures.
   The concentration of lead in the blood is utilized
 as an  index of exposure to assess conditions con-
 sidered to represent a  risk  to health.54 Plasma lead
 concentrations have been shown to be constant at 2
 to 3 /ig/dl over a range of 10 to  150 /^ig/dl whole
 blood.55 Recent studies have indicated  that lead  is
 bound  primarily  to  erythrocyte protein,  chiefly
 hemoglobin, rather than to stroma.56
   Rabinowitz used  a  stable lead  isotope tracer
 (204Pb) to determine the  rate of equilibration of
 blood  lead with  input.21 He found that in human
 subjects with a constant daily oral  intake of 204Pb, a
 virtually  constant concentration was measured  in
 blood after about 110 days. When lead was removed
 from the diet, the concentration  in the blood disap-
 peared with a half time  of approximately 19 days.
 Tola et al.57 reported that the concentration of lead
 in the blood rises fairly rapidly to a new steady-state
 level in about 60 days when men are introduced into
 an occupational lead-exposure situation, a situation
 similar to that cited for exposure chambers in clini-
cal studies.58
  Although  the  body  burden  of lead  increases
throughout  life,48-50-52  measurements   of  specific
organs and systems show that the total burden  is
                                                10-5

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divided between two general pools within the body.
The major portion of the lead  is contained in bone.
This pool is clearly  highly accumulative and, as a
consequence, lead  accumulates here  rather  con-
sistently  and continuously. The second pool com-
prises other organs  and systems and  accumulates
much less.  The  levels of lead in this pool tend to
stabilize early in adult  life and thereafter demon-
strate a turnover rate sufficient to prevent accumula-
tion.
  Since the organs  and systems that  contain the
relatively mobile lead pool are of greater toxicologi-
cal  significance, it is clear  that a mobilizable or
exchangeable lead burden is a more important con-
cept  than is total body  burden.  In this connection,
chelatable urinary lead  has been shown to provide
an index of the mobile portion of the total lead
burden.59'60 Among adults in the general population
there are  no  age-related  differences  in  con-
centrations of  lead  in  whole  blood or in  blood
serum. Thus, in a general way, the blood lead level is
an indicator of the concentration  of  lead  in  soft
tissues,  and the changes in blood  lead levels ob-
served when there are  changes in  exposure levels
probably reflect similar  changes in some organs and
soft tissues.

  Lead exposure causes the development of nuclear
inclusion bodies containing lead in both man61"63
and animals. Although they seem to occur most fre-
quently in the kidney, they have been found in other
organs as well.

  The concentrations of lead in deciduous teeth are
of interest because tooth analysis represents a nonin-
vasive technique and because teeth provide a record
of long-term  lead exposure.  The  dentine  is  par-
ticularly useful in this respect because it is laid down
from the time of eruption  to  the time the tooth is
shed. Concentrations of lead in dentine are reported
to  be  considerably lower  in suburban  school
children than in children residing in areas of  high
lead exposure.64

  Primarily because of  the relative ease with which
hair can be collected, there have been some studies
of the possible use of hair lead as an  index of ex-
posure.  These  studies  have  not  been sufficient,
however, to provide significant information on the
relationship between hair lead  concentrations and
the amount of  exposure. Rabinowitz et  al.65 fed
labeled lead (204Pb) to 3 subjects daily for approxi-
mately  100 days. Levels of isotope in the blood were
immediately elevated but in facial hair there was a
much  more  gradual  response,  with a  delay of
approximately 35 days.

10.3.2 Animal Studies
  Administration of a single dose of lead to rats pro-
duces  high  initial  concentrations  of lead  in soft
tissues which then fall rapidly as the result of excre-
tion and transfer to  bone.66 The distribution charac-
teristics of lead within  the animals' bodies were
found  to be  independent of the  dose over  a wide
range. Castellino and Aloj67 described the rate con-
stants  for  the  elimination  of lead  from various
tissues in  rats following  a  single dose.  Lead was
eliminated from bone much more slowly than from
other tissues. Bolanowska et al.6S reported that the
rate of elimination of a single dose of  lead from rats
became slower with time,  reflecting  progressively
decreasing mobility of the residual  body burden.
  Goldstein  et al.69 sacrificed 21-day-old rats 24
hr after intravenous  injection  of various  single
doses (1, 50. 200 /ug) of labeled lead (2l°Pb) and
found that the concentration of radioactivity in the
brain was directly proportional to the blood radio-
activity.  Studies of OTuama  et al.™ indicate,
however, that this process may not be one of simple
passive diffusion of lead into  neural  tissue. These
latter investigators  sacrificed guinea  pigs at 5, 60,
and 240 min. after the intravenous injection of tracer
doses of lead (2l°Pb) in both subacutely intoxicated
(155 mg PbCO3/day for 5 days) and control animals.
Radioactivity in barrier tissues  (such as choroid
plexus and meninges) rose rapidly, with  concentra-
tions  ranging  to more  than  ten times the
simultaneous brain radioactivity. Subsequently,
there was a fall in the barrier tissue levels, but brain
levels remained fairly constant and low throughout
the period of the study. The apparent discrepancies
may be explained in large part by the differences in
the ages of the animals as well as other factors, in-
cluding species  differences, time of  sacrifice, or  a
more complex mechanism of distribution.
  Rather striking age-related differences in  the dis-
tribution and retention of lead  in rats  have been ob-
served.71 Elimination of a single tracer dose of 203Pb
from the whole body, blood, and  kidney occurred
more rapidly in adult than in suckling rats. In suck-
lings there  was a slight  increase with time in the
203Pb content of the brain following administration
of the dose, whereas the content in  other soft tissues
decreased with time.
  The intracellular distribution  of lead has been
studied in  rat  tissue,  mainly  by  cell-fractiona-
                                                 10-6

-------
tion  techniques.72-73 Membranes,  especially
mitochondria, have shown an affinity for lead. Little
lead is found  in lysosomes,73 however, in contrast
with the intracellular distribution of many other
metals, e.g., mercury, copper, and iron.
  There  are few studies of target organs in which
lead concentrations at the site of the effect have been
specifically determined. In particular, direct assess-
ment of lead level in bone marrow is difficult to car-
ry out, although the sensitivity of the hematopoietic
system to lead has been extensively  investigated.
Formation of nuclear inclusion bodies is observed in
rats with renal lead  concentrations of  about  10
mg/kg (wet weight) of kidney.74 Other effects of lead
were found to occur only at higher levels of organ
concentration. Death in cattle is associated with lead
levels of about 50 mg/kg (wet weight) of kidney cor-
tex."
  The concept of  estimating  the lowest  level  of
metal accumulation  that results in adverse effects in
a target organ has not been well explored in  the case
of lead. This is in contrast with cadmium, for which
estimates have been made of the minimum  con-
centrations in the kidney cortex at which evidence of
renal damage appears.76

10.4  ELIMINATION
  The major  portion  of excreted lead appears  in
urine and feces, but lesser quantities are removed via
sweat, hair, nails, and  exfoliated  skin.

10.4.1 Human Studies
  Fecal  excretion  represents the  major route  of
organic and inorganic  lead elimination. The rate  of
fecal lead excretion has been reported  to  be 100
times the rate of elimination in urine;77-78 however,
most of the lead in  feces represents metal that has
not been absorbed.
  Rabinowitz et al.79 studied the excretion of tracer
lead from the blood of a nonoccupationally exposed
human subject. Urinary and fecal excretion of 204Pb
from the blood amounted  to 38 and 8 /xg/day, ac-
counting for 76 and 16 percent, respectively, of the
measured recovery. The crude estimation  of lead  in
hair, nails, and sweat yielded a value of 4 /ig (8 per-
cent). The urinary  excretion  was similar to the
average daily lead excretion of 31 /^g/day reported
by  Teisinger  and   Srbova.80  Booker  et  al.81  ad-
ministered lead(2'2Pb) intravenously to  2  human
subjects and then recovered 4.4 percent of the dose
in  urine  during  the  first  24 hr. Lead was not
detected in feces. During the second 24  hr, about
1.5 percent was measured  in both urine and feces.
Thus, gastrointestinal transit appears to play an im-
portant role in the rate of excretion in feces of
systemically administered lead.
  The clearance of lead from the blood of man into
urine was found by Vostal82 to be proportional to
the rate of creatinine  excretion, with  urinary  lead
extrapolating to zero at zero creatinine.
  The characteristics of urinary lead excretion may
be affected by the chemical form  of lead. Whereas
all of the lead  in urine of subjects with normal ex-
posure can be precipitated by the addition of agents
such as oxalate, phosphate,  or carbonate, only  one-
third to two-thirds of the lead in  the urine of lead
workers  is  available for  precipitation.83  These
results suggest the presence of a stable lead complex
in the urine of exposed workers.
  Lead is excreted  in  sweat  as  well  as  urine.
Schiels84 reported  that ingestion of lead acetate in-
creased the  lead concentration of sweat twofold to
fourfold.  Schroeder and  Nason85 found the  con-
centration of lead in the  sweat  of lead-intoxicated
subjects to be similar to that in urine.
  Since studies of net lead retention  suggest that, at
low  level exposures, higher  intakes are followed by
higher rates of excretions5-7-17-59 and that lead excre-
tion  appears to  be disproportionately low in cases of
high-level exposure, there is not  yet a predictable
relationship between increases in lead exposure and
in lead excretion.

10.4.2 Animal Studies
  The relative  importance  of lead  excretion from
blood  into urine and  feces  varies with the species
tested. Within  12 hr. 7.4 percent of an intravenous
dose appeared  in the feces of rats compared with a
recovery of 2.3 percent trom urine.86 In sheep, also,
fecal elimination is more  rapid than urinary excre-
tion  of lead.87 In contrast, urinary excretion was re-
ported to be two times greater than fecal excretion in
baboons.89
  There are indications that  most of the translocated
lead  (from blood to intestine) is derived from  bile.
Of the 7.5 percent of an intravenous  dose  of  lead
acetate excreted by sheep in the feces within 6 days,
81 percent originated in bile.87 Similar  results were
obtained from rats.86-89 Although species differences
in gastrointestinal transit time and the presence of a
gallbladder can explain differences in the rate of ap-
pearance of a single injected  dose of lead in the feces,
these factors do not account for differences in the
relative amounts of steady-state lead elimination in
urine and feces.
  Measurements of lead clearance into the urine of
                                                10-7

-------
animals, like  those  in  man,  require  an accurate
measurement  of the free  lead  concentration  in
blood. Since most of the lead  in blood  is bound  to
red cells and to plasma proteins, this measurement is
virtually impossible.
  Whether the renal tubule takes an active part  in
lead excretion is open to question. More recently, it
has been found that the renal tubule cell transports
lead into the  urine,90 perhaps because  of the  pre-
sence of lead-binding  ligands in the tubular  cell.
These observations demonstrate that the renal ex-
cretion  of lead involves more than  filtration of the
metal  at  the  glomerulus.  It  is  likely that the
responses of secretory and reabsorptive  processes to
increased circulating lead  levels contribute to the
relative constancy of urinary excretion in humans5'7
and in  laboratory animals74 that were  exposed  to
high doses of  lead.

10.5 ALKYL LEAD METABOLISM
  The toxic effects caused  by tetraethyl lead and
tetramethyl lead are not produced by the tetraalkyl
compounds themselves, but rather by  the  trialkyl
derivatives formed by dealkylation  in the liver.86-91
Tetraethyl  lead is converted primarily to  triethyl
lead and partly to inorganic lead.92  Triethyl  lead
concentrates in organs and disappears very slowly.
Even after several days,  there is no significant reduc-
tion.  Tetramethyl  lead is  much  less  toxic  than
tetraethyl lead, probably because it is dealkylated to
the trialkyl toxic  form  much  more slowly  than is
tetraethyl lead."
  Since  both   these compounds have  toxic  and
biochemical effects unlike  those of inorganic lead,
the biochemical indices used in assessing inorganic
lead exposure  would not be expected  to have the
same significance  in assessing exposure to  organic
lead. Indeed, in cases of severe, acute tetraethyl lead
poisoning, urinary coproporphyrins and  ALA excre-
tion are not usually elevated, and free  erythrocyte
porphyrins are only moderately and  inconsistently
elevated.94-95 These biochemical tests are therefore
of little use in short-term exposure  situations.  In
long-term exposure situations, however, it is possi-
ble that some of them may be useful. Indeed, Robin-
son96 has shown that in industrial workers exposed
to tetraethyl lead, urinary  excretion of ALA is in-
creased, but not to the same degree as in  workers ex-
posed to inorganic lead who have similar levels  of
total urinary lead excretion (organic plus inorganic).
Bolanowska et al.97 demonstrated that in three fatal
cases of tetraethyl lead poisoning the  ratio of in-
organic lead to triethyl  lead  ranged from  67:1  to
18:1 in the urine. This ratio did not reflect the ratio
of inorganic to triethyl lead in tissues, including the
brain where the ratio was approximately 1:1.


10.6  METABOLIC CONSIDERATIONS IN
THE IDENTIFICATION OF SUSCEPTIBLE
SUBGROUPS IN THE POPULATION
  The discussion on the metabolism of lead has up
to now only  tangentially  specified differences  in
metabolism between  children and  adults (Section
10.2.2). There are, however, physiological dynamics
of child growth and development that have signifi-
cant implications for the increased  risk of children
exposed to lead. There are, as well, differences be-
tween children and adults in the intake, desposition,
etc., of lead.
  Metabolic,  physical, and  other  differences  be-
tween children and adults that must be considered
include: (1) children have considerably less surface
area than adults, e.g., a 2-year-old child has  one-
third  the surface area of an adult; this parameter is
not known to be directly related to  the  risks associ-
ated with lead exposure:98 (2) there is greater  lead
intake by infants on  a per-unit-body-weight basis,
which is probably related  to greater  caloric  and
water requirements; (3)  there is greater intake in
children as well as net absorption (Section  10.2.2).
resulting from greater net respiratory intake along
with greater net absorption and  retention from the
gastrointestinal tract:  (4) the  rapid growth rate of
children may  reduce  the margin of safety against a
variety of stresses, including iron deficiency, etc.; (5)
dietary  habits of children in some respects99"101 are
quite different from those of adults; normal hand-to-
mouth activity such as thumb sucking occurs as well
as  the   habit of  retrieving dirt-contaminated
foodstuffs; (6) in children the  likelihood of protein.
calcium, and  iron deficiency is so great relative to
intake that a negative balance in these factors  may
exist; (7) in  very young  children  metabolic path-
ways99'101 are known to be incompletely developed,
e.g.. the blood-brain barrier in  newborns; and (8)
partitioning of lead  in  the bones of children is
different from that of adults.100-101  Only 60 to  65
percent of the lead body burden is in the bones of
children. More important is the possible lability of
the bone fraction of lead in children, particularly in
the case of coexisting calcium deficiency. Rosen and
Wexlerl02 find an increasing resorption of lead in rat
bone organ culture when calcium in the medium is
reduced.
                                                 10-8

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                                                        10-9

-------
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50. Schroeder, H  A. and I  H. Tipton  The human  body
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61. Cramer, K ,  R  A  Goyer, R  A. Jagenburg, and  M. H.
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62  Galle, P.  and L. Morel-Maroger. Les lesions renales du
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63  Richet, G  , C. Albahary, L. Morel-Maroger, P. Huillaume,
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64  Needleman, H  L. and J.  M  Shapiro. Dentine lead levels
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66. Hammond, P. B  The effects of  chelating  agents  on the
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67. Castellino, N. and S Aloj Kinetics of the distribution and
    excretion of lead in the rat. Brit. J. Ind.  Med. 2/:308-314,
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68. Bolanowska, W , J. Piotrowski, and B. Trojanowska. The
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69. Goldstein, G.  W  , A.   K.  Asbury,  and   I.  Diamond.
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70. O'Tuama, L A., C S. Kim, J. Gatzy, M. R  Krigman, and
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73. Barltrop, D., A. J. Barret, and J  T  Dingle Sub-cellular
    distribution  of  lead  in  the  rat  J.  Lab  Clm  Med
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74. Goyer, R  A., D L. Leonard, J. F Moore, B  Rhyne, and
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    tranuclear  inclusion  body  Arch.  Environ.  Hlth
    20:705-711, 1970.
75. Allcroft, R  and K  L. Blaxter. Lead as a  nutritional
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    conditions. J. Comp Path. Ther.  60:209-218, 1950.
76. Friberg, L., M.  Piscator, G. Nordberg, and T. Kjellstrom
    Cadmium  in the Environment, 2nd  Ed  Ohio, Chemical
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77  Kehoe, R. A. Normal metabolism ot lead Arch Environ
    Hlth. S-232-235, 1964.
78. Kehoe, R. A  Metabolism of lead under abnormal condi-
    tions. Arch. Environ. Hlth. 8 235-243, 1964
79. Rabinowitz, M.  B., G  W. Wethenll, and  J. D  Copple.
    Lead  metabolism in  the  normal human. Stable  isotope
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80. Teismger, J. and J. Srbova. The value  ot mobilization of
    lead by calcium ethylene-diamme-tetraacetate in the diag-
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81. Booker, D. V., A. C. Chamberlain, D Newton, and A. N
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83. Dinischiotu, G.  T , B.  Nestorescu, J.  C  Radielescu, C.
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84. Schiels, D  O. Elimination of lead in  sweat. Aust  Ann.
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 85   Schroeder, H. A and A  P. Nason. Trace element analysis
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      bile. Nature  757588, 1946
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      1977.
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           11. BIOLOGICAL  EFFECTS  OF  LEAD  EXPOSURE
 11.1 INTRODUCTION
  As noted in Chapter 2, air-quality criteria docu-
 ments present the scientific knowledge of the rela-
 tionship between pollutant concentrations and their
 adverse effects on public  health and the environ-
 ment. This chapter addresses the important human
 health and biological effects of lead exposure.
  Section 11.2 treats the biochemical and pathologi-
 cal  basis of the various health effects of lead, center-
 ing on enzymology and the subcellular and cellular
 aspects of lead effects on the various organ systems.
 Section  11.3  presents a brief  overview  of clinical
 lead poisoning — that is, lead exposure leading to a
 constellation  of adverse health effects that  require
 medical intervention. It is not the purpose of that
 subsection to suggest that  airborne lead invariably
 induces clinical  lead poisoning as defined in this
 document; rather, it seeks to state the consequences
 to health, both immediate and  long term, of the up-
 per range of exposure to this pollutant regardless of
 its source and to state this in a discrete portion of the
 document.
  The  respective sections on  organ systems  have
 been ordered  according to  the  degree of known
 vulnerability to lead of each system. The emphasis is
 not only on the three systems classically considered
 most sensitive — hematopoietic,  nervous,   and
 renal — but also on reproduction and development
 in view of lead's effects on the fetus, and, therefore,
 on pregnant women. Some effects can be considered
 to involve a number  of  organ  systems, and the
 available data on multisystemic effects are presented
 in the final subsection.
  Subdividing the chapter on  the health  effects of
 lead into organ systems was done for the purpose of
easier discussion. It must be kept in mind that, in
 reality, all systems function  in delicate  concert to
preserve  the  physiological  integrity  of  the whole
organism. Furthermore, all systems are interdepen-
dent in the organism, so that not only are effects in a
critical organ transmitted to other systems but also
 low-level effects, which  may be construed as less im-
 portant in a single specific  system, contribute to the
 cumulative  or additive adverse effects of minimal
 biological response in a number of systems.
 11.2 CELLULAR  AND  SUBCELLULAR
 EFFECTS OF LEAD
 11.2.1 Effects on Enzymes
   In general, the effects of lead on enzymes may be
 manifested in several ways. Lead, in common with a
 number of other metals, has an affinity for a number
 of complexing groups resident in  the structure of
 many  biomolecular  entities,   such  as  imidazole
 nitrogen, the cysteine sulfhydryl group,  and the e-
 amino group of  lysine. An effect may be imparted,
 therefore, by binding-site competition with the na-
 tive ion, by perturbation of the structural  integrity of
 enzymes, or by the impediment of substrate-enzyme
 binding.
  Cellular damage caused by lead may also permit
 the movement  of enzymes  into  the circulatory
 system, with a resulting elevation of enzyme activity
 in, for instance,  plasma.
  The effects of lead  on  enzymes  and enzyme
 systems have been studied in both animals and ex-
 posed  human subjects  and in vitro and  in   vivo.
 Clearly, many of these studies in the literature are of
 marginal relevance to this particular document and
 are briefly summarized  for reference reading  with-
 out evaluation.
  On  the  other  hand, a number of other enzym.e
 systems are of such distinct relevance that they are
 better elaborated in the specific sections on organ
 effects. For example, the enzymology relating to the
 heme  biosynthetic pathway is  discussed  in Section
 11.4.
  Enzymes that  have been shown to be affected by
 lead in animal studies are presented in Table  11-1,
and results of studies on enzymes in humans are pre-
sented in Table 11 -2.

 11.2.2 Organellar and Cellular Effects
  It is of interest to duscuss briefly the subcellular
distribution of lead before further comment is made
on cellular effects.
                                               11-1

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  TABLE 11-1. ENZYMES AFFECTED BY LEAD IN ANIMAL
                    STUDIES
Enzyme
Lipoamide dehydrogenase
DNAase
Serum glutamic oxaloacetic
transaminase (SGOT)
Serum glutamic pyruvic
transaminase (SGPT)
Serum alkaline phosphatase
(AP)
Erythrocyte and liver AP
Acid phosphatase
Catalase
Cholmesterase
a-Mannosidase
/3-Acetyl glucosammadase
Succinate oxidase
Cytochrome c reductase
Glutamate dehydrogenase
Cytochrome oxidase
Rat brain adenyl cyclase
/3-Glucuronidase
/3-Galactosidase
Effect on activity
Inhibited
Enhanced
Enhanced and
transitory
Enhanced and
transitory
Lowered
Variable
Quenched or
markedly inhibited
Variable
Markedly inhibited
Increased
Increased
Decreased
Decreased
Decreased
Decreased
Decreased
Elevated
Elevated
Reference
1
2.3
4-7
4-7
7
7.8
7,9,10
11-13
56.14
15
15
16
16
16
16
17
18
18
  TABLE 11-2. ENZYMES AFFECTED BY LEAD IN HUMAN
                    STUDIES
Enzyme
SGOT and SGPT
SGOT and SGPT
Serum alkaline phosphatase
Acid phosphatase
Aldolase
Cholinesterase
Glutlathione reductase
Glucose-6-phosphate
dehydrogenase
Effect on activity
Enhanced
No effect
Reduced
No effect
Enhanced
Inhibited
Enhanced
Inhibited

Reference
19-21
22
23
24.25
26
27-29
30
30

  Castellino  and  Aloj,31  using 210Pb, found  a
decrease in radioactivity over a 24- to 72-hr time in-
terval  in the nuclear fraction and  an increase of
210Pb in the mitochondria fraction using liver. Over
the same time interval, an increase in radioactivity
occurred  in  the  kidney  in  both  nuclear  and
mitochondria! fractions, and there was a decrease in
microsomes.  Mitochondrial binding  was  particu-
larly strong.
  Similarly, Barltrop  et  al.32  measured  203Pb in
heart,  liver,  kidney, and spleen  following in-
traperitoneal (i.p.) administration. Their results in-
dicated that most of the  lead  accumulated in the
mitochondria.
  A detailed study of the rat kidney by Goyer et al.33
showed that  over a  protracted  period  the  cell
nucleus accumulated the highest proportion of lead.
  Under lead  challenge, a cellular reaction typical
of a variety of animal species is the formation of in-
tranuclear inclusion bodies, the early experimental
history of which  has been reviewed  by Goyer and
Moore.34 The  presence of  considerable lead in these
bodies has been verified by X-ray microanalyses;35
ultrastructural studies show that this entity consists
of a rather dense core encapsulated  by a  fibrillary
envelope.
  The  work of Goyer,33-36 indicates that these inclu-
sion bodies  are a complex of lead and protein, the
protein moiety having characteristics of the residual
acidic  fractions of proteins in  normal  nuclei. The
morphological integrity  of these  inclusion bodies
collapses on treatment in vitro with  metal chelants
such as EDTA. A role for the inclusion body as a
cellular protective mechanism  during transcellular
lead transport  has been postulated.36
  How the localization of lead in  nuclear inclusions
relates to nuclear function has not been established;
however Choie and Richter37 have shown that i.p.-
administered  lead enhances  DNA  synthesis  and
proliferation of renal  tubular cells.  The  effects of
lead on cell division are detailed in Section 11.2.4.
Disaggregation occurs in  the ribosome in the pre-
sence of lead.1-38
  Animal experiments and human studies, mainly
centered on cellular energetics and  morphological
aberrations, have shown mitochondria to  be highly
sensitive to lead. Teras  and Kakhn39  showed de-
creased respiratory rates  in mitochondria of rabbit
tissue   under   chronic lead challenge  using a-
ketoglutarate, succinate, and  pyruvate as substrates.
Phosphorylation was also retarded.
  A marked sensitivity of the pyruvate-NAD reduc-
tase system  in kidney mitochondria  of lead-intoxi-
cated  rats  is suggested by the  work of Goyer and
Krai I,40 who  note impairment of pyruvate-depen-
dent respiration using ADP/O ratios and respiratory
control rates  (RCR's) as indices. Succinate-medi-
ated respiration  in lead-intoxicated  rats, however,
was not different from that of control animals.
  Rhyne and Goyer41 state that their observations of
decreased oxygen uptake rates for both State III and
IV  in succinate-dependent  respiration in
                                               11-2

-------
mitochondria of the kidney from lead-intoxicated
animals may be evidence of decreased succino-ox-
idase enzyme, which would also be consistent with
decreased mitochondrial protein.
 Walton42 reported an accumulation of lead in gran-
ules produced  in  isolated rat-liver  mitochondria
following incubation in media containing lead, with
the lower end of the range of the free lead  level
employed approaching that found in lead-poisoning
victims. It was noted that lead-rich granules, unlike
those obtained  with calcium, were not dispersed
after treatment with dinitrophenol.  This finding
would indicate that lead removal after deposition is
difficult. The above observations and other studies
prompt  the suggestion that lead effects are  twofold:
(1) energy diversion to the active accumulation of
lead would prevent ATP synthesis and the preserva-
tion of ionic gradients in the membrane; and (2) the
chemical action of lead would promote ATP hy-
drolysis, and lead would complex with essential SH
groups of mitochondrial enzymes and  interact with
anions.  The net result is  the  inability of cells to
maintain themselves structurally and metabolically.
  Recent studies by Kimmel et al.43 on the chronic
long-term exposure of rats to lead showed that sub-
cellular effects of lead on the renal system were ap-
parent when comparatively low levels of lead (5, 50,
and 250 ppm in drinking water) were administered
prenatally and up  to 9 months of age postnatally.
Light  microscopy showed  karyomegaly and
cytomegaly at all dose levels.  Electron microscopic
examination indicated swollen mitochondria,
numerous dense lysosomes, and intranuclear inclu-
sion bodies at 50 and 250 ppm. Furthermore, con-
siderable  alteration  in the activity of heme bio-
synthetic pathway  enzymes (8-ALA synthetase and
ferrochelatase) was observed  at 50 and 250 ppm.
The blood lead values for  the different dose regi-
mens ranged from  5  /ig/dl for control animals and
10 fj.g/dl for the 5 ppm group to 25 /ug/dl for the 50
ppm group and 70 /u-g/dl for the 250 ppm animals.
  Cramer et al.44 studied renal biopsy tissue of five
workers having varying periods of exposure to lead.
Although the typical lead-induced nuclear inclusion
bodies were found only in those with short exposure,
all subjects showed mitochondria! changes.
Mitochondria  in the  tubular  lining  cells  showed
swelling and distortion of cristae, with some of the
mitochondria transected by cristae.
  An important comment here relates to the indica-
tions of  impaired  mitochondrial  function  of
erythroid tissue in  humans  that can be assessed  by
changes in levels of free erythrocyte (actually zinc
erythrocyte)  protoporphyrin (FEP)  and  urinary
coproporphyrin.   The  discussion  of  the
hematopoietic system in Section 11.4 includes treat-
ment of this relationship.
  In addition, the intramitochondrial stages of heme
synthesis have been suggested to have an intermedi-
ary role in introcellular metabolism and are proba-
bly required for the continued transfer of iron from
extracellular  sites  to  normoblasts  of
reticulocytes.45'46
  The  in vivo effects  of  lead  on erythrocytes in
humans include:  accumulation of lead, increased
osmotic resistance, increased mechanical  fragility,
increased glucose consumption, increased potassium
loss in  incubation,  decreased  sodium-  and
potassium-dependent ATPase activity in membrane
fragments, and elevation in the number of immature
red cells.47'49  A more  detailed  discussion of
erythrocyte-lead  relationships  is given in  the
hematopoietic section.
  Jandl and coworkers50 demonstrated that the up-
take of 59Fe by human reticulocytes was almost com-
pletely inhibited  by 5 x 10-4  M lead and that its in-
corporation  into  hemoglobin  was almost entirely
prevented. This resulted in an elevated level of iron
in the erythrocyte membrane.
  The  major cellular  pathology of concern in the
kidney with reference to lead is that of the proximal
convoluted  tubular cells.  Initial  atrophy of the
epithelial cells  in this region is  followed by  cell
regeneration along with an increase in intertubular
connective tissue, basement  membrane  thickening,
and round  cell proliferation.  Tubular  cell
mitochondria swell and degenerate, as noted before,
and glomeruli show increased cellularity.51 Tubule
cells also show  the presence of nuclear inclusion
bodies, a description of which has been  made (vide
supra).
  In the suckling-rat model for lead encephalopathy
employed by Pentschew and Garro52-53 in which lead
exposure of  the pups is via milk from mothers fed
lead carbonate, epithelial cell dysfunction in brain
capillaries is evidenced by abnormal permeability to
Trypan  Blue and Thorotrast  (colloidal  thorium
dioxide). The lesion possibly centers on interference
with an energy-regulating mechanism peculiar to its
barrier function.
  Schlaepfer54 has suggested that the neuropathy of
lead poisoning may be caused by  initial damage to
the supporting cells of the nervous system. Dorsal
root ganglion capsular cells show a proliferation and
accumulation of dense bodies in their cytoplasm that
microscopically  possess the  features of  a  heavy
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metal. It is possihk that the metabolism of the cap-
suJai  cells  is  impaired,  which then  causes  the
degeneration of associated neurons and axons  and
hps a deleterious effect on the ganglion cells. A com-
mon  site for intoxication  in both the capsular cells
and the Schwann cells ot the  peripheral nervous
system  has been suggested to account  for both ax-
onal  degeneration and segmenta! demyelination55
because these two  cells  have a common embryologi-
cal origin.56
  Moore et  al.,57 in a study of the cardiac effects of
lead  in the drinking water of rats, found that when
rats were exposed  to lead in drinking water at a level
similar to levels previously found in Glasgow, Scot-
land, there  was a significant inhibition of cardiac
ferrochelatase  and  8-aminolevulinic   acid  dehy-
dratase that  was maximal after 6 months. Moreover,
electron microscopy revealed  marked changes in
myocardium and  myocardial  mitochondria.

11.2.3  Effects of Lead on Chromosomes
   The  examination of  chromosomes for damage is
technically difficult. The e\ aluation of the relevance
of many studies can  therefoie be equally difficult.
Because the  appropriate separation of chromosomes
into  two  chromatids and equal  redistribution of
chromatids during cell  division are necessary for the
reproduction of stable new cells for the maintenance
of healthy  tissue, the implications of  injury to
chromosomal material  are profound, and interrup-
tion of the processes involved can be serious.  Incor-
rect  division of cells by  the breakage of the
chromatid, the migration of  an  inappropriate set of
chromatids into either portion of a dividing cell, the
abnormal  reproduction of the complementary new
chromatid to complete a viable chromosome in the
new cell, and other deviations from the normal  pro-
cess can produce abnormal cells. Such chromosomal
aberrations  can,  therefore, be  responsible for the
production of such serious consequences  as genetic
defects in  offspring of the affected organism.
   In the last few years, a number of  reports have
been published on the chromosomal effects  of ex-
cessive exposure  to  lead  in  animals3  and
humans.56'68 Although some of these  reports  have
been essentially negative,63'65 others have concluded
that  there is a definite increase in  the number of
chromatid and chromosome changes in subjects who
are occupationally exposed  to  lead.56'62  Thus, the
literature  is  controversial in regard to chromosomal
abnormalities induced  by exposure to  lead.
   O'Riordan and Evans63 did not find any signifi-
cant increase  in chromosomal  damage  in  male
workers exposed to lead oxide furnes in a shipbreak-
ing yard. These shipbreakers had blood lead values
ranging from 40 to over 120 /ug'dl. Schmid et al.64
found no evidence of increased chromosomal aber-
rations in peripheral lymphocytes, studied both  in
vivo and in  vitro, in lead manufacturing  workers.
Furthermore, Bauchinger et al.65 found no abnor-
malities in the chromosomes of policemen  with ele-
vated blood  lead levels (20 to 30 percent above the
mean for the control group).
  An increase in chromosomal aberrations in people
occupationally exposed to lead whose mean blood
lead values were 38 to  75 /^tg/dl has been reported,
however, by Forni and Secchi58 and by Schwanitz
et  al.56  Moreover, Deknudt  et al.60 reported
chromosomal damage in a group of 14 male workers
with signs of lead poisoning. Although the workers
were exposed to zinc and cadmium as well as lead,
the authors  concluded that lead should  be con-
sidered responsible for the aberrations. The study by
Forni  and  Secchi58  showed that  the  rates of
chromatid changes were higher  in 65 workers with
preclinical and clinical signs of lead poisoning but
were not significantly raised for workers with  past
poisoning. Forni et al.62 also examined  11 subjects
before  and during initial  occupational exposure  to
lead. The increase in the rate of abnormal chromatid
metaphases (the separation of the pair of chromatids
during normal  cell  division) was doubled after 1
month  of exposure, was  further increased after 2
months, remained in this stage up to 7 months, and
then decreased. The fact that most alterations were
of the  chromatid type, that is, occurring in  cell
culture  after DNA synthesis,  indicates that  these
could be culture-produced aberrations and may not
reflect a realistic in vivo situation. Also, a number of
participants  dropped out in the later stages of this
study.  Thus, the actual biological  significance  of
these results is unknown.
  In a  recent report, Bauchinger et al.66 found that
chromosomal  aberrations  were  significantly  in-
creased in a group of 24 male workers occupied  in
zinc electrolysis and exposed to zinc, lead, and cad-
mium. The workers had clearly elevated blood  lead
and blood cadmium levels in comparison with a con-
trol group. The  authors emphasized the possibility
of  a synergistic  effect of several  metals on the
chromosomes. They also pointed out the similarity
between this group and the group studied by Dek-
nudt et al.60 in regard to exposure to a combination
of lead, zinc, and cadmium. Referring to studies in-
dicating the mutagenicity of cadmium, Bauchinger
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and his colleagues66 were inclined to consider cad-
mium as being mainly responsible for aberrations;
but Deknudt  et  al.60  concluded that  the  abnor-
malities found  were  caused  mainly by  lead  rather
than by combinations of the  three metals.
  The question of whether chromosomal  abnor-
malities occur  in humans as a result of lead ex-
posure, either alone  or in combination with other
pollutants, remains unanswered.67 Furthermore, the
human health significance of chromosomal abnor-
malities seen in lymphocyte cultures, a method used
in some of the studies reported, is not yet known.68
An assessment  of the possible  mutagenic  effects of
lead is further hampered by the technical difficulties
that are inherent in the study of chromosomes.

11.2.4 Carcinogenesis
  Lead salts have been shown to be at least co-car-
cinogenic  in rats and mice.69 The ultrastructure of
experimentally lead-induced renal  tumors  in
animals70  is characterized by cellular and nuclear
hypertrophy, the  presence of numerous lysosomes
and microbodies, and the absence of the infolding of
basal  plasma membranes that  is normally seen in
renal  tubular lining cells. These tumor cells do not
contain intranuclear inclusion bodies, and the lead
content of the tumors is less than that  in adjacent
renal cortex. Renal adenomas and carcinomas were
first observed in rats by Zollinger71 in 1953 follow-
ing long-term injections of  lead phosphate.  Later
Kilham et al.72 reported similar tumors in wild rats
believed to have been exposed to lead fumes from
burning refuse in  a city dump. Lead-induced renal
epithelial  tumors  have since been  confirmed by  a
number of investigators.70'72'73
  Swiss mice fed diets containing 0.1 percent basic
lead  acetate [Pb(C2H3O2)2-2Pb(OH)2]  developed
both benign and malignant renal tumors.73 The same
compound fed to  rats at the  0.1 or 1 percent level
similarly induced both benign and malignant kidney
tumors,70'74 and the incidence and size were related
to the duration of lead  feeding.74 In male  Sprague-
Dawley rats fed a diet containing 1  percent basic
lead  acetate, Oyasu  et al.75 observed  2 cerebral
gliomas and  13  kidney  tumors in 17  animals.
Van Esch and Kroes73 reported renal changes but no
neoplasms in 2  groups of  22  and 24 male hamsters
fed, for up to 2 years, a  standard laboratory diet
containing 0.1 or 0.5  percent basic lead acetate.
  Renal tumors were  observed  in rats  fed diets
containing   1   percent   lead   acetate
[Pb(C2H3O2)2.3H2O],76 and Goyer and Rhyne77 re-
ported that 60 to 80 percent of rats on a diet contain-
ing 1 percent lead acetate for more than 1 year
developed renal adenomas or carcinomas with an in-
crease in both size and incidence of carcinomas re-
lated to duration of exposure.
  Subcutaneous or intraperitoneal injections of lead
phosphate repeated over a period of several months
also induced  renal  tumors. The  total  doses ad-
ministered varied between 120 and 680 mg lead in
the animals developing the tumors.71'78
  In  addition to renal  neoplasms, tumors of  the
testes, the adrenal, thyroid, pituitary, and prostate
glands, and the brain have been reported in Wistar
rats fed lead acetate.79
  The morphologic and  co-carcinogenic effects of
lead  on  the  respiratory  system were studied  by
Kobayashi and Okamoto.80 Male and female golden
hamsters were given a combination of 1 mg lead ox-
ide and 1 mg benzo[a]pyrene intratracheally once
weekly for 10 weeks; lung adenomas occurred in 11
of the 26 animals within 60 weeks.  One adenocar-
cinoma  of  the  lung was  also  observed.  Any
differences in  frequency of occurrence  between
males and females were not mentioned. Such tumors
did not occur in animals given the same dose of lead
oxide or  benzo[a]pyrene  alone. It  should be noted,
however, that because lead compounds are only a
small fraction of total particulates in air, there may
be  enough  particulates  even  without  lead for
benzo[a]pyrene to be adsorbed so as to  cause  in-
creased carcinogenicity.
  Tetraethyl  lead (TEL) [Pb(C2H5)4]  is an impor-
tant,  widely  used, antiknock  additive for motor
fuels. Epstein and  Mantel81  reported  that  sub-
cutaneous injection of 0.6 mg of TEL given as four
equally divided doses to Swiss mice between  birth
and 21 days of age produced malignant lymphomas
in 1 of 26 males and 5 of 41 females, compared with
1 of 39 males and none of 48 female control animals.
The tumors were observed 36 to 51 weeks after the
first injection in treated females.
  No definite relationship between carcinogenicity
and occupational exposure to lead has been estab-
lished from human  studies.  In 1963,  Dingwall-
Fordyce and Lane82 found only marginal evidence
for any significant incidence of malignant diseases in
their study of 425 persons who had been exposed to
lead while working in a battery factory.
  A study of the causes of mortality among lead
smelter and lead battery workers in 1975 concluded
that the incidence of malignant neoplasms, although
somewhat  greater   than  expected,  was  not
statistically different from the incidence in the non-
exposed population.83 This seems to  support the
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conclusion of a Working Group of the International
Agency for Research on Cancer (IARC) that there is
no evidence suggesting that exposure to  lead salts
causes cancer in humans.69 The IARC view is sup-
ported by the fact that the comparable level of lead
exposure that has been  associated with malignant
tumors in experiments on  rodents is considerably
higher than the toxic dose in humans.69

11.3 CLINICAL LEAD POISONING
  Lead poisoning gives rise to recognized but non-
specific syndromes including acute encephalopathy,
chronic encephalopathy, peripheral neuropathy,
chronic nephropathy, and anemia.
  Encephalopathy is the  most severe acute clinical
effect of lead  poisoning  and may  emerge  rather
rapidly  with the onset  of intractable  seizures
followed by coma and  cardiorespiratory arrest.
When the outcome is fatal, death often occurs within
48 hours of  the onset of encephalopathy.
  In  its fulminant form, development  of en-
cephalopathy occurs in less than a week. Periods of
vomiting and apathy progressing  to  stupor are in-
terspersed with  periods  of hyperirritability,  poor
memory, inability to  concentrate, mental  depres-
sion, persistent headache, and tremor. Several  re-
ports85'86  indicate  that  children with acute  en-
cephalopathy  may  also  incur  acute renal  injury
(Fanconi syndrome), showing hyperaminoaciduria,
glycosuria, and hyperphosphaturia.
  Pediatric  patients with lead poisoning frequently
exhibit antisocial behavior and other behavioral dis-
orders, including loss of motor skills  and speech.
They  may  also  exhibit  convulsive  disorders;
however, there  are no  clinical features that  dis-
tinguish  lead-induced   convulsions from other
seizure disorders. These findings are usually associ-
ated with blood lead levels in excess of 60 ^tg/dl and
with increased density (in X-rays) at the end of long
bones  (lead lines).  Because  the  latter indicates
prolonged absorption of lead, this clinical picture is
termed chronic encephalopathy. The above is very
similar to the pattern seen with recurrent episodes of
acute  lead  poisoning with or without  acute en-
cephalopathy, and the latter has been described by
Byers and Lord87 as well as Perlstein and Attala.88
However,  there may  have  been   unrecognized
episodes of acute encephalopathy at a previous time.
  The peripheral neuropathy of lead poisoning cen-
ters on motor involvements with little effect on the
sensory systems. This involvement  may assume three
clinical forms: (1)  severe  pain and tenderness  in
trunk and extremity muscles giving way to weakness
and slow recovery; (2) the more common painless
peripheral extensor weakness; and (3) neuropathic
and myopathic features that  are indistinguishable.
This pattern is generally seen  in workmen after 5 or
more years of chronic exposure.
  Patients with a history of one or more episodes of
acute  lead  intoxication  develop  a  nephropathy
characterized by progressive and rather irreversible
renal insufficiency. Progressive azotemia and some-
times hyperuricemia are noted. Late lead nephropa-
thy generally is recognized at an irreversible stage.
  The question of renal sequelae as a result of acute
lead  poisoning in  children has been  addressed in
several reports. Henderson89 noted that survivors of
childhood lead poisoning in Australia demonstrate a
very high frequency of chronic nephritis. Tepper,90
however, did not confirm this in his Boston studies.
Apparently, the length of exposure is of significance,
as Tepper's subjects had incurred acute lead poison-
ing during  preschool years whereas the Australian
groups may have had exposure to lead for longer
periods of time.
  The anemia of lead poisoning is hypochromic and
sometimes  microcytic. It is  also  associated  with
shortened red cell  life span, reticulocytosis, and the
presence of basophilic-stippled cells. Further discus-
sion of the hematopoietic effects is contained in Sec-
tion 11.4.
  Kline studied five patients having  chronic  lead
poisoning.91 At autopsy, evidence was found for lead
encephalopathy in all,  as  well  as  evidence for
chronic myocarditis. The latter was characterized by
interstitial  fibrosis with  a  serous   exudate  and
relatively few inflammatory cells. From these obser-
vations, routine electrocardiographic studies and
close scrutiny for  evidence of myocardial  damage
was recommended  by the author.91
  Approximately 25 percent of young  children who
survive an  attack  of acute encephalopathy sustain
severe  permanent  neurological sequelae.92-94  Two
studies92-93 have indicated that a pediatric victim of
acute  encephalopathy has an almost 100  percent
chance of  severe  permanent  brain damage when
returned to the same environment.
  In its most severe form, acute lead  encephalopa-
thy may  be  followed  by  cortical  atrophy,  hy-
drocephalus  ex vacua,  severe convulsive disorder,
mental incompetence, and blindness.  These results
are becoming rare, however, and subtle neurological
deficits and mental impairment are the more com-
mon outcomes.
  Many children with documented prior attacks of
symptomatic lead  poisoning develop  aggressive,
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hostile, and destructive behavior patterns. Although
seizure disorder  and behavior abnormalities may
diminish during adolescence, mental incompetence
is permanent.2'87
11.4 HEMATOLOGICAL EFFECTS OF LEAD
11.4.1  Anemia
  Anemia of varying degree is a manifestation (often
the  earliest  one)  of clinical  lead  intoxication.
Classically, the anemia is mildly hypochromic and
sometimes microcytic. The anemia is associated with
reticulocytosis (because of the shortened red cell
survival) and the presence of basophilic stippling.
Childhood lead  poisoning is  most frequently ob-
served in children  1  to 6 years old and  of lower
socioeconomic status; in both these groups the pre-
valence of iron deficiency is quite high. A combina-
tion of iron deficiency  and increased lead intake
results in more severe anemia. Anemia, however, is
also observed in children with increased lead intake
who are not iron deficient. Six and  Goyer95 demon-
strated that dietary  iron deficiency  in rats produced
increased lead retention in liver, kidney, and bone
with increased urinary 8-ALA excretion. Kaplan et
al.96 showed that the uptake of lead by erythrocytes
in the presence of iron was decreased. These findings
raised the possibility that iron-deficient children are
more susceptible  to the toxic effects of lead.
  Although it is well known that anemia occurs in
severe  lead intoxication, the threshold blood lead
level at which anemia occurs  is not clearly estab-
lished. In lead workers, Sakurai97 could not demon-
strate any  difference in hemoglobin level up to a
blood lead level of  50 /zg/dl. Tola  et al.98 reported
an effect of blood  lead level  on hemoglobin in a
study of 33 workers at the  beginning of  their ex-
posure to lead in  an occupational setting and found
that after 100 days of exposure, at the time  when the
average blood lead  level had reached 50 /u.g/dl, the
average hemoglobin level had decreased to  13.4 g/dl
from the initial value of  14.4 g/dl  (p  =  < 0.001).
Pueschel" observed a negative correlation between
hemoglobin level  and  blood  lead  level  in  40
children with blood lead levels ranging between 30
and 120/ng/dl. In this study, however, the ages of the
individual  children  are not stated. A number of
other studies also  bear  out the  above  observa-
tion.100-'02 It is known that in children aged 1 to 6
years there is a progressive physiological increase in
hemoglobin level and that both iron deficiency and
lead intoxication  are most frequent in the  youngest
children.
  The  mechanism of anemia in lead poisoning ap-
pears to be a combination of decreased erythrocyte
production as a result of the interference of lead with
hemoglobin synthesis and increased destruction as a
result of direct damage by lead to the red cell itself.
The specific effects of lead at various steps in
erythropoiesis are discussed below.
  Approximately 90 percent of blood lead  travels
with the erythrocytes103'104 as the lead is rapidly
transferred from plasma to erythrocytes.  Rosen et
al.loohave shown that plasma lead levels are a con-
stant 2 to 3 jug/dl over  a range of 10 to 150 /ig/dl
whole  blood. McRoberts,105  however, has  shown
that the plasma levels  can fluctuate considerably
and are associated with the appearance of symptoms
in cases of occupational exposure. Kochen104 has
shown that erythrocytes primarily serve as a  carrier
for blood lead, with a binding capacity well  above
those lead levels associated with even very heavy ex-
posure.  It would appear, then, that the whole blood
content  of  lead  is relatively  independent  of
hematocrit.

11.4.2  Effects  of  Lead  on  Erythrocyte
Morphology and Survival
  In lead poisoning, even  in absence of iron defi-
ciency,  the  erythrocytes are microcytic  and  hy-
pochromic. Basophilic stippling is a frequent but in-
constant feature  of  lead poisoning and has been
employed as a method of monitoring workers in the
lead industry. This test has the disadvantage of being
nonspecific, as basophilic stippling may be observed
in the erythrocytes of individuals with thalassemia
trait and in several types of hemolytic anemia.
Moreover, a  good correlation between the amount
of stippled erythrocytes and blood lead level has not
been observed.106 Recently  Paglia and Valentine107
have indicated  that the  basophilic stippling in lead
poisoning results from the inhibition of the enzyme
pyrimidine-S'-nucleotidase,  which  under  normal
conditions plays a prominent role in the cleavage of
residual  nucleotide chains  that  persist  in  the
erythrocytes after extrusion of the nucleus.
Decreased activity of this enzyme in persons with
elevated blood lead  levels is  observed even when
basophilic stippling is not morphologically evident,
and it probably contributes to the shortening  of the
erythrocyte survival. It  is  known, in  fact,  that a
severe chronic  hemolysis is present in people who
are  genetically  defective  in  pyrimidine-S'-
nucleotidase.108
  Osmotic fragility is decreased in  lead poisoning.
This is   a  common  feature of many  microcytic
anemias, as it  expresses the increased  surface-to-
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volume  ratio  that  results  from  the  reduced
hemoglobin  content of individual  erythrocytes. In
lead poisoning, however, an increased osmotic resis-
tance also results from a direct effect of lead on the
erythrocyte  membrane because increased osmotic
resistance may be produced by lead in vitro.l09 In-
creased osmotic  resistance  has been proposed  as a
screening test for lead poisoning  in  children.110
Other  evidence  of direct  damage to the red  cell
membrane  in lead  poisoning  is  the  markedly
lowered  activity  of the sodium- and  potassium-de-
pendent membrane ATPase, which is indispensably
coupled to active cation transport."1 Shortening of
erythrocyte survival has been shown by Hernberg et
al."2   using  tritium-labeled  difluorophosphonate
and by Berk et al.113 using  detailed isotopic studies
of a patient with  severe acute lead poisoning. Leikin
and  Eng"4  observed shortened  survival time in
three out of seven children  with lead poisoning and
anemia These studies indicated that hemolysis is not
the exclusive  mechanism of anemia  and  that
diminished erythrocyte production plays an impor-
tant role.
   An additional factor is a  large  component of in-
effective erythropoiesis. This was demonstrated by
the detailed study of the patient of Berk et al.113 in
whom  a  marked  increase of labeled stercobilin was
observed after  administration  of labeled  I4C-
glycine, a heme precursor. The presence of increased
amounts of this heme catabolite in the urine demon-
strates altered hemoglobin synthesis as  a result of
metabolic blockage  or premature  intramedullary
destruction of red cell precursors, or both.

11.4.3 Effect of Lead on Heme Synthesis
   The effects of lead on heme synthesis are quite
well known both because  of their prominence and
because  of the large number of  studies in humans
and experimental animals. The process of heme syn-
thesis results in the formation of protoporphyrin IX,
a  complex  molecule  from  small building blocks,
glycine and succinate (as succinyl coenzyme A); it
culminates with the insertion of iron at the center of
the porphyrin ring. The initial  and final  steps of
heme  synthesis  take  place  in the  mitochondria,
whereas most intermediate  steps  take place in the
cytoplasm  (Figure  11-1).  Heme  is formed in the
mitochondria, and it is also an essential constituent
of the  cytochrome system located in  the inner  crest
of the  mitochondria themselves and is essential to
cell respiration.  Besides being a constituent of the
cytochrome system and of  several other heme pro-
teins in  the body, heme is the prosthetic group of
                                                                   MITOCHONDRIA!- MEMBRANE
                   MITOCHONDRION
                        FERRO-
                        CHELATASE
      SUCCINYL-CoA
                        Fe + PROTOPORPHYRIN
          « ALASYNTHETASE
             (INCREASE)
              Pta (DIRECTLY OR BY

              DEREPRESSION)
   ft-ALA
 DEHYDRASE
 (DECREASE)
                            COPROPORPHYRIN
                               (INCREASE)
  PORPHOBILINO^EN (PEG)

     Figure 11-1. Lead effects on heme biosynthesis.
hemoglobin, the protein that transports oxygen from
the respiratory system to every cell  of the body.
Hemoglobin represents 33 percent of the weight of
red cells; so a  normal 70-kg male with a red cell
mass of 3000 ml  has  I kg of hemoglobin, approx-
imately 35 g of which are heme. Therefore, with a
red cell life span of 120 days, the daily production of
heme for hematopoietic use is only around 300 mg.
  Lead interferes with heme  synthesis at  several
points. The two most important steps affected are the
condensation of two molecules of 8-aminolevulinic
acid (8-ALA) to form the porphobilinogen  ring (at
the step catalyzed by the enzyme, 8-aminolevulinic
acid dehydratase) and the insertion of iron into pro-
toporphyrin IX (catalyzed by the enzyme, ferroche-
latase). Other steps in the heme synthesis are affected
by lead, such as 8-ALA-synthetase and coprogenase;
these, however, may be affected  indirectly through
feedback derepression.
11.4.3.1  EFFECTS OF  LEAD  ON  8-AMINO-
LEVULINIC ACID DEHYDRATASE (8-ALAD)
AND 8-ALA EXCRETION
  This enzyme is highly sensitive to the effect of lead
and is directly inhibited by chelation of essential SH
groups. The inhibition may be completely reversed
by reactivation of the  SH group in vitro by reducing
compounds  such  as  mercaptoethenol and
dithiothreitol.  The observation that 8-ALAD is in-
hibited by lead  was first reported by Nakao et al."5
and DeBruin"6 in 1968. Hernberg et al.117 demon-
strated that the  logarithm of the activity of 8-ALAD
was negatively correlated with blood lead level over
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a range from 5 /tig/dl (the lowest value .->Kserved) to
95  /^g/dl.  In a detailed study of 25  healthy  in-
dividuals with blood lead levels below 16 pcg/dl, the
same investigators found a similar correlation even
in this  lowest  range."8 These data  suggested  the
direct inhibition  by  lead  of 8-ALAD  with  no
threshold effect because the enzyme was 50 percent
inactivated at a blood lead level of 16 Mg/dl and 90
percent inactivated at a blood lead level of 55 ng/d\.
These observations have been confirmed by several
other laboratories"9"123 for the general population,
for industrial workers, and for children. In a study
of 123 subjects, including 44 lead  workers and 79
nonexposed persons (blood lead range of 4.5 to 9.3
//.g/dl), Wada et al.124 noticed a similar exponential
negative correlation between  blood  lead and 8-
ALAD.  In a subsequent investigation,125 the  same
author  studied  8-ALAD in three groups:  (1) 10
families (each including parents and one child) from
a village far north of Tokyo with average blood lead
of 8.3 Mg/dl (range  5 to  10), (2)  10  families  from
central Tokyo with average blood lead of 12.8 jug/dl
(range 9 to  17),  and  (3)  10 male  workers  with
average blood lead of 26.5 /xg/dl (range  14 to 36). In
this s'tudy, a significant negative correlation between
log ALAD and blood lead was found by combining
groups  1, 2,  and 3 or  groups 1 and  2. In the first
group, however, no such correlation could be dem-
onstrated. Because this latter group comprised only
10 families from a small  village, it is possible  that
failure to observe any relationship could be caused
by the very  narrow range of blood  lead (5 to 10
Mg/dl) and/or by genetic factors.
  More recently Granick et al.126 studied the  ratio
of 8-ALAD  activity before and  after reactivation
with dithiothreitol in 65 children with blood  lead
levels  between  20 and 90  fj.g/d\.  By regression
analysis, they estimated in this series that a ratio of
reactivated/nonreactivated 8-ALAD  of 1  (corres-
ponding  to no  inhibition) would  occur at a blood
lead level of 15 /^ig/dl. Because of the wide range of
variation  and the small  number  of  observations,
however, the confidence limits of their estimate are
quite large.  On the other hand, Hernberg et al."8
have shown  a  negative correlation  in  individuals
with blood lead levels below 16 /*g/dl, whereas the
lowest blood lead level studied by Granick et al.126
was 20 /tg/dl. For these reasons, the observations of
Granick et al.126 do  not contradict the evidence by
Hernberg et al."8 that 8-ALAD is already inhibited
at the lowest  levels of  blood lead observed  in
humans in industrialized countries. Because the  in-
hibition of this enzyme is a direct effect of lead in the
 blood, its correlation with blood lead is not surpris-
 ing, and 8-ALAD activity may be used to estimate
 blood lead with a good degree of accuracy. The in-
 hibition  of 8-ALAD in erythrocytes reflects a simi-
 lar effect of lead  in body tissues, as shown by the
 studies of Secchi et al.120 which demonstrated that,
 in 26 persons without  industrial exposure to  lead
 and with blood lead levels between 12 and 56 jiig/dl,
 there was a  clear correlation  between erythrocyte
 and liver 8-ALAD and an expected negative  cor-
 relation  between blood  lead and  8-ALAD  in
 erythrocytes. Millar et al."9showed that when suck-
 ling rats were fed diets containing lead there was a
 significant  and  commensurate reduction  of  8-
 ALAD activity not only in erythrocytes but also in
 liver  and brain tissues. In a recent study by Roels et
 al.,127 however, changes  in tissue  ALAD  and  free
 tissue protoporphyrin (FTP) were not found follow-
 ing postnatal lead administration  in the rat. Lead
 was administered in the drinking water (0, 1, 10, 100
 ppm) from parturition until day 21. In the offspring,
 an increase  in Pb-B  and a reduction in ALAD ac-
 tivity were found in the 10 and 100 ppm groups but
 no  differences in hematocrit, hemoglobin, or FEP
 were observed. Lead storage in the kidney of the 100
 ppm  group  was associated  with a  marked rise  in
 kidney FTP but no differences  were  found  in either
 ALAD or FTP in either liver, heart, or brain.
  The inhibition  of  8-ALAD is  reflected in  in-
 creased  levels  of its substrate, 8-ALA,  in  urine.
 Plasma 8-ALA has been shown128 to be elevated  in
 children  with  severe  lead  poisoning; however,
 because  of  the  technical cumbersomeness of the
 techniques for  measuring 8-ALA,  few  data  are
 available on 8-ALA plasma levels at lower blood
 lead levels. On the other  hand, urinary 8-ALA has
 been used extensively as an indicator of excessive ex-
 posure to lead, and it has even been suggested  as a
 screening tool for lead poisoning.129 Its use for this
 purpose has,  however, been rejected because of the
 wide  range of individual variability  in daily excre-
 tion observed in some studies130'131 Industrial use of
 this technique has been satisfactory,  however.
  Several studies have  indicated that an  excellent
 correlation exists between blood lead level and the
 logarithm of the  level of urinary 8-ALA. Selander
 and Cramer132 first  described  this  relationship in
 150 lead  workers with blood lead ranging between 7
 and 92 /Ltg/dl. Their  observations have been  con-
firmed by other  studies123-124'133 in which  a similar
correlation was observed, in one case, even in the
 lower blood lead  level range.  Selander  and
Cramer132 noticed that if lead workers were divided
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into two groups, those with blood lead levels below
and above 40 /u,g/dl, two different linear correlation
slopes  could be derived, although  with  a lesser
degree of correlation than the exponential relation-
ship derived from the entire group. As cited in the
NAS  publication,2  studies from  Chisholm's
laboratory showed a similar exponential correlation
between blood lead level and urinary 8-ALA is 51
children aged 1 to 5 having blood lead levels rang-
ing between 25 and 75 /ug/dl. In 55  adolescents with
blood  lead  levels ranging  from  8  to  40  /^g/dl,
however, no clear correlation could be observed. It
appears that apart from this last observation (which
is  restricted to adolescents, the  great majority of
whom had blood lead  levels in a very narrow range:
14 to 24 /tg/dl). all other studies reported show a
clear exponential increase in 8-ALA  urinary excre-
tion with increase in blood lead. These observations
parallel the reported  exponential inhibition of the
enzyme 8-ALAD and  indicate that this is one of the
earliest effects of lead on heme synthesis.
   The urinary excretion of 8-ALA does not exceed
the normal  range (0.6 /ig/dl) until the blood  lead
level reaches 40 jug/dl. The normal range, however,
is  derived  from values obtained from individuals
with blood lead levels up to 40 /^g/dl. It is apparent
that if 8-ALAD were  inhibited by lead without any
threshold of  concentration  and  if  8-ALA were
similarly affected, the definition of a  normal range
of 8-ALA  excretion  for individuals  with a blood
lead level less than 40 /u.g/dl would be ambiguous at
best.  Some of the discrepancies  reported  in  the
literature could  in  part reflect the larger variability
of 8-ALA urinary excretion  in comparison  with
erythrocyte 8-ALAD. In a detailed study by Alessio
et al.123 of 169 males with blood  lead levels ranging
from 5 to 150 /ng/dl, the correlation between blood
lead and 8-ALAD was much greater than with urin-
ary 8-ALA. For these  reasons and because of the un-
certainty of defining a normal range, it is generally
accepted that urinary 8-ALA becomes clearly ab-
normal at blood lead levels greater than 40 /Ag/dl. It
has been postulated that there may be an excess of 5-
ALAD activity, so that normal 8-ALA metabolism
is still sustained by even  50-percent-inhibited
enzyme at  blood lead levels near 40  /ig/dl. Above
this value, however, the inhibition results in func-
tional  impairment  and clear accumulation of 8-
ALA, and increased  urinary excretion may be ob-
served. A recent study suggests  that ALA may, in
fact, be  toxic systemically.  The relative contribu-
tions from decreased  utilization of ALA, as a result
of ALAD inhibition and the derepression of ALA-
synthetase, to urinary levels of ALA at blood levels
at which excretion is significant  cannot be deter-
mined at this time.

11.4.3.2  EFFECTS  ON  IRON INSERTION  IN
PROTOPORPHYRIN
  The accumulation of  protoporphyrin in the
erythrocytes of humans  with  lead  intoxication has
been known since the 1930's.135 Its use as an indica-
tor of lead  body burden, however, has been limited
by the  technical difficulties  associated with the
measurement of protoporphyrin by solvent partition
and spectrophotometry.  In 1972, the development
of a simpler and more accurate technique, combin-
ing simplified extraction and fluorometry, made the
measurement of protoporphyrin a  widely used and
accessible test.136 As discussed in Chapter 9, several
modifications  of  this  technique have  been
developed, including an  instrument  that measures
protoporphyrin by direct fluorescence in  capillary
blood samples without any extraction or manipula-
tion of the  blood sample.
  Accumulation  of protoporphyrin  in  the
erythrocytes is the result of decreased efficiency  of
iron  insertion into protoporphyrin, the final step in
heme  synthesis, which takes place  inside the
mitochondria. When this step is blocked by the effect
of lead,  large amounts of protoporphyrin without
iron  accumulate  in the erythrocyte,  occupying the
available heme pockets in hemoglobin. Hence, pro-
toporphyrin,  rather than heme, is incorporated  in
the  hemoglobin molecule  where it  remains
throughout the  erythrocyte life span (120 days).
  The accumulation of  protoporphyrin  in  lead
poisoning  is  different  from that  observed  in
erythropoietic  protoporphyria,  a congenital  dis-
order in which excess protoporphyrin is produced
after heme synthesis is complete. In that case, the ex-
cess of protoporphyrin formed (as a result  of a con-
genital defect in  ferrochelatase) is attached to the
surface of hemoglobin at a site that bridges the  a-
and /3-chains of hemoglobin.137-138 Because this type
of  bond  to  hemoglobin  is  very  loose  in
erythropoietic  protoporphyria,  protoporphyrin
diffuses through the plasma into the skin  where it in-
duces photosensitivity. In  lead intoxication, on the
other hand, the  protoporphyrin  in hemoglobin is
bound more firmly to the heme pocket; hence,  no
diffusion into the plasma occurs and no photosen-
sitivity  is  observed, despite  extremely  elevated
erythrocyte protoporphyrin levels.
  An additional  important difference between the
increased protoporphyrin  level in the erythrocytes
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of persons with lead intoxication and erythropoietic
protoporphyria is the fact that only in the former is
the center of the protoporphyrin molecule occupied
by zinc.139 This difference is probably caused by the
different affinity for zinc of protoporphyrin in the
heme pocket. In lead intoxication, then, the largely
prevalent species is zinc protoporphyrin, whereas in
erythropoietic protoporphyria it is an  unchelated
protoporphyrin base. These two compounds differ in
fluorometric spectra and the two conditions may be
easily distinguished by spectrofluorometry.140 Zinc
protoporphyrin, attached  in the  heme pocket  of
hemoglobin, is also the prevalent species observed in
iron  deficiency, another condition  in which an in-
creased level of protoporphyrin is  observed in the
erythrocytes.
  Accumulation  of protoporphyrin  in  the
erythrocytes in lead poisoning indicates a failure of
the last step of heme synthesis. This  could result
either from a direct effect of lead on ferrochelatase
itself or  from an effect of lead on mitochondrial
membranes of erythroid tissue in bone marrow,  with
consequent  failure  of iron transport.  The latter
mechanism would make iron, one  of the two  sub-
strates of ferrochelatase, less available to enzyme ac-
tion, with subsequent accumulation of the unutilized
substrate, protoporphyrin IX.
  Interference  by  lead  with  the  mitochondrial
transport of iron in the normoblast appears to be the
most  likely mechanism underlying the  increased
level protoporphyrin in the erythrocytes. Four facts
support this statement: (1) iron accumulation within
the erythrocyte  is diminished by the  presence  of
lead, whereas iron incorporation into heme  is com-
pletely  inhibited;  (2)  lead  is  deposited  on   the
mitochondrial membrane, where it produces  pro-
found  ultrastructural changes;  (3)  iron transport
through  the  mitochondrial  membrane  is   ac-
complished by both energy-dependent and  energy-
independent  mechanisms   that  are  impaired  by
lead;141  and  (4) in  iron  deficiency  (when  fer-
rochelatase activity is normal but iron is scarce) zinc
protoporphyrin bound in  the heme pocket is  ac-
cumulated,  whereas  in  erythropoietic  pro-
toporphyria  (when iron  is normal  but  ferro-
chelatase activity  is decreased142'143) free pro-
toporphyrin base loosely attached to the hemoglobin
surface is formed.
  Experimental  evidence from  animal  studies  and
epidemiologic  human   studies,  using  intact
mitochondria, have demonstrated the failure of iron
incorporation into protoporphyrin in the presence of
lead. These studies cannot clarify whether the effect
of lead is exerted on the enzyme itself or on overall
mitochondrial  function.  It  is  possible  that
mitochondrial transport of iron and ferrochelatase
are both affected by lead.
  The effect of lead on iron incorporation into pro-
toporphyrin is not limited to  the normoblast and/or
to the hematopoietic system. Formation of the heme-
containing protein, cytochrome P450, which is an in-
tegral  part  of  the  liver  mixed-function  oxidase
system, may also be inhibited  by lead.144 Accumula-
tion of protoporphyrin in the presence of lead has
been shown  to occur also  in cultured cells of chick
dorsal root  ganglion, indicating that inhibition of
heme synthesis takes place in the neural  tissue as
well.145 These observations, and the fact that lead is
known to disrupt mitochondrial structure and func-
tion, indicate that the lead  effect on heme synthesis is
exerted in all  body cells, possibly with  different
dose/response curves holding for effects in different
cell types. On the other hand, it must be noted that
increased  levels of  protoporphyrin  in  the
erythrocyte reflect an accumulation of substrate and
therefore  imply  a functional  alteration  of
mitochondrial function in  the same way that the in-
creased urinary excretion of urinary 8-ALA implies
impairment. In other words,  if a reserve activity of
ferrochelatase exists, such  as has been suggested for
8-ALAD, accumulation of protoporphyrin  in the
erythrocytes indicates that this has been hampered
by the lead effect to the point that  the substrate has
accumulated. For these reasons, as well  as for its im-
plication of  the  impairment of mitochondrial func-
tion, accumulation of protoporphyrin has been taken
to indicate  physiological  impairment  relevant  to
human health.146
  The elevation of erythrocyte protoporphyrin was
shown to be exponentially correlated  with blood
lead level by PiomelU in a  study of 90 children,
covering the blood lead level range from 5 to 90
Mg/di.147 In  a later study  of  1038  children,  568 of
whom  had  blood lead   levels greater  than 40
/n'g/dl,148 this correlation was confirmed, and it was
clearly shown that all  children  with  blood  lead
levels greater than 60 /^g/dl  had erythrocyte pro-
toporphyrin  greater than 250 /xg/dl red blood cells
(RBCs). Kamholtz et al.149 and Sassa et al.15° also
showed a similar degree of correlation and indicated
that a value of 140 jug FEP/dl RBC's would appear
to be a more appropriate cut-off point for screening
children  for lead poisoning.  This  value, also sug-
gested  by McLaran  et  al.,151  was  accepted by
Piomelli  et al.,152 who indicated that more than 70
percent of children with a  blood lead level of 40 to
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49 jug/til have erythrocyte protoporphyrin in excess
of this value. Several additional studies have con-
firmed the exponential  correlation between  blood
lead  and  erythrocyte  protoporphyrin  in  chil-
dren 140,153-156 and in lead workers. 123.133.140,157,158

  Sassa et al.150 demonstrated that a better correla-
tion  was  observed  between  blood  lead  and
erythrocyte protoporphyrin in children with a steady
blood lead level. This finding suggested that  a sig-
nificant part of the scatter observed when blood lead
is  correlated to erythrocyte protoporphyrin on  a
random basis  is the result of fluctuations of lead
caused by day to day variation and experimental er-
ror.
  Lamola et al.140 demonstrated that the slope of
elevation of erythrocyte  protoporphyrin versus
blood lead is steeper in  children than in adult lead
workers.  This observation was confirmed  by  Roels
et  al.159  who also demonstrated that the slope  of
elevation is similar in children and females. Reigert
et al.160 and Levi et al.161 also demonstrated that an
elevation of erythrocyte protoporphyrin  can predict
which  children tend  to increase their  blood lead
level and suggested that erythrocyte protoporphyrin
is  a more valuable  indicator  of  childhood body
burden of  lead than the blood  lead level itself.  In
adult workers, the elevation of erythrocyte pro-
toporphyrin was shown to correlate with blood lead
level, ALAD, ALA-U, and the duration  of exposure
to  lead.158  Chisholm  et  al.162 suggested that  in
children  erythrocyte porphyrin  is a better indicator
of overexposure to lead than blood lead. In addition
to being  elevated  in lead intoxication,  erythrocyte
protoporphyrins may also be elevated in iron defi-
ciency, but to a  lesser degree. Several studies have
indicated that erythrocyte protoporphyrin  levels are
an excellent indicator of the body iron store164-165
and that these levels may also be used  to discrimi-
nate between the microcytic anemia of iron deficien-
cy (where they are elevated) and of thalassemia trait
(where they are normal).166-'68
  These observations and the data collected on over
300,000  children screened by both erythrocyte pro-
toporphyrin and blood lead in New York City were
the basis for the statement by the Center for Disease
Control (CDC) in which an elevation of erythrocyte
protoporphyrin above 60 /ug/dl of whole blood in
the presence of a blood lead level above 30 /tig/dl
were  indicated as cut-off points for the  detection of
childhood lead poisoning.146
  Most  studies  on the  relationship  between
erythrocyte protoporphyrin  and  blood lead  have
focused on persons (children or adult workers) with
markedly  elevated blood  lead.  Some  studies,
however,  have shed light on  the  threshold  level
below  which no  effect  is observed. In a study of
children with blood lead levels over the range of 20
to 40  jug/dl, Sassa et  al.lso  could not detect  any
threshold  effect.  Data  from  Roels et  al.,159 who
studied 143 school children having blood lead levels
ranging from  5  to  40 /*g/dl, indicate  a threshold
effect at blood lead  levels between 1 5 and 20 ng/dl.
In a study by Piomelli et al.l69of 1816 childien aged
2 to 12 years (median  age 4.7 years), the threshold
for no effect of  blood  lead  on erythrocyte proto-
porphyrin was estimated to be 15.5 /xg/dl, using both
probit  analysis  and segmental curve-fitting  tech-
niques.
  Because an  elevation of erythrocyte  pro-
toporphyrin is caused also by iron deficiency, it is
important to take into consideration the iron state of
the population under study in any evaluation of the
relationship of this hematological index to  lead ex-
posure. No information is available with regard to
the iron state of the population studied by  Sassa et
al.150 In the Roels  study,159 similarly, no direct
measurements of the  iron  status  were obtained;
however, the children studied ranged in age from 10
to 15 years, a group in which iron-deficiency anemia
is uncommon. Moreover, the differences  in blood
lead were clearly  related to living near or away from
lead-emitting smelters. There is no reason to believe
that the children who live near a smelter should have
lower iron  stores  than the children who live in rural
areas. Also, in the same study, it must be noted that
the hematocrit of the children living in the rural area
was slightly  but  significantly lower than  the
hematocrit of  the children living near the  smelter;
therefore,  if anything,  the prevalence of  any iron
deficiency  may  have  been  greater  in the rural
children (with the lowest EP) than in the children
living near the smelter (with the highest EP). These
facts suggest that iron-deficiency anemia was not a
factor in the elevation of erythrocyte protoporphyrin
observed in this study, but that  this EP increase was
directly related to lead. In the  study of Piomelli et
al.,169 an analysis  of children aged 2 to 4 years versus
children older than 4 years failed  to show  any
difference  in the  EP/blood lead  relationship. This
indicates that iron-deficiency  anemia, which is much
more prevalent in the younger children, did not in-
fluence the EP  response. Moreover,  in the same
study, the iron stores were measured in children with
blood  lead levels < 15 /Ag/dl and in children with
blood lead levels of 15 to 28 /wg/dl and no difference
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was observed. It appears, therefore, that the effect of
the lead on EP, which is extremely well documented
at the much higher blood lead level, occurs also in
children with  blood lead levels between  15 and 28
  These studies  consistently demonstrate that  an
elevation of erythrocyte protoporphyrin, which indi-
cates physiological impairment of heme synthesis
and mitochondrial function, can  be detected  in
children at a blood lead level  that is  well  below
levels  normally  encountered   in  screening  pro-
cedures.

 1 1.4.4 Other Hematological Effects

  The effects of lead on 8-ALAD and on iron incor-
poration in protoporphyrin are  the best known. In
lead intoxication, however, other abnormalities of
heme synthesis are observed. These include  an  in-
creased activity of 8-ALA synthetase,170 which may
result  by derepression,  according to the scheme of
negative feedback control proposed by Granick and
Levene.171 In vivo inhibition of coproporphyrinogen
and uroporphyrinogen decarboxylases in rabbits172
and inhibition  of uroporphyrinogen I synthetase173
have been reported.  On the other hand,  no ac-
cumulation of porphobilinogen has been  observed in
humans. An  increased excretion of coproporphyrin
in the urine of lead workers and children with lead
poisoning is  well known. Urinary  coproporphyrin
has been used extensively as a clinical indicator of
lead poisoning. It is not known, however, whether
this effect results from  specific  enzyme inhibition,
from upstream accumulation of substrate secondary
to  inhibition of iron  incorporation  into  proto-
porphyrin, or from both; or, alternatively, whether it
is expressed  as a disturbance   of  coproporphyrin
transport through  the  mitochondrial  membrane.
Similarly, no  data  are available  to establish a
threshold blood lead  level below which no excess
coproporphyrin excretion in the  urine takes place.
  Besides the  effect of lead on heme synthesis,
hemoglobin synthesis may also be impaired because
of inhibition  by lead of  the synthesis of globin (the
protein  moiety of hemoglobin).  Kassenar et al.174
showed impairment of globin synthesis.  This work
was confirmed by the results of Wada et al.170 White
and  Harvey175  showed a decreased synthesis of a
chains compared to /3 -globin chains. Recently, Ali
et al.176 have  shown an effect on  globin synthesis in
vitro on human reticulocytes at lead concentrations
as low as 1O6 M, which corresponds to a  blood lead
level of 20 /ig/dl.
 11.4,5  Summary of Effects  of  Lead  on  the
 Hematopoietic System
   A  number of  significant  effects  on  the
 hematopoietic system in humans have been observed
 in lead poisoning. These effects are prominent in
 clinical lead poisoning, but they are still present to a
 lesser degree even in persons with lower body bur-
 dens  of lead.
   Anemia is a clinical fixture of lead  intoxication. It
 results from both increased erythrocyte destruction
 and  decreased hemoglobin synthesis. Erythrocytes
 are microcytic and have abnormal osmotic fragility
 as a  result of direct effect of  lead  on  the  cell
 membrane, and show basiphilic stippling caused by
 the  inhibition  of pyrimidine-5'-nucleotidase.
 Erythrocyte survival time  is  shortened, and  this
 results in  hemolysis.
   In children, a threshold level for anemia is about
 40 /nd Pb/dl,  whereas the  corresponding value for
 adults is about 50 /^,g Pb/dl.
   Lead interferes with hemoglobin synthesis  by in-
 hibiting synthesis of the globin moiety and affecting
 several steps in the synthesis of the heme molecule.
 Most sensitive to lead in the heme synthetic pathway
 is the activity  of the enzyme 8-ALAD,  a zinc-acti-
 vated enzyme  that mediates the conversion of  two
 molecules of 8-ALA into prophobilinogen. Inhibi-
 tion of this enzyme results in increased plasma levels
 and urinary excretion of 8-ALA.  Lead also inhibits
 the  last  step  (incorporation   of iron  into  pro-
 toporphyrin), which takes place in the mitochondria,
 probably  by  interference  with the  mitochondrial
 transport  of iron and coproporphyrin.  This  effect
 results  in the accumulation  of  coproporphyrin,
 which is  excreted  in the urine,  and  of pro-
 toporphyrin, which is retained in the erythrocytes, in
 the heme molecule. The overall effect of lead is a net
 decrease in  heme  synthesis,   which  in  turn
 derepresses the enzyme involved in the first step of
 heme synthesis, 8-ALA synthetase.
   Inhibition of 8-ALAD  occurs  at  extremely  low
 blood lead levels and  has been shown to start at a
 blood lead level of 10 /xg/dl. The resultant increased
 urinary 8-ALA excretion also starts at a very  low
 blood lead level and becomes pronounced at a blood
 Ieadlevel240ju,g/dl.
  The precise  threshold for coproporphyrin excre-
tion is not well established. It is probably similar to
the threshold for  8-ALA. but it is less specific. An
 increase in erythrocyte protoporphyrin occurs at a
threshold  blood  lead  level of  approximately 16
      in children. In  adult females, the threshold is
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probably similar. In adult males, the threshold is
probably slightly  higher  (20 to  25 /ug/dl).  The
threshold for increase in 8-ALA synthetase is not es-
tablished, but increases have been noticed at blood
lead levels of 240/ug/dl.
  Although  doubt exists as to the health-effects sig-
nificance of 8-ALAD inhibition, increased urinary
8-ALA excretion above 40 /ug/dl is accepted as an
effect probably  reflecting  physiological  impair-
ment.2 Elevation of erythrocyte protoporphyrin has
the same implication of physiological impairment in
vivo as is found in urinary 8-ALA. Also, because
elevation of erythrocytic protoporphyrin  indicates
impairment  of  mitochondrial function, it is  con-
sidered of greater physiological  relevance.177 For
these reasons, the consensus of clinicians who partic-
ipated in the preparation of the statement in 1975 by
CDC together  with  the  American Academy  of
Pediatrics was that this finding should be used as an
indicator of a  significant and  worrisome  body
burden of lead.
11.5  EFFECTS  OF LEAD  ON  NEURO-
PHYSIOLOGY AND BEHAVIOR
  Neurological and  behavioral  deficits have  long
been recognized as some of the more severe conse-
quences of toxic exposure to lead.178-'82 What levels
of lead exposure are necessary to produce specific
deleterious neurological or behavioral effects and
whether such effects are reversible, however,  have
been controversial  medical issues extensively de-
bated since the early 1900's. Much of the impetus for
debate on   the subject  has  been  generated by
progressively increasing medical concern over an
evolving  scientific literature  that has  consistently
suggested, as more information is gained,  that lead
exposure levels previously accepted as harmless are
actually sufficient to cause significant neurological
or behavioral impairments. At present it is generally
accepted  that, at toxic, high levels of lead  exposure
that produce blood lead levels greater than  80  to
100 ^ig/dl,  a person is at unacceptable risk for the
occurrence of the clinical  syndrome of  fulminant
lead encephalopathy.  This  syndrome  includes
neurological and other  symptoms of such severity
that immediate medical attention and, frequently,
hospitalization  is demanded  in  order to  avoid ir-
reversible neural damage  or  death. The  risk in-
volved is unacceptable because of the  unpredic-
tability of the symptoms observed at high blood lead
levels.  Based  on  the literature reviewed  below,
it  now also appears that  lower levels of lead ex-
posure, yielding blood levels below 80 /u.g/dl, pro-
duce much less well-defined but  medically signifi-
cant  neurobehavioral deficits in  apparently
asymptomatic adults and children, that is, in the ab-
sence of the neurological  symptoms or other signs
that typify acute lead intoxication requiring immedi-
ate clinical treatment.
  The range of lead exposures necessary to produce
the more subtle, subclinical neurobehavioral deficits
is difficult to estimate with certainty and remains a
matter of  considerable controversy.  There is some
evidence reviewed  below  that suggests that  such
effects may occur at blood lead levels even as low as
30 to 40 /u.g/dl, whereas certain other negative find-
ings  suggest the  lack of neurobehavioral effects at
blood lead levels less than  80 /ng/dl. In an effort to
estimate the exposure levels necessary for manifesta-
tion  of the full range of neurobehavioral effects of
lead, the present  discussion will critically review the
literature dealing with the obviously  toxic effects of
high level lead exposures and with the more subtle
neurobehavioral effects associated with  lower ex-
posure levels.
  The relevant  literature  on the neurobehavioral
effects of lead has been derived from  studies of both
humans and other  mammalian species. Such effects
have  been  indexed by  means of a  variety  of ap-
proaches, including: (1) the assessment of structural
neuropathology  by  classical  histological  and
ultrastructural analyses of morphological damage;
(2) the analysis of altered neurochemical parameters
or processes by various biochemical  assays; (3) the
assessment of altered electrophysiological responses
in both the central and peripheral nervous system;
(4) the assessment of neurobehavioral effects both by
neurological  examinations and  diverse  types  of
behavioral testing  methods; and (5)  the assessment
of alterations in neuropharmacological responses
affecting many of the types of variables assessed by
the other approaches. The effects of toxic, high-level
exposures to lead  have been well documented  by
most of these approaches. At lower-level exposures,
however, the demonstration of lead effects by any of
the above  types of assessments has been complicated
by several other  methodological considerations that
should be noted as  a prelude to any critical review of
the literature.
  Data about lead exposure have been obtained via
two  basically different methods, epidemiological
and  experimental. Unfortunately,  these
methodological  techniques are  highly  correlated
with  the species studied;  that is, epidemiological
techniques,  with their  unique problems,  provide
most human  data,  and experimental techniques are
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used  to  provide most nonhuman data. Although
epidemiological studies  have immediate environ-
mental relevance at the human level, there are often
difficult  problems associated with interpretation of
the findings. With epidemiological studies, the exact
parameters of the most recent exposure level, the
duration of any level of exposure, and the mode of
intake usually cannot be  entirely  known. Similarly,
any  previous  lead  levels and  exposure durations
usually cannot  be definitively established. It is also
possible  that other variables that were highly corre-
lated with the presence of environmental lead, such
as  socioeconomic  level, previous behavioral  or
neurological  damage, etc., are responsible for the
effects observed rather than lead exposure alone.
There is a  need  for appropriate  and  sensitive
measures of exposure effects, especially when testing
for low-level effects for which  less-than-dramatic
neurobehavioral deficits can be expected. Neverthe-
less,  the  contribution of lead  exposure  to any
neurobehavioral deficit(s) can  be reasonably  esti-
mated with proper  controls for many of the above
extraneous factors.
  Obviously such parameters as exposure levels and
durations can be defined  with much more precision
in experimental studies carried out in  the laborato-
ry. Unfortunately, however, appropriate experimen-
tal designs are  frequently lacking. In  addition, en-
vironmental relevance of experimental laboratory
data is limited by  two major considerations.  The
most  serious of these is  the fact that nonhuman
models are, of necessity, typically used for the estab-
lishment  of dose-response curves,  and  it is  well
known that a large species difference  exists in sen-
sitivity to lead,52 so that adequate nonhuman ex-
posure models are  difficult  to  devise.  A second
problem  is that animal experiments frequently use
doses of lead much higher than would be expected to
occur in the environment. Besides the question of ex-
posure levels, experimenters  must attend to proper
experimental controls for possibly reduced nutrition
levels because of food palatability, if  the delivery
system is  via food or water; effects of altered mater-
nal behavior, if the delivery is via the mother's milk
or the placenta,  etc. Further, if central nervous
system (CNS)  alterations  are  noted,  it is  often
difficult to separate damage caused by direct versus
indirect effects  on  neural tissue.  Again, despite the
above   difficulties,  useful  data  on  the
neurobehavioral effects of lead have been obtained
through animal studies, with  potential  implications
for understanding human exposure effects.
  Key variables that have emerged in  determining
the effects of lead on the nervous system include (1)
the duration and intensity of exposure and (2) age at
exposure. In  reference to age at exposure, evidence
exists for greater  vulnerability of the developing
nervous  system in the young  than of the  fully
matured nervous system in adults. Particular atten-
tion will, therefore, be accorded to the discussion of
the neurobehavioral effects of lead in children as a
special group at risk.
11.5.1 Human Studies
11.5.1.1 EFFECTS  OF  HIGH-LEVEL  LEAD
EXPOSURES
  The severely deleterious effects of exposures to
high levels of lead, especially for prolonged periods
that produce overt signs of acute lead intoxication,
are by now  well documented  in  both  adults and
children. The most profound effects that occur in
adults are referred to as the clinical syndrome of
lead  encephalopathy, described  in  detail by
numerous investigators.183'186 Early  features of the
syndrome that may develop within weeks of initial
exposure include dullness,  restlessness, irritability,
poor  attention  span,  headaches, muscular tremor,
hallucinations, and loss of memory. These symptoms
may  progress  to  delirium,  mania, convulsions,
paralysis, coma, and death. The onset of such serious
symptoms can often be quite abrupt, with convul-
sions, coma, and even death occurring very rapidly
in  patients  that  shortly  before were  apparently
asymptomatic  or  exhibited  much  less  severe
symptoms  of  acute  lead  intoxication.185-187
Symptoms of encephalopathy similar to  those  that
occur in  adults have been reported to  occur in in-
fants  and  young  children,85,90,185,188,189 wjth  a
markedly  higher  incidence  of severe  en-
cephalopathic symptoms and deaths occurring in
them  than in adults.  This  may reflect the greater
difficulty in recognizing early  symptoms in young
children  that allows  intoxication  to proceed  to  a
more  severe  level  before treatment  is  initiated. In
regard to the  risk of death in children, the mortality
rate for prechelation therapy period encephalopathy
cases  was approximately  65  percent.190 Various
authors have  reported the following mortality  rates
for  children experiencing lead encephalopathy since
the  inception of chelation therapy as the standard
treatment approach: Ennis and Harrison,191 39 per-
cent;  Agerty,192 20 to 30 percent; McKhann and
Vogt,189 24 percent; Mellins and Jenkins,193 24 per-
cent; Levinson and Zeldes,194  19 percent; Tanis,195
18 percent; and Lewis  et al.,19 5 percent. These data,
as well as other data tabulated more recently,2 indi-
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cate that once lead poisoning has progressed to the
point of encephalopathy a life-threatening situation
clearly exists and, even with medical intervention, is
apt to result in a fatal outcome.
  The morphological findings in cases of fatal lead
encephalopathy  vary.'97'199  On  macroscopic  ex-
amination  the  brains  are  often  found  to be
edematous and congested. Microscopic  findings of
cerebral  edema, altered capillaries (endothelial hy-
pertrophy and hyperplasia), and a perivascular glial
proliferation are often noted. Neuronal damage is
variable and may be caused by anoxia. In some cases
gross and microscopic changes are minimal.198 The
neuropathologic findings as reported are essentially
the same for adults and children. Lead encephalopa-
thy is considered  by  some to  be primarily  a
vasculopathy, with the  encephalopathy reflecting
perturbed blood-brain barrier function;198'199 that
is, damage to  neuronal elements may be secondary
to lead effects on the vascular system. Evidence for
such effects has been advanced by Pentschew.198
  Pentschew198 described neuropathology findings
for 20 cases of acute lead encephalopathy in infants
and young children. The most common finding was
activation of intracerebral capillaries characterized
by dilation of the capillaries with swelling of the en-
dothelial cells. Diffuse astrocytic proliferation in the
gray and white matter  was also present. According
to  Pentschew, this  proliferation  is the  earliest
morphological response  to  an  increase  in  per-
meability of the blood-brain  barrier (dysoria).
  Concurrent with  the  dysoric alterations  were
changes that Pentschew198  attributed to
hemodynamic disorders. These  ischemic  changes
were manifested as cell  necrosis,  perineuronal in-
crustations, or neuronophagia (loss of neurons). The
isocortex and the basal ganglia  were areas of pre-
dilection for the ischemic changes. Pentschew con-
cluded that the structural changes in infantile lead
encephalopathy  are a  mixture  of dysoric and
hemodynamic parenchymal alterations.  In  the
cerebellum, which in a restricted  sense is the pre-
dilection  area of damage, the changes are purely
dysoric.
  In addition to producing the above effects on the
CNS, lead also clearly causes damage to peripheral
nervous systems (PNS) of both man  and animals at
toxic, high  exposure levels.  The PNS changes in-
volve predominantly the large  myelinated motor
fibers.200 Pathologic changes in the  PNS consist of
segmental demyelination and in some fibers, axonal
degeneration.200 The lead effect appears to be in the
Schwann  cell, with concomitant disruption of the
myelin membranes.201 Remyelination has been ob-
served in animal studies, suggesting  either that the
lead effect  may be reversible or that not all of the
Schwann cells are affected equally.201 Reports of pes
cavus deformities  resulting  from  old peripheral
neuropathies in  humans,202 however,  suggest that
lead-induced  neuropathies  of  sufficient severity
could result in permanent peripheral  nerve damage.
Morphologically,  the neuropathy is charac-
teristically  detectable only after prolonged or high
exposure to lead  or both; data from experimental
studies indicate  that there are distinctly different
sensitivities among different species.
  Perhaps  of even greater concern than the occur-
rence of fatalities are the neurological sequelae that
occur  in cases of  severe  or prolonged nonfatal
episodes  of lead encephalopathy  that  are
qualitatively quite similar to those seen with many
types of traumatic or infectious cerebral injury, with
the occurrence of  permanent  sequelae being more
common in children than in adults.85-90.193 The most
severe sequelae in children are cortical atrophy, hy-
drocephalus, convulsive seizures, and severe mental
retardation.85-90-193 More subtle sequelae also occur,
such as impaired motor coordination, altered senso-
ry perception, shortened attention span, and  slowed
learning. These latter effects have been reported in
children with known high  exposures to lead but
without a  history  of the  life-threatening forms of
acute  encephalopathy.85'86-91'203 Of historical in-
terest here  in relation to the extremely slow progress
in recognizing the full consequences of lead intox-
ication is the fact that, although many cases of child-
hood lead  poisoning had been  reported  since the
early 1900's,180~182 it was several decades before the
work  of McKhann and  Vogt189 and Byers  and
Lord85 called attention to the long-term irreversible
neurobehavioral sequelae of acute lead intoxication.
  Establishing precise threshold values for lead ex-
posures necessary to produce the above acute intox-
ication symptoms or sequelae  in humans is difficult
in view of the usual inaccessability of extensive data
on  environmental lead levels  contacted by the vic-
tim, the period of exposure, or the body burdens of
lead existing prior to the manifestation of clinically
significant  symptoms. Nevertheless, enough infor-
mation is available to allow for reasonable estimates
to be made regarding the range of blood lead levels
needed to produce acute encephalopathic symptoms
or  death.  According to  Kehoe204'206 blood  lead
levels well in excess of 120 /u,g/dl are usually necess-
ary to produce such deleterious irreversible effects
for adults. Recurrent bouts of lead  intoxication in
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 the absence of acute encephalopathy may also lead
 to progressive mental deterioration. Other data ex-
 ist, however,187 that suggest that acute lead intoxica-
 tion,  including severe gastrointestinal symptoms or
 signs of encephalopathy or both, can occur in adults
 at lead levels somewhat less than 100 /ug/dl; but am-
 biguities in these data make interpretation difficult.
   The data on  threshold levels for children  indi-
 cate that lower blood lead levels have been  asso-
 ciated with the occurrence of acute encephalopathy
 symptoms and death. Probably  the most  extensive
 compilation of information bearing on this point is a
 summarization187  of  data from  the  work  of
 Chisholm84-207 and Chisholm and Harrison.90  That
 data compilation relates the occurrence of acute en-
 cephalopathy and death in children in Baltimore to
 blood lead levels determined by the Baltimore City
 Health  Department (dithizone method) between
 1930 and 1970. Elevated blood lead levels associ-
 ated with asymptomatic cases or less severe signs of
 acute lead   poisoning  were also  tabulated.
 Asymptomatic increased  lead absorption was ob-
 served at blood levels ranging from  60 to 300 ^tg/dl
 (mean  =   105  /itg/dl).  Acute lead  poisoning
 symptoms, other than signs of encephalopathy,  were
 observed from approximately 60 to 450 /itg/dl (mean
 =  178  fj.g/d[). Signs of mild encephalopathy (hy-
 perirritability, ataxia, convulsions)  and severe en-
 cephalopathy  (stupor, coma, convulsions repeated
 over a 24-hr period or longer) were associated  with
 blood lead levels of approximately 90 to 700 or 800
 Aig/dl, respectively (means =  328  and  336 ^ig/dl,
 respectively). The distribution of blood  lead levels
 associated with death (mean = 327 ^g/dl) was es-
 sentially the same as for levels yielding either  mild
 or severe encephalopathy. These data suggest that
 threshold blood lead  values for death in children are
 essentially identical to those for acute encephalopa-
 thy and that such effects are manifested in children
 starting at blood lead levels of approximately 100
 /itg/dl. Other  evidence  reviewed below, however,
 suggests that the threshold for acute  encephalopathy
 effects in the most highly susceptible children may,
 in some rare instances, be  somewhat lower than the
 100  /ng/dl  figure arrived at on the basis  of the
 Baltimore data compilation presented above.
  Occasionally appearing  in the literature since the
 1930's are scattered reports  of acute lead encepha-
 lopathy or death  occurring in  children  at what
were formerly considered to be moderately elevated
blood lead levels. For example, Cumings185 listed
 references to studies  on acute lead encephalopathy
that appeared from 1938 to 1956. Several of the re-
 ports purportedly demonstrated acute encephalopa-
 thy in children at blood lead levels even down to 30
 to  50  ^tg/dl.  Detailed  analyses  of the  articles
 referenced, however, indicate  that the actual data
 reported in most did not clearly associate such low-
 level exposures  to the occurrence  of acute en-
 cephalopathy symptoms. Still, cases in at least some
 of  the  referenced  articles and in other  reports
 reviewed  below suggest  that acute encephalopathy
 occurred  in a few children at blood lead levels
 below 100  /Ltg/dl. Again, the  ambiguities  in  these
 data  regarding confirmation of lead  exposure and
 elimination of alternative etiological factors make
 interpretation difficult. A further precaution has to
 do with the analytical  methods themselves  in terms
 of using good methods with skilled personnel.
   In  1938,  Gant208 reported on five cases  of acute
 lead  encephalopathy in  children under  2  years of
 age. Blood lead levels of 60 and 80 /u,g/dl, as well as
 190,  240,  and 320 ^g/dl,  were obtained  for the
 different children upon first admission to the hospi-
 tal. All five had convulsions.  Smith187 listed a 3-
 year-old female patient as having a blood lead level
 of 60 /ig/dl at the  time  of  acute lead intoxication
 from paint ingestion, followed by death attributed to
 plumbism 2 days after a 70 jug/dl reading  was ob-
 tained during a period  when only mild symptoms of
 lead poisoning were present.  In 1956, Bradley et
 al.209 reported  that 19 children under 5 years old
 from  a low income area of Baltimore were found to
 show CNS   symptoms  that included  irritability,
 lethargy, or convulsions at blood lead levels below,
 as well as above, 100 /u,g/dl.  Eight children who had
 been previously classified as asymptomatic and who
 had blood lead levels of 50 to 80  p,g/dl  were later
 hospitalized  during the  study210 for  treatment of
 acute lead encephalopathy; blood lead levels at the
 time of later hospitalization were not reported but
 were  likely further elevated. Other  data  are re-
 ported2" on 10 children  from a low-income area of
 Providence, Rhode  Island who were selected at 4 to
 8 years of age for a follow-up investigation of possi-
 ble long-term  neurobehavioral deficits resulting
 from earlier acute encephalopathy episodes. Blood
 lead assays obtained at the time of the initial hospi-
talization  of the children  because of  acute  en-
cephalopathy symptoms  (4 out of 10  had  convul-
sions, 8 out of 10 had ataxia, 7 out of 10 had drowsi-
ness, and 6 out of 10 had irritability) yielded max-
imum blood lead values that averaged 88 ±  S.D. 41
/ttg/dl. Because  individual cases were not described,
however, no clear  association  between  particular
lead intoxication symptoms and specific blood lead
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levels can be established. Overall, the above reports
suggest that at  least some children — perhaps
especially inner-city children less than 4 years old —
 may be vulnerable to acute encephalopathy at blood
lead levels of 80 to 100 /ng/dl.
  From the preceding discussion, it can be seen that
severity of symptoms  varies widely  for different
adults or children as a function of increasing blood
lead levels. Some show irreversible CNS damage or
death at levels less than 100 /ug/dl, whereas others
may not show any of the usual clinical signs of lead
intoxication even at blood lead  levels in the 100 to
200 /ug/dl range.  This difference may be caused (1)
by individual biological variation in susceptibility to
lead effects; (2)  by  changes in  blood lead values
from the time of initial damaging intoxication; (3) by
better tolerance  for a gradually accumulating lead
burden; or (4) by any number  of other  interacting
factors, such as nutritional state or inaccurate deter-
minations of blood lead. In  any case, in  attempting
to estimate exposure levels for adverse health effects
of lead, the range of exposure levels yielding damag-
ing effects to the most susceptible individuals needs
to be emphasized rather than any  average  level  at
which such effects are seen. For adults, it would ap-
pear that the most susceptible individuals do not ex-
hibit  acute encephalopathy  symptoms until blood
lead  levels  of  100 /ug/dl   are  reached or,  more
typically, are substantially  exceeded. In regard  to
children, the majority of cases showing acute en-
cephalopathic symptoms have blood lead levels of
 100 ^tg/dl or more. For a very few cases, levels as
 low as 80 jug/dl  have been  reported.

 11.5.1.2 EFFECTS OF LOW-LEVEL LEAD EX-
POSURES
   Also of  great  relevance  for  establishing  safety
limits for exposure to lead is the question of whether
exposures lower than those producing symptoms of
overt  acute intoxication may  exert  more  subtle,
subclinical  neurobehavioral effects in  apparently
asymptomatic adults or children. Attention has been
focused in particular on whether exposures leading
to blood lead levels in the 30 or  40 to 80 /xg/dl range
may lead to neurobehavioral deficits in  the absence
of any classical  signs of lead encephalopathy. The
 literature on this subject is somewhat limited and
controversial but still  allows for certain statements
to be made about the possible hazard of low  to
moderate lead exposure levels.
   If  such  neurobehavioral  deficits  occurred  in
adults with great frequency,  one might expect this to
be reflected by higher rates of absences or reports of
neurologically  related  symptoms among  occupa-
tionally exposed  lead  workers.  Some  recent
epidemiological studies have  investigated  possible
relationships between  moderately elevated blood
lead levels and general health as indexed by records
of sick absences that have been certified by physi-
cians. No correlation between elevated blood lead
levels and  sickness rates or types of symptoms re-
ported were found212 for groups of workers in a lead
storage battery factory from high-, medium-, and
low-exposure areas versus control  workers in nonex-
posure areas of the same plant. It should be noted,
however, that mean blood lead levels for workers in
the three exposure groups were 60, 50, and 42 /J.g/d\,
respectively, compared with 45  /ug/dl for the so-
called  nonexposure control  group,  rendering the
conclusions of the report of dubious value. Similar
negative findings were reported by Robinson213 for
tetraethyl-lead  (TEL)  workers having  mean blood
lead values of 43 fj.g!dl and daily urinary excretion
of 0.089 mg of lead per liter urine over an 8- to 10-
year period (3 to 4 times the rate for control group).
Data on sickness rates were based  on a retrospective
study of records over a 20-year period. Absence or
sickness reports, however, are probably not sensitive
enough measures to detect subtle neurobehavioral
symptoms.
  Only a few studies have employed more sensitive
psychometric and neurological testing procedures in
an effort to demonstrate subclinical  lead-induced
neurobehavioral  effects  in adults.  For example,
Morgan and Repko214 reported preliminary results
of an extensive study of behavioral functions in 190
lead-exposed workers  (mean  blood  lead level  =
60.5 ±  17.0 /ug/dl). I" 68 percent of  the subjects,
blood lead was <80 ju.g/dl. The majority of the sub-
jects were  exposed between  5 and 20 years. The
authors examined 36 nonindependent  measures of
general performance and  obtained 44  measures of
sensory, psychomotor,  and psychological  functions.
Initial data analysis suggested that blood lead levels
correlated  with several reaction-time measures, and
8-ALAD changes correlated with effects on hand-
eye coordination. This study, therefore,  suggested
that  below  a blood lead level of 80  pig/dl some
behavioral changes did occur in  adult workers.  In
addition, variability of performance increased with
increasing  blood  lead  level;  however,  only during
period  of high-demand performance did a worker's
capacity  clearly  decrease as a result  of lead ex-
posure.  Unfortunately, aspects of the Morgan and
Repko   work  can be criticized  because  of
methodological  problems, including reported  ap-
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paratus failures  during  testing of subjects. Also,
findings analogous to those reported by Morgan and
Repko were not obtained in a similar study215  that
found no differences between control and  lead-ex-
posed workers on a number  of psychometric  and
other performance tests.
   In addition to the above study213 suggesting possi-
ble CNS dysfunctions, numerous investigations have
provided  electrophysiological data indicating  that
peripheral neuropathy symptoms are associated at
times with blood  lead  values  <  80 /Ltg/dl.   As
reviewed  by Seppalainen,216  reductions  in  nerve
conduction  velocities  and  electromyographic
deficits  have been observed in patients with known
lead  poisoning  but  without clinical neurological
symptoms.217-219  More  recently,  such peripheral
nerve deficits were established by Seppalainen220 for
lead workers whose blood lead levels were as low as
50 ng/d\  and had never  exceeded 70 /ng/dl during
their entire exposure period (mean = 4.6 years), as
determined by regular monitoring. Similar results
were obtained in a study by Melgaard et al.221 on au-
tomobile mechanics exposed to TEL and other lead
compounds in  lubricating and high-pressure oils.
Results  of a multielemental analysis of the worker's
blood  for lead, chromium,  copper,  nickel,  and
manganese indicated a  clear association  between
lead exposure and peripheral nerve damage. Half of
the workers (10 of  20)  had  elevated blood  lead
levels  (60 to  120  /ig/dl) and  showed  definite
electromyographic deficits. Mean blood lead level
for the control  group was 18.6 /^ig/dl. Melgaard et
al.221  reported additional results on associating lead
exposures with polyneuropathy of unknown  etiology
in 10 cases from the general  population. Another
study reported  recently by Araki et al.222 provides
further  confirmation of the  Seppalainen220  and
Melgaard et al.221 findings in that evidence for  pe-
ripheral neuropathy effects were reported for lead-
industry workers with blood lead values of 29 to 70
/ug/dl. The very  low blood lead levels, below 50
Mg/dl, reported  in  some of  the  above  studies,
however,  should  probably be  viewed with caution
until further confirmatory data are reported on sam-
ples of  larger  size using  well  verified blood assay
results.
  In  summary,  the  above  studies, when  taken
together, appear to provide reasonably strong  evi-
dence that subclinical peripheral neuropathies occur
in some  adults having blood lead levels in the 50 to
70 ftg/dl range. Furthermore,  although it could be
argued that substantially  higher lead body burdens
existing  before the time of some of the studies were
actually responsible for producing the neuropathies,
it appears that in at least one case220 blood levels al-
ways below 70  /tg/dl  were  sufficient  to cause
peripheral  nerve  dysfunctions. That study  by
Seppalainen220 was also generally methodologically
sound, having been well controlled for the possible
effects of extraneous  factors  such as temperature
differences at the nerve conduction velocity assess-
ment sites. On the other hand, it should be noted that
the data reported for control subjects were obtained
at an earlier time (1971 to 1973) than data for the
lead exposed subjects (early 1973); and no blood
lead levels were reported for the control subjects.
Still, when the Seppalainen220 results are viewed col-
lectively with the data from other studies reviewed
above, strong evidence appears to exist for  periph-
eral neuropathies occurring in  adults at blood lead
levels of 50 to 70  /xg/dl or, possibly,  at even lower
levels.
  In addition to suspected neurobehavioral effects
of relatively low-level lead exposures  in  adults,
there is an  increasing concern that  low-level ex-
posures producing blood lead levels of 40 to  80
jug/dl (or even less) in children may  induce subtle
neurological  damage, especially to the very young
developing CNS. This issue has attracted much at-
tention and generated considerable controversy dur-
ing the past decade. The evidence for and against the
occurrence of significant neurobehavioral deficits at
relatively low levels of lead exposure is, at this time,
quite mixed  and largely interpretable only  after a
thorough critical review of  the  methodologies
employed in each of the various important studies on
the subject.
  One  of the  major approaches  that  has  been
employed is the retrospective analysis of lead levels
existing in populations of apparently asymptomatic
children that are then divided into nonexposed con-
trol  and one or more lead-exposed  experimental
groups  for comparisons of their performance  in
various neurological and psychometric tests. A few
studies have  been  followed by subsequent  further
reevaluation  of the same children by the same in-
vestigators in an effort to assess whether indications
of continuing neurobehavioral impairment still ex-
isted. Among the major studies that have employed
this  basic approach  and that are widely cited  in
regard to this  issue,  those of de la Burde and
Choate,223'224 Perino  and Ernhart,225 Albert  et
al.,226 and Landrigan et  al.227 suggest significant
effects of asymptomatic, low-level lead exposure. In
contrast, the studies of Kotok,228 Lansdown et al.,229
and  McNeil et al.230 report  generally  negative
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results. Two other studies, one by Landrigan et al.231
and one by Kotok et al.,232 although not reporting
clearly statistical iy significant differences between
moderately lead-exposed  and control subjects,
nevertheless report certain findings that are  highly
suggestive of a relationship between  moderate lead
exposure and cognitive impairment.
  Among the several studies presenting evidence for
CNS deficits being associated with blood levels of
less than 80 /xg/dl  are the work of de la Burde et
al.223.224 an(j perino and  Ernhart.225De la Burde et
al.22^ observed dysfunctions of the CNS, fine  motor
dysfunction,  impaired  concept  formation,  and
altered behavioral profile in 70 preschool children
exhibiting pica and elevated blood lead levels (in all
cases above 30 /xg/dl, mean =  59 Mg/dl)  in com-
parison to matched control subjects not engaging in
pica. In a follow-up study on the same children (at 7
to 8 years old), de la  Burde224  reported further
confirmation  of continuing CNS  impairment as
assessed by a variety of psychological and neurologi-
cal tests. This was despite the fact that many of the
blood lead levels of the  lead-exposed children had
by then dropped significantly from the  initial study.
In general, the de la Burde et al.223-224 studies appear
to be methodologically sound, having many features
that strengthen the case for the validity  of their find-
ings. For example, there were appreciable numbers
of children (67 lead-exposed and 70 controls) whose
blood lead values were obtained in preschool years
and who were  old enough (7 years) during the
follow-up study to cooperate adequately for reliable
psychological  testing. The  specific psychometric
tests employed were well standardized and accepted
as sensitive indicators of minimal brain damage, and
the neurobehavioral  evaluations were carried out
blind, that is,  without the evaluators  knowing which
were control or lead-exposed subjects
  The  de la Burde223-224 studies might  be criticized
on several points, none of which in the final analysis
provide  sufficient  grounds for rejecting their
validity.  One difficulty  is that blood lead  values
were not determined for control subjects in the in-
itial study, but the lack of history of  pica, as well as
tooth lead analyses done  later for the follow-up
study,  render it very improbable that appreciable
numbers of lead-exposed subjects might have been
wrongly assigned to the control group.  Also,  results
indicating  no measurable  coproporphyrins  in the
urine of control subjects  at the time of initial  testing
further help to confirm proper assignment of those
children to the nonexposed control group. A second
point of criticism addresses the probably inappropri-
ate use of multiple chi-square statistical analyses in
the manner employed to analyze the results of the
study. Upon recomputation of the statistical signifi-
cance of observed differences, by means of the more
appropriate Fisher's exact probability test and ac-
counting for the number of tests conducted, several
measures originally reported to be  statistically sig-
nificant still turn out to be significant at p <0.05 or
lower. One last problem  relates to ambiguities in
subject  selection that complicate interpretation  of
the full meaning of the results obtained. Because it is
stated  that  the  lead-exposed  group  included
children with blood lead levels of 40 to 100 /Ag/dl,
or of at least 30 p.g/dl  with "positive radiographic
findings of lead lines  in  the  long  bones, metallic
deposits  in the  intestines, or both," the reported
deficits  might be readily  attributed to  blood  lead
levels  as  low   as  30  /ig/dl.  Other evidence,101
however, suggests that such a simple interpretation
may not be completely accurate. That is, the work of
Belts et al.101 indicates that lead lines are usually not
seen unless blood  levels exceed 60 figldl for most
children at some  time  during exposure, although
some (approximately 25  percent)  may  show  lead
lines at blood lead levels of 40 to 60  /Lig/dl.  Vir-
tually none have lead lines at levels  below 40 /ug/dl.
In view of this, the de la Burde results probably can
be  most reasonably interpreted  as demonstrating
lasting neurobehavioral deficits at blood lead levels
in excess of 50 to 60 /xg/dl.
  Similar  conclusions  are also warranted  on  the
basis of results of the Perino and Ernhart study,225
which  demonstrated  a  relationship between
neurobehavioral deficits and blood lead levels rang-
ing from 40 to 70 /ug/dl in a group of 80 inner-city
preschool black children.  One of the  more interest-
ing aspects of the findings, is that the normal correla-
tion of .50 between parent's intelligence and that of
their offspring was found to be reduced to only .10 in
the lead-exposed group, presumably because of the
influence  of another  factor  (lead) that interfered
with the normal intellectual development  of the
lead-exposed children. Many of the methodological
virtues of  the de la Burde  studies223-224 were also
present  in the  Perino  and Ernhart225  work, and
blood lead determinations and statistical analyses
appeared  sound. About  the  only  alternative  ex-
planation for these results  might be differences in the
educational backgrounds  of the parents of the con-
trol subjects when compared with lead-exposed sub-
jects, because parental  education level was found to
be significantly negatively related to the blood lead
levels of the children  participating  in  this study.
                                                11-20

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 Parents of children in  the lead-exposed group had
 significantly poorer educational backgrounds than
 the control group parents. The  importance of this
 point lies in the fact that several other studies233'235
 have demonstrated that  the  higher  the parental
 education level, the more rapid the development
 and the higher the intelligence quotients (I.Q.'s) of
 their children. It is nevertheless  interesting that the
 de la Burde studies and the Perino and Ernhart work
 point to essentially the same  conclusion, i.e., that
 neurobehavioral deficits occur at blood lead levels
 possibly as low as 40 ju,g/dl. Also, in both cases, the
 children studied were from inner-city, low-income
 areas.
   Two  other studies with positive findings had, for
 the most part, some serious methodological  limita-
 tions. Albert et  al.226 found that  asymptomatic
 children (5 to 15 years old) whose blood lead levels
 at an earlier age were  elevated (> 60 Aig/dl) later
 had significantly more mental disorders and  poorer
 school performance than a control group with lower
 lead  levels in both blood and deciduous teeth. Un-
 fortunately, however, no assay of the lead burden, in
 either blood or teeth, was done for about one-half of
 the children in the control  group; and no significant
 effects were reported for children with lead levels <
 60 (tig/dl. Also, another major criticism is that some
 children in the  control group had relatively high
 blood lead levels (> 40 /ng/dl). In another study,
 Landrigan et al.227 found that  asymptomatic, lead-
 exposed children living near a smelter scored signifi-
 cantly lower than matched controls on measures of
 performance I.Q. and finger-wrist tapping. The con-
 trol children in  this study  were,  however, not well
 matched by age or sex  to  the  lead-exposed  group,
 although it should be pointed out that  results re-
 mained statistically significant  even after appropri-
 ate adjustments were made for  age  differences.
   In another relevant study, presented in a doctoral
 dissertation   by  Rummo,211 significant
 neurobehavioral deficits were found (hyperactivity,
 lower scores on McCarthy  scales of cognitive func-
 tion,  etc.) for children who  had  previously ex-
 perienced high levels of lead exposure that had pro-
 duced acute lead encephalopathy. Mean maximum
 blood lead levels for those children at the time of en-
cephalopathy were 88 ± S.D.  40  ^g/dl. Children
with  moderate degrees  of blood  lead  elevation,
however, were not significantly different from con-
trols on any measure of cognitive functioning, psy-
chomotor performance, or hyperactivity. On the
other hand, if the data for performance on the
McCarthy  General Cognitive  Index  or several
 McCarthy Subscales are plotted graphically, as in
 Figures  11-2 and  11-3, then a rather interesting
 relationship between  test performance and  levels
 and duration of lead exposure becomes apparent.
                 SHORT-TERM  LONG-TERM ENCEPHALOPATHY

                  DEGREE OF LEAD EXPOSURE
 Figure 11-2. McCarthy General Cognitive Index scores as a
 function of degree of lead exposure.211
                     T
I
                   MOTOR
                   PERCEPTUAL
                   VERBAL
                   MEMORY
                   QUANTITATIVE
                 SHORT-TERM  LONG-TERM  ENCEPHALOPATHY
                  DEGREE OF LEAD EXPOSURE
 Figure 11-3. Scores on McCarthy Subscales as a function of
 degree of lead exposure.211
  Although the scores for short-term moderate-ex-
posure subjects are essentially the same as  control
values, an interesting  aspect is that the scores  for
long-term  moderate-exposure subjects  consistently
fall below those for control subjects and lie between
the latter  and the encephalopathy group  scores.
Thus, it would appear that long-term moderate lead
exposure may, in  fact,  exert subtle neurobehavioral
effects. This might be  shown to be statistically sig-
nificant by means of other  types of analyses or if
larger samples were assessed. It should be noted that
(1)  the maximum blood lead levels for the short-
term and long-term exposure subjects were all >40
                                               11-21

-------
jiig/dl (means  = 61  ±  S.D.  7 and 68 ± S.D. 13
jug/dl,  respectively), whereas control  subjects all
had blood lead levels below 40 jug/dl (mean = 23 ±
S.D. 8 fig/d\); and (2) the control and lead-exposed
subjects were inner-city (Providence, Rhode Island)
children well matched for  socioeconomic  back-
ground, parental education  levels, incidence of pica,
and other pertinent factors.
  A somewhat similar pattern of  results emerged
from a more recent study by Kotok  et al.232 in which
36  Rochester, New  York,  control group children
with blood lead levels < 40  /ug/dl were  compared
with 31  asymptomatic children having distinctly ele-
vated blood  lead levels (61  to 200 /zg/dl). Both
groups were well matched on important background
factors, including, notably, their propensity to ex-
hibit pica. Again, no clearly statistically  significant
(p  <.05) differences between the  two  groups were
found on a number of different tests of cognitive and
sensory functions.
  As indicated, however, by  test  results from the
Kotok et al. study232 presented in Table 11-3, the
mean scores of the control-group children were con-
sistently higher than those of the iead-exposed group
for all six of the ability classes listed.  Also, in one
case the level of significance achieved  borderline
significance (.10 >p >.05), a pattern of results that
hints at a trend existing toward lower ability levels
for the lead group.  The authors cautiously  stated
that "the data do not prove that these children have
sustained no neurologic damage by lead" and that
"later  longitudinal testing  may demonstrate cogni-
tive or educational  deficiencies."  They  also  indi-
cated that "evaluation of behavior,  neurologic, or
motor functioning was not carried out"  and noted
that "subtle cognitive and fine motor changes were
demonstrated in an extensive and  carefully con-
trolled evaluation of asymptomatic children resid-
ing in the vicinity of an El Paso  lead smelter."227
They go on to imply that the earlier exposure to lead
in infancy of the El  Paso children  and their longer
period  of exposure (mean  =  6.6  years versus  < 3
years for the Rochester group) might account for the
disparity  in results .between the two studies. Their
results, on the other hand, plus the pattern seen in
the Rummo2" study, can be  construed as evidence
consistent with the  findings  of the de  la  Burde
studies223'224 and others reviewed above that report
results  linking low to moderate levels of lead ex-
posure  to significant behavioral impairments.
  Other studies have produced mixed or negative
results in attempts to determine whether  a relation-
ship exists between  lead exposure  and  CNS deficits
 TABLE 11 -3. COMPARISON OF TEST RESULTS IN LEAD
            AND CONTROL GROUPS"?
Ability class
Social maturity
Spatial
Spoken vocabulary
Information-
comprehension
Visual attention
Auditory memory
Group
Lead
Control
Lead
Control
Lead
Control
Lead
Control
Lead
Control
Lead
Control
Mean 1 Q
123 5 ±
126 3 ±
92.0 ±
100 8 ±
91 7 ±
92 9 ±
945 ±
963 ±
897 ±
93.3 ±
93 0±
999 ±
± SD
227
177
180
187
139
137
149
166
183
230
240
320
Significance
P>
.10 >p >
p>
p >
p >
p>
.10
.05
10
.10
.10
.10
using various standardized psychometric techniques,
neurologic examinations,  and ratings  by  teachers,
parents, or experimenters. For example,  Kotok228
reported  earlier  that  developmental  deficiencies
(using  the Denver  Development  Screening  test,
which is a somewhat insensitive measure of develop-
ment) in a group of  asymptomatic children having
elevated lead levels (58 to 137 /ug/dl) were identical
to those in a control group similar in age, sex, race,
environment, neonatal condition, and presence of
pica, but whose blood lead levels were lower (20 to
55 /u,g/dl). The deficiencies could be correlated with
inadequacies  in  the children's  environment.
Children in the lead-exposed group, however,  had
blood lead levels as high as 137 /ug/dl, whereas some
of the controls had blood lead levels as high as 55
/*g/dl. Thus, the study was in effect a comparison of
two  groups with  different degrees  of elevation in
lead exposure rather than one of lead-exposed ver-
sus  nonexposed control children.
  In several studies of children living in the vicinity
of smelters or factories, significant neurobehavioral
effects  have typically not been found  at moderate
elevations  of blood lead  levels.   For   example,
Lansdown et al.229  found a relationship  between
blood lead level in children and  the distance they
lived from lead-processing facilities, but no rela-
tionship between blood lead level and mental func-
tioning was found. Only a minority of the lead-ex-
posed sample had  blood lead levels over 40 /^ig/dl,
however, one would  not expect a striking relation-
ship between mental  functioning and lead levels be-
low such a level.
  In an extensive, generally thorough study, McNeil
et al.230 found that a sample of children living near a
lead smelter in El Paso was comparable medically
                                               11-22

-------
and  psychologically  to matched  controls  living
elsewhere in the same city other than in the direct
effects of lead  (blood lead level, free  erythrocyte
protoporphyrin levels, and X-ray findings).  Lead-
exposed children in the group living near the smelter
did, however, have  significantly different per-
sonality  test  results,  which were  ascribed by the
authors as being due to recent upheaval in  the lives
of the lead-exposed children who had been recently
forced to move from the vicinity of the smelter. Con-
siderable community  unrest existed  at the time of
both the McNeil et al. study230 and the  work of
Landrigan  et al.227 on the El Paso smelter area
population, which grew out of circumstances associ-
ated with the discovery of the lead  exposures and
disposition of legal matters surrounding them. The
impact of the extraneous unrest on both studies has
tended to cloud interpretation of the true meaning of
their respective results  which in turn have become
quite controversial. See Appendix E for more infor-
mation. The personality test results of the McNeil et
al.230 study could nevertheless have been caused by
the  effects of lead on the  exposed group. Also,  it
should be noted that a few suggestive trends toward
statistical significance for  certain interactions be-
tween lead and  age of subjects (p  <.10) were re-
ported  for  some  of the cognitive-function  test
measures.
  Based on the above  results, the authors of the
Lansdown et al.229 and the McNeil230 papers con-
cluded that  no evidence was found  for the occur-
rence of neurobehavioral effects at subclinical lead
exposure levels in their studies. Perhaps that conclu-
sion could be generalized to suggest that no signifi-
cant CNS deficits typically  occur as a  result of
subclinical,  low to  moderate lead exposures of
children living  in the vicinity of smelters or other
lead-processing facilities.  To the extent that those
children may  differ  in significant  ways from the
inner-city children shown by  de la Burde,223-224
Perino  and  Ernhart,225  and  Albert226  to  have
neurobehavioral impairments at blood lead levels as
low as 40 to 50 /tg/dl,  ambiguous results from the
smelter children are not necessarily contradictory to
the  better established findings of significant  CNS
effects  for  inner-city  children.  Furthermore,  it
should be noted that reports of peripheral neuropa-
thies for both  populations of  children at low to
moderate lead exposure levels, as described, may in-
dicate that both groups are at significant risk for at
least that type of neural tissue damage.
  An additional approach, different from the  basic
strategy employed in the above  studies,  has been
 utilized in other studies in an effort to demonstrate
 that low or moderate blood lead levels cause signifi-
 cant neurobehavioral  deficits. This approach  con-
 sists of identifying populations of children with diag-
 nosed  neurobehavioral deficits of unknown etiology
 and assaying blood lead or making other assessments
 in order to link past lead exposures to the children's
 present neurobehavioral impairments. Thus, for ex-
 ample, efforts have been made to implicate moder-
 ate or  low level lead exposures as a causative factor
 in at least some cases of  hyperactivity of unknown
 etiology. The possibility that such low-level lead ex-
 posures induce hyperactivity has gained credence
 through the well documented87'203 fact that hyperac-
 tivity  is one of the frequent  neurobehavioral se-
 quelae observed in children who survive episodes of
 acute encephalopathy resulting from high-level lead
 exposures. The  evidence for and  against  the  hy-
 pothesis that low-level lead exposures produce hy-
 peractivity has been accumulating at  a  rapid rate
 during the past  few years and has generated  con-
 siderable  controversy on the subject. Only a few of
 the more  salient findings are viewed below and in
 the section on animal studies (Section  11.5.2).
   In a case-control study, David et al.236 compared
 the incidence of elevated blood lead levels in five
 groups of children: (1) a pure hyperactive group
 with no apparent cause for hyperactivity; (2) a group
 of hyperactive children with a highly probable cause
 of hyperactivity, e.g., prematurity; (3) a group of hy-
 peractive  children with a possible cause; (4) a group
 of children who had recovered from lead poisoning;
 and (5) a  nonhyperactive control group. Pure hy-
 peractive   children  had  statistically  significantly
 higher blood lead  levels (mean =  26.2 ±  8 ^ig/dl)
 than controls (mean =  22.2 ± 9.6 /ug/dl), whereas
 children with a highly probable cause did not (mean
 = 22.9 + 6.6 ^ig/dl). Similarly, the pure hyperactive
 children tended to excrete more lead than controls
 or probable cause hyperactives when given a single
 d®se of penicillamine. Although the causal relation-
 ship between lead exposure and hyperactivity cannot
 be said to be proved by this study, the data of David
 et al.,236 when placed with findings of hyperactivity
 in children known to  have  recovered from   lead
 poisoning and numerous animal studies demonstrat-
 ing alterations in  motor activity following lead ad-
 ministrations, might be interpreted as supporting the
 hypothesis that  a relationship  between moderate
 lead exposure and altered motor activity exists.
  On the other  hand, several other points argue
against acceptance of such a thesis at this time. For
one thing, the David et al.236 study itself and the
                                               11-23

-------
author's conclusion* can be questioned on several
bases. In that study, for example, the closeness of the
match  of  subjects in  the five groups on  variables
other than age and sex is not clearly specified by the
authors. Also,  the  interpretation of differences in
blood lead levels in the 7-to-8-year-old children is
fraught with numerous problems, not the least of
which is the fact that such levels are probably not
very accurate indices of long-past lead exposures
that presumably  occurred  during preschool  years.
Many factors in the interim between presumed lead
exposure and assay for lead could affect the results,
including  possible differentially higher incidences of
pica in the hyperactive children than in control sub-
jects. Klein et al.237 have noted that pica may be part
of certain behavioral syndromes that exist even in
the absence of lead exposure, but that would pre-
dispose the  affected child toward more lead  inges-
tion by virtue of the habit's presence. Indeed, there is
evidence that among  mentally subnormal children
whose mental deficiency can be definitely attributed
to etiologies other than lead poisoning that there is
both a high incidence of pica and moderately  ele-
vated blood lead.238 Last, it should be noted  that a
number of other investigators,211,227.229,230,239 wno
expressly  looked for  evidence of lead-induced hy-
peractivity  as  part  of  their  screening  for
neurobehavioral deficits associated with blood lead
levels as low as 40 /xg/dl, failed to find any signifi-
cant effects that support  the  thesis that  low-level
lead exposures induce hyperactivity. Thus,  even
though  the  hypothesis  is  intriguing and  certainly
worthy of further investigation, it cannot be stated at
this time that sufficient evidence exists to establish
hyperactivity as a neurobehavioral deficit clearly as-
sociated with low or moderate lead exposures.
  In addition to the above data bearing on possible
links between subclinical lead  exposures and the in-
duction of hyperactivity, certain recently reported
data240 provide evidence implicating  increased
heavy  metal absorption, including  lead uptake, in
the etiology  of  learning  disabilities.  More
specifically, children  identified for other classifica-
tion purposes as having learning disabilities were
found to have significantly elevated levels of lead, as
well as cadmium and some other metals, in their hair
when compared with control children not classed as
learning disabled. In fact, a discriminant function
analysis yielded 98 percent accuracy in classifying
children as normal or learning disabled based on a
combined factor of cadmium,  cobalt,  manganese,
chromium,  and lithium levels. Lead was not  in-
cluded in this five-metal discriminant function, since
its predictive value was well served by cobalt and
cadmium because of a significant negative correla-
tion between lead and cobalt (r = .67;p <.01)and a
significant  positive correlation  between  lead  and
cadmium (r =  +  .53; p  <.01). Unfortunately for
present purposes, no  blood lead levels or possible
past  exposure  histories  were  provided  for the
children in the above study.240
  Other recent  studies analogous in basic approach
to that employed by  David et al.236  and Pihl  and
Parkes240 have provided intriguing new information
tending to  link prenatal lead exposures to the later
development of mental retardation.  For example,
Beattie et  al.241 identified 77 retarded children and
77  normal children matched  on age,  sex,  and
geography. The residence during the gestation of the
subject  was identified, and  a first-flush morning
sample oft-" water was obtained from the residence.
Of 64 matched pairs, no normal children were found
to come from homes served with water  containing
high lead levels (>800 /xg/liter), whereas 11 of the
64 retarded children  came from homes served  with
water containing high lead levels. The authors  con-
clude that pregnancy in a home with high lead in the
water supply increases by a factor of  1.7 the risk of
bearing a  retarded child.
  In a follow-up to the Beattie study, Moore et al.242
obtained lead  values from  blood  samples drawn
during the second  week of life and stored on filter
paper. These samples had been obtained as part of a
routine phenylketonuria screening study and were
kept on file. Blood samples were available for 41 of
the retarded and 36  of the normal children in the
original study by Beattie. Blood lead concentrations
in the  retarded children  were significantly higher
than values measured in  normal children. Mean
blood   lead  for  retardates was   1.23  ±  0.43
jtMol/liter (25.5 ± 8.9 /ug/dl) and for normals was
1.0 ±   0.38  /LtMol/liter  (20.9 ±  7.9 fj-gldl).  The
ditterence  in lead  concentrations were  significant
(p = 0.0189) by the Mann-Whitney test.
  These two studies suggest that lead exposure to the
fetus during the critical period of brain development
may cause perturbations in brain organization that
are expressed later in  mental retardation syndromes,
and they raise  for careful scrutiny the risks of in-
trauterine exposure to lead. Insufficient information
exists, however, to allow estimation of the levels of
lead exposure of pregnant women that might cause
those prenatal effects in the fetus that may result in
later neurobehavioral impairments.
  One last adverse effect of lead on neural function
in children remains to be considered,  and that is the
                                                 1-24

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possible  induction  of peripheral  neuropathies by
low-to-moderate lead exposures. It is generally ac-
cepted that lead-induced peripheral  neuropathies,
although frequently  seen in adults after prolonged
exposures,  are extremely rare in children. Several
articles243'245 in the literature, however, do describe
case histories that confirm the occurrence of lead-in-
duced peripheral  neuropathies,  as  indexed by
electromyography, assessments of nerve conduction
velocity, and observations of other overt neurologi-
cal  signs, such as tremor, wrist and foot drop, etc.
Some of these frank neuropathic effects have been
observed for several cases at blood lead levels of 60
to  80 yug/dl,245  and in  other  cases  peripheral
neuropathy was associated with blood lead values of
30 jotg/dl; however, in the latter  cases, lead lines in
long bones suggest probable past exposures leading
to prior blood lead levels at least as high as 40 to 60
fj.gldl and probably in excess of 60 /^ig/dl (based on
the data of Belts et al.101)- In each of the present  case
studies, there was reported some,  if not complete,
recovery of affected motor functions after treatment
for lead poisoning. Further, it should be noted that a
tentative association has been hypothesized between
the existence of sickle cell disease and increased risk
of peripheral neuropathy as a consequence of child-
hood  lead exposure. Most of the cases reported in-
volved inner-city black children, several with sickle
cell trait. In summary, it appears that  (1) evidence
for  frank peripheral neuropathy  in children  cer-
tainly exists; (2) such neuropathy can be associated
rather well with blood lead levels at least as low as
60 /xg/dl; and (3) evidence suggests that inner-city
children  with sickle cell disease may be at  special
risk.

  Further  evidence  for  lead-induced  peripheral
neuropathies in children is provided by the data of
Landrigan et al.231 derived from  a study of children
living in close proximity to a smelter in Idaho.  The
nerve conduction velocity results from this study are
presented in Figure 11-4 in  the form of a scatter
diagram relating  peroneal nerve  conduction
velocities (NCV) to blood lead levels in the children
studied. No clearly pathologic conduction velocities
were  observed,  although a statistically significant
negative correlation  was found between peroneal
NCV and blood lead levels (r =  0.38, p <.02 by
one-tailed t test). These results, therefore, provide
evidence for significant slowing of nerve conduction
velocity  and,  presumably,  advancing  peripheral
neuropathy as a function of increased blood  lead
levels. The data do not allow for clear statements to
be made regarding any threshold for  a  pathologic
slowing of NCV.
         —I	1	1	1	1	1	1	1	r-
         Y (CONDUCTION VELOCITY) = 54 8 - 045 x (BLOOD LEAD)
       _ Ir = -038) (n = 2021
5  672°
O
O  5160 -
   6200
   5680 -   •
      0   15   30   45   60  75  90  105  120  135   150
                     BLOOD LEAD, MB/dl
Figure 11-4. Peroneal nerve conduction velocity versus blood
lead level, Idaho, 1974.231
11.5.1.3 SUMMARY AND CONCLUSIONS FOR
HUMAN STUDIES
  Rather than simply recapitulating in briefer form
the findings  reviewed above, an  attempt will  be
made here to integrate information derived from the
review and to focus on certain key issues concerning
the impact of lead on human  neurobehavioral func-
tions. Among the key  points to be addressed are: (I)
the internal exposure levels, as indexed  by  blood
lead  levels,   at   which   various   adverse
neurobehavioral effects occur; (2) the reversibility
of such deleterious effects; and (3) the population(s)
that appear to be most susceptible to neural damage.
  Regarding the  first issue,  it would appear  from
data reviewed above  that surprisingly low levels of
blood lead can, at times, be associated with the most
extreme effects of lead poisoning, including severe,
irreversible brain damage as  indexed by the occur-
rence of acute or chronic encephalopathy symptoms
or death or both. For most adults, such damage does
not occur until blood lead levels well in excess of
120 ftg/dl  are  reached. Evidence does  exist,
however, for the  occurrence  of acute encephalopa-
thy and death in some adults at  blood lead levels
somewhat below  120  pig/dl. For children, the effec-
tive blood lead levels for producing encephalopathy
or death are  lower,  typically starting  at approx-
imately 100 /Ltg/dl. Again,  however, good evidence
exists for the occurrence of encephalopathy in some
at lower levels, i.e., 80 to 100 fj.g/d\.
                                                11-25

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  It should be emphasized that once encephalopathy
occurs death is not at all an improbable outcome,
regardless  of the  quality   of  medical  treatment
available at the time of any acute crisis. In fact, cer-
tain diagnostic or treatment procedures themselves
tend  to exacerbate matters  and push the outcome
toward fatality if the nature and  severity of the prob-
lem are not fully recognized  or are misdiagnosed. It
is also crucial to note the rapidity with which acute
encephalopathy symptoms or death can develop in
apparently asymptomatic individuals  or in  those
only apparently mildly  affected by  elevated body
burdens  of  lead.  It  is  not  unusual  for  rapid
deterioration to occur,  with convulsions or  coma
suddenly appearing and  progressing to death within
48 hr. This strongly suggests that even in apparently
asymptomatic  individuals  rather  severe neural
damage probably does exist at high blood lead levels
even though  it  is not yet overtly manifested in ob-
vious encephalopathic symptoms. This tends to be
borne out by studies showing that children having
high blood lead levels (over 80 to 100 /ttg/dl), but
not  observed to  manifest  acute encephalopathy
symptoms, are  permanently, cognitively impaired,
as are individuals who survive acute episodes of lead
encephalopathy.
  Other evidence tends to confirm that some type of
neural damage does exist in  asymptomatic children,
and not necessarily only at very high levels of blood
lead. The body of studies on low- or moderate-level
lead effects on neurobehavioral functions,  as sum-
marized in Table 11-4, present  overall a rather im-
pressive array of data pointing to that  conclusion.
Several well-control led  studies have found effects
that  are  clearly statistically  significant,  whereas
others have  found nonsignificant  but borderline
effects. Even some  studies reporting generally non-
significant findings at times contain data confirming
statistically significant effects, which the authors at-
tribute to various  extraneous factors. Another way
to look at the situation  is to consider that elevated
blood lead level is the single common factor extant
in all of the  groups showing significant behavioral
deficits in  the different studies. It  should also be
noted that, given the'likely subtle nature of some of
the behavioral  or  neural effects probable at  low
levels of lead exposure, one would not expect to find
striking differences in every instance.  The  blood
lead levels associated with neurobehavioral deficits
in asymptomatic children appear to be in excess of
50  to  60  Atg/dl. Great   uncertainties  remain,
however,  as to whether these exposure levels (ob-
served blood lead  levels) represent the levels that
were  responsible for the  behavioral  deficits  ob-
served. Monitoring of lead exposures in the subjects
has in all cases been highly intermittent during the
period of life preceding the behavioral assessment.
In most cases, only one or two blood lead values are
provided per subject.
11.5.2 Animal Studies
  Pentschew and  Garro52  initially described  an
animal  model  of lead  encephalopathy in  which
morphological changes occurred similar to those re-
ported in  children. Neonatal rats were exposed to
lead by feeding mothers a diet containing 4 percent
lead carbonate. The lead was then transmitted to the
suckling young via the  mothers'  milk. Between 23
and 29 days  of age, 90  percent  of  the  animals
developed  paraplegia lasting  no  longer  than  2
weeks. Eighty-five to 90 percent of the paraplegic
animals died during this period.
   Neuropathological examination of these animals
revealed capillary  activation, glial  proliferation,
areas of transudation, and  spotty hemorrhages, pri-
marily in the cerebellum and the striatum. The white
matter of the cerebral hemispheres, especially the
corpus collosum, was also involved,  though to a
lesser extent.  Ischemic neuronal  changes  in  focal
distribution were  rare  and were localized  in the
cerebral cortex. Pentschew and Garro52 concluded
that the lead encephalopathy of the suckling rat was
caused by  a disorder in the  permeability of the
capillaries, resulting in dysoric encephalopathy. The
suckling rat therefore differs from the human in that
the  latter  shows a  mixture of both  dysoric  and
hemodynamic alterations.  Further verification of
the dysoric nature of lead encephalopathy  in the
suckling rat was provided by Lampert  et al.,53 who
used either  colloidal thorium  dioxide  (Thorotrast)
or  Trypan Blue, neither of which normally pene-
trates  the  blood-brain  barrier.  In suckling  rats
poisoned with 4 percent lead carbonate,  however,
both  Thorotrast and Trypan  Blue were  found to
penetrate the striatum and  cerebellum.

  Since the initial  description by Pentschew  and
Garro,52 lead  encephalopathy  in the rat  has been
replicated  by Thomas et al.246  Michaelson  and
Sauerhoff,247and Krigman and Hogan.248

  Clasen et al.249 reported lead encephalopathy in
juvenile Rhesus monkeys exposed to 0.5 g of lead
per  day  for  6 to  18  weeks.  They  reported
morphological changes similar to those occurring in
humans, which consisted of edematous changes in
the cerebellar and subcortical white matter. Diffuse
                                               11-26

-------
            TABLE 11 -4. SUMMARY OF RESULTS OF HUMAN STUDIES ON NEUROBEHAVIORAL EFFECTS
                                  AT MODERATE BLOOD LEAD LEVELS

Reference
De la Burde and
Choate (1972)223
De la Burde and
Choate( 1974)22*


Penno and
Ernhart (1974)225

Pueschel et al
(1972)99
Landrigan et al.
(1975)22?






Rummo (1974)2n






Population
studied
Inner city
(Richmond, VA)
Follow-up
same subjects


Inner city
(New York, NY)

Inner city
(Boston, MA)
Smelter area
(El Paso, TX)






Inner city
(Providence, Rl)






N/group
Control = 72
Lead= 70
Control =67
Lead= 70


Control = 50

Lead =30
Control = 56
Lead= 56
Control = 46
Lead= 78






Control Ss= 45

Short Pb Ss= 15


Long Pb Ss= 20

Post enceph Pb= 10

Kotok et al
(1977)232







Kotok (1972)228


Lansdown et al.
(1974)229
McNeil etal.
(1975)230











Inner city
(Rochester, NY)







Inner city
(New Haven, CT)

Inner city
(London, England)
Smelter area
(El Paso, TX)










' Mean test scores obtained for control children are

Control =36 1

Lead= 31 1






Control =25 1
Lead= 24 1

Control= 172
Lead= 43
Control= 61-152 1

Lead= 23-161 1









Age at
testing, yr
4
4
7
7


3-6

3-6
7
?
3-15 (x= 9.3)
3-15 (x= 8.3)






4-8 (x= 5 8)

4-8 (x= 5 6)


4-8 (if = 5 6)

4-8 (x= 5 3)

9-5.6 (x= 3 6)

7-5.4 (iT= 3 6)






1-5 5 (x= 2.7)
0-5 8 (x= 2.8)

6-16
6-16
5-1 8(Mdn= 9)

5-1.8(Mdn=9)









Blood lead,
ME'dl
Not assayed'
40-lOQi1
See above6
See above8


10-30

40-70
<40
>40
<40
40-68






x= 23+ 8

7= 61+ 7


x= 68± 13

x= 88± 40

11-40

61-200






20-55
58-137

<40
40-60 +
<40

>40









Psychometric
tests employed
Stanford-Bmet IQ
Other measures
WISC Full Scale IQ
Neurologic exam
Other measures

McCarthy General
Cognitive
McCarthy Subscales
Stanford-Bmet IQ
Neurologic exam
WISC Full Scale IQf
WPPSI Full Scale
IQt
WISC + WPPSI
Combined
WISC + WPPI
Subscales
Neurologic testing
McCarthy General
Cognitive
McCarthy Subscales


Neurologic exam
rating
Objective neuro-
logic tests
IQE tor suability
classes-
Social maturity,

Spatial relations;
Spoken vocab, Info
comprehension,
Visual attention,
Auditory memory
Denver
Developmental
Scale
WISC
WAIS
McCarthy General
Cognitive
WISC-WAIS Full
Scale IQ
Oseretsky
Motor Level
California Person-
ality
Frostig Perceptual
Quotient
Finger-Thumb
Apposition
Summary of results
(C= control, Pb=lead)a
C= 94 Pb= 89
C >Pb on 3/4 tests
C= 90 Pb= 87
C better than Pb
C >Pbon9/10
tests

C= 90 Pb= 80
C>Pb on 5/5 scales
C='Pb=86
C better than Pb
C=93Pb=87

C= 91 Pb= 86

C=93Pb=88
OPbon
13/14 scales
C >Pb on 4/4 tests
C= 93, S= 94,
L= 88, P= 77
C+S>L>Pon5/5
tests

C+SL >P
on ratings
C+S>L>Pon
3/1 2 tests
IQ Equivalent for
each
C=126Pb=124

C=101Pb=92,
C= 93 Pb= 92;
C= 96 Pb= 95,
C= 93 Pb= 90
C= 100 Pb= 93
C>Pbonl/3
Subscales

C= 100
Pb= 101-105

C= 82 Pb= 81

C= 89 Pb= 87

C= 101 Pb= 97

C= 80 Pb= 72

C= 100 Pb= 103

C=27Pb=29
indicated by C = x, mean scores for respective lead exposed groups are indicated by Pb - x" (except for Rummo^ study where C - contrt
Levels of
significance11
p<.05
N.S-P<01
p <.01
p<.01
N.S-p<,001


p<01
NS.-p<.OI
—
p <.001
N.S.

NS.

p < 01

N.S -p < 01
N.S -p < 001
NS.-p<.01
(P vs C)

NS.-p <.01
(P vs C)

N.S
N S.-p < 01
(pvsC)


p < 10 for
spatial

p >. 10 for all
other ability
classes

NS


NS


N.S

N.S

N.S.

NS

NS

N.S
j|, S = short term lead ex
posed subiects. L - long term lead-exposed group and P = post enceprialopathv lead group)
"N S = non significant,
i e p > 05 Note exception of p < 05 Note exception of p < 10 listed for
"•Urinary coproporphyrm levels were not elated
° Or 30 jig/dl or above with positive radiologic findings The latter suggest ei
* Assays for lead in teeth
i showed the Pb-exposed
group to be approximately b
spatial ability results
in Kotok et al 232 study


irlier exposure in excess of 50-60 /ig/dl
vice as high as controls (:
202 ug/s vs 112 ug/i
!, respectively)


f Used for children over 5 years of age
8 Used for children under 5 years of age
                                               11-27

-------
astrocytosis and glial  nodules  were found in white
matter along with perivascular exudate.
  Lead encephalopathy in the mouse was first de-
scribed by Rosenblum  and Johnson250-  who,  like
Pentschew and  Garro, used the suckling animal. In
contrast to  the  rat brain,   the  striatum  and
cerebellum of mice fed either 0.5 or 1 percent lead
carbonate displayed only faint  staining with Trypan
Blue (except for a single animal with darkly stained
cerebellum) and only occasional  paraplegia.  The
most striking vascular change in the poisoned mice
was  the  appearance of  intervascular  strands
throughout the  brain,  especially in the hippocampus
and basal ganglia.  Rosenblum  and Johnson250 con-
cluded that no cerebral edema and focal destructive
lesions were found in the mouse brains. Therefore,
the histological response of the suckling mouse ex-
posed to lead differs from that  seen in the suckling
rat. These differences are probably not attributable
to different exposure  levels (4  percent carbonate in
the rat versus  1  percent in the mouse), because the
food consumption  per unit body weight is three  to
four times greater in the mouse than in the rat, mak-
ing the external exposures roughly equivalent.
  Wells et al.251 have recently  reported on experi-
mental lead encephalopathy in calves.  Four Jersey
bull calves were exposed to 20 mg/kg/day of lead
acetate, beginning at 3 months of age and  lasting for
8 to 273 days. Histological evaluation of the brains
of exposed animals revealed focal vacuolation of the
neuropil,  neuronal necrosis,  and changes  in the
capillary walls  in the cerebral cortex and  in subcor-
tical areas. Lesions in these cattle  were  similar  to
those  seen in children with lead encephalopathy in
that  both show not  only vascular  changes in  the
brain   with  edema  but  also   areas  of neuronal
necrosis.
    In summary, the  histopathological changes as-
sociated  with  lead   encephalopathy  vary among
species and are characterized  by their relative in-
volvement of neuronal degeneration and vasculopa-
thy. The fact that lead encephalopathy is reported to
occur  in the absence  of cerebral edema in  man,198
mouse,250 and guinea  pig252 is argument for a direct
neuronal involvement of lead.  Recent studies have,
in fact,  suggested direct neuronal  alterations by
lead.   Bull et   al.25?  reported  that lead  interferes
with  potassium-stimulated  respiration  of  rat
cerebral  cortex slices, and Nathanson et al.17  re-
ported that  lead inhibited  brain  adenyl  cyclase in
vitro.  No distinction can be made in these studies,
however,  between neurona! and other cell types.
Thus,  a  direct biochemical effect  of lead on  the
neuron cannot be definitively concluded from these
studies.
  The  relative involvement  of the capillary bed in
the lead encephalopathy may depend on the degree
of maturation at  the time of exposure.  Bouldin et
al.252 for example,  were able to  produce lead en-
cephalopathy in  adult guinea pigs with no cerebral
edema  or increased capillary permeability, whereas
the suckling rat shows these  effects almost  ex-
clusively.
  Since the initial description of lead  encephalopa-
thy in the rat by  Pentschew and  Garro,52 considera-
ble effort has been made to define more closely the
extent  of CNS involvement at  subencephalopathic
levels of lead exposure. This experimental effort has
focused almost exclusively on the developing organ-
ism. The interpretation of a large number of experi-
ments  dealing with  early exposure to  lead have,
however, been confounded by a number of flaws in
experimental design.
  Perhaps the most  notable  of these  experimental
shortcomings has been the presence of undernutri-
tion in  experimental animals. Changes in nutritional
status during early brain development are known to
produce changes  in behavior.254'255 Castellano and
Oliverio,256 for example, reported a marked delay in
neurological development, an increase in explorato-
ry locomotor activity, and a lowered avoidance per-
formance in mice that were  undernourished during
early development by being reared in large litters.
Neurochemical processes have also been shown to be
affected by early undernutrition. Eckhert et al.257 re-
ported  changes   in  cholinergic enzyme  activities
when rats were  placed  on  protein-deficient  diets
during various  periods  of development.  Their
results indicate that "the relationship between the
activity of individual cholinergic enzymes,  nutri-
tional status and developmental age is complex and
is not the same for different brain regions or even the
same brain region exposed to undernutrition during
different periods of  development." Therefore, in
reviewing the animal literature concerned with the
neurotoxicology of lead exposure, the possible con-
tribution  of undernutrition  must  be considered.
Furthermore, the possibility also exists that lead and
undernutrition may be having a synergistic effect on
nervous system   development.  In  this  case,  the
methods of pair-feeding currently employed in some
studies247-258 may not provide adequate control for
this undernutrition.  Examples of  dietary  factors
known to  affect  susceptibility of lead toxicity have
been reviewed by Goyer and  Mahaffey.259
  Animals fed diets containing lower than  recom-
                                                1-28

-------
mended concentrations of nutrients generally retain
higher concentrations of lead in tissues than animals
on  normal  diets.259  However,  almost  nothing  is
known about the effects of elevating nutrient intake
above recommended levels — which is the case with
most commercial  laboratory chows — on the tox-
icity of lead. Additional research  is needed in this
area, and until further data are available on the in-
fluence of varying degrees of overnutrition, varia-
tion in nutrient intake must be suspected of altering
the toxicity  of lead.

11.5.2.1  DEVELOPMENT
  Several laboratories have reported  on the effects
of perinatal lead exposure on physical,  reproduc-
tive, and neurological development.247,250,260,251 ijn.
fortunately, in a number of studies either no control
was provided for undernutrition,250'260-262 or under-
nourished pair-fed controls showed similar develop-
mental delays,247 thus masking any direct  effects of
lead.
  Maker et  al.263 also examined the effects of lead
exposure  on  brain   development  in mice.  Two
methods were used in an attempt to control  for the
effects of early undernutrition. In the first experi-
ment, two pair-fed litters were  used. Pair-feeding
was accomplished  by allowing a litter access to an
amount of normal chow equivalent to that consumed
by a litter on a 0.8 percent lead  diet.  Both pair-fed
litters showed a reduction in brain weight at 30 days
of age, as did the lead-treated animals. The two pair-
fed litters, however,  differed in the relative reduc-
tion in brain  weight, one  showing  an  identical
response to the lead-treated groups and one showing
brain weights intermediate  between  controls and
lead-treated animals.  A second attempt to alter the
nutritional state of the animals was accomplished by
altering litter  sizes (3 pups versus 6 pups). Body
weights of control  animals  of the two litter size
groups were equivalent, however, so that varying the
litter size over this  range did not effectively produce
undernutrition. Therefore, the conclusion of Maker
et al.263 that underconsumption of food alone does
not account  for the slow development  of litters on a
lead diet is not supported by their  data.
  Reiter  et al.264 examined development in rats ex-
posed to  lead both prenatally  and  during  lactation
via the mothers' milk. They reported a delay in both
the age at eye opening and the age at development of
the  air  righting reflex in the  50 ppm treatment
group. This exposure level was shown to produce no
depression in growth, which suggested a direct effect
of  lead  on  nervous system  development.  No
 difference in the development of the acoustic startle
 response  was observed. Kimmel et al.,265  using a
 similar experimental design, also reported delays in
 both surface and air righting in rats exposed to 50 or
 250 ppm lead; and no differences were found  in
 either auditory startle, pinna detachment, eye open-
 ing, ear opening, or incisor eruption.
   Sexual  maturation  appears to be one aspect of
 development that is quite sensitive to disruption by
 lead exposure. Kimmel et al.265 reported a dose-re-
 lated delay in vaginal opening  in  female  rats ex-
 posed to  25,  50, or 250 ppm lead acetate in the
 drinking water starting at conception.  In the group
 exposed to  25 ppm lead, no differences in  growth
 rates  were observed. This suggests a direct effect of
 lead on sexual maturation rather than a change sec-
 ondary to body weight changes.
   Der et  al.266 reported on the combined effect of
 parenteral administration of lead acetate and  low
 protein diet (100 /xg subcutaneously daily,  ages 20
 to 61  days)  on sexual development in the Sesco rat.
 Lead significantly delayed the age at which  vaginal
 opening occurred in  animals on the control diet.
 Females given lead in combination with low  protein
 diets  did  not exhibit  vaginal opening  through 61
 days of age. The authors interpret these data on the
 basis  of  a  lead/protein-deficiency  interaction.
 However, since animals were given 100 /xg  of lead
 per day regardless of body weights and since their
 body  weights were at  26 percent  of control, the
 dosage of lead per unit body weight was 400  percent
 greater than lead-treated animals on a control diet,
 which may  account for  the  additional delay in
 maturation.
  Gray and Reiter261 studied the effects of lead ad-
 ministration (5 mg/ml  in the drinking water  at par-
 turition) on sexual maturation in the mouse. Vaginal
 opening was delayed about 4 days in lead-treated
 animals. No delay in development was seen in pair-
 fed controls, further suggesting a primary effect of
 lead on sexual maturation. Furthermore, no delay in
 sexual maturation was observed  in animals when
 lead was discontinued at weaning. Therefore,  the
 presence of  lead at the time of maturation appears
 essential for the lead-induced delay and may be re-
 lated  to its  effects on  circulating hormones at  the
 time of puberty.

 11.5.2.2 LOCOMOTOR ACTIVITY
  In  the  animal model,  the  most  commonly
employed behavioral index of lead toxicity has been
 locomotor activity. As with other behavior, locomo-
tor activity is influenced by a variety of factors that
                                               11-29

-------
include sex, age, time and duration of testing, type of
measurement, etc.  The  relative  influence of these
factors on  the observed activity  will vary with the
experimental method employed. The endpoint being
measured is activity (not  necessarily  ambulation),
and  the  nervous-system processes responsible for
this activity and their relative contributions may be
different. Tapp,267  for  example, compared  seven
different measures  of activity in the rat and  found
virtually no intercorrelation. These results suggest
that  the  tests he employed were not measuring the
same behavior.  Capobianco  and Hamilton268 ex-
amined the effects  of various brain lesions on am-
bulation as measured  by  three  different  methods:
open-field, stabilimeter, and activity wheels. These
different  measures of  activity were  affected
differently by a given brain lesion. Lesions of the
diagonal band, for example, produced increased ac-
tivity in  the  running wheel, decreased  activity in a
stabilimeter, and no change in activity in an  open
field.
  Not only is the type of activity-measuring device
                                       important, but also of importance is the  length of
                                       time over which the activity is measured. Short-term
                                       measurements  of  activity  in  a novel environment
                                       have been termed  exploratory activity or locomotor
                                       reactivity and primarily reflect the animal's reaction
                                       to the novel environment. This reactivity in turn will
                                       be affected by  the structure of the environment. In
                                       order to  determine spontaneous or basal activity
                                       levels, an animal must reside in an environment over
                                       long periods  of time. Once the animal is established
                                       in the environment, the activity levels of the animal,
                                       especially the rodent, will  be  highly dependent on
                                       the time of day.
                                         Therefore, in reviewing the lead literature, it must
                                       be  remembered that locomotor activity  measure-
                                       ments do not represent a unitary behavior; careful
                                       consideration must be given to the particular experi-
                                       mental methods employed.  In  addition, attempts to
                                       extrapolate the results of an activity measurement in
                                       animals directly to the clinical situation are unwar-
                                       ranted. A brief summary of pertinent studies is given
                                       in Table 11-5.
           TABLE 11-5. EFFECTS OF LEAD EXPOSURE ON LOCOMOTOR ACTIVITY IN LABORATORY ANIMALS
Reference
Allen etal.2"

Bornschemetal.270



Brown2'1



Dnscoll and
Stegner2'2


Gray and Reiter2"



Hastings etal.2"





Species
Monkey

Mouse, (Charles
River) CD-I


Rat (Bar F -
Rabbitry)


Rat (Simonsen)



Mouse, (Charles
River) CD-I


Rat, (Long-
Evans,
Charles
River)


Enposure conditions
0.5-9 mg/kg/day for 12
weeks
5 mg/ml lead acetate in
drinking water, starting
at parturition

35 mg/kg P.Q to dams
from parturition to 21
days

10 * and 10 2 M lead
acetate in drinking water
from conception

5 mg/ml lead acetate in
drinking water, starting
at parturition

0.2 or 1.0 mg/ml from
parturition to 21 days




Test conditions, in order of
presentation
Lead concen 1 Method
(ration, IJLI% 2 Length of testing Nutritional
Blood Brain 3 Group size status
4 Age
160-400 Observed locomotor Normal
activity
120-190 200-306 Proximity counter Undernourished
3 hours
Individual
35 days
Photoactometer
20mm
Individual
49 days
Open-field Undernourished
2min
Individual
31 days
Residential maze Undernourished
90-240 min
Individual
30,50, 130 days
Control Running wheel Normal
= 11±4 3 weeks
0.2 mg/ml Individual
= 29± 5 30-51 days
1.0 mg/ml
= 42±4
Results
Hyperactivity
(qualitative measures)
Normal



Normal



Hypoactive (61% of
control)


Hypoactive (75-80% of
control)


Normal





 Kostasetal.2"
Rat(Long-Evans)
 Blue Spruce
0 05-5.0% lead acetate in
 mother's chow from
 parturition until 21 days.
 Continued in offspring at
 0 25-25 ppm in chow
 until 35 days
                                                  1-30
Shuttle box, activity  Normal • 0.05% group Hyperactivity in shuttle
 wheel          undernourished in    box (182% of control).
1 hr            5-5.0%          Normal in activity
Individual                       wheel
75-77 days; 90-93
 days
                                  (continued)

-------
TABLE 11-5 (continued).
Reference
Overman275





Reiter2"

Reiteretal.276



Reiteretal.261

Cahilletal.2"



Reiteretal.26*



Sauerhoff and
Michaelson"*
Sauerhoff2'9


Silbergeld and
Goldberg262,280,28i


Sobotka and Cook2'2
Species
Rat, (Long-
Evans
Charles
River)


Rat, Sprague
Dawley,
Charles River



Rat, Sprague
Dawley, Blue
Spruce



Mouse, Charles
River, CD-I


Rat, Sprague
Dawley, CO



Mouse,
Charles River,
CD-I

Rat, Sprague
and Sobotka et al 28! Dawley (Charles




Sobotka et al 2«<



Wmnekeetal."5





Zenicketal 2«






River)



Dog (Beagle)



Rat (Wistar)





Rat, Sprague






Exposure conditions
10, 30, 90/mgAg/day by
intubation from 3-21
days of age



5% lead carbonate in
mother's chow from
parturition to 16 days,
50 ppm in drinking water
for remainder of
experiment
5,50 ppm in drinking
water. 40 day
pretreatment of parents.
Continued from
conception through
adulthood
5 mg/ml lead acetate in
drinking water from
parturition until 45 days

4% lead carbonate in
mothers' chow from
parturition to 16 days
post-partum, 40 ppm in
drinking water
2, 5, 10 mg/ml lead
acetate in drinking water
starting at parturition

8-91 mg/kg/day by
intubation from 3-21
days of age



1 or 4 mg/kg/day orally
from 2 weeks to 5
months

1 38 g lead acetate/kg of
chow (745 ppm Pb) for
60 days pretreatment to
mothers. Continued in
offspring from
conception to testing
750 or 1000 mg/kg/day to
females on restricted
watering schedule from
21-99 days of age
Exposure continued
through gestation and
weaning
Lead concen
(ration, ng %
Blood Brain
21 days
90 mg/kg
= 226± 21
35 days
90 mg/kg
= 56±5






180 day 180 day
males males
0=5±0.5 0=18±1
5=6±04 50=20+2
50= 10± 50= 27± 2
06




29 days
88± 1 1







22 days
81 mg/kg
= 71±12
35 days
81 mg/kg
= 23+ 1 4




16 days
266
190 days •
285









Test conditions, in order of
presentation
1 Method
2 Length of testing
3 Group size
4 Age
Jiggle platform
Four days
Individual
22-65


Jiggle cage,
Residential maze
4 mm, 14 days
Individual; group of 3
13-44 days; 120-160
days
Residential maze
5 days
Groups of 3
120 days


Residential maze
2 days
Individual
100 days
Selective activity
meter
24 hours
Groups of 6
26-29, 50
Proximity counter
3 hours
Individual
30-150 days
Photoactometer
30mm
Individual
24-28 days


Open field
—
Individual
3-4 months
Open field
3 mm, on consecutive
days
Individual
90-140 days

Open field
3 mm, on 10
consecutive days
Individual
22-32 days


Nutritional
status Results
Normal Hyperactive





Undernourished Transient hyperactivity
(200% of control at 13
days). Normal at 44
days. Normal levels in
adults; but disrupted
ultradian rhythms.
Normal Hypoactivity (53-78% of
controls)




Undernourished Normal



Undernourished Hyperactive at 29 days
(140-190% of control)
Normal at 50 days


Undernourished Hyperactivity (300-400%
of control)


Normal Normal





Not indicated Hypoactive



Normal Hyperactive (129% of
control)




Undernourished Initial hypoactivity in
100 mg/kg group (days
1 and 2) Hyperactive by
the 7th test day.



      11-31

-------
  The  data  to  be  reviewed  here  suggest  that
perinatal lead exposure produces  an  altered reac-
tivity of an animal to a novel environment. Reac-
tivity is increased  in the young animal, but this in-
creased reactivity disappears as the animal matures.
In the adult animal, on the other hand, the lead ex-
posure results in a reduced reactivity. As will  be
seen, the exact nature of the change in locomotor ac-
tivity brought about by this altered responsiveness
will  depend heavily on the structure of the test en-
vironment.
  Sauerhoff and Michaelson278 and Sauerhoff279 ex-
posed lactating females to lead using a modification
of the  Pentschew  and  Garro52 exposure  regimen.
Litter mates were tested as a group at 25 to 28 days
of age  in a test case similar to the home cage. The
data were collected in four blocks of 3 hr and one
block of 12 hr, extended over 4 days. Although they
are presented as counts per hour for a 24-hr period,
data represent reactivity  attributable  to  multiple
short-term exposures to a novel environment, and,
therefore, are not comparable with data obtained by
continuous sampling over a 24-hr period. Offspring
of a lead-exposed mother exhibited elevated activity
levels.  Since only one group (n = 6 pups) was tested
from each treatment, however, no statistical test can
be applied to these data.
  Using a similar  exposure regimen, Reiter258 and
Reiter  et al.276 exposed animals to 5 percent lead
carbonate  in  the  chow  starting  at  parturition.
Animals  were  repeatedly  tested  at various ages,
beginning at  13 days of age, using a 4-min jiggle
platform  activity measurement.   This  measuring
device detects both locomotor activity and station-
ary body movements. They reported an increased
activity (200  percent  of  control) in  13-day-old
animals.  This elevated  activity declined  with  age
and  returned to control  levels by 44 days of age.
Comparisons were made with pair-fed controls since
this exposure resulted in a significant growth impair-
ment.  Whether  this return to  normal  levels was
caused by maturation or by repeated testing was not
determined in this study. Animals were also tested as
adults (120 days) in a residential maze, which allows
continuous measurement of activity over  extended
periods of time; this test showed no differences in the
activity levels as a result of treatment. However, the
ultradian rhythms of activity seen in control animals
during the nocturnal  period (short-term,  4/hr
oscillation  in activity) were absent in lead-exposed
animals.
  Overmann275  used a  similar jiggle platform  to
measure activity in 22- to 65-day-old rats.  As in the
Sauerhoff and  Michaelson study,278 animals  were
rotated between testing cages, and, therefore, the ob-
served increase in  activity  was consistent  with a
lead-induced change in locomotor reactivity. In this
experiment, pups were directly exposed by daily in-
tubation ranging from  10 to 90 mg/kg/day. This ex-
posure is similar to  that  used  by  Sobotka  and
Cook,282 who employed intubation levels of 9 to 81
mg/kg/day, but who reported no differences in ac-
tivity in a photoactometer.
  One striking  difference between these two experi-
ments was in the  reported blood lead levels, shown
in Table 11-6. Therefore, the higher internal ex-
posure seen in Overmann's experiment may have ac-
counted for  the  difference  in  the  observed
behavioral  effects,  although  differences  in  experi-
mental  protocol may  also have  accounted for
differences in the behavioral effects.
  TABLE 11-6. LEAD EXPOSURE AND RESULTING BLOOD
LEAD LEVELS IN EXPERIMENTS MEASURING LOCOMOTOR
                 ACTIVITY IN RATS
                                Blood leaa,/*g/dl
      Experiment
                           21 to 22 days
                                        35 days
Sobotka and Cook ^
 and Sobotka etal.283
  (81 mg/kg/day)
Overmann275
  (90 mg/kg/day)
  71 ± 124
226 1 ± 21 1
              23+ 1.4
              56 ± 4.6
  Two different laboratories have  reported on  the
effects of lead administration on open-field activity
in 30- to 40-day-old rats. Driscoll and Stegner272 re-
ported a decreased activity in animals tested  for 2
min. Zenick et al.286 tested animals for 3 min  in an
open field on 10 consecutive days. On the first 2 days
of testing, animals from  the high  exposure group
(1000 mg/kg/day  in  the drinking water of  the
mother)  showed a decreased activity similar to that
reported by Driscoll and Stegner.272 By the seventh
day of testing, however, these animals were ambulat-
ing at a  higher level than controls. These  data can
also be interpreted as an increased  locomotor reac-
tivity  in lead-treated animals that  is  initially
manifested in an open field as decreased ambulation.
With  repeated exposure,  the animals show an ele-
vated activity similar to that in previously  reported
studies. The difference in the direction of lead-in-
duced change in initial activity levels in these open
field experiments as compared to the jiggle  platform
experiments258'275 is  probably a result of  the
differences in  the size of the test environments. The
larger open field results in decreased activity in
lead-exposed hyperreactive animals, whereas in the
                                               11-32

-------
 smaller jiggle platform the animals show increased
 activity.
   Finally, Hastings et al.273 reported no differences
 in running-wheel activity of 30-day-old animals ex-
 posed to lead by suckling with mothers receiving 1
 mg/ml  lead  in the drinking water. This exposure
 resulted in blood lead values of 42 /j.gldl at weaning.
 Since animals do not normally show much running
 activity upon initial exposure to the running wheel,
 the effects of this lead exposure on reactivity cannot
 be adequately tested. These results do demonstrate
 that long-term running wheel activity (3 weeks) was
 not disrupted in these young, lead-exposed animals.
   At or about the time  of sexual maturation, lead
 exposure has not been shown to alter activity levels
 in the rat. As previously indicated, Sauerhoff and
 Michaelson278  and  Reiter et  al.276 found  no
 differences in activity  in animals tested between 44
 and  50 days of age. These were animals which were
 reported to have increased activity at a younger age.
 Brown271  also reported no  differences in locomotor
 activity in animals tested at 49 days of age either in
 an photoactometer or  in an open field.
   Available  data also suggest  that perinatal ex-
 posure to lead may produce a decreased reactivity in
 the adult animals. Kostas et al.274 measured locomo-
 tor activity in adult rats exposed to either 0.05, 0.5,
 or 5.0 percent lead carbonate in the chow from par-
 turition until weaning  and  to 0.25, 2.5, or 25 ppm
 from weaning until 35 days of age. Two  measure-
 ments of activity were employed. Animals tested for
 1 hr  in a shuttle box activity cage were found to have
 increased activity, whereas animals tested in running
 wheels showed no  difference from controls. This
 lack of sensitivity of the running wheel to lead-in-
 duced changes in  activity is consistent with the find-
 ing of Hastings  et al.273 Again,  the nature of the
change in  shuttle  box activity may be interpreted  in
terms  of   a  lead-induced   decrease in reactivity
toward a novel environment, since  rats made more
 reactive would  tend to freeze in  this environment,
thus  causing decreased  ambulation.  Winneke   et
 al.285 found a similar change in reactivity as indi-
 cated by open-field activity scores over 5 successive
 days of testing. Lead-treated rats had significantly
 elevated activity on the first 3 days of testing, and
 activity had returned to normal on days 4 and 5.
  Reiter et al.264  reported a lead-induced decrease
 in activity in adult animals tested  in a residential
maze. This test system allowed for  measurement of
various components of the animals'  activity, includ-
 ing exploratory, diurnal, and nocturnal activity. Ex-
ploratory  activity was  initially suppressed in lead-
 treated animals, but this difference disappeared as
 the animals became established in the environment.
 On  the other  hand, activity levels remained sup-
 pressed during the nocturnal period.
   In a second study, Reiter et al.276  reported  no
 difference in residential-maze activity of adult lead-
 treated animals.  They speculated that the lack of a
 lead effect on  locomotor activity in the second ex-
 periment  may have been the result of the choice of
 animal supplier (Charles River). Since the Charles
 River animals were normally less active in the maze,
 it may have been difficult  to  lower  their activity
 further with treatment. Differences in experimental
 protocol, i.e., differences in  dose and period  of ex-
 posure, however, also may have accounted for the
 differences in observed activity.
   In summary, data on the rat suggest that perinatal
 exposure  to  lead may produce an increased reac-
 tivity which disappears as the animal matures. This
 effect could result from  a delay in  normal matura-
 tion of forebrain inhibitory systems.287 As the lead-
 treated animals mature, they pass through a period
 of normal reactivity  which then  progresses  to  a
 decreased reactivity in the adult animal. These data
 would be  consistent with a maturational lag seen in
 children288 and pose an interesting hypothesis that
 requires further testing.
  Sobotka et al.284 have reported decreased ambula-
 tion  in young dogs exposed to lead and tested in a 7-
 by 7-ft open field.  Allen et al.269 exposed infant
 monkeys to lead via their formula and reported hy-
 peractivity from  3 to 5 months of  age. These data
 and the data of Sobotka et al.284 are consistent with
 the lead-induced  increase in reactivity seen in the
 young rat. The  data  of Allen et al.269  must be
 qualified, however, since no quantitative measure of
 activity was made.
  In a series of often  cited papers, Silbergeld and
 Goldberg262'280'281  reported  lead-induced hyperac-
 tivity in mice.  Lactating females were exposed  to
 lead acetate in the drinking  water, starting at par-
 turition, in concentrations  of either  2,  5,  or 10
 mg/ml. The authors reported a 300- to 400-percent
 increase in locomotor activity that extended from 30
 to 150 days of age in the offspring. The lack of a con-
 trol for the growth  retardation found in the  lead-
 treated  groups makes  interpretation  of these data
 difficult. As previously  indicated,  Castellano and
 Oliverio256 reported that early undernutrition pro-
duces hyperactivity in mice. Therefore, the observed
hyperactivity may  have  resulted from the under-
nutrition, independent of a lead effect. Greater con-
cern, however, stems from the subsequent failure of
                                               11-33

-------
two different laboratories261 -270,289 to replicate the
findings of Silbergeld and Goldberg, using the same
strain of mouse and the same exposure regimen.
  Bornschein et al.270 exposed  lactating  mice to 5
mg/ml lead acetate and tested offspring in activity
chambers  identical to those employed  by Silbergeld
and Goldberg.262,280,281  jney were unable to verify
lead-induced  hyperactivity  in  mice  even though
undernutrition was also present in their animals.
  Gray and Reiter261  were also unable to demon-
strate hyperactivity in  lead-exposed mice, using a
residential maze to measure activity.  Furthermore,
Reiter et al.289 were unable to find differences in the
activity of mice experimentally exposed to lead from
birth  to 45 days in Goldberg's laboratory and then
transported to the author's laboratory for behavioral
testing.
  Silbergeld  and Goldberg280-281 also studied  the
locomotor response of lead-exposed mice to various
drugs that are used in the treatment and diagnosis of
minimal brain dysfunction  in children. Most nota-
bly, they reported that their lead-treated, hyperac-
tive mice responded paradoxically to the stimulants
amphetamine and methylphenidate.  Examination of
the activity  data  following  administration  of
methylphenidate281  raises questions as to the exact
nature of the paradoxical  response.  Both control
and lead-treated animals responded with increased
locomotor   activity  following  40  mg/kg  of
methylphenidate; however, the response of the lead-
treated mice was markedly attenuated. Within 90 to
120 min,  animals were below their predrug  level.
This time course in the response would be expected
if the  lead-treated animals  were  entering  into
stereotypic behavior  (a behavioral  pattern  char-
acteristically  seen  following  high  doses  of
amphetamine-like compounds).290 Although  the
authors state  that no stereotypic behavior occurred
in lead-treated  animals,  no quantitation of  this
behavior was made. Furthermore,  this stereotypic
behavior has  been observed in lead-treated mice by
other  investigators.270 Again, the possible contribu-
tion of early undernutrition to these results must be
considered. Bornschein et al.270 found this paradoxi-
cal lowering of  activity in  undernourished mice
following  10 mg/kg of d-amphetamine, but only dur-
ing the second hour following drug administration.
In the first hour, activity showed the expected in-
crease, although to  a lesser extent than in controls.
These authors postulated that early undernutrition
shifts  the  dose-response curve to the  left such that
animals given  high levels of  amphetamine  (10
mg/kg) enter  into stereotyped behavior sooner than
controls, which prevents the occurrence and the
recording of locomotor activity.
  Reiter258 examined the dose-response relationship
to amphetamine  in control, undernourished, and
lead-exposed rats. He  found, as did Bornschein et
al.,270 that undernutrition shifted the dose-response
curve to the left. Lead treatment, on the other hand,
shifted the  dose-response curve to the right. Thus,
under the appropriate conditions, lead exposure per
se can be shown to produce an  attenuated response
to amphetamine. The occurrence of a true paradoxi-
cal  response, however, is questionable.
  The  lead-induced  attenuated response  to
amphetamine  has been  observed  regardless  of
whether  the reported predrug  activity levels were
elevated,280-281  normal.258-282 or depressed.26« The
determination of the exact nature of this  altered
response, i.e., altered CNS sensitivity versus  altered
absorption, distribution, and metabolism, requires
further study.


11.5.2.3  LEARNING  ABILITY
  There  is little doubt that acute, high-level lead ex-
posure in  young  children can   produce overt
manifestations of neurotoxicity.182-203 Mental retar-
dation is an established sequela of lead-induced en-
cephalopathy in children.85-86 The extent and nature
of lead-induced neurotoxicity following long-term
low-level lead  exposure during the  developmental
years is also of continuing interest. As indicated pre-
viously, restrospective  studies in children are
generally equivocal and are compromised by serious
experimental design limitations, e.g., unsatisfactory
documentation of lead-exposure history prior  to
behavioral testing and inappropriate or unsatisfacto-
ry control groups.291
  In an attempt to overcome some of these limita-
tions, investigators have turned  to animal models of
chronic,  low-level exposure. The major  portion of
this work has been carried out  in  rats. Table 11-7
provides a summary of the pertinent studies,  includ-
ing exposure  conditions,  testing  conditions, and
results. In an attempt to structure this literature and
facilitate evaluation,  the organization  shown  in
Table 11 -8 has also been developed. It separates the
data along two lines: (1) tasks that reportedly are, or
are not, sensitive to changes arising from  the ex-
posure conditions and  (2) the stage of learning dur-
ing which effects  are, or are not, demonstrable. The
acquisition column indicates investigations of the
rate at which  animals form associations between
stimulus and  reinforcement conditions. Measures
                                               11-34

-------
utilized to quantify the process are numbers of days
and  trials  or problem presentations required to
reach some predetermined  level of performance.
The  percentage of the test population attaining  the
defined criterion  per  unit time  is also a common
measure. The performance column includes studies
of the quantitative nature of the behavior after the
desired criterion has been attained. The reversal/ex-
tinction column contains studies of behavior  ob-
served following the removal of (extinction) or
alteration of (reversal) the conditions that produce
reinforcement.
                     TABLE 11-7. PROTOCOLS USED FOR THE STUDY OF ANIMAL LEARNING
Behavioral task
Reference Species
Brady Rat
et al."2
Brown, D »i Rat













Brown, S Rat
eta!?"



Driscol! and Rat
Stegner?"






Overmannzw Rat











Snowdon?« Rat




Sobotka Rat
etal.zH

Apparatus
water
T-maze
T-maze

T-maze

T-maze

T-maie

T-maze

T-maze

T-maze

water
T-maze

Shuttle-
box
Y-maze

Shuttle-
box
Shuttle-
box
Shuttle-
box
E-maze

E-maze

E-maze

2-compart-
ment chamber
2-compart-
ment chamber
Ope rant

CF maze


CF maze

Shuttle-
box

Reward
neg.

pos

pos.

pos

pos

pos

pos

pos

neg


neg.

pos.

neg

neg

neg.

pos.

pos

pos

neg.

neg

pos.

pos.


pos.

neg.


fas*3
Simult
BD
Succ.
B.D
Succ.
BD
Succ
B.D
Succ
B.D
Succ
BD
Succ
B.D
Succ
B.D
Spatial
discrim.

2-way

Simult.
BD
2-way

2-way

2 -way

Spatial
discrim.
Tactile
discrim.
Visual
discrim
1-way

Passive
avoid
Temporal
disc
Maze
learning

Maze
learning
2-way


lead exposure
Period11
PG,G,L

L

L

L(lst lOd)

l(lastlld)

L(lastlld)

L(lastlld)

Birth to
day 10
Various
(8 days to
5 weeks)
5 weeks

PG,G,L,PW

PG,G,L,PW

PG,G,L,PW

PG,G,L,PW

L

L

L

L

L

I

Adult
exposure
andPW
L

3-21 days
post-
pa rtum
Le«lc
500 GAVe

100 W

25 GAV«

35 GAV«

35 GAV3

70 GAV«

140 GAV«

5IP«

100 IP«


100 IP«

2070 DT<

2070 DTI

2070 DT<

2070 DT'

5,16,49
GAV
5,16,49
GAV
5,16,49
GAV1
5,16,49
GAV
' 5,16,49
GAV
5,16,49
GAV
2.7,4.4
66IP«

44IP«

5 15,44
GAV

Number
Litter
per test
group
4

7

7

7

?

7

7

7

7


1

7

7

7

7

1

7

?

7

7

7

7


17

6-7


Subjects
per test
group
17

6

7

5-6

5-6

5-6

5-6

7

66


8

4

5

12

12

7

7

7

7

7

7

8-10


36

28-34


Gro*ttld
rate
N

N

N

N

N

N

A

N

7


7

A

A

N

A

N

N

N

N

N

N

A


A

7


Blood lead, ^tit\
Peak
7

7

7

46

20

19

7

288

7


7

7

7

7

7

33,174
226
33,174
226
33,174
226
33,174
226
33,174
226
33,174
226
7


7

11
21
23
At test
7

7

7

7

7

7

7

23

7


7

7

7

7

7

15,23,
56
7

7

7

7

7

7


7

?


Learning
performance
Impaired

Impaired

Impaired

Impaired

No effect

No effect

Impaired

Impaired

No effect


No effect

Impaired

Improved

Impaired

Improved

No effect

Impaired on
reversal
No effect
No effect
Impaired

No effect

Impaired

No effect


Impaired

Impaired


                                                                                         (continued)
                                              11-35

-------
TABLE 11-7 (continued).
Behavioral task


Idari ovnnc.,ro Number


Reference Species Apparatus Reward
Sobotka and Rat 2-
Cook282 compartment
chamber
Shuttle-
box
Shuttle-
box
Operant

Slecta2" Rat Operant

Shapiro Rat Operant
et al.29'
Hastings Rat Shock
et al 2" grid
Shock
grid
Operant

Wmneke Rat Lashley
etal285 jumping
stand
Bornschem298 Mouse Operant

Bornschem299 Mouse Operant

Sobotka Dog T-maze
et al.2"


VanGelder Sheep Operant
et al.^oo

Operant

Operant

Carson Sheep CF maze
et a) 301,302
and VanGelder
etal.300 CF maze

neg.


neg.

neg.

neg

pos

pos

neg

neg

pos

pos


pos

pos

pos



pos


pos

pos

pos.


pos



laska


Period*1
passive 3-21 days
avoid

1-way

2-way

Spatial
discrim.
Fl
schedule
VI 30
schedule
Flinch

SEA

Succ
BD
Simult
PD4SD

Simult
BD
Simult
BD
Simult
RD


Auditory
discrim.

Fl
schedule
Fl
schedule
Maze
learning

Maze
learning
post-
partum
—

—



PW (day
22-57)
PW (day
90-126)
L

L

L

PG,G,L
PW

L

L

2-week-
5 month
post-
partum
Adult ex-
posure
9 weeks




G


5 days
12 weeks
Litter
per test
Levelc group
5,15,44« ?
GAV

	 7

	 7

?

50,300 —
1000 W<
.09 - 52 —
IP'
109,
546 W' 3
109,
546 W' 3
109, 3
546 W
745 DTf —


103,546 5
2730 W'
109,546 7
W'
14W' -



100 GAV' —


1000 DT' —

530 OT» —

2.3,4.5' —
DT

2,4,8,16' —
DT
Sublets
per test
group
5-8


5-8

5-8

5-8

3

7


10

10
10

10


15

14

10



4


5

5

6-8


4


Growth
rate
N


N

N

N

7

7


N

N
N

N


A

N

N



7


7

7

7


7

Blood lead « "'rli


Peat
18,61,71


18,61,71

18,61,71

18,61,71

9,28,40

7


29,42

29,42
29,42

29


79
190
80
180
85



7


30

17

17-25


57,81
123,162

Learning
At test performance
? No effect


? No effect

? Impaired

? Impaired
reversal
7 Altered

' Altered

No effect
5,9
Less
5,9 aggressive
5,9 No effect

29 Impaired


29,120 Impaired

29 Impaired
reversal
— Impaired



? Impaired


30 No effect

17 No effect

9-14 No effect


— No effect

post partum
Operant

Bowman and Monkey WGTA
Bushnell303
aSucc B P ~ Successive brightness discrimination
Simult 80 = Simultaneous brightness discrimination
1 way = One way avoidance
2 way = Two way avoidance
FP = Form discrimination
SD = Sue discrimination
Flinch = Tail flinch test
SEA = Shock elicited aggression
CF maze = Close field maze

Operant = Operant chamber
WGTA = Wisconsin General Test Apparatus
bPG= Pregestation period, external exposure to dam
pos

pos



Simult
FD4SD
—

G= Gestation period,
1= Lactation period,
G

L,PL

2,3,4,5' —
DT
0.3,1.0 —

6-8

4

7

—

17,25

50,85

9,14 Impaired

50,85 Impaired
reversal
external exposure to dam
external exposure to dam
PW= Post weaning period, external










CDT= Diet
GAV= Gavage
IP= Intrapentoneal
W= Drinking water
.
°N= Normal
A= Altered

'mj/Vg/day
'ppm










exposure to pup






















































        .1-36

-------
   A review of the studies listed in Table 11-7 leads
 to the following general critique. Few animal studies
 adequately simulate the lead exposure  conditions
 found in young children either with respect to the
 levels of exposure  or  the timing of the exposure.
 There is often an  inadequate or nonexistent history
 of lead exposure  with  respect to both the  external
 and internal dose. In regard to the general experi-
 mental  designs,  several  design deficiencies  fre-
 quently occur. These include: (1) limited sample size
 or larger samples derived from  a few litters — the
 latter permits genetic effects to have an  inordinate
 influence on the results — and (2) inappropriate ap-
 plication of statistical methods and confounding of
 variables, e.g., maternal undernutrition or neonatal
 growth retardation, which results in an inability to
 determine specific causes for demonstrated effects.
 The selection of behavioral tasks is often made  with
                           little or no apparent rationale that would aid in the
                           formulation  and  testing  of hypotheses  and  in-
                           terpretation of data. Finally, most  investigators do
                           not provide adequate documentation of the relative
                           sensitivity of the behavioral tasks being used  which
                           could be accomplished with the use of a  standard
                           reference compound. Since this has not been done,
                           failure to observe a disruption in task acquisition or
                           performance could be taken to mean that (1) the task
                           is not sensitive enough to detect the deficit or (2) the
                           neural systems which mediate the behavior on that
                           task are not affected by lead at the  exposure levels
                           examined.

                             In  spite  of the  extensive methodological
                           differences in these studies, several conclusions can
                           be drawn  from the data shown in Tables  11-7 and
                                     TABLE 11-8. STAGE OF LEARNING
        Treatment
        effects
                                  Acquisition
                                                        Performance
                                                                                Reversal extinction
       Present
       Absent
Bradyetal292a
Brown304b
Carson et al 3d b
Driscoll and Stegner272at>
Hastings et al.273b
Overmann?94a
Snowdon295b
Sobotkaetal283a
Wmnekeet al.285b
Miller etal 305b

Bornschem etal 298 b
Carson etal 3°°b
Hastings et al2?3b
Overmann29i ab
Sobotkaet al283a
Wmnekeet al 285 b
Shapiro etal 297 b
Slecta296b
Bornschem et a!298b
Overmann294 ab
Sobotkaetal283a
Bornschem etal.298 b
Bowmansosb
                         Overmann294a
                         Sobotkaeta|283a
                         Miller etal 305 b
 aNegative reinforcer
 "Positive remtorcer
  Although learning paradigms are being used to
demonstrate effects of lead on CNS function, the
present data do not permit  a  clear distinction be-
tween the effects of lead exposure on cognitive func-
tion (learning/memory)  and  effects on  sensory-
motor  function, arousal, or motivation,  which in
turn  can  produce  performance  differences.
Therefore, some of the studies  appearing in the col-
umn titled "Acquisition" (Table 1 1-8) may, in fact,
belong  in  the  "Performance" column.  This  is
especially true of studies  that report large group
differences on the first day of acquisition  (cf.  292,
299). New studies specifically designed to test for
this distinction must be conducted.
  Tasks that use both positive and negative reinfor-
                           cers  appear to  be equally sensitive to disruption
                           following lead exposure  (Table 11-8).  Therefore,
                           lead  exposure does not appear  to have a  selective
                           effect on a specific motivational system.

                             Treatment ettects have been  reported  both  by
                           those investigators using manual testing procedures
                           which require a high degree of experimenter-subject
                           interaction (cf. 285, 292, 304)  and  by those using
                           automated operant chambers with minimal experi-
                           menter-subject interaction (cf. 283, 294, 306). Thus,
                           reports  of significant  treatment effects cannot  be
                           ascribed to experimenter bias.

                             The effects appear to persist beyond the immedi-
                           ate  exposure  period  with behavioral  disruption
                                                  1-37

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demonstrable  in  animals with normal  blood lead
levels (cf. 283, 285, 304, 306).
  Procedures have been inadequate for reproducing
qualitative and  quantitative changes in behavior.
This has limited  the ability to test hypotheses per-
taining to  the  site  of action  of lead-induced
behavioral changes.
  It is not yet clear whether the observed effects are
direct  effects  of lead on  the developing  nervous
system or whether the  effects are indirectly mediated
through treatment-induced  alterations in maternal
behavior, maternal milk, or one of several potential
peripheral target systems in the neonate.
  Some types of learning problems  appear to  be
more  sensitive to lead-related  disruption  than
others.  For  example,  in   the  passive  avoidance
paradigm, acquisition and extinction are reportedly
not sensitive.282-294 Simple pattern discrimination
is  also  apparently  insensitive  to  lead expo-
sure.285'294-301  Other  forms of  visual  discrimina-
tion such as size285-301 and brightness
                                  271.292.304.306
ap-
pear to be particularly sensitive. The two reports of
altered  size  discrimination285301  may  in  fact  be
special cases of brightness discrimination since the
different size stimuli (white pattern on a black back-
ground)  also reflect   different  amounts  of light.
Further testing will be necessary to resolve this issue.
Active-avoidance tasks are  also  being  used suc-
cessfully to examine effects obtained following lead
exposure. Both one-way avoidance294-306 and two-
way, shuttle-avoidance tasks272-283 reflect a disrup-
tion in  normal behavior.  The one  exception is a
negative finding by Sobotka et al.2s3 using a one-way
avoidance task. This negative effect may be related
to the fact that shock  was terminated automatically
after 5  seconds,  independent of  the  animals'
behavior. This is not  the usual  procedure,  and its
effect cannot be evaluated since no data were pre-
sented for this particular task.
   Deficits in task performance do not appear to be
species  specific  since  they   are  reported  for
ratS)272,283,294,304  mice,298  dogs,305  sheep,30'  and
monkeys.303 Furthermore, recent studies suggest that
behavioral alterations may be  present in rats ex-
posed to lead  following  weaning.296-297 These  re-
ports are contrary to the generally held opinion that
adult or post-weaning rats are insensitive to lead ex-
posure. 293.295,301  Since the  number  of  reported
studies using adult  exposure protocols is extremely
limited,  however, it is not possible to rule  out the
suggestion that these conflicting data merely reflect
differences in task  sensitivity. More research using
adult exposure  protocols  and  more sophisticated
behavioral testing paradigms will be  necessary to
resolve the conflict.

11.5.2.4  EFFECTS OF LEAD ON AGGRESSIVE
BEHAVIOR
  Two reports appeared in the literature in  1973
which suggested that lead exposure produced an in-
creased  aggressiveness. Silbergeld  and Goldberg262
reported that mice exposed to either 5 or  10 mg/ml
of lead  had a "heightened  frequency of fighting as
determined by the incidence of bite frequencies ob-
served  on litter-mate males housed together."
Sauerhoff and Michaelson278 also referred to an in-
creased  aggressiveness in lead-exposed rats during
the fourth week of development. In  neither report,
however, was there an  attempt to quantitate  these
observations  of increased aggression.
  Hastings et a I.306 exposed lactating rats to lead (0,
109, or  545 ppm) from parturition to 21 days. This
lead treatment produced no change in growth in the
offspring. Individual  pairs  of male offspring (from
the same treatment groups) were tested at 60 days of
age  for  shock-elicited  aggression.  Lead-exposed
groups showed significantly less aggressive behavior
than the control group.  There were no significant
differences among the groups  in the  flinch/jump
thresholds to shock. This latter finding suggests that
the differences seen in the shock-elicited aggression
were not caused by differences in shock threshold.
  Gray  and  Reiter261 reported on  the aggressive
behavior of mice exposed to 5 mg/ml lead acetate
from parturition. Aggressive behavior was measured
by introducing an adult male intruder into the home
cage of an individual experimental  male. Control
males wounded the intruder 85 times on the average
during a 14-hour test period, whereas intruders to
lead-treated and pair-fed male cages had means of
32 and 35, respectively. Therefore, the reduced ag-
gressive behavior seen in these experiments cannot
be explained by lead exposure alone,  because similar
reductions were  observed  in  pair-fed  controls.
Nevertheless, in both  the rat and the mouse a quan-
titative examination of aggressive behavior suggests
that lead  can cause a decrease rather  than an in-
crease in aggressive behavior.

11.5.2.5  NEUROCHEMISTRY
  The effects of in vivo lead exposure on a variety of
neurochemical  substances and  processes have been
studied  in the past several years (see Table 11-7).
Perhaps most notable are the investigations of lead
effects on  both putative neurotransmitter systems
and on  energy metabolism in the central nervous
                                                11-38

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system. Much of the work, by its nature, has required
the  use of experimental  animal  models for broad
screening for possible  effects across many  different
transmitter systems or for testing  specific hypotheses
of  altered   transmitter   functions.  Unfortunately,
these studies on the neurochemical effects of lead ex-
posure are hindered by the same problems in experi-
mental design as  those discussed in the section on
behavioral studies.
   Research  on  neurotransmitter systems  has  con-
centrated primarily on the effects  of lead  exposure
on cholinergic and monoaminergic functions, proba-
bly  because  of the extensive background  literature
that  exists  on  the basic  neurochemistry  of those
                                      transmitters and because of the  documentation  ex-
                                      tant on the neurophysiological and behavioral roles
                                      played by  these  transmitters.  The  approaches
                                      employed  in  these  studies  have  included:  (1)
                                      biochemical assays of steady-state levels of transmit-
                                      ter  substances  in  brain tissue;277'283'288-307'315  (2)
                                      assessment of synthesis and turnover rates;309'3'5 (3)
                                      measurement of the activity of enzymes responsible
                                      for  transmitter  synthesis or  degrada-
                                      tion;283,309,3i 1,313,316-318  (4)  assessment  of transport
                                      processes involved in synaptic uptake of transmitters
                                      or  their precursors;308-309-316 and (5) assessment of
                                      synaptic release mechanisms308-309-315-316  (see Table
                                      11-9).
                      TABLE 11-9. IN VIVO EFFECTS OF LEAD EXPOSURE ON NEUROCHEMISTRY
Lead concentration
Reference
Silbergeld and
Goldbergsoe
Species Exposure
Mouse 5 mg/ml lead acetate in
drinking water starting at
parturition
Nutritional Blood,
status ^g/dl
Under- ?
nourished
Brain,
//g/g Neurochemical parameter
i 1) High affinity transport of
phenylalanme, glycme,
leucme, NE, 5HT, GABA,
DA, cholme, andtyrosine
Results
1) Decreased high affinity
transport of dopamme
and cholme
Increased high affinity
Silbergeld etal.309  Mouse
5 mg/ml lead acetate in     Under-
 drinking water starting at    nourished
 parturition
Carroll etal.316    Mouse  2, 5,10 mg/ml lead acetate  Under-
                       in drinking water starting   nourished
                       at parturition
Brown et al.3'8     Rat    7 5mg/kg (IP) from birth    Normal
                       to 10 days of age
Goiter and        Rat    5% lead acetate in         Under
 MichaelsonSW            mother's diet from par-     nourished
                       turition to 16 days post
                       partum, 40 ppm m drink-
                       ing water
                      Intubated with l.Omg/day
                       from parturition to 16
                       days post partum, 40 ppm
                       in drinking water

Michaelson and    Rat    5% lead acetate in         Under
 SauerhofPH              mother's diet from par-     nourished
                       turition until day 16, 25
                       ppm in drinking water

Sauertioff and      Rat    4% lead carbonate in       Under-
 Michaelson"8            mother's diet from par-     nourished
                       turition until 16 days, 40
                       ppm in diet

Grant etal.^io      Rat    0,25,100 or 200             ?
                       mg/kg/day by gavage on
                       postnatal days 3-25
2) Steady-state ACh NE DA


l)ACh release
2) Steady state NE, HVA,
  VMA
3) MAO
4) Cholme transport

1)K+ -induced release of
  ACh and cholme
2) Spontaneous release of
  ACh
3) Steady-state levels of ACh,
  cholme
4) CAT CBK AChE


AChE
 (regional brain analysis)
                                                     Steady-state NE, DA
  transport of tyrosine
2) Increased steady state
  levels of NE

1) Decreased 40%
2) Increased 27, 41,15%
  respectively
3) Increased 20%
4) Decreased 50%

1) Inhibited K+-induced
  release of cholme and
  ACh
2) Increased spontaneous
  ACh release
3) No change in steady state
  levels
4) No change

No change in medulla
 oblongata, corpus
 striatum, cerebellum,
 cerebrum or hippocampus
 Inhibited in midbrain
 (16%)

Increased NE at 33 days of
 age (13%),
 no change in DA
                                     '   Control =0.1   1) Steady-state DA        1) Decreased DA (20%)
                                           4%= 0.88  2) Steady-state 5HT, GABA,   2) No change
                                                       andiNE
                                   0= 16     0.15
                                  25= 26     0.38
                                  100= 43     0.51
                                  200= 63     0.68
                                                     Steady-state NE, DA
Steady-state NE, DA
 (regional brain analysis)
                     Decreased DA (20%)
No change
                                                                                                      (continued)
                                                      11-39

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TABLE 11-9 (continued).


Reference Species
Hrdma3'3 Rat




ModaketaP" Rat







Sobotkaetal.283 Rat

Shih and Hanm3i5 Rat



Cahillet aM" Rat




Silbergeld and Mouse
Chisolm3'9

Gerberetal.3i2 Mouse


Bhatnagar3i7 Rat
(200-
250
8)
Bull et al 253 Rat
(200-
400
g)


Holtzman and Hsu32" Rat



Abbreviations
ACh - Acetylcholme
CAT Cholme acetylUanferase
AChE AcetylctwhnKteiase
NE - Norepmephnne
DA Oopamme
5HT - 5-hydroKjrtryptamine (serotoni
GABA - Gamma ammobutyric acid
CPU - Cholme phosphokmase
Lead concentration
Nutritional Blood, Brain,
Exposure status ^g/dl ullt
0.2 and 1.0 mg/kg IP ' ? ?
(100g)for45days

Brain stem NE,
5HT
1% lead acetate in drinking Under- Control = 0 '
water at parturition nourished 1% = 245






8-91 mg/kg/day by intuba- Normal 8-71 —
tionfrom 3-21 days of age
4% lead carbonate in Under- ? ?
mother's chow from par- nourished
tuntion to 21 days, 40
ppm in diet
5, 50 ppm in drinking Normal 180 day 180 day
water. 40 day pretreat- 0=5 0 = 18
ment of parents continued 5=6 5 = 20
from conception through 50 =10 50 = 27
adulthood
5 mg/ml lead acetate in Under- ? 1
drinking water starting at nourished
parturition
0.1-1000 mg/l lead acetate ' ? '
in drinking water for one
year
0,1, 2% lead acetate for 70 ' ' '
days


1) 67 n M in vitro lead — — —
chloride
2)3, 12, 60 mg/Pb/Kg total Impaired Control=008 0.06
dose over 2 weeks growth in 60 3=13.2 017
mg/kg group 12= 72.6 0.41
60= 380 1.02
4% lead carbonate at 2 Under- ' ?
weeks postpartum nourished,
reduced
brain weights






in)




Neurochemical parameter
Cerebro-corticol
ACh, AChE

NE - 20-27% decrease
5HT - No change
1) Steady-state ACh
2) CAT
3) AChE





1) Steady-state NE, DA, 5HT
2) AChE
1) Steady-state ACh, cholme
2) ACh turnover


Steady-state NE, DA




Brain HVA and VMA


Steady-state 5HT


Tyrosinase activity



K+ stimulated respiration
of cerebral slices

K+ stimulated respiration
of cerebral slices

Cerebral and cerebellar
rmtochondrial respiration













Results
ACh = 32-48% increase
AChE • No significant
change


1) Increased ACh in dien-
cephalon(12%)
2) Increased in medulla-
pons, hippicampus and
cerebral cortex (11-12%)
3) Lower in medulla-pons,
midbrain and dien-
cephalon (10-20%)
1) No change
2) Decreased (marginal)
1) No change in ACh, in-
creased cholme
2) Decreased ACh turnover
(33-51%)
Decreased DA at 28 days of
age
Increased NE at 180 days of
age

Increased 33 and 48%


No change


No effect



Inhibition

Inhibited at 12 and 60
mg/kg exposure level


Impaired respiration after 2
weeks of treatment











        11-40

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   Several  studies utilizing  high  levels of lead  ex-
 posure have reported inhibition of cholinergic func-
 tion.  In a series  of  experiments on the mouse,
 Silbergeld  et al.308-309 and Carroll et al.316 reported
 decreased  potassium-induced  release  of
 acetylcholine  (ACh)  and   decreased  high-affinity
 transport of choline. Unfortunately, no control  for
 growth retardation was provided in  these experi-
 ments and  relatively high external exposures to lead
 were required to produce the effect. This was also
 true in the rat studies reported by Modak et al.3"
 and Shih and Hanin.315 At  lower levels of external
 exposure,  with  no accompanying growth retarda-
 tion, no consistent effects on  cholinergic function
 have been  reported (cf. 283 and  318). Thus, if im-
 paired cholinergic  function  during in  vivo lead ex-
 posure is also found in the absence of undernutri-
 tion, and/or growth retardation, which is probable in
 view of the in vivo work reported later in this section,
 then its relevance to behavioral effects  seen at lower
 exposure levels will need examination.
   The effects of lead exposure  on  catecholamine
 function have also been extensively studied. Find-
 ings have  been  reported of increased steady-state
 levels of norepinephrine,277-307'308 increased activity
 of monamine oxidase  (MAO),309 increased synap-
 tosomal  transport of the precursor tyrosine,308 and
 increased amounts of the norepinephrine metabolite,
 vanillyl mandelic acid, and homovanillic acid in the
 brain.319 In studies  on  steady-state  levels  of
 norepinephrine,  changes have been reported either
 in the absence of undernutrition227 or  when values
 have  been  compared to pair-fed controls.307 How-
 ever, inconsistencies within  a given laboratory (cf.
 278 vs. 307), absence of similar findings in different
 laboratories (cf. 283 and 310), and findings of de-
 creased steady-state levels313 make any conclusions
 regarding  lead-induced  changes  in  noradrenergic
 systems equivocal. This uncertainty is also found in
 the reports on dopamine changes following lead ex-
 posure (cf.  277,  278, 314 vs. 283, 307, 310).
  Human studies  attempting to  relate subclinical
 lead exposures to signs of altered  brain monoamine
 function  have been  initiated utilizing urinary levels
 of monoamine neurotransmitter metabolites  as in-
 dices of CNS monoamine turnover rates. Although
 initial studies on catecholamine excretion have sug-
gested a lead effect, an appended note by Silbergeld
 and Chisholm319 indicated difficulty in finding one
of the earlier reported effects in subsequent studies.
This clinical  study again emphasizes  some of the
 problems and  uncertainties that have  beset in-
vestigations of low-level toxicity. Also, as indicated
 by Wender et al.,321 urinary metabolites reflect pri-
 marily peripheral  nervous  system  activity.  In
 another study322 altered levels of 5-hydroxyindole
 acetic acid (5-HIAA) were reported in the urine of
 occupationally lead-exposed battery factory
 workers,   suggesting   possible  lead  effects  on
 serotonin  (5-hydroxytryptamine)  systems.  No
 parallel supportive evidence from animal studies has
 been advanced for such an  effect, however, and in
 fact most  reports claim negative findings for any
 type  of measurements  of  brain serotonin  func-
 tion.283-308'312-314
   The reasons for the inconsistencies of lead-in-
 duced changes  in  monaminergic and cholinergic
 functions may be the result in part of interlaboratory
 differences in dosing regimens and other variations
 in  experimental protocol.  One note  of caution,
 however, is appropriate here in that highly variable
 results are seen within  different  laboratories, even
 with the same exposure regimens, assay procedures,
 etc., from experiment to experiment. This might sug-
 gest that some subpopulations of rats or mice might
 be resistant to lead effects on  monoamine transmit-
 ters whereas others are more vulnerable, possibly
 because of genetic factors, subtle variations in diet,
 etc.  More carefully controlled studies in the future
 that explicity manipulate such variables (genetics,
 nutrition,  etc.) may reveal lead  effects  even at low
 exposure levels,  given  the  right circumstances or
 population segment tested.
   Finally,  the  recent  report  of Nathanson  and
 Bloom323  indicated that in  vitro  lead exposure in-
hibits adenyl cyclase activity (I50 =  2.4 /u.M). This
enzyme is responsible  for  the  synthesis  of cyclic
adenosine 3',5'-monophosphate (c-AMP) which has
been shown to play an important role in the mechan-
ism of action  of a number of hormones,  including
neurotransmitters. The  effects of lead exposure on
adenyl cyclase and the resultant effects on neuro-
transmitter systems warrant further investigation.
  Several recent reports have dealt with the effects
of lead exposure on brain-energy metabolism. Bull
et al.253 reported that both in vivo and in  vitro lead
exposure  inhibited potassium-stimulated  respira-
tion. Of  interest was  the  finding that lower brain
levels of lead (approximately l/30th) were required
to inhibit respiration in vivo than in vitro. Also, these
results were seen in animals showing normal growth
(12 mg/kg group). Similar  findings of  inhibited
respiration using isolated mitochondria  were re-
ported by Holtzman and Hsu320 and by Brierley.324
  In contrast to the general lack of consistent effects
on steady-state levels of cholinergic substances and
                                               11-41

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associated enzymes, consistent evidence for effects
of lead on cholinergic synaptic uptake and release
mechanisms have been reported.
  More specifically, lead resembles other divalent
cations in that it appears to interfere with chemically
mediated synaptic transmission as demonstrated by
studies of peripheral neural functions. Kostial and
Vouk325 reported  that in vitro perfusion of the cat
superior cervical ganglion with 4.8 fj,M lead nitrate
depressed  or blocked nerve transmission. Contrac-
tion  of  the  nictitating  membrane  during
acetylcholine perfusion was unaltered. Also, perfu-
sion of the  ganglion with  excess calcium  restored
acetylcholine release  and  thus  reversed the  lead
blockade.  From these findings Kostial  and Vouk
concluded that lead depressed synaptic transmission
by  impairing acetylcholine release from  the  pre-
synaptic terminals.
  Manalis  and  Cooper326 and  Cooper  and
Manalis327 showed that lead can influence both pre-
and  postsynaptic events. Using the frog (Rana  ip-
piens) sciatic-nerve/sartorius-muscle preparation in
vitro, they demonstrated that the principal effect of
lead  was  on  presynaptic  transmitter  release,
although lead had a weak,  curare-like effect on the
postsynaptic response to applied acetylcholine. They
confirmed the findings of Kostial and Vouk325 that
lead depresses  the phasic  release of transmitter
evoked by nerve stimulation. They further observed
that  lead  increases  spontaneous  release  of
acetylcholine as evidenced by increased miniature
end-plate potentials (MEPP's).  These  MEPP's
represent the response of the postsynaptic membrane
to released acetylcholine in quantities that are in-
sufficient to depolarize the membrane to threshold
levels. In  a subsequent  experiment  Kober  and
Cooper328 demonstrated that in the frog, lead blocks
synaptic transmission in the sympathetic ganglion by
competitive antagonism  of spike-evoked  entry  of
calcium into the presynaptic nerve  terminals with a
resultant reduction in acetylcholine release.
  Experiments by  Silbergeld et al.329-330 indicated a
similar blockade of transmitter release by lead in the
rat. Furthermore,  they reported a reduced force of
contraction  in  the . phrenic-nerve/diaphragm  pre-
paration  from  mice exposed to lead from  birth
through 60 days of age. The nerve-muscle prepara-
tion from  these  lead-exposed  animals showed  a
reduction in force of contraction with nerve stimula-
tion. Also, a reduced force of contraction  was re-
ported upon direct stimulation of the muscle.  This
observation  agrees  with  the  weak  postsynaptic
effects of lead reported by  Manalis and Cooper;326
but  unfortunately,  no data  were  presented  by
Silbergeld  et al.329-330 on  the  muscle contraction
following electrical stimulation, so the relative im-
portance of this finding cannot  be  evaluated.
Finally, Cooper and  Steinberg331 demonstrated that
lead is also capable of blocking neural transmission
at the adrenergic synapse. They measured the con-
traction force of the rabbit saphenous artery follow-
ing stimulation of the sympathetic nerve endings.
Again, the results indicated that lead blocks muscle
contraction  by an  effect  on  the  nerve terminals
rather  than an  effect on the  muscle.  Since  the
response recovered when calcium concentration was
increased in the  bathing solution, it was concluded
that lead does  not  deplete  transmitter stores in
the  nerve  terminals  but  more  likely  blocks
norepinephrine release.
   In summary, in vitro experiments have  demon-
strated that lead  interferes with synaptic transmis-
sion in the peripheral nervous system. This effect ap-
pears to be related to  a competitive  inhibition
of  calcium-mediated,  evoked  release of  the
neurotransmitters. Further, lead was shown  to  in-
crease  the spontaneous release of transmitter from
some synapses.
  The  effects of  lead on synapses within the CNS
have not been  extensively  studied. Carroll et  al.,316
however, reported a decrease in potassium-induced
release of both choline and acetylcholine from corti-
cal minces  of mice chronically exposed to lead.
These changes in acetylcholine metabolism suggest
that, as is the case of the peripheral nervous system,
the central cholinergic function may be depressed by
lead. This is further supported by  a  report of Shih
and Hanin315 that lead exposure decreased in vivo
acetylcholine turnover rate in cortex, hippocampus,
midbrain, and striatum (35, 54, 51, and 33 percent
decreases, respectively) in  rat brain  after neonatal
lead exposures. Along with the in vitro findings, this
provides additional evidence  supportive of lead-in-
duced  dysfunctions of cholinergic synaptic uptake
and release mechanisms.  Unfortunately,  these
results and many from the above peripheral function
studies were obtained at rather high exposure  levels
and most were  performed on  undernourished or
growth-retarded animals.
  One final note  concerns the relationship between
levels of lead in blood and brain. Several studies on
rodents have reported simultaneous lead values for
blood and  brain  resulting from lead exposures of
various durations. Bornschein et al.270 exposed mice
to  5  mg/ml lead acetate starting at parturition.
Brain/blood ratios showed a steady increase from 20
                                               11-42

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to 100 days of age. Ratios of 1.05, 2.55, and 4.08
were reported for mice at 20, 40, and  100 days of
age, respectively.  This increase in  the  brain/blood
ratios resulted from both a steady increase in brain
lead levels (increasing from 200 /ug % at 20 days of
age to 584 jitg % at 100 days of age) and a decrease
in blood lead levels (decreasing from  190 ppm at 20
days to 143 ppm at 100 days).
   Cahill et al.277 reported blood and brain levels of
lead in rats exposed from conception to either 0, 5,
or 50 ppm lead in the drinking water. At parturition,
brain/blood ratios of offspring were 0.91 and 0.5 for
exposure levels  of 5 and 50 ppm,  respectively. At
180  days of age, these ratios  were 3.3 and  2.7,
respectively. A ratio of approximately 1  was also re-
ported by Grant et al.310 in 30-day-old rats exposed
to various levels of lead from 3 to 25 days of age.
These data  are  consistent  with  the  results  of
Bornschein  et  al.270  and  indicate  that  initially
brain/blood ratios are approximately unity but that
with continued exposure the ratios steadily increase.

11.5.2.6  SUMMARY  AND CONCLUSIONS
  Data obtained in laboratory animals,  such as that
reported in the rat by Pentschew and Garro,52 indi-
cate  that encephalopathy is produced by high-level
perinatal exposure to lead. This encephalopathy oc-
curs to varying  degrees in different species and is
characterized  by the relative involvement of
neuronal  degeneration and vasculopathy.
  It seems clear that with regard to CNS toxicity the
developing organism  represents the population  at
greatest  risk.  Whether this  increased  risk  is  at-
tributable to a  greater sensitivity  or to  a  greater
susceptibility of the  developing organism will  re-
quire further testing. That is, with a given external
exposure, the CNS  of  the  developing  organism
reaches  a  higher concentration  of lead  and  is
therefore more  susceptible to poisoning. Whether
the threshold for a given effect of lead is  lower in the
immature nervous system versus the adult will need
to be determined.
  There  is also good  evidence that  perinatal  ex-
posure to lead even at moderate exposure levels will
produce  delays  in both  neurological  and sexual
development. Because these effects  have been dem-
onstrated to occur in the absence of either under-
nutrition or growth  retardation, it has been sug-
gested that they represent direct effects of lead in the
respective organ systems.
  In the animal studies, locomotor activity has been
the most commonly used  behavioral  index of lead
toxicity. The data  reviewed   here  suggest that
perinatal exposure to lead produces an increase in
the animal's behavioral reactivity. If the test condi-
tions are appropriate, this increased reactivity will
be  manifested  as  increased  locomotor  activity,
although some text situations will show reduced ac-
tivity. Therefore, the altered activity  levels per se
are merely reflective of a more basic nervous system
dysfunction.  Close  scrutiny  of the available data
would also suggest that altered locomotor activity in
young animals occurs only at moderately  high  ex-
posure levels. A comparison  of the data of Sobotka
and Cook282 and Overmann275 are of interest in this
regard (see Table 11-4). Using gastric intubation,
Overmann reported  hyperactivity in  young  rats
whose  21-day blood lead levels  were 226 /ug/dl.
Sobotka  and  Cook,  using  a  similar exposure regi-
men, found normal activity levels with 22-day blood
lead levels of 71 /ug/dl. It appears, therefore, that
this early change in  reactivity occurs at fairly high
blood lead levels. It may be, then, that the changes
in activity currently  reported in laboratory animals
are more representative of a post-encephalopathic
hyperactivity than of subclinical effects as has been
suggested.
  On the other hand, the reactivity changes reported
in older animals with  lifetime exposure occur at
much lower blood levels (cf.  264,  277, and 285).
  Finally, reports on the effects of lead exposure on
the  acquisition  and/or  performance  of  operant
responses indicate that perinatal exposure to moder-
ate and low levels of lead may disrupt this behavior.
Thus, external exposures that result in blood lead
levels ranging from  30 to 80 /Ag/dl have been  re-
ported to  disrupt  cognitive  function (see  Table
11 -5). As is true with the clinical data, this area re-
quires further investigation.
  It has  been  repeatedly indicated  that  serious
methodological problems  exist  in  the  animal
literature which make it difficult to interpret many
of'the available data. Future research in this area
would benefit from more tightly controlled experi-
ments including:
   1.  Better  documentation  of internal exposure,
      not only with  respect to lead levels but also
      with respect to correlative indices of lead tox-
      icity, e.g., ALAD, protoporphyrin, etc.
   2.  The use of exposure protocols that do not pro-
      duce confounding variables such as under-
      nutrition,  differences in both litter size and
      number of litters per treatment  group, etc.
   3.  Validation of  behavioral  tests  using  both
      positive control substances  and  cross corre-
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      lation with other  physiological  indices. This
      would include research aimed at more closely
      defining both the  relative sensitivity  of the
      CNS compared to other organ systems as well
      as the contribution of other indirect actions of
      lead on the resulting behavioral changes.

11.6 EFFECT  OF  LEAD  ON  THE  RENAL
SYSTEM
11.6.1  Acute Effects
  More than  60 years ago an English toxicologist,
Thomas Oliver,332 distinguished acute effects of lead
on the kidney from lead-induced chronic nephropa-
thy. Acute renal effects of lead are seen in persons
dying of acute lead poisoning or suffering from lead-
induced  anemia and/or  encephalopathy and are
usually restricted to  nonspecific  degenerative
changes in renal tubular lining cells, usually cloudy
swelling, and  some degree of cellular necrosis. Cells
of the  proximal  convoluted  tubules  are  most
severely  affected.  As long  ago as 1928, Pejie333
emphasized that the degenerative changes in prox-
imal tubules,  rather than the vascular changes often
referred to in earlier studies, are primary evidence
of injury to the kidney in lead poisoning. Many sub-
sequent studies have shown at least three pathologi-
cal alterations in the renal tubule with onset during
the early or the acute phase of lead intoxication in
the kidney. These include the formation of inclusion
bodies in nuclei of proximal tubular lining cells and
the development of functional as well as ultrastruc-
tural changes in renal tubular mitochondria.
  Dysfunction of proximal renal tubules (Fanconi's
syndrome) is  manifested  by  aminoaciduria,
glycosuria, and  hyperphosphaturia,  and was first
noted  in  acute lead  poisoning  by  Wilson  and
coworkers in  1953.334 Plasma amino acids were nor-
mal, which suggested that the aminoaciduria and
other functional abnormalities were of renal origin.
Subsequently, aminoaciduria in children with acute
lead poisoning  was  observed by Marsden  and
Wilson335 in England, and Chisholm85'86 found that
9  of 23  children  with  lead encephalopathy had
aminoaciduria,  glycosuria,  and hypophosphatemia.
Aminoaciduria  was  seen  more  consistently in
Chisolm's studies than the other two manifestations
of tubular damage. Thus, the amino acid transport
system is probably  more sensitive to the toxic actions
of lead than  the transport systems for  glucose and
phosphate. The aminoaciduria was generalized in
that the amino acids excreted  in  greatest amounts
were those normally present in urine. The condition
was related to severity of clinical toxicity and was
most marked in children with encephalopathy. The
aminoaciduria disappears  after  treatment with
chelating  agents  and clinical remission of  other
symptoms of lead toxicity.85 This is an important ob-
servation relative to the long-term or chronic effects
of lead on the kidney.
  In a group of children with slight lead-related
neurological  signs, generalized aminoaciduria was
found in  8 of 43 children with blood lead levels of
40  to  120 jig/dl."  It  should be  noted  that  the
children reported to have aminoaciduria in the study
of Pueschel" were not specifically  identified as to
their lead exposure. Thus, it is not possible to state
what level of lead exposure within the blood lead
range of 40 to 120 ngld\ was associated with the
effects. A similar  renal tubular syndrome has been
reported to occur in industrially exposed adults.336

11.6.2 Chronic Effects
  There is convincing evidence in the literature that
prolonged lead exposure in humans337 can result in
chronic lead  nephropathy. Cramer et al.337 in 1974
reported on a group of 7 lead-exposed workers who
had been exposed  up to 20 years. Aminoaciduria was
not found, and inulin clearance and renal blood flow
were also reported normal. The average blood lead
level was 100 Aig/dl, the minimum was 71 pgldl, and
all had strikingly high urinary ALA excretion. Some
with very long exposures were reported  to have  in-
terstitial  and peritubular fibrosis, determined  by
renal biopsy. This pathological finding is commonly
referred  to as chronic lead nephropathy, which is
characterized by  slow development of contracted
kidneys with pronounced arteriosclerotic changes,
fibrosis, glomerular atrophy, and hyaline degenera-
tion of these vessels.  This is a progressive disease,
sometimes resulting in renal failure. It seems to oc-
cur sporadically,  primarily  in industrially exposed
workers  and in older adults who  have been diag-
nosed as having lead poisoning early in life. There is
also some evidence  that  it  occurs  in  long-time
drinkers of lead-contaminated whiskey, as reported
by Morris et al.338 in the cases of 16 adults treated
over  a  10-year  period.  This  study reported lead
poisoning manifested by the same  symptoms found
in children. The most specific pathological  change
reported was the presence of large  numbers of acid-
fast intranuclear  inclusions within  the cells  of the
kidney tubules and liver. Ball and Jorenson339  re-
ported a high frequency of saturnine gout resulting
from the consumption of  lead-contaminated
whiskey, convincingly demonstrating reduced renal
uric acid clearance associated with plumbism.
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   In a series of 102 cases of lead poisoning studied
 by Lilis  et al.,340 18  cases of clinically verified
 chronic  nephropathy  were found. For  the whole
 series, the mean blood lead level was approximately
 80  Aig/dl,  with  a  range  of  42  to  141  ju,g/dl.
 Nephropathy  was  more  common  among patients
 who  had been exposed to  lead for more than 10
 years than among those who had been exposed for
 less than 10 years.  In both studies,  reduced  urea
 clearance preceded reduced creatinine clearance.
   In the Danilovic study,341 7 of 23 cases had blood
 lead  levels of about 100 to 200 yu.g/dl. In the studies
 of Albahary et al.,342 blood lead levels were not re-
 ported but exposure levels must have been quite high
 because  the mean ALA excretion was  about 37
 mg/24 hr for 29 workers. These studies indicate that
 the nature of the  effect is glomerulovascular,  with
 reduction  in  clearance of urea and,  in more
 protracted exposures, also of endogenous creatinine.
 Also, reduced clearance of uric  acid was observed in
 the study of Albahary et al.342
   In  the recently reported studies of Wedeen et
 al.,343 eight subjects suspected of excessive occupa-
 tional exposure were  given detailed  examinations
 for renal function. Four of the subjects showed signs
 of abnormal  renal function.  In one  subject with
 asymptomatic renal failure, chelation therapy in-
 creased the  glomerular filtration rate, the p-amino
 hippurate (PAH) extraction, and the maximal PAH
 excretion rate, and improved the proximal tubule
 ultrastructure, despite decreased renal plasma flow.
 Three of the subjects showed proximal tubule abnor-
 malities  via biopsy. In eight subjects, lead-induced
 nephropathy was  established  by  exclusion.   The
 blood lead values of the individuals ranged from 48
 /xg/dl, for the subject having  asymptomatic renal
 failure, to 98 /xg/dl. The lead levels of the other two
 subjects in the preclinical renal dysfunction category
 were  51 and 66 ,wg/dl. All subjects showed glomeru-
 lar filtration rates of less than 87  ml/min/1.73m2.
 The authors suggest on the basis of these studies that
 lead nephropathy may be an important occupational
 hazard in the U.S. lead industry.
   A series of reports from Queensland, Australia,344
 points to a  strong association between severe lead
 poisoning in childhood  including central  nervous
 system symptoms  and  chronic  nephritis in early
 adulthood. Henderson345 followed up 401 children
 who had  been diagnosed as having lead poisoning in
 Brisbane between 1915 and 1935. Of these 401 sub-
jects, 165 had died, 108 from nephritis or hyperten-
 sion.  This is greatly in excess of expectation. Infor-
 mation was obtained from 101 of the 187 survivors,
 and  17  of  these  had   hypertension  and/or
 albuminuria. In a more recent study, Emmerson346
 presented  a criterion for  implicating  lead as an
 etiological  factor  in  such  patients:  the patients
 should  have an excessive urinary excretion of  lead
 following administration of calcium EDTA. In his
 study,  32  patients with chronic renal disease at-
 tributable to lead poisoning had similarly elevated
 excretion of lead. The presence of intranuclear in-
 clusion bodies  is very helpful in establishing a rela-
 tionship between renal lesions and  lead toxicity, but
 inclusion  bodies are not always present in persons
 with chronic lead nephropathy.
  Attempts to  confirm  the relationship  between
 childhood lead intoxication and chronic nephropa-
 thy have not been successful in at least two studies in
 the United  States. Tepper90 found no evidence of
 chronic renal disease in 42 persons with a well-docu-
 mented history of childhood plumbism  20 to 35
 years earlier at  the  Boston  Children's  Hospital.
 Likewise, Chisolm347 found no evidence of renal dis-
 ease in 62 adolescents known to have had lead intox-
 ication  11 to 16 years earlier. An important distinc-
 tion between the Australian group and patients in
 the United  States was that none of Chisholm's347
 subjects showed evidence of increased residual body
 lead burden following the EDTA mobilization test.
 This difference has suggested to Chisholm that lead
 toxicity in the Australian children must have been of
 a different type, with a more protracted course than
 that experienced by the American children. Most
 children in the United States who  suffer from lead
 toxicity do so early in childhood, between the ages of
 1 and 4, the source usually being oral ingestion of
 flecks of wall paint and plaster containing lead.
 11.7 REPRODUCTION AND DEVELOPMENT
 As reviewed thus far in the present chapter, the ad-
 verse effects of lead on the hematopoietic, nervous,
 and renal systems have been well  documented across
 a wide range of exposure levels and represent a triad
 of symptoms classically associated with lead poison-
 ing. Extensive evidence for ad verse effects of lead on
 reproduction and development  has also  been  ac-
 cumulating in the literature for many years and has
 become a matter of increasing medical  concern.
 Data from both human and animal  studies indicate
that  lead  exerts gametotoxic, embryotoxic, and,
 possibly, teratogenic effects that  impact on the pre-
 and postnatal survival and development of the fetus
and newborn, respectively.  In addition, it appears
that the viability and development  of the fetus may
also be markedly affected by lead indirectly via  ad-
                                                1-45

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verse  effects on  various  health  parameters,  e.g.,
nutritional state or blood chemistry, of the expectant
mother. The vulnerability of the fetus to such  lead
effects while in utero has contributed to concern that
pregnant women may be a special group at risk for
lead poisoning. Certain information on adverse  lead
effects on male  reproductive  functions, it should
also be noted, has led to additional concern regard-
ing the impact of lead on men.

11.7.1  Human Studies
  Data suggesting that lead exerts adverse effects on
human reproductive functions have existed  in the
literature since before the turn of the century. For
example, Legge,348 in summarizing the reports of 11
English factory inspectors in  1897, found that of 212
pregnancies in 77 female lead workers only 61 living
children  were produced. Fifteen workers had never
become pregnant. There were 21 stillborns, miscar-
riages occurred 90 times, and, of 101 children born,
40 died in the first year. Legge also noted that when
pregnant animals were fed lead they always aborted.
He concluded   that maternal exposure to  lead
resulted in a direct action of the element on the fetus.
  In 1911, Oliver180 published statistics in Britain
on  the effect of lead on pregnancy  (Table  11-10)
which showed that the miscarriage rate was elevated
among women employed in industries in which  they
were exposed to  lead.
       TABLE 11-10. STATISTICS ON THE EFFECT
            OF LEAD ON PREGNANCY""
                             Number of    Number of
                             abortions and  neonatal deaths
                             stillbirths per   (1irst year) per
         Sample                 1000 females   1000 females
Housewives
Female workers (mill work)
Females exposed to lead
premantally
Females exposed to lead
after marriage
432
476

86.0

133.5
150
214

157

271
  Since the time of the above studies, women have
been largely  excluded from occupational exposure
to lead. Even before the effects of industrial lead ex-
posure  on pregnancy were  documented, however,
lead compounds were known for their embryotoxic
properties and were often used  to induce criminal
abortion.349 In a study by Lane,350 women exposed
to lead  levels of 75 /^ig/m3 were examined for effects
on reproduction. Longitudinal data on 15 pregnan-
cies indicated an increase in the number of stillbirths
and abortions. No data were given on urinary lead in
women, but men in this sample had urinary levels of
75 to 100 /ig/liter.
  In a more recent study351 of the pregnancies of 104
Japanese women married to lead workers before and
after their husbands began  lead work, miscarriages
increased to 84.2/1000 pregnancies from a prelead
rate  of 45.6/1000. The miscarriage rate for 75
women not exposed to lead was 59.1/1000.
  Another recent study by Fahim et al.352 in humans
suggests that subtoxic lead  absorption during preg-
nancy may be associated with an increased incidence
of preterm delivery and early membrane rupture:
253  women delivered in Rolla, Missouri (Region
I), which is 60 to 80 miles  from  lead smelters, and
249  women  delivered  in Columbia,  Missouri
(Region II), where there is no lead industry. The in-
cidence of term pregnancies with early membrane
rupture was 17 percent in Region I and 0.41 percent
in Region II.  The incidence of premature deliveries
was  13.04 and  3 percent, respectively.  A high cor-
relation was found between lead concentrations in
maternal and  fetal blood:  both were significantly
higher in the cases of preterm pregnancies and early
membrane ruptures than in term pregnancies.
  Pregnancy  is a stress that may place a woman at
higher risk for  lead exposure. Both iron deficiency
and calcium deficiency increase the susceptibility of
lead toxicity, and women have an increased risk of
both deficiencies during pregnancy and postpartum.
The  cause of the increased  perinatal mortality may
be a mutagenic or teratogenic effect of lead.353
  The above studies clearly demonstrate an adverse
effect of lead  on human  reproductive  functions,
ranging from reduced pregnancy rates to increased
incidence  of  miscarriages, premature  deliveries,
and  stillbirths. The  mechanisms underlying these
effects are unknown at this time. Many factors could
contribute to the above results,  ranging from lead
effects on  maternal nutrition  or  hormonal  state
before  or  during  pregnancy to more  direct
gametotoxic,  embryotoxic,  or  teratogenic  effects
that  could  affect fertility  or fetal  viability during
gestation.  Efforts have been made  to define more
precisely  the  points  at  which lead  may  affect
reproductive  functions both  in  the human  female
and male, and in other animals, as reviewed below.
  In regard to potential lead effects on ovarian func-
tion  in human females, Panova354 reported a study
of 140 women  working  in  a printing plant for less
than  1 year (1  to 12 months) where  ambient air
levels were <7 fj.g lead/m3. Using a classification of
various age groups (20 to 25, 26 to 35, and 36 to 40)
and  type of ovarian cycle  (normal, anovular, and
disturbed  lutein  phase),  Panova  claimed  that
statistically significant differences  existed  between
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 the lead-exposed and control groups in the age range
 of 20 to 25 years. It should be noted that the report
 does not show the age distribution, the level of sig-
 nificance, or the data on specificity of his method of
 classification. Also, Zielhuis and Wibowo,355 in a
 critical review of the  above study, concluded that
 study design and  presentation of data are such that it
 is difficult to evaluate the author's conclusion that
 chronic exposure to low lead in  air leads  to a dis-
 turbed function of ovaries. It should be noted that
 no consideration  was given to the  dust levels of lead,
 an important factor in print shops.
   Unfortunately, little else besides the above report
 exists in the literature in  regard to assessing  lead
 effects on ovarian function or other factors affecting
 human female fertility. Nor are there  many studies
 offering firm data on maternal variables, e.g., hor-
 monal state,  that are known to affect  the ability  of
 the pregnant woman to carry the  fetus full term.  In
 addition, there are no studies that demonstrate con-
 clusively a direct lead-induced teratogenic  effect on
 the human fetus, although the transfer of lead across
 the human placenta and its potential  threat to the
 conceptus have been recognized for more than a cen-
 tury.356 Nevertheless,  documentation  of placental
 transfer of lead to the fetus and data on  relevant
 parameters, e.g., fetal blood lead levels  resulting
 from such transfer, help to  build  the case for  a po-
 tential, but as yet not clearly defined, threat for sub-
 tle teratogenic and  other deleterious health effects.
  The  placenta!  transfer of lead has  been estab-
 lished, in part, by various studies that have disclosed
 measurable quantities  of lead in  human fetuses or
 newborns. An  analysis of  human  fetal tissues by
 Barltrop357 demonstrated that placental transfer  of
 lead began as early as the 12th week of gestation and
 that total lead content increased throughout fetal
 development, with the highest concentrations occur-
 ring in bone, kidney, and liver, and lesser, but sig-
 nificant,  amounts occurring in  blood, brain,  and
 heart. Barltrop has also pointed out  that the dis-
 tribution of lead  within the fetus  at different stages
 of development is probably more important than the
 total amount present at birth.
  Of interest  in this regard are the data  of Schroeder
 and Tipton,358 who  showed that the mean lead level
 in brains of stillborn U.S. children (n = 22) was 10
 ppm (dry ash), but that there was  an  undetectable
 level for normal  infants, young children, and teens
(0 to 19 years; n =  23). In this study,  however, the
 levels of detection are not stated, so that the relative
 increase in level cannot be assessed. Also, it is not
clear to  what extent fetal  tissue preparation  and
preservation were controlled for contamination.
  Wibberly and coworkers359 have  recently found
that placental  lead  levels in the case of stillbirth or
neonatal death were significantly higher than in the
case of normal births. Placenta!  levels were greater
than 1.5 /j.g/g in only 7 percent of the normal births,
whereas levels were greater than this in 61 percent of
the stillbirths  or neonatal  deaths.  This  does not
mean that lead is a  causal factor in such deaths and
could indicate that  lead accumulates in the placenta
in times of fetal stress.
  There  are a number of recent studies on the
passage of lead  through the placental barrier as
assessed by lead levels in cord blood and/or mater-
nal blood. For example, in the study of Gershanik et
al.,360,361  98  cord-blood  samples  matched  with
maternal blood samples showed a high correlation
between lead levels in infants (mean = 10.1 /Ag/dl)
and  their mothers  (mean  =  10.3  /xg/dl), with a
product moment  correlation coefficient of 0.6377.
This suggests that infants may be born with blood
lead levels  that  essentially  match  those  of their
mothers. In regard  to assessing groups at risk for
such prenatal exposure, these authors also studied a
group  of 218  cord-blood samples (170 urban, 48
rural) and observed that the mean urban value (9.7
/xg/dl) was significantly different (p <0.05) from the
mean rural  value (8.3  ju.g/dl), suggesting  a higher
risk  of urban newborns for prenatal lead exposure.
Similarly, Scanlon362 sampled cord-blood randomly
from normal infants whose mothers had suburban (n
= 15) or urban (n = 13) residences. The average ur-
ban value was 22.1  /xg/dl (10 to 37 /Ag/dl), whereas
the corresponding  suburban  level was 18.3 /u.g/dl.
Smoking was   without  significant effect  on  these
levels.  These results tend to confirm the findings of
Gershanik  et  al.361 Harris and Holley,363 on the
other hand, surveyed cord and maternal blood in 24
pairs (11 suburban and 13 urban) and found a  mean
cord-blood value of 12.3 ^tg/dl and a mean maternal
blood level of  13.2 /u.g/d\. No significant difference
Was therefore seen in cord-blood levels as a function
of maternal residence, though a larger sample might
have yielded significant effects since the ones found
were in the  same direction as those  found in  other
studies.
  That the prenatal exposure of the fetus to  lead,
even in the absence  of teratogenic effects, may be of
consequence in regard to adverse health  effects is
demonstrated  by  studies relating fetal and cord-
blood levels to  some changes  in fetal  heme synthesis
and claimed incidences of premature births. Haas et
al.364 examined 294 mother-infant pairs for blood
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lead levels as well as for the corresponding urinary
ALA levels. The maternal blood mean was 16.89
Hg/dl and the fetal  blood mean was 14.98, with a
correlation of 0.538 (p <0.001). In the infants, the
levels of blood lead  and  urinary  ALA were
positively correlated (r  =  0.1877,  p  <0.01).
Whether  a  biological  significance  exists here,
however, is not clear. According to the authors,364
the positive correlation  between lead in blood and
urinary ALA for the group as a whole indicated
there was already an effect  at  lower blood  lead
levels, i.e., increased susceptibility of heme  syn-
thesis.
  In a study of Fahim365 on cord-blood lead levels,
blood lead values in pregnant women having  pre-
term  delivery and  premature membrane rupture,
and residing in a lead belt area (mining and smelting
area), had significantly higher blood lead levels  than
women delivering at full term. A confusing aspect of
this study, however,  is the similarity of blood  lead
levels in women in the nonlead and lead belt areas.
Though a number of other problems may be  seen
with the analytical aspects of this study, it must be
noted that among the 249 pregnant women in the
control group outside the lead belt area the percen-
tage of women having preterm  deliveries and  pre-
mature rupture were 3 and 0.4 percent, respectively,
whereas the corresponding values for the lead  area
(n =  253) were  13.04  and  16.99 percent, respec-
tively.
  With reference to more subtle prenatal effects,
Palmisano et  al.366  noted failure  to thrive  and
neurological deficits in a 10-week-old infant whose
mother  had   lead  poisoning  concomitant   with
alcoholism during pregnancy. When this infant was
challenged with a chelating agent, an abnormal urin-
ary excretion of  lead was observed, indicating in-
trauterine exposure. Postnatal exposure in this case
was  ruled out. Other, more controlled laboratory
studies on animals (discussed later) also suggest that
teratogenic effects occur,  but usually only at  very
high lead exposure levels.
  A report367 on fatal birth defects in children  con-
ceived during a period of time when their father was
lead poisoned hints at important effects of lead on
the fetus being mediated via human males as well as
females. Certain  other  studies369'370 demonstrated
likely lead  effects  on various  aspects  of   male
reproductive  functions.
  Lancranjan  et  al.368  have  reported   that
moderately increased lead absorption (blood  lead
mean  =  52.8 /xg/dl) resulted  in gonadal impair-
ment. The effects on the  testes were shown to be
direct  in  that  tests  for  hypothalamopituitary in-
fluence were negative. A group of 150 workmen who
had long-term exposure to lead in varying degrees
was studied. Clinical  and  toxicological criteria were
used to categorize the men into four groups: lead-
poisoned workmen (74.5  /tg/dl) and those showing
moderate  (52.8  f^gld\),  slight  (41  ngld\), and
physiologic (23  /Ag/dl) absorption of lead.  Semen
analysis revealed asthenospermia, hypospermia, and
teratospermia  in  lead-poisoned workers and those
with moderately increased absorption of lead (blood
lead levels = 50 to 80 ^.g/dl for the latter). The ab-
normal spermatozoa  included binucleated,
bicephalus, amorphous, and tapered forms. In con-
trast, slightly increased or physiologic absorption of
lead had no effects  on the reproductive ability of
workmen.
  In the review of Stofen,369 data from the work of
Neskov in the USSR were  reported  involving 66
workers exposed chiefly to lead-containing gasoline
(organic lead). In 58 men there was a decrease or
disappearance of erection, in 41  there was early
ejaculation, and in 44 there was a diminished num-
ber of spermatocytes.
  The literature  reviewed here on lead effects on
human  reproduction and  development leaves little
doubt as to the fact that lead does,  in fact, exert sig-
nificant adverse health effects on reproductive func-
tions. Most studies, however, have  typically  looked
at the effects of prolonged  moderate-to-high ex-
posures to lead, e.g.,  those encountered in industrial
situations, and many  reports do not provide definite
information on  external  exposure  levels or  blood
lead levels at which  specific effects are observed.
11.7.2 Animal Studies
  Animal  experiments  have demonstrated that
levels of lead that are compatible with life have in-
terfered with  normal reproduction. Many  studies
assessed the effects of lead exposure of both parents
on  reproduction. Schroeder and Mitchener,370 for
example,  showed a   reduction in   the number  of
offspring of rats and mice that were given drinking
water containing lead in a concentration of 25 ppm.
In a subsequent report,371 however, it was noted that
animals in the earlier study  were  chromium defi-
cient. No effects were found in animals with normal
diets. The combined  effect of maternal and paternal
oral lead intoxication upon reproductive  perfor-
mance was studied in rats by Morris et al.372 who re-
ported significant reduction in weaning percentage
among offspring of rats fed 512 ppm lead. Stowe and
Goyer373 assessed the relative paternal and maternal
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effects of lead as measured by the progeny of F(
lead-toxic  rats.  Sprague-Dawley female rats being
fed laboratory chow with and without 1 percent lead
acetate were  bred to  normal,  mature, Sprague-
Dawley males. The pregnant rats were continued on
their  respective  rations  with  and  without   lead
throughout  gestation and  lactation. Offspring of
these matings, the F, generation, were fed the rations
of their dams and were mated in combinations as
follows: control female to control male (CF-CM),
control female to  lead-toxic male (CF-PbM), lead-
toxic female to control male (PbF-CM), and lead-
toxic female to lead-toxic male  (PbF-PbM). The
results identifying specific deleterious paternal and
maternal effects of lead toxicity upon rat reproduc-
tion are shown in  Table 11-11.
                   TABLE 11-11. REPRODUCTIVE PERFORMANCE OF  F, LEAD-TOXIC RATS373


Litters observed
Pups/litter
Pup birth weight, g
Weaned rats/litter
Survival rate, %
Litter birth weight/Dam breeding weight, %
Litter birth weight/Dam whelping weight, %
Gestation gam/Pups per litter, g
Nonfetal gestational/Gain/fetus, g


CF-CM
22
11 90 ±
674±
984±
89.80 +
28.04 +
19.09±
11 54 +
3.93 ±
0.40a
015
050
3.20
1.30
0.80
0.60
038



CF-PbM
24
10.10 +
5.92 +
7.04 +
73.70
2230
1597
11 20
483
+
+
±
±
±
050
0.13o
077o
790
0.90c
0.580
074
0.47
Type of mating


PbF-CM
878
5.44
5.41
52.60
19.35
1428
11.17
4.15
36
+
+
+
+
+
+
+
±
030b
0.13c.d
0 74c.d
7.20
1.000
0.66c
0.54
0.42



PbF-PbM
7.75
4.80
2.72
30.00
15.38
11.58
1234
3.96
16
±
±
+
+
+
+
+
+
z,<
8.20o,d,f
1 10C'C'^
0 78C'C'^
1.24
046
aMean ± SEM
^Significantly (p ^005) less than mean for CF-CM
"-Significantly (p < 0 01) less than mean for CF-CM
^Significantly tp 
-------
strated.376 Most other animal studies have utilized
rodents.
  Kennedy et al.377 administered an aqueous solu-
tion of lead to mice (days 5 to 15 of gestation) and to
rats from days 6 to 16 of gestation. At dosage levels
of 7.14, 71.4, and 714 mg/kg body weight there were
no  observed effects on  the  number  of  fetuses
resorbed  or  the number  of viable fetuses.  No
teratogenic effects on gross examination were seen,
and an effect on body weight was observed only at
the highest level employed (714 mg/kg).
  Hubermont et al.378 exposed female rats to lead in
drinking  water  (0.1, 1, and 10  ppm) for 3 weeks
before mating, during pregnancy, and 3 weeks after
delivery.  In the highest exposure group (10 ppm),
maternal and newborn blood and kidney lead values
were elevated. Inhibition of 8-ALAD and elevation
of FEP in tissues were also noted.
  Maisin et al.379 exposed female mice to lead in the
diet (0.1  and 0.5 percent) from  the day of vaginal
plug to 18 days afterwards. The number of pregnan-
cies decreased and the number of embryos succumb-
ing after  implantation increased.
  Similarly, Jacquet380 exposed  female  mice  via
lead in diet (0.125,  0.25, and 0.50 percent) from
vaginal plug to  16 to  18 days afterwards. At the mid-
dle  dosage,  pregnancy  incidence  decreased,  the
number of embryos  dying  before implantation in-
creased, and the number of corpora lutea showed a
decrease.  At the highest dosage,  the number  of
embryos dying after  implantation increased,
whereas  decreases  in  body weight  of  surviving
embryos  were seen.
  Other  studies have  focused on  lead effects on
paternal  reproductive functions.  For example, the
data from studies of rabbits,381 guinea pigs,382 and
rats373'383 indicate that paternally transmitted effects
from  lead can occur, including reductions in litter
size, in weights of offspring, and  in  survival rate.
  Cole and Bachhuber,381  using  rabbits,  were the
first to confirm  experimentally the  paternal effects
of lead  intoxication. The litters  of dams sired  by
lead-toxic  male  rabbits were smaller than those
sired  by control males.  Weller382 similarly demon-
strated reduced birth weights and  survival among
offspring of lead-toxic male guinea  pigs.

  Verma et al.384 fed a 2-percent aqueous solution
of lead subacetate in drinking water to 14 male Swiss
mice  for 4 weeks. The total mean  intake of lead
amounted to 1.65 g. They  placed the male with  3
virgin untreated females for 1 week. The overall in-
cidence of pregnancy, indicative  of  fertility, was
52.7 percent  in the control group as compared to
27.6 percent in the treated group. The fertility of the
treated  males was  reduced  to  50 percent. They
calculated the mutagenicity index (number of early
fetal deaths/total implants)  to  be 10.4 for lead-
treated mice versus 2.9 for  controls (X2 =  10.4, p f
0.05).
  In the study of Maisin et al.,379 male mice received
0.1  and  1 percent lead, as the acetate,  in the diet.
The percentage of abnormal spermatozoa  increased
with increasing  exposure.  Ultrastructural changes
were present.
  In the review of Stofen,369 several studies from
Russian  laboratories  were evaluated. As cited  by
St6fen, Egorova et al., for example, injected lead at
a dose of 2 Mg/kg 6 times over a 10-day period and
observed damage to testes  and spermatozoa.  Stofen
also reported that Golubova et al. found morpho-
logical changes in testes  of rats that received 2 mg
lead/kg but not in rats receiving 0.2 mg/kg.
  Lead appears to be teratogenic in some species, at
least  at  high  exposure   levels. McClain and
Becker,385 for example, administered single doses of
25 to 70 mg/kg of lead nitrate intravenously to preg-
nant rats on  days 8  through 17  of gestation.  A
urorectocaudal syndrom  of malformations was pro-
duced when lead was administered on the 9th day of
gestation. The lead nitrate was increasingly embryo-
and fetotoxic when administered  on later days of
gestation (days 10 to  15) but not teratogenic. Perm
and Carpenter386 as well as  Perm and  Perm387  re-
ported increased embryonic resorption and malfor-
mation rates when  various  lead  salts  were  ad-
ministered to pregnant hamsters on the 8th  day of
gestation. The teratogenic  effect of lead was almost
completely restricted  to the tail region. Malforma-
tions of the sacral and caudal vertebrae, resulting in
absent or stunted tails, were  observed.
  The reasons for the localization of the teratogenic
effects of lead are unknown at this time. Perm  and
Perm387 have suggested that the specificity could be
explained by an interference with specific enzymatic
events  during early  development. Lead  alters
mitochondria! function and  enhances or  inhibits a
variety of enzymes,388 any  or all of which could in-
terfere with normal development.  Perm389 has also
reported  that  in  the presence  of  cadmium  the
teratogenic effect of lead in hamsters is potentiated.
  Studies  by  Giliani390'391  show  that  lead  is
teratogenic  to chick  embryos.  When  2-day-old
embryos were given varying doses of lead acetate
(0.005 to 0.08 mg/egg) and were  examined on the
                                               11 -50

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8th day of incubation, congenital cardiac anomalies
were  demonstrated.390  The  incidence  of cardiac
anomalies rose with increasing doses of lead. Other
important anomalies  were reduced body  size,
micromelia, shortened neck, microophthalmia, rup-
tured brain, shortened beak, twisted neck and limbs,
and everted viscera.391 The most common develop-
mental  anomalies were retarded  growth and  neck
abnormalities.  It  should be noted that in these
studies high, acute doses of lead were administered.
  There is a paucity of information regarding the
teratogenicity and developmental toxicity of chronic
lead exposure. Kimmel et al.265 exposed female rats
chronically to lead acetate via drinking water (0.5,
5, 50, and 250 /j.glg) from weaning through mating,
gestation, and  lactation. No teratogenic effects were
observed, although exposure  to 250 /j.glg lead ace-
tate caused  a  slight  but nonsignificant increase in
fetal  resorptions.  The  lead-treated animals  pro-
duced litters of normal numbers, but the offspring
from the  50- and 250-/ng/g groups weighed less at
weaning and showed delays in  physical  develop-
ment. Reiter et al.264 have also observed delays in
the  development of the  nervous system in offspring
exposed to 50 yug/g lead throughout gestation and
lactation.  Whether these  delays  in  development
result from  a direct  effect of lead  on  the nervous
system of the pups  or  reflect  secondary changes
(resulting from malnutrition, hormonal inbalance,
etc.) is  not clear. Whatever the  mechanisms in-
volved,  these studies suggest that low-level, chronic
exposure to lead may induce postnatal developmen-
tal delays in rats.
  It should be noted that the above reports on nor-
mal developmental delays might be analogous  to
certain  suggested neurobehavioral  effects  of  lead
from in utero exposures of humans (Section 11.5). In
addition,  it has  been   demonstrated392  that  con-
centrations of  lead  of approximately  170 /ug/dl
whole blood can inhibit S-ALAD activity  in  both
blood and brain  of suckling rats. Although brain
tissue was not purged of residual blood, ALAD con-
tribution to brain ALAD activity  would not be ex-
pected to  be significant.  It is possible that 8-ALAD
activity  might  be diminished  in utero at these lead
levels and that lead at these  levels  might have
harmful consequences on neurological development
of the fetus. There is need for more critical research
to evaluate the possible subtle toxic effects of lead to
the  fetus.  This overall  evaluation in the offspring
may need  to be correlated with the possible additive
effects  of paternal  lead  burden.  At  this  time,
however,  insufficient evidence exists to  allow for
 firm statements on exposure levels at which any such
 effects on the fetus from maternal or paternal lead
 burdens might be observed.
 11.8  THE ENDOCRINE SYSTEM
   The endocrine effects of lead are not well defined
 at the present time.  Lead  is known,  however, to
 decrease the thyroid function in man and experimen-
 tal animals. Porritt393 suggested  in 1931  that lead
 dissolved from lead pipes by soft water was the cause
 of hypothyroidism in individuals living in southwest
 England. Later, Kremer and Frank394 reported the
 simultaneous occurrence of myxedema and plumb-
 ism in a house painter. Monaenkova395 in 1957 ob-
 served impaired concentration of 13II by thyroids in
 10 out of 41 patients with industrial plumbism. Sub-
 sequently, Zel'tser396 showed that in vivo I3'I uptake
 and  thyroxine   synthesis  by rat thyroid were
 decreased by  lead  when doses of 2 and 5 percent
 lead acetate solution were administered. Uptake of
 131I, sometimes decreased in men with lead poison-
 ing, can be offset by treatment with thyroid-stimulat-
 ing hormone (TSH).397.398 Lead may act to depress
 thyroid function by inhibiting SH groups or by dis-
 placing iodine in a protein sulfonyl iodine carrier,397
 and the results suggest that excessive lead may act at
 both the pituitary and the thyroid gland itself to im-
 pair thyroid function.
   Sandstead et al.399 studied the effects of lead in-
toxication on the pituitary and adrenal function in
man.  There was  a decrease in secretion of pituitary
gonadotrophic hormones. Their data suggested that
lead may interfere  with pituitary function in  man
and may produce clinically significant hypopituitar-
ism in some. Its effects on adrenal  function were less
consistent,  but  some  of the  patients showed  a
decreased  responsiveness  to  an  inhibitor
(metapyrone) of 11-beta-hydroxylation in the  syn-
thesis of cortisol.
   Excessive oral  ingestion of lead  in  man has
Resulted  in pathological  changes in the  pituitary-
adrenal axis as indicated by decreased metapyrone
responsiveness, a depressed pituitary reserve, and
decreased  immunoreactive ACTH.400'401  These
same  events may also affect  adrenal gland function
inasmuch as decreased urinary excretion of 17-hy-
droxycorticosteroids was observed in these patients.
  Suppression of  responsiveness  to exogenous
ACTH in the zona fasciculata of the adrenal cortex
has been reported in lead-poisoned subjects,402 and
impairment of the zona glomerulosa of the adrenal
cortex has also been suggested.403
  There also is some evidence suggesting that  lead
                                               11-51

-------
may cause a derangement in serotonin metabolism
or utilization. Tryptophan is the precursor  of the
neuroendocrine  regulatory amine,  serotonin. An
effect of lead on serotonin synthesis or utilization is
inferred in part from the observation of Urbanowicz
et al.404  who  reported  a rise in 5-hydroxyindole
acetic acid  (5-HIAA)  excretion in the urine  of
workers heavily exposed to lead. This rise preceded
the rise  in urinary 8-ALA and coproporphyrin.  A
similar  rise  in  5-HIAA  excretion  was noted  in
moderately  lead-exposed workers.322   More re-
cently, however, Schiele et al.,405 using  a different
analytical method, were  unable to find any signifi-
cant elevation in 5-HIAA excretion.

11.9 THE HEPATIC SYSTEM
  The effect of lead poisoning  on liver function has
not been extensively studied. In  a laboratory study
of 301  workers in a lead smelting  and refining
facility,  Cooper et al.406 found serum  glutamic ox-
alacetic  transaminase (SGOT)  activity at  an in-
creased value of 11.5 percent in subjects with blood
lead levels below 70 /ig/dl, 20 percent in those with
a blood lead level of about 70 /tg/dl, and 50 percent
in workers with a blood lead level of about 100
/xg/dl. The correlation  between blood  lead  levels
and SGOT was not statistically significant. In  the ab-
sence of information  on the  possible influence  of
diet, infection,  or  personal  habits, however, the
authors  were unable to draw  any definite conclu-
sions concerning the etiology of these changes.
   The liver is the major  organ  for the detoxification
of drugs. In acute lead  poisoning, the mixed-func-
tion oxidase system of liver endoplasmic reticulum
is impaired.407 The activity of this enzyme system,
involved in  the  hepatic biotransformation  of
medicaments,  hormones, and  many environmental
chemicals, is closely related to  the availability of the
microsomal  hemoprotein, cytochrome P-450.408 It
has been shown that in rats lead induces inhibition of
heme synthesis and, therefore,  causes a reduction in
cytochrome  P-450 levels, with consequent impair-
ment of the mixed-function oxidase system.409 Drug-
metabolizing activities were significantly decreased
in the lead-poisoned animals. Intensity and duration
of these  changes were dose dependent.  In vivo ex-
periments, based on the duration of pentobarbital
sleeping time, provided  further evidence for  the in-
hibition of drug metabolism in lead-poisoned rats.
These data  would  suggest than an enhanced sen-
sitivity to xenobiotics (drugs, pesticides, food addi-
tives, etc.) should  be expected to  occur in lead-
poisoned animals. Alvarez et al.410 studied the effect
of lead exposure on drug metabolism in children and
adults. There were no differences between two nor-
mal children and eight lead-poisoned children  in
their capacities to metabolize two test drugs,  anti-
pyrine and phenylbutazone. This might suggest that
low plasma concentrations of lead do  not have  an
effect on the hepatic cytochrome P-450-dependent
enzymatic activities in  children.  In 2 acutely
poisoned children, in whom  plasma levels of lead
exceeded 60 /ng/di, antipyrine half-lives were sig-
nificantly  longer  than normal, and therapy  with
EDTA led to biochemical remission of the disease
and  restoration  of deranged  drug  metabolism
toward normal.
  Hepatic drug metabolism in eight adult patients
showing marked effects of chronic lead intoxication
on the erythropoietic system was studied by Alvarez
et al.4" The plasma elimination rate of antipyrine,
which,  as  noted  above, is  a drug primarily
metabolized by hepatic microsomal enzymes, was
determined in eight subjects prior to and following
dictation therapy. In seven of eight subjects, chela-
tion therapy shortened the antipyrine half-lives, but
the effect was minimal. The two authors concluded
that chronic lead exposure results in significant in-
hibition of the  heme biosynthetic pathway without
causing significant changes in  hepatic cytochrome
P-450-associated enzymatic activities.

11.10 THE CARDIOVASCULAR SYSTEM
  Under  conditions of  long-term  exposure  at
high  levels,  arteriosclerotic  changes  have   been
demonstrated in the kidney. In 1963, Dingwall-For-
dyce and Lane82 reported a marked increase in the
cerebrovascular mortality rate among heavily ex-
posed lead workers as compared  with the expected
rate. These workers were exposed to lead during the
first quarter of this century when working conditions
were quite bad.  There was no similar increase in the
mortality rate for men employed more recently.
  Hypertension  is an important element in the
etiology of cerebrovascular deaths. Tabershaw and
Cooper412  did  an  epidemiological  study of  1267
workers who had been exposed to lead as a result of
their occupation in either  the battery or lead smelt-
ing industry  between  1947 and 1970. Many  were
found to have blood lead concentrations in excess of
80 Mg/dl. The authors concluded that there was ex-
cess mortality associated with only two categories of
illness, chronic  nephritis and hypertension. The in-
creased incidence of hypertension in lead workers
has  also  been  reported by  Monaenkova  and
Glotova413 and  Vigdortchik.414 On the other hand,
                                               11-52

-------
 Cramer and Dahlberg415 studied the incidence of hy-
 pertension in a population of 364 industrially ex-
 posed men, 273 of whom had a long-term exposure
 to  lead. They subdivided the  workers into lead-
 affected and nonlead-affected  groups based  on the
 urinary  coproporphyrin  test. There  was no
 statistically significant difference between the
 groups nor was the  incidence  higher than that ex-
 pected for nonexposed men  in the general popula-
 tion.  Other reports on the question do not show hy-
 pertension to  be unduly prevalent  among  lead
 workers.350'416 It is not clear, therefore, whether the
 vascular effects of lead in man are direct effects on
 blood vessels or whether the effects are secondary to
 renal effects.
  There are conflicting reports regarding whether
 lead  can  cause  atherosclerosis  in experimental
 animals.  Sroczynski  et al.417  observed  increased
 serum lipoprotein and cholesterol, and cholesterol
 deposits in the aortas of rats and rabbits receiving
 large doses of lead. On the other hand, Prerovska,418
 using similar doses of lead given over an even  longer
 period of time, did not produce atherosclerotic le-
 sions in rabbits.
  Structural  and  functional changes  of the myocar-
 dium have been  noted in children with acute  lead
 poisoning, but, to date, the extent of such studies has
 been  very limited. Cases  have been described in
 adults and in children, always with clinical signs of
 poisoning. There is, of course, the possibility that the
 coexistence of lead  poisoning and  myocarditis is
 coincidental. In many cases in  which encephalopa-
 thy  is  present,  the  electrocardiographic  abnor-
 malities  disappeared  with chelation  therapy,  sug-
 gesting that lead may have been the original etiologi-
 cal  factor.4i9-421   Silver and Rodriguez-Torres421
 noted  abnormal  electrocardiograms in 21  of 30
 children (70 percent) having  symptoms of lead  tox-
 icity. After  chelation  therapy,  the  electrocar-
 diograms remained abnormal in only four (13  per-
 cent)  of the  patients.  Electron microscopy  of the
 myocardium  of  lead-intoxicated  rats  has  shown
diffuse degenerative changes.422 In a review of five
fatal  cases of lead  poisoning  in  young children,
 degenerative  changes in heart muscle were reported
to be  the proximate cause of death.91 It  is not clear
that such  morphological  changes are  a  specific
 response  to  lead intoxication.  Kosmider  and
 Petelnz423 examined 38 adults over 46 years  of age
with chronic lead  poisoning. They found  that 66 per-
cent had electrocardiographic changes, which was 4
times the expected rate for that age group.
  Makasev and  Krivdina424  observed a two-phase
change in the permeability of blood vessels (first, in-
creased   permeability;  second,  decreased per-
meability) in rats, rabbits, and dogs that received a
solution  of lead acetate. A phase change in the con-
tent of catecholamines in the myocardium and in the
blood vessels was observed in subacute lead poison-
ing in dogs.425 This effect appears to be a link in  the
complex mechanism of the cardiovascular pathology
of lead poisoning.
11.11  THE IMMUNOLOGIC SYSTEM
  Recent reports suggest that exposure to lead may
interfere  with  normal susceptibility to  infection.
Hemphill  et al.426 found that mice injected with
subclinical doses of lead nitrate for 30 days showed
greater susceptibility to challenge  with  Salmonella
typhimurium than controls that received a saline in-
jection containing no  lead. Selye et al.427 found that
rats injected with  lead acetate (minimal  effective
dose of 1  mg/100 g  body weight) were susceptible to
a variety of bacterial  endotoxins (toxins produced
by the bacteria themselves)  to which this species is
ordinarily resistant. Administration  of lead acetate
in drinking water to male mice from 4 weeks of age
to sacrifice at 9 to  12 weeks old increased the toxic
response of the mice to 5 classes of viruses against
which it  was  tested.428'429 These  viruses were  an
RNA picornavirus  (encephalomyocarditis),  a DNA
herpesvirus (pseudorabies), an RNA leukemia virus
(Rauscher leukemia),  and RNA arbovirus  B (St.
Louis encephalitis),  and  an  RNA arbovirus A
(western  encephalitis).
  Among the factors  that may be involved  in pro-
ducing this decreased  resistance to infection is the
decreased  production  of antibodies. Williams et
al.430 reported that lead binds antibodies in vitro and
could potentially do so in vivo. Chronic exposure to
mice of lead acetate in drinking water produced a
significant decrease in antibody synthesis,  particu-
larly gamma globulins.431
  Phagocytosis (ingestion of foreign material by a
cell  specialized  for   that  purpose) by alveolar
macrophages is believed to be an important step in
the  removal of dust particles and bacteria from the
respiratory tract.  Consequently, the activities  of
alveolar   macrophages are  important  aspects  of
pulmonary defense. Bingham et al.432 found that the
continuous inhalation  of  lead sesquioxide  aerosol
(10 /tcg/m3 to 150 /ug/m3) by  rats for 3 to  12 months
significantly reduced the  number of alveolar
macrophages. Electron microscopic examination of
the  lungs of rats that had inhaled paniculate lead
oxide (200 /u,g/m3)  for 14  days revealed ultrastruc-
                                               11-53

-------
tural  damage (mitochondria  and  endoplasmic
reticulum) to the alveolar macrophages and the type
I alveolar  epithelial cells.  Biochemically, a  con-
siderable loss in the activity of the benzopyrene hy-
droxylating  enzyme  in  the alveolar  macrophages
was observed by Bruch et al.433
  Few studies have been made of the effects of lead
on the immunologic system in man.  Reigart and
Graber434 studied  12 preschool children having ele-
vated  free  erythrocyte  protoporphyrin and blood
levels 2 40   /u,g/dl   and  seven nonlead-burdened
children  for  evidence of  impairment  of  their  im-
munological  responses.  They  found no differences
between  the  control group and the  lead-exposed
group with reference to complement  levels, to im-
munoglobulins,  or to anamnestic  response  to the
tetanus toxoid antigen.
  Hicks4-35  points  out  that there  is a  need  for
systematic epidemiological studies  on the effects of
elevated  lead levels  on  the incidence of  infectious
diseases in man. The paucity of information cannot
support  the formulation of any  dose-response  rela-
tionship at this time.

11.12 THE GASTROINTESTINAL SYSTEM
  Colic  is usually a consistent early symptom of lead
poisoning, warning of much more serious effects that
are likely to  occur  with continued and prolonged
lead exposure. Although most commonly seen in in-
dustrial  exposure cases, colic is also a lead  poisoning
symptom present in infants and  young children.
  Beritic436 reported on the cases of  13 of 64 men
exposed on their jobs to  occupational  levels of lead.
The 13  had colic, probably lead related, and con-
stipation. They had blood lead levels ranging from a
little less than 40 to 80  /xg/dl as determined  by
polarography, a technique which  tends  to yield
values lower  than the actual blood levels.  The diag-
nosis of lead-caused colic was supported by findings
of high urinary coproporphyrin,  excessive basophilic
stippling,  reticulocytosis, and some degree of
anemia, all of which are other clinical signs of lead
poisoning.
  Although these symptoms are  well documented in
the literature, there are insufficient  data by which to
establish a dose-response relationship for an effect of
lead on  the gastrointestinal  system.

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384  Verma, M.  M, Joshi,  S  R., and   A.  O  Adeyemi.
     Mutagenicity and infertility following  administration of
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     JO(5):486-487, 1974.
385. McClain,  R.  M. and B. A. Becker.  Teratogenicity, fetal
     toxicity.and placenta! transfer of lead nitrate in rats. Tox-
     icol. Appl. Pharmacol 31 72-82, 1975.
386  Perm, V. H.  and  S. J  Carpenter. Developmental malfor-
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387. Ferm, V  H   and D. W. Perm. The  specificity  of the
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     70.35-39, 1967
388. Vallee, B  L.  and D  D Ulmer. Biochemical effects of mer-
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389  Ferm, V.  H. The synteratogenic effect of lead and cad-
     mium. Experientta. 25'56-57, 1969.
390. Giliani,  S.  H.  Congenital  cardiac  anomalies in lead
     poisoning.  Pathol. Microbiol. (Basel). 59:85-90, 1973.
391  Giliani, S. H  Congenital anomalies in lead poisoning.
     Obstet  Gynecol  47-265-269, 1973.
392  Millar, J. A., V. Battistim, R.L  C. Cummmg, F. Carswell,
     and  A.  Goldberg.  Lead  and  8-amino-levulinic acid
     dehydratase  levels in  mentally  retarded children  and  in
     lead poisoned suckling rats. Lancet. 2'695,  1970.
393. Porritt, N. Cumulative  effects  of infinitesimal doses  of
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394  Kremer, H. U. and M.  N.  Frank. Coexisting myxedema
     and chronic plumbism. Ann. Intern  Med. 42'1 130-1 136,
      1955
395 Monaenkova, A. M.  Functional state  of the thyroid  in
     chronic intoxication with some industrial  poisons Gig
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396. Zel'tser, M E. The functional state of the thyroid gland in
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400. Murashov, B. F Functional state of the adrenal cortex in
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 403  Sandstead, H. H., A. M. Michelakis, and T  E Temple.
      Lead  intoxication. Its  effects  on the renin-aldosterase
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      20-356-363, 1970.
 404  Urbanowicz, H., J.  Grabecki, and J. Kozielska The urin-
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 405.  Schiele, R , K. H Schalle, and H.  Valentin. The influence
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      Laboratory  studies  of workers in lead smelting and refin-
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 407.  Alvares, A P., S. Leigh, J. Cohn, and A. Kappas. Lead and
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 409.  Scoppa, P.,  M.  Roumengous, and W. Penning. Hepatic
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 410.  Alvares, A. P , S. Kapelner, S. Sassa, and A. Kappas. Drug
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 411.  Alvares, A. P., A. Fishbem, S. Sassa, K. E. Anderson, and
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 412.  Tabershaw, I. R. and W. C. Cooper. Health Study of Lead
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 413.  Monaenkova, A. M  and K. V.  Glotova. Cardiovascular
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 414.  Vigdortchik.N. A. Lead  intoxication in the etiology of hy-
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 415.  Cramer, K and  L.  Dahlberg. Incidence  of hvpertension
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418.  Prerovska, J. Einfluss von Blei auf biochemische  Veran-
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419.  Myerson, R. M. and J. H. Eisenhauer. Atrioventricular
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420   Freeman, R reversible myocarditis due  to  chronic lead
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      1965.
421.  Silver, W  and R. Rodriguez-Torres Electrocardiographic
      studies  in  children  with  lead  poisoning   Pediatr.
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422.  Asokan, S  K., C. A. Malpass,  Jr , and F  T. Ulmer. Cir-
423
     culation. 44(Suppl. 2):101-104, 1971.
      Kosmider, S.  and  T.  Petelnz. Zini ny  elektrokar-
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      32437-442, 1962.
 424.  Makasev,  K.  K. and L. V. Krovdma. Status  of the in-
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 425  Mambeeva, A  A. and I. D. Kobkova. The concentration
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      in experimental  lead  intoxication.  Izv.  Akad..Nauk
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 426.  Hemphill,F.,M  L. Kaerberle, and W. B. Buck. Lead sup-
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 427.  Selye, H., B. Tuckweber, and L. Bertok. Effect of lead ace-
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      23:289-291, 1971.
                                                        11-65

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   12.  ASSESSMENT  OF LEAD  EXPOSURES  AND ABSORPTION
                            IN  HUMAN  POPULATIONS
12.1 INTRODUCTION
  Although  epidemiological  studies  provide the
most directly relevant data for setting ambient air
quality standards, such investigations are subject to
methodological and practical difficulties. Of most
interest  are  studies relating ambient air lead ex-
posures  directly to human health effects in various
population groups. Unfortunately, few such studies
exist.  Standards setting,  then,  must rely on con-
structing (1) the linkage  between exposures to en-
vironmental sources of lead and the incorporation of
lead from those sources in various segments of the
population as measured by blood lead levels and (2)
the relationship between levels of lead in the blood
and associated health effects.
  This chapter will examine the details of studying
blood lead levels in human populations. Included
will be an examination of the statistical considera-
tions of such investigations as well as a discussion of
the characteristics of the frequency  distribution of
blood lead values and of how these may be used as
tools in setting environmental standards. In addi-
tion, the  effects of geographic and demographic
variables  on  lead  burdens  will be considered.
Finally, the epidemiological and clinical studies on
the relationships between environmental lead ex-
posures  and human absorption will  be described,
and, where available, quantitative estimates of those
relationships will be presented.

12.2 LEAD IN HUMAN POPULATIONS
  In this section, the statistical approaches for
assessing blood lead levels in human populations
will be discussed, as will their applications  and im-
plications. This discussion will be  followed  by  a
description of findings relating to  the geographic
and demographic distributions of blood lead levels.

12.2.1 Statistical Descriptions and Implications
  Many surveys have described blood lead values in
human  populations.  Not  unexpectedly,  the in-
vestigators' choices of statistics to describe central
tendencies and dispersion patterns are not uniform.
This lack of uniformity makes comparison of the
various studies quite difficult. For example, central
tendencies  are  expressed  as either  arithmetic  or
geometric means, and  the  measures of dispersion
also vary. Often the  arithmetic mean of the distribu-
tion is  much larger than the geometric mean.

12.2.1.1  FORM OF THE  DISTRIBUTION  OF
BLOOD  LEAD  LEVELS
  Several authors have either suggested or implied
that the  distribution of blood lead levels for any
relatively homogeneous population closely follows a
lognormal  distribution. '-3  Lognormality has also
been noted for other metals, such as 90Sr in bones of
human populations.4 Snee  has  suggested that the
Pearson system  of curves provides a slightly better
fit for the data of Azar et al. than  the lognormal,5
but the improvement derived from this system does
not seem sufficient to warrant the use of this little-
known technique. Yankel  et al.1 and Tepper and
Levin2 both found their lead data to be lognormally
distributed. Further  analysis of the Houston study of
Johnson  et al.,6 the Southern  California study  of
Johnson  et  al.,7 and the study of Azar et al.3 also
confirmed that a lognormal distribution provided a
good fit to the data. For these reasons, much of what
is presented in this  chapter is based on the accep-
tance that homogeneous populations have a lognor-
mal distribution of blood lead values.
  The lognormal distribution and its application to
biological measurements  are discussed by several
authors.4-8-9 A variable  is said to have a lognormal
distribution if the logarithm of the  variable is nor-
mally distributed. Because of the skewed nature of
the lognormal distribution, the median (50th per-
centile) is a more meaningful estimate of central ten-
dency than the arithmetic mean. For the normal dis-
tribution, the best estimate  of the median is X, the
simple arithmetic mean. For the lognormal distribu-
tion, the best estimate of the median is the geometric
mean (GM):
                                               12-1

-------
          GM = Exp[ 1   (ln(X))/n].      (12-1)
The standard deviation of the logarithms is:
            n
       S = [2 (ln(X,)- ln(GM))2/n-l]12.   (12-2)
            •	 i

The geometric standard deviation, also known as the
standard geometric deviation, is given by:

                GSD = Exp(S).

If only the arithmetic mean, X, and arithmetic stan-
dard deviation, SD,  are given, then the  geometric
mean and the geometric standard deviation  can be
estimated by:10

            GM = X/(l  + SD2/X2)12      (12-3)
and
        GSD = Exp[(ln(SD2/X2 + 1))' 2].   (12-4)
  The geometric standard deviation must  be in-
terpreted differently than the arithmetic  standard
deviation. Using the SD, approximately 68 percent
of the population will fall between (mean - SD) and
(mean + SD). These same limits for the lognormal
distribution become  GM/GSD  and  (GM)(GSD).
For example, if a population  has a geometric mean
blood lead level of 20 with a GSD of 1.3, then 95
percent of the population will  have blood lead levels
between 20/(1.3)' 9A and (20)(1.3)' % or 11.96 and
33.45.

12.2.1.2 PERCENTILE ESTIMATES OF  THE
LOGNORMAL  DISTRIBUTION
  From the GM and GSD, estimates of percentiles
of the lognormal distribution  can easily be obtained
either numerically or graphically. Numerically, the
pth percentile, X , is estimated by
                   (GM)(GSD)ZP
                         (12-5)
where z is the z value from a standard normal table.
The following values are often used:
Percent
Percent
                                Percent
1
2.5
5
10
V
-2.326
-1.960
-1.645
-1.282
25
50
75
90
\J
-.674
0.000
0.674
1.282
95
97.5
99
99.9
H
1.645
1.960
2.326
3.090
  Another method of obtaining percentile estimates
is  a graphical one using lognormal probability
paper.  One  point is placed  where the geometric
mean intersects the 50th percentile. A second point
                                  is placed where (GM) (GSD)2 326 intersects the 99th
                                  percentile. A  line drawn  through  these two points
                                  gives the  estimated cumulative frequency distribu-
                                  tion.  Figure  12-1, for example, is drawn with an
                                  assumed geometric standard deviation of  1.3.
                                                                      GM - GEOMETRIC MEAN
                                                                      GSD = GEOMETRIC STANDARD DEVIATION

                                                                    II  I  I I  I I I  I  !  I  I I  I I I I.
                                            PERCENT OF POPULATION WITH BLOOD-LEAD LEVELS
                                                   EXCEEDING GIVEN VALUE
                                   Figure 12-1. Estimated cumulative distribution ol blood lead
                                   levels for populations in which the geometric mean level is 15,
                                   25, or 40 M9/dl.

                                     From this  description of the distribution, esti-
                                   mates can be obtained of the  percentage of blood
                                   lead  values expected to exceed any given level  for
                                   any given geometric mean blood lead level. For ex-
                                   ample,  (Figure  12-1)  in  the  populations with
                                   geometric mean blood lead levels of 15, 25, and 40
                                   jug/dl whole blood, 0.1, 10, and 68 percent, respec-
                                   tively,  will have  blood lead  levels exceeding 35
                                     As stated  above,  Figure  12-1  was drawn with  a
                                   GSD of  1.3. The effect  of varying  the geometric
                                   standard  deviations on the percentage exceeding  a
                                   specified  blood lead value  is shown in Figure  12-2
                                   because the value of the GSD has been shown to vary
                                   across studies (Table 12-1). A marked effect can be
                                   noted. It  is very important, therefore, to be sure of
                                                            n—i  r  r i—i n i i  i  i—i T ~n n

                                                                                     G*°-
                                                                       GM = GEOMETRIC MEAN
                                                                       GSD = GEOMETRIC STANDARD DEVIATION
                                                                    II   I I  I I I  I I   I  I  I  I I  I I I
                                            PERCENT OF POPULATION WITH BLOOD-LEAD LEVELS
                                                    EXCEEDING GIVEN VALUE

                                   Figure 12-2. Estimated cumulative distribution of blood lead
                                   levels for populations having a geometric mean blood lead
                                   level of 25 ^g/dl, but geometric standard deviations of 1.2,
                                   1.3, or 1.5.
                                               12-2

-------
the value used for the geometric standard deviation
if the lognormal distribution is to be used in setting
environmental standards.
  Because most blood lead data have been reported
as  arithmetic means and standard deviations,  and
because the raw data are not generally available, this
chapter will use the term  "mean"  for  arithmetic
mean.  The  arithmetic  standard deviations,  when
available, will be identified. If the geometric means
are available, they will be reported as geometric
means with  the  geometric standard  deviation pro-
vided.
     TABLE 12-1. ANALYSIS OF VARIANCE FOR THE LOGARITHMS OF BLOOD LEAD VALUES FOR SELECTED STUDIES
                             (Geometric standard deviations given in parentheses)
Study
Idaho'
Seven City Study2
Southern California-Males7
Southern California-Females7
Houston^
Azar3
Population
size
879
1908
64
107
189
149
Replicates
per
observation
3
1
2
2
2
2-8
Number
of
duplicates
16b
171
64
107
189
NAC
Population
variance3
0190
(155)
0090
(1 35)
0.224
(1.60)
0183
(1 53)
0.182
(153)
0148
0.47)
Within group
variance3
0072
(131)
0082
(133)
0.181
(153)
0167
(151)
0.069
(1.30)
0099
(137)
Measurement
variance
0012b
(1 12)
0.063
(1.28)
0.216
(159)
0141
(1.45)
0094
(136)
0049
(1.25)
 a Includes measurement variation
 b Based on a separate Center for Disease Control versus Idaho comparison of 16 samples of 1975 data which are different from the 1974 data for the Idaho study ' The
estimates of population and within group variance come from the original study
 c Not available
 12.2.1.3  VARIATION  IN  BLOOD LEAD
 VALUES
  The total variation in blood lead values for any
 study is composed of three variance components: (1)
 between group, (2)  within group or individual, and
 (3) method variation. The method variance results
 from  both sampling  and  analytical measurement
 variations. The within group variance results from
 the difference  in biological  response among  in-
 dividuals  with  the  same exposure as well as
 demographic  differences in  age, sex,  race,
 socioeconomic  status,  and  environmental  back-
 ground of the  individuals in  a  group. The within
 group variance is a measure of the homogeneity of
 people  in a  group,  but  also  includes  method
 variance. The between group variance results from
 the differences in the composition of people in a
 group,  such  as police  officers  or housewives. In
 studying the effect of lead exposure on blood lead
 levels, it is necessary to separate these sources of
 variation  to  know  whether the  study results  are
 meaningful. If the blood lead sampling and analysis
 errors  are large, any effects of different lead  ex-
posure may not be seen. In a similar manner, if the
group chosen  for a study is not homogeneous, the
within  group  variance may  be so  large  that the
differences in blood  lead  values  cannot be inter-
preted  as resulting from exposure. The sources of
variation  are  estimated in Table  12-1  for several
studies for which the raw data were available.  The
variation  is  expressed in  terms  of the  natural
logarithms of the  blood lead values, and the  cal-
culations  were made using  standard  analysis of
variance techniques. The variances are converted to
geometric standard deviations and these values are
shown in parentheses.
  Table 12-1 shows that a large portion of the total
variation  is caused by measurement variation, ex-
cept possibly for the Idaho1 study. The measurement
variation  was  unusually  large for  the  Southern
California study,7  suggesting  that  results from  this
study should be viewed with caution. Except for the
Southern California study, the GSD for within group
variation was consistently near  1.3. This number in-
cludes both biologic and measurement variation.  It
is possible for the measurement variation to exceed
                                                12-3

-------
the within group variation if there is more than one
reading per individual, however, as was the case in
both the Southern California and Houston studies.
12.2.1.4 PROBLEM OF FALSE EXCEEDENCES
  Lucas"  has described  a  problem that he terms
"false exceedences." For example, a lognormal dis-
tribution  with  a geometric  mean  of 25  and  a
geometric standard  deviation of 1.3 will have 3.7
percent of the distribution above 40. As a hypotheti-
cal example, if half of the variation  is  caused by
measurement variation, then the "true" distribution
would have  a geometric standard deviation of 1.2
and would have only 0.6 percent of the distribution
above 40.
  False exceedences become  a real  problem  if a
threshold  value, such  as 40,  is determined  from
sources of data lacking a large measurement varia-
tion. In such cases, the estimated percentage of the
distribution  above a fixed  level will  be an over-
estimate as shown in the previous paragraph. It is ex-
tremely difficult to  obtain more accurate estimates
because the  appropriate variance can  only  be  esti-
mated indirectly and only in cases where there are
replicate measurements on  the same individual. If,
however, the threshold itself is estimated from data
having this  same measurement variation, then the
problem  is  more difficult.  In such cases,  the ob-
served variances including  measurement variation
may be more appropriate. As the technology of
measurement improves, the problem  will  become
much less significant.
12.2.2 Geographic  Variability in Human  Blood
Lead Levels
   Numerous studies have been conducted through-
out the world establishing  mean blood lead con-
centrations for various remote, rural, suburban, and
urban  populations.  By examining the differences
among the observed levels across these populations,
inferences can be drawn concerning the ubiquity of
lead exposures as well  as their relative magnitudes.
A word of caution, however, must be inserted here.
Many  of  these  data have  been  collected  over a
period of time in which measurement technology for
blood  lead  determinations has changed and im-
proved. Also, sometimes neither  the methods of
analysis nor the sampling scheme used  have been re-
ported.
   Studies of remote populations have  been  used to
estimate the natural  background blood  lead level for
humans.12-'5 Likewise, studies  comparing either
rural or suburban populations have been used to es-
tablish the effect of urban  living on  blood lead
levels. All  these studies, however, can be used to
demonstrate the broad  variety of populations in
which lead  from all environmental sources has been
found in people.
  Only a few  studies12'15 have  focused on  remote
populations. Goldwater and Hoover12 conducted an
international study of urban and rural populations
in which investigators from  14 countries partici-
pated; only non-occupationally exposed adults were
studied.  One   laboratory  did all  the  chemical
analyses. Some of these populations — New Guinea
aborigines, for example —  were thought  to  be
remote from the  effects of  industrialization. The
mean and standard deviations of blood lead for the
aborigines, however, were 22 and 5 /tg/dl,  respec-
tively. Examination of their living habits could shed
no light on the sources of this lead. In contrast to
this, urban residents from Peru in the same study had
a mean of  7 /ng/dl  and a standard deviation of 5
  Stopps13-14 reported data on remote populations.
Table 1 2-2 presents the blood lead means as ranging
from 23 to 12  /ug/100 g.
  In contrast  to the findings of  Goldwater  and
Hoover12 and Stopps,13'14 Hecker et al.15 in a more
recent study of Amazon River Basin Indians, using
anodic stripping  voltammetry, found a mean blood
lead of 0.83 ^tg/dl with a standard deviation of 0.59
in 90 subjects.  The urinary levels were not quite as
low as the blood leads (mean, 7.9 /Lig/dl; SD, 5.7),
but still are low in comparison with the values re-
ported in Goldwater and Hoover.12
     TABLE 12-2. BLOOD LEAD LEVELS OF REMOTE
                POPULATIONS13-14
Populations
Brazilian Indians
Marshall Islanders
Peruvian Indians
Islanders off Australia
Bushmen
New Guinea natives
East Africans
Sample size
11
33
39
28
68
67
63
Blood lead,
M9/100g
23
23
18
17.5
16
13
12
  A number of studies have specifically contrasted
blood lead results between rural, suburban, and ur-
ban populations.2'16-21 Two of the methodologically
better studies are those of Tepper and Levin,2 and
Nordman.16 Tepper and Levin2 conducted a study of
the blood lead levels of 11 groups of housewives
from  8 U.S.  metropolitan  areas. Three of these,
Chicago, New York, and Philadelphia, had urban-
                                               12-4

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suburan comparison groups. Table 12-3 displays the
results of the contrasts between those groups as cal-
culated by Hasselblad and Nelson.22 In every case, a
significant difference was obtained.
 TABLE 12-3.  AGE AND SMOKING-ADJUSTED GEOMETRIC
   MEAN BLOOD LEADS IN URBAN VERSUS SUBURBAN
              AREAS OF THREE CITIES
City
Chicago, IL
Philadelphia, PA
New York, NY
Three cities together
Urban Suburban
1755 1402
2012 1788
1647 1524
1805 1571
Urban excess Significant
353 >001
224 >001
123 >001
234 >001
  Nordman16 studied a series of populations in Fin-
land  including  downtown  urban,  suburban, and
rural  populations.  No  statistically significant
differences were observed between urban and rural
or suburban residents. But, interestingly, none of the
populations studied, which included traffic police-
men,  streetsweepers, downtown Helsinki  residents,
and rural controls, had a mean blood lead level that
exceeded 13.5 jug/dl.
  Other studies permitting urban rural comparisons
include those of Hofreuter et al.,17 Creason et al.,18
Scanlon,19  Gershanik et  al.,20 and Cohen et al.21
Hofreuter et al.,17 in 1960, collected blood samples
from about 120 people in  each of 6 cities and from
162 people in a rural area (central Ohio). Table 12-4
displays the results of these comparisons. In all ur-
ban survey sites, the mean blood  lead level was sig-
nificantly higher than in the  rural survey sites.
   TABLE 12-4. BLOOD LEAD CONCENTRATIONS IN SIX
        URBAN AND ONE RURAL POPULATION


Survey site
New Orleans, LA
Chicago, IL
New York, NY
Cincinnati, OH
Dallas. TX
Denver, CO
Rural

No of
samples
130
97
112
137
128
131
162
Mean
blood lead.
M9 100 g
22
20
20
20
18
19
14

Urban
excess
8
6
6
6
4
5

  Creason  et al.1-8 studied  military recruits in  the
Chicago area at the time of their induction. By  the
very nature of the sample,  only young male adults
were included.  Further,  analysis was restricted to
those having lived at the same home address for two
or more years. The population was  broken down by
race and three residential locations, namely urban,
suburban, and  outstate.  Median blood levels  for
whites  were 22, 20, and 36 /ug/dl for the urban,
suburban, and outstate populations, respectively.
  Scanlon19 reported on umbilical cord blood lead
levels for infants born to Boston area women.  Mean
blood lead levels for urban infants were 22.1 /zg/dl
compared  with  18.3 (Ug/dl  for the  suburban
newborn. This difference was not statistically signifi-
cant.
  Gershanik et al.20 studying a larger sample of cord
bloods in  Shreveport, Louisiana,  however,  found  a
statistically significant difference between urban and
suburban infant  cord blood lead  levels, 9.7 ±  3.9
versus 8.3  ±  2.4 /tg/dl, respectively.
  Cohen et al.21 reported on a rural-urban  com-
parison for children, aged  1 to 5  years, living in  2
rural  counties  and  in   Hartford, Connecticut.
Although the 2 samples were adequately matched on
age, there was a major racial/ethnic difference — the
urban population being either black or Puerto Rican
and the rural primarily white. The mean and stan-
dard  deviation  of  the blood lead concentrations
were 32.7  ± 14.8 and 22.8 ±  11.0 for the urban and
rural populations, respectively.
  Some of these  same studies, as well as others, can
be used to  discern a wider picture of the variability
of blood lead levels.I2-|4J7 In the  Goldwater and
Hoover study,12  urban  population mean blood lead
levels  were found  to  range  from  7  to  25 /ug/dl,
whereas the mean for rural areas  ranged from 9 to
32 ju.g/dl. The wide range  of means in both  popula-
tion types suggests that lead can be found in  many
locations.
  Nordman16  reviewed the available literature on
blood  lead levels  and concluded that "the  Pb-B
mean values for occupationally unexposed rural and
urban populations range from 10 to 26 /ig/dl." Ex-
ceptions to this general range are found, however.
Lower-than-usual blood lead levels have been re-
ported from  some  parts  of Sweden and Finland.
There,  levels in women   were found to  be  10
/ug/dl.16'23  On the  other  hand, higher-than-usual
blood lead values have been reported from  sections
of Italy and France.24'27 Zurlo et al.,24 in particular,
reported very high blood lead levels for adults in the
Milan  area, urban  mean of 30 /ig/dl for males and
23.7 /ig/dl for females.
  Data obtained from  adults  within the  United
States follow a similar pattern.2'17-28 In data from
Tepper and Levin,2 differences were noted in  the
geometric mean  blood lead among the 11  popula-
tions of housewives studied. The lowest blood lead
values  were found in  Houston, Texas, with a GM
and a GSD of 12.5  and 1.31, respectively, whereas
the  highest were found in  Rittenhouse, a section of
                                               12-5

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Philadelphia —GM  and GSD  of 20.6 and  1.33,
respectively.
  In the  1960 Hofreuter et al. study,17 blood sam-
ples were collected from people in six metropolitan
areas and one rural  control site. The mean blood
lead values varied from 14 to 22 jig/100 g. The max-
imum  observed  values ranged  from  38 to  60
Mg/100g.
  Kubota et al.28 studied blood lead  levels in male
residents of 19 intermediate-sized cities across the
United States. Mean blood levels were found to vary
from  7.25 /ug/dl  in Lafayette, Louisiana, to 20.34
Mg/dl in Jacksonville, Florida. The highest reported
value, 109.27  pig/dl,  occurred  in  Fargo,  North
Dakota.  A wide range in values was reported for
each city, the largest being 5.91 to 109.27 fig/dl in
Fargo. Further, the authors report three cities with
mean blood lead levels below 8.00 /ig/dl, namely
Lubbock, Texas, 7.95;  Geneva,  New York,  7.65;
and Lafayette, Louisiana, 7.25  (iig/dl.  These low
values approximate those  found  in parts of Scan-
dinavia.16
  Workers at 23 DuPont  Company plants  were
studied over a 5-year period, 1967 through 1971.29
No time  trend was noted for blood lead levels, and
the samples were pooled per plant for the 5 years.
The geometric mean values  varied from a low of
15.5 jug/lOOgfor the Ashland, Wisconsin, plant to a
high of 21.6 /xg/100 g at the Los Angeles, California,
plant. The overall geometric mean for the 23 loca-
tions was 18.2 pig/100 g.
  Data addressing geographic  variation of blood
lead values in children are not as extensive. For the
United  States,  Fine  et al.,30 Baker et  al.,31  and
Joselow  et al.32 provided the best available infor-
mation. Fine et al.30 studied 6151 children aged 1 to
6 years in 14 intermediate-sized cities in Illinois in
1971. Blood  lead values (Table  12-5) were deter-
mined by an  atomic absorption technique. Mean
values for cities ranged from 19.8 to 32.9 pig/dl; the
mean for all  14 cities was 25.5 /*g/dl. These values
are indicative of sources of lead  in the children's en-
vironment.
  Baker et al.31 determined blood lead  values  for
1672 children aged 1 to 5 living in 19  towns contain-
ing smelters and 3 control towns. The smelter com-
munities were selected  for  study because they had
not previously been  subject to  thorough investiga-
tion.  Blood  lead values were  determined by an
atomic absorption technique.
  The mean blood lead levels for the lead and cop-
per smelter towns did not differ from those control
towns, as shown in Table 12-6. The children  living
TABLE 12-5.  MEAN BLOOD LEAD VALUES FOR CHILDREN
  IN 14 INTERMEDIATE-SIZED CITIES IN ILLINOIS, 197130
City
Aurora
Springfield
Peoria
East St Louis
Decatur
Joliet
Rock Island
East Moline
Harvey and Phoenix
East Chicago Heights
Chicago Heights
Robbins
Carbondale
Rockford
Total
No of
children
screened
449
670
387
376
793
383
285
298
226
172
537
103
264
1,208
6,151
% of city's
children
ages 1-6 yr
screened
5.09
7.28
2.97
4.09
5.84
4.54
5.60
12.32
4.90
17.13
10.36
6.78
17.46
731
614
Mean blood
lead value.
M9'*
28.2
31.5
32.9
286
21 5
27.8
250
23.5
22.6
27.3
25.2
22.2
28.5
19.8
25.5
in zinc smelter towns, however, showed significantly
higher blood lead values than the other three groups.
The lowest mean blood lead value, 9.15 /*g/dl, was
found  in children for McGill, Nevada, whereas the
highest mean value was found  for Bartlesville,
Oklahoma, with 28.60  ptg/dl.
   Joselow et al.32 compared the blood lead levels of
children aged 3  to 5 years in Newark, New Jersey,
and Honolulu, Hawaii, in  1973. The study included
152 children who were  matched for age and sex into
2 groups of 76 from each city. The mean blood lead
value for the Newark children  was 28 /ng/dl, con-
siderably higher  than that found   in  Honolulu
children, 17 /j.gld\.

12.2.3 Demographic Variables and  Human Blood
Lead Levels
   Fewer data are available to evaluate the effects of
age, sex, and race on blood  lead levels.
   Children consistently develop higher blood lead
levels than  do adults in the same environmental set-
ting. In  El Paso, Texas,33 in 1972,  70 percent  of
children 1 to 4 years old living near a primary lead,
copper, and zinc smelter had blood lead levels >40
jig/dl,  and  14   percent  exceeded  60  jig/dl.  In
children 5  to 9  years old, 45 percent exceeded  40
jig/dl, as did 31  percent of measurements  in in-
dividuals 10 to 19 years old  and 16 percent of those
over 19.
   In the vicinity of a primary lead smelter in  Idaho
in  1974, the geometric  mean blood  lead  levels
shown in Table 12-2 were  obtained.1  As can be seen
from Table  12-7, children  under 10 years of age
consistently had higher blood lead values than older
children and adults within the same environment.
                                               12-6

-------
TABLE 12-6. BLOOD LEAD LEVELS (WHOLE BLOOD) IN CHILDREN IN U.S. SMELTER AND COMPARISON TOWNS, 197531
No of
City samples Mean
Comparison towns
Albuquerque. NM 81 177°
Perryville, MO 85 1688
Safford, AZ 92 1526
Total 258 1656
Lead smelter towns
Bixby, MO 48 13 76
Glover. MO 23 1205
Herculaneum. MO 87 1880
Total 158 1634
Copper smelter towns
Ajo, AZ 105 1255
Anaconda. MT 64 1338
Copper Hill, TN 86 1663
Douglas, AZ 97 2047
Hayden, AZ 100 21 24
Hurley, MN 42 1433
McGill, IW 50 9 15
Miami, AZ 94 17 00
Morenci, AZ 100 1387
San Manuel. AZ 101 1801
White Pine, Ml 70 1862
Total 909 1636
Zinc smelter towns
Amanllo. TX 84 2234
Bartlesville, OK 87 2860
Corpus Chnsti, TX 12 1902
Monaco. PA 62 1484
Palmerton, PA 102 1751
Total 347 21 04
aSE - standard error
TABLE 12-7. GEOMETRIC MEAN AND GEOMETRIC
STANDARD DEVIATIONS (IN PARENTHESES) OF BLOOD
LEAD LEVELS BY AGE AND STUDY SECTOR (/ug/dl)
0, . Age years
Study
sector 00 10-19 >20
i 66(1 33) 39(1 26) 38 (1 32)
n 47(130) 33(123) 33(133)
111 34 (1 26) 28 (1 40) 30 (1 35)
Likewise, a study of traffic exposure in Dallas,
Texas,34 found mean blood lead concentrations of
1 2 to 18 /ig/dl in children as contrasted with 9 to 1 4
/u.g/dl in adults, when exposure levels are controlled.
Simpson et al.35 summarized the results of 27
neighborhood screening programs conducted
throughout the United States in the spring and sum-
mer of 1971. They found that children less than 3
years of age had a lower rate of elevated blood lead
than children older than 3 years. Of those under 3
years, 25.8 percent had values of > 40.0 /u.g/dl,
whereas 31 .4 percent of those 3 years of age or older
had values240.0 /u,g/dl.
Percent
exceeding
SEa GM GSD 35»ig'dl
063 168 139 00
074 158 142 24
071 138 1 57 11
041 154 1 57 12
096 124 166 0,0
1 19 11.1 1 58 00
094 172 154 80
066 146 164 44
046 117 145 0.0
095 116 177 16
074 154 1 47 12
086 189 149 31
085 199 142 50
123 128 160 48
052 89 145 00
074 155 159 32
056 129 147 00
055 172 1 37 10
0 74 178 1 34 29
025 148 158 20
1 16 209 1 41 48
191 236 192 310
1 42 184 1 32 00
082 137 149 16
060 165 142 10
066 186 163 95
Elam et al.36 studied pediatric patients in a
Chicago outpatient service. The proportion of
children (Table 12-8) with blood lead values > 50
jug/dl varied with age; the proportion over 50 /^.g/dl
peaked at 18 to 30 months of age.
TABLE 12-8. PROPORTION OF CHILDREN WITH BLOOD
LEAD VALUES BETWEEN 50 AND 99 M9/dl, BY AGE,
CHICAGO 1971-197536
°o Blood lead
Age months 50 to 99 ^g dl
6-17 24
18-30 40
31-42 16
43-52 12
55-66 7
A study of Philadelphia ghetto children37 con-
ducted in 1972 through 1973 provides data relevant
to the relationship between age and blood lead level.
The study population consisted of 1559 black
children aged 6 months to 18 years of age. Table
12-9 presents the blood lead levels by age. In both
                                           12-7

-------
G6PD normal and deficient children, the blood lead
pattern of increase and decrease by advancing age
pertains. The only increase, but a substantial one, is
observed between children less than I  year of age
and  those  1  to  3  years  old.  Blood  lead  levels
     TABLE 12-9. MEAN BLOOD LEAD (ng%) BY AGE, SEX,
   decrease in all succeeding age groups.
     Billick et al,38 analyzed data from New York City
   lead screening programs from 1970 through 1976.
   The data include age in months, sex, race, residence
   expressed as health district, screening information,

AND G6PD STATUS IN 1559 URBAN BLACK CHILDREN37
Age, years
<1
1-3
4-8
9-13
14-18
Sex
Both
Males
Females
Both
Males
Females
Both
Males
Females
Both
Males
Females
Both
Males
Females
Number
61
32
29
289
133
156
404
177
227
394
189
205
242
94
148
G6PD
normal
19 1 + 9.5
195+ 9.0
19 2 ± 9.2
29.1 ±146
30.5 + 15 1
288+ 11.0
25.0+ 126
24 6 ± 13.2
251 + 11.1
21 3± 104
20 4 ± 109
21.7 ± 97
187 ± 97
185+ 101
18.8 + 8.9
Number
9
6
3
40
30
10
55
38
17
44
29
15
21
13
8
G6PD
deficient
18.3 ± 8.2
18.8 ± 8.2
173+ 8.4
33.2 + 15.5
331 + 155
336+ 135
257+ 134
25.2 ± 129
26.1 + 13.5
23.0 ± 12.5
22 1 ± 118
24.8 + 13.9
19.1 + 9.9
18.9 + 9.3
19.5+ 101
and blood lead  values expressed in decades. Only
the first screening data for individual children were
included based  on the analysis of venous  blood.
Only the data (178,588 values) clearly identified as
coming from the first screening of a given child were
   used.  All blood  lead determinations were done by
   the same  laboratory.  The  data  presented are
   preliminary and an exhaustive analysis has not been
   completed. Table  12-10  presents  the geometric
   means for the children's blood lead levels by age and
        TABLE 12-10. GEOMETRIC MEAN BLOOD LEAD LEVELS IN NEW YORK CITY LEAD SCREENING PROGRAM
                              (Calculated on the basis of the Billick et al.38 data)
Group and
year
Blacks
1970
1971
1972
1973
1974
1975
1976
Hispanic
1970
1971
1972
1973
1974
1975
1976
Whites
1970
1971
1972
1973
1974
1975
1976

1-12

27.2
252
223
22.6
222
205
181

21.5
199
187
20.1
19.7
17.4
179

21.0
19.9
17.1
203
18.6
19.1
20.7

13-24

31.2
297
26.3
269
257
22.9
207

24.9
22.9
206
21.8
21.4
196
186

23.9
22.8
20.2
215
20.5
200
172

25-36

31.2
304
267
26.3
255
22.9
21 2

25.5
25.0
22.1
22.5
23.0
20.6
19.2

247
22.9
22.0
219
20.0
19.0
19.1
Age. months
37-48

284
29.8
25.8
25.6
24.4
22.3
209

239
24.9
22.6
231
22.6
209
19.3

25.0
23.0
21.1
22.1
21.1
18.2
18.7

49-60

31 4
28.7
25.0
24.5
23.7
21 7
20.3

241
24.4
22.1
22.2
22.1
206
19.2

23.7
239
21.2
20.6
21.4
19.8
18.4

61-72

229
27.7
24.3
241
22.2
21.8
19.2

24.5
23.9
220
216
20.1
20.0
18.2

24.9
21.9
21.4
21.6
21.3
18.0
177

73*

25.7
27.0
23.8
23.1
221
19.6
19.3

24.0
23.9
21.3
21.7
20.3
18.5
184

22.5
21.7
20.6
21.1
19.6
17.3
17.5
                                               12-8

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race for the 7 years. It should be mentioned that the
means presented were derived by EPA from the raw
data provided by Billick et al.38 Because the blood
lead levels were available to the nearest 10  /u,g/dl,
the midpoints of each interval were used to calculate
the geometric  means. These means were calculated
for each 2-month  interval for each age and  ethnic
group and were then  combined across the  six 2-
month  intervals  using an  unweighted  geometric
mean so as to  minimize any seasonal effects.
   It should be noted  that all racial/ethnic groups
show an increase in geometric mean levels from < 1
to 1 to 2 years of age. Figure 12-3 shows the  trends
for 1970. Similar patterns hold for other years. The
                        AGE, years
Figure 12-3. Geometric means for blood lead values by race
and age, New York City, 1971.
differences in age-associated patterns for the three
racial/ethnic groups may be influenced by the sub-
stantial differences  in  population  sizes  for  the
groups: whites were  the smallest group, Hispanics
were next, and blacks the largest. Table 12-11 shows
the size of the groups for the 7 years.

  TABLE 12-11. NUMBER OF CHILDREN'S INITIAL SCREENS
 IN NEW YORK CITY PROGRAMS BY RACE/ETHNICITY AND
                 YEAR, 1970-197738
Year
1970
1971
1972
1973
1974
1975
1976
White
1,282
2,796
1,350
823
601
656
491
Black
8,839
23,174
16,730
9,722
4,139
4,585
3,755
Hispanic
8,251
18,740
10,153
6,875
2,498
2,620
2,178
ages 8 days to 8 years showed increasing mean blood
lead levels with age: 3.3 ± 2.6 /ug/dl in the first year
of life, increasing with each year to a mean of 11.5 ±
4.9 Mg/dl at age 6 to 8.
   In contrast to studies of children, most studies of
adult populations do not show any marked effect of
aging on blood  lead levels.17'40'41 Nordman found
that males and females over the age of 65 years had
lower blood  lead values than the rest of the adult
population in his study.16
   Effects of sex on blood lead levels appear to be
age dependent. Adult females are commonly found
to have lower levels than males.2-16'17'23'24 Among
children,  however,  sex  does not appear  to  be  a
differentiating factor.42'43 Tepper and Levin2 have
suggested that the differences found in blood lead
levels of adult men and women are not the result of
either differences in  lead intake from food or from
differences in hematocrit levels between them.
   Data for the assessment of race as a factor in blood
lead  levels are  relatively  scarce.l8'25'38.44'45 The
earlier studies18-44 report only the number of cases
above a specified blood lead level.  One study18
shows higher  lead levels for blacks  than Puerto
Ricans, but the other44 reports that blacks had high-
er levels than nonblacks.
  In their study of military recruits, Creason et al.18
compared white and black subjects. Data in Table
12-12 show higher mean values for all black groups
than for the whites.
 TABLE 12-12. BLOOD LEAD LEVELS (/Ltg/dl)18 IN MILITARY
          RECRUITS, BY RACE AND PLACE
                       90th                   90th
   Place   Number  Mean  percent Me   Number   Mean  percent ile
Urban
Suburban
Outstate
58
4
15
38
80
59
85
124
105
203
218
406
31
27
39
69
54
71
  It is of interest to note that the age-associated pat-
tern observed in the United States was not seen in a
West German39 study. In that study, 363 children of
  The Billick et al.38  data  show higher geometric
mean  blood  lead  values for  blacks  than for
Hispanics or for whites. Table 12-13 presents these
geometric means for the three racial/ethnic groups
for 7 years. The consistency of  the association  is
remarkable.
  Numerous data have been published showing the
effect  of  various occupations  on  blood  lead
levels.16-25'40'46 In general,  these data support the
conclusion that workers exposed  to automobile ex-
haust,  lead fumes, or  dust  in  manufacturing carry
higher lead burdens than those who do not.
                                                12-9

-------
  TABLE 12-13. GEOMETRIC MEAN BLOOD LEAD LEVELS
   Cug/dl) IN NEW YORK LEAD SCREENING PROGRAM,
 1970-1976, FOR CHILDREN UP TO 72 MONTHS OF AGE, BY
                RACE AND YEARS'
Year
1970
1971
1972
1973
1974
1975
1976
Black
286
28.5
250
250
239
220
200
Hispanic
24.0
234
21 3
21 9
21 6
198
187
White
23.8
224
204
21 3
20.8
190
186
12.3 RELATIONSHIPS BETWEEN EXTER-
NAL  EXPOSURES  AND  BLOOD  LEAD
LEVELS
  In previous chapters, it has been shown that lead:
     1.  Is emitted from  various sources, primarily
       automobiles and industrial operations.
     2.  Is distributed across the environment.
     3.  Is capable of being absorbed  into the human
       body.
This section will describe the relationships observed
between the different environmental exposures and
the resulting absorption  as measured by blood lead
levels.
  Lead that is emitted from mobile sources, e.g. au-
tomobile exhausts, and from  stationary sources, e.g.
industrial operations, either remains in the  air or
falls out, as discussed in Chapter 6. Studies have
shown a buildup of lead in soil and dust as a result of
emissions from  these two sources. Further, the lead
in soil  and dust does not derive only  from  these
sources but, in addition, from the deterioration and
erosion of lead based paint. Therefore, although soil
and  dust are direct sources  of human  exposure to
lead, they must also be viewed in terms of the pri-
mary mobile and  stationary sources  of the  lead.
Consequently, studies that examine only ambient air
lead exposures may, in fact, underestimate the total
contribution  of airborne lead to the population's
lead burden.
  Efforts to estimate experimentally  the relative im-
portance of combustion of leaded gasoline to total
lead burden in humans have only recently been initi-
ated. Manton  has  presented evidence  from  a
preliminary study using  lead isotope  ratios.47 His
findings suggest that automobiles supplied between 7
± 3 and 41  ± 3 percent of the  lead  in blood of
Dallas  residents during  1972 to 1973. Garibaldi et
al.,48 in a major study being conducted  in Italy, are
attempting such allocations on a much larger scale.
It is hoped that these data will be available shortly.
  Because multiple sources of lead do  exist and
because each can contribute to the total  lead burden
of man, an important question to be addressed is the
contribution of each source to the total body burden.
In this section, individual studies examining the con-
tribution from the major environmental sources of
lead,  that is,  air, soil-dust, paint, food, and water,
will be discussed.

12.3.1 Air Exposures
  Studies of the relationship  of  air exposures to
blood lead levels may  be separated into  two main
categories: epidemiological and clinical.
  Epidemiological studies in turn may be grouped
into three types: those pertaining to populations ex-
posed to mobile  sources of  emission,   those  of
populations exposed to stationary sources, and those
in which only the amount of airborne lead is taken
into  account with no  effort made  to  identify  the
source.
  Studies dealing with mobile sources of lead will be
discussed first, followed by a presentation of station-
ary sources studies. Studies concerned with air lead
levels regardless of sources will  then  follow,  and
clinical studies will complete the presentation. From
this array, the studies that permit  the calculation of
the quantitative relationship between lead in  air  and
lead in blood will be selectively analyzed and  dis-
cussed.
  Clinical studies have the advantage of permitting
precise control over the levels of exposure but have
the disadvantages of studying people under some-
what artifical  conditions and  of  dealing,   by
necessity, with very few subjects. All clinical studies
to  be  presented were  limited   to  adults.
Epidemiological  studies  have the  advantage  of
studying people in their natural  state, but frequently
have  the disadvantage  of rather imprecise estimates
of the exposures encountered. These studies allow
estimates of the relationship to be made for both
adults and children.

12.3.1.1  MOBILE SOURCE STUDIES
12.3.1.1.1 Studies  in  the  United States. A 1973
Houston study examined  the blood lead levels of
parking  garage  attendants,  traffic policemen,  and
adult females living near freeways.6 A control group
for each of the  three exposed  populations  was
selected  by matching for age, education, and race.
Unfortunately, the matching was not altogether suc-
cessful; traffic policemen had  less  education than
their  controls and the  garage  employees were
younger  than their controls. Females were matched
                                              12-10

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adequately, however. The findings for the six groups
studied  are presented in Table  12-14. It should be
noted that the  mean blood  lead  values for traffic
policemen  and parking  garage  attendants,  two
groups regularly exposed to higher concentrations of
automotive exhausts, were significantly higher than
the  means  for their relevant  control  groups.
Statistically significant differences in  mean values
were  not  found,  however, between women living
near a freeway  and control women living at greater
distances from  the freeway.
TABLE 12-14. MEAN BLOOD LEAD LEVELS FOR STUDY AND
           CONTROL GROUPS, HOUSTON
Group
Policemen
Controls
Garage attendants
Controls
Women living
near freeway
Controls
Mean
M9 dl
231
184
283
21 3

129
11 9
SO
921
738
1033
970

447
428
Sample
size
141
150
119
95

120
117

P = 005

P= 005


P >005

  A California study7-49 examined blood lead levels
in relation to exposure from automotive lead in two
communities, Los  Angeles and  Lancaster  (a  city
representative of the high desert).  Los Angeles resi-
dents studied were individuals living in the vicinity
of heavily traveled freeways within the city. They in-
cluded males  and females, aged  1 through 16,  17
through 34, and 35 and over. The persons  selected
from Lancaster represented similar age and sex dis-
tributions. On two consecutive days,  blood, urine,
and  feces  samples were collected. Air  samples were
collected from one Hi-Vol sampler in Los Angeles,
located near a freeway, and two such samplers  in
Lancaster. The Los Angeles sampler collected for 7
days; the  2 in Lancaster were  utilized for 14 days.
On the first day of air sampling, soil  samples were
collected  in each area in the vicinity  of study sub-
jects.
   Lead in  ambient air along the Los  Angeles free-
way  averaged  6.3 ±  0.71 /xg/m\ and in the Lan-
caster area the average was 0.6 ± 0.21 jug/m1. The
mean soil  lead in Los Angeles was 3633 /ig/g,
whereas that found  in  Lancaster was 66.9 Mg/E-
Higher  concentrations of lead were  found in the
blood of  children, as well as  younger and older
adults living near the freeway, than in individuals
living in the control  area. Table 12-15 shows the
mean  blood  lead values  for  the  six  groups.
Differences between  Los  Angeles and Lancaster
groups were significant with the sole exception of the
older males.
                 TABLE 12-15. ARITHMETIC AND GEOMETRIC MEAN BLOOD LEAD LEVELS (//g/dl)
                         FOR LOS ANGELES AND LANCASTER, CA, BY SEX AND AGE7
Los Angeles

Groups by sex
and age, years
Total
Males
1-16
17-34
35-
Females
1-16
17-34
35-
a Standard error
b t test


N
126
56
20
29
7
70
18
41
11




Mean
164
193
235
166
185
142
167
129
147




SEa
07
1 1
25
1 1
20
07
1 8
06
1 5



Geometric
mean
146
172
208
151
171
128
149
11 8
134




N
119
50
21
18
11
69
25
16
28


Lancaster


Mean
105
11 8
11 1
11 8
130
96
102
91
93




SE
04
06
08
09
20
04
07
1 2
05



Geometric
mean
96
108
104
109
11 1
88
96
80
87


Significance
of difference
Pb
«001
«001
«001
003
09
«001
<001
<001
<001


  It has been pointed out by Snee that, in the high-
traffic-density area, the reported 29 percent of sam-
ples in children 1 through 16 years old exceeding 40
jug/dl represented  5  individuals.50 For 3 of these a
second  blood  sample showed approximately  20
Mg/dl; a second sample was not collected from the
other 2. The disparity between blood samples taken
on consecutive days from children in the study calls
into question the validity of using  these values to
quantify the air lead to blood lead relationship. The
differences between  samples for adults, although
somewhat larger than those found  in other studies,
appear acceptable for use in calculations, however.
  A study of the effects of lower-level urban traffic
densities on  blood  lead  levels was undertaken  in
Dallas, Tex., in 1976.34 The study  consisted of two
phases.  One phase measured air-lead  values  for
selected  traffic densities and conditions,  ranging
                                               12-11

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from  £1,000 to about 37,000 cars/day. The second
phase  consisted  of an  epidemiological  study of
traffic density  and blood lead levels among resi-
dents.  Figure  12-4 shows the relationship between
arithmetic means of air lead and traffic density. As
can be seen from the graph, a reasonable fit is shown.
  TABLE 12-17. SOIL LEAD LEVELS BY TRAFFIC DENSITY3*
                      ~i	1	1	1	1	r
                                Y = 0 6598 + 0 0263 X
                                X = cats/day
 "    0  4,0008,00012,00016,00020.00024.00028,00032.00036,00038,000
                   TRAFFIC VOLUME, cars/day

Figure 12-4. Arithmetic mean of air  lead levels by traffic
count, Dallas, 1976."
  In addition, during this phase, data  for indoor-
outdoor comparisons  of air lead  levels  were  col-
lected. In two areas, with traffic densities of 10,000
and 20,000 cars/day,   high   volume  samplers
measured air lead outside of selected houses. At the
same time, indoor air lead values for these houses
were also collected. Table 12-16 shows the findings.
Approximately a tenfold difference was found be-
tween  indoor-outdoor values in both locations.  U
has  been  postulated  that at  least  part of  this
difference is  the result of using air conditioners.
  TABLE 12-16. MEAN AIR LEAD LEVELS (/ug/m3) INDOORS
  AND OUTDOORS AT TWO TRAFFIC DENSITIES, DALLAS,
                    TEX. 197634
10000 cars day

Mean
N
Indoor
0182
9
Outdoor
0918
9
20 000 cars day
Indoor
0199
5
Outdoor
2105
5
   In addition, for all distances measured (5 to 100 ft
from  the road),  air lead concentrations  declined
rapidly with distance from the street. At 50 ft con-
centrations were about 55 percent of the street con-
centration; at 100 ft concentrations were less than 40
percent of the street concentrations. In air lead col-
lections  from 5 to 100 ft from the street, approx-
imately 50 percent of the airborne lead was in the
respirable range (< 1  /urn) and the proportions  in
each size class  remained approximately the same  as
the distance  from the street increased.
   Soil lead concentrations were higher in areas with
greater traffic density (Table 12-1 7). The maximum
soil level obtained was 730 /zg/g.
        Traffic density
         vehicles'day
Soil lead levels
   H9 9
           <1,000
        1,000-13,499
       13,500-19,499
          >19,500
    736
    922
   1109
   1059
  Dustfall samples for  28 days  from  9 locations
showed no relationship to traffic densities, but out-
door  levels were at least  10 limes the indoor  con-
centration in nearby residences.
  In the second phase, three groups of subjects, 1  to
6 years old, 1 8 to 49 years old,  and 50 years and
older, were selected in each of 4 study areas. Traffic
densities selected  were:  < 1,000, 8,000 to  14,000,
14,000  to  20,000,  and 20,000 to 25,000 cars/day.
The  study groups averaged about 35  subjects,
although  the  number varied from  21  to  50.  The
smallest groups were from the highest traffic density
area.  No  relationship between traffic density and
blood lead levels in any age groups  was found
(Figure 12-5).  Blood lead  levels  were significantly
higher in children, 12 to  18 /xg/dl, than in adults, 9
to 14 ngld\.
                                       MALES < 9
                                                                                            MALES >49

                                                                                          FEMALES 19-49
                                                                                          FEMALES >49
                               J_
             <1,000  1,000-13.500  13,500-     19.500-
                              19.50O     38,000
                    TRAFFIC DENSITY, cars/day
Figure 12-5. Blood lead concentration and traffic density by
sex and age, Dallas, 1976.**
  Galke et  al.43 studied blood lead  levels in 187
South Carolina children 1 to 5 years old in relation
to lead  in  soil and  to  automobile  traffic.  The
arithmetic mean blood lead level was related to both
factors, as shown in Table 12-18.
                                                 12-12

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    TABLE 12-18. BLOOD LEAD CONCENTRATIONS IN
 RELATION TO SOIL LEAD CONCENTRATIONS AND TRAFFIC
                    DENSITY"
Automobile traffic density
Soil lead
concentrations.
/*g'g
<585
>585
Total
Low mean
(951-1677
cars/day)
32 (7)a
36(10)
34(9)
High mean
(2446-9637
cars day)
41 (8)
43(11)
42(10)
All densities

35(8)
41 (11)
38(10)
  a Standard deviation of a single observation
  Caprio et al.51 compared blood  lead  levels and
 proximity to  major traffic arteries in a study,  re-
 ported  in  1971, that included  5226 children in
 Newark,  New  Jersey. Over  57  percent  of  the
 children living within  100 ft of roadways had blood
 lead levels greater  than 40 /Ltg/dl. For those living
 between 100 and 200 ft from  the roadways,  more
 than 27 percent had such levels; and at distances
 greater than 200 ft, 31 percent exceeded 40 /ng/dl.
 Table  12-19 indicates that the effect of automobile
 traffic was seen only  in the group that lived within
 100 ft of the road.
 TABLE 12-19. BLOOD LEAD LEVELS IN CHILDREN AGED 1
   TO 5 IN NEWARK, NJ, IN RELATION TO DISTANCE OF
     RESIDENCE FROM A MAJOR ROADWAY, 197151
Distance of residence
from roadway, ft
<100
100-200
>200
number
Percent blood lead levels
<40
42.6
724
684
3401
40-59
493
242
269
1562
>60
81
3.4
47
263
Number
758
507
3961
5226
  No other sources of lead were considered in this
study. Data from other studies on mobile sources in-
dicate, however, that it is unlikely that  the blood
lead levels observed in this study  resulted entirely
from  automotive exhaust emissions.
  Daines et al. studied black women living near a
heavily traveled highway in New Jersey.52 The sub-
jects lived in houses on streets paralleling the high-
way at 3 distances, 3.7, 38.1,  and 121.9 m. Air lead
as well as levels for blood  lead  were measured.
Mean  annual air  lead concentrations were 4.60,
2.41,  and 2.24 ;u,g/m3, respectively, for the 3 dis-
tances. The mean air lead concentration for the area
closest to the highway was  significantly  different
from that in both the second and third, but the mean
air  lead concentration of the third area was not sig-
nificantly  different  from  that of the second. The
results of the blood lead determinations paralleled
those  of the air lead. Mean blood lead levels of the 3
 groups of women,  in order of increasing distance,
 were 23.1, 17.4, and  17.6 /tg/100 g, respectively.
 Again, the first group showed a significantly higher
 mean  that the other two, but the second and third
 groups' blood lead  levels were similar to each other.
 Daines et al.,52 in the same publication, reported a
 second study in which the distances from the high-
 way were 33.5 and 457 meters  and where the sub-
 jects  were  white  upper middle  class  women.
 Although the air  lead levels were trivially different
 at these two distances, the blood lead levels did not
 differ. Because the residents nearest the road were
 already 33 m (+ 100 ft) from it and because other
 studies had shown an exponential decline in air lead
 levels with increasing distance from the road, reach-
 ing background air  lead levels at 250 ft, the explana-
 tion may  lie  in the  fact the air lead levels, although
 statistically   different,  were  insufficient  to  be
 reflected  in the blood lead levels. It is not possible to
 substantiate this possibility because the observed air
 lead values for the  two distances were not reported.
   In  1964, Thomas et al.53 investigated  blood lead
 levels in 50 adults who had lived for at least 3 years
 within 250 ft of a freeway (Los Angeles) and those of
 50 others who had lived for a like period near  the
 ocean or at least 1 mile from a freeway. Mean blood
 lead levels for those near the freeway were 22.7 ±
 5.6 for men and 16.7 ±  7.0 /xg/dl for women. These
 concentrations were higher than  for control subjects
 living near the ocean: 16.0 ± 8.4 p,g/dl for men and
 9.9  ±  4.9 /tg/dl for  women. The higher  values,
 however,  were similar to those of other Los Angeles
 populations.  Measured  mean air concentrations of
 lead in Los Angeles for October  1964 were 12.2.5 ±
 2.70 /u,g/m3 at a location 30 ft from  the San Bernar-
 dino freeway; 13.25 ± 1.90 /xg/m3 at another loca-
 tion 40 ft from the same freeway; 6.40 ±  2.15 /*g/m3
 at a fourth floor location 300 ft from the freeway;
 and 4.60 ± 1.92 /ng/m3 1 mile from the nearest free-
 way.  The  investigators concluded  that  the
 differences observed were consistent with coastal-in-
 land atmospheric and  blood lead gradients  in the
 Los Angeles  basin and that the effect of residential
 proximity to a freeway (25 to 250 ft) was not demon-
 strated.
 12.3.1.1.2 British studies.  In a Birmingham, Eng-
 land, study, mean blood lead levels in 41 males and
 58 females living within  800 m of a highway  in-
 terchange were 14.41 and  10.93 ngld\, respectively,
just prior  to the opening of the interchange in May
 1972.54 From October 1972 to February 1973 the
 respective values for  the same individuals  were
 18.95 and 14.93 /ig/dl.  In October  1973 they were
                                               12-13

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23.73 and 19.21  /u,g/dl. The investigators noted
difficulties in the blood collection method during
the baseline period and changed from capillary to
venous blood collection for the remaining two sam-
ples. To interpret the significance of the change in
blood collection  method,  some  individuals gave
both capillary and venous blood at the second col-
lection.  The means for both  capillary and venous
bloods were  calculated for the  18 males  and 23
females who gave both types of blood.55 The venous
blood mean values for both these males and females
were lower, 0.8 and 0.7 Mi/dl, respectively. If these
differences in means were applied to the means of
the third  series,  the means  for  males  would be
reduced to 24.8 fig/dl and that  for the  females to
18.7 /Ag/dl. These  adjusted means still show an in-
crease over the means obtained for  the first series.
On the other hand, discarding the means calculated
for the first series and comparing only the means for
venous bloods,  namely series two and three, again
shows an increase for both groups. The increase in
blood lead values was larger  than expected follow-
ing the model of Knelson et  al.56 because air lead
values near the road were approximately 1 /ng/m3.
The investigators  concluded that either the  lead
aerosol of very  small particles behaved more like a
gas so that considerably more than 37 percent of in-
haled material  was  absorbed or that ingestion of
lead-contaminated dust might be responsible.
  Studies of taxicab drivers have employed different
variables to represent the drivers' lead exposure,57-58
one being night- versus day-shift drivers;51 the other,,
mileage driven.58 In  neither case was any difference
observed.
  The studies reviewed show that automobiles pro-
duce  sufficient emissions to increase air and nearby
soil concentrations of lead as  well as increase blood
lead  concentrations in children  and adults. The
problem is of greater importance when  houses are
located within 100 ft (30 m) of the roadway.

12.3.1.2 STATIONARY SOURCE STUDIES
12.3.1.2.1  Primary smelters.  Most studies of nonin-
dustry-employed populations living in the vicinity of
industrial sources  of lead pollution were triggered
because evidence of severe health impairment had
been found. Subsequently, extremely high exposures
and high blood  lead concentrations were found. The
following studies document the health problems that
can develop as  well as some of the relationships be-
tween environmental exposure and human response.
12.3.1.2.1.1 El Paso, Texas. In 1972, the Center for
Disease Control, formerly  the Communicable Dis-
ease Center, studied the relationships between blood
lead levels and environmental factors in the vicinity
of a primary smelter emitting lead, copper, and zinc
located in El Paso, Texas, that had been in operation
since the late 1800's.33<59 Estimated lead emissions
from this smelter were 297 metric tons in  1969, 519
metric tons in 1970, and 317 metric tons in 1971r33
These  figures, however,  include  only stack emis-
sions; the quantities in fugitive emissions via ventila-
tion,  windows,  etc.,  are  unknown.  Daily high-
volume samples  collected  on  86 days  between
February and June 1972 averaged 6.6 jug/m3 of lead.
Concentrations ranged  from  0.49 to 75  /*g/m3.
These  air  lead levels fell off rapidly with distance,
reaching, as would be expected, background values
approximately 5 km from the smelter. Levels were
higher downwind, however. High concentrations of
lead in soil and housedust were found, with the high-
est levels occurring near the smelter. The geometric
means of 82 soil and 106 dust samples from the sec-
tor closest to the smelter were 1791  and 4022 pig/g,
respectively. Geometric means of both soil and  dust
lead levels near the smelter were significantly higher
than those in study  sectors 2 or 3 km farther away.
  Sixty-nine percent of children 1  to 4  years old liv-
ing  near the smelter had blood  lead  levels  > 40
/itg/dl, and 14 percent had  blood lead levels  that
exceeded  60 £tg/dl. Concentrations  in  older in-
dividuals were lower; nevertheless, 45 percent of the
children 5 to  9 years old, 31 percent of the in-
dividuals  10 to 19 years old, and 16 percent of the
individuals above 19 had blood lead  levels all ex-
ceeding 40  jug/dl.  The  data presented preclude
calculations of means and standard deviations.
  Data for people aged 1 to 19 years living near the
smelter showed a relationship between blood  lead
levels  and concentrations of lead in soil and dust.
For individuals with blood lead levels >40 /u.g/dl,
the geometric mean concentration of lead in soil at
their homes was 2587 jug/g, whereas for those with a
blood  lead concentration <40 /xg/dl, home soils had
a geometric mean of 1419 /ug/g. For housedust, the
respective geometric means were 6447  and 2067
Mg/g-
  Analysis found the effect of length of residence to
be important only in the sector nearest the  smelter.
Forty-three  percent of the  1-  to  19-year-olds  who
had  lived there  2  or more years had blood  lead
values 240 /u,g/dl, whereas only 18 percent of the 1-
to 19-year-olds who had lived there less than 2 years
had similar levels.
  Additional sources of lead were also investigated.
A relationship was found between blood lead  con-
                                                12-14

-------
centrations and  lead  release from pottery, but the
number of individuals involved was very small. No
relationships were found between blood lead levels
and hours spent out of doors each day, school atten-
dance, or employment of a parent at the smelter. The
reported prevalence of pica also was minimal.
  It  was concluded that the primary factor associ-
ated with elevated blood lead levels in the children
was ingestion or inhalation of dust containing lead.
Data on dietary  intake of lead  were not obtained
because the climate and  proximity to the smelter
prevented any farming  in the area.  It was unlikely
that  the dietary lead  intakes of the children  from
near the smelter and farther away were significantly
different.

 12.3.1.2.1.2 Kellogg,  Idaho. In 1970, EPA carried
out a study of a  lead smelter in Kellogg, Idaho.60-61
The study was part of a  national effort to determine
the effects of sulfur dioxide, total suspended particu-
late, and suspended sulfates, singly and in combina-
tion  with other  pollutants, on  human  health.  It
focused on mixtures of the sulfur compounds and
metals. Although it was demonstrated that children
had  evidence  of lead absorption, insufficient en-
vironmental data  were reported to allow further
quantitative analyses.
  In  1974,  following the hospitalization  of two
children with suspected  acute lead poisoning, CDC
joined the State of Idaho in a comprehensive study of
children in the area.'<62 The studies conducted in this
area  unfortunately used  a  bewildering  array of
designations in their reports, but all are related to
the same industrial complex.

  The source  of exposure was  a'smelter  whose
records showed that emissions of lead into the at-
mosphere averaged 8.3 metric tons per month from
1955 to 1964,  11.7 metric tons from 1965 to Sep-
tember  1973,  and 35.3 metric tons from October
1973 to September 1974.62 In September 1973, a fire
destroyed the main filtration facility for the smelter.
The study was initiated in September 1974, after two
children were hospitalized with symptoms of lead
poisoning. At that time, blood lead levels 240 jug/dl
were found in 385 (41.9 percent) of 919 children less
than 10 years old who were examined. About 99 per-
cent of the 172 children living within  1.6 km of the
smelter had blood lead values 240 /xg/dl. The mean
blood concentration declined with distance from the
point of emission (Table 12-20).  Blood  lead levels
were consistently higher in children 1 to 4 years old
than in  those 5 to 9 years old. In addition, higher
levels in children were associated with reported ac-
tive  ingestion  of  lead-containing material  (pica),
with lower socioeconomic status,  and  with parental
employment at  the smelter or at a lead mine. A  sig-
nificant negative relationship between blood lead
TABLE 12-20. GEOMETRIC MEAN BLOOD LEAD LEVELS BY AREA COMPARED WITH ESTIMATED AIR LEAD LEVELS FOR 1 - TO
  9-YEAR-OLD CHILDREN LIVING NEAR IDAHO SMELTER (Geometric standard deviations, sample sizes, and distances from
                                        smelter are also given)'
Area
1
2
3
4
5
6
GM
blood lead
M9 dl
659
477
33.8
322
275
21 2
GSD
1 30
1 32
1 25
1.29
1 30
1 29
Sample
size
170
192
174
156
188
90
Estimated
air lead,
MQ'm
180
14.0
67
3 1
1.5
1 2
Distance from
smelter,
Km
0- 1 6
1 6- 4.0
4.0-100
100-240
24 0-32 0
about 75
  a EPA analysis of data from Yankel et al

level and hematocrit value was found. Seven of 41
children (17 percent)  with blood  lead levels 280
jug/dl were diagnosed by the  investigators as being
anemic on the basis of hematocrit less than 33 per-
cent, whereas only 16 of 1006 children (1.6 percent)
with blood  lead  levels < 80 /ig/dl  were so diag-
nosed.
  Although no overt  neurologic disease was  ob-
served  in   children   with  higher  lead  intake,
differences were found in nerve conduction velocity.
Details of this finding were discussed in a previous
chapter.
  Beginning in 1971, ambient concentrations of lead
in the vicinity of the smelter were determined from
particulate matter  collected  in  high-volume  air
samplers.  Data  indicated that monthly  average
levels measured in 1974 (Figure 12-6) were three to
four times the levels measured in 1971.63 Individual
exposures to  lead  were estimated  by  interpolation
from these high-volume data, and a strong correla-
tion was  found  between  the  estimates  and  the
measured  blood lead levels (r  + 0.72).
                                               12-15

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Figure 12-6.  Monthly ambient  air  toad concentrations in
Kellogg, Idaho, 1971 through 1975.63

  Subsequently, Yankel et  al.  published additional
information concerning the  1974 study as well as the
results of a follow-up study conducted in 1975.J The
follow-up was  undertaken  to  determine  the effec-
tiveness of control measures initiated after the 1974
study.
  Between August 1974 and August 1975, the mean
annual  air lead  levels decreased  at  all stations
monitored (Figure 12-7). In order of increasing dis-
tance from the smelter, the concentrations in the two
years were  18.0 to 10.3 /ig/m3, 14.0 to 8.5 /*g/m3,
6.7 to 4.9 /ig/m3, and, finally, 3.1 to 2.5 jug/m3 at 10
to 24  km.  Similar  reductions were noted  in  the
housedust lead concentrations.
  In a separate report, von  Lindern and Yankel de-
scribed reductions in  blood lead levels of children
for whom determinations were made in both years.60
It was pointed out that the children with the highest
blood lead  levels in 1974 had  been relocated; their
removal and subsequent relocation would compli-
cate  any analysis in which  they were included. To
compensate for this, the authors also presented sepa-
rately the blood lead levels  for those children living
in the same home both years. This greatly reduced
the number of observations reported.  The  results
(Table  12-21)  demonstrate that significant  reduc-
tions in blood  lead concentration  can  be effected,
and  that they were observed in each study area. In
areas III, IV, and V, all mean blood lead levels were
<40/tg/dl.
  The  report of Yankel et al.1 showed that there
                                                                                 f	] AUG 1974
                                                                                 rrm AUG 1975
                               LnJL
         1      2      3      4      567
                   BY AREA (SEE TEXT)
Figure 12-7. Annual ambient air lead concentration, by area,
betore the August 1974 and August 1975 surveys.1

were reductions in environmental  lead contamina-
tion between 1974 and 1975, and that the correla-
tions between blood lead levels and environmental
or demographic factors were consistent  from one
year to  the  next.  Five factors  influenced,  in a
statistically significant manner, the probability of a
child developing an excessive blood lead level:
    1. Concentrations of  lead  in  ambient  air
       (/ig/m3).
    2. Concentration of lead in soil (ppm).
    3. Age (years).
    4. Cleanliness of the home (subjective evalua-
       tion coded 0, 1, and  2,  with 2 signifying
       dirtiest).
    5. General  classification  of the parents'  oc-
       cupation (dimensionless).
  Although the strongest correlation found was be-
tween  blood lead  level and air  lead  level,  the
authors concluded that it was unlikely that inhala-
tion of contaminated air alone could explain the ele-
vated blood  lead levels observed.
  Yankel and  von  Lindern  reasoned  that  even
though air lead was the principal source, a major
route of  exposure was the ingestion of lead  in soil
and dust.1 They proposed that to protect the health
                                              12-16

-------
  TABLE 12-21. MEAN BLOOD LEAD LEVELS IN CHILDREN LIVING IN VICINITY OF A PRIMARY LEAD SMELTER, 1974 and 1975
Group
Blood levels
>80|iig/d|a
in 1974 test
Retested in
1975
Difference
Blood levels
>60 but <80
/ig/dlin 1974
test
Retested in
1975
Difference
Blood levels
in 1974 test
Retested in
1975
Difference
Study area and data set
I II III
N X N X N X
— 902 - 80.0 — —
7 523 1 610 — —
— -380 — -190 — —
— 64.5 — 696 — —
18 474 8 50.3 — —
— -172 — -19.3 — —

— 523 — 470 — 456
9 374 23 36.0 20 39.8
— -14.9 — -110 — - 58

IV V
N X N "X

_
_ _ _ _
— — — 61.0
— — 3 51 0
— — — -10.0

— 43 7 — 43.4
14 374 8 33.5
— - 6.3 — - 99
  a Adapted from von Lindern and YankelB-
of the children in this area the regulation of environ-
mental standards must take into account all of these
routes of exposure.
  These  investigators developed  a mathematical
model based on the 1974 data that included each of
the five factors that had been shown to be correlated
with increased blood lead levels. The model, shown
below, can be used to estimate the effect of varia-
tions in the environmental factors on mean blood
lead levels in children:
1 n (Pb-B) =3.1+ 0.041 (Air) + 2.1 x 10'5 (Soil) +
0.087 (Dust)  + 0.018 (Age) +  0.024 (Occupation).
        (See above for definition of units).   (12-6)
12.3.1.2.1.3 CDC-EPA  study. Baker et   al.,31  in
1975, surveyed 1774 children 1 to 5 years old, most
of whom lived within 4 miles of 19 lead, copper, or
zinc  smelters located in various parts of the United
States. Blood  lead  levels were  modestly  elevated
near two of the 11  copper and two of the five  zinc
smelters. Although  blood lead  levels  in  children
were  not  elevated  in the vicinity of three  lead
smelters, their FEP  levels were somewhat  higher
than those found in controls. Increased levels of lead
and cadmium in hair samples were found  near  lead
and zinc smelters; this was considered  evidence of
external  exposure.  No environmental determina-
tions were made for this study.

12.3.1.2.1.4 Meza Valley,  Yugoslavia. A Yugosla-
vian study in the Meza  Valley investigated  ex-
posures to  lead from  a mine and a smelter  over a
period of years.64'69 The mine and  smelter are lo-
cated near a river flowing in the valley. The smelter
produces about 23,000 metric tons  annually. After
control equipment was installed on 1 of 2 lead-emit-
ting stacks, emissions were calculated to be  203.2
metric tons/year. In 1967, 24-hr lead concentrations
measured from 4 different days varied from 13 to 84
^g/m3 in the village nearest the smelter, and con-
centrations of up to 60 /^g/m3 were found as far as 5
km from the source. Mean particle size in 1968 was
<0.8 fj.m. The lead levels were about 25,000 ppm in
the most contaminated area. Analysis of some com-
mon foodstuffs showed concentrations that were 10
to 100 times higher  than corresponding foodstuff
from the least exposed area (Mezica).64
  After January  1969 when partial control of emis-
sions  was  established at  the smelter,  weighted
average weekly exposure was  calculated to  be 27
(itg/m3 in the village near the smelter. In contrast to
this, the city of Zagreb,65 which has no large station-
                                               12-17

-------
ary source of lead, had an average weekly air lead
level of 1.1 Atg/m-\
  In 1968, the average concentration  of ALA in
urine samples  from 912 inhabitants of six villages
varied by village from 9.8 to 13 mg/liter.  A control
group had a mean ALA of 5.2 mg/liter. Data on lead
in blood and  the age  and  sex distribution  of the
villagers were not given.64
  Of the 912 examined, 559 had an ALA level > 10
mg/liter of urine. In 1969, a more extensive study of
286 individuals with ALA > 10 mg/liter was under-
taken.66 ALA-LJ  decreased  significantly  from the
previous year. When the published data were ex-
amined  closely, there appeared to be some discre-
pancies  in interpretation. The exposure from dust
and from food might have been affected by the con-
trol devices, but no data were collected to establish
this. In  one village, Zerjau,  ALA-U dropped from
21.7 to 9.4 mg/liter in children 2  to 7 years of age.
Corresponding ALA-U values for 8- to 15-year-olds
and for adult  men and women were reduced from
18.7 to 12.1, from 23.9 to 9.9,  and from 18.5 to 9.0
mg/liter, respectively. Because lead concentrations
in air65  even after 1969 indicated  an average expo-
sure of 25 /ug/nv\ it is  possible that some other ex-
planation should be sought. The author  indicated in
the report that the decrease in  ALA-U showed "the
dependence on meteorologic, topographic, and tech-
nologic  factors."66 Lead  in blood was  determined,
but according to the report "determination of lead in
blood could not  be  used for  exposure evaluation
because all  obtained values were  in  the normal
limits" (under 80 ^tg/dl  blood as defined by the
author)/1'1 In light of current knowledge, this  defini-
tion of normal levels is excessively high.
  The excretion of nonchelated lead in  urine in 8.5
percent  of 209 individuals was above 0.1 mg/liter.
The highest value recorded was 0.19 mg/liter. When
treated with Ca EDTA, the mobilized  lead  in the
urine of these individuals ranged from 0.5  to 4.2
mg/liter, indicating the presence of total body bur-
dens ranging from normal to ten times normal.66'68
  Another finding of this project  was a significant
increase  in reticulocytes, especially  in children.66
Forty-seven  percent of exposed adults  complained
of pain in their bones compared with only 3 percent
of the controls.
  Fugas et al.69 in a later  report estimated the time-
weighted average exposure of several  populations
studied during the course of this project. Stationary
samplers as well as personal monitors were used to
estimate the exposure to  airborne lead for various
parts of the day. These values were then coupled
with estimated proportions of time at which these ex-
posures held.  In Table  12-22, the estimated time-
weighted blood lead values as well as the observed
mean blood lead levels for these studied populations
are presented. An increase in blood lead values oc-
curs with increasing air lead exposure.
 TABLE 12-22. MEAN BLOOD LEAD LEVELS IN SELECTED
 YUGOSLAVIAN POPULATIONS, BY ESTIMATED WEEKLY
        TIME-WEIGHTED AIR LEAD EXPOSURE69


Population
Rural I
Rural II
Rural III
Postmen
Customs officers
Street car drivers
Traffic policemen


N
49
47
45
44
75
43
27
Time-
weighted
air lead
ng/m3
0.079
0094
0.146
1.6
18
21
30
Mean blood
lead level.
Aig/dl
79
11.4
105
183
10.4
24.3
12.2

SO
4.4
4.8
4.0
9.3
33
105
5 1
 12.3.1.2.1.5 East Helena, Montana.  EPA in 1972
 investigated a lead-emitting smelter complex in East
 Helena, Montana.60 The quantities of lead emissions
 were not known. Air lead concentration, measured
 in 1969, yielded averages from several stations that
 varied from 0.4 to 4 ptg/m3; the maximum 24-hr
 value was found to be  15  jug/m3.  In the  city of
 Helena, the average concentration was 0.1  /^g/m3.
 Lead in soil was found to be 4000, 600, and  100
 /Ag/g at distances of 1.6, 3.2, and 6.4 km (1,2, and 4
 miles), respectively, from the smelting complex. Un-
 contaminated soil near the Helena Valley showed a
 mean of  16 Mg/g.  Deposited  lead  (dustfall) was
 found  to vary from 3 to 108 mg/m2-month  in East
 Helena and from 1  to 7 mg/m2-month in Helena.
  Studies on  humans by  Hammer et al.61 were
 limited to children; lead values in  hair and blood
 were found to be higher in East Helena  than in
 Helena, the respective averages being 15.6 ±  5.1
 and 11.6 ±  4.0 /tg/dl in blood and about 40 and 13
 ppm in hair. The hair values indicated differential
 exposure to lead. However, in the opinion of the in-
 vestigators, although the blood lead values indicated
 an elevated  exposure, it had not been excessive. No
 adverse health effects  had  been noted in these
 children.

 12.3.1.2.1.6 Other smelter studies. Other  reports in
 the literature  have also shown  that people living
 near smelters have increased burdens of lead  in their
 bodies.70'72 It is clear, therefore, that emissions from
 primary lead smelters can cause elevated blood lead
 levels and other indicators of increased lead burdens
 in populations living near these stationary emission
 sources.
                                               12-18

-------
   The  question of the accuracy  of the reported
 analytic results in these studies is difficult to address
 because they spanned a period of time in which ma-
 jor strides were taken in improving analytical tech-
 nology. Hence, the more  recent studies are  likely,
 but not necessarily, to provide more accurate infor-
 mation.

   Although many  of  the reports specified that the
 blood lead levels were done in duplicate, this unfor-
 tunately does not  ensure their accuracy. This prob-
 lem is discussed in more detail in Chapter 9.

 12.3.1.2.2  Other  industrial  sources.  Exposures
 from both a primary and secondary smelter in the in-
 ner-city area of Omaha, Neb. have been reported by
 Angle et al. in a series of publications.73-76 Studied
 from 1970  to  1977 were  children  from an  urban
school immediately adjacent to a small battery plant
and  downwind from two other  lead  emission
sources, schools in a mixed commercial-residential
area, and schools in  a suburban setting.  Children's
blood lead levels were obtained by macro technique
for 1970 and 1971, but Delves micro assay was used
from 1972 on. The difference for the change in tech-
niques was taken into account in the presentation of
the data.  Air lead values were obtained  by Hi-Vol
samplers, and  dustfall values also were collected.
Table 12-23 presents the authors' summary of all the
data, showing that as air lead values decrease and
then increase, dustfall and blood lead values follow.
The authors used regression models, both log-linear
and semilog, to calculate air lead/blood lead ratios
and obtained values  of 10.04 and 0.4, respectively.
The 0.4 value is equivalent to a ratio of 10.4 at an air
lead level of 1.0 /ng/m-1.
      TABLE 12-23. AIR, DUSTFALL, AND BLOOD LEAD CONCENTRATIONS IN OMAHA, NEB., STUDY, 1970-19778'75'76
Group
All urban children, site m
1970-71
1972-73
1974-75
1976-77
Children at school c. site c
1970-71
1972-73
1974-75
1976-77
All suburban children, site r
1970-71
1972-73
1974-75
1976-77
rPb-B« Pb-A= -095(N= 10)
Pb-B = 10 04 Pb-A + 1706
r1n Pb-B • Pb-A = 0 91 (N = 10)
1n Pb-B =04 Pb-A t 286
Air
lig m3 iNlb

1 48 ±
043 ±
010 ±
052 +

1 69 ±
063 +
0 10 ±
060 ±

079 +
029 +
0 12 ±






0 14(7,65)
008(8,72)
003(10,72)
007(12.47)

0 11(7,67)
0 15(8,74)
003(10,70)
0 10(12,42)

006(7,65)
004(8,73)
005(10,73)
—




Dustfall
Mg m3 - mo iN)c


106
60
88


259
143
339


46
29






—
± 03(6)
± 0 1(4)
(7)

—
+ 24(5)
+ 4 1(4)
(7)

—
± 1 1(6)
± 09(4)
—




Blood
M9 dl (N)d

31 4
233
204
228

346
21 9
192
228


196
14.4
182





± 07(168)
± 03(211)
± 0 1 (284)
± 07(38)

± 15(21)
± 06(54)
± 09(17)
± 07(38)

—
± 05(81)
± 06(31)
± 0.3(185)




  Blood lead 1970-71 is by the macro technique corrected for an established laboratory bias of 3 ^g dl macro-micro all other values are by Delves micro assay
  N - Number of months number of 24-hour samples
 CN - Number of months
  N - Number of blood samples
  Specific  reports  present  various  aspects  of the
work done. Black  children in the two elementary
schools closest to the battery plant had higher blood
leads (34.1 ^g/dl) than  those  in elementary and
junior high schools farther away (26.3 /xg/dl). Best
estimates of the air exposures were 1.65 and  1.48
Mg/m3,  respectively.73 The later study compared
three  populations: urban  versus  suburban  high
school students, ages 14 to 18; urban black children,
ages 10 to 12, versus suburban whites, ages 10 to 12;
blacks, ages  10 to 12, with blood lead over 20 ^g
percent versus schoolmates with blood lead levels
below  20 fj.g percent.74 The urban versus suburban
high school  children  did  not differ  significantly,
22.3 ± 1.2 to 20.2 ±  7.0  ;u,g/dl, respectively,  with
mean values  of air lead concentrations of 0.43 and
0.29 /wg/m3. For the 15 students who had environ-
mental samples taken from their homes, correlation
                                                12-19

-------
coefficients between blood lead levels and soil and
housedust lead levels were  0.31  and 0.29 respec-
tively.
  Suburban 10-to-12-year-olds  had  lower blood
lead levels than their urban counterparts,  17.1  ±
0.7 and 21.7 + 0.5 /ug/dl, respectively.74 Air  lead
exposures were  higher  in  the urban than  in  the
suburban population, although the average exposure
remained less than 1 /ig/m3. Dustfall lead measure-
ments,  however,  were  very much  higher: 32.96
mg/m2-month  for urban 10-to-12-year-olds versus
3.02 mg/m2-month for suburban ones.
  Soil lead and housedust lead exposure levels were
significantly higher for  the  urban black  high-lead
group than for the urban low-lead group. A signifi-
cant correlation (r = 0.49) between blood lead and
soil lead levels was found.
  In a  Dallas, Texas, study of two secondary  lead
smelters, the average  blood lead  levels of exposed
children was found to be 30 ^ig/dl versus an  average
of 22 ju.g/dl in  control children.77 For the  two study
populations, the air and soil lead levels were 3.5 and
1.5 /ug/m3 and  727  and 255 ppm, respectively.
Direct  automobile traffic exposure was not con-
sidered.
  In Toronto, Canada, the effects of two secondary
lead smelters on the blood and hair lead levels of
nearby residents have been extensively studied.78.79
In a preliminary report, Roberts et al.78 stated that
blood and hair lead levels  were higher in children
living near the two smelters than in children living in
an urban control area. Biologic and  environmental
lead levels were reported to decrease with increasing
distance from the smelter stacks.
  A later and more detailed report identified a high
rate of lead  fallout  around  the  two secondary
smelters.79 Fallout in the vicinity of the smelters was
caused primarily by large paniculate fugitive emis-
sions rather than stack  emissions. Lead  emissions
from the two smelters were estimated to be 15,000
and 30,000 kg/yr. Lead  concentrations in soil were
as high as 40,000 and  16,000 ppm, respectively,
close to the 2 smelters  and dropped off exponen-
tially with  distance.  They reached  urban back-
ground levels of 100 to 500 ppm, 200 to 300 m from
the smelter. Horn, in a later report, pointed  out that
the extremely high soil levels were the result of some
samples containing scrap battery plate; in his report
he states that  the soil lead  levels, excluding those
contaminated  samples,  approached  8000  ppm  in
nonresidential areas and exceeded  4000  ppm  in
several  residential yards.80 He  also pointed  out
several other deficiencies in the data.**0 A general
criticism he leveled at the study's interpretation was
that  the authors concluded  that soil  lead was  the
main source of lead, a putative finding in Horn's
view, especially  considering that few soil samples
were taken.
  Lead concentrations in dustfall were much higher
at 1  of the 2 smelters, exceeding 1500 mg/cm2-
month. These concentrations also exhibited an expo-
nential decrease with distance similar to that  ob-
served for soils. Because the lead  fallout occurred
over a small  area  and consisted primarily of large
particles (in some  cases the mass median diameter
was  as large as 4.6 ± 1.3 /*m), it was believed that
the emissions originated mainly from dust-produc-
ing operations at low height rather than from stack
emissions.78
  Lead concentrations in air ranging from 1.0 to 5.3
/ug/m3 were only twice those found  at other Toronto
urban sites away from the smelter (0.8 to 2.4 /^g/m3).
The  range of daily  concentrations was much greater.
At 60 m  from the stack, lead in 96 air samples
ranged from 0.5 to 725 jug/m3, whereas at 220 m 94
samples varied from  <0.5 to 14 /xg/m3. Two groups
of children  living within  300 m  of each  of  the
smelters had geometric mean blood levels of 27 and
28 ptg/dl, respectively; the geometric mean for 1231
controls was  17 /j,g/dl. Twenty-eight percent of the
sample children  tested near  one smelter during the
summer and 13 percent of the sample children tested
near the second smelter during the winter had  blood
lead  levels >40 /ig/dl. Only 1 percent  of the con-
trols had blood lead levels >40 ng/d\. For children,
blood lead concentrations increased with proximity
to both smelters but this trend did  not hold  for
adults generally.
  Lead levels in hair samples averaged 41 /Ltg/g in
the smelter areas and 13 fig/g in the control area.78
Blood lead and hair lead levels were found to be re-
lated, thus indicating a fairly constant  rate of ab-
sorption. The authors concluded that for children
with excessive lead  absorption the major route of
lead  intake was ingestion of contaminated dirt  and
dust.78'79  Increased  excretion of 8-aminolevulinic
acid  and coproporphyrins was observed  in most of
these  cases, and  increased density of  bone
metaphyses was observed in four children.
  Blood lead levels in 293 Finnish individuals aged
15 to 80 were significantly correlated with distance
of habitation from a secondary lead  smelter.81 The
geometric mean blood lead concentration for  121
males was 18.1 /xg/dl; that for 172  females was 14.3
Aig/dl. In  59  subjects who spent their entire day at
home, a positive  correlation was found between
                                               12-20

-------
 m. Only one of these 59 individuals had a blood lead
 >40 fj.g/d\, and none exceeded 50 /u.g/dl.
   A  weaker  correlation  was  obtained  between
 ALAD activity and distance from the smelter, this
 being due almost entirely to the female subjects. Ex-
 amination of ALAD activity  for males showed it to
 be similar  regardless of distance from the smelter.
 The authors speculate that this could be caused by
 other lead  exposures  in the male population.
   Two reports from  the USSR describe effects of
 lead in an area near  a smelter.82'83 Average con-
 centrations of lead in air were as high as 4.1 /Ag/m3 at
 a distance of 1500  m; peak exposures at this distance
 reached 9.7 ^tg/m3. Neurological disturbances were
 noted  in 50 percent of the subjects from the smelter
 area, compared with 6 percent in controls. No data
 were given on age,  sex, and type of disturbances.82 In
 a  later study, children from the  area were found to
 excrete more coproporphyrin than controls and also
 more lead.83 The highest lead concentration in urine
 was  reported to  be 50 /ug/liter.
   Studies of the effects of storage battery plants have
 been reported  from   France and  Italy.84-85 The
 French study found  that children  from  an  in-
 dustrialized area containing  such a plant excreted
 more ALA than those living in a different area.84 In-
 creased urinary excretion  of lead and  copropor-
 phyrins was found in  children living up to 300 ft
 from a battery plant in Italy.85 Neither study gave
 data on plant emissions or lead in air.
   These studies demonstrate that stationary sources
 within  urban areas do contribute to increases in air
 lead levels. They show not only that mean exposure
 levels are higher but that the range of exposures en-
 countered in their  vicinities is much larger for daily
 or longer averaging times than in the vicinity of
 mobile sources. Increases of 2 to 3 /ug/m3 in air lead
 concentrations  have  been  associated  with higher
 blood lead levels in exposed populations.
  Although the  significantly higher air  lead con-
 centrations decrease rapidly with distance from  the
 point of emission, they contribute, together with
 mobile emissions, to the generally higher air  levels
found in urban areas  and thus to the  higher blood
 lead  levels found in urban populations.

 12.3.1.3 URBAN  POPULATION STUDIES

  Another  group  of  studies dealing  with urban
populations examined air  lead  and  blood lead
values without considering the specific sources of the
lead  in the air.2-3'16-41'42 Azar  et al.3 obtained 24-hr
air lead exposures for  150 males over a 2- to 4-week
 period using personal  samplers. Study groups con-
 sisted of 30 men in each of 5 city-occupation catego-
 ries.  The subjects included  cabdrivers,  plant
 employees, and office  workers.  From  two to  eight
 blood samples were obtained from each subject dur-
 ing the  air monitoring  phase.  Blood lead deter-
 minations were done in duplicate. Table 12-24 pre-
 sents the geometric means for air lead and blood
 lead for  the five groups.  The geometric means were
 calculated  by EPA from the raw data  presented in
 the authors' report.3

  TABLE 12-24. GEOMETRIC MEAN AIR AND BLOOD LEAD
 LEVELS 0*9/100 g) FOR FIVE CITY-OCCUPATION GROUPS3
              (Data calculated by  EPA)
Geometric
mean
Group
Plant employees
Starke, FL
Plant employees
Barksdale. Wl
Cabdrivers
Philadelphia, PA
Office workers
Los Angeles, CA
Cabdrivers
Los Angeles CA
air lead
IJ-g m3
0.59
061
2.59

297

602

Geometric
mean
blood lead
GSD ng 100 g
204
239
1 16

1 29

1 18

15.4
128
22 1

184

242

Sample
GSD size
1 41
1 43
1 16

1 24

1 20

29
30
30

30

30

  Regression equations calculated by the authors for
members  of  each of the individual study groups
revealed no slopes significantly greater than zero. In
view of the rather narrow range of lead exposures
observed within the groups, this result is not surpris-
ing. Examination of the slopes for each study group
showed they  were homogeneous  and thus could  be
combined. The specific method of combination can
be argued, however. Azar et al. chose to use dummy
variables to represent the differing intercepts of the
study groups  because the  intercepts were not homo-
geneous. In effect, this means drawing a line with a
pooled  slope of 0.153 through the average blood
lead concentration.
  The Tepper and Levin2 study, described in detail
previously,  included  both  air   and blood  lead
measurements.  Housewives were recruited  from
"locations  in  the vicinity of air monitors." Women
included were > 19 and  < 80 years of age, had no
history of  lead poisoning, and had not  eaten wild
game. Table  12-25 presents the geometric mean air
and  blood lead  values obtained in the study,  as
calculated  by EPA  from the raw data.  Geometric
mean air  lead values ranged from 0.17 to 3.39
                                              12-21

-------
/u,g/m3,  and geometric  mean  blood  lead  values
ranged from 12.5 (1.31) to 20.6 (1.33) /ug/dl.
 TABLE 12-25. GEOMETRIC MEAN AIR AND BLOOD LEAD
        VALUES FOR 11 STUDY POPULATIONS2
              (Data calculated by EPA)
                               Blood lead
                      Geometric
                        mean
Community
Los Alamos, NM
Okeana, OH
Houston, TX
Port Washington, NY
Ardmore, PA
Lombard, IL
Washington, DC
Rittenhouse, PA
Bridgeport, IL
Greenwich Village, NY
Pasadena, CA
air lead
^g m3
017
032
085
1 13
1 15
1 18
1 19
1 67
1 76
208
339
GM
149
156
125
154
180
13.9
192
206
176
166
175
GSD
1 28
1 39
1 31
1 28
1 38
1 27
126
1 33
1 27
1 28
131
Sample
size
185
156
186
196
148
146
219
136
146
139
194
  Nordman reported a population study from Fin-
land'6 in which data from five urban and two rural
areas were compared. This study was described in
detail above. Air lead data were collected by sta-
tionary samplers. All levels were comparatively low,
particularly in the rural environment, where a con-
centration of 0.025  /u,g/m3 was seen. Urban-subur-
ban levels ranged from 0.43 to 1.32 /Ltg/m3.
  A study was undertaken by Tsuchiya et al.41 in
Tokyo using male policemen who worked, but not
necessarily lived, in the vicinity of air samplers. In
this  study, five zones  were established, based on
degree of urbanization, ranging from central city to
suburban. Air monitors were established at various
police stations within  each zone.  Air sampling was
conducted from September 1971 to September 1972;
blood and urine samples were obtained from 2283
policemen in August and September 1971.  Findings
are  presented in  Table  12-26.  A  consistent  cor-
relation between air and blood lead means for the
five  zones is shown.
 TABLE 12-26. MEAN AIR AND BLOOD LEAD VALUES FOR
           FIVE ZONES IN TOKYO STUDY41
Zones
                    Air lead
                        3
Blood lead
 n g 100 g
                    0024
                    0,198
                    0.444
                    0.831
                    1.157
  170
  17 1
  168
  180
  197
  Goldsmith42 obtained data for elementary school
(9- and 10-year-olds) and high school students in 10
California communities. Lowest air lead exposures
were 0.28 /xg/m3 and highest were 3.4 /itg/m3. For
boys in elementary school, blood lead levels ranged
from 14.3 to 23.3 /ug/dl; those for girls ranged from
13.8 to 20.4 /ug/dl for the same range of air lead ex-
posures.  The high school student population was
made up of only males from some  of the 10 towns.
The air lead range was 0.77 to 2.75 /u,g/m3 and the
blood lead range was from 9.0 to  12.1 /ug/dl. For the
high school students the town with the  highest air
lead value did not have the highest blood lead  level.
A further comment on  methodology pertains to the
fact that a  considerable lag time occurred between
the collection and analysis of the blood samples.
12.3.1.4 CLINICAL  AND EXPERIMENTAL
STUDIES   IN   RELATION  TO   AIR
LEAD/BLOOD  LEAD RATIOS
  Griffin and his colleagues undertook two studies
using volunteers exposed in a gas chamber to an ar-
tificially generated aerosol of submicron-sized  parti-
cles  of  lead dioxide.86  All volunteers were  intro-
duced into the chamber 2 weeks prior to the initia-
tion  of  the  exposure; the lead  exposures  were
scheduled to last 16 weeks, although the volunteers
could drop out whenever they wished. Twenty-four
volunteers, including 6 controls, participated  in the
 10.9 /u.g/m3 exposure study. Twenty-one subjects, in-
cluding 6 controls, participated in the 3.2 /ug/m3 ex-
posure study. Not all volunteers completed the ex-
posure regimen.  Blood lead levels were found to
stabilize after approximately 12 weeks.  Among  11
men exposed to  10.9 /ng/m3 for  at least 60 days, a
stabilized mean level of 34.5 ± 5.1 /u-g/dl blood was
obtained, as compared with an  initial level of 19.4
±  3.3 /ig/dl.  All but 2  of the 14 men exposed  at 3.2
/ig/m3 for at  least 60 days showed increases  and a
stabilized level of 25.6  ± 3.9 /ug/dl was found, com-
pared with  an initial level of 20.5 ± 4.4 /ug/dl. This
represented an increase of about 40 percent above
the base level.
  From  the  data Table  12-27  was constructed,
which shows the  time needed to reach specific  blood
lead levels at the two air lead concentrations. As can
readily be seen even at the lower exposure, it takes
only 7 weeks for the population mean blood level to
increase by 5 /ug/dl.
  In  the article, the  authors  described both the
chemistry  and particle size of the lead aerosols
generated.  In general,  the aerosols used  in this ex-
periment were somewhat  less complex chemically,
as well as somewhat smaller, than those found in the
ambient environment.  Griffin   et al.,86 however,
point out that good agreement was achieved on the
basis of the comparison of their observed blood lead
                                              12-22

-------
     TABLE 12-27. LENGTH OF TIME NEEDED FOR MEAN BLOOD LEAD VALUES TO REACH SPECIFIED LEVELS AT TWO
                                          EXPOSURE LEVELS

Exposure
group
1
1
1
2
2
2

Air lead
level M9 ^
109
109
109
32
32
32
Avg baseline
blood lead
level ^g dl
200
200
200
208
208
208
Target
blood lead
level ^g dl
25
30
35
25
30
35
Time needed
10 reach
target level wk
1 to 2
4
6
7
Not reached
Not reached
levels with those predicted by Goldsmith and Hex-
ter's equation,87 that is, log,0 blood lead =  1.265 +
0.2433 logu) atmospheric exposure.
  In contrast to  the study of Griffin  et  al. that
approximates the  exposure  regimen of  environ-
mentally exposed persons, Kehoe studied long-term
exposures under conditions approximating those of
occupationally exposed  individuals.88  Kehoe  ex-
posed a subject to an air lead as the sesquioxide first
at 75 jug/m3 then at  150 /iig/m3. Definite increases in
urinary and blood lead  levels emerged under each
exposure. There appeared to be a plateau reached in
the blood lead levels upon a steady state exposure.
  Gross compiled data from  lead balance studies
conducted  by Kehoe between 1934 and  1972 and
determined that increases  of levels in  blood, urine,
and  feces under controlled clinical exposure were
0.38 jug/dl, 0.88 /ug/day, and  2.50 ^g/day, respec-
tively,  for  each increase  of  1  /Mg/m3 in  air  lead
levels.89
  The derivation of these estimates is  currently un-
known but was based on the results of  ingestion and
inhalation studies carried out on 16 individuals over
21,000 person-days. During this period, there were
102 study periods for the  16 subjects. None of the
subjects experienced harmful effects as  a result of
the lead exposures, the  highest of which were  ap-
proximately 30 /ig/m3 on a 24-hr basis (every  other
day to 6 days per week) for study periods up to 628
days. With a single exception, in none of the subjects
did the blood level  exceed 40 /Ag/dl.
  Rabinowitz  and  colleagues  have conducted
studies of lead metabolism by stable  isotopes that
permit  the determination of blood/air lead relation-
ships.90-91 In one study, a single volunteer was con-
fined in a hospital's metabolic research ward for a
period  of 109 days for 23  hr a day.90  He was then
removed into a "clean"  room in  which the  air was
filtered to remove the particulate lead. For the first
15 days in  the room,  his daily  lead intake was
supplemented by lead additions to the diet to com-
 pensate for the loss of air lead intake. At the end of
 this 15-day period the dietary lead supplement was
 discontinued. He immediately showed  a declining
 blood  lead   level  that  eventually  reached  a
 minimum. He  then  left  the "clean" room and his
 blood lead level went back up. Unfortunately, his
 blood lead did not stabilize after  his exit from the
 "clean" room.
   A further  report  presents  data,  involving addi-
 tional volunteers, from which a blood  to air lead
 ratio can  be  derived.91  Subsequent to a stabilizing
 period in a metabolic ward, they entered the filtered
 air room and  blood lead levels decreased. The blood
 lead  levels did stabilize upon exit from  the clean
 room.
   Chamberlain et al.92-93  reported on  studies in
 which gasoline containing tetraethyl lead labeled
 with  203Pb was burned in an internal combustion
 engine and the resulting tagged lead exhaust aerosol
 was inhaled  by 6  volunteers.  The  lead con-
 centration92 was typically about 6 mg/m3 and the
 total particulate 30 mg/m3. The aggregates of parti-
cles about 0.6 /j.m in diameter were stable; those f
0.01 /j,m tended to coagulate. Exposures  were for 30
min or less, and the progress of the lead through the
body was monitored. It was found that about 40 per-
cent of the particles  was  retained,  and that 60 per-
cent was exhaled. The lung clearance rate for :03Pb
activity varied markedly, depending on whether the
aerosol was irradiated. The transference of activity
to the blood peaked  at 50 hr  after inhalation at 48
percent of the initial lung burden. At 72 hr, about
half of the lead had been removed to bone and other
tissues and the  other half had become attached to
red cells.  The  amount of 203Pb in the  blood was
found  to decline  with  a  biological half life of 16
days.
  Chamberlain  et al. then extrapolated  these high-
level, short-term exposures to  longer term ones. The
following formula and data were used to calculate a
blood-to-air level ratio:
                                               12-23

-------
_
          [% Deposition] [% Absorption] [Daily
                  ventilation]
            [Blood volume] [0.693]
       where: a = blood to air lead  ratio
            T.,7=  biological half life
                                        (12-7)
              1/2
            Data used were:
            1.  Airborne level =  1
            2.  Exposure  = 24 hr/day
            3.  Daily ventilation =  15m3/day
            4.  % Deposition =40*
            5.  % Absorption =50*
            6.  Blood volume =  5400 ml

 *These values were determined experimentally in this study, all others are authors'
  assumptions

  Using  the above equation and  values, Cham-
berlain et al.93 obtained a ratio of 1.2, in contrast to
a value of 1.1 reported in an earlier report,92 where
slightly  different assumptions were  made. In this
earlier report,92 data from Kehoe88 and Williams et
al.94 were  used in  a similar manner to  calculate
ratios of 1.1 and 1.1, respectively. It is interesting to
note the difference  in  the  ratios  calculated by
Gross89 and Chamberlain et al.92 from the Kehoe
data. However, the  extrapolation of Chamberlain et
al.  of the short-term to long-term exposure is in
close agreement with the results of Kehoe and of
Williams et al., as Chamberlain et al. calculated
them.
  Chamberlain's ratios have been recalculated by
Bridbord95 on  the  basis  of a more active person's
daily ventilation of 20 m3. This, he  states, would
yield a ratio of 1.6 /xg/dl for each 1 /tig/m3 of air lead
exposure.

12.3.1.5  BLOOD/AIR LEAD RELATIONSHIPS
  Summarization of the relationship between lead in
air  and  lead in blood requires the consideration of
several distinct lines of evidence. These include: the
minimal air lead concentration at which blood lead
levels are first elevated, the form and magnitude of
the relationship, the proportion of the population
whose blood lead level exceeds any specific value at
any given air  lead  concentration, and whether the
form or magnitude of the relationship varies de-
pending on whether the air lead exposure is increas-
ing, remaining constant, or decreasing.
  On the first point, only a few studies have  suffi-
ciently precise estimates of air lead exposures to per-
mit this calculation, namely Yankel et al.1  and Azar
et al.3 EPA used William's 9<> test on the data from
both these studies to determine the air lead levels at
which blood lead levels were found to be signifi-
cantly higher than the geometric mean blood lead
levels of the groups  exposed to  the lowest air lead
level, which thus served as controls. William's test is
a multiple comparison  test  designed  to  make such
comparisons.
  For data from  the  Yankel et  al. study,1  EPA
pooled the lowest two  air lead  exposure areas (V
and VI) to form the control group.
  The test showed that  area IV  was the first, in  the
ordered data, that showed  significant elevation of
blood lead values. The  corresponding air lead con-
centration for this area was 1.7 //.g/m3.
  EPA, using this same  test for the Azar et  al.
study,3 showed that blood lead values for the Phila-
delphia cabdrivers were significantly different from
that  for  the pooled Starke and  Barksdale plant
employees that constituted the control  population.
Blood  lead  values for  the Los Angeles office
workers were also significantly higher than those of
control populations. The corresponding air lead ex-
posures were 2.6 and 3.1 /ig/m3, respectively.
  The clinical study of Griffin et al.86 provides data
that support the results  of the EPA analysis of Azar
et al.3 data. The data show that individuals exposed
to 3.2 ^u.g/m3 had a definite increase in their blood
leads as a result of this exposure.
  Thus, the available data are consistent as to  the
value of air lead concentration at which blood lead
levels begin to  increase.  The Yankel et al. data1
demonstrated this increase at 1.7 /ng/m3; the Azar et
al, data,3  at 2.6 ^ig/m3.  These results are not incon-
sistent because the Azar et al. study did not have a
population exposed to a level of air lead between 1
and 2.6/xg/m3.
  The derivation of the functional relationship  be-
tween air lead exposure and blood lead levels  has
technical  difficulties because the true form of this
relationship is  not  linear.  No matter  what  the
difficulty  in making  this assessment is,  the form of
the relationship is extremely important because it is
used to determine the effect of a change in the blood
lead levels as a function of the air lead values.
  Some studies, by the  very nature of their design,
only permit calculating the ratio between a change in
blood lead and associated change in the air lead con-
centration. For these situations, the calculated ratio
can be considered as an  estimate  of the average ratio
over the range of the air lead levels encountered.
  For those studies in which a functional relation-
ship can be derived, this ratio can be estimated for a
given air  lead  concentration  by evaluating  the
derivative of  the functional relationship  at  that
                                               12-24

-------
value. This ratio is subject to considerable change
over  the range of air lead levels encountered, de-
pending on the form of the relationship that was fit-
ted. We have chosen, wherever possible, to use the
author's own model for the relationship.
  The earliest attempt to  use epidemiological data
to calculate a blood-to-air lead relationship was
made by Goldsmith and Hexter.87 A linear regres-
sion equation of the  logarithm  of  the  blood lead
level  on the air lead  level was performed on data
from the Three-City Study.40 Data from Kehoe's ob-
servations  on 4 individuals experimentally exposed
to 10  and 150 /ng/m3 in a pattern equivalent to a nor-
mal work exposure were  found to fit the equation.
The slope  of this line was not significant below 2
^ig/m3 of air exposure, possibly because few observa-
tions  were  available in the Three-City Study below
that level.  The derived slope of the regression line
suggests an increase of 1.3 /ng/dl for each microgram
of air lead.
  Azar et al.3 used a log-log model to fit their data;
the data, as well as the regression line, are presented
in Figure 12-8. The slopes, that  is,  the ratios, were
calculated from the equation, log Pb-B =  1.2557 +
0.153 (log Pb-A), at the four air lead values shown
in Table 12-28. These slopes ranged from 2.6 at an
air lead of  1.0  /u,g/m3 to 0.7 at an air lead of 5.0
/ig/m3.  It is important to note that all four air lead
concentrations of interest are well within the range
of the air levels observed.
                                            RKERS
                           * LOS ANGELES CAB DRIVERS
                           • BARKSDALE, WISCONSIN
                           7STARKE, FLORIDA
                           • PHILADELPHIA CAB DRIVE RS
                          	1	I	1	
                    TOTAL AIR LEAD,M9/m

Figure 12-8. Blood lead  versus air  lead for  urban  male
workers.3
         TABLE 12-28. ESTIMATED BLOOD LEAD TO AIR LEAD RATIOS FOR FOUR AIR LEAD CONCENTRATIONS
Study
Epidemiological
Azara
Tepper-Levinb
Nordmanb
Nordmanb
Fugasb
Johnsonb
Johnsonb
Tsuchiyab
Goldsmith"
Goldsmith"
Yankel-von Lindern3
Chamberlainc-Williams
Dainesb
Clinical
Griffin"
Griffinb
Rabinowitzb
Grossc
Chamberlain^
Chamberlainc-Kehoe
Population

Adult males
Adult females
Adult males
Adult females
Adults
Adult males
Adult females
Adult males
Children males
Children females
Children
Adults
Black females

Adult males
Adult males
Adult males
Adults
Adults
Adults
Sample
size

149
1908
536
478
330
64
107
591
202
203
879
482
(unknown)

11 @109
14® 3.2
2
(21 ,000 person-days)
7
5
Ratio at
air lead concentrations,
fi g/m3
10 20 35

2 57 1 .43 0.89
0.87 0.92 1.00
(0.42)0
(0.11)
(2.64)
(0.80)
(0.60)
(3.84)
(2.30)
(1.70)
1.16 121 1.27
(1 10)
(2.30)

(1.40)
(1.65)
(17,2.5)
(0.38)
(1.20)
(110)

50

0.66
1.08








1.37









 a Authors' regression equation evaluated at specific air lead
 b EPA calculation
 c Authors' calculations
 d Ratios presented in parentheses are not calculated from any regression equation
                                                 12-25

-------
  One of the authors. Snee,M) has since reanalyzed
the data  using a more complicated model for the
relationship. His newer model  attributes less of the
increase in blood  lead to air  lead exposures and
more  to geographic area differences. The improve-
ment in fit by use of this newer model is insignificant.
Furthermore, in the new model, the area differences
are correlated with the  air lead differences. For
these  reasons, the original model is believed to be
more  appropriate for estimating the total effect of
air lead.
  Yankel et al.1  used a log-linear model (Equation
12-6) to fit their data. The slopes of the four air lead
values shown in  Table 12-28 were calculated from
this equation. These ranged from 1.2 at an air lead
level of 1.0 /u.g/m3 to 1.4 at an air lead of 5.0 /Ltg/m3.
Again, all air lead concentrations were within the
range of the data.
  One assumption  inherent in the calculation of the
regression of blood lead on air lead using standard
least  squares is that the air lead values have  been
measured with no error. Unfortunately, this assump-
tion is not correct. Obviously, the monitored air lead
values are not the  exact values inhaled by the sub-
jects in the exposure area. The effect of measurement
error in  the independent variable  is discussed by
Kendall  and Stuart.97 In general,  the calculation
regression coefficients are underestimates of the true
values. If either the error in the dependent variable,
or the error in the independent variable, or the ratio
of the two errors were known, then improved esti-
mates could be calculated.
  The Yankel et al. study1 gives sufficient informa-
tion to estimate  the effect of this  problem. The
authors assigned  1  of 33  different estimated ex-
posure levels to each individual in the study. If the
within level  variances  of  blood  lead  values are
pooled for these 33  levels, the result is  a pooled
GSD  of 1.28. Using the value of 1.28 for the error in
the dependent variable, the regression coefficient of
0.041 reported by Yankel and von Lindern becomes
0.052  This adjustment  increases  the  estimated
blood lead to air lead ratio from 1.21  to  1.44 at  2
/ttg/m3and from 1.37 to 1.69 at 5 /ag/m3.
  This  problem may exist  in some of the other
studies, but it is not a serious problem in  two of the
other more  important studies.  In the Azar study,3
personal samplers were used, so that individual ex-
posures were measured more accurately than in any
other epidemiologic study. In  the Griffin  study the
air lead levels were controlled extremely closely, so
that there was almost no variation  in the exposure
value.
  The reanalysis of the Tepper-Levin study2 as re-
ported by Hasselblad and Nelson22 was used to esti-
mate the relationship of air lead to blood lead levels.
A log-linear model was used  that allowed for age
and smoking differences, as well as the air  lead ex-
posure. This form of the model was chosen because it
gave a better  fit to the data  than did  the  log-log
model. The slopes were calculated  from  the log-
linear model at the four air lead values shown in Ta-
ble  12-28.  These slopes ranged from 0.9 at  an air
lead of 1.0  ju,g/m3 to 1.1 at an air lead of 5.0 ;ug/m3.
The air lead  values only ranged  from 0.2 to 3.4
/ug/m3, however.
  Daines  et  al.  reported  two  studies examining
variations in  blood lead ratios with distance from
busy highways.52  The studies were conducted in
Camden, New Jersey,  and involved  black  females.
Only one of these  studies can  be used to determine
the  blood lead/air lead ratio because no air lead data
were reported for the other  study.  In this  study,
blood lead levels  of  black  females  living in resi-
dences that were 3.7, 38.1, and 121.9m distant from
the  highway were determined. Yearly mean air and
blood lead levels for these three groups  are pre-
sented in Table 12-29. From these  values a ratio
may be calculated as follows:

ratio =     .     '   =  2.3 for the total  population.

Using a similar calculation,  housewives were found
to have a ratio of  3.
TABLE 12-29. YEARLY MEAN AIR AND BLOOD LEAD LEVELS
    OF BLACK FEMALES IN RELATION TO DISTANCE OF
         RESIDENCE FROM A BUSY HIGHWAY
Study
area
Area A
AreaB
AreaC
Distance from
highway, m
37
381
121 9
Air lead
MQ 'm'
4.60
241
2.24
Blood lead
/ug'IOOg
23.1
174
17.6
  In Yugoslavia, Fugas et al. in the study described
earlier,69  estimated  the weekly time-weighted  air
lead exposures of eight population groups. The esti-
mates were based on air lead values monitored at
various locations and estimated proportions of time
the individuals spent at those locations. The  time-
weighted  exposure  estimates, sample sizes,  and
blood  lead levels for  this  study  were presented
earlier (Table   12-22).  A  weighted regression
analysis was chosen for these data because the sam-
ple sizes  of the  customs  officers and  policemen
varied from those for the other groups. The range of
air leads was from 0.079 to 3.0 jug/m3. The resulting
slope is 2.64, and is presented in Table 12-28.
                                               12-26

-------
   Snee50 has criticized the inclusion of the streetcar
 drivers because of differences in  social status and
 habits from the other groups. The effect  of removing
 these  subjects would be  to  reduce the calculated
 slope. This group was not removed because the air
 lead exposure was more precisely  estimated than in
 other studies.
   Data on Tokyo policemen reported by Tsuchiya et
 al.41  and  discussed  in detail  previously  in  this
 chapter may also be used to calculate a slope. Unfor-
 tunately, the slope that is derived can only be looked
 upon as confirmatory evidence and not as additional
 evidence  because of the  time  difference  between
 sampling  the air and sampling the blood. Another
 possible complicating factor  is the rural-urban gra-
 dient  that  parallels  the  air lead concentrations.
 Weighted regression analysis was used on the blood
 and air lead data reported in Table 12-26. The esti-
 mated slope is 3.8 and  is  recorded in Table 12-28.
 The observed range in  air lead  concentrations was
 0.024 to 1.157/Ag/m3.
   From the Johnson et al. study  in California,6 esti-
 mates of the ratio  between blood and air lead levels
 can be derived. Because  of  analysis problems en-
 countered  in  the  blood   lead  determinations  of
 children, it was decided that  a valid estimate could
 not be derived. Therefore, only data for adults will
 be treated  here.  It was decided to  pool  the data for
 adults and present separate ratios for males and
 females aged 17 and above. Geometric  mean blood
 lead levels were used in the calculation  because the
 blood  lead data  were found to follow a  log-normal
 distribution.
   For males, the pooled geometric means were 15.5
 and 11.0   /ng/dl for Los  Angeles and  Lancaster,
 respectively. For females,  the corresponding values
 are 12.1 and 8.4 pig/dl. The ratio was calculated as
 follows for males: ratio = (15.5-11.0)/(6.3-0.6) =
 0.8. The ratio for females  was 0.6. These values are
 tabulated  in Table 12-28.
   Nordman in his doctoral dissertation16 reported
 on blood and air lead levels for several  populations
 in Finland (Table 12-30). Because of the  large varia-
 tion in the sample sizes for these populations, EPA
calculated a weighted regression equation. The slope
of the equation was estimated for both males and
females separately and is 0.4 and 0.1, respectively,
as presented in Table 12-28. It should be noted that
the range of air lead concentrations covered  by this
study was 0.025 and 1.32 jiig/m3.
   Data from Goldsmith42 on elementary and  high
school children in a number of California towns can
also be used in the calculation of the slopes. EPA has
   TABLE 12-30. BLOOD AND AIR LEAD LEVELS BY SEX IN
            FINNISH POPULATION STUDY"
                         Male blood lead
                                     Female blood lead,
Group
Pertummaa
Pyhaiarui
Suburban
Downtown
Policemen
Street sweepers
Air lead.
/ig/nv
0.025
0.025
0.74
090
1.32
1 32
N
243
—
37
142
28
86
Avg
12.1
—
10.6
11 4
13.5
133
so
4.5
—
28
33
2.8
41
N
256
93
81
37
—
11
Avg
9.6
8.6
97
8.5
—
104
SD
3.5
25
26
2.0
—
3.0
 separately analyzed the raw data from this study for
 elementary school males and females. The results of
 these analyses show ratios of 2.30 and 1.70, respec-
 tively (Table 12-28).
   Chamberlain  et al.92 analyzed the  data  of
 Williams et al.96 on occupationally exposed persons
 using personal monitors.  Chamberlain adjusted the
 occupational  exposures  to  24-hr exposures by
 calculating the elevation in blood lead from a non-
 exposed population. He calculated a slope of 1.1.
   Clinical studies also provide data useful in  quan-
 titating the relationship between blood and air lead.
 Griffin et al.,86 in their clinical  study of the largest
 number of subjects to date, exposed individuals to 2
 levels of  air  lead  concentrations, 10.9  and  3.2
 /u,g/m3. The study design, it was believed, precludes
 fitting an overall equation to these data, and a sepa-
 rate calculation of a ratio is presented for the two ex-
 periments. In both  experiments, the background air
 lead levels were estimated to be 0.15 /ng/m3. In the
 3.2 /ig/m3 air lead exposure, the men increased their
 mean blood lead levels from  20.5 to 25.6  /iig/dl.
 This yields a ratio of  1.65 (25.6-20.5)/(3.2-0.15).
 The 10.9 jU.g/m3 air lead exposure resulted in an in-
 crease of blood lead levels from 19.4 to 34.5 pig/dl.
 This gives a ratio  of 1.40 (34.5-19.4)/(10.9-0.15).
 These values are shown in Table 12-28.
  Chamberlain et al.92 reanalyzed the Kehoe results
 by adjusting the 37.5-hr exposures per week to a 24-
 hr equivalent. They used data from 5 subjects whose
 24-hr equivalent exposures ranged from 0.6 to 73.5
 jug/m3. The calculated ratios ranged from 0.6 to 2.0,
 with an overall mean of 1.1 for the data.
  In contrast to  the analysis of Kehoe's work by
 Chamberlain in which a  1.1 ratio  was calculated,
 Gross89 reports a ratio of 0.38 for these data. At this
 time, no details are  available  concerning his
 methods.  Therefore, the apparent discrepancy be-
 tween these two analyses cannot be evaluated.
  Chamberlain  et  al.,92-93 as  discussed  earlier,
calculated  ratios  of 1.1 and 1.2 based on the ex-
                                               12-27

-------
trapolation of a short-term exposure to a long-term
one. The calculation involves a number of experi-
mentally determined as well as assumed numbers.
  As described  previously, Rabinowitz  et  al.91
studied  three individuals  for metabolic changes in
blood lead as a function of changes in the air lead
concentration.  In contrast to the  other clinical
studies described wherein air lead levels were in-
creased, in this study the  subjects were placed in a
"clean room" in which the air was filtered.  This
study, therefore,  pertains to the situation in which
the air lead concentration has decreased. The blood
lead levels  were determined from the stabilized
mean both when the subject was breathing normal as
well as filtered air. One of the men did not have a
stabilized blood  lead  after returning to breathing
normal air; therefore, he could not be used in deter-
mining the ratio. The relevant  data for calculating
the ratio are  included in Table 12-31.
      TABLE 12-31. BLOOD AND AIR LEAD DATA
             FROM CLINICAL STUDY91
Subject
D
E
Estimated
Normal air,
yu g/m3
0.91
0.91
air lead
Filtered air,
n g/m3
0072
0.072
Blood
Normal air,
ng/100g
20.2
16.3
lead
Filtered air,
jig/100 g
18.8
142
  The calculation for subject D was done as follows:
ratio =  (20.2-18.8)/(0.91-0.072)  =  1.7.  The
calculation for subject  E results  in a ratio of 2.5.
  Only  one data set (Azar et al.3) is available  on
which to estimate a dose-response relationship, that
is, the  proportion of a  population exceeding  a
specified blood lead level for any specific exposure.
The  reasons for the paucity of data are twofold: (1)
access is needed to the raw data and (2) the exposure
data should be relatively precise.
  The regression equation for the Azar study3 has
already been  discussed. The mean  square error
(MSE) about this equation was calculated for all five
areas combined.  From the MSE,  estimates of the
percentage of the  population exceeding  a given
blood lead level for a given air lead level are given
by:
                        Percent =
100
f   r1'
r  T
         log .(blood lead)- 1.2257-0.1531 log.„(air lead)'
                         MSE1'2
where: N(x) is the cumulative normal integral of a
standard normal  variable up to the point x.  These
percentages are given in Table 12-32 for a range of
air lead values.
                                                  These tabulated percentages may not be represen-
                                                tative of the general population, since they are based
                                                on a single study of 149 subjects. They are presented
                                                because they are the best estimates available  of a
                                                dose-response relationship.
                                                 TABLE 12-32. ESTIMATED PERCENTAGE OF POPULATION
                                                EXCEEDING A SPECIFIC BLOOD LEAD LEVEL IN RELATION
                                                          TO AMBIENT AIR LEAD EXPOSURE*
Air lead,
(ig/rr>3
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
6.0
7.0
8.0
Percent exc<
200
ng/dl
15.22
26.20
34.12
40.23
45.15
49.23
52.69
55.67
58.27
60.57
64.45
67.63
70.28
seding blood lead level ot
300
>tg/dl
0.59
1.67
2.88
4.12
5.35
6.57
7.75
8.90
1001
11.09
13.16
15.10
16.92

400
*xg/di
0.02
0.07
0.16
0.26
0.38
0.51
0.66
0.81
0.97
1.14
1.48
1.83
2.20
 a Data derived tram trie equation of Azar et al3
  The  last element in defining the relationship be-
tween lead in blood and lead in air is a discussion of
the  effect  that varying  the concentration of lead in
air  has on the blood lead levels. Most  of the data
previously presented have dealt with steady state or
increasing air lead concentrations. This  section will
summarize the results of studies showing  the effect of
decreasing the concentration of lead in air on the
blood lead levels of human populations.
  Rabinowitz et al.'s study 91 provides estimated
ratios for two subjects under carefully controlled
conditions who experienced a decrease  in their air
lead concentrations. For the two subjects, a 1 p-g/m3
decrease in air lead levels resulted in a  2 /ug/100 g
decrease in blood lead levels.
  Baker98 presented data to the EPA Science Ad-
visory Board showing decreases in blood lead levels
in the vicinity of an Idaho smelter between 1974 and
1975 (Table 12-33). Information  from  all study
areas combined indicated that blood lead levels had
decreased by 2.3 /xg/dl  for each 1  /xg/m3 reduction
in air lead. This same investigator provided addi-
tional information  in a separate communication to
EPA showing that, when analyses were limited to
children of nonsmelter workers, blood lead levels
decreased  2.0 /*g/dl in all study areas for each
decrease of 1 pig/m3 of air lead. If the  analyses in-
cluded only  those children of nonsmelter workers
exposed to air lead levels ranging from 0.5 to  10
                                               12-28

-------
/ig/m3, blood  lead  levels decreased 1.3 /^g/dl for
each unit decrease  in air lead and also showed  a
higher ratio at greater air lead concentrations. From
these analyses, it seems apparent that a  single ratio
cannot describe the data  from  this study.

 TABLE 12-33. COMPARISON OF BLOOD LEAD LEVELS IN
  CHILDREN WITH AIR LEAD LEVELS FOR 1974 AND 1975
                 (EPA analyses)
Blood lead levels,
IL g/dl
Study
area
1
2
3
4

1974
69
49
36
33

1975
46
38
32
27

Dlff
23
11
4
5
A

1974
18
14
6.7
31
ir lead levels,
t* g/m

1975
103
8.6
4.9
2.5

Dlff
77
5.4
1.8
0.6
Pb-B diff 1
Pb-A diff
3.0
2.0
2.2
80
  Data  from Angle  and Mclntire's studies73'76 in
Omaha also provide data in this regard. They found
blood lead levels of urban children, aged 6 to 18, to
consistently decrease during the years 1970 to 1973.
This decrease was almost 10 ^tg/dl  across all study
groups.  Furthermore, this decrease has been found
to be closely correlated with a decrease in air  lead
from about 1.5 to less than 0.5 /ug/m3. In a reanalysis
of the full data base, Angle has calculated an overall
equation of Pb-B =   10.04 (Pb-A) +  17.06,  r =
0.95.
  Data  from New York City analyzed  by HUD38
and  described  in  detail  in  the demographic
variability section of this chapter  may also provide
supportive data  for  the  notion that a decrease in
blood lead level is associated with decreased air lead
exposure. In the New York lead screening program
geometric mean blood lead values have been noted
as decreasing consistently from  1970 to 1976. Dur-
ing this  time, some changes occurred in the number
of children  sampled, so that the more recent years
have far fewer data points than the earlier years. No
significant break in the trend was observed as the
change in sample size was noted. Data from one Hi-
Vol air  station provided  continuous air lead values
over this period in New York City. The air  lead
values measured there, not really representative of
the exposure of the children  being studied,  have
been following a similar pattern. It is also interesting
to note that lead in gasoline in  New York City was
also  being reduced during this period.
  The  quantitative  estimates provided  from  the
three studies discussed show decreasing air lead con-
centrations vary from a minimum of 1.3 to 8 or 10
^ug/dl. These data  suggest that  a greater  ratio may
hold for decreases in air lead than for steady state or
increasing exposures.
  In summary, in all quantitative studies presented,
a positive relationship between blood lead and air
lead has been found. The form and magnitude of the
relationship, however, has not been found to be con-
stant but varies in the studies reviewed. Table 12-28
summarizes the quantitative estimates derived from
the review and analysis of the literature.
  In general, the data show that the blood lead to air
lead ratio is not constant over the range of air ex-
posure encountered (it varies in most  studies be-
tween  1 and  2), that  males appear to have higher
ratios than females, and that children have a slightly
higher ratio than adults. Also, the data suggest that
more attention should be given to studies of decreas-
ing air lead concentrations in  that the ratios derived
from such studies appear higher than those of steady
state or increasing exposures.

12.3.2 Soil and Dust Exposures
  The relationship of exposure to lead contained in
soil and housedust and  the quantity  of  lead  in
humans, particularly in children, has been the sub-
ject of scientific investigation for some time.78'"-'05
Duggan and Williams105 have recently published an
assessment of the risk of increased blood  lead result-
ing from the ingestion of lead in dust. Some of these
studies have been concerned with the effects of such
exposures:78-"-102 others have concentrated on the
means by which the lead  in soil and dust becomes
available to the body.103.104
  In one of the  earliest investigations,  Fairey and
Gray  conducted a retrospective  study  of lead
poisoning cases  in  Charleston,  South  Carolina.99
Two-inch core soil samples were collected from 170
randomly selected sites in the city  and  were com-
pared  with soil  samples taken from the yards  of
homes where 37  cases of lead poisoning had occur-
red. The soil lead values obtained had a wide range,
from  1 to 12,000 ppm,  with 75 percent  of the sam-
ples containing  less than 500 ppm.  A significant
relationship between  soil lead  levels and  lead
poisoning cases was established;  500 ppm was used
as  the cutpoint  in the  chi-square contingency
analysis.  This study was the first  to examine this
complex  problem and, although data support the
soil lead hypothesis, they were not such  as to allow
for quantification of the relationship between soil
lead and blood lead levels. Furthermore, because no
other source of lead was measured, the  association
found might have been caused by confounding addi-
tional sources  of lead, such as paint or air.
                                               12-29

-------
  A later study by Galke et al., also in Charleston,
used a house-to-house survey to recruit 194  black
preschool children.43 Soil  lead, paint lead, and air
lead exposures as measured by traffic density were
established  for each child. When the population was
divided into 2 groups based on the median soil lead
value  (585 /ttg/g), a 5-/ug/dl difference in blood lead
levels  was  obtained.  Soil  lead  exposure for this
population  ranged from 9 to 7890 jtg/g. A multiple
regression analysis of the data showed that vehicle
traffic pattern, when defined by area of recruitment
(i.e., high or low); lead level in exterior siding  paint;
and lead in soil were all independently and signifi-
cantly related to blood lead levels.
  Barltrop et al.'°° described two studies in England
investigating the soil lead to blood lead relationship.
In the first study, children aged 2 and 3 and their
mothers from two towns chosen for their soil lead
content each had their blood lead level determined
from a capillary sample. Hair samples were also col-
lected and  analyzed for lead. Lead content  of the
suspended paniculate matter and soil was measured.
Soil samples for each home were  a composite of
several 2-in. core  samples taken  from the yard of
each home. Chemical analysis of the lead content of
soil in the  two towns showed a two- to threefold
difference,  with the values in the control town being
about 200 to 300 ppm compared with about 700 to
1000 ppm in the exposed town. A difference was also
noted in the mean air lead content of the two towns,
0.69 //.g/m3 compared with 0.29 /u,g/m3, respectively.
Although  this difference  existed,  both  air lead
values were thought low enough not to affect the
blood level values differentially. Mean surface soil
lead concentrations for the two communities were
statistically different, the means for the high and low
community  being 909 and 398 ppm, respectively.
Despite this difference, no statistically significant
differences  in  mothers'  blood  lead  levels  or
children's blood or hair levels of lead were noted.
There was,  however,  suggestive  evidence  of  a
difference in hair lead levels for  children. Further
statistical analysis of the data, using correlational
analysis on either raw or log-transformed blood lead
data,  likewise failed to show a statistical relationship
of soil lead with either blood lead or hair lead.
  The second  study   was  reported  in both pre-
liminary and final form.100-101 In the more detailed
report,101 children's homes were classified by their
soil lead content into three groups, namely <  1,000,
1000  to 10,000, and > 10,000 ppm.  As shown  in Ta-
ble 12-34, children's  mean blood  lead levels in-
creased correspondingly from 20.7 to 29.0
Mean soil lead levels for the low and high soil ex-
posure groups were  420 and  13,969 ppm, respec-
tively.  Mothers'  blood levels,  however, did  not
reflect this trend; nor were the children's fecal lead
levels different across the soil  exposure  areas.
      TABLE 12-34. MEAN BLOOD AND SOIL LEAD
       CONCENTRATIONS IN ENGLISH STUDY101
Category
of soil lead,
ppm
<1000
1000-10000
> 10000

Sample
size
29
43
10
Children's
blood lead
M g/dl
20.7
23.8
29.0

Soil lead,
ppm
420
3390
13969
  Other studies have investigated the relationship of
dust lead to absorption.33'78-102'106 Some of these also
included measurements of soil lead.
  Lepow et al.,106 for example, studied the lead con-
tent of air, housedust, and dirt, as well as the lead
content of dirt on hands, food, and water, to deter-
mine the cause of chronically elevated blood lead
levels in ten  2- to 6-year-old children in Hartford,
Connecticut. Lead based paints had been eliminated
as a  significant source of lead  for these children.
Ambient air  lead concentrations varied from 1.7 to
7.0 /ug/m3. The mean lead concentration in dirt was
1,200 /tg/g and in dust, 11,000 /ng/g. The mean con-
centration  of lead in dirt on children's hands was
2,400 ppm. The mean weight of samples of dirt from
hands was 11 mg, which represented  only a  small
fraction of the total dirt on hands. Observation of
the mouthing behavior in these young children lead
to the conclusion that the hands-in-mouth exposure
route  was the principal cause of excessive  lead
accumulation in these children.
  Angle et  al.,74  studying children  in  Omaha,
Nebraska, found  several interesting associations be-
tween soil or housedust lead  concentrations and
blood lead  levels.  In  this report,  three groups of
children were compared: (1) suburban versus urban
high  school,  (2)  suburban versus urban 10- to  12-
year-olds, and (3) black elementary school children
with  blood lead  < 20  versus > 20.  Air lead levels,
all of which were less than 1 Mg/m3, were not shown
to be related  to blood lead levels. Soil and housedust
were associated,  although  not  always statistically
significantly.
  Creason et al.,102 studying hair metal levels in the
New York metropolitan area, used both dustfall and
housedust as their exposure variables. Three
geographic areas in metropolitan New York were
chosen to represent  an exposure gradient. Limited
dustfall and housedust samples were taken to verify
                                               12-30

-------
 the gradient and  to  estimate  its  magnitude. Hair
 samples were collected from residents in locations
 enrolled in other  air pollution studies. Mean total
 environmental and hair lead levels were then com-
 pared. Hair lead levels ranged from 12 /ng/g in the
 low area to 17 /u,g/g in the high. Mean dustfall and
 housedust  lead levels ranged from 2 to 16  mg/m2-
 month, and  from  279  to 766  /xg/g,  respectively.
 Hair  lead  levels in both  children and adults were
 found to be significantly related to both dustfall and
 housedust  lead. No attempt was made to determine
 the original source of these dusts. Further, the study
 design did not permit the establishment of which of
 the two dust types or both were the actual contribu-
 tors to  the hair lead  levels. The investigators con-
 cluded that the primary cause of elevated blood lead
 levels in children was ingestion  or inhalation of dust
 containing lead.
  Two other studies, which were described in more
 detail in Section 12.3, can be used to examine  the
 relationship of lead in  soil and dust  with  lead  in
 blood.1-34 Yankel et al. showed that lead in both soil
 and dust was independently  related to blood lead
 levels. In their opinion, 1000 ppm soil lead exposure
 was cause for concern.  Reanalysis of the  Dallas
 traffic study showed a significant slope of blood lead
 levels in relation to soil lead levels (j3  = 0.0662).34
 Lastly,  Shellshear's case report from New Zealand
 ascribes a medically diagnosed  case of lead poison-
 ing to high soil lead content in the child's home
 environment.107
  Two studies  have investigated the mechanism by
 which  lead  from  soil  and  dust  gets  into  the
 body.103-104 Sayre  et al.  in Rochester, New York,
 demonstrated the  feasibility  of housedust being a
 source of lead for children.l03 Two groups of houses,
 one inner-city and the other suburban, were chosen
 for the study. Lead-free sanitary paper towels were
 used to collect dust samples from house surfaces and
 the hands of children.108 The medians for the hand
 and household samples were used as the cutpoints in
 the chi-square  contingency analysis. A statistically
 significant  difference between the urban and subur-
 ban homes for dust  levels was  noted, as was a
 relationship between household  dust levels and hand
 dust levels.106
  Ter Haar and  Aronow104   investigated  lead
absorption  in children that can  be attributed to  in-
gestion of dust and dirt. They reasoned that because
the proportion of the naturally occurring isotope
 2l°Pb  varies for paint chips, airborne  particulates,
fallout dust, housedust, yard dirt, and  street dirt, it
would be possible to identify the sources of ingested
 lead. They collected  24-hr excreta from 8  hos-
 pitalized children for the first day of hospitalization.
 These children, 1 to 3 years old, were suspected of
 having elevated body burdens of lead, and one cri-
 terion for the suspicion was a history of pica. Ten
 children of the  same age level, who  lived in good
 housing in Detroit and the suburbs, were selected as
 controls and 24-hr excreta were collected for them.
 The excreta were dried and stable lead as well  as
 210Pb content  was determined.  For  seven  hospi-
 talized  children, the stable lead  mean value was
 22.43 jug/g dry  excreta, and the eighth child had a
 value of 1640 /ug/g. The  controls' mean for stable
 lead was 4.1 /xg/g dry excreta. However, the respec-
 tive means for  2i°Pb expressed  as  pCi/g dry matter
 were 0.044 and 0.040. The  authors concluded that
 because there is no significant  difference  between
 these means for 210Pb, the hypothesis that  young
 children with   pica eat  dust   is  not  supported.
 However, all that the data,  in fact, do show is that
 both groups of children were comparable as to the
 amounts of  2U)Pb and vastly different in respect  to
 stable lead per gram of dry excreta. The hospitalized
 children ingested larger  amounts  of material con-
 taining stable  lead. Granting that the hospitalized
 children ingested leaded paint chips and the controls
 did not, does not permit the conclusion that all the
 2l°Pb found in all the children  originated in food
 and that no dirt and dust was  ingested by control
children whereas  hospitalized  children  ate  only
 paint chips.
  The data from all these studies can be summarized
 fairly succinctly. There is evidence that children can
 pick up  lead from their environment by getting it on
 their hands.  Duggan and Williams105 have  sum-
 marized the literature on the amounts of  lead  in-
 gested by ingestion of dust. In their opinion, a quan-
 tity of 50 /ig of lead is ingested daily by children by
 means of street dust. As yet there are  no solid data
directly demonstrating the next link, that is, transfer
of dust and soil from hand to mouth. A clinical case
 report has indicated, however, that soil lead levels
can lead to  excessively elevated blood  lead levels.
 Also, the data of Barltrop101 and Galke et al.43 indi-
cate that soil lead exposures, often found in urban
settings, can contribute between 5 and 8 ,ug/dl to the
 blood's lead burden.33-101
  The consensus appears  to be that observable in-
creases in blood  lead levels occur at soil or dust lead
exposures of 500 to 1000 ppm. From the data avail-
 able  in the  literature, a summary  table  (Table
 12-35)  was  constructed  by  EPA.  A  regression
analysis was used to relate the logarithm of the
                                               12-31

-------
blood lead to the logarithm of the soil lead. From
the regression, a coefficient, b, the mean percent age
increase in blood lead for a two fold increase in soil
                      TABLE 12-35. SUMMARY OF SOIL LEAD/BLOOD LEAD RELATIONSHIPS
lead, can be calculated:
        % increase =  100 [exp(b/loge(2»]
(12-7)


Study
Charleston, SC43
Kellogg, ID1
Dallas, TX34
England101

Age,
years
1-5
1-9
1-5
2-3
Regression
coefficient,
log-log
0.0432
0.0528
0.0662
0.0840
Geom mean
blood lead,
Mg/di
36.4
375
11.4
23.2
Geom mean
soil level.
Mg/g
451.6
1518.1
91.6
1849.1
Mean % increase
in Pb-B for 2 x soil
level
3.0
3.7
4.7
6.0
  Table 12-35 shows a surprising consistency in the
percentage increase in mean blood lead levels for a
twofold increase in soil lead levels (3 to 6 percent),
given the wide diversity in populations studied and
soil  levels  encountered.  The Charleston study in-
volved black preschool children living in the inner
city  with several additional known environmental
sources of lead. The Idaho study was of a smelter site
in a rural  setting. Barltrop's data from England
showed virtually  no  environmental source other
than that from soil. The Dallas study was of a com-
munity that was  relatively lead free. It is  interesting
to note that the larger estimates of the percentage in-
crease in blood  lead occurred in the children with
the lowest blood lead levels.
12.3.3 Food and Water Exposures
  In  typical  urban  settings,  food probably con-
stitutes  the body's largest direct  source  of lead
because almost every item in the diet contains some
measurable amount of the metal.
  Three approaches have been used to estimate die-
tary intake of lead: duplicate meals, market basket
surveys, and fecal lead  determinations. The esti-
mated dietary  lead  intake of  Americans  has
decreased  markedly  since the  presentation  of
Kehoe's data in  the 1940's, which indicated, based
on fecal lead determinations, that the  daily  intake
was  between 100  and 350 /ug/day.88 Most of the
more recent comparable data2-109-110 have  reduced
that estimate to between 50 and 150 /^tg/day. The
California study of Johnson et al.7 points to a daily
intake of about  100 to  150 jug, such intake being
similar for both  rural and urban populations. Also,
Chisholm  and Harrison,109 in a study of children
aged 12 to  35 months, found a mean fecal excretion
rate of 1 32 fig/day, and Barltrop and Killola a value
of 130/ng.110
  Much recent work  has been concerned with the
lead content  of  the market basket or total diet in
which the  content of foods meeting typical nutri-
tional needs is analyzed. The foodstuffs are assem-
bled in  accordance with national food sample sur-
veys. One such  study111-112 has indicated that the
lead content of the diet of young adults averages 150
to 200 jig/day,  and another113 cites a figure of 254
/itg/day for 15- to 20-year-old males. At least 30 per-
cent of this amount in the latter study was attributed
to the consumption of canned foods. Kolbye111 and
Mahaffey et al.112 have suggested an average food-
based intake of 80 to 100 fj.g of lead for children 12
to 35 months old. Additional  studies  in this field
have been reviewed by Mahaffey.112
  Despite the above estimates of dietary lead con-
tent, the quantitative relationship between  dietary
intake and blood lead levels is not well established;
the bulk of the studies described in Chapter  10 that
address this relationship, however, point to a sus-
tained value of 6 /ig/dl for 100/Ag of dietary lead in-
take.
  Water, itself,  can also be a source of significant
quantities of lead with  the metal present in the sup-
ply itself. More frequent, however, is an increase in
the quantity of particulate or dissolved lead as water
is  delivered from the  treatment  plant to the user
through the lead pipes often found in older housing.
Most  natural waters contain only from 10 to  20
/u,g/liter of lead  and most problems occur when lead
piping is used in areas in which the drinking water is
lead solvent; that is, it is soft and has a low pH.
  Although  the use of lead piping has  been  largely
prohibited  in   recent  construction,  occasional
episodes of poisoning from this lead source still oc-
cur. These cases most  frequently involve  isolated
farms or houses in rural areas, but a surprising situa-
tion was revealed  in 1972 when Beattie et al."4-115
showed the seriousness of the situation in Glasgow,
Scotland, which  had very pure  but soft drinking
water as its source. They demonstrated  a clear asso-
ciation between blood lead levels and  inhibition of
the enzyme ALAD in children living in houses with
(1) lead water  pipes and lead  water tanks, (2)  no
                                               12-32

-------
lead water tank but with more than 60 ft of lead pip-
ing, and (3) less than 60 ft of lead piping. The mean
lead content of the water as supplied by the reservoir
was 17.9  /xg/liter; that taken from the  faucets of
groups  1,  2, and 3 was 934, 239, and 108 jig/liter,
respectively.
  Another  English study116  showed a  clear
difference between the bone  lead content  of the
populations of Glasgow and London, the  latter hav-
ing a  hard, relatively nonsolvent water supply.
  In a study of 1200 blood donors in Belgium,117
persons from homes with  lead piping and supplied
with corrosive water had significantly higher blood
lead levels.
  In Boston, Mass., an investigation was made of
water distributed via lead pipes. In addition to the
data  on  lead  in water, account  was  taken  of
socioeconomic and demographic factors  as  well as
other sources of lead in the environment.118'119 Par-
ticipants,  771  persons  from 383 households,  were
classified into age  groups of <6, 6 to 20, and  >20
years of age for analysis.118 A  clear association be-
tween water lead and blood lead was apparent (Ta-
ble 12-36). For children under 6 years of age, 34.6
percent of those consuming  water  with lead above
the U.S. standard  of 50 jug/liter had a blood lead
value 2 35 ^g/dl, whereas only  17.4 percent of those
consuming water within the standard had blood lead
values of 2 35 /ug/dl.

 TABLE 12-36. BLOOD LEAD LEVELS OF 771 PERSONS IN
   RELATION TO LEAD CONTENT OF DRINKING  WATER,
                BOSTON, MASS.118

              Persons consuming water; (standing grab samples)





x2
p
Blood lead
levels, jtg/dl
<35
235
Total
= U35, df = 1
<001

No
622
61
683



Percent
91
9
100



No
68
20
88



Percent
773
227
1000



Total
690
81
771


  Greathouse et al. have published an extensive
regression  analysis of  these data."9  Blood  lead
levels were found to be significantly related to age,
education of head of household, sex, and water lead
exposure. Of the two types of water samples taken,
standing grab and  running grab, the former was
shown to be more closely  related  to blood  lead
levels than the latter.
  As noted in Chapter  10 of this document, roughly
10 percent of lead in solid foodstuffs is absorbed by
adults; the corresponding value for liquids  is about
50 percent. The relative risk for exposure to water-
borne lead is, therefore, considerably greater.
12.3.4 Effects  of Lead  in the  Housing Environ-
ment: Lead in Paint
  A major source of environmental lead exposure
for  the  general population comes from  lead  con-
tained in both interior and exterior paint on dwell-
ings. The  amount of lead present, as well as its ac-
cessibility, depends upon the  age  of the residence
(because  older buildings are  painted  with  paint
manufactured before lead content was  regulated)
and  the  physical condition  of the paint.  It is
generally  accepted by the public and by health pro-
fessionals  that lead based paint is the major source of
pediatric lead poisoning  with clinical symptoms in
the United States.120
  The level and distribution of lead paint in a dwell-
ing is a complex function  of history, geography, eco-
nomics, and  the decorating habits of its residents.
Lead pigments were the first pigments produced on a
large commercial scale  when the paint industry
began its growth  in the early 1900's.  In the 1930's
lead pigments were gradually replaced with zinc and
other opacifiers.  By  the  1940's, titanium  dioxide
became available  and has now become the most
commonly used pigment for  residential coatings.
There was no regulation  of the use of lead in house
paints until 1955, when the paint industry adopted a
voluntary  standard that limited the lead  content in
paint, for interior uses, to no more than 1 percent by
weight of  the nonvolatile solids. At about the same
time, local jurisdictions began adopting  codes and
regulations that prohibited the sale and  use of in-
terior paints containing more than 1 percent lead.121
  In spite of the change in paint technology and
local regulations governing its use, and contrary to
popular belief,  interior paint  with significant
amounts of lead was still available in the 1970's. A
1971 study in New York City found that 8 of  76
paints tested had a lead content ranging from 2.6 to
10.8 percent, well above  the city's legally permissi-
ble 1 percent level.122 Later studies by the National
Bureau of Standards123 and by the  Consumer  Pro-
duct Safety  Commission124 showed  a  continuing
decrease in the number of interior paints with  lead
levels greater than 1 percent. By 1974, only 2 per-
cent of  the interior paints sampled were found to
have greater than 1 percent lead in the dried film.124
  The  level  of lead  in  paint in a residence  that
should be  considered a hazard remains in doubt. Not
only is the total amount of lead in  paint important,
but  also the accessibility by a child of the  painted
                                               12-33

-------
surface  as well as the frequency of ingestion.  At-
tempts to set ;>r> acceptable lead level, in situ, have
been unsuccessful  and preventive control of lead
paint hazards has been concerned with levels of lead
in paint currently manufactured.  In  one  of  its
reviews, NAS concluded' "Since control of the lead
paint hazard is difficult to accomplish  once multiple
layers have been applied in homes over two to three
decades, and since control  is more easily  regulated
at the time of manufacture, we recommend that the
lead content of paints be set and  enforced at time of
manufacture."125
  Legal control  of lead  paint hazards is  being at-
tempted by  local  communities  through health  or
housing codes and  regulations. At the Federal level,
the Department  of Housing  and Urban  Develop-
ment has issued regulations for  lead hazard abate-
ment in housing units assisted or supported by its
programs.  Generally, the lead  level  considered
hazardous ranges from 0.5 to 2,5  mg/cm2, but the
level of lead content  selected appears to be depen-
dent more on the sensitivity of field measurement by
different regulatory bodies (using X-ray fluorescent
lead detectors)  than on  direct biological dose-
response  relationships.   Regulations  also  require
lead hazard  abatement when the paint is loose, flak-
ing, peeling, or broken, or in some cases when it is on
surfaces within reach  of a child's mouth.
  Some studies have  been carried out to determine
the distribution of lead levels in  paint in residences.
A survey of lead  levels in  2370 randomly selected
dwellings  in Pittsburgh provides some indication of
the lead levels to be found.126 Figure 12-9  shows the
distribution curves for the highest lead level found
in dwellings for three age groupings. The curves bear
out the statement  often made that  paint with high
levels of lead is most frequently found in pre!940
residences. One cannot assume,  however,  that high
level lead paint is absent  in dwellings built after
1940. In the case  of  the houses surveyed  in Pitts-
burgh, about 20 percent of the residences built after
1960 have at least one surface with more than 1.5
mg'cm2\ead

  The distribution of  lead  within an  individual
dwelling varies considerably. Figure 12-10 presents
the distribution of the highest paint lead measure-
ments  on walls,  doors,  and windows for all the
buildings sampled. These data show that the lead is
not uniformly distributed throughout the units. Lead
paint  is most frequently found  on  doors  and win-
dows where lead levels greater than 1.5 mg/cm2 were
found on 2 percent of the surfaces surveyed, whereas
                   LEAD LEVEL (XI. mg/crn

Figure 12-9. Cumulative distribution of lead levels in dwelling
units.'"
only about  1 percent of the walls had lead levels
greater than 1.5 mg/cm2.126
  The  literature120 generally accepts the premise
that the presence of lead in  paint is a necessary but
not sufficient condition for  a hazard  to be present.
Accessibility in  terms of peeling,  flaking, or loose
paint is also a necessary condition for the presence of
a hazard. Figure  12-11  shows  the distribution of
lead levels and  nonintact conditions  for  dwellings
and surfaces for the Pittsburgh sample. Of the total
samples surveyed, about 14 percent of the residences
would  have accessible  paint  with a lead content
greater than 1.5 mg/cm2.
  It is not possible to extrapolate the results of the
Pittsburgh survey nationally; however,  additional
data from a pilot study of 115 residences in Wash-
ington, D.C., showed similar results.127
  An  attempt was made in  the  Pittsburgh study to
obtain  information about the correlation between
                                                12-34

-------
Al
    01 -
Figure 12-10. Cumulative distribution of lead levels by loca-
tion in dwelling, all ages.12*
the quantity and condition of lead paint in buildings
and the blood lead of children who  resided there.I2X
Blood lead analyses and socioeconomic data for 456
children were obtained along with the information
about  lead  levels  in  the dwelling.  Figure  12-12
shows-the cumulative distribution of the blood lead
levels  for this group. Figure 12-13 is a  plot of the
blood  lead  levels versus the  fraction of surfaces
within a  dwelling  with  lead  levels  of at least  2
mg/cm2. Analysis of the data shows a low correlation
between the blood  lead  levels of the children and
fraction of surfaces with lead levels above 2 mg/cm2,
but a stronger correlation between the blood lead
levels  and condition of the painted surfaces in the
dwelling in  which children  reside.  This latter cor-
relation  appeared to  be independent  of  the lead
levels  in the dwellings.
  Two other studies have attempted to relate blood
lead levels and paint lead as determined by X-ray
fluorescence. Reece et al. in Cincinnati studied 81
                    LEAD LEVEL (X), mg/cm

Figure 12-11. Cumulative distribution of lead levels in dwell-
ing units with unsound paint conditions.126

children  from  two  lower  socioeconomic  com-
munities.12'*  Blood  leads were  analyzed  by  the
dithizone method. There was considerable lead in
the home environment, but it was not reflected in the
children's blood lead. Analytic procedures used to
test the hypothesis were not described; neither were
the raw data presented.
  Galke et  al. in their study of inner-city  black
children  measured the paint lead, both interior and
exterior, as well as soil and traffic exposure.43 In a
multiple regression  analysis,  exterior siding paint
lead was found to be significantly related to blood
lead levels.
  Although  most of the evidence indicates  that the
source of exposure in childhood lead poisoning  is
almost invariably peeling lead paint  and broken
lead-impregnated  plaster  found in  poorly main-
                                                12-35

-------
                                       1    0 1  0.01
                      PERCENTILE
Figure 12-12. Cumulative frequency distribution of blood lead
levels found in Pittsburgh housing survey.12*

~5
w 30
EAD LEV
ro
01
n 20
o
0
CO ic
1 1 1 1 1 1 1 1 1
	 SURFACES IN BAD CONDITION, i e , PEELING,
_ CHALKING, OR POOR SUBSTRATE

-6 	 * 	 -3 	 ' 	
— • o


1 1 1 1 1 1 1 1 1


-J
•-
—



      0   01   02

           FRACTIONS OF SURFACES WITH LEAD >2 mgrfi
03  04  05   06   07   08   09

                        2
Figure 12-13. Correlation of children's blood lead levels with
fractions of surfaces within a dwelling having lead concentra-
tions >2 mg Pb/cm2.
tained houses,  there are  also  reports of exposure
cases  that cannot be equated  with  the presence of
lead paint. Further, the analysis of paint in homes of
children  with lead poisoning has not consistently
revealed  a hazardous lead content.120 For example,
one paper reported 5466 samples of paint obtained
from the  home  environment of lead poisoning cases
in Philadelphia between  1964 and 1968. Among
these 5466 samples of paint, 67 percent yielded posi-
tive findings defined as paint with more than  1 per-
cent lead.130
  Data published or made available by the Center
for Disease Control, Department of Health, Educa-
tion, and Welfare, also show that a significant num-
ber of children with undue lead absorption occupy
buildings that were inspected for lead-based paint
hazards,  but  in which  no hazard could be demon-
strated.131.'32 Table 12-37  summarizes the data ob-
tained from  the HEW  funded  lead-based  paint
poisoning control projects for fiscal years  1974,
1975, and  1976, plus the transition  quarter July 1,
1976 to September 30,  1976. These data show  that in
about 40 to 45 percent of confirmed cases of ele-
vated blood  lead levels, a possible source of lead
paint hazard  could not be located. The implications
of these  findings are  not  clear.  They should not,
however, weaken the  role of lead-based paint as a
major environmental   source of lead for children.
                                   The findings are presented in order  to  place in
                                   proper perspective both the concept of total lead ex-
                                   posure and the concept that lead paint is one source
                                   of lead that contributes to the total body load. The
                                   background contribution of lead from other sources
                                   is still not known even for those children for whom a
                                   potential lead-paint hazard has  been  identified; nor
                                   is it known what proportion of lead came from which
                                   source.
                                    TABLE 12-37. RESULTS OF SCREENING AND HOUSING
                                   INSPECTION IN CHILDHOOD LEAD POISONING CONTROL
                                             PROJECT BY FISCAL YEAR«1,132
                                                                                  Fiscal year3
                                                        Results
                                                                          1976"2
                                                                                   1975'3
                                                                                             1974"i
No. children
screened
No children
with elevated
lead exposure
No. dwellings
inspected
No dwellings
with lead
hazard
500,463
69,131"
50,276
28,333
440,650
28,597c
30,227
17,609
371,955
16,228=
23,096
13,742
                                    a Fiscal year 1976 includes transition quarter
                                    b CDC Classes II-IV
                                    0 Confirmed blood lead level ^4
                                   12.3.5  Secondary Exposure of  Children  from
                                   Parents' Occupational Exposure
                                     Excessive  intake and absorption  of lead  for
                                   children can result when a parent who works in a
                                   dusty environment with a high lead content brings
                                   dust home on his clothes, shoes, or even his automo-
                                   bile. Once home, this dust  is then available to his
                                   children.
                                     Excessive  intake and absorption also can occur
                                   when children  voluntarily  ingest nonfood items,
                                   such as clay, plaster, or paint chips. This is the classi-
                                   cal pica, which refers to the intentional ingestion of
                                   nonfood material rather than to the passive, nonin-
                                   tentional ingestion of dust  from a dirty finger  or
                                   piece of candy that has  been dropped and thus con-
                                   taiminated.
                                     Landrigan et al.62 reported that the 174 children
                                   of smelter workers who lived within 24 km of the
                                   smelter had significantly higher blood lead levels, a
                                   mean of 55.1 jag/dl, than the 51 1 children of persons
                                   in other occupations who lived  in the same  areas
                                   whose mean  blood lead level was 43.7  yitg/dl.
                                     Analyses by EPA staff of the data  collected in
                                   Idaho showed that employment of the father at the
                                   lead smelter, at a zinc smelter, or  in the lead mine
                                                12-36

-------
resulted in higher blood lead levels in the children
living  in  the  same house  with  such fathers than
children whose fathers were employed in different
locations (Table 12-38).
  TABLE 12-38. GEOMETRIC MEAN BLOOD LEAD LEVELS
    (Mg/dl) OF CHILDREN BY PARENTAL EMPLOYMENT
              (EPA analysis of 1974 data)
Age and
study
area
1 to 3
years
1
2
3
4
5
6
4 to 9
years
1
2
3
4
5
6
Lead smelter
worker


77.1(12)a
56.8(11}
33 7(6)
29 6(4)
—
—


73 6(32)
49.6(21)
33.3(21)
30.9(4)
24.5(2)
—
Lead/zinc
mine worker


65.7(25)
53.5(21)
545(15)
360(16)
31.8(29)
—


65 8(28)
43 8(32)
35.5(39)
33.0(53)
27.1(79)
—
Zinc smelter
worker


663(11)
55.1(6)
32.3(2)
41.7(4)
—
—


59.3(16)
51 9(4)
35 2(7)
35 6(5)
—
—
Other
occupation


65.9(13)
48 5(30)
34.8(26)
31.5(22)
27.2(16)
22 4(34)


59.2(33)
449(67)
32 1 (58)
29 1 (44)
26 4(60)
20 5(56)
 a Sample sizes in parentheses
  The effect associated  with parental employment
appears to be much more prominent in the most con-
taminated study areas nearest to the smelter. This
may be the effect of an  intervening socioeconomic
variable: the lowest paid workers, employed in the
highest exposure areas within the industry, might be
expected to live in the most undesirable locations,
which are closest to the  smelter.
  The importance  of the infiltration by lead  dusts
into clothing,  particularly  the  undergarments, of
lead workers has been demonstrated in a number of
studies of the effects of smelters.133 It was noted in
the  United Kingdom that elevated blood lead levels
were found in the wives and children of workers
even when they resided some considerable distance
from  the facility. It was most prominent  in  the
families  of workers  who themselves had elevated
blood lead levels. Quantities of lead dust were found
in workers' cars  and homes.  It apparently is  not
sufficient for a factory merely to provide outer pro-
tective  clothing  and  shower  facilities  for lead
workers. In another  study in Bristol, from 650 to
1400 ppm of lead  was found in the undergarments of
workers as compared with 3 to 13 ppm in  undergar-
ments of control subjects. Lead dust will remain on
the clothing even  after laundering: up to 500 mg of
lead has been found to remain on an overall garment
after washing.134
  Baker et al.13s found blood lead levels >30 /ig/dl
in 38 of 91 children whose fathers were employed at
a secondary lead smelter in Memphis, Tenn. House-
dust, the only source of lead  in the homes of these
children, contained a mean of 2687 /ig/g compared
with 404 /ug/g in  the homes of a group of matched
controls. Mean blood  lead levels  in the  workers'
children  were significantly higher than  those  for
controls and were closely correlated with the lead
content  of household dust.  In homes with lead in
dust < 1000 jug/g, 18 children had a mean blood
lead level of 21.8 ± 7.8 /xg/dl, whereas  in  homes
where lead in dust was >7000 jxg/g, 6 children had
a mean blood lead level of 78.3 ±  34.0 jug/dl.
  Landrigan et al.62 also reported a positive history
of pica for  192 of the 919 children studied in  Idaho.
This history was obtained by physician and nurse in-
terviews of parents. Pica was  most common among
2-year-old children  and  only 13 percent of those
with pica were above  age 6. Higher blood lead levels
were observed in children with pica than in those
without  pica. Table  12-39  shows the mean blood
lead levels in children as they  were affected by pica,
occupation of the father, and distance of  residence
from the smelter. It  is interesting that, among the
  TABLE 12-39. GEOMETRIC MEAN BLOOD LEAD LEVELS FOR CHILDREN BASED ON REPORTED OCCUPATION OF FATHER,
                       HISTORY OF PICA, AND DISTANCE OF RESIDENCE FROM SMELTER"
Lead
smelter
worker


Area
1
2
3
4
5
6
Distance
from
smelter, km
1.6
1.6 to 4.0
4.0 to 10.0
100 to 24.0
24.0 to 320
75


Pica
78.7
50.2
335
—
—
—

No
pica
74.2
52.2
33.3
303
24.5
—
Lead/zinc mine
worker


Pica
753
57.1
36.7
38.0
31.8
—

No
pica
63.9
469
33.5
32.5
27.4
—
Zinc smelter
worker


Pica
697
627
36.0
40.9
—
—

No
pica
59.1
50.3
396
369
—
—
Other
occupations


Pica
70.8
37.2
33.3
—
28.0
173

No
pica
59.9
46.3
32.6
394
26.4
21 4
                                               12-37

-------
populations  living nearest to the smelter, environ-
mental exposure appears to be sufficient at times to
more  than overshadow the effects of pica, but this
finding may also be caused by inadequacies inherent
in collecting data on pica.
  These data indicate that in a heavily contaminated
area,  blood  lead  levels in children may be signifi-
cantly increased by the intentional ingestion of non-
food materials having a high lead content.
  Data  on the  parents'  occupations  are, however,
more  reliable. It must be remembered also that the
study   areas   were   not  homogeneous
socioeconomically. In addition, the type of work an
individual does in an industry  is probably  much
more  important than simply being  employed in a
particular industry. The presence in the home of an
industrial employee exposed occupationally to lead
may produce increases in the blood lead levels rang-
ing from 10 to  30 percent.
12.3.6 Miscellaneous Sources of Lead
  Although  no studies are available, it is conceiva-
ble that  destruction of lead-containing plastics (to
recover copper), which has caused cattle poisoning,
also could become a source of lead for humans. A
more general  problem  is waste disposal,  because
lead-containing materials may be incinerated and
may thus contribute to increased air lead levels. This
source of lead has not been  studied  in detail.
  The consumption  of illicitly distilled liquor has
been shown to produce clinical cases of lead poison-
ing. Domestic and imported earthenware with im-
properly fired glazes have also been related to clini-
cal lead  poisoning. This source becomes important
when  foods or  beverages high in acid are stored  in
containers made from these materials because the
acid releases lead  from the walls of the containers.
  Particular cosmetics popular among some Orien-
tal  and Indian ethnic groups  contain high  percen-
tages of lead that sometimes are absorbed by users in
quantities sufficient to be toxic.
12.4 SUMMARY
  Blood lead levels in homogeneous human popula-
tions  have almost  invariably been found to be log-
normal. A number of such data sets were examined
and they displayed a geometric standard deviation
(GSD) ranging from 1.3 to 1.5.
  From  the lognormal distribution, given  a mean
blood lead level and an  estimated geometric stan-
dard deviation, it  is possible to predict the percen-
tages of a population whose blood lead levels exceed
a specified value. It is also possible to estimate the
likely increase in mean blood  lead levels for a
population exposed to specific increases in environ-
mental lead. Coupling these two procedures  pro-
vides a method by which standards may be chosen to
protect the health of the population.
  Blood lead levels have been found to exhibit  con-
siderable geographic variability. Generally they are
lowest in  rural settings, higher in suburban areas,
and highest  in inner-city areas. These values follow
the presumed  lead exposure gradient. Blood  lead
values were  also found to vary by age, sex, and race.
although  in a somewhat  more complex fashion.
Generally, young children have the  highest levels,
with little difference between sexes. In older  seg-
ments of the population, after eliminating occupa-
tional exposure in lead workers, males have a higher
blood lead than females. The published data com-
paring the blood lead  levels of various racial and
ethnic groups  of the  population suggest that blacks
have  higher blood  lead levels  than whites,  with
Puerto Ricans sometimes at  an intermediate level.
  Results of the numerous studies of environmental
exposures of man have indicated strongly  that  man
does indeed  take up lead from each source to which
he is exposed  Equally important, these studies  have
shown that the blood lead level is the summation of
the absorption from each of these sources.
  Data for the two most widespread environmental
sources other than food permit summary statements
concerning  their  quantitative  relationship  with
blood lead levels: ratios between blood  lead levels
and  air   lead exposures were  shown  to range
generally from 1:1 to 2:1. These were not,  however,
constant  over  the range of air lead concentrations
encountered. There  are suggestive data indicating
that the ratios for children are in the upper end of
the range and may even be slightly above it. There is
also some slight suggestion that the ratios for males
are higher than those for females.
  For soil lead exposures,  a consistent  association
with  blood lead levels has been established.
Children exposed to  higher soil and housedust  lead
concentrations have  been shown  to  have elevated
concentrations of lead on their hands, but an associ-
ation of  elevated blood lead levels with elevated
hand lead levels has not yet been established. Quan-
titatively, blood lead levels  have been shown to in-
crease 3 to 6 percent when the soil or dust lead  con-
tent is doubled.
  Significant water lead exposures  in this country
have  occurred only in places using leaded pipes
coupled with  a soft  water  supply. Such  exposures
have  been shown to be associated with significant
                                               12-38

-------
elevations of blood lead. They have also been linked
to cases of mental retardation.
   Exposure to  leaded  paint still comprises a very
serious problem for American children in urban set-
tings.  Although new regulations governing the lead
content of paint should alleviate the problem in new
housing,  the poorly enforced regulation and lack of
regulation  of the past  have left a heavy burden of
lead exposures  from  paint. Most of  the studies on
lead poisoning  in children have assumed an associ-
ation with  leaded  paint, but very rarely have these
studies measured the amount of exposure. There is,
nevertheless,  strong  suggestive evidence  that  the
contribution from this source can be very significant.
   Lead exposure via food  is thought to be the source
of a significant  portion of blood lead. Direct  quan-
titative  equations  describing   the  relationship   of
blood to food lead levels have not been published,
but studies described in Chapter 10 do  address this
relationship.

 12.5 REFERENCES FOR CHAPTER 12
   1  Yankel.A J  , I von Lmdern, and S D Walter The Silver
     Valley lead  study  The relationship between childhood
     blood  lead levels and environmental  exposure  J  Air
     Pollut  Cont. Assoc. 27-763-767, 1977
   2. Tepper, L. B. and L. S. Levin A survey of air and popula-
     tion  lead levels in  selected American communities.  En-
     viron.  Qual  and Safe, Supplement II- Lead. 152-195,
     1975.
   3. Azar.A.,R.D Snee, and K  Habibi. An epidemiologic ap-
     proach to community air lead exposure using personal air
     samplers Environ Qual  and Safe., Supplement II- Lead.
     254-288, 1975
   4. Schubert,  J.. A. Brodsky, and  S  Tyler.  The lognormal
     function as a stochastic mold of the distribution of stron-
     tium-90 and  other fission products in humans  In. Health
     Physics, Vol. 13  New York. Pergammon Press. 1967. p
     1187-1204.
   5  Snee, R  D.  Development of an Air Quality Value for
     Lead from Community Studies. E I. du pont de Nemours
     & Co., Wilmington.  Delaware. Technical Report  No
     PLMR-3-77  January  1977
   6  Johnson, D.  E., J. B. Tillery, J   M. Hosenfeld,  and J W
     Register  Development  of  Analytic  Techniques  to
     Measure Human Exposure to  Fuel  Additives  Southern
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120. Lin-Fu. J.  S. Vulnerability of children to lead exposure
     and  toxicity. New  England  J   Med. 289:1229-1233,
      1289-1293, 1973.
121. Berger, H.  W.  The  NBS lead  paint poisoning project:
     Housing and other aspects. National Bureau of Standards,
     Gaithersburg, Maryland. Technical Note No. 759. Febru-
     ary  1973.
122. Bird, D. New York Times, August 8, 1971.
1 23. Lead Paint Survey Sampling Plan and Preliminary Screen-
     ing  Report  10958.  National  Bureau  of Standards,
     Gaithersburg, Maryland. 1973.
124. A Report to Congress in Compliance with the Lead Based
     Paint Poisoning Prevention Act. Consumer Product Safety
     Commission, Washington, D. C. December 1974.
125 Recommendations for the Prevention of Lead  Poisoning
     in Children. Assembly of Life Sciences, National Academy
     of Sciences, Washington, D. C. July 1976. 85 p.
126. Shier, D. R. and W. G. Hall. Analysis of Housing Data
     Collected  in a  Lead-Based Paint  Survey  in  Pittsburgh,
     Pennsylvania. National Bureau of Standards, Washington,
     D. C (In preparation.)  1977.
127. Hall, W.. T. Ayers, and  D. Doxey. Survey Plans and Data
     Collection and Analysis Methodologies: As a Result of  a
     Pre-Survey for  the Magnitude  and Extent of the Lead
      Based Paint Hazard in Housing. National Bureau of Stan-
     dards,  Gaithersburg,  Maryland.  Report  No.  NBSIR
      74-426. January 1974.
                                                        12-42

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128.  Urban, W D. Statistical Analysis of Blood Lead Levels of
     Children Surveyed in Pittsburgh, Pennsylvania: Analytical
     Methodology and Summary  Results.  Final  contract re-
     port, Contract IAA-H-35-75, Department of Housing and
     Urban Development, Washington, D. C. April 1976
129.  Reece, R. M., J. A  Reed, C S. Clark, R. Angoff. K.  R.
     Casey, R. S. Challop, and E. A. McCabe. Elevated blood
     lead levels and the in situ analysis of wall paint by X-ray
     fluorescence  Amer. J.  Dis. Child. ;24'500-502, 1972.
130  Tyler, R. L. Philadelphia combats "silent epidemic" in the
     "ghetto"  lead  poisoning control.  J.  Environ  Hlth
     35-64-71, 1970
131  Hopkins,  D. R. and  V  N. Houk.  Federally-assisted
     screening projects for  childhood lead  poisoning control.
     The  first three  years  (July 1972-June  1975). Amer  J
     Public Hlth. 66:485-486, May 1976
132. Morbidity and Mortality Weekly Report. Department of
     Health, Education, and  Welfare, Rockville,  Maryland.
     February 11, 1977.
1 33. Martin, A. E., F  A Fairweather, R St. J. Buxton, and R.
     M. Roots Recent  Epidemiological Studies of Environ-
     mental Lead of Industrial Origin. Luxembourg, Commis-
     sion of the European Communities. 1975.
134. Medical Aspects of Lead Absorption in Industrial Pro-
     cesses. Lead Development  Assoc., London,  England.
     1973.
135. Baker, E. L  , D.  S. Folland, T. A. Taylor, M.  Frank, W.
     Peterson, G   Lovejoy, D Cox,  J. Housworth, and P. J.
     Landrigan.  Lead poisoning  in children  of lead workers;
     house contamination with industrial dust. New England J
     Med.  296:260-261, 1977
                                                        12-43

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             13. EVALUATION OF  HUMAN  HEALTH  RISKS
         FROM  EXPOSURE  TO  LEAD  AND  ITS  COMPOUNDS
 13.1 INTRODUCTION
  The preceding chapters of this document have de-
 scribed  lead  production,  the  eonomics  of lead
 utilization, the dispersion of lead  in the environ-
 ment — particularly in air, dust, and soil —and,
 finally,  have reviewed the effects  of lead  on the
 health of man. Although attempting to relate these
 various issues to  one  another, this chapter
 specifically will attempt to assess and to quantitate
 the health effects that arise from exposure of man to
 lead in  the environment and, more precisely, from
 exposure to lead in air. Six central questions to be
 addressed are as follows:
     1. What are the sources of lead in the environ-
       ment? (Sections 13.2 and  13.3)
     2. What are the routes and mechanisms by
       which lead from these  sources  enters  the
       body? (Sections 13.2 and  13.3)
     3. What part do averaging times for these ex-
       posures play? (Section 13.4)
     4. How does the body respond to the entrance
       of lead? (Section 13.5)
     5. Are there groups within populations  which
       are particularly vulnerable to lead? (Section
       13.6)
     6. What is the magnitude of the risk exposures
       in terms of the number of persons exposed in
       various subgroups of populations? (Section
       13.7)
Each of the above questions is addressed  separately
as a subsection of this chapter, and the relevant sec-
tion  is noted beside each question.
  Now that  the  questions to be  addressed  in this
treatment of risk assessment have been outlined, it is
necessary to  define the  terms which will  be
employed. These include:
     1. Dose is the amount or concentration of a
      chemical  that is presented over time  to an
      organism, organ, cell, or subcellular compo-
      nent. Ideally, dose should be defined as the
      amount or concentration of the chemical at a
      specific intracellular site of effect.
     2. External dose is the amount of the contami-
       nant in the external environment (air, water,
       food, etc.) to which humans are exposed.
     3. Effective dose or internal dose is the amount
       of the contaminant absorbed by the body.
     4. Effect is a biologic change which results from
       exposure to a chemical.
     5. Dose-effect  relationship is a quantitative
       relationship  between  the dose and  the
       specific effect that is established after grada-
       tions in the severity of an effect  have been
       measured.
     6. Critical effect is the first adverse  functional
       change, reversible or  irreversible, to  be
       caused  by exposure to a particular chemical.
     7. Subcritical  effect  is  a change  that  is
       demonstrable by biochemical or  other test,
       but which does not  appear  to impair func-
       tion; some such changes may be adaptive in
       nature.
     8. Critical dose or critical concentration is the
       level of a chemical at which the critical effect
       appears.
     9. Critical organ is  the organ which manifests
       the critical effect; it need not be the organ
       with the highest concentration of the chemi-
       cal nor  that which ultimately suffers the most
       serious injury.
  Dose-effect  relationships will  vary among  the
members of a  population. Response is the  propor-
tion  of the population that manifests a  particular
effect at  a particular dose  level.1  This  is  a more
restrictive definition  of response than  that used in
bioassay as described by Finney.2 The relationship
between dose and the proportion responding is the
dose-response relation, which will most commonly
be expressed by a sigmoid-shaped curve.

13.2 SOURCES, ROUTES,  AND MECHAN-
ISMS OF ENTRY
13.2.1  Sources
  Of the estimated 161,225 metric tons of lead emit-
                                               13-1

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ted into the atmosphere in 1975, the combustion of
gasoline additives and waste oil accounted  for 95
percent of total inventoried  emissions. Each of the
remaining emission  sources accounts for only  a
small part of the total quantity of lead, but has the
potential of creating localized situations of high air
lead concentrations, e.g., primary lead smelters.
  Once lead is introduced into the air it undergoes a
variety of processes  including dry deposition, pre-
cipitation, and resuspension. These  processes result
in a variable proportion of lead being retained in the
air  and then being  distributed over  a wide area.
Other portions are deposited  on land, in dust, and on
water, resulting in increased lead concentrations in
each.
  Other uses  of lead result in additional human ex-
posure. The addition of lead  to paint makes lead
directly available  by ingestion of paint  chips and
paint-saturated plaster.  In addition it becomes in-
directly available through dust contaminated with
lead freed by the weathering process of paint. This
primary source is currently under regulation, but a
vast stock of housing painted with high-lead-content
paint still exists.
  Lead's malleability and ductility have resulted in
the use of this metal in  pipes for carrying drinking
water. When  such  pipes are  used in areas with soft
water of low pH, a  potential exists for heavy lead
contamination of drinking water.  It  is difficult to
estimate the overall magnitude of this danger, but
there have been specific localized examples in the
United States.
  A final quantitatively significant source of lead  is
the human diet. Lead present in foodstuffs is the sum
of the amount present  in the raw foodstock and of
lead introduced via processing and packaging. Can-
ned products such as vegetables and milk have been
shown to contain higher quantities of lead than the
same products packaged differently. This is due, in
part, to the presence of lead solder in the seams of
cans. Baby foods have also been shown to have high-
er lead contents because of  the preservatives used.
The origin of lead in raw food stocks is still a matter
of some controversy, although part  of it is likely to
be the consequence of man's activities which result in
making lead  available for uptake by  animals and
plants. Such redistribution and subsequent uptake of
lead by plants is well illustrated by fivefold increases
in the amount of lead present in tree rings over a 50-
year period.
  It is important to realize that human exposure and
intake are not limited to the primary sources of lead
in the environment but, rather, to the sum of prim-
ary, secondary, and tertiary sources. Table 13-1 dis-
plays these sources.
TABLE 13-1. SOURCES OF LEAD FOR HUMAN EXPOSURES
Primary
exposure
source
Air

Secondary
exposure
source
Dust and
soil
Tertiary
exposure
source
Food
Runoff water
Paint


Water from
leaded pipes

Food
Water

Dust and
soil
Aira

Runoff water
Aira
  Reentramment
13.2.2 Routes and Mechanisms of Entry
  Chapter 10 presents data on the entry of lead into
the human body. Two routes of entry are of principal
importance, inhalation and ingestion. Intake of air-
borne lead is governed by the physical and chemical
state of inhaled  lead, particle size retention  in the
lung,  and absorption  from the lung into the red
blood cells.
  The second major route of entry is ingestion, both
of food and of  nonfood material.  Uptake is con-
trolled by the nutrient balance of the food ingested,
particularly that of iron, by  the physical  nature of
the lead-bearing material  ingested,  and by the
chemical composition  of the substance. Here, too,
the lead is absorbed  by circulating red blood cells.
  The total internal dose of lead which confronts the
organ systems of the  body is the sum of the lead in-
take by both routes of entry, inhalation and  inges-
tion. Thus the total internal dose represents the sum-
mation of all external sources to  which the body  is
exposed.  Some  of  these  exposures  may   be  of
different relative significance in diverse population
groups due to variances  in metabolism or behavior
among different  segments of the population.
13.3  EVIDENCE  OF INCREASED  BLOOD
LEAD  LEVELS  IN HUMANS EXPOSED TO
ENVIRONMENTAL LEAD

13.3.1 Relationships Between Blood Lead Levels
and Single-Source Exposures
  Research  has been conducted on all six major ex-
posure sources — air,  dust, soil,  water, paint, and
food. Chapter 12 provided the detailed description,
evaluation,  and  findings of  those studies. Not all
sources have been studied with the  same intensity,
                                                13-2

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and food has been studied least. In addition, food as
a tertiary exposure source is difficult to evaluate.
Lead content in food due to packaging and process-
ing has been studied more thoroughly than contribu-
tion  from that lead present at the point of origin.
  Single-source studies of air have included both
epidemiological and clinical investigations. Clinical
data uniformly demonstrate the actual uptake of air-
borne lead into blood, and epidemiologic data also
generally support such a relationship.
  Studies concerned  with  dust  and  soil lead  ex-
posures will  be considered together since in many
studies the investigators did not attempt to deal with
these sources separately. Considerable evidence  ex-
ists that these exposures can be significant determi-
nants of blood  lead levels. Furthermore,  investiga-
tions of children exposed to lead-contaminated dust
have  demonstrated  more  lead  on  the children's
hands, thus documenting a plausible route of entry
which is  due to normal oral behavior  in  young
children.  It may be worth  reiterating here that  the
dose of lead ingested from  dust and soil appears to
be additive to that inhaled from air.
  The popular  assumption that lead-based paint is
the single causative agent  of elevated blood lead
levels in children has resulted in limiting the defini-
tion  of high-risk children to those residing in older
housing. As a result, lead screening programs have
been established with the sole purpose of identifying
children with elevated lead levels  among  those liv-
ing in old housing. Abatement  efforts have fre-
quently been unable to find  lead paint sources  for
children with  high  blood  levels found  by  such
screening programs. The possible contributory role
of airborne  lead  to  the  lead  burden  of  urban
children has until recently received little attention.
  Finally, studies from Glasgow and  Boston have
shown elevated blood  lead  levels in conjunction
with  elevated levels of lead in the  drinking water.
  Secondary effects of occupational exposure have
been examined in children whose parents work in
lead  industries. It has been found that parents carry
home lead-contaminated dust. Significant relation-
ships between  house  dust  levels  and blood lead
levels have  invariably been  established  in these
studies.

13.3.2 Multiple-Source Exposures
  Studies measuring the quantity of lead in multiple
sources, around primary lead smelters or in  urban
settings, have consistently demonstrated an additive
relationship between blood lead levels and exposure
to the several sources studied.
 13.3.3 Effect  of Host  Factors  on  Blood  Lead
 Levels
   Host characteristics that mediate the relationship
 between  exposure to lead and blood lead level have
 been examined in several studies. In particular, age
 has  been shown to be a significant factor in deter-
 mining blood lead levels; this  relationship is dis-
 cussed below in more detail in the section (13.6) on
 populations at greatest risk.
   Sex differences have been found to be age  related.
 Particularly among  preschool boys and girls, vir-
 tually  no difference  has been  established. In  the
 adult population, however, males generally exhibit
 higher levels than females.
   Data on the  racial/ethnic factor  are sparse. One
 study has reported  that black children have higher
 lead levels than do white children. Although the sig-
 nificance of the racial/ethnic factor cannot be estab-
 lished at  this time, it seems reasonable to assume that
 it  is the socioeconomic rather than  the  genetic
 dimension of this variable that may prove to  be rele-
 vant.
   Socioeconomic  variables  such  as  income and
 education have not been examined adequately  as in-
 dependent factors. Associated characteristics such as
 residence in old housing, or proximity to high-den-
 sity  traffic arteries or to stationary sources  such as
 smelters, have been shown to be directly relevant.
   In epidemiological studies the health status as a
 variable  has not been examined. Conditions such as
 iron deficiency anemia, other states of malnutrition,
 sickle cell anemia,  and lactose  intolerance  as host
 factors  in  lead  intake and  determinants of
 physiological and pathological  changes have only
 recently come under study. No findings are available
 as yet.
 13.3.4 Summary of the Quantitative Relationship
   Statistical evaluation of the data collected  from
 population and clinical studies has been presented in
 the previous chapter. There it was noted that the
 weight of the evidence indicates that blood lead
 levels follow a  lognormal distribution in exposed
 populations with a geometric standard deviation of
 1.3 to 1.5. It was also seen that the lognormal distri-
 bution has properties that make it amenable to use in
 the standard-setting process, since it permits an esti-
 mate of  the  proportion of the population whose
 blood lead levels exceed any specified level.
   Detailed  examination  of  the  clinical  and
epidemiological  studies relating air lead  levels to
blood lead levels is presented in Chapter 12. Evi-
dence indicates that a positive relationship exists be-
                                                13-3

-------
tween blood and air lead levels, although the exact
functional relationship has not  yet been clarified.
Available data indicate that in the range of air lead
exposures generally encountered by the population,
the ratio of the increase in blood lead per unit of air
lead is  from  1  to 2.  It appears  that the  ratio for
children is in the upper end  of the range and that
ratios for  males may  be  higher  than  those for
females.
  Quantitative relationships can also be established
between blood lead levels and exposure to lead in
soil. There is general agreement that blood lead
levels begin to  increase at  soil lead levels of from
500 to  1000 ppm. Mean percent increases in  blood
lead levels, given a twofold  increase in  soil lead
levels, ranged from  3 to 6. This is a remarkable con-
sistency, given  the  divergence  of the populations
studied.
 13.4  AVERAGING-TIME  CONSIDERATIONS
   One of the major areas of concern in dealing with
quantitation  of  the relationship between  a  health
effect and an external dose of some environmental
pollutant is the determination of how long  an ex-
posure  must occur before there is an effect.
   Evidence presented in Chapter 12 indicates that a
5 /xg/dl increase in blood lead can result from an air
lead exposure of 3.2 ^g/m3for a period of 7 weeks.
Furthermore, FEP levels have been shown  to  in-
crease within 2  weeks of an  increase of blood lead
levels. Therefore, an air lead exposure of 3.2  /Ag/m3
lasting  about 1  to 2 months  can definitely increase
the blood lead level.

 13.5  BIOLOGICAL AND ADVERSE HEALTH
EFFECTS OF LEAD IN MAN
   Lead does not presently have associated with it
any biological effect in man which can be considered
beneficial; therefore, any consideration of the health
effects of lead in man must be done from a point of
view  that acknowledges the  absence of any  health
benefit/health cost  ratio.
   An additional and extremely important  aspect of
 lead's effect on health impairment that must be con-
sidered in risk assessment is the question of whether
 these effects are reversible once present.
   Physiological damage to central nervous  system
 tissue is presently widely accepted as being irreversi-
 ble; thus prevention of lead exposure is most  urgent
 when  one considers  severe neurological effects.
 Irreversibility is also accepted  in the case of renal
 tissue damage resulting from  chronic lead exposure,
 particularly  in cases  where  these  effects are
 manifested morphologically.
  We speak of physiological  irreversibility in the
cases of neurological or renal tissues, but the con-
cept of irreversibility of an effect  being  likely or
assured by nonbiological factors such as continuing,
long-term exposure to airborne lead must also be
considered. Hematological effects are of relevance
here.  Although  a number of these hematological
effects may be biochemically reversible,  if the prob-
ability of the  person being removed  from the ex-
posure setting  inducing these effects  is slight or non-
existent,  for whatever reason, then  defacto irrever-
sibility exists.
  This section summarizes the biological effects of
lead on man with particular reference to significance
of these effects for human health. Much of the atten-
tion in this section will be directed to those biologi-
cal  effects  which may collectively  be  termed
"subclinical."  By definition, subclinical effects are
disruptions in function, which may be demonstrated
by special testing but not by the classic techniques of
physical  examination; using  the term "subclinical"
in no way implies that those effects are without con-
sequences to human health.

13.5.1  Assessment of Hematological  Effects of
Lead
  A multiplicity of  effects  of  lead on  the
hematopoietic system exists. These effects were dis-
cussed in detail  in Chapter  11, Section 3, and are
briefly summarized here.

 13.5.1.1  ANEMIA
  Anemia is a classic manifestation of clinical lead
 intoxication, often occurring  prior to neurological
 and other  system impairment. The mechanism  of
 anemia in  lead exposure  apparently involves  both
 decreased production of hemoglobin and enhanced
 destruction of erythrocytes. Reports on  children in-
 dicate  that  statistically  significant  decreases  in
 hemoglobin levels begin to appear  at a blood lead
 level of 40 yu.g/dl or somewhat  below. In  adults a sig-
 nificant  decrease  in hemoglobin level appears  to
 become evident at a blood lead level of 50 /u,g/dl.

 13.5.1.2 LEAD  EFFECTS  ON  HEME  SYN-
 THESIS
  A large number of studies have been  done on the
 effects of lead on heme synthesis in humans. Lead
 interferes with heme synthesis at several points along
 the heme-biosynthetic pathway. The two most im-
 portant  points of interference are:  (1)  the  con-
 densation  of two  units of  8-aminolevulinic acid
 dehydratase to form porphobilinogen and (2) the in-
                                                13-4

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sertion  of iron  into  protoporphyrin  IX  which is
catalyzed by the enzyme ferrochelatase.

 13.5.1.3  EFFECT  OF LEAD  ON  8-AMINO-
LEVULINATE DEHYDRATASE (8-ALAD)
AND S-AMINOLEVULINIC ACID (8-ALA) EX-
CRETION
   A number of studies have  shown the high sen-
sitivity of 8-ALAD to lead and the negative correla-
tion between blood  lead  and the logarithm of 8-
ALAD  activity.  These studies  are described  in Sec-
tion 11.3. It appears that this relationship holds true
for industrial workers, the general population, and
children.
   The dose-response  relationship  between  blood
lead and the logarithm of ALAD activity appears to
be linear coefficient of correlation  (r)  =  0.84.
ALAD inhibition is first noted at whole blood levels
of 10 to 20 /tg/dl (Chapter 11). This high degree of
sensitivity makes application and interpretation of
the test difficult. ALAD inhibition is virtually com-
plete at blood lead levels of 70 to 90 ^g/dl.
   Data summarized by Hernberg3 suggest that heme
biosynthesis is not decreased by ALAD inhibition
until activity of the enzyme has fallen to less than 20
to 30 percent of normal. In addition to its  effect on
red  blood  cell  ALAD,  lead  appears to  inhibit
ALAD activity in liver. It has also been suggested
that in young children lead may inhibit activity  of
ALAD in brain.

13.5.1.4  EFFECT OF LEAD ON  IRON  INSER-
TION INTO PROTOPORPHYRIN
   Accumulation of protoporphyrin  in erythrocytes
in lead exposure is the result of lead-induced  inhibi-
tion of the intramitochondrial enzyme,  ferro-
chelatase. The  inhibitory effect  of lead  on  fer-
rochelatase may either be direct or may be mediated
by  a disruption  in  the function of mitochondria]
membranes.
  The effect of lead on the formation of heme is not
limited to the hematopoietic system. Experimental
animal studies have shown a lead effect on the heme-
requiring protein, cytochrome P-450,  an  integral
part of the hepatic mixed-function oxidase (Chapter
11), the  systemic function of which is detoxification
of exogenous substances. Heme synthesis inhibition
also takes place in neural tissue.
  The elevation of free erythrocyte protoporphyrin
(FEP) has been shown by a large number of studies
to be exponentially correlated with blood lead level
in  children and  adults.
  Present information shows that at relatively fixed
blood  lead  values  children and  probably women
have higher  protoporphyrin  levels in  their blood
than adult males. The exact  reason for this is  not
known, but it may be of endocrinological origin.
  Elevation  in protoporphyrin  is considered  not
only to be  a biological  indicator  of impaired
mitochondria! function of erythroid tissue but also
an  indicator of accumulation of substrate for  the
enzyme ferrochelatase.  It therefore  has the  same
pathophysiological meaning as increased urinary 8-
ALA (vide supra). For these reasons accumulation of
protoporphyrin has been   taken  to  indicate
physiological impairment in humans, and this clini-
cal concensus is expressed in the 1975 Statement of
the Center for Disease Control (CDC), USPHS. The
criterion used by CDC to indicate an effect of lead
on heme function is an FEP level of 60 /ug/dl in  the
presence of a blood  lead level  above 30 /^.g/dl whole
blood.
  More recent  information relating to threshold of
lead effects  indicates that FEP levels begin to  in-
crease  at a blood lead value  of 15 to 20 jtg Pb/dl
blood  in children and women and, at  a somewhat
higher  value, 20 to 25 /u.g Pb/d 1 blood, in adult men.

13.5.1.5 OTHER  EFFECTS ON  HEME SYN-
THESIS
  There are  other abnormalities of heme synthesis
that are a result of lead exposure. For example, it is
well known that  an increased  urinary copro-
porphyrin level is found in lead poisoned children
and lead workers. It is not known whether this effect
results from specific  enzyme  inhibition,  from
upstream accumulation of substrate secondary to the
inhibition of iron insertion into protoporphyrin, or
from   a disturbance  of coproporphyrin transport
through the mitochondrial membrane.
  An increased activity of 8-ALA synthetase is seen
in lead intoxication, but this change probably arises
as a negative feedback control to 8-ALA response to
inhibition upstream in the heme-biosynthetic path-
way. Few  data exist to quantitate the health signifi-
cance of this effect.

13.5.1.6 EFFECTS OF LEAD ON GLOBIN SYN-
THESES
  Hemoglobin synthesis may also be impaired by the
inhibition  by lead of globin biosynthesis.  Globin is
the  protein moiety of hemoglobin. One recent study
shows an effect on globin synthesis in vitro on human
reticulocytes  at lead concentrations corresponding
to a blood lead level of 20 /ig/dl.
                                               13-5

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13.5.2  Assessment of Neurobehavioral Effects of
Lead
  As reviewed in Chapter 11, an extensive literature
documents the adverse effects of lead on the central
and peripheral nervous systems of many human and
nonhuman mammalian species.  Only limited dose-
response data  exist that might allow external lead
exposure parameters to be linked directly to the oc-
currence of particular  neurobehavioral effects. In
contrast, more data exist relating blood lead levels
to neurobehavioral deficits; major emphasis her« is
therefore focused on the concise summarization of
relationships between human blood  lead levels and
neurobehavioral effects.

13.5.2.1 CENTRAL  NERVOUS   SYSTEM
EFFECTS
  Among the most profoundly deleterious effects of
lead poisoning are those associated with severe CNS
damage that occur at toxic high exposure levels. The
acute overt manifestations of neural  damage at high
lead exposure levels include such symptoms as ir-
ritability, stupor, convulsions, and/or coma, which
characterize the  well-known encephalopathy syn-
drome. Such symptoms at times occur abruptly dur-
ing  the course of much  milder  symptomatology or
even in  apparently asymptomatic lead  poisoned in-
dividuals and may progress to death within 48 hr.
  Even in the absence of death or prolonged uncon-
sciousness, it is now widely accepted that irreversi-
ble  neural damage typically occurs as one of the se-
quelae of nonfatal  lead encephalopathy episodes.
Such permanent neural damage  is reflected by signs
of continuing CNS impairment ranging from subtle
neurobehavioral deficits to severe mental retarda-
tion or continuing mental incompetence. What is not
yet  universally agreed upon, however, are the lead
levels sufficient to produce lead encephalopathy and
its sequelae.
  In regard to the issue  of threshold levels for lead
encephalopathy, blood  lead levels of 120 /xg/dl or
more are currently widely accepted  as necessary to
produce  encephalopathy symptoms  in  adults.  The
published evidence bearing on this point, however, is
very limited. Included  among such  evidence are a
few scattered   reports   suggesting  that acute  en-
cephalopathy or death may occur in  adults at blood
lead levels under  100 ^g/dl (from 80 to 100 /Ag/dl),
but  the rarity of such cases and ambiguities in the re-
ported data render it difficult to accept those reports
as evidence  for encephalopathy in adults at blood
lead levels below 120 Mg/dl.
  Much better evidence exists for the occurrence of
lead encephalopathy in children at blood lead levels
below 120/ig/dl or even 100/ig/dl. That is, it is well
documented that such symptoms  occur for  some
children beginning  at the 100  /zg/dl  level; also,
several  scattered reports suggest that somewhat
lower threshold levels may obtain, i.e., in the 80 to
100  /u-g/dl  range, although  such reports  must  be
viewed  with caution  as in the case for analogous
results for adults.
  As indicated earlier, the issue  of  whether  ap-
parently asymptomatic children experience subtle
neurobehavioral deficits at low-to-moderate blood
lead levels in the 40 to 80 ^ig/dl range remains a sub-
ject  of much  controversy.  A  thorough,  critical
review  of  the relevant  literature  presented  in
Chapter 11, nevertheless, leads to the conclusion
that  blood  lead levels of 50 to 60 /*g/dl are likely
sufficient to cause significant neurobehavioral  im-
pairments for at least some apparently asymptomatic
children. The impairments consist mainly of cogni-
tive  or  sensory-motor integration  deficits, but  do
not  appear  to  include the  occurrence of hyper-
activity; that latter effect seems to be much better es-
tablished as one of the neurological sequelae follow-
ing encephalopathy  at higher lead levels.

13.5.2.2  PERIPHERAL  NEUROPATHY
EFFECTS
  In addition to the above CNS effects, peripheral
nervous system damage also results from exposures
to lead. Such effects have  been best documented as
occurring after long,  chronic, high-level exposures
in adults exhibiting other symptoms of lead intoxica-
tion. Recent studies  of apparently asymptomatic
adults,  usually  occupationally  exposed to  lead,
however, present reasonably strong evidence for  pe-
ripheral  neuropathy  at more moderate lead  ex-
posure levels, i.e., at blood lead  levels  in the range
of 50 to 70 /zg/dl. Peripheral neuropathy effects  are
typically associated with  adult  exposures, having
been reported much less frequently for children. A
few reports of lead-induced peripheral neuropathies
in children, however,  contain evidence for the  oc-
currence, in some rare  instances, at blood lead levels
as low as 50 to  60 /ug/dl.

13.5.2.3 RESULTS OF ANIMAL STUDIES  AS
SUPPORTIVE EVIDENCE
  Review of the literature on  the neurobehavioral
effects of lead in animals provides evidence suppor-
tive of the above  conclusions from human  studies.
That is, there appears  to be a differential sensitivity
of newborn or young animals of many species to  the
neurobehavioral effects of  lead. This applies both to
                                               13-6

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the induction of lead  encephalopathy at high ex-
posure  levels  and  more  subtle  neurobehavioral
deficits at lower, more moderate exposure levels. In
regard to specific types of subtle neurobehavioral
effects, hyperactivity appears to occur  mainly at
blood  lead levels in excess of 70 to 80 /u.g/dl and,
therefore, probably most closely parallels the post
encephalopathic hyperactivity well demonstrated as
one  of the  sequelae  of  lead  encephalopathy in
humans.  Other behavioral changes, interpreted as
indicative of cognitive impairments resulting from
CNS effects,  appear to occur in  animals at blood
lead levels below those associated with acute en-
cephalopathic effects,  i.e., in the 30 to 80  ^tg/dl
blood lead level range. This parallels rather closely
the effects observed for humans, especially children,
except that cognitive deficits have not been very well
documented in the children at levels below 50 to 60
/iig/dl. The external  lead  exposures yielding  the
above results for animals, however, typically appear
to be much higher than those producing comparable
effects in  humans;  the  comparability  of animal
studies and human studies is therefore often ques-
tioned. If one focuses  on  the resulting blood lead
levels  achieved, regardless  of  associated external
dose,  however,  the  results  of  the animal studies
parallel those of the human studies remarkably well.
   In discussing the neurobehavioral effects of lead,
above in the present section and in Chapter 11, a dis-
tinction has repeatedly been  made between thresh-
old  levels  yielding severe  symptoms  of lead
encephalopathy  seen at high exposure  levels  and
more  subtle  neurobehavioral deficits observed at
lower exposure levels. This approach may inappro-
priately convey an impression of such effects occur-
ring  in a discrete,  step-like  fashion as  particular
threshold blood lead levels are reached. It is impor-
tant to note that this may occur insofar as shifting
from  apparent no-effect  levels to levels at which
fairly  well  substantiated  neurobehavioral  effects
have been  found to occur,  i.e., around 50 to  60
/ig/dl; beyond that point, however, further increases
in relative levels of neural damage, as indicated by
increasingly  severe neurological  or  behavioral
deficits, occur in a more or less smoothly ascending
fashion in relation to increasing blood lead  levels.
These  relationships are  presented later  in  an
approximate  manner  in  Table  13-2.  Due  to
differences in individual susceptibility, it should be
emphasized that the upper end of the range of blood
lead levels at which  subtle neurobehavioral effects
have been reported to  occur for  some individuals
merges or overlaps substantially with the lower end
of  the  range  at  which  much  more  severe  en-
cephalopathic symptoms have  been observed,  and
that the shift from subtle to severe neural symptoms
may be quite abrupt.
13.5.3  Effects of  Lead  on  Reproduction  and
Development
  Although the effects of lead  exposure in humans
have usually been associated with the hematopoietic,
neural,  and renal systems,  concern needs  to be
equally directed to the  entire area  of reproduction
and development, with special  emphasis on  the
vulnerability  of pregnant  women  or,  more  ac-
curately, the vulnerability of the fetus.
  Attention in this area is focused on two aspects of
reproduction: (1)  the gametotoxic  effects  of lead,
i.e., lead  effects on spermatogenesis and  ovarian
function,  and  (2)  postconception  events  through
delivery.
13.5.3.1 HUMAN GAMETOTOXICITY
  Some data involving  effects of lead exposure on
the fertility of males exist, and  these have been ob-
served at blood lead levels of 50 to 80 /u,g/dl  under
conditions of occupational exposure. With regard to
women, one study on lead effects (see Reproduction
and Development section, Chapter 11) raises  the
possibility that the ovarian cycle may be disturbed in
the age  range of 20 to 25 years with air lead  levels
around 7 /ig/m3.

13.5.3.2 POSTCONCEPTION  LEAD EFFECTS
  Both  early  literature and more  current studies
conclusively show that  lead crosses the placental
barrier. Such fetal  exposure therefore commences at
about the end of the first trimester  (12  weeks)  and
continues  throughout fetal  development.  As  has
already  been pointed out, the distribution of lead
within the fetus at different stages of development is
probably more important than the total amount pre-
sent at birth.
  Tissue analysis also demonstrates that, in Ameri-
cans from newborns through persons aged  19  years,
brain lead levels appear to be most elevated at birth
and then diminish  with development.
  A number of studies show passage of lead through
the placental barrier by  comparing cord blood lead
and maternal  blood lead  levels.   These studies
further  serve to shed some light on the  effect of
various factors in infant blood lead  values.
  In a group of cord blood/maternal blood match-
ings, infant blood levels  were highly correlated with
those of their mothers. A second study showed that
                                                13-7

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blood values for infants whose mothers were urban
residents were  significantly higher than those of
rural infants.
  A study done in  a  lead-belt area of the United
States raises the possibility that lead may affect the
course of normal delivery  of children since  there
were more  incidents of preterm delivery and pre-
mature membrane rupture in pregnant women in this
region compared to a group from a relatively  unex-
posed area.

13.5.4 Other Health Effects

13.5.4.1  RENAL EFFECTS
  Nephropathy is a condition usually considered in
its  chronic form  and that  can best  be related to
prolonged exposure to  lead  with a corresponding
blood lead level of about 70 /^g/dl. Because chronic
lead nephropathy  results only after prolonged or
repeated exposures, it is impossible to recapitulate
accurately  the  exposure history; therefore, deter-
mination of an exposure threshold for this condition
is impossible.

13.5.4.2 EFFECTS OF LEAD  ON THE  EN-
DOCRINOLOGICAL,   HEPATIC,  CAR-
DIOVASCULAR,  AND   IMMUNOLOGICAL
SYSTEMS
  Although  some studies  have  been done  in
reference to each of the systems in this subsection,
there exists too little quantitative information relat-
ing blood  lead  levels  to  the endocrinological,
hepatic, and cardiovascular systems.


13.5.5  Does-Effect/Response Relationships

  In any discussion of the risk  assessment directed
toward a particular agent, such as lead, two ques-
tions arise:
    1. What are the  lowest levels of the internal
       dose (blood lead level) that give rise to any
       biological effect?
    2. What dose-response  relationships are ob-
       tained  that define a proportion of a popu-
       lation manifesting a given biological effect at
       a particular internal dose?
  Information summarized in the preceding section
dealt with relationships between blood lead levels
and various biological effects of lead. Many of the
data discussed above concerned threshold levels at
which health effects of lead  are first observed  in
different population groups. Table 13-2 summarizes
the threshold  levels  at  which  various  specific
hematological  and neurobehavioral  effects have
been observed for particular subpopulations.
  A number  of investigators  have  attempted  to
quantitate more precisely  lead's  dose-response
relationship, i.e., the proportion of a population ex-
hibiting health effects at a given blood lead level.
                       TABLE 13-2. SUMMARY OF LOWEST OBSERVED EFFECT LEVELS
Lowest observed
effect level
10
15-20
25-30
40
40
40
50
50-60
50-60
80-100
100-120
Effect
ALAD inhibition
Erythrocyte protoporphyrin elevation
Erythrocyte protoporphyrin elevation
Increased urinary ALA excretion
Anemia
Coproporphynn elevation
Anemia
Cognitive (CNS) deficits
Peripheral neuropathies
Encephalopathic symptoms
Encephalopathic symptoms
Population group
Children and adults
Women and children
Adult males
Children and adults
Children
Adults and children
Adults
Children
Adults and children
Children
Adults
 Due to the limited availability of data, most such at-
 tempts have  been  restricted to  effects  on  the
 hematologic system, in particular the elevation of
 FEP, the inhibition of ALAD activity, and the ex-
 cretion of ALA in the urine.

   In regard to defining dose-response  relationships
 for hematological effects, three different assessments
 of such relationships have been carried  out4-6  and
published.  For  example, in  the approach  of
Zielhuis,4  dose-response  relationships  were
developed for ALAD, ALA-U, and FEP as obtain-
ed for adults,  male and  female, and  children. In
Figure 13-1  are presented the dose-response data for
children and adults for ALAD at inhibition levels of
40 and 70 percent. In Figure 13-2, a corresponding
relationship for  urinary  ALA is given for adult
males, and Figure  13-3 presents the corresponding
                                                13-8

-------
data for FEP  in  adult  males,  adult  females,  and
children.
                   30        50        70

                 BLOOD LEAD LEVEL, /Jg Pb/dl
Figure 13-1. Dose-response curve (or percent ALAD inhibi-
tion for adults and children as a (unction  of blood  lead
level.4
                                        Tig/liter
                                  \f  >10mg/liter
          I	L
                            I     I    I
                   30        50        70

                 BLOOD LEAD LEVEL, ,ug Pb/dl
Figure 13-2. Dose-response curve for ALA in urine (ALA-U)
as a function of blood lead level.4

  As can be seen from Figure 13-1, there appears to
be a marked difference at 40 percent  inhibition of
ALAD activity between children and adults, such a
difference decreasing as one goes to 70 percent in-
hibition. For example, at 20 /ng/dl  blood lead, ap-
proximately  10 percent  of adults show 40 percent
enzyme inhibition, whereas the corresponding value
for children is somewhat above 80 percent. It should
also be noted that there is apparently a steep rise in
the linear portion  of these  sigmoid relationships,
e.g., 20 percent of adults show a 40 percent inhibi-
tion in ALAD at 20 /u.g/dl blood lead,  whereas vir-
tually all of the adult population shows 40 percent
inhibition  at 40  jug/dl. A similar  steepness in the
curve is seen in regard to children.
  Figure  13-2 presents dose-response data for ALA
in urine exceeding two discrete levels, >5 and  > 10
mg/liter, with increasing blood lead. It may be seen
that the response in the linear portion of the curve is
much less steep than for ALAD. For example, for
approximately 5  percent of adults, the no-response
 level for ALA >5 mg/liter is about 30 //.g/dl blood
 lead. At 60 /ug/dl blood lead, the corresponding per-
 centage of the population showing this response is in
 excess of  80 percent. The corresponding plot for
 ALA > 10 mg/liter shows a less steep slope than the
 former case. At 60 /ng/dl  blood lead, the corres-
 ponding percentage of the adult population is ap-
 proximately 40.
   The composite dose-response plot presented  in
 Figure 13-3 shows an  increased response in FEP in
 adult females  compared to adult males. Children
 show a greater response than adult males only up to
 blood lead levels of about 45  /ug/dl.  The data  of
 Zielhuis are extracted from a number of reports.  In
 Figure 13-4, interestingly, wherein are contained the
                                                      O j
                                                      5 >
 ° fe
 SA
                      30         50

                    BLOOD LEAD LEVEL, us Pb/dl
Figure 13-3. Dose-response curve for FEP as a function of
blood lead level.4
                       20       30

                  BLOOD LEAD LEVEL, wg Pb/dl
Figure 13-4. Dose-response curve for FEP as a function of
blood lead level.5
                                                 13-9

-------
dose-response data of Roels et al.5 for FEP in adult
males, adult females, and children, it  appears that
children  show  the  most  heightened  response,
followed by adult females, and the least response in
adult males. The slope for the linear portion of  the
response curve is quite steep in the case of children;
20 percent of the children show elevated response
(82 /xg/dl rbc) at 20 /ug/dl  blood lead, whereas vir-
tually all the children exceed this value at 35 jtg/dl
blood lead.
  The dose-response data of Piomelli6are presented
in Figure 13-5 and  consist of composite plots  for
mean plus 1  standard deviation (33  /Ag/dl whole
blood) and the mean plus 2 standard deviations  (51
Mg FEP/dl whole blood). In the data presented in
Figure 13-5. blood lead levels in excess of 28 /ug/dl
whole blood were not used in the calculations. It  ap-
pears from the above that there exists a threshold at
about 15 ;Lig/d\ whole blood.
NOTE- POINTS OUTSIDE THE RANGE OF THE SOLID LINES
    WERE NOT USED IN CALCULATIONS
                FEP>MEAN+ 1S.D 133 pg/dll   '
                  BLOOD LEAD LEVEL. Bg Pb/dl
 Figure 13-5. Dose-response curve for FEP as a function of
 blood lead level.6

   EPA has carried out analyses of the data from the
 Azar et al. study7 and calculated a dose-response
 curve for urinary ALA (Figure 13-6).  These dose-
 response curves were plotted for two different cut-
 off points. These points were  the mean  values for
 blood lead levels less than 13/ig/100 g, plus 1 stan-
 dard  deviation  and plus 2 standard  deviations,
 respectively. From the mean plus 2 standard devia-
 tions curve, it is readily apparent that the linear por-
 tion of the curve is quite steep. At a blood lead level
 of 20 jtxg/dl, only 6 percent of the population exceed
 the  mean plus 2 standard deviations value of the
 control population, whereas  at a blood  lead level of
 50, 50 percent of the population exceeds that value.
 Furthermore, when one examines the  figure at  40
                                                   the value at which ALA in urine is taken to
                                             suggest health impairment, the Azar et al. data show
                                             that about  30 percent of the population  shows an
                                             elevation in this parameter.
                                             < 80
                                             S
                                             250
                                                    1
T
T
                                                                              MEAN + 1 S D
                                                                              MEAN + 2SO
                                                                              MEAN ALA-U = 0 32 FOR BLOOD
                                                                                        LEAD< 13jjg/dl
                                                             BLOOD LEAD LEVEL, fig Pb/dl
                                             Figure 13-6. EPA calculated dose-response curve for ALA-U
                                             (from Azar et al.7).
                                                In Table  I 3-3 are tabulated proportions of the
                                             study populations in  the Zielhuis and  Azar reports
                                             showing elevated  urinary  ALA versus blood  lead
                                             level. The data  for Zielhuis are as cited in Figure
                                             13-2, the percentage of subjects with ALA-U greater
                                             than 5 mg/liter being used. The Azar data in Table
                                             13-3 refer to the mean plus two standard deviations
                                             data  set. For purposes  of comparison  of  dose-
                                             response data for  FEP,  the studies  of  Zielhuis,4
                                             Roels,5 and Piomelli6 are tabulated in Table 13-4.
                                             As in the case for the table of ALA-U data, it should
                                             be kept in  mind  that  differences  exist  in  cut-off
                                             points  for FEP response  to lead  in  the various
                                             studies.
                                               TABLE 13-3. ESTIMATED PERCENTAGE OF SUBJECTS
                                              WITH ALA-U EXCEEDING 5 mg/liter FOR VARIOUS BLOOD
                                                               LEAD LEVELS
Blood lead levels
M9 dl
10
20
30
40
50
60
70
Zielhuis4
0
0
6
24
48
76
96
Azar et al
2
6
16
31
50
69
84
                                                  13-10

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   TABLE 13-4. ESTIMATED PERCENTAGE OF CHILDREN
   WITH EP EXCEEDING CUT-OFF POINTS FOR VARIOUS
                BLOOD LEAD LEVELS
Blood lead
level. M8/dl 2
10
20
30
40
50
60
70
80

ielhuisa°° Roels et al b%
0 3
6 27
22 73
37 100
49
— ^
	
—

Piomelli c°<,
9
11
48
80
_-
__.
_
—
aEP > EP of children with Pb-B < 20 ^S'dl
bEP >8? Mq dl cells
CEP >EP ol 33 Mq dl




 13.6 POPULATIONS AT RISK
  Population  at  risk  is a  segment  of  a defined
population exhibiting characteristics associated with
significantly higher probability of developing a con-
dition, illness, or other abnormal status. This high
risk may result from either greater inherent suscep-
tibility or from exposure situations peculiar to that
group. What is meant by inherent susceptibility is a
host characteristic or status that predisposes the host
to a greater risk of heightened response to an exter-
nal stimulus or agent.
  In  regard  to  lead, two  such populations  are
definable. They are  preschool  age  children,
especially those living in urban settings, and preg-
nant women, the  latter group owing mainly to the
risk to the conceptus. Children are such a population
for  both of the reasons above, whereas pregnant
women  are at  risk primarily due to the inherent
susceptibility of the conceptus.

13.6.1  Children as a Population at Risk
  Children are developing and growing  organisms
exhibiting certain differences from adults in terms of
basic physiologic  mechanisms, capability of coping
with  physiologic stress, and their  relative metabol-
ism of  lead.  Also, the behavior of  children fre-
quently places them   in different relationship  to
sources of lead in the environment, thereby enhanc-
ing  the  opportunity   for them  to   absorb  lead.
Furthermore, the occurrence of excessive exposure
often  is not realized until serious harm is done.
Young children do not readily communicate a medi-
cal history of lead exposure, the early signs of such
being common  to so many other disease  states that
lead is frequently not recognized early as a possible
etiological  factor  contributing to the manifestation
of other symptoms.
 13.6.1.1  INHERENT SUSCEPTIBILITY OF
 THE YOUNG
   Discussion of the physiological vulnerability of
 the young must address two discrete areas. Not only
 should the basic physiological differences be con-
 sidered that one would expect to predispose children
 to a heightened vulnerability to lead, but also the ac-
 tual clinical evidence must be considered that shows
 such vulnerabilty does indeed exist.
   In Chapter 10, Section  10.6 was devoted  to the
 metabolic considerations in identifying susceptible
 subgroups. Factors  discussed  in  that  section in-
 cluded: (1) greater lead intake of infants on a per
 unit body weight basis, which is probably related to
 greater caloric and water  requirement; (2) greater
 intake as  well  as net absorption (see GI section),
 greater net respiratory intake as well  as greater net
 absorption and retention from the GI tract; (3) rapid
 growth rate may reduce the margin of safety against
 a variety  of  stresses including iron,  calcium,  and
 vitamin deficiency; (4) dietary habits of children are
 quite  different  from adults; normal hand-to-mouth
 activity probably results in the transfer of lead-con-
 taminated dust and dirt via thumb sucking or in
 retrieval  of  dirt-contaminated foodstuffs; (5) the
 metabolic requirements for protein,  calcium,  and
 iron are so great relative to intake that  a negative
 balance in these factors may exist; (6)  in very  young
 children metabolic pathways and factors such as the
 blood-brain barrier are  known to be incompletely
 developed; and (7) partitioning of lead in the bones
 of children is different from that of adults. Only 60
 to 65 percent of the lead body burden is in the bones
 of children, and this fraction may be more labile.
  Hematologic and  neurologic effects in children
 have been shown to have lower thresholds per unit of
 blood lead than in adults.  In particular,  the lowest
 observed effect levels for FEP and anemia are lower
 for children  than adults.  With  reference  to
 neurologic effects, the onset of encephalopathy  and
other  injury to the nervous system appears to vary
 both regarding likely lower thresholds in children
 for some effects  and  in. the typical  pattern  of
 neurologic effects presented, e.g., in encephalopathy
or  other  CNS  deficits being more  common  in
children versus peripheral neuropathy being more
often seen in  adults. Not only are the effects more
acute  in  children  than in adults,   but  also  the
neurologic sequelae are usually much more severe in
children.
  Upon careful examination of the data, it should be
noted that certain geographic or socioeconomic fac-
                                               13-11

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tors appear to emerge as important  factors deter-
mining the differential susceptibility of some groups
of children for  lead-induced  neurologic  damage.
That is, there seems to be distinct variation in effects
or a lack thereof as reported for children in different
studies depending  upon the geographic areas from
which the study populations were drawn. For exam-
ple, the few credible reports of lead encephalopathy
in children at blood lead levels less than 100 /ig/dl
all concern  children  from  inner-city  areas.
Similarly, statistically significant effects or  border-
line  effects  indicative  of more  subtle neurobe-
havioral  deficits  in  lead-exposed  children  at
moderately elevated blood lead levels have been-re-
ported for groups of children drawn from inner-city
populations of urban centers. In contrast, only a few
statistically significant neurobehavioral effects have
yet been reported  for  populations of children ex-
periencing similar  elevations in blood lead levels,
but residing near primary smelter facilities in semi-
rural areas.
   One cannot  determine with any certainty the
specific factors that might contribute to the apparent
differential sensitivity of inner-city children to the
neurobehavioral  effects  of  lead.  Several
possibilities,  however,  might  be  reasonably  con-
sidered, including  the following:

    1. Parameters  of lead  exposure  probably
       differed  substantially  for  the  populations
       under study; the smelter area children, for
       example, may have experienced much more
       gradual  accumulations of  lead  during the
       course  of  long-term,  low-level exposures
       versus probable repeated  brief episodes  of
       somewhat  higher level exposures being
       superimposed on any  long-term, low-level
       exposures for the inner-city children.
    2. The exposures of the smelter children likely
       included significantly higher levels of other
       metallic species, e.g., zinc, that are known to
       reduce the pathological impact  of  lead on
       many organ systems.
    3. Differences in  nutritional status likely ex-
       isted  between  the  smelter  and  inner-city
       children, with the latter probably  having a
       higher  incidence of  iron, calcium,  and
       vitamin deficiency; or  other  differences  in
       dietary content and habits might be invoked
       as an explanation.
    4. Interactions  between  lead  exposures  and
       other  factors associated with  the stresses  of
       urban versus nonurban living may also con-
       tribute to the  apparent  differential suscep-
       tibility of inner-city chilren.

13.6.1.2 EXPOSURE CONSIDERATIONS
  Children's dietary habits as well as the diets them-
selves differ markedly from  adults and, as a result,
place children in a different relationship to several
sources of lead. The dominance of canned milk and
processed  baby  food  in the diet of many young
children is an important factor is assessing their ex-
posure to lead since both those foodstuffs have been
shown  to contain higher amounts of lead than com-
ponents of the adult diet.  The importance of these
lead sources is not their relationship to airborne lead
directly but, rather, their role in providing a higher
baseline lead burden to which the airborne contribu-
tion is  added
  Children ordinarily undergo a  stage of develop-
ment in which they exhibit mouthing behavior, for
example, thumbsucking. At this time they are at risk
of picking up lead-contaminated soil and  dust on
their hands and hence  into their mouths where it can
be  absorbed.  Scientific evidence documenting  at
least the first part of the chain is available.
  There is, however, an abnormal extension of the
mouthing behavior, called  pica, which  occurs in
some  children.  Although diagnosis  of this is
difficult, children who exhibit  this trait have been
shown to  purposefully eat nonfood  items. Much of
the  lead-based paint  problem  is known  to  occur
because children actually ingest chips of leaded
paint.

13.6.2 Pregnant Women  and the Conceptus as  a
Population at Risk
  There are some rather inconclusive data indicat-
ing that women may in general be at somewhat high-
er risk to lead than men. However, pregnant women
and their concepti as a subgroup are demonstrably at
higher risk.  It should  be pointed out that,  in fact, it
really  is not the pregnant woman per  se who is at
greatest risk but, rather,  the  unborn  child she is
carrying.  Because of obstetric complications, how-
ever, the  mother herself can also be at  somewhat
greater risk. This  section  will first describe  the
general evidence for  all women  and then  the evi-
dence  that pertains  to pregnant women exclusively.
  Studies have demonstrated that  women, like
children,  in  general  tend  to  show a  heightened
response of erythrocyte protoporphyrin levels upon
exposure to  lead.  The exact  reason  for this
heightened response is not known but may relate to
endocrine differences  between men  and women. In
                                                13-12

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particular, the levels of testosterone may play a role
in this response.
  As  stated above,  the  primary  reason  pregnant
women are a high-risk group is because of the fetus
each is carrying. In addition, there is some sugges-
tive evidence that lead exposures may affect mater-
nal  complications of delivery.
  With reference  to  maternal complications  at
delivery, information in the literature suggests the
incidence  of preterm delivery and  premature mem-
brane rupture relates to maternal blood lead level.
Further study  of this relationship as well as studies
relating to discrete health effects in the newborn are
required.
  Vulnerability of the developing  fetus to lead ex-
posure arising  from  transplacental transfer  of
mother's blood lead content was discussed in Section
11.6.  This process starts  at the end of the first tri-
mester. Cord blood studies involving mother-infant
pairs  repeatedly have shown a correlation between
maternal and fetal blood lead levels.  Furthermore,
the  observed positive correlation  of  urinary ALA
levels with blood lead levels in newborns indicates
that some heme-biosynthetic derangement is  ap-
parent at birth and must therefore have commenced
in utero.
  Further suggestive evidence, cited in Chapter 11,
has been  advanced for prenatal lead exposures of
fetuses possibly leading to later higher instances of
postnatal mental retardation among the affected off-
spring. The available data  are  insufficient to state
with any certainty that such effects occur or to deter-
mine with any precision what levels of lead exposure
might be required  prior to or during pregnancy in
order to produce such effects.
 13.7  DESCRIPTION OF U.S. POPULATION IN
 RELATION  TO PROBABLE LEAD  EX-
 POSURES
   In this section estimates are provided of the num-
 ber of  individuals potentially at  risk  to lead  ex-
 posures. Unfortunately the latest census data  are
 only from 1970,8 although some estimates are avail-
 able from the National Center for Health Statistics
 for 1975.9 This is unfortunate since some significant
 changes are thought to have occurred in the popula-
 tion structure since the 1970 census.
   Because most lead exposures, excepting areas with
 primary lead smelters, occur in what the Bureau of
 the Census calls urban areas, an estimate of the po-
 tential risk of airborne lead exposure can be made
 from the total urban population of the United States.
 That  this may be an acceptable first approximation
 can be gleaned by  comparing the  frequency distri-
 bution of air lead concentrations for urban and rural
 National Air Sampling Network stations in Chapter
 7.  This comparison   readily  shows  a  distinct
 difference in exposure  between the two types of sta-
 tions. Based on examination of the urban stations as
 well as of literature data on both  air  lead and  soil
 and dust lead values, a strong case can be made to
 support the  assumption that the area which  the
 Bureau of the Census calls the central city of the ur-
 ban areas is at even higher risk of lead exposure.
   Therefore, in  regard to  exposures  other  than
 localized  point  stationary  sources  of lead,   the
 population at risk is the urban one and, in particular,
 the central city  residents. For  the United States in
 1970, these values were 149 and 64 million  people,
 respectively8 (Table 13-5). From  the  table it  can
        TABLE 13-5. POPULATION AND PERCENT DISTRIBUTION, URBAN AND RURAL, BY RACE 1970 CENSUS4
Area
Urban
Inside urbanized areas
Central cities
Urban fringes
Outside urbanized areas
Rural
Total. United States
White °,
H03>
128.773(724)
100.952(568)
49.547(279)
51,405(289)
27.822(15.7)
48.976 (27 6)
1 77 773
Black and
other °0
HO3)
20,552 (80 7)
17,495 (68.7)
14,375 (565)
3,120(123)
3,057 (12.0)
4,911 (19.3)
25.463
Total %
HO3)
149.325(735)
118.447(58.3)
63,922 (31 5)
54,525 (26.8)
30,878(15.2)
53.887 (26.5)
203,212
readily be seen that a higher proportion of the non-
white population lives in urban areas than whites
(80.7 versus 72.4 percent) and is possibly subject to
greater exposure to airborne lead. Furthermore, this
disparity is even greater when  one considers the
central city population only, which may be subject to
even higher levels of lead pollution from a multitude
of sources.
  From the previous discussion of populations at
risk, however, two subgroups of this total population
were  defined  as  being  at  even  higher  risk —
children,  especially those under  5, and  pregnant
                                                13-13

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                      TABLE 13-6. NUMBER OF BIRTHS BY RACE AND SIZE OF POPULATION8
Urban areas of qiven
size from 1970 census
                                               White
                                                                 Black
                                                                                   Others
                                                                                                  Total
  > 100,000
  50-99.999
  10-49,999
    59,999
 772.230
 286.706
 600.166
1.432.162
321.412
 37,024
 65790
148 136
24,394
 4182
10.394
28790
1.118.036
 327,912
 676.350
1.609,088
  Total
                                             3 091 264
                                                                572.362
                                                                                   67.760
                                                   3.731.386
                                                                       Births
urban areas ot given
size from 1975 census
> 100,000
50-99,999
10-49,999
59,999
Total
White
571.478
222.735
478.382
1.279.401
2.551 996
Black
276.387
37.885
64481
132828
511.581
Others
26.332
5.921
13.039
35.329
80.621
Total
874.197
266.541
555.902
1.447.558
3.144 198
women. There is insufficient evidence at this time to
determine whether any racial or ethnic group suffers
an innate susceptibility to lead.
  In  the  United  States  in  1970  about  12 million
children under 5 years of age  lived in urban areas.
Approximately 5 million of these children lived in
central city areas.8 Since between-census  population
estimates  are  not available for  urban-rural com-
parisons, the only way to  use  the 1975  population
estimates is to assume that the percent distribution
obtained in 1970 still holds true. If in fact that is the
case, the  more recent estimates would be  about  11
million children, in urbanized areas and 4.6 million
in the central city. An estimate  made by the National
Bureau of Standards of the total child  population
with  blood lead values equal to or greater than  40
yttg/dl in a recent year was 600,000.10 This total is
clearly a cause for concern in view of the health data
presented  in Section  13.4 above.  Of course, the use
of this figure, based on the many lead-screening pro-
grams conducted in this country, is not meant to im-
ply that all  of these  values resulted from airborne
          lead.  They probably do not, since paint  lead  ex-
          posures are an additional important source. But, on
          the other hand,  the addition of an airborne com-
          ponent of lead exposure on top of these levels would
          adversely affect the public health. If airborne lead
          were the only contribution to these children's lead
          values, the potential health effects ascribable to that
          exposure could be significant.
            The difficulty  in estimating the number of preg-
          nant women exposed to air lead is even greater;  this
          is  because the number of pregnant women is  not
          tabulated on  an urban-rural basis. Therefore,  for
          this document, the number of pregnant women will
          be estimated from  the number of live births (Table
          13-6).8  Unfortunately these data also are not tabu-
          lated  on  an  urban-rural  basis but,  rather, on  a
          population size of  place of residence. It can readily
          be seen that the total  number of births has declined
          in  the time 1970 to 1975. If one assumes only  the
          highest  population size category to be at risk of lead
          exposure, there are still almost 900,000 newborns at
          risk of lead absorption from their mothers.
 13.8  REFERENCES FOR CHAPTER 13
   1  Nordman.C H Environmental lead exposure in Finland.
     A  study on selected  population  groups  Dissertation.
     University of Helsinki. Helsinki 1975
   2. Fmney, D.  J.  Statistical method  in biological assay.
     Charles Griffin and Co.,  London  1971  p. 5.
   3  Hernherg,  S.  Biochemical.  Suhchnical  and Clinical
     Responses to Lead and Their Relation to Different Ex-
     posure Levels, as Indicated by the Concentration of Lead
     in Blood In. Effects and  Dose-Response Relationships of
     Toxic  Metals. G.  F. Nordberg (ed ). Elsevier Scientific
     Publishing Co . Amsterdam 1976  Part B15
            4  Zielhuis. R. L Dose-response relationships for inorganic
               lead- I Biochemical  and hematological  responses.  Int.
               Arch Occup. Hlth  J5-1-18, 1975
            5  Roels, H ,  Buchet, J  P., R. Lawrie, and G. Hubermont.
               Impact of air pollution by lead on the heme biosynthetic
               pathway in school-age children.  Arch  Environ. Hlth.
               31 310-316, 1976.
            6  Piomelli. S  Reanalysis of data from S. Piomelh, C. Sea-
               man. D, Zullow, A. Curran. and B. Danidow Metabolic
               evidence of lead toxicity  in "normal"  urban children
               Clin. Res.  25.-495A.  1977  Presented to  Environmental
               Protection  Agency  staff and consultants.  Research
               Triangle Park. N.C September 28. 1977.
                                                   13-14

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A?ar. A . R  D Snee. and K Hahihi  An epidemiological       9   U S National Center for Health Statistics, Vital Statistics
approach to  community air lead exposure  using personal           ot the  U  S ,  1975, Data tor 1975  Births Unpublished -
air samplers  Environ Qual Sat'. Suppl  II 254-290. 1975           provided by NCHS
U  S  Bureau of  the Census, Statistical Abstracts of the      10   National  Bureau  of  Standards  Survey  Manual  for
United States 1976 (97th Ed )  Washington, D C  1976 p           Estimating the Incidence of Lead Paint in Housing. NBS
1 8, Table  19                                                  Technical Note 92 1. September 1976
                                                  13-15

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                                      APPENDIX A
                                       GLOSSARY*
Absorption (of lead): Transfer of lead into an organ-
  ism via intestinal wall, alveolar surface, or skin.
Accumulation (of lead):  Net positive difference be-
  tween intake and output of lead over an extended
  period.
Acetyl coenzyme A (CoA): Coenzyme, derived prin-
  cipally from the metabolism of glucose and fatty
  acids, that takes part in many biological acetyla-
  tion reactions; oxidized in the Krebs cycle.
Acetylcholine: Compound  released  from  certain
  autonomic nerve endings; acts in the transmission
  of nerve impulses to excitable membranes.
Acetylcholinesterase: Enzyme  in excitable
  membranes that inactivates acetylcholine.
(3-Acetyl glucosaminadase: Enzyme that hydrolyzes
  the terminal glucosaminidic bonds of odd-num-
  bered oligosaccharides to  yield N-acetyl-
  glucosamine and the next lower even-numbered
  oligosaccharide.
Acid-fast: Describes a cell or bacterium that retains
  a dye that has a negatively charged molecule.
Acid phosphatase: Enzyme  that hydrolyzes, in an
  acid  medium,  monophosphoric  esters,  with
  liberation of inorganic phosphate.
Adenocarcinoma: Carcinoma derived from glandu-
  lar tissue or in which the tumor cells form recog-
  nizable glandular structures.
Adenoma: Benign epithelial tumor in which the cells
  form recognizable  glandular  structures or  in
  which the cells are clearly derived from glandular
  epithelium.
Adenosine  diphosphate  (ADP):  Coenzyme  com-
  posed  of adenosine  and  two  molecules of
  phosphoric acid; important in intermediate cellu-
  lar metabolism; a  product of the  hydrolysis of
  adenosine triphosphate (ATP).
 Adenosine triphosphate (ATP): Nucleotide occur-
   ring in all cells, where it serves in the storage of
   energy and in the transfer of energy in metabolic
   processes; composed  of adenosine and  three
   molecules of phosphoric  acid.
 'Compiled from standard reference works and. to a lesser extent, from information
furnished by experts in the respective disciplines
Adenosine triphosphatase (ATPase): Enzyme that
   mediates the removal of water from ATP: ATP +
   H2O—>ADP + orthophosphate.
Adenyl cyclase:  Enzyme that catalyzes the forma-
   tion  of cyclic adenosine-3', 5'-monophosphate
   (cyclic AMP).
Adenylic  acid: (1)  Generic name  for  a  group of
   isomeric nucleotides; (2) Phosphoric acid ester of
   adenosine;  also  known as  adenosine
   monophosphate (AMP).
Adrenaline: See Epinephrine.
Adrenergic:  Describes  the  chemical  activity  of
   epinephrine or epinephrine-like substances.
Adrenergic synapse:  Synapse  at  which
   norepinephrine is liberated when  a nerve impulse
   passes.
Advection: Process  of transport of an atmospheric
   property, or substance within the atmosphere,
   solely by the mass motion of the  atmosphere.
Aerodynamic diameter: Expression  of aerodynamic
   behavior  of an  irregularly shaped  particle  in
   terms of the diameter of an idealized particle; that
   is,  aerodynamic  diameter is the diameter of  a
   sphere  of unit  density  that has aerodynamic
   behavior identical to that of the particle in ques-
   tion. Thus, particles  having the  same  aero-
   dynamic diameter may have different dimensions
   and shapes.
Aerodynamic drag: Aerodynamic resistance; retard-
   ing force that acts upon a body moving through a
   gaseous fluid and that is  parallel with the  direc-
   tion of motion of the body.

Aerodynamic particle size:  Sphere  of unit density
   that has aerodynamic behavior identical to that of
   the particle in question.

Aerosol: System in which the dispersion medium is a
   gas and the dispersed phase—composed of solid
   particles or liquid droplets—does not settle out
   under the influence of gravity.
Aerosol particles: Solid particles 10-'2to 10-' ^.m in
   diameter, dispersed in a gas.
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Agglomeration: Process by which precipitation par-
  ticles grow by collision with an assimilation  of
  cloud particles or other precipitation particles.
Aitken dust counter:  Instrument for  determining
  dust content of the atmosphere; a sample of air is
  mixed, in an expandable chamber, with a large
  volume of dust-free air containing water vapor.
  Upon  sudden  expansion,  the chamber  cools
  adiabatically below its dewpoint, and droplets
  form with the dust particles as nuclei and are
  counted by means of a grid under a microscope.
Aitken  nuclei:  Microscopic  particles  in  the at-
  mosphere that serve as condensation  nuclei for
  droplet growth during the rapid adiabatic expan-
  sion produced by  an  Aitken  dust counter (see
  above).
Aldolase: Enzyme that acts on a ketose-1-phosphate
  to yield  dihydroxy-acetone phosphate plus an
  aldehyde; e.g., fructose-1,  6-diphosphate  =
  d ihydroxy acetone phosphate   + D-
  glyceraldehyde-3-phosphate.
Alkaline phosphatase: Enzyme that  hydrolyzes,  in
  alkaline  medium,  monophosphoric esters, with
  liberation of inorganic phosphate; found  in
  plasma and serum, bone, etc.
Alkalinity:  Excess of hydroxyl ions  over hydrogen
  ions, generally expressed as milliequivalents per
  liter.
Alveolar  macrophages: Rounded  granular
  phagocytic cells, within the alveoli of the lungs,
  that ingest inhaled material.
Ambient air: The surrounding, well-mixed air.
Aminoacyl  synthetase:  Enzyme that catalyzes the
  coupled  reactions  of amino acid activation  in
  which an amino acid is first attached to adenosine
  monophosphate  and  then  to  a  transfer-RNA
  molecule.
e-Amino group of lysine: The amino group, NH2, at-
  tached to e, or 5th, carbon atom from the carbox-
  yl carbon in the amino acid,  lysine: H2N-CH2-
  CH 2-CH 2-CH 2-CH (NH 2)-COOH.
8-Aminolevulinic  acid (ALA, or 8-ALA): COOH-
  CH2-CH2-CO-CH2-NH2; intermediate in the bio-
  synthesis of heme-containing compounds; formed
  from succinyl-coenzyme A and glycine.
8-Aminolevulinic acid  dehydratase  (ALAD):
  Enzyme  in heme biosynthetic pathway that medi-
  ates formation of  porphobilinogen from  8-
  aminolevulinic acid.
8-Aminolevulinic acid synthetase (ALAS):  Enzyme
  in heme biosynthetic  pathway that mediates the
  formation of 8-aminolevulinic acid  from suc-
  cinyl-CoA via 2-amino-3-ketoadipate.
Amphetamine: a-Methylphenethylamine.  Drug
  used to stimulate the central nervous system, in-
  crease  blood  pressure,  reduce  appetite, and
  reduce nasal congestion.  Abuse may lead to de-
  pendence, characterized by strong psychic depen-
  dence associated with an increase in REM (rapid-
  eye-movement)  sleep,  hunger,  apathy, and
  depression.
Anamnestic  response: Rapidly increased  antibody
  level  following renewed  contact with a specific
  antigen, even after several years.
Anodic stripping voltammetry: An  electrochemical
  method of analysis.
Anophthalmia: Developmental defect characterized
  by complete absence of the eyes or by the presence
  of vestigial eyes.
Anorexia: Loss of appetite.
Anoxia: Relative lack of oxygen; caused by inade-
  quate perfusion of tissues by blood carrying nor-
  mal amounts of oxygen or by normal perfusion of
  blood carrying reduced amounts of oxygen.
Antipyrine (CnH,2ON2): Compound used as an an-
  tipyretic, analgesic, and antirheumatic drug.
Area source: Consists of a number of point sources
  arranged in  a two-dimensional array.
Astrocytic proliferation (astrocytosis): Proliferation
  of astrocytes owing to the destruction of nearby
  neurons during  a hypoxic  or hypoglycemic
  episode.
Ataxia: Failure of muscular coordination.
Atmospheric turbulence: Motion of the air (or other
  fluids)  in which  local velocities and pressures
  fluctuate irregularly in a  random manner.
Avoidance task: Behavioral testing procedure used
  to measure an animal's avoidance and escape per-
  formance. In a one-way task only one response is
  appropriate, whereas in a two-way task either of
  two responses is  appropriate, depending on the
  existing test conditions.
Axonal  degeneration: Degeneration of axons, the
  processes or nerve fibers  that carry the unidirec-
  tional  nerve impulse  away from the nerve cell
  body.
Balance experiments: Experiments on man or other
  animals that involve quantitative measurements
  of intake (via respiration  and ingestion) and loss
  (via exhalation and excretion) of a specific ele-
  ment or substance. A positive balance means that
  more is taken in than is lost over a specific time.
Basophilic  stippling:  Spotted  appearance  of
  relatively immature red blood cells that contain
  cytoplasmic material that stains deeply with basic
  dyes.
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Biosphere: The part of the earth's crust, waters, and
   atmosphere where living organisms can subsist.
Blood-brain barrier: The  barrier  created by semi-
   permeable cell walls and membranes to passage
   of some molecules from the blood to the cells of
   the central nervous system.
Body burden: The total amount of a specific sub-
   stance (for example, lead) in an organism, includ-
   ing the amount stored, the amount that is mobile,
   and the amount absorbed.
Bond energy: The enthalpy change that accompanies
   the  breaking of a  chemical  bond between  two
   atoms. The total bond energy of a molecule gives
   a measure of its thermodynamic stability.
Boundary layer:  Layer of fluid in the  immediate
   vicinity of a bounding surface; refers ambiguously
   to the (1)  laminar, (2) turbulent, (3) planetary, or
   (4) surface boundary layers.
Brainstem: Stemlike portion of the brain connecting
   the cerebral hemispheres with the spinal cord.
Bremsstrahlung: Radiation  that is  emitted by an
   electron  accelerated  in  its  collision  with  the
   nucleus of an atom.
Brownian movement:  Random movements  of  dis-
   persed  small  particles  suspended in a  fluid;
   results from random  collisions between  the
   molecules of the dispersing medium and the parti-
   cles of the dispersed phase.
CaEDTA: Edathamil  calcium disodium, which is
   the  calcium  disodium salt  of  ethylene-
   diaminetetraacetate, a chelating agent. CaEDTA
   is used in the study, diagnosis,  and treatment of
   poisoning  by various  heavy metals, including
   lead.
CaEDTA mobilization test: Test in which a known
   quantity of CaEDTA is injected parenterally  and
   the amount of lead excreted in  urine during a
   known period beginning immediately thereafter is
   measured. This procedure is used both clinically
   and  experimentally and is thought to provide an
   index  of the mobile fraction of the total body
   burden of lead.
Carcinogenesis: Development of carcinoma; or, in
   more recent usage, producing any kind of malig-
   nancy.
Carcinoma:  Malignant new  growth made up of
   epithelial  cells tending to infiltrate the surround-
   ing tissues and  give rise to metastases.
Cascade impactors: Low-speed impaction device for
   use in sampling both solid and liquid atmospheric
   suspensoids; consists of four pairs of jets (each of
   progressively smaller  size)  and sampling plates
   working in series and designed so that each plate
   collects particles of one size range.
Catalase:  Enzyme that catalyzes the decomposition
   of hydrogen peroxide;  contains  four  hematin
   groups per molecule; found in liver and red blood
   cells.
Catecholamines: Group of sympathomimetic amines
   containing  a  catechol  moiety;  especially
   epinephrine, norepinephrine, and dopamine.
Catenation: Property of an element that enables it to
   link to itself to form chains, e.g., carbon.
Cerebellum: Large  dorsally projecting part  of the
   brain having the special function of muscle coor-
   dination and maintenance of equilibrium.
Cerebral  anoxia: Relative  lack of oxygen  in  the
   brain.
Cerebral cortex: Thin layer of gray  matter on  the
   surface of the cerebral hemisphere,  folded  into
   gyri, with about two-thirds  of its area buried in
   the depths of the fissures.
Chelate:  Chemical compound  in  which a  metallic
   ion  is  sequestered and  bound into  a  ring by
   covalent bonds to two or more nonmetallic atoms
   in the same molecule.
Chelant: Chemical compound  that will  react with
   metals to form chelates; a chelating agent.
Cholinergic: Stimulated,  activated,  or  transmitted
   by acetylcholine;  applied to those nerve fibers
   that liberate acetylcholine at  a synapse when a
   nerve impulse passes.
Cholinesterase: Enzyme that catalyzes  the  hy-
   drolysis of acylcholine to choline and an anion.
Chemical  energy: Energy produced or absorbed in
   the process of a chemical reaction.
Chi-square test: Test of statistical significance based
   on frequency of occurrence;  used to test pro-
   babilities or  probability  distributions (goodness
   of fit), statistical  dependence  or  independence
   (association),  and  common  population
   (homogeneity).
Chlorinity: Measure  of chloride content, by mass
   (g/kg), of water; sometimes determined to permit
   calculation of salinity.
Choroid plexus: Any of the highly vascular, folded
   processes that project into the third,  fourth,  and
   lateral ventricles of the brain.
Chromatid: One of the pair of stands, formed by
   longitudinal  splitting of a chromosome,  that are
  joined by a  single centromere in somatic cells
   during mitosis; one of a tetrad of strands formed
   by  lengthwise splitting of paired  chromosomes
   during the diplotene stage of meiosis.
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Chromophore: Any chemical group whose presence
  gives a decided color  to a compound and that
  united with certain other groups to form dyes.
Chromosomes: Threadlike structures in  animal  or
  plant nuclei, seen during karyokinesis (nuclear
  division characteristic of mitosis), that carry the
  linearly arranged genetic material.
Chronic nephritis: Chronic inflammation  of the kid-
  neys.
Coagulation:  Process that  converts  numerous
  droplets into  a smaller  number of larger pre-
  cipitation particles.
Coalescence:  Merging of two liquid drops into a
  single larger drop.
Colic: Paroxysmal pain in the abdomen, caused by
  spasm, distention, or obstruction of any one of the
  hollow viscera.
Colloidal materials: See Colloidal system.
Colloidal system: An intimate mixture of two sub-
  stances, one of which, called the dispersed phase
  (or colloid), is uniformly distributed  in a finely
  divided state through the second substance (dis-
  persion medium); the dispersion medium may be
  a gas, liquid, or solid.
Combustion nucleus: Condensation nucleus formed
  as a  result of  industrial or natural combustion
  processes.
Complement: Complex proteins in normal serum
  that interact to combine with  antigen-antibody
  complex, producing lysis when the antigen is in an
  intact cell; important in host  defense mechanism
  against invading microorganisms.
Complex: Chemical compound in which a part of the
  molecular bonding is of the coordinate type.
Complexing:  Formation of a complex compound;
  see Complex.
Condensation: Physical process by which  a vapor
  becomes a liquid or solid; opposite of evapora-
  tion. In  meteorology,  the  term is  limited to
  transformation of vapor to a  liquid.
Condensation nucleus: Particle,  either liquid  or
  solid, upon which condensation of water vapor
  begins in the atmosphere.
Condensation particles: See Aitken nuclei.
Confidence interval: A range of values (a, 
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Cumulative frequency distribution: Proportion of a
  distribution that lies below a given value.
Curie:  Unit  of  radioactivity;  quantity  of  ra-
  dionuclide that has 3.7 x  1010 disintegrations per
  minute (dpm).
Cysteine: Amino acid that occurs as a constituent of
  glutatione and of cystine.
Cytochrome c: Small heme protein containing one
  atom of iron per molecule; its principal biologic
  function  is  in  electron  transport.  See
  Cytochromes.
Cytochrome  c oxidase  (cyt. a3): Enzyme  that
  catalyzes  the  oxidation  of  Cytochrome c:  4
  reduced  Cytochrome c  + O2  =  4  oxidized
  Cytochrome c + 2H2O.
Cytochrome c reductase: Enzyme that catalyzes the
  reduction of oxidized cytochrome c: NADH2 +
  oxidized cytochrome c  =  NAD  +  reduced
  cytochrome c.
Cytochrome P-450: a 6-type cytochrome, one of the
   mixed-function  oxidases in  the  microsomal
   system responsible for the oxidation of steroids
   and drugs  and other foreign compounds.
Cytochromes: Complex  protein/heme  respiratory
   pigments occurring  in  plant and animal cells,
   usually in mitochondria, that function as electron
   carriers in biological oxidation.
Demyelination: Destruction of the myelin, a fatlike
   substance  forming  a sheath  around  the  nerve
   fibers.
Density: Ratio of mass of a substance to the volume
   occupied by it (usually expressed in g/cm3).
Dentine: Also dentin; chief substance or tissue of the
   teeth, that surrounds the tooth  pulp  and  is
   covered by enamel on the crown and by cemen-
   tum on the roots of the teeth.
Denver Development Screening Test: Rating scales
   employed to assess four  areas of child develop-
   ment: (1) gross motor, (2) fine  motor-adaptive,
   (3) personal-social, and (4) language.
Deoxyribonucleic acid (DNA): A nucleic acid in the
  form  of a doublestranded helix  of  a   linear
  polymer; made up of repeating units of 2-deoxy-
   ribose, phosphate, and a  purine or a pyrimidine;
  carrier of  genetic information coded  in the se-
   quence of purines or pyrimidines (organic bases).
Deposition: (1) Deposit of particles from the am-
  bient  air  or  atmosphere  onto a  surface;  (2)
  removal  of particles from inhaled air by  the
  respiratory tract.
Detection limit: A limit below which an element or
  compound can not be detected by the method or
  instrument being used for analysis.
Dichotomous  sampler:  Air-sampling  device that
  separates particulates into two fractions on the
  basis of diameter; the cutpoint varies with the size
  of the  aperture.
Diffusion: In  meteorology, the exchange  of  fluid
  parcels between regions in space in apparently
  random small-scale motions.
p-Dimethylaminobenzaldehyde: Ehrlich's  reagent;
  (CH3)2N-C6H4.CHO.
Diphenylthiocarbazone: See Dithizone.
Dispersion: Distribution of finely  divided particles
  in a medium.
Dithizone:  Diphenylthiocarbazone; C6H5N:N-CS-
  NH-NH-C6H5; reagent used in the  analysis of
  lead.
Dithizone  methods: Colorimetric methods  of
  analysis for lead that involve the reaction of lead
  with dithizone to form lead dithizonate, which is
  measured spectrophotometrically at 510 nm.
Dopamine: Hydroxytyramine, produced  by the
  decarboxylation  of dopa (dihydroxy-
  phenylalanine), which is an intermediate product
  in the  synthesis of norepinephrine.
Dorsal root ganglion: Group of sensory nerve cell
  bodies located on the posterior root of each spinal
  nerve; joins peripherally with ventral, or motor,
  root to form the nerve before it passes outside the
  vertebral column.
Downwind:  In the same direction that the wind is
  blowing; on or toward the lee side.
Dry deposition: The deposit of particles on a surface
  in the  absence of precipitation.
Dust: Solid materials suspended in the atmosphere
  in the  form of small irregular particles, many of
  which  are microscopic in size.
Dustfall: Dry deposition of airborne dust particles.
Dysoria:  Any abnormality  of vascular permeability.
E. coli: Short, gram-negative,  rod-shaped, enteric
  bacterium.
Edema: Presence  of abnormally large amounts of
  fluid in the intercellular tissue spaces of the body;
  usually applied to the  demonstrable  accumula-
  tion of excessive fluid in the subcutaneous tissues.
Electromyographic:  Pertaining  to electromyogra-
  phy, the  recording  and study of the  intrinsic
  electrical properties of skeletal muscle.
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Electron  microprobe:  X-ray  method  in  which
  electrons from a hot-filament source are acceler-
  ated  electrostatically, then focused  to  an  ex-
  tremely small point on the surface of a specimen
  by  an electromagnetic lens;  method  for non-
  destructive analysis of chemical composition by
  measurement of  resulting backscatter or  other
  phenomena.
Electronegativity: Electro-affinity.
Encephalitis: Inflammation of the brain.
Encephalopathy: Any degenerative disease  of  the
  brain.
Epidemiology: Study of the  distribution and deter-
  minants of disease in  human population groups.
Epinephrine: Hormone secreted by adrenal medulla
  that acts to increase blood pressure by means of
  stimulation of heart action and constriction of pe-
  ripheral blood vessels.
Episodal: Adjective in current usage that denotes an
  air pollution episode; that is  the occurrence of
  short-term,  peak  air  pollutant concentrations of
  crisis proportions.
Epithelial: Pertaining to  or composed of epithelium;
  that is, covering of external or internal body sur-
  faces, including linings of vessels and other small
  cavities, composed  of cells joined together with
  cementing substances.
Equilibrium vapor  pressure: Vapor pressure of a
  system in which two or more phases of a substance
  coexist in equilibrium.
Erosion: Movement of soil or rock from one point to
  another by  the action of  the sea, running water,
  moving ice, precipitation, or wind.
Erythrocyte porphyrin:  See Free  erythrocyte pro-
   toporphyrin.
Erythrocyte protoporphyrin: See Free Erythrocyte
   portoporphyrin.
Erythrocytes:  Red blood cells.
Erythropoiesis: Formation of red blood cells.
Ethylenediaminetetraacetic  acid (EDTA): Used in
   the form of calcium-disodium salt as a chelating
   agent to complex with lead and other metals and
   remove them from the body by urinary excretion.
Evaporation: Physical process by which a liquid or
   solid is transformed to the gaseous state; opposite
   of condensation.
Evoked-response technique: A  technique  widely
   used in  electrophysiology in which a stimulus
   (e.g., electric shock,  light flash, click) is applied
  peripherally to the electrode  used to  detect the
   response.
Exencephaly:  A  developmental anomaly  charac-
  terized by an imperfect cranium, the brain lying
  outside the skull.
Exposure level: Concentration of a contaminant to
  which the population in question is exposed.
Exudate-. Material, such as fluid, cells, or  cellular
  debris, that has escaped from blood vessels and
  has been deposited in tissues or on tissue surfaces,
  usually as a result of inflammation; contains high
  content  of protein, cells, or  solid  materials
  derived from cells.
Fallout: In air pollution, paniculate matter that falls
  to the surface of the earth through the action of
  gravity;  a passive phenomenon  unrelated to at-
  mospheric or mechanical motion.
Fanconi syndrome: In this document, the  triad of
  glycosuria,  hyperaminoaciduria,  and   hy-
  pophosphatemia  in the  presence  of  hy-
  perphosphaturia that is associated with injury to
  proximal renal tubular cells.
Flinch/jump  thresholds:  Behavioral  testing  pro-
  cedure used to measure pain threshold by measur-
  ing sensitivity  to shock.  The shock intensity at
  which animals first flinch  and  first  jump in
  response to foot shock is recorded.
Flux: Rate of flow of  some quantity, often used in
  reference to some form  of energy; also called
  transport.
Fornix: General term for an archlike structure or the
  vaultlike space created by such a structure; fornix
  of cerebrum—efferent pathway of the hippocam-
  pus.
Free erythrocyte  porphyrin  (FED):  See Free
  erythrocyte protoporphyrin.
Free erythrocyte protoporphyrin (FEP): Intermedi-
  ate in the biosynthesis of heme; specifically, the
  immediate precursor to heme synthesis in which
  one  atom  of iron  is  inserted into  the  pro-
  toporphyrin nucleus to  form heme.  Used  in-
  terchangeably  with erythrocyte  protoporphyrin
  and erythrocyte porphyrin.
Fugitive dust: Dust that escapes from industrial pro-
  cesses, soil surfaces, roadways, etc.; dust that can-
  not be contained by air pollution  control prac-
  tices.
/3-Galactosidase:  Enzyme that  hydrolyzes galac-
  tosides (compounds containing a sugar and a non-
  sugar component) to produce D-galactose.
Galena: Lead sulfide ore.
Ganglia: Plural  of ganglion, a general  term for a
  group of nerve cell bodies located outside the
  central nervous system; basal  ganglia—masses of
  gray matter in the cerebral hemisphere.
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Gastrointestinal  mucosa: Mucous membrane of the
   stomach and intestine.
Geometric mean: An estimate of the median of a log-
   normal  distribution, calculated as the  anti-
   logarithm of the mean of the logarithms of the ob-
   servations.
Geometric standard deviation: A  measure of disper-
   sion for a  lognormal distribution; it is the anti-
   logarithm  of  the  standard  deviation  of the
   logarithms of the observations.  (Also known as
   standard geometric deviation.)
Glacier: Mass of land  ice flowing slowly (at present
   or in the past) from an accumulation area to an
   area of ablation.
Glacier ice: Any ice that  is or once was part  of a
   glacier.
Glomerular filtration: Filtration of plasma by the
   glomeruli  of  the kidney  that  removes fluids,
   electrolytes,  glucose,  amino  acids, and  other
   small molecules; 80 to 85 percent of water and
   virtually all of the other substances are reab-
   sorbed by the proximal tubules.
Glomerulus: Anatomical term designating a tuft or
   cluster  of  blood vessels  or nerves; often used
   alone to designate renal glomeruli,  which are
   coils of blood vessels, one projecting into the ex-
   panded end or capsule of each of the uriniferous
   tubules of the kidney.
Glucose-6-phosphate  dehydrogenase:  Enzyme im-
   portant in  maintenance of adequate concentra-
   tions of reduced glutathione in  red blood cells.
   Deficiency of this enzyme is inherited as  a  sex-
   linked  trait;  it mediates the reaction, D-
   glucose-6-phosphate +  NADP =  D-glucono-8-
   lactone 6-phosphate + NADPH2.
/3-Glucuronidase:  Enzyme that  mediates  the hy-
   drolysis  of natural and synthetic glucuronides;
   yields /3-D-glucuronate as a product.
Glutamate  dehydrogenase: Enzyme that mediates
   the removal of hydrogen atom(s) from glutamate,
   the salt or ester of glutamic acid,  which is a dicar-
   boxylic amino acid.
Glutathione: Tripeptide that serves as a coenzyme
   and  acts  as  a  respiratory carrier  of  oxygen.
   Reduced glutathione (GSH) is present in red cells
   and is  associated  with  glucose-6-phosphate
   dehydrogenase and  reduced  nicotinamide
   adenine dinucleotide phosphate  in  maintenance
   of red cell  integrity.
Glycosuria: Presence in the urine of glucose, a sim-
   ple sugar formed from more complex sugars and
   normally retained  in the body  as a source of
   energy.
Grignard process: A relatively common synthetic
   procedure for the preparation of organometallic
   compounds from an organomagnesium precursor.
Groundwater: All subsurface water, especially that
   part that is in the zone of saturation.

Half-life: Time required for a system decaying at an
   exponential rate (such as an element in radioac-
   tive disintegration) to be reduced to one-half its
   initial size, intensity,  or numerical amount.
Haze: Fine dust or salt particles dispersed  through a
   portion  of the atmosphere; the  particles are so
   small they cannot be felt or individually seen with
   the  naked  eye,  but  they  diminish horizontal
   visibility and give the atmosphere a characteristic
   opalescent appearance that subdues all colors.
Hematofluorometer: Commercially available porta-
   ble  spectrofluorometer  used  to  measure
   erythrocyte protoporphyrin (porphyrin) directly;
   in wide use in lead screening programs.
Hematopoiesis:  Formation  and  development  of
   blood cells.
Hematopoietic system: System of cells in bone mar-
   row, spleen, and lymph nodes concerned with for-
   mation of cellular elements of the blood.
Hemin:  Crystalline  chloride of heme,
   C34H33N404FeCl.
Heparin:   Mucopolysaccharide  acid occurring
   naturally in various tissues, especially the  liver
   and  lungs; sodium heparin, a mixture obtained
   from  animal tissues, is an anticoagulant used in
   vivo and in vitro.
High-volume sampler: Device for taking a  large
   sample of air in a minimal span of time, routinely
   about  2000 m3/24 hr  (1.38 m3/min), or even as
   high as 2880 m3/24 hr  (2 m3/min).
Hippocampus: Curved elevation in the inferior horn
   of the lateral ventricle of the brain; important
   functional component of the limbic system, the
   system controlling autonomic functions and cer-
   tain aspects of emotion and behavior.
Histidine residue:  One  of the naturally  occurring
   peptide  linkages  in  a  protein,  containing the
   chemical group, imidazole:
                   HC =  C-
                     I      I
                    N    NH
                     V
                       C
                       H
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Homovanillic acid: A methylated metabolite of hy-
  droxytyramine:
                HO
                         \\
CH2-COOH
Hydrocephalus: Condition characterized by abnor-
   mal accumulation of fluid in the cranial vault, ac-
   companied by enlargement of the head, promi-
   nence of the forehead, atrophy of the brain, men-
   tal deterioration, and convulsions.
Hyperactivity: Abnormally  increased activity.
   Developmental  hyperactivity  of children  is
   characterized by constant motion—exploring, ex-
   perimenting, etc.—and is usually accompanied by
   distractibility and low tolerance for frustration. It
   usually abates during adolescence.  May result
   from brain damage or psychoses.
Hyperkinesia: Abnormally increased motor function
   or activity; see Hyperactivity.
Hyperkinetic:  Characterized by  abnormally in-
   creased muscular movement.
Hyperkinetic-aggressive behavior disorder: A dis-
   order characterized by overactivity,  restlessness,
   distractibility, and short attention  span.
Hyperphosphaturia:  Above-normal amounts  of
   phosphate compounds in the urine.
Hyperuricemia: Abnormal  amounts of uric acid  in
   the blood.
Hypochromic anemia: A condition characterized  by
   a  disproportionate  reduction of red  cell
   hemoglobin, compared with  the  volume  of
   packed cells.
Hypophosphatemia: Abnormally decreased amount
   of phosphates in  the blood.
Hypothalamus: Portion  of the  diencephalon that
   forms the floor and part of the lateral wall  of the
   third ventricle of the brain.
Imidazole group: See Histidine residue.
Impactor: General term for instruments that sample
   atmospheric particles by impaction; such devices
   consist of a  housing that constrains  the air flow
   past a sensitized  sampling plate.
Impinger: Device used to sample dust or other parti-
   cles in the air; draws in a measured volume of air
   and directs it through  a jet to impact on a wetted
   surface.
In situ: In the original location.
Interstitial  fibrosis: A  progressive formation  of
   fibrous tissue in the interstices in any structure; in
   the lungs, it reduces aeration of the blood.
In vitro: Outside the living organism.
In vivo: Within the  living organism.
Iron deficiency: A deficiency  of iron-containing
  foods in the diet such  that not enough iron is
  available for incorporation into newly formed
  hemoglobin; iron deficiency within the body may
  also result from poor intestinal absorption of iron
  in spite of a dietary sufficiency.
Ischemia:  Deficiency of blood in a part, caused by
  functional constriction or actual obstruction of a
  blood vessel.
Ischemic:  Pertaining to, or affected with, ischemia.
Isocortex-. Neopallium; that  portion of the cerebral
  cortex  showing stratification and  organization
  characteristic of the most highly evolved type of
  cerebral tissue.
Isokinetic sampling: Taking  a sample of air without
  changing the speed or direction of the air as it en-
  ters the sampler.
Jiggle  platform: Apparatus used in behavioral test-
   ing  to  measure an animal's activity. Generally
   consists of a spring-loaded  platform  equipped
   with a detector for measuring movement.
a-Ketoglutarate: Salt  of a-ketoglutaric  acid,  a
   dibasic keto acid occurring as an intermediate in
   carbohydrate (Krebs cycle) and protein metabol-
   ism.
Kilocalorie: Unit of heat energy equal to 1000 calo-
   ries; also known as large  calorie.

Lactic acid dehydrogenase (LDH): Catalyzes reduc-
   tion of pyruvic  acid by  reduced  nicotinamide
   adenine dinucleotide; prevents buildup of pyru-
   vate in anaerobic glycolysis.
Leached:  Subjected to the  action of  percolating
   water  or other liquid  that removes  the soluble
   substances.
Lead particles: Lead-containing particles.
Lead poisoning (syn. lead intoxication, plumbism,
   saturnism): A disease condition reflecting the ad-
   verse effects  of the absorption  of lead into the
   system.
Lead  subacetate  (syn.  lead  monosubacetate,
   monobasic  lead  acetate):  Pb(C2H3O2)2-2Pb
   (OH)2.
Learning  paradigm: A particular set of experimental
   conditions used to study  learning.
Ligand: A molecule, ion, or atom that is attached to
   the central atom of a coordination compound, a
   chelate, or other complex.
Line source: Consists of a number of point sources
   arranged in a straight  line, usually across  wind
   (see Point source).
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Lipoamide dehydrogenase: Trivial  name for
   lipoamide oxidoreductase; enzyme catalyzing the
   reaction, NAD + dihydro-lipoamide =  NADH2
   + oxidized lipoamide.
Lithosphere: The rigid outer crust of rock on the
   earth, about 80  km  deep;  more recently, with
   development of plate tectonics theory, the outer
   100 km  of the earth's surface.
Lognormal  distribution:  A  variable  whose
   logarithms follow a normal  distribution.
Lumen: The cavity  or  channel   within a tubular
   organ; in this document, intestinal.
Lymphocyte: Mononuclear leukocyte (a white blood
   cell) with a deeply staining nucleus  containing
   dense chromatin; chiefly a product of lymphoid
   tissue, it participates  in humoral and cell-medi-
   ated immunity.
Lysosome:  Submicroscopic  organelle,  found  by
   electron microscope in  many types of cells,  that
   contains various hydrolytic  enzymes and is nor-
   mally involved  in localized intracellular  diges-
   tion.
a-Mannosidase: Enzyme  that catalyzes  the  hy-
   drolysis  of a-D-mannoside to an aocohol and D-
   mannose, a  simple sugar.
Mass median diameter (MMD): Geometric median
   size of a  distribution of particles, based on weight.
Mass median equivalent diameter (MMED): Conve-
   nient parameter for characterizing airborne par-
   ticulates; divides the total mass of aerosol  parti-
   cles into two equal parts: half the mass resides in a
   relatively smaller number of particles larger than
   this  median size and half resides in a relatively
   larger number  of particles  having  diameters
   below this median size.
Maze:  System  of intersecting paths used in tests of
   intelligence  and learning  in experimental
   animals.
McCarthy Scales of Intelligence: A standardized in-
   tellectual assessment instrument (appropriate for
   ages 2.5 to 8.5 yr), consisting of five  subtests
   yielding  individual scores in (1) verbal, (2) per-
   ceptual-performance, (3) quantitative, (4) memo-
   ry, and (5)  motor, as well as yielding a general
   cognitive index comparable to an  intellectual
   quotient (I.Q.) score.
Mean:  Used  synonymously  with the  arithmetic
   mean; that is, the sum of the observations divided
   by the sample size.
Meninges: Three membranes that envelope the brain
   and  spinal cord; the dura mater, pia mater, and
   arachnoid.
Messenger  RNA  (mRNA): Linear  polymer of
   nucleotides that is transcribed from and comple-
   mentary to a single strand of DNA; carries infor-
   mation for protein synthesis to the ribosomes.
Metabolites: End products of metabolic  processes
   that transform one compound into another in liv-
   ing cells.
Microcytic anemia: Condition in which the majority
   of the red cells are smaller than normal.
Micromelia: Developmental anomaly characterized
   by abnormal smallness or shortness of the limbs.
Microsome: One of the finer granular elements of
   protoplasm; part of  the  endoplasmic reticulum,
   site of various metabolic and  synthetic  processes
   including incorporation of amino acids into pro-
   teins.
Mist:  Microscopic and more or less hygroscopic
   water  droplets  suspended in the  atmosphere.
   Relative humidity when  mist  is present is often
   less than 95 percent.
Mitochondria: Small   organelles found  in  the
   cytoplasm of cells; principal sites of generation of
   energy, they  contain  enzymes of the Krebs  and
   fatty acid cycles and the  respiratory pathway.
Mobilizable lead: The fraction of the total  lead con-
   tent of the body that can be removed by chelating
   agents.
Molal: Containing one mole or one gram molecular
   weight in 1000 grams (1 kg) of solute.
Molar: Containing one mole or one gram molecular
   weight of solute  in 1000  ml (1  liter) of solution.
Mole: That amount of chemical compound whose
   mass in grams is equivalent to its formula mass,
   i.e.,  mass numerically equal  to the molecular
   weight and most frequently expressed as the gram
   molecular  weight  (the weight of one  mole ex-
   pressed in grams).
Midbrain:  Mesencephalon;  portions of the adult
   brain derived from the embryonic midbrain.
Miniature end-plate potentials (MEPP's): Small po-
   tential changes in the neighborhood of the  end
   plate representing the response of the membrane
   to release of acetylcholine in quantities  insuffi-
   cient to depolarize the membrane  to threshold
   levels.
Monoamine: Organic compound  to which  an amine
   (-NH2group) is attached; e.g., serotonin.
Monamine oxidase: Flavoprotein that catalyzes the
   aerobic oxidation of physiological  amines to the
   corresponding aldehydes and ammonia; acts upon
   serotonin, a nervous  system regulator, to yield 5-
   hydroxy-indolealdehyde.
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Monominergic: Stimulated, activated, or transmit-
  ted by monoamines; applied to nerve fibers that
  liberate monoamines at a synapse when a nerve
  impulse passes.
Motor skills: Skilled movements that depend on the
  integrity of the nervous system for control.
Mutagenicity:  Property of being  able to  induce
  genetic mutation, i.e., a permanent, transmissable
  change in the genetic material.
Myelopathy. Pathology of the muscle fibers.
Myxedema: Nonpitting edema characterized by dry,
  waxy type of swelling, with abnormal deposits of
  mucin in the skin and  other tissues; associated
  with hypothyroidism.
Nasopharynx:  The  part of the pharynx that lies
  above the level of the  soft  palate; the pharynx
  being the muscular, membranous sac between the
  mouth, the nares, and the esophagus.
National Air Surveillance Networks (NASN): Net-
  works of monitoring stations for sampling air to
  determine extent of pollution. Established jointly
  by Federal and state governments.
Neoplasm:  An  aberrant new growth  of abnormal
  cells or tissue in which the growth is uncontrolla-
  ble and progressive.
Nephritis: Inflammation of the kidney.
Nephropathy: Disease of the kidneys.
Nerve conduction: Passage  of  a  nerve impulse
  manifested  by an electric impulse  that  travels
  along the nerve.
Neuropathy:  Functional disturbances and/or
  pathological changes in the  peripheral nervous
  system; affects the neurons (nerve cells, including
  cell body, axon, and dendrites).
Neuropil: Dense feltwork of interwoven cytoplasmic
  processes of nerve cells and of neuroglial cells in
  the central nervous  system and  in some parts of
  the peripheral  nervous system.
Nictitating membrane: Thin membrane, or inner or
  third eyelid, present in many animals; capable of
  being drawn across the eyeball, as for protection.
Norepinephrine: Hormone secreted by neurons; acts
   as a transmitter substance at the peripheral sym-
   pathetic nerve endings and probably in certain
   synapses in the central nervous system.
Normal distribution (Gaussian distribution): Funda-
  mental  frequency  distribution  of  statistical
  analysis. A continuous variate,  x , is said to have
  a  normal  distribution  or  to be  normally dis-
  tributed if it possesses  a density function, f(x),
  that satisfied the equation:
     f(x) =
            
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 Point source: A single isolated stationary source of
   pollution.
 Polarography:  An  electroanalytical  technique  in
   which the current through an electrolysis cell is
   measured as a function of the applied potential.
 Polyneuropathy:  Disease that involves  several
   nerves.
 Polysomes:  Complex  of ribosomes bound together
   by a single messenger ribonucleic acid (mRNA)
   molecule. Also known as polyribosome.
 Porphobilinogen (PEG): Intermediate in  the bio-
   synthesis  of heme that does not accumulate under
   normal circumstances.
 Porphyrin: Any one of a group of iron-free or mag-
   nesium-free  cyclic  tetrapyrrole  derivatives that
   occur universally in protoplasm. They form the
   basis of the  respiratory  pigments,  such  as
   cytochromes  and  chlorophyll,  of animals and
   plants.
 Precipitation:  Any or all forms  of water particles,
   liquid or  solid, that fall from the atmosphere and
   reach the ground.
 Prevailing wind direction: Wind  direction most fre-
   quently observed during a given period.
 Primary smelting: Extraction  of metal from ore.
 Promotional energy: Energy required to promote an
   electron from its free atom ground state to the hy-
   bridization state required for bonding.
Protoporphyrin (PP): Porphyrin that is the protein-
   free  precursor  to hemoglobin,  myoglobin,
   catalase, and certain respiratory  pigments.
Protoporphyrin IX: An isomer of protoporphyrin.
Proximal convoluted  tubules: Convoluted portion
   of the vertebrate nephron (functional  unit of the
   kidney) lying between Bowman's capsule and the
   loop of Henle; functions in resorption of sugar,
       ,Cl~,  and water.
Psychomotor: Pertaining to motor effects of cerebral
   or psychic activity.
Pyrimidine-5'-nucleotidase: Enzyme  that mediates
   hydrolysis of pyrimidine-5'-phosphate to yeild in-
   organic phosphorus  and  the corresponding
   pyrimidine nucleoside.
Pyrrole: Heterocyclic ring compound, consisting of
   four carbon atoms, one nitrogen atom,  and five
   hydrogen atoms, that  is  a component of
   chlorophyll,  hemin,  and many other important
   naturally occurring substances.
Pyruvate:  Salt of pyruvic acid, an important inter-
   mediate in carbohydrate (Krebs cycle) and pro-
   tein metabolism.
Reentrainment: Resuspension of paniculate matter,
   especially dust, in the ambient air; see text dicus-
   sion of resuspension.
Reference method: In this document, the official, ac-
   cepted  method for sampling and analysis of an
   element or compound; method to  which other
   methods are compared for accuracy  and preci-
   sion, and/or for reporting of data.
Relative humidity: Dimensionless ratio  of actual
   vapor pressure of the air to the saturation vapor
   pressure; usually expressed as percent.
Renal insufficiency: State in which the kidneys are
   unable  to remove a sufficient proportion of the
   effete, or spent, matter of the blood.
Reticulocytosis:  Increase in  the  number  of
   reticulocytes  (young red  blood cells  showing
   basophilic network under vital staining) in the pe-
   ripheral blood.
Ribonucleic acid (RNA): Nucleic acid in the form of
   a  linear polymer, usually a single strand, com-
   posed of  repeating  units  of  nucleotides (the
   organic  bases; adenine,  cytosine, guanine, and
   uracil) conjugated to ribose and kept in sequence
   by phosphodiester bonds.  Involved  in-
   tracellularly in protein synthesis.
Ribosomes: Complex small  particles in the living
   cell,  composed of various proteins  and three
   molecules of RNA; site of synthesis of proteins.
Sampling  error:  Difference  between  a measured
   value and the true value  that results  from sam-
   pling techniques and procedures.
Sampling train: Pollutant collecting device consist-
   ing of a series of components through which an air
   stream  passes. Components  usually  include
   prefitter; pipes or ducts; means for measuring  air
   flow; an air pump; and a detector or sensor that
   gives an immediate  reading  or a  collector  in
   which the pollutant is subsequently measured.
Saturnism: Lead poisoning.
Schwann cell: One of the large nucleated masses of
   protoplasm  lining  the  inner  surface  of  the
   neurilemma,  a  membrane wrapping  the nerve
   fiber.
Secondary smelting: Extraction of metal from scrap
   and salvage.
Sedimentation: The act or process of deposition of
   sediment; can refer (1) to the deposition of air-
   borne particulate matter on a surface or (2) to the
   deposition  and accumulation of solid matter  on
   the bed of a body of water.
Seizure: Sudden onset or recurrence of a disease or
   an attack; specifically, an epileptic attack, or con-
   vulsion.
                                               A-ll

-------
Septum-frontal forebrain: Describes anatomical
  connections in the brain between the septal area
  and  the forebrain.
Sequela: Any lesion or affection that follows or  is
  caused by an attack of disease.
Serotonin: A vasoconstrictor, 5-hydroxytryptamine,
  found in serum and many body tissues, including
  the  intestinal mucosa, pineal body, and  central
  nervous  system, especially  the  hypothalamus,
  midbrain, basal ganglia, and spinal cord; believed
  to be a neurotransmitter that plays a  regulatory
  role in the central nervous system.
Serum  glutamic-oxaloacetic transaminase (SGOT):
  Enzyme  that transfers an  amino group from L-
  glutamic  acid  to  oxaloacetic  acid, forming 8-
  ketoglutaric acid  plus L-aspartic  acid.  Ox-
  aloacetic and 8-ketoglutaric acids are both major
  intermediates in the citric  acid cycle  (Krebs cy-
  cle), the energy-generating cycle.
Serum glutamic-pyruvic transaminase (SGPT):
  Enzyme  that transfers an  amino group from L-
  glutamic  acid  to pyruvic  acid,  forming 8-
  ketoglutaric acid plus L-alanine. 8-Ketoglutaric
  acid is a major intermediate  in the Krebs cycle,
  and pyruvic acid is the immediate precursor  of
  acetylcoenzyme A,  which  combines  with ox-
  aloacetic acid to form citric acid in the citric acid
  cycle (Krebs cycle).
Shuttle box: Two-compartment  chamber used  in
  animal  behavior; the movement from one com-
  partment to the other is  the  behavior  that  is
  studied.
Soret band: Band  in the violet end  of the spectrum of
  hemoglobin.
Spina bifida: Developmental anomaly characterized
  by defective closure of the bony encasement of the
  spinal cord.
Stabilimeter: Device used to measure an animal's ac-
  tivity by measuring  vertical movement  of the
  floor.
Stack  emissions:  Effluents  released  into  the at-
  mosphere  from the exhaust  flue of a building;
   usually refers to pollutants but  can refer to steam
   or other nonpolluting effluents.
Standard  deviation: A measure  of dispersion  or
   variation, usually taken as the  square root of the
   variance.
Standard geometric deviation:  Measure  of disper-
   sion of values  about a  geometric mean; the por-
   tion of the frequency distribution that  is one stan-
   dard geometric deviation to either side of the
   geometric mean accounts  for  68 percent of the
   total samples.
Standard normal  deviation:  Measure of dispersion
  of values about a mean value; the positive square
  root of the average  of the squares  of the  in-
  dividual deviations from the mean.
Stanford-Binet I.Q. Test: A standardized intellec-
  tual assessment instrument (appropriate for ages
  2 yr to adult), yielding a general intelligence quo-
  tient (I.Q.) score.
Steady state exposure: Exposure to an environmen-
  tal pollutant whose concentration remains con-
  stant for a period of time.
Stoichiometry. Numerical  relationship of elements
  and compounds  as reactants and products  in
  chemical reactions.
Stratosphere: Atmospheric shell about 55 km deep
  that begins where the troposphere ends, at  10 to
  20 km from the earth's surface.
Striatum: Corpus striatum; subcortical mass of gray
  and white substance in front of and lateral to the
  thalamus in each cerebral hemisphere.
Stroma: Supporting tissue or matrix of an organ, as
  distinquished  from  its  functional element,  or
  parenchyma.
Subclinical lead poisoning: Toxic effects of lead that
  do not produce clinically  discernible signs.
Succinate:  Salt of succinic  acid, important inter-
  mediate in carbohydrate (Krebs cycle) -and pro-
  tein metabolism.
Succinoxidase: Complex enzyme system, containing
  succinic dehydrogenase  and cytochromes,  that
  catalyzes the conversion of succinate and molecu-
  lar oxygen to fumarate ( a Krebs cycle intermedi-
  ate).
Succinyl coenzyme A: COOH(CH2)2COOH-S-CoA;
  compound  formed  from  succinic   acid  and
  coenzyme A in the citric acid cycle (Krebs cycle).
  It  provides free energy for the synthesis of a
  molecule of ATP and can  participate in acylating
  reactions for the introduction of a succinyl group;
  it also participates in other metabolic reactions,
  such as the synthesis of porphyrins.
Sulfhydryl group:  The -SH  group  occurring  in
   reduced glutatione and  in cysteine.
Superior cervical ganglion:  A group of nerve cell
   bodies located outside the central nervous system,
   situated near the cervix.
Surface water: All bodies of water  on the surface of
   the earth.
Synapse: Region of contact between processes of two
   adjacent neurons.
Synaptic uptake:  Movement of a chemical into the
   neuron in the area of the  synapse.
                                               A-12

-------
Synaptosomal transport: Uptake of a chemical into
   isolated synapses.
Synergetic: Working together; an  agent that works
   synergistically with one or  more other agents.
Synergistic effects:  Joint  effects  of  two or  more
   agents, such  as drugs that  increase each other's
   effectiveness  when taken together.

Telencephalon:  Paired cerebral vesicles, from which
   the cerebral hemispheres are derived.
Teratology: Science that deals with  abnormal
   development of the fetus and congenital malfor-
   mations.
Teratospermia:  Presence of malformed spermatozoa
   in the semen.
Temperature inversion: Layer of air  in which tem-
   perature increases with altitude; very little tur-
   bulent exchange occurs within it.
Terminal velocity: See Terminal fall  velocity.
Terminal fall velocity (terminal velocity): Particu-
   lar falling speed, for  any  given  object  moving
   through  a fluid  medium  of specified  physical
   properties, at which the drag forces and buoyant
   forces exerted by the fluid on the object just equal
   the gravitational force acting on the object, after
   which it falls at constant speed unless it moves
   into sir layers of different physical properties. In
   the atmosphere, the latter effect is so gradual that
   objects such  as raindrops,  which attain terminal
   velocity at great heights above the surface, may be
   regarded as continuously adjusting their speeds to
   remain at all times essentially in the terminal fall
   condition.
Topography: (1) General configuration of a surface,
   including its  relief; may be a land or water-bot-
   tom surface; (2) natural surface  features of a
   region, treated collectively as to form.
Transaminases:  Enzymes that catalyze the transfer
   of an amino group of an amino acid to a keto acid
   to  form  another  amino  acid;  also  known as
   aminotransferases.
Transfer RNA  (tRNA): Smallest ribonucleic acid
   molecule  found  in cells; its structure is comple-
   mentary to messenger RNA and it functions in
   transferring amino acids from their free state to a
   growing polypeptide chain.
Transformation: In this document, changes in physi-
   cal or chemical form of lead-containing particles
   or  compounds that occur  with time and space
   during atmospheric and environmental residence
   and/or transport.
Translocation:  Transfer  of metabolites,  nutritive
   materials, or other substances from one part of a
   plant to another.
Transport: In this document, movement of lead and
   its compounds from one place  to another in the
   environment.
Transudation: Passage of serum or other body fluid
   through a  membrane  or tissue surface; may  or
   may not be the result of inflammation.
Troposphere: The atmospheric  shell  extending
   about  10 to 20 km from the earth's surface.
Trypan Blue: An acid, azo dye used in vital staining;
   under  normal conditions, it does not  enter most
   areas of the brain from the blood.
Tumor: Any abnormal mass of cells resulting from
   excessive cellular multiplication.
Turbulence: State of fluid flow  in  which instan-
   taneous velocities  exhibit  irregular  and ap-
   parently random fluctuations so that, in practice,
   only statistical properties can be recognized and
   analyzed;  turbulence  can  transport  suspended
   matter at rates far in excess of rates of transport
   by diffusion and conduction in  a laminar flow.
Two-way aviodance tasks: See Avoidance task.
Tyrosine: Amino acid (p-hydroxyphenylalanine,
   CgHjjOjN) found in   most  proteins  and  syn-
   thesized metabolically from phenylalanine. It is a
   precursor  of dopamine and of  the  hormones,
   epinephrine,  norepinephrine,  and
   triiodothyronine.

Ultradian rhythms: Biological  rhythm with a fre-
   quency higher than circadian (24 hr).
Uncertainty: Standard  deviation  of  a sufficiently
   large number of measurements of the same quan-
   tity by the same instrument or methods; the non-
   correctable  inaccuracy of the instrument.
Upwind: Toward the direction from which  the wind
   is flowing;  counter to the wind.
Urobilinogen: Colorless compound formed  in the in-
   testine by the reduction of bilirubin (a  bile pig-
   ment that is a breakdown product of heme); some
   is excreted  in the feces where  it is oxidized  to
   urobilin; some is reabsorbed and reexcreted in the
   bile (as bilirubin) or in the urine.
Uroporphyrin: Any of several  isomeric,  metal-free
   porphyrins, occurring in small quantities in nor-
   mal urine and feces.
Vacuolization: Formation of vacuoles,  any small
   spaces or cavities formed in the protoplasm of a
   cell.
                                               A-13

-------
Vacutainers:  Registered trademark of sealed  am-
  pules, maintained under a slight vacuum and con-
  taining  an  anticoagulant, into which blood sam-
  ples may be drawn directly.
Vanillyl mandelic acid (vanilmandelic acid): A ma-
  jor metabolite of the catechloamines;  used to
  assess quantitatively the endogenous production
  of catecholamines.
Variance: A measure of dispersion or variation of a
  sample from  its expected value. It is  usually
  calculated as a sum of squared deviations about a
  mean divided by the sample size.
Wechsler Intelligence Test (WISC): A standardized
  intellectual assessment  instrument (appropriate
  for ages 6 yr to 16 yr 11 mo), consisting of 12 sub-
  tests designed to yield verbal and performance in-
  tellectual scores.
Wet deposition: Removal  of  particles from  the at-
  mosphere via precipitation; rainout.
Wind: Air motion relative to the surface of the earth.
  Vertical  components  are  relatively  small,
  especially near the surface of the earth; hence, the
  term denotes almost exclusively the horizontal
  component.
WPPSI Test: A version of the WISC test, but consist-
  ing of 10 subtests representing a downward exten-
  sion  of the  WISC  appropriate for  younger
  children (ages 4 to 6.5 yr).
Xenobiotics: Chemicals foreign to biologic systems.

X-ray diffraction analysis: Analysis of the crystal
  structure of materials by passing Xrays through
  them  and registering the diffraction (scattering)
  image of the rays.

X-ray powder  diffraction techniques:  Analytical
  techniques in which an X-ray beam of known
  wavelength strikes a finely ground powder sam-
  ple; the crystal planes of the powder diffract the
  beam and these diffraction  lines are recorded on
  photographic film.

X-ray spectrography: Analytical method employing
  an X-ray spectrometer (instrument for producing
  the X-ray spectrum of a material and measuring
  the wavelengths of components) that is equipped
  with photographic or other recording apparatus.

Zinc erythrocyte porphyrin: The biochemically cor-
  rect form for the erythrocyte  protoporthyrin or
  porphyrin that is elevated  in lead exposure or
  iron deficiency anemia.  Used interchangeably in
  this  document  with   erythrocyte  porphyrin,
  erythrocyte protoporthyrin, and free erythrocyte
  porphyrin or protoporthyrin.
                                              A-14

-------
                          APPENDIX B
    PHYSICAL/CHEMICAL DATA FOR  LEAD COMPOUNDS
B.I DATA TABLES
             TABLE B-1. PHYSICAL PROPERTIES OF INORGANIC LEAD COMPOUNDS'
Solubility, g/100 ml

Compound
Lead
Acetate
Azide
Bromate
Bromide
Carbonate
Carbonate,
basic
Chloride
Chlorobromide
Chromate
Chromate,
basic
Cyamide
Fluoride
Fluorochloride
Formate
Hydride
Hydroxide
lodate
Iodide
Nitrate
Nitrate, basic
Oxalate
Oxide
di Oxide
Oxide (red)
Phosphate
Sulfate
Sulfide
Sulfite
Thiocyanate
Abbreviations
a - acid
al - alcohol
alk - alkali
d - decomposes
expl - explodes

Formula
Pb
Pb(C2H3O2)2
Pb(N3)2
Pb(BrO3)2-H2O
PbBr2
PbCO3
2PbCO3-Pb(OH)2

PbCI2
PbCIBr
PbCrO4
PbCrO4-PbO

Pb(CN)2
PbF2
PbFCI
Pb(CHO)2
PbH2
Pb(OH)2
Pb(l03)2
Pbl2
Pb(N03)2
Pb(OH)(NO3)
PbC204
PbO
PbO2
Pb304
Pb3(P04)2
PbSO4
PbS
PbSO3
Pb(SCN)2
glyc - glycol
i - insoluble
s - soluble
M W - molecular weight
S G - specific gravity
M P - melting point

M W
207.19
32528
291 23
481 02
367.01
26720
77560

27810
32256
32318
546.37

25923
24519
261.64
29723
20921
241.20
557.00
461 00
331.20
28620
29521
22319
239.19
68557
811.51
30325
239.25
28725
323.35







SG
11 35
325
—
553
666
66
6 14

585

6.12
6.63

-
824
705
463
—
—
6 155
616
4.53
593
528
953
9375
9.1
7
62
75
—
382







MP
3275
280
expl.
d180
373
d315
d400

501
—
844
—

—
855
601
d190
d
d145
d300
402
d470
d180
d300
888
d290
d500
1014
1170
1114
d
d190






Cold Hot
water water
I I
443 22150
0 023 0 0970
1.38 Sis
0.8441 4 71 'f»
000011 d
i i

099 334'oo
—
6x10-6 i
i i

si s s
0 064
0.037 01081
1 6 20
—
0.0155 Sis
00012 0003
0 063 0 41
3765 127
194 s
000016
00017
i i
i i
14x10-5 i
0 00425 0 0056
8.6x10-5 —
i i
005 02






Other
solvents
sa
sglyc
—
—
sa
sa,alk
SHNOg

lal
-
sa.alk
sa.alk

sKCN
sHN03
—
lal
—
sa.alk
sHNO3
s.alk
s.alk
sa
sa
s.alk
sa
sa
s.alk
—
sa
sa
s.alk






                                B-1

-------
         TABLE B-2. TEMPERATURE VARIATION OF THE VAPOR PRESSURES OF COMMON LEAD COMPOUNDS*
Temperature °C
Name
Lead
Lead bromide
Lead chloride
Lead flouride
Lead iodide
Lead oxide
Lead sulfide

Formula
Pb
PbBr2
PbCI2
PbF2
Pbl2
PbO
PbS

MP
3274
373
501
855
402
890
1114

1 mm
973
513
547
solid
479
943
852
(solid)
10mm
1162
610
648
904
571
1085
975
(solid)
40mm
1309
686
725
1003
644
1189
1048
(solid)
100mm
1421
745
784
1080
701
1265
1108
(solid)
400mm
1630
856
893
1219
807
1402
1221

760mm
1744
914
954
1293
872
1472
1281

B.2. THE CHELATE EFFECT
  The stability constants of chelated complexes are
normally several  orders of magnitude higher than
those of comparable monodentate complexes; this
effect is called the chelate effect and is very readily
explained in terms of kinetic considerations. A com-
parison  of the binding of  a single bidentate ligand
with that of two molecules of a chemically similar
monodentate ligand shows that, for the monodentate
case, the process can be represented  by the equa-
tions:
                                          (B-l)


                                          (B-2)
M-B +  B
                                      The overall equilibrium constants, therefore, are:
The related expressions for the bidentate case are:
                                                                    k,k3

                                                                    k2k4
          For a given metal, M, and two ligands, B and B-B,
        which are chemically similar, it is established that k,
        and k have values similar to each other, as do k,
              d                                          £
        and kb, k4 and kd; each of these pairs of terms repre-
        sents chemically similar processes. The origin of the
        chelate effect lies in the very large value of k3 rela-
        tive to that of kc. This comes about because k3 repre-
        sents a  unimolecular  process,  whereas kc  is  a
        bimolecular rate constant. Consequently, K2  »K,.
          This concept can, of course, be extended to poly-
        dentate ligands; in general, the more extensive the
        chelation,  the more  stable  the  metal  complex.
        Hence, one would anticipate, correctly, that poly-
        dentate chelating  agents such as  penicillamine or
        EDTA can form  extremely  stable complexes with
        metal ions.
               M + B-B^     NM-B-B
                          ki
(B-3)
                                           (B-4)
                                     B.3 REFERENCES FOR APPENDIX B

                                     1  Handbook of Chemistry and Physics, 56th Ed. R.C Weast
                                       (ed.)  Cleveland, The Chemical Rubber Co. 1975.
                                     2  Stull. D.R, Vapor pressure of pure substances- Organic com-
                                       pounds. Ind Eng. Chem. 59(4V517-540. 1947
                                                B-2

-------
                                      APPENDIX  C
             ADDITIONAL  STUDIES  OF  ENVIRONMENTAL
                         CONCENTRATIONS OF  LEAD
  This collection  of studies is intended  to extend
and detail the general picture of lead concentrations
in the environment  and  in proximity to  identified
major sources as portrayed in Chapter 7. The list is
by no means all-inclusive, but  is intended to be
representative and to supplement the data cited in
Chapter 7.
C.I  GENERAL  AMBIENT   AIR  CON-
CENTRATIONS

C.I.I  Seven-City  Study
  A special lead study (Seven-City Study) was con-
ducted for  12-month  periods  between  1968  and
1971  in  Cincinnati, Los Angeles,   Philadelphia,
Houston, New York City, Washington, D.C.,  and
Chicago.  Samples  of ambient air were analyzed by
atomic  absorption  spectroscopy.  The monthly
average   lead concentrations  obtained  are sum-
marized in Table C-l.
  This study, specifically designed to measure  am-
bient lead concentrations at a variety of sites within
each of  the  cities,  incorporated  techniques  that
would provide the most precise measure of ambient
lead concentrations  available.  A membrane filter
was used instead of a glass filter, and the samples
were collected continuously over 2 to 3 days rather
than collected in biweekly 24-hr periods as in the
NASN. The high annual average lead concentrations
found in the Los Angeles area are largely attributa-
ble to heavy automotive  emissions.

C.I.2 Birmingham,  Alabama
  During 1964  and  1965, seasonal levels of trace
metals were determined from suspended particulate
samples collected  at 10 area sampling sites at  Bir-
mingham, Alabama, as  a  part  of  the  Alabama
Respiratory Disease and Air Pollution Study initi-
ated in 1962.  This monitoring  study produced data
representative of area source  industrial  pollution.
Samples from each of the 10 sites were composited
on a seasonal basis to give a total of 40 pooled sam-
ples. The lead data are summarized in Table C-2.
The maximum seasonal lead  concentration (3.5
yu.g/m3) occurred  at Birmingham site 4 during  the
winter. Only 2 sites showed average concentrations
 > 2 /Lig/m3 for the year, Birmingham site 4 (3.0
/Lig/m3) and Tarrant (2.3 Mg/m')- These results are
typical for  a medium-sized  industrialized  urban
area.

C.I.3  Kanawha Valley, West Virginia3
  A comprehensive air pollution study was con-
ducted in the Kanawha River  Valley in the vicinity
of Charleston, West Virginia  (Figure C-l), during
1964 and 1965. Twenty-four-hour samples of sus-
pended particulate matter were collected  at  14
strategically located sites. Samples  from  selected
sites were composited on a seasonal basis (fall 1964,
winter  1964 and 1965, and summer 1965) and  the
composites were analyzed for trace-metal content by
the NASN emission spectrographic procedure. The
data for lead are presented in Table C-3. Highest
concentrations of suspended lead were found during
the fall of 1964 at the St. Albans, Kanawha City, and
Charleston sites.
  Lead in dustfall measurements (settled  particu-
lates) for the same stations are also presented in
Table C-3. The dustfall was collected by exposing
wide-mouth jars for a period of 1 month; then com-
posite samples were analyzed. The highest average
concentrations  of settled lead  occurred  at  the
Smithers site (11.2 mg/m2-mo), and  at the  South
Charleston-East site (11.6 mg/m2-mo).
  The  combustion  of solid fuels (coal and  coke) is
the primary source of lead emissions in the Kanawha
Valley. Additional sources are metallurgical opera-
tions, asphalt  hot-mix production, and  other  in-
dustrial processes. In most cases, these sources have
inadequate air  pollution control equipment. The
lead concentrations found are somewhat  low when
                                              C-l

-------
TABLE C-1. SUMMARY OF MONTHLY AVERAGE LEAD
 CONCENTRATIONS FOUND IN SEVEN-CITY STUDY'
                              Monthly concentration,
TABLE C-2. SEASONAL LEAD CONCENTRATIONS IN
    BIRMINGHAM, ALABAMA, AREA, 1964-1965
City
LOS Angeles






Philadelphia








Cincinnati




Los Alamos

Houston





Chicago






Washington, D.C






New York






aC -commercial, 1 -
site
type3
C
P
o
R
R
R
R
1
C
M
C
C
1
R
M
R
R
R
R
C
R
1
P
F
F
R
C
R
C
C
C
M
R
R
R
M
R
M
C
R
R
M
R
R
C
c
R
R
F
R
R
M
M
R
R
M
R
R
R
R
Months
of data
12
19
1 £.
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
7
12
12
12
7
12
12
12
12
12
12
11
12
12
12
12
12
12
12
12
Min
2.4
9 fi
£.0
2.1
2.7
2.1
1.4
1.7
2.5
1.3
1.2
2.6
1.5
0.9
0.6
0.6
1.1
0.8
0.7
1.3
0.8
1.2
0.5
0.1
0.2
0.1
0.1
0.7
0.7
1.2
1.5
1.0
0.6
0.6
1.0
1.1
1.0
1.3
1.4
1.2
0.9
1 1
1.2
0.7
1.2
1.6
1.4
1.0
0.9
1.8
0.8
1.1
1.4
1.4
1.3
1.2
0.8
0.9
0.9
0.8
industrial. R - residential, M - mixed. F - 1
Max
5.8
RS
O.Q
5.0
5.4
4.4
3.9
7.0
7.6
2.7
2.6
5.1
3.0
2.0
1.7
1.5
2.6
1.7
1.6
3.1
2.6
2.8
1.2
0.5
0.5
0.3
0.3
2.7
1.9
3.2
4.1
2.2
1.4
1.2
1.7
1.7
2.1
2.2
2.3
2.2
2.7
2.1
3.5
1.6
2.2
3.9
2.8
1.7
1.6
3.5
1.8
2.9
2.6
2.1
2.2
2.7
1.9
1.6
1.4
1.4
:arm, and P
Avg
4.2
3.6
3.8
3.1
2.5
3.7
4.8
1.9
1.8
3.8
2.2
1.4
1.1
1.1
1.7
1.3
1.0
2.0
1.5
2.2
0.9
0.3
0.3
02
0.2
1.2
1.1
2.2
2.4
1.3
0.9
0.8
1.3
1.4
1.6
1.8
1.9
1.6
1.3
1.6
2.0
1.1
1.7
2.3
1.8
1.2
1.1
2.4
1.1
1.7
2.1
1.7
1.7
2.1
1.4
1.2
1.2
1.1
-park
Seasonal average concentrations Study period
	 average
Place Site Spring Summer Fall Winter concentration
Bessemer 1 09 0.7 1.1 06 0.8
Birmingham 3 0.7 14 17 14 1.3
Birmingham 4 32 2.8 2.3 3.5 3.0
Birmingham 5 12 1.6 1.8 08 14
Birmingham 7 12 1.4 13 1.8 14
Fairfield 1 06 05 0.6 03 0.5
Irondale 1 06 04 0.9 0.6 0.6
Mt. Brook 1 05 0.6 10 0.5 0.6
Tarrant 1 11 18 30 34 23
Vestavia 1 08 0.8 05 07 07

one considers the diversity of industrial activity and
the meteorological and topographic characteristics
prevailing. The highest values found were associated
with sampling sites adjacent to major traffic arteries,
which demonstrates the contribution from mobile
sources.

C. 1 .4 Study of Lead Deposition in 77 Cities4
Settled particulates were collected in 77 mid-
western cities from September through December
1968. Within each city, sites were chosen to repre-
sent residential, commercial, and industrial areas.
The lead content of the settled particulates was
determined by atomic absorption spectrophotome-
try, and the depositions were expressed as mg/m2-
mo. The highest amounts found in residential, com-
mercial, and industrial areas were in South Bend,
Indiana (80 mg/m2-mo in November); Nashville,
Tennessee (346 mg/m2-mo in October); and Omaha,
Nebraska (137 mg/m2-mo in November); respec-
tively. Maximum readings by month occurred in
Muncie, Indiana (industrial) (105 mg/m2-mo in Sep-
tember); Nashville, Tennessee (commercial) (346
mg/m2-mo in October); Omaha, Nebraska (in-
dustrial) (137 mg/m2-mo in November); and
Waterloo, Iowa (industrial) (94 mg/m2-mo in
December). The data are summarized in Table C-4.

C.2 SOURCE-ORIENTED AMBIENT AIR
CONCENTRATIONS

C.2. 1 Southern Solano County, California5
The State of California Air Resources Board
coordinated a joint study, conducted by several state
agencies between March 1970 and November 1971,
to determine the cause of death of a number of
horses in the Benicia area from 1968 to 1970. Figure
C-2 is a map of this area showing sampling site loca-
tions. The evidence strongly suggested that the
                                           C-2

-------
                           TABLE C-3. LEAD DATA FROM KANAWHA VALLEY STUDY*
Lead m suspended participates. ^ g 'm^
Sampling sites,
location and no
Falls View (1)
Smithers (5)
Montgomery (6)
Cedar Grove (7)
Marmet(11)
KanawhaCity (13)
Charleston (15)
West Charleston (17)
North Charleston-W (19)
South Charleston-E (20)
Dunbar(22)
St Albans (24)
Nitro (25)
Nitro-West (27)
Fan
1964
—
04
—
0.5
—
21
—
—
—
27
—
1.3
1.0
—
Winter
1964-1965
02
03
0.6
04
0.5
0.8
09
07
07
0.6
0.4
0.9
1 4
01
Spring
1965
—
0.3
-
02
—
0.6
—
—
-
0.6
—
03
0.2
—
Summer
1965
	
0.0
—
04
—
05
—
—
—
1.0
—
04
0.3
—
Study period
average
—
0.2
—
0.4
—
1.0
—
—
—
1 2
—
0.7
0.7

Lead in settled participates,
mg/m^/mo
study period
average
—
11 2
6.7
48
3.8
2.8
_
_
8.6
11 6
—
3.0
3.4
—
Figure C-1. Locations of fixed sampling stations in Kanawha
River Valley.3

      TABLE C-4. DATA ON LEAD DEPOSITION IN 77
               MIDWESTERN CITIES4
                    (mg/m2/mo)
Lead deposition

Area
Residential
Commercial
Industrial

Concentration,
geometric mean
524
9,80
1278

Lead deposition

Month
September
October
November
December
Concentration
geometric mean
911
871
915
806
horses died of lead poisoning that was caused by in-
gestion  of lead deposited on  pasture grass from a
smelter  plant at Selby, California. The  ambient air
concentrations  of particulate  lead  were typical of
those found in urban and suburban areas. It was con-
cluded that horses in this area should not be allowed
                                                    to subsist on pasture grass alone, but should receive
                                                    supplemental feed. Tables C-5 and C-6 contain the
                                                    data on suspended and deposited lead obtained dur-
                                                    ing the study. Note that  the fallout rates are on a
                                                    daily basis.
Figure C-2. Air sampling sites for Southern Solano County,
California, study.*
C.2.2 Omaha,Nebraska6
  In April and May of 1968, a study of settled lead
by the EPA Division of Health Effects Research
showed central Omaha, Nebraska, to have the high-
est  concentrations  of deposited  lead of 22  mid-
western cities. Because automobile emissions should
reflect the relatively low  population density, the
possibility of a significant  contribution to air lead
                                                C-3

-------
TABLE C-5. LEAD CONCENTRATIONS IN AIR DETERMINED
BY ANALYSIS OF SUSPENDED PARTICULATE, SOUTHERN
SOLANO COUNTY, CALIFORNIA, MARCH-MAY 1970s
Distance
from Lead concentrations, ng/rrv^
Site km High Low Mean
Carqumez Bridge 1.9 845 035 3.49
Elliot Cove 30 0.93 0.27 0.52
Babson house 37 0.82 0.58 0.70
Braitodump 5.6 069 0.07 0.64
Walsh house 5.7 0.62 0.14 0.40
Braito TV transmitter
site 7.7 1.07 0.25 0.59
Wesner pasture 78 0 56 0.40 0.42
Wesner pasture 8.0 066 011 0.38
Wesner pasture 83 0.51 0.03 0.27
Gomez pasture 10.0 0.28 0.03 011
Wesner house 10.2 022 002 014
San Francisco0 220 3.50 1.15 2.12
Fremontb 20 0 2 24 0.59 1 04
SanRafaelb 19.2 2.04 041 1.14
a Location of suspected lead emissions source See text
D 1969 data provided by Bay Area Air Pollution Control District
TABLE C-6. TOTAL LEAD AND LEAD FALLOUT
DETERMINED BY ANALYSIS OF DUSTFALL SAMPLES,
SOUTHERN SOLANO COUNTY, CALIFORNIA,
JUNE-SEPTEMBER 1970s
Distance
from Sample Total Total Lead
Selby,3 period, solids, lead. fallout,
Site km days mg jig mg/m2-day
Carqumez
Bridge 1.9 30 49.2 1435 2.78
Braitodump 5.6 30 58.7 195 0.38
Braito TV trans-
mitter site 7.7 60 101.7 520 050
Wesner
pasture 8.0 31 370 185 0.35
Wesner
pasture 80 31 162 155 0.29
Wesner
pasture 8.0 31 171 4 195 0.37
Wesner
pasture 8.0 31 1098 255 0.48
Wesner
pasture 8.0 31 351. '7 210 0.39
Wesner
pasture 80 31 220.2 4535 8.51
Wesner
pasture 8.0 30 83.5 430 0.83
Wesner
pasture 8.3 30 163.6 705 1.37
Gomez
pasture 10.0 32 45.0 150 0.27
Drachman
pasture 13.4 30 26.5 75 0.15
a Location of suspected lead emissions source See text
from other sources (two battery plants, one refinery)
in the central city area was considered. Conse-
quently, from May to November 1970, monitoring
of air lead in Omaha was conducted at five sites: one
industrial (I), one commercial (C), one mixed (M),
and two residential (R). All samples were taken at
15-ft elevation, and all data were reported as the
composited averages of 24-hr samples collected 3
times weekly. The monthly composite average of air
lead concentrations at the sampling sites is shown in
Figure C-3. Air lead levels in central Omaha at sites
C and I were not only comparable with those of simi-
lar sites in Chicago, New York City, and Houston
from the same months, as reported by EPA, but the
maximum monthly mean at the industrial site (in
July) exceeded the maximum monthly mean of all
sites in these other cities.
5.0 | 	 , 	 . 	 1 	 1 	 1 	 1
40
"l
5.
0 30
P
<
CC
H
z
UJ
CJ
z
o
u
§ 20
UJ
_J
cc
<
1.0
0
M
Figure
posite
and ti
hour
peak
patter
c.2.:
Th
a res
in th
i ft i i i
1 *v ATMOSPHERIC LEAD -OMAHA
/ \ MONTHLY COMPOSITE
/ \ MAY - NOVEMBER 1970
I V
/ \
*' \
j!
§1 \
- 7
/
--J \ / ^
s \ / .
\ / \
V \
£™™ERCML >>?
--_.' \f
**>. . RESIDENTIAL _--." 	
1 1 1 1 1
AY JUN JUL AUG SEP OCT NOV
TIME, months
i C-3. Omaha, Nebraska study: mean monthly corn-
atmospheric lead at industrial, commercial, mixed,
wo residential sites. Mean is that o( representative 24-
jamples collected three times weekly. The autumnal
at all but the industrial site parallels the usual Omaha
n for partteulates.*
* El Paso, Texas7-8
e El Paso, Texas, study was initiated in 1971 as
alt of the discovery of increased lead deposition
e vicinity of a local smelter whose emissions
C-4

-------
rose from 256 MT in 1969 to 463 MT in 1970. The
El Paso City-County Health Department then began
special ambient air and soil sampling in addition to
routine operation  of their nine-station paniculate
sampling  network. Particulate samples  were col-
lected  with  high-volume  samplers  over 24-hr
periods and were then analyzed for lead by atomic
absorption spectroscopy. The results for 1971 from
the nine-station network  are  given in Table  C-7.
Daily sampling at 6 selected  sites  in Smeltertown
was continued beginning  in February  1972. Daily
lead concentrations at four ground level sites ranged
from 0.49 to 75 /ug/m3 and averaged 6.6 /Ag/m3 over
86  days.  Average concentrations of 3.6  and  6.5
jug/m3 were found at 2 rooftop sites.

  TABLE C-7. LEAD CONCENTRATIONS IN SUSPENDED
PARTICULATE AIR SAMPLES FROM EL PASO, TEXAS, 197V
Location
Airport
Northeast
Canutillo
Shorty Way
Tillman
Ysleta
Coronado
Kern
Executive
Distance
from
smelter,
km
128E
16 NE
152NW
8NW
4.8 SE
21.6SE
48N
24E
1.6NE
No of
samples
84
73
45
75
70
71
94
26
65
Suspended atmospheric
lead concentration, n g 'm^
Range
0 38 to 5 82
012 to 3.68
010to1 50
0 18 to 4 51
002 to 22. 16
018 to 4 81
0 08 to 8 62
012 to 7.28
026 to 6.67
Average
096
076
046
1 03
269
1 39
083
272
1 16
C.2.4 Helena Valley, Montana9
  During the summer and fall of 1969, a source-
oriented study of the Helena Valley, Montana, area
(Figure C-4) was undertaken using dustfall bucket
and  high-volume sampling techniques. During this
period, Helena  residents were exposed to an average
daily lead concentration of 0.1 ^.g/m3, with max-
imum concentrations of up to 0.7 /Ag/m3. The resi-
dents of the  East Helena area  were exposed to an
average daily concentration of 0.4 to 4.0 /u.g/m3, de-
pending upon proximity to the source, with max-
imum daily exposures of up to 15 /ig/m3. Within a 1-
mile radius of the East Helena smelter, settled par-
ticulate lead values ranged from 30 to 108 mg/m2/
mo.  Table C-8  summarizes the dustfall  and sus-
pended paniculate data acquired during this study,
and  Figure  C-4  shows  the  deposition  of  lead
(dustfall) in the area.
Figure C-4.  Settleabte  paniculate lead  radial distribution
from Helena Valley environmental pollution study.9

C.2.5 Southeast Missouri10
  Studies were carried out in 1971 in the Viburnum'
Trend or New Lead  Belt in southeast Missouri to
determine  the  magnitude  and distribution of at-
mospheric pollutants from lead mining and smelting
operations. This industrial district has become one
of the world's largest lead-producing  areas by min-
ing more than 392,277 MT of lead, or 75 percent of
the entire U.S. lead  production,  during 1970. Set-
tleable particulates were collected monthly at  10
locations in western  Iron County shown in Figure
C-5. Annual  averages for each site  are included in
the figure; monthly maximum values are listed in
Table C-9. Annual averages for suspended lead col-
lected  in Glover, Mo. (Site 43,  southeastern Iron
County), by high-volume sampler were 3.4 /ug/m3
(20 samples) in 1970, 5.3 ^g/m3 (32 samples) in
1971, and 5.6 /zg/m3 (28 samples)  in  1972.
   TABLE C-8. PARTICULATE DATA SUMMARY FROM HELENA VALLEY, MONT., ENVIRONMENTAL POLLUTION STUDY'
                                   Settleable particulate lead, mg/m^/mo
 a Distance and compass direction from smelter stack
 ^ Minimum detectable
                         Suspended particulate lead
                       in glass fiber filter sample, ^
Station
1
2
3
4
6
Location3
0.8 mi;
2.5 mi;
0.4 mi;
4.5 mi;
0.5 mi;
34°
105°
112°
274°
2°
Jun
3
1
54
1
—
Jul
19
4
106
4
—
Aug
10
3
5
3
—
Sept
19
9
63
7
27
Oct
40
10
108
7
60
No samples Max
76
87
85
82
34
5.3
2.5
16.0
7.0
15.0
Mm
< mdb
< md
< md
< md
0.2
Average
0.45
0.24
1.25
0.10
3.89
                                               C-5

-------
                                                   C.2.6 Helsinki, Finland11
                                                     Investigators for  the Agricultural  Research
                                                   Center in Tikkurila, Finland, an industrial and resi-
                                                   dential area near Helsinki, found high lead levels in
                                                   soil. To clarify the origin of this excess lead, the In-
                                                   stitute of Occupational Health conducted a dustfall
                                                   lead survey in the area.  Eighty collectors were lo-
                                                   cated over a 40-km2 area for a period of 1 month,
                                                   October  6  to  November  7, 1970. Individual ashed
                                                   samples  were analyzed by emission spectrography
                                                   and the  water-soluble fractions were  analyzed  by
                                                   atomic absorption spectroscopy.
                                                     The highest lead deposition values in Helsinki
                                                   were observed in areas with heavy traffic and ranged
                                                   from  10  to 20 mg/m2/mo as compared to 0  to 4
                                                   mg/m2/mo in predominantly housing and residential
                                                   areas.
                                                     In the  Tikkurila area, industrial contributions in-
                                                   creased  deposited  lead  values fortyfold in some
                                                   areas. The  deposited lead values ranged from back-
                                                   ground in outlying areas to as high as 200 mg/m2/mo
                                                   near a lead smelter, with most of the values below
                                                   100mg/m2/mo.

                                                   C.2.7 Meza River Valley, Yugoslavia12
                                                     In 1967, work was  initiated in the community of
                                                   Zerjav, situated in the Slovenian Alps on the Meza
             TABLE C-9. PEAK DEPOSITION RATES OF LEAD MEASURED IN SOUTHEAST MISSOURI"
Figure C-5. Annual average of settleable paniculate lead at
sites near Missouri lead mine and smelter, g/m2/hio.10
1971
May-June
July
August
September
October
November
Station
no
6
7
10
7
7
3
Wind
direction
E
SSE
NE
SSE
SSE
WNW
Disiance, m
81
91
633
91
91
61
Lead deposi-
tion rate,
mg/m^/mo
588
554
457
776
510
201
Wind frequency, %
prevailing direction
18(S), 12(WNW)
14(SSE), 13(S), 10(SSW)
14(SSE). 1KS). 10(SSW)
22IS). 12(SSE). 12(SSW)
10IN) 10IW). 1CHSE). 11 IESE)
26(SV12(SSW) 10(WSW).8(SSE)
River, to  investigate contamination by lead of the
air, water, snow, soil, vegetation, and animal life, as
well as the human population.  The smelter in this
community produces about 19,954 MT of lead an-
nually; until  1969  the  stack emitted lead  oxides
without control by filters or other devices. Five sam-
pling sites with high-volume samplers operating on a
24-hr basis were established in the four principal set-
tlements within the Meza River Valley (Figure C-6):
(1) Zerjav, in  the center,  the site of the smelter,
housing 1503  inhabitants;  (2) Rudarjevo, about 2
km to the  south of Zerjav with a population of 100;
(3) Crna,  some 5 km to the southwest, population
2198, where there are two sites (Crna-SE and Crna-
W); and (4) Mezica, a village about 10 km to the
                                                   northwest of the smelter with 2515 inhabitants. The
                                                   data in Table C-10 are sufficient to depict general
                                                   environmental  contamination  of striking  propor-
                                                   tions.

                                                   C.2.8 Ontario,Canada13
                                                     Studies of lead concentrations in soils, vegetation,
                                                   and the ambient air were conducted in the vicinity of
                                                   a secondary smelter and a battery  manufacturing
                                                   plant in a large urban area in southern Ontario. For
                                                   comparative purposes, data were also collected in a
                                                   similar control  neighborhood that had no such in-
                                                   dustrial sources. Emissions of lead from the smelter
                                                   were estimated to be 17 tons per year; from the bat-
                                                   tery plant, 6 tons per year.  Averages and ranges of
                                               C-6

-------
Figure C-6. Schematic plan of lead mine and smelter from
Meza Valley, Yugoslavia, study.12

 TABLE C-10. ATMOSPHERIC LEAD CONCENTRATIONS (24-
 hr) IN THE MEZA VALLEY, YUGOSLAVIA, NOVEMBER 1971
                 TO AUGUST 197212
Sue
Mezica
Zeriav
Rudanevo
CrnaSE
Crna W
Pb concentration M9/m^
Minimum
01
03
05
01
01
Maximum
2360
2165
3280
2585
2220
Average
242
295
384
337
284
lead concentrations are summarized in Table C-l 1.
Both soil and foliage samples showed definite trends
toward reduced concentrations with increasing dis-
tance from the industrial sources.
C.3  CONCENTRATIONS OF LEAD IN SOILS
AND URBAN DUSTS
  As mentioned in Chapter 5, surficial materials in
the continental United States contain an average of
about 15 ppm of lead; 94 percent of the  measure-
ments showed 30 ppm or less. Higher concentrations
are encountered in the vicinity of lead ore deposits
and, of course, in the proximity of human  activities
involving lead. Soils apparently receive lead in the
amounts of about 1  /u,g/cm2/yr from precipitation
and  0.2 /xg/cm2/yr from  dustfall14 in areas remote
from intensive human activity. These small addi-
tions to the lead content of the soil are not detectable
by ordinary means because they add only about 0.2
percent to the total lead  in the top 6 in of the soil.
Lead levels are higher in surface soils than  in deeper
layers. Swain and Mitchell15 studied lead profiles in
8 soil types in  Scotland  and showed  that  the lead
content at 115 cm (45 in) averaged one-half that at
the surface. The reduction of concentration with
depth is also substantiated by the findings of others.
Goldschmidt16 proposed the theory that lead is con-
centrated in the humus or organic fraction of soils in
forests because it is taken up slowly by tree roots and
transported  to  the  leaves, which  fall and decay.
Tyler17 points out that a passive ion exchange favors
an accumulation of lead and  other heavy metals in
dead organic  matter,  litter,  and  humus.   He also
states that most plant material subjected to decom-
position usually shows an increase in the concentra-
tion  of  lead, cadmium, nickel, iron, copper, etc.,
calculated on dry weight.
  The use of leaded gasolines has produced elevated
soil lead levels adjacent  to most  streets and road-
ways. This phenomenon was first observed as early
as 1933  in  England,18 and  has been  intensively
                TABLE C-11. COMPARISON OF LEAD LEVELS IN THE SURROUNDINGS OF TWO
                       LEAD INDUSTRY FACILITIES AND AN URBAN CONTROL AREA"
Industry or
area
Secondary smelter
Mean
Range
Battery plant
Mean
Range
Urban control area
Mean
Range
Soil ppm
(0 5 cm depth)
2.615
133(021.200
1 996
95 to 1 7 300
482
18 to 1.450
Tree foliage ppm
Unwashed
250
38 to 3.530
149
34 to 459
73
15 to 253

Washed
187
27 to 2.740
76
1610387
43
10 to 124
Air, ^ig/m
(24-hour samples)
Max 744
221b
Max 31 0
1 02C
Max 40
  "April 1973 to May 1974
  bNovember 1973 to May 1974
  cJanuary 1974 to April 1974
                                                C-7

-------
studied in  recent  years.19  An  example of  this
phenomenon is  taken  from  a  study  of  the  Saline
Branch watershed,  which includes Champaign, Il-
linois.  One facet of this comprehensive study20 con-
sisted of analyses for lead in soil at increasing dis-
tances  from a low-traffic-volume  street  (400 vehi-
cles/day) and  a  high-traffic-volume street (14,000
vehicles/day).  As shown on curve  A in Figure C-7,
lead concentrations stabilized  at  about 20 ppm
beyond 15  meters from the low-volume street and
rose slightly near the house.  Unfortunately, the ex-
terior construction of the house is not described. As
curve B in Figure C-7 shows, lead concentrations of
about  1800 ppm in the  soil adjacent to the high-
volume street are 9 times higher than in soil adjacent
to the  low-volume street; the concentration drops
rapidly to a minimum  of 30 ppm a little more than
20 m from the street and then rises again abruptly
near the house to 90 ppm. This house is described as
brick and unguttered.  Although some  leaching of
lead from painted trim  may be involved, the increase
near the house is believed attributable chiefly to lead
particles in traffic dust washed from the  unguttered
roof by rain and deposited in the soil  next  to the
house.
                 DISTANCE FROM STREET, meters
Figure C-7. Soil transects by two streets: Curve A = low-
traffic-volume (400 veh/day); Curve B = high-traffic-volume
(14,000 veh/day).20
  Soil lead levels in the vicinity of stationary sources
of lead emissions are often very high, and, unlike the
rapid drop-off near highways, very extensive. This is
particularly true for old installations. Figure C-8
shows levels recently found near an old smelter in El
Paso, Texas.2' Similar data, compiled from a 3-year-
old  Russian   lead  smelter,22 are   shown in
Table C-12. The concentration decrease with both
depth and distance is also apparent here. Informa-
tion on soluble lead levels in soil near a similar com-
plex in Great Britian is presented in a report by Lit-
tle and  Martin.23 Barltrop reported values up to
30,000 fjig/g in villages in the eastern half of Der-
byshire County, England.24 In this instance, the soil
included lead contamination from old mine tailings
and possible natural  mineralization, i.e.,  the con-
centrations  were  not exclusively  atmospheric  in
origin.
Figure C-8. Surface soil levels (ppm) of lead in  El Paso,
Texas, and Dona Ana County, New Mexico, 1972.21
 TABLE C-12. LEAD CONTENT OF SOIL NEAR 3-YEAR-OLD
         RUSSIAN SMELTER, E. KAZAKHSTAN
              (mg/100 g air-dried soil)8
Distance from
source, m
500
1.000
2.000
3.000
5.000
16.000
Surface
layer
239711
90163
1 4207
1 2192
01031
00943

25 cm
41747
1 8368
07432
05991
00649
00778
Soil depth
75 to 100 cm
00748
—
00545
00474
00233
00292
  Multiplying by 10 yields ppm

  Table  C-13, derived from studies done in 1959
and  I960,25  gives  lead  levels of soil  adjacent  to
another Russian lead smelter. The plant is located in
a  valley  surrounded by  mountains  that  hinder
natural ventilation. In addition, plant emissions are
inadequately controlled. Methods of sample prep-
aration and  analysis of the soil samples are  not
given, however;  nor  is  it stated whether the soil
weights used were for dried or undried material.
   Paluch and  Karweta26 reported observations  on
soil lead near a new lead-zinc primary smelter in Po-
land. Soil analyses were made in several areas prior
to operation of the factory and after  1 year of opera-
tion.  Samples were extracted with hot concentrated
hydrochloric acid and analyzed for  lead content by
the dithizone  method. Levels found are given in
milligrams of lead per kilogram of dried soil. Values
                                                 C-8

-------
              TABLE C-13. LEAD CONTENT OF SOIL IN VICINITY OF RUSSIAN LEAD PLANT IN KAZAKHSTAN"
Distance
from
source
km
On grounds
05
1 0
1 5
20
30
50
400
Lead content of soil, mg'100 ga
Number
of
samples
12
10
20
6
6
4
4
4


Maximum
11 1700
2.420 0
1.1700
7200
1 .070 0
3400
970
30
0 to 1 cm depth

Minimum
1 .300 0
4700
1300
1700
2500
1300
800
25


Average
5.5460
1.1560
6130
3690
5300
2350
885
27


Maximum
6.800 0
6500
9900
7200
6100
2600
460
Trace
25 cm depth

Minimum
5100
1300
2000
700
700
1000
400
Trace


Average
3.1430
4580
4300
3400
2600
1800
430
Trace
  Multiplying by 10 yields ppm
given are the average of three samples. Two sites are
of particular interest, a woods of young pines 2 km
from the smelter and a tree nursery at 3 km. Before
and after lead  levels in the top 5 cm  of soil at these
locations were 39 and 89 mg/kg  for the former, and
54  and  81  mg/kg for the latter. At other  sampling
sites  the data  were quite variable,  but these were
agricultural lands subject to cultivation, to fertiliza-
tion, or to both. The wooded sites were not disturbed
in this manner.

C.4 REFERENCES FOR APPENDIX C

 1.  Tepper,  L. B. and L. S. Levin  A survey of air and popula-
    tion  lead levels in selected amencan communities Pre-
    pared by University of Cincinnati, Cincinnati, Ohio, under
    Contract No. PH-22-68-28. U  S  Environmental  Protec-
    tion  Agency  Washington,  D C.  Publication  No  EPA-
    RI-73-005. 1973.
 2  Mauser, T.  R., J  J  Henderson, and  F  B. Benson. The
    polynuclear hydrocarbon and metal  concentration of the air
   over  the Greater   Birmingham Area  Human Studies
    Laboratory,  U.  S.  Environmental  Protection Agency
   Research  Triangle Park, N C. Unpublished Report.
 3 Kanawha  Valley Air  Pollution Study. U.S Environmental
   Protection Agency.  Research Triangle Park, N.C Publica-
   tion No. APTD-70-1  March  1970.
 4. Hunt, W. F., C. Pmkerton, O  McNulty, and J  Treason  A
   study  in trace element pollution of air in 77  midwestern
   cities. In: Trace Substances in Environmental Health  IV. D.
   P  Hemphill (ed.). Columbia, University ot Missouri Press.
    1971.  p 56-58.
 5, Maga,  J A.,  F B.  Hodges. C B. Chnstenson.  and  D J.
   Callaghan. A Joint Study of Lead Contamination Relative to
   Horse  Deaths in  Southern  Solano  County Los Angeles,
   State of California Air Resources Board.  September 1972
   178 p
 6 Mclntire, M. S and C. R. Angle Air lead Relation  to lead
   in  blood  of black school children  deficient in  glucose-6-
   phosphate dehydrogenase. Science. / 77/520-522,  August
   1972.
 7. Henderson, J.  J. and P. A. Hudson. Unpublished trip report
   re- the City of El Paso and State  of Texas (Air Control
   Board) vs.  American  Smelting  and  Refining  Company
   (ASARCO), Cause No. 70-1701. Air Quality Enforcement
   Office, EPA Region  VI. Dallas, Texas. May 12, 1972
  8 Shearer, S D  and J. J Henderson. El Paso Smelter Bneting
    Paper, Environmental Monitoring and Support Laboratory,
    U S  Environmental Protection Agency  Research Triangle
    Park, N C May 1972
  9. Helena Valley, Montana, Area  Environmental  Pollution
    Study. U.S Environmental  Protection  Agency  Research
    Triangle Park, N C. Publication AP-91  January 1972
 10 Purushothaman. K  Air Quality  Studies ot  a Developing
    Lead Smelter  Industry  Rolla, University of Missouri Press
    1972  13  p
 1 1  Laamanen, A   and  A  Ryhanen  Aerial distribution  ot
    dustrall  lead  in [he  neighborhood  ot some  lead emitters
    Suomen  Kemistilehti. (Helsinki)  44 367-371, 1971
 12 Fugas. M , D.  Ma|ic, R  Paukovic, B. Wilder,  and Z  Skanc
    Biological Significance ot  Some  Metals as Air Pollutants.
    Final Report  Part  1  Lead  U S Department ot Health,
    Education, and Weltare, Consumer Protection and Environ-
    mental Health Service  Washington, D.C  January 1974
 13 .Lmzon, S  N , B L  Chai, P. J. Temple, R. G  Pearson, and
    M  L Smith Lead contamination  ot urban soils and  vegeta-
    tion  by emissions  from secondary  lead  industries  J. Air
    Pollut Control Assoc 26(7)  650-654,  1976
 14 Lead- Airborne Lead in Perspective Washington. D.C.Ra-
    tional Academy of Sciences  1972 p 28
 15  Swaine, D J. and R  L Mitchell. Trace element distribution
    in soil profiles J. Soil Sci  / /(2V347-368, 1960.
 16. Goldschmidt,  V M  The principles ot distribution of chemi-
    cal elements in minerals and rocks J Chem Soc (London.)
    655-673.  1937
 I 7. Tyler, G  Heavy metals pollute nature, may reduce produc-
    tivity Ambio. /(2):52-59, 1972
 18  Dunn. J  T  and H  C. L Bloxam  The occurrence of lead,
    copper, zinc, and arsenic compounds in atmospheric dusts,
    and the sources of these impurities J Soc  Chem Ind. Lon-
    don Trans. Commun  52.189-192  1933.

 19. Smith, W. H. Lead contamination of the roadside ecosystem.
    J. Air Pollut. Control Assoc. 26(8):753-770, 1976
20.  Rolfe, G.  L. and A  Haney An Ecosystem Analysis  ot En-
    vironmental Contamination by Lead Institute for Environ-
    mental Studies, University of Illinois at Urbana-Champaign
    Research Report No. 1. August 1975. p 53-56

21  Human  Lead  Absorption  -  Texas.  U.S.  Department ot
    Health,  Education, and Welfare  Atlanta, Georgia.  Mor-
    bidity and Mortality Weekly Report. 22(49).405-407, 1973
                                                      C-9

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22  Pakhotina, N.S. Sanitary hygienic evaluation ot industrial         dusts for  human populations. Arh.  Hig  Rada  Toksikol.
    emissions by a zinc-lead  combine. In: Survey of USSR         (Yugoslavia.) 26/81-93,  1975.
    Literature on Air Pollution and Related Occupational Dis-     25. Smokotnma, T. N. Hygienic evaluation of air pollution with
    eases. U  S  Public Health  Service.  Washington, D.C         wastes from a lead plant Hig. Sanit. (USSR). 27(6):87-90,
    j.93-97, 1960.                                                 1962.
23  Little, P. and M H. Martin. A survey of zinc, lead and cad-     26. Paluch, J. and  S. Karweta. The accumulation ot zinc and
    mium in soil and natural vegetation around a smelting com-         lead in soil and plants In- Lectures of 6th lnt'1 Congress of
    plex. Environ  Pollut. 3:241 -254, July I 972.                      Forestry Specialists for Smoke Damage. Katowice. (Poland.)
24  Barltrop, D.  Significance  ot  lead-contaminated soils and         1968. p 127-138
                                                          C-10

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                                      APPENDIX D
             UNITS  AND METRIC CONVERSION  FACTORS
  In each of the disciplines dealing with lead in  a
sector of  the environment, conventions for units
have evolved that are convenient to each but not al-
ways familiarly translatable from one to the other,
even when expressed in metric units. There are also
two distinct categories of measurements: concentra-
tions and  transfer  rates. Within  each category of
measurements,  straightforward conversion factors
translate the quantitites from one system of units to
another. Connections between the two categories are
bridged  only by mathematical models of varying
complexity that account for all significant transfer
rates, both into and out of a given  context, as well as
measure that context's capacity  to  distribute and
equilibrate any  net change  that will  add to or
substract from its initial  concentration.
D.I  CONCENTRATIONS

  Airborne lead concentrations are customarily re-
ported in units of mass per volume: micrograms of
lead per cubic meter of air (/u.g/m3). Concentrations
of lead in soils and dusts are  reported in units of
mass per mass: micrograms of lead per gram of the
parent material  (/Ag/g),  or as parts per million
(ppm). When ppm refers to mass, the expression is
interchangeable with /i,g/g.

  Concentrations of lead in water (dissolved or sus-
pended) may be reported in parts per billion (ppb)
or micrograms per liter (/xg/liter). For our purposes,
a liter of water can be equated with 1000 g, and units
of /Lig/liter  can  be  interchanged  with  ppb or
nanograms per gram (ng/g).

  Concentrations of lead in food are usually given in
parts per  million  (ppm),  micrograms per  gram
(/Mg/g), or milligrams per kilogram (mg/kg), all of
which are interchangeable.
  Concentrations of lead in blood may be reported
in micrograms  per  deciliter  (^ug/dl)  or  in
micrograms per 100 grams (/ug/100 g). These are not
equivalent since  1 dl of blood weighs between  105
and 106 g.

D.2 TRANSFER RATES

  In general, transfer rates describe the movement
of material from one medium or context to another
in units of mass per time or  mass per quantity (mass
or volume) of a parent material. Some rates include
a linear or area dimension to express the transfer per
unit of interface between media.
  The lead in ores that  is transfered to smelters and
hence to manufactured products is described by pro-
duction figures and reported in tons (short) per year
(tons/yr)  or tonnes (metric) per year  (MT/yr). The
attendant dispersal of some  of that lead into the air,
water, and soil is described by emission factors: tons
per year  (tons/yr), kilograms  per day  (kg/day),
pounds per ton of raw material or product (Ib/ton),
pounds per thousand gallons (lb/103gal), grams per
kilometer (g/km), etc.
  The most familiar transfer rate between media is
perhaps the dustfall or  deposition rate, reported in
tons  per square  mile per  year  (tons/mi2/yr),
milligrams per square meter per month (mg/m2/mo),
etc.
  The culminating concern is with transfer rates, in-
volving the human body, through inhalation and in-
gestion followed by retention  and  absorption into
fluids and tissues, and, finally, excretion, all of
which are commonly expressed in micrograms per
day, micrograms per kilogram of body weight per
day, or,  even, as micrograms per square  meter of
body surface.
                                              D-1

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D.3 UNITS

  1 m = lOVm = 102cm =  10'3km = 3.281 ft =
        39.37 in
  Im2= 104cm2 = 10-ftkm2 = 10.76ft2 =
        1550 in2
  Im3 = 106cm3 = 999.97 liters = 35.31 ft3 =
        6.1 x 104in3 = 264.2gal

  1 g =  106 Mg = 103 mg = 10-3 kg = 0.035 oz =
        0.0022  Ib

  1 tonne (metric) = 1000 kg = 106g =
        1.1023 tons (short)
D.4 CONCENTRATION CONVERSION
FACTORS
  1 ppb (mass) = 1 ng/g = 1/ug/kg
  1 ppm (mass) =  1 pglg =  1 mg/kg
  1 mg/liter (water) »  ] ppm -a* l^g/g
  1 /ag/liter (water) —  1 ppb
  1 /u.g/dl  (blood) « 0.95 /ug/100g (blood)
D.5 TRANSFER RATE CONVERSION
FACTORS
   1 mg/m2/mo = 2.85 x 10-3tons(short)/mi-2/mo
   1 tonne/yr = 2.74 kg/day =
       1.1023 tons (short)/yr
   1 /ig/day = 3.53 x 10-8oz (av.)/day
                                            D-2

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                                     APPENDIX  E

           ABSTRACT OF  A  REVIEW  OF THREE  STUDIES

                  ON  THE  EFFECTS OF  LEAD  SMELTER

                       EMISSIONS  IN EL  PASO, TEXAS
                                  Presented by Warren R. Muir
                                Council on Environmental Quality
                                       Washington, D.C.
                            At the International Conference on Heavy
                                   Metals in the Environment
                                    Toronto,  Ontario, Canada
                                         October 1975
  The committee reviewed two independent studies conducted in  1973 by Dr. Landrigan (CDC) and Dr.
McNeil  (ILZRO) to determine the effects  of community lead exposures near the ASARCO smelter in El
Paso, Texas. The CDC study used a random sample approach  to group participating children, and in the
ILZRO  study match paired groups were selected  on the basis of residence. In both studies the criteria for
subclassification with regard to lead exposure were blood lead levels. Neuropsychological dysfunction was
evaluated by several tests including WISC, WPPSI, and McCarthy scales. Statistical differences in test results
could not be directly correlated to blood lead levels.
  The opinion of the committee was that no firm conclusions could be drawn from the studies as to whether or
not there are subclinical effects of lead on children in El  Paso and that the reports and data made available
have not clearly demonstrated any psychologic or neurologic effects in the children under study. It noted the
absence  of major chronic clinical effects, and concluded that these studies therefore do not bear upon the con-
clusions of other investigations under different conditions and those in which clinical effects have been con-
firmed. However, because of inherent problems of study design and the limitations  in the tests used, this find-
ing should not lead to a conclusion that low levels of lead have no effects on neuropsychological performance.
Ellen Silbergeld, Ph.D., NIH, Eileen Higham, Ph.D., and  Mr.  Russell Jobaris, Johns Hopkins University,
Department of Medical Psychology, served as special consultants.
  The committee decided to limit its focus to a review of the three studies, and to attempt to account for and
interpret the differences between the studies. Thus, aspects not related to differences were not emphasized.
  The committee limited its consideration to  the following materials: (1) reports  of the three studies under
consideration; (2) other materials provided by the authors of the studies; (3) background information and
documents collected by Dr. Muir in El Paso. This presentation today consists of excerpts from a draft com-
mittee report.
E.I HISTORY
  El Paso is situated on the Mexican border in the  western part of Texas. A lead smelter owned by American
Smelting and Refining Company (ASARCO) has been located on the southwestern border of the city, on the
Rio Grande River, since 1887. The area most conspicuously involved in the studies, Smeltertown, was a 2 x 6
block area located  between the plant and  the river. Smeltertown is no longer in existence, having been
destroyed in December 1972. About 2 km  south of Smeltertown is Old Fort Bliss, a considerably smaller
community, whose inhabitants were considered in some,  but not all, of the studies.
  The ASARCO smelter produces lead, zinc, copper, and cadmium. Particulate matter is removed from air-
borne wastes in a series of baghouses; remaining emissions contain  approximately 40 Ib of lead per day.
  The E! Paso City County Health Department began an investigation of the ASARCO smelter in early 1970,
in preparation for an air pollution suit filed  by  the city in April  1970. As part  of this investigation. Dr.

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Bertram Carnow was hired by the city as a consultant. At his suggestion, the city began to sample the blood
lead levels of El Paso children to determine whether any had been over-exposed to lead. This included a large
number of Smeltertown children. Based upon early results in  1971, Dr. Carnow visited El Paso, and saw a
selected group of children with high blood lead levels. He interviewed the children, and reviewed their medi-
cal records. The information contained in the medical histories, and Dr. Carnow's interviews, constitute the
observations reported by Dr. Carnow in the paper presented to the American Pollution Control Association
(APCA). The clinical observations were in a paragraph of a paper otherwise devoted to a consideration of the
effects of the smelter on the environment as a whole, and the extent of its emissions. This report contains no
details on the age, exposures, individual signs and symptoms,  or diagnostic criteria used in the ten cases re-
ported. Our committee focused its attention, therefore, upon the two full-scale follow-up epidemiological
studies conducted by Dr. Landrigan (CDC) and Dr.  McNeil  (ILZRO).
  In 1973 ASARCO began a separate investigation of the population of Smeltertown, and asked Dr. James
McNeil of the International Lead Zinc Research Organization (ILZRO) for his assistance in the examination
and possible treatment of children with elevated blood levels greater than 60 mg/100 ml.
  As a result of public concern over widespread lead poisoning throughout the city of El Paso, the mayor re-
quested aid from the Federal Government. A separate protocol for a Center for Disease Control (CDC) study
was submitted to and approved by the Public Health Board  in 1973 with the understanding that the two
studies would proceed independently,  with those children in the ILZRO sponsored study being excluded
from the CDC study.
  In the summer of  1973, CDC and ILZRO proceeded independently to collect data for their respective
studies. CDC's examinations were done in two weeks in June 1973, while McNeil's were carried out over the
course of the summer with the aid of the El Paso public school system.
  The CDC group supplied to the Committee data in detail, which were sufficient to allow the committee to
conduct statistical tests and analyze characteristics of groups. For the ILZRO study, this committee requested
data sufficient to carry out similar in-depth analyses.  All of the requested data were supplied; however, they
were not in such a form  as to allow recalculation of most of the statistical findings of the study or to allow
comparison with the CDC findings.


E.2 STUDY DESIGN
  The environmental sampling that was performed was common for both of these studies. In the selection of
study and control populations, the Landrigan  CDC study used a classical approach of a random  sample
survey to determine the prevalence of abnormal blood lead values. The 13 census tracts most adjacent to the
smelter were divided into three areas. The sampling frame was designed to obtain about 100 study subjects
from each area for various age groups. Of 833 occupied residences, interviews were obtained from 758 study
subjects in the 1-19 age group. The participating children were divided into a lead-absorption group (40-80
^tg/100 ml) of 46 and a control group « 40 /ug/100 ml) of 78. There is no detailed description as to how the
children were chosen.
  CDC used these same children as the basis for the later study of neuropsychological dysfunction. All but 3
children chosen for study came from the 1972 prevalence survey; 5 children with known preexisting defects
such as with a history of symptoms compatible with acute lead poisoning  or acute lead encephalopathy and
those who had received  chelation therapy were excluded.
  While it is understood that a number of Smeltertown children with blood lead levels over 40 //.g/100 ml
were eventually involved in litigation,  most of them took part in the studies. However, on the recommenda-
tion of the lawyers representing the children, at least one group of 18 did not participate in the ILZRO study.
In the absence of identification by names of the individuals  in the three studies, it has been impossible to
evaluate the effects of non-participation.
  The ILZRO study was very different; 138 children from Smeltertown agreed to participate in a study. Resi-
dence, not blood lead, was the selection criterion. Two control groups were chosen, and were reported to have
been matched on age, sex, ethnic background, and income, with one set chosen from El Paso and another set
for those 8 years of age or under from a rural area about 12 miles from the smelter. This classification had the
effect of grouping together children who, under the CDC criteria, would have been in "lead" and "control"
groups.

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  The criteria used for subclassification of children with regard to lead exposure were based in both studies
on the blood lead level. Whereas the CDC study utilized  blood lead values obtained at only  two points in
time, ILZRO, which was faced with the problem that many children had repeated blood lead measurements
with marked variations over a period of 18 months (the levels being generally lower after exposure was dis-
continued), classified children  on the basis of the average of the "two highest" recorded values.
  This criterion results in a substantial increase in the number of children in the apparently higher blood lead
category and a corresponding  decrease in the number of those in  the apparently lower blood  lead level
category.
  Although  it is understandable that this type of selection was used to avoid underestimating the problem of
lead intoxication in the population examined, it ultimately resulted in muddling of the separation between
groups (and  possibly obscuring  eventual differences). For example, the selection for analysis of children from
the same geographical area, subclassified according to blood lead level, in the ILZRO study, may give the im-
pression that the effects of lead itself are being studied in a homogeneous population. However, since  ex-
posure was geographically the same, other factors inherent to each individual child may be responsible for the
difference in blood lead level observed.
  An additional method of classification could  have been the use  of free erythrocytic protoporphyrin
measurements (FEP) which have been shown to provide an indication of metabolic effects of lead absorption
on metabolism, particularly useful  in  blood  lead level  ranges (40-60 /ug/100 ml) where analytical and
biological fluctuation may result in uncertain classification. (The ILZRO study included this test but did  not
include it as a basis for  data analysis.) Absence of elevation of free erythrocytic protoporphyrin may indicate
those instances where high blood lead levels were spurious.
  The following psychometric  tests were employed by the two studies:
      1.  Wechsler Intelligence  Scale for Children, WISC (CDC. ILZRO)
     2.  McCarthy Scales of Children's Abilities (ILZRO)
     3.  Wechsler Preschool and Primary Scale of Intelligence, WPPSI (CDC)
     4.  Lincoln-Oseretsky Motor Development Scale (ILZRO)
     5.  California Test of Personality Adjustment (ILZRO)
     6.  Frosting Perceptual Quotient (ILZRO)
     7.  Bender Visual-Motor  Gestalt Test (CDC, ILZRO)
     8.  Peabody
     9.  WRAT
     10.  Wepman
     11.  Draw-a-person
  All of the tests selected by both studies were appropriate for the ages of the children to whom they were  ad-
ministered. Since the common ground for these studies is the WISC test, with the WPPSI used by CDC and the
McCarthy Scales by ILZRO for the younger children in their studies, the Committee concentrated on these
three tests and the results obtained for them.
E.3  RESULTS
  The study by CDC reports results for 27 children given the WPPSI (12 with blood lead levels 40-80 ;u.g/100
ml and 15 with blood lead levels less than 40/ig/100ml) and for 97 children tested with the WISC (34 in  the
"lead group" and 63 in the "control group"). Statistical analyses were performed on grouped data with one-
tailed tests. Significant differences between lead and control groups are reported in this study for the perfor-
mance IQ's of the WICS and WPPSI. In subtest scores, significant differences were found in Coding on  the
WISC and Geometric Design on the WPPSI. When data from both tests are combined, a significant difference
between lead and control groups on performance IQ is found. No differences were found between groups in
verbal IQ's or full-scale IW's of the WISC or WPPSI.
  The ILZRO study based on match pairing solely by residences reports no significant differences in scores
on the WISC or McCarthy scales between groups with increased lead absorption and pair-matched controls.
Statistical analysis was by means of two-way analysis  of variance by age and blood lead levels.
  The two studies base much of their conclusions upon psychometric and neurological testing of children
from El  Paso and Smeltertown. The reported significant differences and psychometric and neuromotor func-
tions in the CDC study were clouded by potentially important methodological  difficulties. These included

                                               E-3

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age differences between case and control groups,  limited statistical treatment of the psychometric data col-
lected, and, in the ILZRO study, the use of an average of the two highest blood lead levels to categorize lead
exposure.
  In addition, both the studies shared the following inherent problems-.
     1. Non-random exclusion  of large groups of children
     2. Uncertainties as to the selection of control groups
     3. Reliance upon  blood lead as the indicator of lead exposure and intoxication in analyses of data
     4. Measurement of a limited aspect of psychological behavior
     5. Lack of consideration of the potentially disruptive influences on test taking of the razing of Smelter-
       town, closing of its school, resettlement, litigation,  and public controversy
     6. Inability to rule out possible preexisting conditions
  The Committee stressed the last issue, noting the likelihood that any behavioral or genetic factors that pre-
dispose an individual child to ingest or absorb more lead than another child equally exposed may  itself be
correlated to he result of psychometric testing. In other words an increased blood  lead level may reflect,
rather than cause, a preexisting difference  in  intelligence  or  behavior, an issue inherent in virtually  all
retrospective studies of the effects of low  level blood lead.
  The opinion of the committee was that no firm conclusions could be drawn from the studies as to whether or
not there are subclinical effects of lead on children in El Paso and that the reports and data made available
have not clearly demonstrated any psychologic or neurologic effects in the children under study. It noted the
absence of major chronic clinical effects, and concluded that these studies therefore do not bear upon the con-
clusions of other investigations under different conditions and those in  which clinical effects have been con-
firmed. However, because of inherent problems of study design and the limitations in the tests used, this find-
ing should not lead to a conclusion that low levels of lead have no effects on neuropsychological performance.
                                                 E-4                     *»S GOTERltMEin PRINTING OFFICE 1978— 757-140/6681

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