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
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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
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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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
1-3
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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-
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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-
1-5
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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
1-6
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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
1-7
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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-
1-8
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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
1-9
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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.
1-10
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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.
1-11
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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
-------
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
-------
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
-------
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
-------
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
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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
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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
4-7
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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
4-8
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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
-------
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
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atmosphere by atomic absorption spectrometry Anal
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and lead-210 in rainwater Nature 216(5 I 1 3).353-355,
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33 Lagerwerff, J V and A W Specht Contamination ot
roadside soil and vegetation with cadmium, nickel, lead,
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34 Olson, K. W and R K Skogerboe Identification of soil
lead compounds from automotive sources Environ Sci
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36. American Society tor Testing and Materials. Standard
method for collection and analysis of dustfall (settleable
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517-521, 1975.
37. Hinners, T , J. Kent, W Ternll, T Heiderscheit, R Bur-
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38. Smith, W H Metal contamination of urban woody plants
Environ Sci Technol. 7(7)631-636, 1973
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Corneliussen, and C F Jelinek. Food exposures to lead.
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method of test for lead in the atmosphere by colonmetric
dithizone procedure D3112-72T. Ar.nu. Book ASTM
Stand. Pt 26:633-641, 1975.
41. Coulson, D. M., D L. Haynes, M. F. Balazs, and M. P.
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Asbestos, Beryllium, Lead, Cadmium, Selenium, and Mer-
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exhaust—experimental techniques. Environ. Sc. Technol.
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Pierson Sulfunc acid and nitrate emissions from oxida-
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44 Ter Haar, G L., D L Lenane, J. N. Hu, and M. Brandt.
Composition, size, and control of automotive exhaust par-
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45 Sampson, R. E. and G. S. Springer Effects of exhaust gas
temperature and fuel composition on paniculate emission
from spark ignition engines. Environ. Sci. Technol.
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46 Ganley, J T and G S Springer Physical and chemical
characteristics of particulates in spark ignition engine ex-
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47 Moran. J B , M J Baldwin, O J Manary, and J. C.
Valenta. Effect of fuel additives on the chemical and
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APTD-1567 1973
49 Hirschler, D A , L. F Gilbert, F W. Lamb, and L. M.
Niebylski Paniculate lead compounds in automobile ex-
haust gas Ind. Eng Chem. 49(7) 1 1 31-1 142, 1957
50. Hirschler. D A. and L. F Gilbert. Nature of Lead in ex-
haust gas. Arch Environ Health S'297-31 3, 1964.
51 Habibi. K Characterization of paniculate matter in vehi-
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52. Kunz. W G , Jr . E S. Jacobs, and A. J. Pahnke Design
and performance of muffler lead traps for vehicles. Pre-
sented before Union Indersyndical de I'ndustne du
Petrole. Pans. France January 1975
53 Gandrud, B W and A L. Lazrus. Design of system for
removing water-soluble materials from IPC-1478 filter
paper. Environ Sci Technol. 6(5H55-457, 1972
54. Luke, D. L., T. Y. Kometam, J. E. Kessler, T. C. Loomis,
J. L. Bove, and B. Nathanson. X-ray spectrometric
analysis of air pollution dust. Environ Sci. Technol.
6(13):1105-1 109, 1972.
55 Kometam, T. Y , J. L. Bove, B. Nathanson, S. Sieben-
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matter on paper and glass fiber filters for trace metal
analysis by atomic absorption spectrometry. Environ. Sci.
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56 Witz, S. and R. D. Macphee. Effect of Different Types of
Glass Filters on Total Suspended Particulates and Their
Chemical Compounds. Southern California Air Pollution
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58. Scott, D. R., W A. Loseke, L. E Holboke, and R. J.
Thompson. Atomic absorption and optical emission
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1977
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Metals Interscience Publishers, Inc , New York 1944
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65 Huntzicker, J J , S K I-nedlander. and C I Davidson.
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Time variations of lead, copper, and cadmium concentra-
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(T G Lovering, ed ) U S Geological Survey Professional
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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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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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6-28
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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
-------
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
•cu
16
V)
E
~3i
iu
>
UJ
S «
UJ
_j
cc
<
Z
UJ
<5
2
< 8
.j
<
D
Z
Z
<
Z
<
S
4
1
-
8C
10
1
3
4(
8
PV
67
^ 1 AUG. 1974
PT??1 AUG 1975
-
-
_
49
71
li
::.: il CONTROL
::: !^1 1 5 T 16
i I n n n
1 2 3 4 567
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
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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.
7-12
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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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1967.
46. Zurlo, N. and A M Griffini Lead contents in food and
beverages consumed in Milan. In- Proc. Inter Symp on
Environmental Health Aspects of Lead. Amsterdam, Oct.
1972. Luxembourg, Commission of the European Com-
munities. 1973. p 93-98.
47. Boudene, C . F. Arsac, and J. Meminger. Study of air and
population lead levels in France. Arch Hig. Rada
Tekisol 26(Suppl.): 179-189, 1975.
48. Durum, W. H. Reconnaissance of Selected Minor Ele-
ments in Surface Waters of the U.S. U.S. Dept. of Interior,
Geologic Survey. Washington, DC USGS Circular No.
643. 1971.
49. Durfor, C N., and E. Becker. Public Water Supplies of the
100 Largest Cities in the United States, 1962. U S Dept. of
Interior, Geologic Survey. Washington, D.C. USGS Water
Supply Paper No. 1812. 1964 364 p.
50 Chemical Analysis of Interstate Carrier Water Supply
Systems. U.S Environmental Protection Agency. Research
Triangle Park, NC Pub. No. EPA 430/9-75-005 1975 88
P-
51. Rolfe, G. L. and A. Haney. An Ecosystem Analysis of En-
vironmental Contamination by Lead. Inst for Env.
Studies, U. of Illinois, at Urbana-Champaign, 111. Res.
Kept. No. 1. 1975. p. 22-34.
52. McCabe, L. J. et al. Survey of community water supply
systems. J. Amer. Water Works Assn. 62(1 1):670, 1970.
53. Hem, J. D. and W. H. Durum. Solubility and occurrence
of lead in surface water J Amer Water Works Assn
<55(8):562-568, 1973.
54. Lazrus, A L., E Lorange, and J. P. Lodge, Jr. Lead and
other metal ions in U.S. precipitation. Environ. Sci. Tech.
4(l):55-58, 1970.
55 Kopp, J F. and R C Kroner. Trace Metals in Waters of
the United States; A Five-Year Summary of Trace Metals
in Rivers and Lakes of the Untied States (Oct. 1, 1962 -
Sept. 30. 1967). US Dept. of Interior, Federal Water
Pollution Control Administration, Cincinnati, Ohio.
1967 218 p
56. Environmental Health Criteria Vol. 3., Lead. United Na-
tions Environment Program/World Health Organization,
Geneva. Switzerland. 1977. p. 59-65.
57. Berg, B. A., and C. Zenz. Environmental and clinical con-
trol of lead exposure in a nonferrous foundry J. Amer.
Ind. Hyg. Assoc 28(2) 175-178. 1967
58 Pegues, W. L. Lead fume from welding on galvanized and
zinc-silicate coated steels J. Amer. Ind. Hyg. Assoc.
2/(3):252-255, 1960.
59 Tabershaw, I R., B. P W Ruotolo, and R P. Gleason
Plumbism resulting from oxyacetylene cutting of painted
structural steel. J. Ind Hyg. Toxicol 25(5):189-191,
1943
60. Rieke, F E. Lead intoxication in shipbuilding and
shipscrapping, 1941-1968. Arch Env. Health.
;9-521-539. 1969
61 Brandt, A. D and G. S. Reichenbach. Lead exposures at
the government printing office J. Ind. Hyg Toxicol.
25(10):445-450, 1943.
62. Tsuchiya, K. and S. Harashima. Lead exposure and the
derivation of maximum allowable concentrations and
threshold limit values. Brit. J. Ind. Med 22(3):1 81-1 86,
1965.
63. Linch, A. L., E G Wiest, and M. D. Carter. Evaluation of
tetraalkyl lead exposure by personal monitor surveys. J.
Amer Ind. Hyg. Assoc. 3/(2V170-179, 1970.
64 H. M Chief Insp of Factories H M Great Britain Dept.
of Employment. Annual Report, 1971. London, Her Ma-
jesty's Stationery Office. 1972. p. 60, 95.
65. Scarlato. G , S Smirne, and A. E. Poloni. L'encefalopatia
saturnina acuta dell adulto. Acta Neurol. 24:578-580,
1969.
66. Mal|kovic, J. A case of occupational poisoning with lead
carbonate and stearate. Sigurnost u Pogonu. 75:123-124,
1971.
67 Sakurai, H., M. Sugita, and K Tsuchiya Biological
response and subjective symptoms in low level lead ex-
posure. Arch. Env. Hlth. 29:157-163, 1974.
68 Committee on Toxicology, National Research Council.
Recommendations for the Prevention of Lead Poisoning
in Children. Consumer Product Safety Commission,
Washington, D.C. 1976. p. 45, 51
69. Piver, W. T Office of Health Hazard Assessment, NIEHS,
Personal communication to H. L. Falk, Assoc. Dir. for
Health Hazard Assessment, NIEHS, Research Triangle
Park.N.C. January 10, 1977.
70 Vaughn, D. A., C. Iteadi, R. A. Markle, and H. H. Krause.
Environmental Assessment of Future Disposal Methods
for Plastics in Municipal Solid Waste. U.S. Environmental
Protection Agency, National Environmental Research
Center, Cincinnati, Ohio. Pub No. EPA-670/2-75-058.
1975. 86 p.
71 Control Techniques for Lead Air Emissions. (Draft final
report.) U.S. Environmental Protection Agency, EPA Con-
tract No. 68-02-1375, Cincinnati, Ohio. October 1976.
424 p.
7-16
-------
72. Hankin, L., G H. Heichel, and R A Botsford Lead on Geochim. Cosmochrm. Acta. (London). 3.?:1 247-1294,
painted handles of kitchen utensils. Clin Pediat 1969.
/5(7):635-636, 1976 74 Jaworowski, Z. Stable lead in fossil ice and bones. Nature
2/7-152-153, January 13, 1968.
73. Murozumi, M.,T J Chow, and C. C. Patterson. Chemical 75 Ruhling. A and G Tyler An ecological approach to the
concentrations of pollutant lead aerosols, terrestrial dusts, lead problem Bot. Notis. (Stockholme) /2/'321-342,
and sea salts in Greenland and Antarctic snow strata 1968.
7-17
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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
-------
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.
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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
-------
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
-------
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
-------
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-
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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.
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85 Schroeder, H. A and A P. Nason. Trace element analysis
in clinical chemistry Clm. Chem. /7461-473, 1971
86. Costellmo, N., P Lamanna, and B. Gneco. Biliary excre-
tion of lead in the rat Brit. J. Ind. Med. 23237-239, 1966.
87 Blaxter, K L. and A. T. Cowic Excretion of lead in the
bile. Nature 757588, 1946
88. Cohen, N , M. Eisenbud, and M E. Wrenn. The Retention
and Distribution of Lead-210 in the Adult Baboon. An-
nual Rept to the U.S. Atomic Energy Commission (Oct I,
1962 -Sept. 30, 1967). U.S. Dept of Interior Cincinnati,
Ohio 1967 218 p.
89. Cikrt, N Biliary excretion of 2°3Hg, MCu, 52Mn, ^Pb in
the rat. Brit. J. Ind. Med 29 74-80, 1972
90. Vostal, J Mechanisms of renal lead excretion. Biochem
Pharmacol Conf Issue. 2 207, 1963.
91. Cremer, J E and S. Callaway. Further studies on the tox-
icity of some tetra- and tnalkyl lead compounds Brit. J
Ind. Med. 18-277-282, 1961
92 Bolonowska, W. Distribution and excretion of tnethyl
lead in rats. Brit J. Ind Med. 25.203-208, 1968
93. Cremer, J E. Toxicology and biochemistry of alkyl lead
compounds Occup Health Rev 7714-19,1965.
94. Gutniak, O , H Koziolowa. and E Kowaiski Free pro-
toporphynn content of erythrocytes in chronic tetraethyl
lead poisoning. Lancet / 1 137-1 138, 1964
95 Seattle, A D., M R Moore, and A. Goldberg. Tetraethyl-
lead poisoning. Lancet 2'12-1 5, 1972
96. Robinson, T. R Delta-ammo levulmic acid and lead in
urine of lead antiknock workers Arch Environ Hlth.
2S-133-139, 1974.
97 Bolanowska, W , J Piotrowski, and H Carczynski
Triethyllead in the biological material in cases of acute
tetraethyllead poisoning. Arch Toxicol. 22 278-282,
1967.
98 Ziegler, E. E , B B Edwards, R. L. Jensen, K P.
Mahaffey-Six, and J. J Fomon Absorption and retention
of lead by infants. Ped Res 12. In Press. 1978
99 National Research Council. Recommendations for the
prevention of lead poisoning in children. National
Academy of Sciences Washington, D C July 1976.
100. Lin-Fu, J S. Vulnerability of children to lead exposure
and toxicity N. Engl J, Med I. 289(23).1229-1 233, 1973.
101 Lin-Fu J. S. Vulnerability of children to lead exposure
and toxicity. N. Engl. J Med. II 289(24)T 289-1293,
1973
102. Rosen, J. F and E E Wexler Studies of lead transport in
bone organ culture. Biochem Pharmacol 26 650-652,
1977.
10-11
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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
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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
11-3
-------
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
.1-4
-------
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
11-5
-------
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,
11-6
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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-
11-7
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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
11-8
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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
11-9
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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
11-10
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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
11-11
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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
11-12
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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
11-13
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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
11-14
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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-
11-15
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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
11-16
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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
11-17
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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-
11-18
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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
11-19
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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
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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
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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
-------
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
-------
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
-------
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-
11-43
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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.
1-44
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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
1-46
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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
11-47
-------
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
11-48
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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
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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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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
-------
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
-------
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
-------
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
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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
-------
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
-------
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
-------
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
-------
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
-------
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.
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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
-------
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
-------
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
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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
-------
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
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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
-------
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
-------
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.
A-l
-------
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.
A-2
-------
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,
-------
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).
A-8
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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) =
-------
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
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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.
E-2
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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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