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P.2 

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EPA 600/8 77 017 

December 1977 

Special Series 

Air Quality Criteria for 

WDEJI 

Office of Research and Development " 

U.S. Environmental Protection Agency

 ; -egg? 

Washington, D.C. 20460 'T^ T 
P.3 

RESEARCH REPORTING SERIES 

Research reports of the Office of Research and Development, U.S. Environmental Protection 

Agency have been grouped into series. These broad categories were established to facilitate further 

development and application of environmental technology. Elimination of traditional grouping 

was consciously planned to foster technology transfer and a maximum interface in related fields. 

These series are: 

1. Environmental Health Effects Research 

2. Environmental Protection Technology 

3. Ecological Research 

4. Environmental Monitoring 

5. Socioeconomic Environmental Studies 

6. Scientific and Technical Assessment Reports (STAR) 

7. Interagency Energy-Environmental Research and Development 

8. "Special" Reports 

9. Miscellaneous Reports 

This report has been assigned to the SPECIAL series. Air quality criteria documents are issued, as 

mandated by the Clean Air Act, to provide the basis for decisions by the Administrator, EPA, 

regarding the need for national ambient air quality standards. 

EPA REVIEW NOTICE 

This report has been reviewed by the Office of Research and Development, EPA, and approved for 

publication. Mention of trade names or commercial products does not constitute endorsement or 

recommendation for use. 

AVAILABILITY NOTICE 

This document is available through the Library Services Office, MD-35, Research Triangle Park, 

N.C. 27711. The printed version will also be available from the Superintendent of Documents, U.S. 

Government Printing Office, Washington, D.C. 20402. 

Publication No. EPA-600/8-77-017 
P.4 

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 sal e by the Superintendent of Documents', U.S. Government 

Printing Office, Washington, D.C. 20402 
P.5 

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 protect 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 secondary 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 pollutant in question, the document does not constitute a complete, in-depth scientific 

review. The references cited do not constitute a complete bibliography. The objective 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 intake. It is necessary, therefore, to evaluate the relative contribution made by inhalation and ingestion of atmospheric lead to the total body burden. 

The Agency is pleased to acknowledge the efforts and contributions of all persons' and groups who have participated as authors or reviewers to this document. In 

the iast analysis, however, the Environmental Protection Agency is responsible for 

its content. 

DOUGLAS M. COSTLE 

Administrator 

U.S. Environmental Protection Agency 

in 
P.6 

ABSTRACT 

This document summarizes current knowledge about the relationships of airborne lead to man and his environment. The effects that have been observed to occur 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 exposure 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 sequesters 95 percent of the body's lead burden. Significant biological indices of exposure to lead include microgram quantities of lead and of erythrocyte protoporphyrin (EP) per deciliter of blood (/xg/dl). Adverse effects range from elevated EP and mild anemia at 20 to 40 fig Pb/dl—through gastrointestinal, renal, 

and hepatic pathologies—to severe neurobehavioral impairment at >80 to 120 fig 

Pb/dl, sometimes culminating at those levels in convulsions and abrupt death. 

Preschool children and developing fetuses are the populations at greatest risk. 

IV 
SCIENCE ADVISORY BOARD 

SUBCOMMITTEE ON SCIENTIFIC 

CRITERIA FOR ENVIRONMENTAL LEAD 

P.7 

1 

The substance of this document was review by a Subcommittee on Scientific Criteria 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 Environmental 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, Connecticut 06504 

MEMBERS: 

Dr. Samuel S. Epstein, Professor of Occupational and Environmental Medicine, 

School of Public Health, University of Illinois, P.O. Box 6998, Chicago, Illinois 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 Environmental 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 College 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, Department 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. Environmental Protection Agency, Crystal Mall Building 2, 1921 Jefferson Davis 

Highway, Arlington, Virginia 20460 
P.8 

CONTRIBUTORS AND REVIEWERS 

Mr. Gerald G. Akland, Environmental Monitoring and Support Laboratory, Environmental 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, London 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, Corvallis, 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, Environmental 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, Environmental 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, Environmental 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 
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 Technology, 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. Environmental 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, University of North Carolina, Chapel Hill, North Carolina 27514 

Dr. John Horn, Environmental Consultant, 758 Oxford Street, West, London, 

Ontario, Canada N6M1V2 

Dr. Robert J. M. Horton, Senior Research Advisor, Health Effects Research 

Laboratory, Environmental Research Center, U.S. Environmental Protection 

Agency, Research Triangle Park, North Carolina 27711 

Mr. Allen G. Hoyt, Health Effects Research Laboratory, Environmental 

Research Center, U.S. Environmental Protection Agency, Research Triangle 

Park, North Carolina 27711 

Dr. F. Gordon Hueter, Associate Director, Health Effects Research Laboratory, 

Environmental Research Center, U.S. Environmental Protection Agency, 

Research Triangle Park, North Carolina 27711 

Dr. Emmett S. Jacobs, Division Head, Additives and Environmental Studies, E. 

I. du Pont de Nemours and Company, Inc., Petroleum Laboratory, 

Wilmington, Delaware 19898 

vn 
^ p in 

Mr. Gary L. Johnson, Industrial Environmental Research Laboratory, Environmental 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, Environmental 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, Environmental 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, Educat ion. and Welfare, 1090 Tusculum Avenue, 

Cincinnati. Ohio 45226 

Dr. Alec E. Martin, Visiting Scientist, Office of Health Hazard Assessment, National 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 Agency, 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, Washington, D.C. 20460 

Ms. Margarita M. Morrison, Technical Information Specialist, Program Operations 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, University of North Carolina, Chapel Hill, North Carolina 27514 

Dr. D. F. Nataush, Professor of Chemistry, Colorado State University, Fort Collins, 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 Longwood Avenue, Boston, Massachusetts 02115 

Dr. Stata Norton, Department of Pharmacology, University of Kansas Medical 

Center, Kansas City, Kansas 66110 

viii 
P.11 

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, Environmental 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 
P.12 

********

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 Huygersstcaat 20, Amsterdam, Netherlands 

Dr. R. L. Zimdahl, Professor of Botany and Plant Pathology, Colorado State 

University, Fort Collins, Colorado 80523 
CONTENTS 

Paiie 

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 Particulate 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 
P.14 

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 f©r 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 Chefiical 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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Page 

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 Decomposition 8-13 

8.4 References for Chapter 8 8-13 

9. QUANTITATIVE EVALUATION OF LEAD AND BIOCHEMICAL 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 

11.1 Introduction 11-1 

11.2 Cellular and Subcellular Effects of Lead 11-1 

11.2.1 Effects on Enzymes , 11-1 

11.2.2 Organellar and Cellular Effects 11-1 

11.2.3 Effects of Lead on Chromosomes 11-4 

11.2.4 Carcinogenesis 11-5 

11.3 Clinical Lead Poisoning 11-6 

11.4 Hematological Effects of Lead 11-7 

xiii 
1PP I (•• P.16 

Page 

11.4.1 Anemia 11-7 

11.4.2 Effects of Lead on Erythrocyte Morphology and Survival 

11-7 

11.4.3 Effects of Lead on Heme Synthesis 11-8 

11.4.4 Other Hematological Effects 11-13 

11.4.5 Summary of Effects of Lead on the Hematopoietic 

System 11-13 

11.5 Effects of Lead on Neurophysiology and Behavior 11-14 

11.5.1 Human Studies 11-15 

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 

11.1 OThe 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 Dast 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' Occupational 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, arid 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 SingleSource Exposures 13-2 

13.3.2 Multiple-S®urce Exposures 13-3 

xiv 
P.17 

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 CONCENTRATIONS 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 
T"*-

FIGURES 

Page 

4-1 Sequence of operations involved in monitoring for lead in the environment 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 EFcrus t 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 .. 6-11 

6-13 World lead smelter and alkyl lead production since 1750 A.D. .. . 6-11 

6-14

 210Pb in Storbreen glacier ice, 1954-1966 6-11 

6-15 Predicted deposition velocity at indicated height for fi » = 20 cm/sec 

and z 0 = 3.0 cm 6-14 

6-16 Predicted deposition velocities at 1-m height for z 0 = 3.0 cm ... . 6-14 

6-17 Predicted deposition velocities at 1 m for /x « = 200 cm/sec 6-14 

6-18 Regression of percentage lead particulates removed by dry deposition 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 function of log of distance from edge of highway 6-15 

6-21 Atmospheric lead concentration at freeway site in Palo Alto, California, 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 
P.19 

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 concentrations 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 feeding 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 exposure 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 populations in which the geometric mean level is 15, 25, or 40 /xg/dl.. 12-2 

12-2 Estimated cumulative distribution of blood lead levels for populations having a geometric mean blood lead level of 25 /xg/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 
P.20 

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 particulate 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 
P.21 

TABLES 

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 major 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 samples 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 7 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 annual 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 /xg/m3 

7-3 

xix 
P.22 

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 (Ammodytes and Clupea) 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-trafficvolume road (interstate highway) 8-6 

8-5 Lead concentrations of predominant organisms from the rural, urban, 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 freshwater 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 acetate 10-4 

11-1 Enzymes affected by lead in animal studies 11-2 

11 -2 Enzymes affected by lead in human studies 11-2 

11 -3 Comparison of test results in lead and control groups 11 -22 

11-4 Summary of results of human studies on neurobehavioral effects at 

"moderate" blood lead levels 11 -27 

11 -5 Effects of lead exposure on locomotor activity in laboratory animals 11 -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 11 -35 

11 -8 Stage of learning 1.1-37 

11-9 In vivo effects of lead exposure on neurochemistry 11 -39 

11-10 Statistics on the effect of lead on pregnancy 11-46 

11-11 Reproductive performance of F, lead-toxic rats 11 -49 

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 versus 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 
Number ft*' 

12-6 Blood lead levels (whole blood) in children in U.S. smelter and comparison 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 

Mg/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 program, 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 estimated 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 concentrations 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 
P.24 

Number Page 

12-36 Blood lead levels of 771 persons in relation to lead content of drinking 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 employment 12-37 

12-39 Geometric mean blood lead levels for children based on reported occupation 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 compounds B-2 

C-1 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 particulate, Southern Solano County, California, March-May 1970. C-4 

C-6 Total lead and lead fallout determined by analysis of dustfall samples, Southern Solano County, California, June-September 1970 C-4 

C-7 Lead concentrations in suspended particulate air samples from El 

Paso, Texas, 1971 C-5 

C-8 Particulate data summary from Helena Valley, Montana, environmental 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-11 Comparison of lead levels in the surroundings of two lead industry 

facilities and an urban control area C-7 

C-12 Lead content of soil near 3-year-old Russian smelter, E. Kazakhstan C-8 

C-13 Lead content of soil in vicinity of Russian lead plant in Kazakhstan C-9 

xxn 
ABBREVIATIONS AND SYMBOLS 

A 

AAS 

ALA 

ALAD 

ALAS 

ALA-U 

8-ALA 

APHA 

ASTM 

ASV 

b.p. 

B.W. 

°C 

Ca 

Cd 

CDC 

(Ch3)4Pb 

(CH3)6Pb2 

(C2H5)4Pb 

(C6H5)4Pb 

(C2H5)6Pb2 

cm 

CNS 

co3= 

CP 

CPG 

CP-U 

Cu 

DA 

dl 

DNA 

EDTA 

EP 

EPA 

°F 

Angstrom (101 0 meter) 

Atomic absorption spectroscopy 

Delta-aminolevulinic acid 

Delta-aminolevulinic acid 

dehydratase 

Delta-aminolevulinic acid 

synthetase 

Delta-aminolevulinic acid in urine 

Delta-aminolevulinic acid 

American Public Health 

Association 

American Society for Testing and 

Materials 

Anodic stripping voltammetry 

Boiling point 

Body weight 

Degrees Celsius (centigrade) 

Calcium 

Cadmium 

Center for Disease Control 

(Atlanta, Ga.) 

Tetramethyl lead (also TML or 

Me4Pb) 

Hexamethyl lead 

Tetraethyl lead (also TEL or 

Et4Pb) 

Tetraphenyl lead 

Hexaethyl lead 

Centimeter 

Central nervous system 

Carbonate ion 

Coproporphyrin 

Coproporphyrinogen 

Coproporphyrin in urine 

Copper 

Dopamine 

Deciliter 

Deoxyribonucleic acid 

Ethylenediaminetetraacetate 

Erythrocyte protoporphyrin; also 

erythrocyte porphyrin 

U.S. Environmental Protection 

Agency 

Degrees Fahrenheit 

FDA 

59Fe 

Fe 2 03 

FEP 

ft 

g 

GSH 

G-6-PDH 

ha 

5-HIAA 

hr 

IARC 

ICRP 

in 

i.p. 

K 

kcal 

RCR 

kg 

km 

1 

LC, 

LC50 

m 

M 

max 

Me3PbAc 

(Me3Pb)2S 

MeV 

MEPPs 

mg 

Mg 

min 

MMED 

ml 

mo 

m.p. 

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 

XXlll 
P.26 

MT 

Na 

NADH 

NAS 

NASN 

NE 

ng 

Ni 

nm 

NO"3 

NSF 

NVS 

P 

Pb 

204pb 

Pb + + 

Pb-A 

Pb-B 

PbBr2 

PbBrCl 

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 (2l0Pb, etc.) 

Diavalent lead ion 

Concentration of lead in air 

Concentration of lead in blood 

Lead bromide 

Lead (II) bromochloride 

PbBrCl-NH4CI Lead bromochloride-ammonium 

[Pb(C2H302)2-

2Pb(OH)2] 

PbCl2 

PbC03 

PbCr64 

PbF2 

Pb(N03)2 

PbO 

PbOx 

(PbO)2 

Pb3 04 

Pb(OCOCH3)2 

Pb(OH)2 

Pb(OH)Br 

Pb(OH)Cl 

Pb(OH)2C03 

PbO.PbS04 

Pb4 0(P04 ) 2 

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(P03)2 

Pb3(P04)2 

Pbs(P04)3OH 

PbS 

PbS04 

PBG 

pCi 

PIXE 

PH 

PO? 

PP 

ppb 

ppm 

PVC 

RBC 

RNA 

s.c. 

scm 

sec 

SGOT 

SGPT 

SH 

S02 

SO? 

85Sr 

STEL 

TEL 

TML 

TVL 

USPHS 

Zn 

ZnS 

ZPP 

Mg 

fi\ 

jum 

> 

< 

xxiv 

Lead metaphosphate 

Lead orthophosphate 

Lead hydroxqpmxqpqwzn 

Lead sulfide 

Lead sulfate 

Porphobilinogen 

Picocurie (IO"12curie) 

Proton-induced X-ray emissions 

Log of the reciprocal of the 

hydrogen ion concentration 

Phosphate ion 

Protoporphyrin 

Part per billion 

Part per million 

Polyvinyl chloride 

Red blood cell; erythrocyte 

Ribonucleic acid 

Subcutaneous 

Standard cubic meter 

Second 

Serum glutamic oxaloacetic 

transaminase 

Serum glutamic pyruvic 

transaminase 

Sulfhydryl 

Sulfur dioxide 

Sulfate ion 

Radioisotope of strontium 

Short-term exposure limit 

Tetraethyl lead 

Tetramethyl lead 

Threshold value limit 

U.S. Public Health Service 

Zinc 

Zinc sulfide 

Erythrocyte zinc protoporphyrin 

Microgram 

Microliter 

Micrometer 

Greater than 

Less than 

Approximately 
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 transport 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 environment? 

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 significance 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 represents a potential pathway for human lead exposure 

via inhalation or ingestion. The actual lead content 

in each source may vary by several orders of magnitude. Potential exposure patterns are further confounded by human activity patterns and by 

differences between indoor and outdoor environments. 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 background 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 (figlg). 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 airborne lead have been estimated to approximate 

0.0006 fig Pb/m3 of air (or 5 x 107 /xg Pb/g air). 

Natural concentrations in fresh water have been estimated to be about 0.5 /xg/liter of water (about 5 x 

IO4 fig Pb/g water) and in ocean water about 0.05 

fig Pb/liter of water (about 4.9 x 10"5 fig 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 fig Pb/m3 of air (about 8 

x 105 fig Pb/g air). Concentrations of airborne lead 

in U.S. cities, at sites not conspicuously influenced 

by major sources, average 1 fig Pb/m3 of air (8 x IO4 

fig 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 

10" fig Pb/g TSP. 

The shape of buildings in urban areas may cause 

large horizontal and vertical variations in lead con1-1 
P.28 

centrations. In the absence of such structures, the 

vertical gradient would usually be relatively small. 

During periods of maximum traffic density on freeways, airborne concentrations of lead immediately 

adjacent to the freeways may reach 20 /xg/m3 for a 

few hours. In the immediate vicinity of large stationary sources having no air pollution controls, concentrations of airborne lead may reach 300 /xg/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 patterns. The small number of indoor air lead studies 

conducted have shown indoor concentrations to be 

one-third or less the level measured outdoors. Indoor levels vary widely depending on type of structure, 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 particles that have settled on a surface and that can be 

readily redispersed in the atmosphere. In an aerometric 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 discharged into the work environment by mechanical 

means. Dustfall is a measure of the settled particulate, 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 exposure 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 depends on the deposition rate and the frequency and 

efficiency with which accessible surfaces are 

cleaned. Lead accumulation resulting from deposition 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 outdoors clearly may vary by one to two orders of magnitude. 

Concentrations of lead in solution in most urban 

water supplies are below 10 /xg Pb/liter of water 

(0.01 fig Pb/g water), but some values >50 /xg/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 supplies. Lead values as high as about 2000 /xg/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. Estimates of daily intake vary from about 100 to 350 fig 

Pb/day. Recent studies in the Unitd States estimate 

the adults ingest about 200 fig 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. Processed milk has been reported to contain more lead 

than fresh cow's milk — about 20 to 40 /xg/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 automobile 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 exposure. 

Workers involved in uncontrolled (without pollution controls) mining, smelting, and manufacturing 

processes where lead is used, have the highest level 

of potential exposure. Although occupational conditions have generally been substantially improved, in 

some cases lead concentrations in the air in work 

places have been measured at 1000 /xg/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 distribution of lead in the environment. Contamination 

1-2 
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 constitute the major source of lead emissions to the atmosphere. In 1975, some 189,000 MT of lead (16 

percent of total production) used in antiknock compounds were converted to 142,000 MT of atmospheric emissions (88 percent of total lead emissions). 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 recent years and will probably continue to do so. 

Based on 1975 estimates, combustion of waste oil 

and incineration of solid waste are the major contributors 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 incinerators. Other stationary sources of lead emissions 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 immediate vicinity of small, uncontrolled battery recycling 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 contamination. Lead is emitted to the atmosphere primarily 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 vertical and horizontal distribution (mixing with concomitant 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 pollutants. Much of the work on lead particulate chemistry before 1973 was limited to elemental analyses 

and did not include analyses of associated ions. Information from elemental analyses 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 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 compounds 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 sulfate, 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. Consequently, 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 techniques for environmental lead have enjoyed considerable 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 
P.30 

general practice, precise and accurate results are 

difficult to obtain, particularly for biological samples. 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 establish and maintain adequate quality control. 

Ambient air monitoring procedures designed 

specifically for assessing population exposure patterns present particularly difficult problems. Total 

mass concentration, particle size distribution, and 

chemical composition of lead aerosols all vary considerably 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 atmospheric concentration of lead, duration of exposure, and incremental changes in blood lead levels 

is not constant. Although measurements of atmospheric lead levels are an essential ingredient in 

population exposure assessment, other indices of exposure such as blood lead and free erythrocyte 

porphyrin (FEP) levels are also essential for the 

characterization of human population exoosures. 

Blood lead may be measured by several general 

techniques that presently appear to be satisfactory in 

the hands of qualified analysts who have a sophisticated 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 comparisons have demonstrated the need for standardizing methodology, using reference standards, and obtaining blood lead determinations from those 

laboratories having highly skilled personnel accustomed 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 epidemiological data. Measurements ofbiological 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 erythrocyt e 

porphyrin. 

1.2 EFFECTS OF LEAD ON MAN AND HIS 

ENVIRONMENT 

In the summary material presented in the preceding section, attention was directed to all the exposure 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 sequential statements of present knowledge concerning: 

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 absorption, 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 particulate 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 deposition 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 airborne 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 gastrointestinal absorption, an inverse relationship be1-4 
P.31 

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 exposed to environmental lead, it is important to distinguish 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 secondary exposure to airborne lead consists of ingestion 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 surfaces 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 absorptidn 

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 commercial processing raises the lead content of food significantly. 

Another important depot of lead in the environment 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 customary habit of putting their hands, objects, and 

materials in their mouths. There is evidence demonstrating 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 expression of this relationship. Rather, a number of studies 

show that, with sustained daily ingestion of 100 /xg 

of lead, the maximum increase in steady-state levels 

of blood lead ranges from 6 to 18 /xg/dl. These 

variations probably relate to nutritional factors, 

biological variability, unreported sources of exposure, differences in analytical techniques, or previous 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 undoubtedly greater for them. Because of higher metabolic 

activity, children also inhale relatively more airborne lead than do adults. Therefore, the contribution 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 threecompartment model. The first compartment, circulating 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 transfer. In nonoccupational^ exposed adults, such 

storage approaches 95 percent of the total body 

burden. The skeleton is a repository of lead that reflects the long-term cumulative exposure of the individual ; body fluids and soft tissues reflect more recent 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 exposure 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 ex1-5 
P.32 

posure setting, and (2) a single, acute, controlled exposure 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 substantially 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 BIOLOGICA L AND ADVERS E 

HEALTH EFFECTS OF LEAD IN MAN 

There are various physiological levels and exposure ranges at which the effects of lead in man occur. Furthermore, lead affects man at the subcellular, 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 subcellular changes observed are primarily the development 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 aberrations and carcinogenesis. At the present time, no 

conclusive statements can be made about the induction 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 carcinogens, there are no data corroborating these findings in man. 

Among the systemic and organic effects of lead, 

important areas are its hematologic, neurobehavioral, and renal effects. Attention must also be 

given, however, to the effects of lead on reproduction and development as well as its hepatic, endocrine, cardiovascular, immunologic, and gastrointestinal 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 destruction and decreased hemoglobin synthesis. In 

children, a threshold blood lead level for production of these symptoms of anemia is approximately 

40 fig Pb/dl, and the corresponding value for adults 

appears to be 50 /xg Pb/dl. 

Hemoglobin synthesis is impaired by lead via inhibition of synthesis of the globin moiety and inhibition 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 excretion of 8-ALA. Also inhibited by lead is the incorporation 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 protoporphyrin, which is retained in the erythrocytes. The 

overall effect of lead is a net decrease in heme synthesis. (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 /xg/dl. Though the 

health-effect significance of inhibition at a blood 

level of 10 /xg/dl is open to debate, the increased 

urinary 8-ALA excretion that occurs with increasing 

inhibition at 40 /xg/dl is accepted as a measure of 

probable physiological impairment in vivo. This 

threshold level for urinary 8-ALA excretion (40 

/xg/dl) appears to be true for both adults and 

children. 

An increase in free erythrocyte protoporphyrin 

(FEP) occurs at blood lead levels of 16 /xg/dl in 

children. In adult females, this threshold is probably 

similar. In adult males, the value is 20 to 25 /xg/dl. 

The precise threshold for coproporphyrin, while not 

well established, is probably similar to that for 

8-ALA. Elevation ot free erythrocyte protoporphyrin has the same implications of physiological 

impairment in vivo as urinary 8-ALA. To the extent 

that the protoprophyrin elevation is a likely indicator of the impairment of mitochondrial function in 

1-6 
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 associated 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, irreversible brain damage as indexed by the occurrence 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 /xg/dl, some evidence suggests that acute 

encephalopathy and death may occur in some adults 

at blood lead levels slightly below 100 /xg/dl. For 

children, the effective blood levels for producing encephalopathy or death are lower than for adults, 

with such effects being seen somewhat more often, 

starting at approximately 100 /xg/dl. Again, 

however, evidence exists for the occurrence of 

encephalopathy in a very few cases at lower levels, 

down to about 80 /xg/dl. 

It should be noted that once encephalopathy occurs, 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 apparently only 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 suggests that at high blood lead levels, even 

when individuals are asymptomatic, rather severe 

neural damage can exist without overt manifestations. Studies show that apparently asymptomatic 

children with high blood lead levels of over 80 to 

100 /Ag/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 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 present overall an impressive array of data 

pointing to that conclusion. Several well-controlled 

studies find effects that are clearly statistically significant, 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 behavioral effects at subclinical exposures are considered 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 /xg/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 nervous system in laboratory animals are also quite extensive. 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 exposure 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 toxicity. Data indicate that increased locomotor activity 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 postencephalopathic 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 
P.34 

the acquisition and/or performance of operant 

responses indicate that perinatal exposure to moderate or low levels of lead may disrupt this type of 

behavior. Thus at blood lead levels ranging from 30 

to 80 /xg/dl, cognitive function appears to be disrupted 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 inclusion 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 exposed 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: gametotoxicity and post-conception events. 

In regard to potential lead effects on human 

ovarian function, one study has shown that shortterm exposure at ambient air levels of less than 7 

/ig/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 involving occupational exposure similarly suggests 

that moderately increased lead absorption (blood 

lead mean = 52.8 /ig/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 induced in laboratory animals with lead, but it should 

be emphasized that the production of such effects 

probably requires acute, high exposures. Unfortunately, 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 lowlevel lead exposure may induce postnatal developmental 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 function in man have been observed, with decreased 

secretion of pituitary gonadotrophic hormones being 

noted but adrenal function effects being a less consistent 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 suggesting 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 exposure, 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 pregnant women — not only on fetal health and development, 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 tri1-
mester, 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 setting 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 consequence for adverse health effects is shown by studies 

relating fetal levels to changes in fetal heme synthesis 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 susceptibility of an individual to lead toxicity. Women 

have an increased risk of both deficiencies during 

pregnancy and postpartum. 

Some available but unconfirmed information indicates that the risk of premature rupture of the amniotic 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 /xg/dl may be associated with a 

higher incidence of premature delivery and premature membrane rupture, but these observations 

require confirmation. In adult males, levels of 50 to 

80 /xg/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 exposures. Effects on offspring have been shown to involve the gametotoxic effect of lead on males as well 

as females in a number of animal species. 

At lead levels presently encountered in occupational exposure, no significant cardiovascular effects 

are discernible. Clinical data for children suffering 

from chronic lead poisoning resulting in death indicate that extensive myocardial damage occurs. It is 

not clear that the associated morphological changes 

are a specific response to lead intoxication. However, in many instances where encephalopathy is 

present, the electrocardiographic abnormalities disappear with chelation therapy. 

There are insufficient data pertaining to the effects 

of elevated blood lead levels and the incidence of infectious diseases in man to allow the derivation of a 

dose-response relationship. Neither can a doseresponse 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, however, has now caused some concern that lead may 

represent a potential threat to the ecosystem. For example, studies have shown a fivefold increase in lead 

in tree rings during the last 50 years; this accumulation may serve as a useful index of patterns of environmental 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 trapped along roadways were tested for lead concentrations. All but one of the species living in habitats adjacent to high-volume traffic showed high concentrations of lead. This was especially true in urban 

areas. 

Lead toxicity in aquatic organisms has been observed and studied experimentally. Symptoms of 

chronic lead poisoning in fish include anemia, possible damage to the respiratory system, growth inhibition, 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 
P.36 

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 retained by plants. Meteorological factors are also important in determining the fate of lead that comes 

into contact with plants. Large deposits of inert insoluble 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 inorganic lead compounds are generally of low 

solubility, there is little incorporation and accumulation 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 promoted the concept that the effects of lead are dependent 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 invariably been found to be lognormal. Most data sets of 

homogeneous populations display a geometric standard 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 /xg/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 occupational 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 relationship 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 between 1 and 2 and that it was not constant over the 

range of air exposures. This implies that an increase 

of 1 /xg/m3 of air lead results in an average increase 

of 1 to 2 /xg/dl in blood lead levels. Suggestive evidence 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. Department 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 preliminary analysis of these important research findings 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 Hispanics 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, and generally 

the maximum is found in 2- to 4-year-olds. 

1-10 
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 unwise 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 concentrations 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 supply and using leaded pipes. Such exposures have 

been shown to be associated with significant elevations 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 settings. Although new regulations of 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. Most of the studies on lead poisoning 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 contribution from this source is very significant for certain segments of the population. 

Food lead exposures are thought to be a source of 

a significant portion of blood lead. Precise quantitative 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 emitted 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 exposure: (1) Lead in paint makes lead available by ingestion; (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 ingestion. 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 ingestion includes both food and nonfood materials. 

In the case of children, the nonfood material has 

especially important implications. Thus the total internal dose is a function of all external sources with 

which the body comes into contact. The relative significance of any given exposure source depends on 

the specific exposure circumstances and certain attributes of the population at risk. 

1.4.1 Use of Blood Lead Levels in Risk Assessment 

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 exposures 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 involving children exposed to lead-contaminated dust 

have demonstrated lead on the children's hands. 

1-11 
P.38 

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 attributable to direct inhalation of atmospheric lead as 

well as with respect to the ingestion of dust contaminated 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 exposure 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 relationship. 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 properties that make it of value in arriving at acceptable 

maximal exposures, since it makes it possible to estimate 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 commonly found in the environment. The relationship is 

dependent on many factors, including rate of current 

exposure and the history of past exposure. The observed 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 assessment is the evaluation of effects of long-term, lowlevel, or intermittent exposures. In such circumstances, 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 /xg/m3 over a period of about 7 weeks was related 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-exposure 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 adverse health effects on man at this time must be considered from a medical point of view that 

acknowledge s 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 physiological 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 neurological 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 concomitant iron deficiency. Increased lead intake 

prompts a more severe anemia. This is of special importance in children 1 to 6 years old of lower socioeconomic status, since this group also has a high incidence of iron deficiency. 

The literature relating blood lead levels to a 

statistically significant reduction in hemoglobin 

points to a threshold level of 40 /xg/dl for children 

and a corresponding value of 50 /Ag/dl for adults. 

The question of a low-threshold or no-threshold 

1-12 
TABLE 1-1. BLOOD LEAD LEVELS VERSUS LOWESTOBSERVED-EFFECTS LEVELS 

Lowest level 

lor observed 

effects, tig 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 

Coproporphyrin 

elevation 

Anemia 

Cognitive (CNS) 

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 /xg/dl). This value seems to apply 

for both children and adults. 

Elevation of erythrocyte porphyrin is better accepted 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 /xg/dl for children 

and adult females and 20 to 25 /xg/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 exposure. Although it may be argued that certain of the 

initial hematological effects (such as ALAD inhibition) 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 indicators 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 encountered as the hematological deficits reach clinical magnitudes. Children are most clearly the 

population at risk for neurologic effects. The 

neurologic effects, including both peripheral neuropathies and signs of CNS damage, are first encountered for some children as blood lead levels reach 50 

to 60 /xg/dl; and they very rapidly intensify in 

severity as a function of increasing blood lead elevations. Of great medical concern is the very steep upward rise in the risk for permanent, severe 

neurological damage or death as blood lead elevations approach and exceed 80 to 100 /xg/dl in 

children. Inner city children are of particular concern with respect to the manifestation of lead-induced neurologic deficits, as documented by the evidence 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 exact 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 placental 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 
P.40 

being associated with elevated blood lead levels in 

women, and some impairment in the heme biosynthetic 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 primarily concerned with threshold levels at which 

health effects of lead are first observed in different 

population groups. Of additional interest is the proportion 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 inhibition of ALAD, elevation of ALA-U, and elevation 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 published and one done by EPA (see Chapter 13). 

TABLE 1-2. ESTIMATED PERCENTAGE OF SUBJECTS WITH 

ALA-U EXCEEDING 5 mg/lrt«r FOR VARIOUS BLOOD LEAD 

LEVELS 

Blood lead 

level, pg/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 protoporphyrin 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.8 % 

0 

6 

22 

37 

49 

~ 

-

-

Roels et al. 

estimate,15 % 

3 

27 

73 

100 

-

— 

-

-

Piomelli 

estimate,0 % 

9 

11 

48 

80 

-

-

-

-

EP >EP of children with blood lead levels <20 pg/dl. 

bEP >82(ifl/<ll cells. 

C

EP >33MS/<1I1.4.3 Populations at Risk 

The concept of "special risk" is defined as a 

population segment exhibiting characteristics associated 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 populations are currently definable: preschool children and 

unborn fetuses, with pregnant women as the recipient 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 physiological factors include: (1) greater lead intake on a perunit-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 mechanisms 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 probably 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-sucking or tasting of nonfood objects. Such behavior 

poses a risk of increased contact with dust and soil 

contaminated with lead. Clinical evidence also exists 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 placental barrier and does so at an early stage in 

embryonic development. Although quantitative expressions 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 
P.41 

bone lead may be mobilized and the hematopoietic 

system may be placed at higher risk to lead exposure. In addition, data suggest that elevated blood 

lead levels in pregnant women may result in increased 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 EXPOSURES 

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. Therefore, for other than point stationary sources of lead, 

it is the urban population that is at risk, and in particular, 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 

/xg/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 
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 expected from the presence of such pollutant in the ambient air, in varying quantities. 

Air quality criteria are of necessity based on presently available scientific data, which in turn reflect 

the sophistication of the technology used in obtaining those data as well as the magnitude of the experimental 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 concentrations— averaged over a suitable time 

period — of pollutants in the same atmosphere and 

their adverse effects upon public health and the environment. Criteria are issued to help make decisions 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 exposure at specific levels of a pollutant. In contrast, 

air quality standards are prescriptive; that is, they 

prescribe what a political jurisdiction has determined 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 remain airborne), the sources, levels, and effects of exposure 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 primarily 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 remain suspended in the air and enter the human body 

only by inhalation, but other lead-containing particles 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 exposure of the human population. 

This criteria document sets forth what is known 

about the effects of lead contamination in the environment on human health and welfare. This requires that the relationship between levels of exposure to lead, via all routes and averaged over a 

suitable time period, and the biological responses to 

those levels be carefully assessed. Assessment of exposure 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 exposure and response. The first portion of the document is devoted to lead in the environment — physical and chemical properties; the monitoring of lead 

in various media; sources, emissions, and concentrations of lead; and the transport and transformation 

of lead within environmental media. The latter section 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 Standards 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 obtained by roasting. The metal is soft, malleable, and 

ductile; it is a poor electrical conductor, and it is 

highly impervious to corrosion. This unique combination 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 already 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 significance 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 production 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 Description 

Atomic weight 

Atomic number 

Oxidation states 

Density 

Melting point 

Boiling point 

Covalent radius (tetrahedral) 

Ionic radii 

Resistivity 

207.19 

82 

+2, +4 

11.35g/cm3at20°C 

327.4°C 

1744°oC 

1.44 A 

1.21 A (+2), 0.78 A (+4) 

21.9 xlO"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 variations reflecting geological evolution.3

 There is no 

radioactive progenitor for

 2<)4Pb. However, 206Pb, 

207Pb, and 2tmPb are produced by the radioactive 

decay of

 238U, 23SU, and 232Th, 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(|oPb/204Pb isotopic ratio, for example, varies from 

approximately 16.5 to 21, depending on the source.4 

TABLE 3-2. ISOTOPES OF LEAD 

Isotope 

204Rb 

206pb 

207Rb 

208pb 

210pb 

210pb 

211 p b 

211pb 

212pb 

212pb 

214pb 

214Rb 

Average 

abundance. % 

1.4 

26.3 

20.8 

51.5 

— 

— 

— 

— 

— 

— 

— 

— 

Decay mode 

Stable 

Stable 

Stable 

Stable 

Ii 

a 

Ii 

a 

Ii 

a 

ii 

a 

Energy. MeV 

— 

— 

— 

0.017 

0.047 

1.4 

0.82 

0.36 

0.24 

0.72 

0.35 

Half-life 

Stable 

Stable 

Stable 

Stable 

22 yr 

22 yr 

36.1 min 

36.1 min 

10.6 hr 

10.6 hr . 

26.8 min 

26.8 min 

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 chemistry of lead is dominated by the divalent ( + 2) oxidation 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 toCH r For lead, the PbH 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 
P.44 

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 catenated 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., 

PbF2, PbCl 2 ) or virtually insoluble (PbS04 , 

PbCr04) in water; the notable exceptions are lead 

nitrate, Pb(N03)2, and lead acetate, Pb(OCOCH3)2. 

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 carbon) are entirely different from those of the inorganic 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 photolysis when exposed to light. The physical properties 

of some of the more important organolead compounds are summarized in Table 3-3. 

TABLE 3-3. PROPERTIES OF MAJOR ORGANOLEAD COMPOUNDS 

Compound 

Tetramethyl lead 

Tetraethyl lead 

Tetraphenyl lead 

Hexamethyl lead 

Hexaethyl lead 

Formula 

(CH3)4Pb 

(C2H5)4Pb 

(C6H5)4Pb 

(CH3)6Pb2 

(C2H5)6Pb2 

Appearance 

Colorless liquid 

Colorless liquid 

White solid 

Pale oil 

Yellow oil 

m.p.. C 

-27.5 

-130 

223 

38 

36 

b.p.. C 

110 

82a 

Decomposes 

Decomposes 

100b 

At 13 mm pressure. 

At 2 mm pressure. 

Because of their use as antiknock agents in 

gasoline and other fuels, the most important 

organolead compounds are the tetraalkyl compounds 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 extremely large quantities (Chapter 5) by the reaction 

of the alkyl chloride with lead-sodium alloy:7 

4NaPb + 4C2H,C1 — (C2H5)4Pb + 3Pb + 4NaCI 

The methyl compound, TML, is also manufactured 

by a Grignard process involving the electrolysis of 

lead pellets in methylmagnesium chloride:7 

2CHJvlgCI + 2CH3C1 + Pb (CH3)4Pb + 

2MgCl 2 

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 bromochlorolead. Such inorganic compounds apparently 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 few 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 substrates. 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 CHELATION 

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 central position in the complex, as exemplified by 

the lead atom in tetramethyl lead (a), which is 

H3C# CH, 

H,C 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 significant 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. 

H2 0 

O 

O. 

CH. / 

Pb 

NH„ 

.NH. 

\ 

\ CH, 

I 

•C 

O 

H2 0 

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 functions by changing the tertiary structure of the protein 

or by blocking the approach by a substrate to the active 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 excreted by the body. For simple thermodynamic 

reasons (see Appendix B), chelate complexes are 

much more stable than monodentate metal complexes, 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 <x> 

CH2 -CO 

N-CH2-CH2-N 

/ 

/ 

J 

\ 

O-C-CH. 

O 

CH2 -CO . 

O 

EDTA 

(c) 

CH. 

HS — C CH c ; 

CH3 NH2 

PENICILLAMINE 

O 

OH 

(b) (d) 

3-3 
P.46 

lead poisoning are ethylenediaminetetraacetate ions 

(EDTA) (c), D-penicillamine (d), and their derivatives. EDTA is known to act as a hexadentate ligand 

toward metals.9 Recent X-ray diffraction studies 

have demonstrated that D-penicillamine is a tridentate ligand (binding through S, N, and O) toward 

cobalt,10 chromium," and lead,12 but monodentate 

toward mercury.1315 

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 

1. Moeller, T. Inorganic Chemistry. John Wiley and Sons, 

Inc., New York. 1953. 966 p. 

2. Dyrssen, D. The changing chemistry of the oceans. Ambio. 

/(l):21-25, 1972. 

3. Russell, R. and R. Farquhar. Lead Isotopes in Geology, 

lnterscience. New York. I960. 

4. Doe, B. Lead Isotopes. Springer-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 of Group IV B. 

Organometallic Chem. Rev. A 30:95, 1970. 

7. Shapiro, H. and F. W. Frey. The Organic Compounds of 

Lead, lnterscience 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, 113-119. 

9. Richards, S., B. Pedersen, J. Silverton, and J. L. Hoard. 

Stereochemistry of ethylenediaminetetraacetate complexes. Inorg. Chem. 5:27-33, Jan. 1964. 

10. de Meester. P. and D. J. Hodgson. Model for the binding 

of D-penicillamine to metal ions in living systems: Synthesis and structur e of L-histidinyl-D-penicillaminatocobalt (III) monohydrate. [CO(L-his) (Dpen)]H2 0. J. Am. Chem. Soc. 99(1 ):10l-104. 1977. 

11. de Meester, P. and D. J. Hodgson. Synthesis and X-ray 

structure of L-histidinyl-D-penicillaminatocobalt (III) 

and L-histidinyl-D-penicillaminatochromium (111). J. 

Chem. Soc. Chem. Commun. 280, 1976. 

12. Freeman, H. C , G. N. Stevens, and 1. F. Taylor, Jr. Metal 

binding in chelation therapy: The crystal structure of Dpenicillaminatolead (II). J. Chem. Soc. Chem. Commun. 

/ 0:366-367, 1974. 

I 3. Wong. Y. S.. P. C. Chieh, and A. J. Carty. The interaction 

of organomercury pollutants with biologically important 

sites. Can. J. Chem. 5/:2597, 1973. 

14. Wong, Y. S., P. C. Chieh, and A. J. Carty. Binding of 

methylmercury by amino-acids: X-ray structure of D, Lpenicillaminatomethylmercury (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 includes 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 contingent 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 inherent 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 environment 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 carried out with almost any precision deemed necessary, 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 available. Another serious problem is the present lack of 

instrumentation for the continuous analysis of aerosol. 

Monitoring for lead involves an operational sequence, 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 influenced by the kind of data needed, the types of 

samples collected, the analytical capabilities available, 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 required. 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 compendium 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 involved 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 criteria for location of samplers. The various samplers 

used to collect lead data are described. Methods for 

collecting dustfall, water, soil, and vegetation samples 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 interferences that have been encountered. 

The analytical section is lengthy because of the 

4-1 
P.48 

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 

DETERMINE 

SAMPLE 

STORAGE AND 

TRANSPORT 

REQUIREMENTS 

OBTAIN SAMPLES 

ANALYZE SAMPLES 

PREPARE 

SAMPLE !

« » MEASURE I 

LEAD j 

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-containing particles, adsorbed gases, liquids, and solid samples 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 Site Selection 

The location of sample collection devices has important 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 encountered 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 located 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 criteria, 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 frequency are also important in the overall sampling 

strategy. It should be noted, however, that it is not 

possible to discuss sampling plans outside the context 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 quantity 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 investigated. 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 impaction 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 
fim).8

 Generally, it is not possible to estimate the error under any specified conditions. But such errors 

may be minimized by avoiding eddy formation, turbulence, 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 occur 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, impactors, and impingers. 

4.2.3.1 HIGH-VOLUME SAMPLER 

The most widely used method for sampling airborne particulates in the 0.1- to ]0-fim range is the 

high-volume air sampler,910 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 

m

3

/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 collection. The lead content is then determined by one of 

the analytical methods described in 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 subsequent 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 standard deviation for total particulate collection has 

been reported of 3.7 percent over the range 80 to 

125 /ug/m-\ The disadvantages of the high-volume 

sampler include the lack of separation of particulates by size, the interferences by impurities in the 

filters with some analytical procedures, and the particle fracturing that occurs on impact, which 

precludes subsequent determination of size distribution.9

 In addition, high-volume samplers are 

usually operated nonisokinetically; this results in an 

underestimation of the airborne concentration of 

large particles. "I f there is appreciable mass in particles with aerodynamic diameters greater than 

about 10 fim, 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 precision of total particulate collection of the highvolume sampler is estimated at ± 0.5 /ug/m3

. Of 

course, such comparisons apply only to the particular conditions and methodology of sampling and 

analysis used in that study. 

4.2.3.2 DICHOTOMOUS 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. 

Measurements'4 have indicated that airborne particulates 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.16 The dichotomous sampler uses virtual 

impaction to avoid the particle bounce errors frequently encountered with cascade impactors.17

 Virtual 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 fim 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 fim in 

4-3 
P.50 

diameter, whereas only 20 percent was found to be 

in larger particles. Other tests to evaluate the performance of dichotomous 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., every 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 

voltammetr y analysis. 1 9 Atmospheri c concentrations of lead ranging from 0.1 to 2.0 /xg/m3 

were measured at monitoring stations in Chicago 

and Washington using tape samplers.19 Diurnal cycles in airborne lead concentrations were obtained 

that correlate with manmade sources of lead. 

4.2.3.4 IMPACTORS AND IMPINGERS 

Impactors are multistage particulate collection 

devices designed to provide a number of size fractions. 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 collected at each stage depends on the air velocity, 

geometry, and previous stages. The last stage consists 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 collected. Five fractions are usually obtained: < 1.1, 

1.1 to 2.0, 2.0 to 3.3, 3.3 to 7, and > 7 ^m. 

Results obtained by the NASN22 indicate that lead 

particulates typically have mass median diameters in 

the range of 0.25 to 1.43 fim. Analysis by optical 

emission spectrography indicated that for particles 

less than 0.5 fim in diameter, the lead content was 2 

to 4 percent. A cascade impactor has also been applied 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 impactor.25 

Impingers collect atmospheric aerosols by impingement onto a surface submerged in a liquid.29 

Impactors are sometimes called dry impingers. As in 

impactors, impingement relies on the inertia! 

characteristics of the particle for collection on a surface. High collection efficiencies for particles as 

small as 0.1 fim 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 atmosphere, 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-/um 

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.2728 

The procedures using iodine monochloride have 

been described and are claimed to be effective.26 In 

one experiment, two bubblers containing the solution were placed in series in the sampling train. 

Head levels corresponding to about 2.0 /xg/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 quantitative. 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 
P.51 

analysis of lead in water have been extensively described.2930

 Sample containers may be either glass 

or plastic. Thedynamicsof 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 /ttg/liter, with 

an average value of 6.6 /ug/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 concentration 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 /xg 

Pb/cm2' year from rainout or washout or both, and 

0.2 fig 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 highway.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 representative site should be selected. The vertical integrity 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 obtain results representative of the conditions being investigated. Most of the analytical procedures used 

for airborne particulates are applicable to soils, but 

the results may not be comparable. Many techniques, including optical emission spectrography, Xray 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 gravitational settling. The settling velocities of larger 

particles (^ 5 to 10 fim) are such that they will be 

transported shorter distances than the smaller particles ( < 1 fim), which have nearly negligible settling 

velocities. Thus dustfall collections can be used to 

monitor the dispersion of particulate lead from a 

specific source. The collections are made by placing 

open containers at appropriate sites free of overhead 

obstructions.910 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, presenting 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 indicated consistently that the lead content of particulates 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 extensive 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 figlg dry weight, although levels as high 

as 31 figlg have been cited.1 Plants can absorb soluble 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 between 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 sampling 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 
P.52 

materials is generally carried out by random selection 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 involved. 

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 samples 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 container 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 surface contamination with minimum leaching of constituents from leaf tissue can generally be accomplished by using dilute solutions of selected synthetic 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 involves nationwide sampling of foods representing 

the average diet of an 18-year-old male (i.e., the individual 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 otherwise 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 

I 

II 

III 

IV 

V 

VI 

VII 

VIII 

IX 

X 

XI 

XII 

Food group 

Dairy products 

Meat, fish, and 

poultry 

Grain and cereal 

products 

Potatoes 

Leafy vegetables 

Legume vegetables 

Root vegetables 

Garden fruits 

Fruits 

Oils, fats, and 

shortening 

Sugar and adjuncts 

Beverages 

(including water) 

Total 

Food consumption 

Avg. 

g/day 

consumed 

756 

290 

369 

204 

59 

74 

34 

88 

217 

52 

82 

697 

2922 

% ol 

total 

diet 

26.1 

9.9 

12.6 

7.0 

2.0 

2.5 

1.2 

3.0 

7.4 

1.8 

2.8 

24.9 

4.2.6 Source Sampling 

Sources of lead have been well identified and include automobiles, smelters (lead and other nonferrous 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 emissions.34

 A complete discussion of sources of lead 

emissions is given in Chapter 5. The following sections 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-/xm membrane filter and an activated carbon 

adsorption tube.40 In a study of manual methods for 

4-6 
measuring emission concentrations of lead and other 

toxic materials,41 use of a filter, a system of impingers, a metering system, and a pump was recommended. The recommended solution in the impingers 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 sampling trains must be designed to trap and retain both 

gaseous and particulate 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 dilution tube was designed to segregate fine combustionderived aerosols from larger lead particles ablated 

from combustion chamber and exhaust deposit.42 In 

this procedure, hot exhaust was ducted into a 56-cmdiameter, 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 exhaust 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 fim, 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 measurement of anomalously large aerosol sizes because of 

condensation of low-vapor-pressure organic substances onto the lead particles. This effect may be 

offset, however, by fallout processes that apply primarily 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 dilution tunnels have been used with good success.434748 

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 intervals.47

 Similar tunnels have been used in which a 

centrifugal fan located upstream is used rather than 

a positiv e displacemen t pum p locate d 

downstream.43 This geometry produces a slight positive pressure in the tunnel and expedites transfer of 

the aerosol to holding chambers for studies of aerosol 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 performed using total filtration of the exhaust stream to 

arrive at material balances for lead using rather low 

back-pressure metal filters.4549-

51

 The cylindrical 

filtration unit used in these studies is better than 99 

percent effective in retaining lead particles.51 Supporting 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 automobiles. Each has its appropriate area of application, depending on the objectives of the various 

research program carried out. The air dilution tunnel 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.5355 If the sample is large, 

then the effects of these trace elements are negligible, 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 
P.54 

filter determines the ashing technique. In other 

methods of analysis — X-ray fluorescence, for example — 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 selection 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 efficiency 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 inadvisable in most cases,5455

 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 available 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 relative effectiveness of dry ashing (either at low temperatures in an oxygen plasma or at high temperatures) and of wet ashing by acid dissolution is a 

subject of current concern. Either technique will 

give good results if employed properly.455 

4.3 ANALYSIS 

A variety of useful analytical procedures is available 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 equipment 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 available in the literature.3429 

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 National 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 complex. 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.440 

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 determination of particulate lead in the atmosphere. 

The colorimetric dithizone method has the advantage of acceptability by professional organizations. 

In addition, the required apparatus is simple and 

relatively inexpensive, the absorption is linearly related 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 procedure 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 reported.26

.

55

.

58

.

64

-

65 

In AA, the lead determination is made by measuring the resonance absorption of lead atoms. The attenuation of the light beam passing through the sample is logarithmically related to the concentration of 

the atoms being measured. The lead atoms in the 

sample must be vaporized either in a precisely controlled 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 
beam, after passing through the flame, is separated 

in a monochromator and detected with a photomultiplier. 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 particulate samples from the 

NASN were accomplished by AA to an indicated 

precision of 11 percent, with a 0.15 /ug/m3 detection 

limit.58 

Atomic absorption requires as much care as other 

techniques to obtain highly precise data. Background absorption, chemical interferences, background light losses, and other factors can cause errors. 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 improved performance involving nonflame atomization 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.6667 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 solutions. The electrochemistry of lead is based primarily on the plumbous ion, which behaves reversibly 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 working electrode may be a mercury film on a waximpregnated 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 corresponding to the oxidation of the lead. The area of the 

peak corresponds to the quantity of lead ions available at the stripping voltage. 

ASV was applied to the analysis of lead in 2-hr 

samples obtained with a spot tape sampler.19 Between 80 ng and 2.4 /xg 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 particulate 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 precision.4

 Extension to 0.1-ppb levels is attainable 

with modified techniques. 

Differential ASV69 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 number 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 observing the optical emission spectra of material excited in a spark, arc, or flame. The wavelength and 

intensity of the characteristic emission wavelengths 

of the elements provide both qualitative and quantitative data on composition. Before 1960, the emission spectrometer was the most common instrument 

in trace-detection laboratories.72 

When used for a single element such as lead, emission 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 environmental contamination by automotive lead, sampling 

times were much reduced by using a sampling technique in which lead-free porous graphite was used 

both as the filter medium and the electrode in the 

spectrometer.7073 Lead concentrations of 1 to 10 

4-9 
P.56 

/xg/m3 could be detected after a half hour flow at 

800 to 1200 ml/min through the filter. 

Scott et al. analyzed composited particulate samples obtained with high-volume samplers for about 

24 elements, including lead, using a direct-reading 

emission spectrometer.74 Over 1000 samples collected 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 particulates. 

4.3.5 Electron Microprobe 

When an intense electron beam is incident on a 

material, it produces, among other forms of radiation, X rays whose wavelengths depend on the elements present in the material and whose intensity depends on the relative quantities of these elements. 

This X-radiation is the basis of the electron microprobe method of analysis. An electron beam that 

gives a spot size as small as 0.2 fim 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 IO14 to 

IO"16 grange.75 

Ter Haar and Bayard76 applied the electron 

microprobe method to the analysis of the composition of airborne lead-containing particles. Particles 

collected on membrane filters were mounted on 

special substrates and analyzed for lead compounds.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 composition of lead compounds in the sample ranged 

from a low of 0.1 percent to a high of over 37 percent. 

Electron microprobe analysis is not a widely applicable monitoring method. It requires expensive 

equipment, complex sample preparation, and a highly 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 innershell electron. 4

 This fluorescenc e allows 

simultaneous identification of a range of elements, 

including lead. For example, 22 elements were identified and quantitatively analyzed in particulate 

samples from dichotomous samplers without intermediate 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 irradiation source. X-ray tubes,16'

23

 electron beams,75 and 

radioactive isotope sources77 have been used extensively.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 latter technique requires a very low level of excitation.16 

X-ray emission induced by charged-particle excitation (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 occurred in 1970, and an interference-free sensitivity 

down to the picogram range was demonstrated.80 

The excellent capability of accelerator beams for Xray emission analysis is partially due to the 

relatively low background radiation associated with 

the excitation. The main contributio n is 

Bremsstrahlung from secondary electron emission. 

The high particle fluxes obtainable from accelerators also contribute to the sensitivity of the PIXE 

method. Literature reviews83"

86

 on approaches to Xray elemental analysis agree that protons of a few 

MeV energy provide a preferred combination for 

high sensitivity analyses under conditions less subject 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 appeared.81'

82 

Advantages of X-ray fluorescence methods include the ability to detect a variety of elements, the 

ability to analyze with little or no sample preparation, 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 stripping voltammetry are restricted to measurement of 

total lead and thus cannot identify the various compounds of lead. The electron microprobe and other 

X-ray fluorescence methods provide approximate 

data on compounds on the basis of the ratios of elements present.76

 Gas chromatography using the 

electron capture detector has been demonstrated to 

be useful for organic lead compounds.28 Powder Xray 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 absorption 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 distribution of lead aerosol is important in considering 

questions regarding exposure by inhalation; sampling with cascade impactors or dichotomous 

samplers is necessary to such evaluations. To determine 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 environmental variables implicit in site monitoring, the 

development of useful biological monitoring techniques may be of more direct utility. 

4.5 REFERENCES FOR CHAPTER 4 

1. Lead: Airborne Lead in Perspective. National Academy of 

Sciences, Washington, D. C. 1972. 330 p. 

2. Stern, A. C. (ed.). Air Pollution. 2nd ed. Academic Press, 

New York, 1968. 

3. Lovering, T. G. (ed.). Lead in the Environment. Geological Survey Professional Paper 957. U.S. Government 

Printing Office, Washington, D.C. 1976. 90 p. 

4. Skogerboe, R. K., A. M. Hartley, R. S. Vogel, and S. R. 

Koirtyohann. Monitoring for lead in the environment. In: 

Lead in the Environment. (W. R. Boggs, ed.). Report to 

NSF® RANN. U.S. Government Printing Office, Washington, D.C. 1977. (In press.) 

5. Ott, W. R. Development of criteria for siting air monitoring stations. In: Proc. 68th Annual Meeting, Air Pollution 

Control Association, Boston, Vol. 2, Paper No. 75-14.2. 

June 1975. 17 p. 

6. Guidelines: Air Quality Surveillance Networks. U.S. Environmental Protection Agency, Office of Air Programs, 

Research Triangle Park, N.C. Publication No. AP-98. May 

1971. 16 p. 

7. Sampling Location Guidelines. U.S. Environmental Protection Agency, Division of Atmospheric Surveillance. 

November 1972. 

8. Watson, H. H. Errors due to anisokinetic sampling of 

aerosols. Am. Ind. Hyg. Assoc. Q. /5(l):21-25. 1954. 

9. Warner, P. O. Analysis of Air Pollutants. John Wiley & 

Sons, New York. 1976. 329 p. 

10. Air Quality Criteria for Particulate Matter. U.S. Dept. of 

Health, Education, and Welfare, National Air Pollution 

Control Administration, Washington, D.C. Publication 

No. AP-49. 1969. 

11. Wedding, J. B., A. R. McFarland, and J. E. Cermak. Large 

particle collection characteristics of ambient aerosol 

samplers. Envir. Sci. Tech. //:387, 1977. 

12. Davidson, C. I. Ph.D. Dissertation. Calif. Inst. Technology, Pasadena, Calif. 1977. 

1 3. Berlin, A., P. Del Castilho, and J. Smeets. European intercomparison programs. In: Environmental Health Aspects 

of Lead. Commission of the European Communities. Luxembourg. 1973. p. 1033-1049. 

14. Whitby, K. T„ R. B. Husar, and B. Y. H. Liu. The aerosol 

size distribution of Los Angeles smog. J. Colloid Interface 

Sci. J9(l): 177-204, 1972. 

15. Lippmann, M. and W. B. Harris. Size-selective samples for 

estimating "respirable" dust concentrations. Health 

Physics. 8(2):155-163, 1962. 

16. Dzubay, T. G. and R. K. Stevens. Ambient air analysis 

with dichotomous sampler and X-ray fluorescence 

spectrometer. Environ. Sci. Tech. 9(7):633-688, 1975. 

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23. Paciga, J. J. and R. E. Jervis. Multielement size characterization of urban aerosols. Environ. Sci. Technol. 

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4-11 
P.58 

24. Bernstein, D. J., M. T. Kleinman, T. J. Kneip, T. L. Chan, 

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33. Lagerwerff, J. V. and A. W. Specht. Contamination of 

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42. Habibi, K. Characterization of particulate lead in vehicle 

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53. Gandrud, B. W. and A. L. Lazrus. Design of system for 

removing water-soluble materials from IPC-1478 filter 

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4-13 
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 surface materials taken at 8-in. depths in the continental United States1

 show a median lead concentration 

of 15 ppm. Ninety-five percent of these measurements show 30 ppm of lead or less, with a maximum 

sample concentration of 700 ppm. In natural processes, 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.25 In addition, minute amounts of 

radioactive

 210Pb 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 background 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 ju-g/m3 or rural airborne particulate matter were derived from surface materials containing 15, and rarely more than 30, ppm lead as 

cited above, then the natural contribution to airborne lead would range from 0.0004 to 0.0012 

Mg/m3. In fact, levels as low as 0.0012 to 0.029 

/ug/m3 have been measured at a site in California's 

White Mountains.7 In contrast, however, annual 

average lead concentrations in urban suspended particulate matter8

 range as high as 6 /Lig/m3. Clearly, 

therefore, most of this urban particulate 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 5-1.9 Approximately 85 percent of the primary lead produced in this country is from native mines,10

 where it 

is often associated with minor amounts of zinc, cadmium, copper, bismuth, gold, silver, and other 

minerals.10 Missouri ore deposits account for about 

80 percent of the domestic production. 

EXTERNAL EMISSIONS 

SCRAP 

598 

DOMESTIC 

ORES 

483 

FOREIGN 

ORES 

96 

METAL 

IMPORTS 

90 

SECONDARY 

PLANTS 

512 

PRIMARY 

PLANTS 

582 

TOTAL 

SUPPLY 

1363 

METAL 

PRODUCTS 

245 

CERAMICS 

AND PIGMENTS 

72 

ALKYLS 

190 

BATTERIES 

634 

OTHER 

36 

EXPORT 

19 

UNREPORTED 

USES AND 

STOCK CHANGES 

187 

Figure 5-1. Approximate flow of lead through U.S. industry in 

1975, metric tons.9 

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 

1976 of 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 annually. Lead in pigments, gasoline additives, ammunition, foil, solder, and steel products is widely 

dispersed and therefore is largely unrecoverable. 

5-1 
P.61 

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 

(70,013) 

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) 

52,011 

(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) 

a

 Short lons/yr given in parentheses. 

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 initial recipient. Estimated lead emissions to the atmosphere 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 combustion, contribute insignificant lead emissions to 

the atmosphere. 

Lead particulates emitted in automotive exhaust 

may be divided into two size classes. Particles initially 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 suspended 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, 1975»•» 

Source category 

Annual emissions, 

MT/yr 

Emissions as percentage of 

Subtotal 

Mobile subtotal 142,000 100 

Gasoline combustion 

Stationary subtotal 

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 

142,000 

19,225 

100 

100 

10,430 

1,630 

400 

100 

1,079 

844 

755 

619 

493 

•400 

272 

1,014 

436 

313 

112 

54.3 

8.5 

2.1' 

0.5 

5.6 

4.4 

3.9 

3.2 

2.5 

2.1 

1.4 

5.3 

2.3 

1.6 

0.6 

328 

161,225 

1.7 

88.1 

6.5 

1.0 

0.2 

0.1 

0.7 

0.5 

0.4 

0.4 

0.3 

0.2 

0.2 

0.6 

0.3 

0.2 

0.1 

0.2 

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. 

O LEAD SMELTING AND REFINING PLANTS (7); • TETRAMETHYL AND TETRAETHYL LEAD PLANTS (5) 

PRIMARY PRODUCTION FOR 1976 = 652, 877 MT 

A STORAGE BATTERY MANUFACTURERS (> 188) 

Figure 5-2. Location of major lead operations in the United States, 1976.1' 

• LEAD MINES (25 LARGEST); 

PRODUCTION = > 95% OF DOMESTIC OUTPUT 

5-3 
P.63 

These larger particles, which may be tens of 

micrometers or larger in diameter, behave in the atmosphere like the larger lead particulates emitted 

from most stationary sources and fall to the ground 

in the vicinity of the traffic producing them. The distribution 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 driving 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 contained in the gasoline burned by the vehicle will be 

emitted as fine particulate, and approximately 40 

percent will be emitted as coarse particulate. The remainder of the lead consumed in gasoline combustion 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 considerable importance. A measure of its significance 

is reflected in the waste oil combustion values in Table 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 incorporated into the dust and washed into sewers or onto adjacent 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 promulgated by EPA16

 that limit the average concentration 

of lead additives in gasoline will contribute to a 

further reduction in future automotive lead emissions. 

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 industries. 

A new locus for lead emissions emerged in the 

mid-sixties, however, with the opening of the 

"Viburnum Trend" or "New Lead Belt" in southeastern 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 |ead-producing nations. An extensive 

study to assess the impact of the expanding lead industry 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 significantly 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 figlg at the roadway, declining to a fairly constant 100 to 200 figlg 

beyond about 400 ft from the roadway.17 

Another possible source of land or water contamination is the disposal of particulate lead collected by air pollution control systems. The potential for impact on soil and water systems of the disposal of dusts collected by these control systems has 

not been quantified. 

The lead-containing particles emitted from stationary sources occur in various sizes. Those emitted 

from uncontrolled stationary sources generally include particles larger than 1- to 2-fim mass mean 

diameter, and therefore tend to settle out near the 

source. These large-particle emissions add considerable 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 atmosphere, where iong-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 fim) 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-fim 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 emissions from these sources is unknown. 

5.3 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, D.C. Professional Paper 574-D. 

1971. 74 p. 

2. Chamberlain, A. C. Interception and retention of radioactive aerosols by vegetation. Atmos. Environ. 4:57-77, 

1970. 

3. Chow, T. J. and C. C. Patterson. The occurrence and significance of lead isotopes in pelagic sediments. Geochim. 

Cosmochim. Acta. (London). 26:263-308, 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 environments of man. Arch. Environ. Health. 77:334-360, 1965. 

6. Burton, W. M. and N. G. Stewart. Use of long-lived 

natural radio-activity as an atmospheric tracer. Nature. 

756:584-589, 1960. 

7. Chow, T. J., J. L. Earl, and C. B. Snyder. Lead aerosol 

baseline: Concentration at White Mountain and Laguna 

Mountain, California. Science. 7 78(4059):401-402, 1972. 

8. Akland, G. G. Air Quality Data for Metals, 1970 through 

1974, from the National Air Surveillance Network. U.S. 

10 

II 

Environmental Protection Agency, Research Triangle 

Park, N.C., Pub. No. EPA 600/4-76-401. 1976. 

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. 

Mineral Facts and Problems. U.S. Bureau of Mines 

Bulletin 667, U.S. Department of Interior, Washington, 

D.C. 1975. p. 1243. 

Lead Industry in May 1976. Mineral Industry Surveys. 

U.S. Department of Interior, Bureau of Mines, Washington, 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 Protection Agency, Research Triangle Park, N. C. EPA Contract No. 68-02-1375. 1976. 424 p. 

Commodity Data Summaries, 1977. U.S. Department of 

The Interior, Bureau of Mines, Washington, D. C. January 

1977. 

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, Washington, D.C. 1973. 116 p. 

Ter Haar, G. L., D. L. Lenane, J. N. Hu, and M. Brandt. 

Composition, size, and control of automotive exhaust particulates. J. Air Poll. Control Assoc. 22(l):39-46, 1972. 

Federal Register. Regulation of fuels and fuel additives. 

5S(234):33. 734-33. 741, Dec. 6. 1973. 

Wixson, B. G. and J. C. Jennett (eds.). An Interdisciplinary Investigation of Environmental Pollution by Lead and 

Other Heavy Metals from Industrial Development in the 

New Lead Belt of Southeastern Missouri. (Interim report.) 

National Science Foundation, Research Applied to National Needs (RANN), Rolla and Columbia, Missouri, The 

University of Missouri. 1974. 480 p. 

12 

13 

15 

16 

17 

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 semiquantitative estimates of the movement of lead within and 

among the various environmental media. This is 

largely because the physical and chemical transformations occurring within the lead cycle are not well 

understood. The purpose of this chapter is to summarize 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. 

FOOD 

PROCESSING 

.; WATER : 

:

: SUPPLIES :: 

> PLANTS •:•>: 

:•:•:•:•:•:•:•:•:•:•:•: 

• EARTH : 

:

 ISOILI : 

MINING 

OPERATIONS 

JO'lN'D'OStRV > 

u. r , , 

. » / ^.AUTOMOBILES j—•- ;, 

L ± I 

; ATMOSPHERE ;. 

I (LEAD AEROSOL \-

: AN D ;'• 

; ORGANIC LEAD) ;'• 

:£:£;£: "Ir^x^'oust':::::::!"^' Si::::::::::*:::*:::*:::*:*: 

OTHER LEAD 

CONTAINING 

PRODUCTS 

AND WASTES 

" ' FALLOUT" " ly.'.; 

:-:::

:

 AN D RAINOU T '•:•:'•: 

T ~~ 

:':'.yy.'': OCEANS #$ + - * ^ESTUARIES-:;! 

LAKES AND RIVERS 

'•>:•:•: SEDIMENT S •: 

Figure 6-1. Simplified ecologic flow chart for lead showing 

principal cycling pathways and compartments. 

6.2 PHYSICAL AND CHEMICAL TRANSFORMATIONS 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 discussion of these changes will be divided into mobile and 

stationary source categories. This division is somewhat arbitrary in that the pollutants from both 

source categories are well mixed in the atmosphere. 

In those cases in which one type of source predominates (e.g., freeways or smehers), the approach 

should be reasonably realistic. 

6.2.1 Physical Transformations 

6.2.l.l SIZE DISTRIBUTION OF PARTICLES 

FROM MOBILE SOURCES 

Automotive exhaust is the primary source of particulate lead introduced ubiquitously into the atmosphere in urban areas. The size of the particles 

emitted may range from a few hundredths of a 

micrometer in diameter to several millimeters, depending on the operating mode, age of exhaust 

system, fuel lead content, speed and load, acceleration, deceleration, engine condition, and other factors. 

Numerous environmental processes, including 

transformation, transport, deposition, and mechanisms 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 investigators.1

"

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 accumula6-1 
I i u p i Ii •»•'»'" 'I 

P.66 

tion in the exhaust system. The data demonstrate 

that smaller lead particles make up the largest fraction 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 distribution 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 receptor 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 gravitational settling and other scavenging processes 

that occur during atmospheric transport. Figure 6-5 

compares differential mass distributi@ns at the 

California receptor sites with those at a freeway site. 

These distributions are generally bimodal, indicating that particulate lead in the atmosphere may consist of lead emitted by autos and lead that has been 

deposited on surfaces (soil) and re-entrained via atmospheric turbulence (fugitive dust); or fihe bimodal 

distribution may reflect emission patterns. The 

results of these studies generally indicaue that more 

than half of the lead particles are typically less than 

1 fim 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 particulate emissions from automobile exhaust and found that 95 percent of the 

total particulate lead was in particles with mass median equivalent diameters (MMED) less than 0.5 

fim. All samples were taken at steady-cruise conditions and thus do not represent the typical discharge 

of particles under wide-open-throttle accelerations, 

decelerations, and short-term cruise and idle conditions typical of urban traffic. The varying modes 

result in the discharge of much larger particles. 

Robinson and Ludwig" reported MMIED of 0.25 

fim for urban and rural areas; 25 percent of the particles were smaller than 0.16 fim, and 25 percent 

were larger than 0.43 fim (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. 

< 50 — 

1000 

500 

100 

50 

10 

5 

r 

-

-

— 

_ 

~ 

i 

1 

i 

1 

I / 1 / 

\i 

i 

i\ 

V 

1 

1 

l 1 

T ^ 

h 

(I 

ii 

/?! •v. \. 

ONSTO60MPH ELERAT 

k CITY-TYPE DRIVING -*| o 

l l I 

1 1 I I 

TOTAL LEAD EXHAUSTED 

FINE PARTICLES. 0-5 um _ 

AND UNCLASSIFIED LEAD: 

I COARSE PARTICLES, > 5 HIT 

A l 

1 i -

\ 1 }'-

V

 \ \ '- \ \\ 1 -

iV h 

60 MPH | 

ROAD ] CITY-TYPE 1 

LOAD [• DRIVING J -

1 1 1 1 

636 640 650 

RUN NO. 

Figure 6-2. Effect of various driving conditions on the amount 

of lead exhausted.4 

30 40 50 60 70 80 90 

PARTICLES WITH DIAMETER <D,wl % 

Figure 6-3. Effect of speed on size distribution of exhaust particles at different road load cruise conditions and using Indolene HO 0 fuel.3 

Gillette and Winchester15 examined the effect of age 

on the size distribution of lead aerosols. They found 

that lead aerosol size distributions do not vary 

greatly from one source area (essentially an area of 

heavy automobile traffic) to another, and that the 

6-2 
crometen 

UJ a 

UJ OIAM 

UJ PARTIC NAMIC 

O 

UJ 

10.0 

8.0 

6.0 

4.0 

2.0 

1.0 

0.8 

0.6 

0.4 

I 

— 

-

/ l 

I I I I I I I k 

M — AUTO EXHAUST / 

/

 Pb

 / / 

J 1 PASADENA Pb 

A-^ ^ A" 111/72) 

/ ^^ T (2/74) 

I 

/ — 

-

— 

_ 

— 

— 

— 

_ 

— 

I.. 

40 60 80 90 95 

MASS IN PARTICLES < D , percent 

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 D_ is the aerodynamic, 

unit density particle diameter.''' 

0.2 

a. 

a 

ro 

< «- — 0.6 

hE 

E 

< 0.4 

FREEWAY Pb ' 

*•* 

• 

* 

PASADENA Pb 

~ ,*--^ -

- /* # 

, ' / 

'"' 

1 

(5/7:0 rj 

A. / \ 

£*W a 

^ ^ -

(11/721 

1 

1 

r \ / ^ 

\f \ 

o \ -

V (2/74) — 

.Nft ^ 

O 0.2 — 

0.1 1.0 10 

MEAN DIAMETER ID I, micrometers 

Figure 6-5. Differential mass distributions for lead 1 m from a 

freeway, May 1973, and at Pasadena sampling sites, November 1972 and February 1974. (The abscissa is the mean 

diameter, and the dashed lines assume that the smallest particle size is 0.01 /um and the largest 50 /im. Alog Dp = interval 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; im/m T = fraction of mass occurring in a given 

particle size range.)1" 

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 characteristics of the lead aerosol size distribution as a 

result of nonprecipitative atmospheric mechanisms 

for equivalent particle radii larger than 0.2 fim. 

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. l fim in 

diameter.316 Electron micrographs of the exhaust 

particles have shown that although the particle aggregates of about 0.5 fim were stable, samples of the 

gas that had been inhaled showed mor e 

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 processes generate submicrometer-sized lead particulate, whereas lead emissions from material handling 

and mechanical attrition operations associated with 

smelters consist of larger ( > 1 fim) 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 fim, 

whereas in the urban area, 75 percent were smaller 

than 1 fim. 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 probably affected by topographic influences in a manner 

similar to other pollutants. Because of the mountainous location of half of the six primary lead 

smelters in the United States, however, and because 

these three smelters are probably the largest singlepoint emitters of lead, the topographic influence on 

transport and dispersion is important. 

6-3 
P.68 

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

Sample area 

Chicago 

Cincinnati 

Philadelphia 

Los Angeles 

(DTN) 

Pasadena 

Vernon (rural) 

San Francisco 

Cherokee (rural) 

Mojave (rural) 

No. Ol 

samples 

12 

7 

7 

8 

7 

5 

3 

1 

1 

25% 

Avg. 

0.19(7)b 

0.15(3) 

0.14(3) 

0.16(7) 

0.18 

0.17(4) 

0.11 

0.25 

— 

Range 

0.10-0.29 

0.09-0.24 

0.09-0.25 

0.10-0.22 

0.05-0.25 

0.12-0.22 

0.06-0.13 

— 

— 

Distributio 

Avg. 

0.30 

0.23 

0.24 

0.26 

0.24 

0.24 

0.25 

0.31 

0.27 

i by particle size. u,m 

MMEDa 

Range 

0.16-.64 

0.16-0.28 

0.19-0.31 

0.19-0.29 

0.08-0.32 

0.18-0.32 

0.15-0.31 

— 

— 

75% 

Avg. 

0.40(10) 

0.44 

0.41 

0.49(7) 

0.48(6) 

0.40 

0.45(2) 

0.71 

0.34 

Range 

0.28-0.63 

0.30-0.68 

0.28-0.56 

0.39-0.60 

0.13-0.67 

0.28-0.47 

0.44-0.46 

— 

— 

MMED = mass median equivalent diameter. 

Numbers in parentheses indicate number ol samples available for a specific value when different from total number of samples. 

I I T 

MEZA VALLEY 

ZAGREB 

SEP-OCT 1971 

JAINJ-FEB 1972 _ 

MAY-JUL 1972 " 

AUG-SEP 1972 

JAN-FEB 1973 

1 5 10 30 SO 70 90 95 99 

MASS < DIAMETER, percent 

Figure 6-6. Cumulative mass distribution of lead particles by 

size.18 

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 principally in the particulate form. 

2. The mass median equivalent diameters of the 

lead-bearing particles are typically less than 

l fim, 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 atmospheric convection and turbulence processes. 

4. The size distributions are such that significant 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.1019 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 fig 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 /ng/m3of air, a peak of about 0.5 /ug/m3 

could be measured as the car passed by. The data reported 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 Harrison et al.22

 found levels as high as 0.59 /xg/m3 (9.7 

percent of total lead) at a busy gasoline service station. 

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 
P.69 

times higher) than organic lead levels. The results 

are entirely consistent with the studies of Huntzicker 

et al.,10 who report an organic component of 6 percent 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 percentage 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 Tables 6-2 and 6-4), and the potential exposure level is 

similarly magnified. 

FOR ORGANIC AND PARTICULATE LEAD23(Mg/m3) 

Sample 

no.a 

1 

2 

3 

4 

5 

6 

7 

8 

9 

10 

Avg. 

Cincinnati 

Organic Particulate0 

0.2 

0.0 

0.0 

0.2 

0.4 

0.2 

0.2 

0.4 

0.2 

0.2 

0.2 

1.5 

0.9 

0.9 

1.9 

3.7 

1.6 

1.8 

1.3 

1.5 

2.4 

1.7 

Den 

Organic 

0.2 

0.5d 

1.4d 

0.3 

0.2 

0.1 

0.0 

0.2 

0.2 

0.5d 

0.2 

ver 

Particulate 

2.3 

1.8 

1.6 

1.7 

1.0 

1.8 

2.2 

1.8 

2.0 

— 

1.8 

Washington, D.C. 

Organic Particulate 

0.0 

0.2 

0.1 

0.3 

0.1 

0.1 

0.1 

0.2 

0.4 

0.2 

0.2 

1.4 

1.4 

1.5 

1.0 

1.1 

0.8 

1.7 

1.2 

0.8 

1.6 

1.2 

St. 

Organic 

0.5 

0.2 

0.4 

0.2 

0.3 

0.2 

0.3 

0.4 

0.4 

1.3d 

0.3 

Louis 

Particulate 

2.0 

2.0 

1.8 

2.5 

1.9 

1.8 

2.2 

2.2 

2.0 

1.2 

2.0 

Philadelphia 

Organic Particulate 

0.5 

1.1d 

0.2 

0.4 

0.8 

0.4 

0.0 

0.3 

0.1 

0.1 

0.3 

1.3 

1.7 

2.9 

2.4 

1.1 

1.1 

1.7 

2.1 

1.8 

2.3 

1.8 

Chi 

Organic 

0.2 

0.4 

0.2 

1.6d 

0.2 

0.2 

0.3 

0.1 

0.2 

0.2 

0.2 

:ago 

Particulate 

5.9 

5.6 

5.3 

3.5 

4.6 

5.5 

5.8 

4.8 

5.0 

5.1 

5.1 

Sample no. represents order in which samples were taken. Cities were not sampled concurrently. 

All values are average ot two determinations, 

determined by NASN method (6). 

Organic lead averages do not include these values because the replicate values tor 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 

City 

Cincinnati 

Denver 

Washington, D.C. 

St. Louis 

Philadelphia 

Chicago 

aAII values are averages 

Total lead3 

Organic. 

ug/m 

0.2 

0.2 

0.2 

0.3 

0.3 

0.2 

of ten determinations 

particulate Pb x 

Particulate, 

jig/m3 

1.7 

1.8 

1.2 

2.0 

1.8 

5.1 

too 

Particulate. 

% of total 

89 

90 

86 

87 

86 

96 

TABLE 6-4. ANALYSES OF FIVE REPLICATE SAMPLES 

TAKEN IN AN UNDERGROUND PARKING GARAGE23 

Organic 

lead, 

Sample no. /J.g/m 

1 1.9 

2 1.9 

3 1.9 

4 1.8 

5 2.2 

Average (X) 1.9 

Relative standard 

deviation (Srel)a 7.9% 

a0 . Standard deviation ,„ „ Srel = x 100 

Organic 

lead. 

% 

15.7 

17.1 

17.6 

14.9 

18.0 

16.7 

7.9% 

Particulate 

lead, 

/ig/m3 

10.3 

9.2 

8.9 

10.3 

10.0 

9.7 

6.7% 

Total 

lead. 

Mg/m3 

12.2 

11.1 

10.8 

12.1 

12.2 

11.6 

5.2% 

Average 

As the lead alkyl compounds of gasoline are subjected to the elevated temperatures and pressure of 

combustion, they are converted to lead oxides, 

which function to inhibit engine knock. The lead oxides 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 particulate 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 fim 

have a composition similar to lead-containing 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 (Fe203), 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 
P.70 

TABLE 6-5. AVERAGE COMPOSITION OF PARTICULATE LEAD COMPOUNDS EMITTED IN AUTO EXHAUST8'

2

'

4 

Compound, wt. % 

aNH„CI- /3NH4CI- 2NH4CI- 3Pb3 (P04 lj" 

Exhaust source PbCIBr 2PbCIBr 2PbCiBr PbCIBr "bCIBr 

CarB: 

City type cycle, fuel plus TEL motor mix only 68 24 6 2 — 

City type cycle, added sulturc 70 30 — — — 

City type cycle, added phosphorusd 35 18 17 10 20 

Constant speed, 60 mph, road load 60 20 20 — — 

Full-throttle accelerations 85 10 5 —- — 

CarM: 

City type cycle, fuel plus TEL motor mix only 33 40 5 22 — 

Constant speed, 60 mph, road load 30 30 35 5 — 

Full-throttle accelerations 90 10 — — — 

aX-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. PbSO. and PbO-PbCI-Br-hLO occurred ocasionally in concentrations of 5 percent or less. 

cSulfur 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 Eight-Mile Roadb 

Lead compound Zero time 18 hour Near road 400 yd Rural site0 

PbCi^ 104 83 iT2 105 5~4 

PbBr2 5.5 0.5 4.0 0.7 0.1 

PbBrCI 32.0 12.0 4.4 0.6 1.6 

Pb(OH)CI 7.7 7.2 4.6 8.8 4.0 

Pb(OH)Br 2.2 0.1 2.0 1.1 — 

(PbO)2PbCI2 5.2 5.6 2.8 5.6 1.5 

(PbO)2-PbBr2 1.1 0.1 0.7 0.3 — 

(PbO)2PbBrCI 31.4 1.6 2.0 0.6 1.0 

PbC03 1.2 13.8 15.6 14.6 30.2 

Pb3(P04)2 — — 0.2 0.3 — 

PbOx 2.2 21.2 12.0 25.0 20.5 

(PbO)2PbC03 1.0 29.6 37.9 21.3 27.5 

PbOPbS04 — 0.1 1.0 4.6 5.0 

PbS04 0.1 — 2.2 6.0 3.2 

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. 

State highway in Detroit carrying about 100,000 cars a day. 

°Samples were taken 400 yd from a lightly traveled roadway. 

(PbO) occurring as the 2 PbC^PbBrCl dou- by X-ray diffraction. This is particularly 

ble salt. Lead sulfate and lead phosphate ac- true for particles in the 2- to 0.5-micrometer 

count for 5 to 6 percent of these deposits. size range. 

(These compositions resulted from the com- 6. There is considerably more soot and carbustion of low-sulfur and low-phosphorus bonaceous material associated with small 

fuel.) particles than with coarse particles re3. PbBrCI is the major lead salt in particles of 2 entrained after having been deposited after 

to 10 micrometers equivalent diameter, with emission from the exhaust system. This car2 PbBrCI -NH4C1 present as a minor constit- bonaceous material accounts for 15 to 20 

uent. percent of the finer particles. 

4. Submicrometer-sized lead salts are pri- 7. Particulate matter emitted under typical 

marily 2PbBrCl-NH4Cl. driving conditions is rich in carbonaceous5. Lead-halogen molar ratios in particles of type material. There is substantially less such 

less than 10 microns MMED indicate that material emitted under continuous hot 

much more halogen is associated with these operation. 

solids than the amount expected from the 8. Only small quantities of 2PbBrCl«NH4CI 

presence of 2PbBrCl»NH4Cl, as identified were found in samples collected at the tail6-6 
P.71 

pipe from the hot exhaust gas. Its formation 

therefore takes place primarily during cooling and mixing of exhaust with ambient air. 

Hirschler and Gilbert4 found similar results and 

speculated that higher gas temperature during fullthrottle operations reduced the tendency for the ammonium-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 significantly with driving conditions, engine condition, 

type of fuel, and age of exhaust system. Particles > 2 

fim in the exhausted particulate are primarily lead 

bromochloride. The very large particles, a consequence 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 disagreement in the early literature concerning the loss of 

halogens by these lead compounds. Pierrard26 suggested that PbBrCI 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 carbonates and lead oxides. Pierrard26obtained data on 

aged lead aerosol that indicated that the lead particle surfaces had already been converted to a 

relatively insoluble form such as oxide, carbonate, 

or basic halide; this would be consistent with a conversion mechanism expected to release the less reactive hydrogen halide rather than the more reactive 

molecular halogen. Dzubay and Stevens28 observed 

a diurnal variaton in the bromine-to-lead concentration ratio in atmospheric particulate indicative 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 proportions of lead carbonates ana lead oxides increased. 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 particulate lead increased when 

diluted exhaust was irradiated by light in the wavelength 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 

S02 . Irradiation significantly increased the sulfate 

concentration of the particulates and was accompanied by a shift to smaller particle sizes. A shift of 

nitrate-bearing particles to smaller sizes, with and 

without addition of S02 , was also observed with irradiation. The amount of nitrate present was 

decreased in the presence of S02 . 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 N0 3 

concentrations decrease. 

The information available regarding the chemical 

composition of lead particles emitted from automobiles 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 presence of SOz, 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 Unfortunately, their experimental approach did 

6-7 
P.72 

not rely on a particularly definitive method 

of identification. Indeed, the electron microprobe 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 characteristics of the particles can provide only circumstantial indications of the compounds 

that are present. This is particularly true for 

lead-bearing particles because compounds of 

several other elements are also typically present. Habibi et al.,5

 for example, have shown 

that the particles often include iron as well as 

lead compounds. The percentage composition 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 percentage of the total, its mass percentage may be 

quite different, depending on the size distributions 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, significant 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 chromate 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 produced 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 S0 2 usually associated with lead smelting 

operations, coupled with the possible interactions 

between lead particles and SOz, imply that the compounds 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 interact in a complex manner. The transport mechanisms 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 particulate 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 particulate 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 elevations 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 fim, and 85 percent 

were under 4 fim in diameter. Figure 6-8 shows a 

typical relationship of particle size to distance from 

the highway. Cholak etal. 1 2 and Schuck and Locke32 

did similar studies with similar results. As shown in 

Figures 6-4 and 6-5, Huntzicker et al.10 demonstrated that the large particle mode (Dp >7 fim) in 

the freeway distribution is severly attenuated at the 

Pasadena site. 

0 I 1 1 I 

-

-

-

TRAFFIC VOLUME, 

vehicles/day 

1 0 - 58,000 

\ 6 - 47.000 

ft • - 44,000 

\ O - 19,800 

"^-o^ZjZlI^ 

1 1 1 1 

1 

• -

-

-

—o1 

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 

% HAVING MEAN MASS DIAMETER LESS THAN 

Figure 6-8. 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 Chow3335 measured dissolved 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 concentrations 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 /ig/kg in the northern hemispheric oceans. Chow and Patterson35 

revised this estimate downward to 0.07 figlkg. There 

appears to be no difference between lead concentrations in deep water in the Atlantic and Pacific. These 

investigators calculated that industrial lead is currently being added to the oceans at about 10 times 

the rate of introduction by natural weathering, with 

significant amounts being removed from the atmosphere by precipitation and deposited directly 

into the ocean. Their data suggest considerable contamination of surface waters near shore, diminishing 

toward the open ocean.35 These investigators conclude that lead emissions from automobiles are the 

primary source of pollution of ocean surface water. 

0 

1000 

20OO 

3000 

4000 -1 

—<r 

i f 

fi It 

6 

i 

o— 1 

1 

^ ^ ** <*? 

1 

1 f 

O - ATLANTIC 

(BERMUDA) 

O - MEDITERRANEAN 

40°39'N, 05°48'E 

d- PACIFIC 

29°13'N, 117°37'W 

I 

-

— 

LEAD IN SEA WATER, vg/kg 

Figure 6-9. Lead concentration profiles in the oceans. " ^ 

Duce, Taylor, Zoller, and their co-workers36'

38 

have investigated trace-metal concentrations (including 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 particulate pollution. Enrichment 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 com6-9 
P.74 

parison in Figure 6-11 is that 90 percent of the particulate pollutants in the global troposphere are injected in the northern hemisphere.39

 Since the residence 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 manmade) sources. 

TABLE 6-7. CONCENTRATION RANGE AND MEAN EFcru8 t 

VALUES FOR ATMOSPHERIC TRACE METALS COLLECTED 

OVER THE ATLANTIC NORTH OF 30° N 36 

Concentralion 

range, 

ng'scm 

t rcrust. 

qeom. mean3 

Al 

Se 

Fe 

Co 

Mn 

Cr 

V 

Zn 

Cu 

Cd 

Pb 

Sb 

Se 

8-370 

0.0008-0.011 

3.4-220 

0.006-0.09 

0.05-5.4 

0.07-1.1 

0.06-14 

0.3-27 

0.12-10 

0.003-0.62 

0.10-64 

0.05-0.64 

0.09-0.40 

1.0 

0.8 

1.4 

2.4 

2.6 

11 

17 

110 

120 

730 

2,200 

2,300 

10,000 

Calculated on the basis of the mean crustal abundances of Taylor." 

Figure 6-10. Midpoint collection location for atmospheric 

samples collected from R. V. Trfdenf north of 30°N, 1970 

through 1972.36'

38 

Murozumi et al.41 have presented supportive evidence. Their data show that long-range transport of 

lead aerosols emitted from automobiles has significantly polluted the polar glaciers. They collected 

• NORTH ATLANTIC WESTERLIES 

D SOUTH POLE 

CogivTB" 

M 

s«n 

|Pb«- U -

rffB" 

J * JBL 

Figure 6-11. The EFcrug t 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 factors. The EFcrus t 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 concentrations in the Antarctic were below the detectable 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; supporting data are shown in Table 6-8. 

The results and conclusions of Murozumi et al. 

were criticized by Mills,42 who suggested the increase 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 re6-10 
0.20 

0.18 

0.16 

0.14 

0.12 

0.10 

0.08 

O.OE 

0.04 

0.02 

n 

' I T-TV" 1 1 1 1 

J.iy , T l 1 1 

1 , 1 1 1 1 | 

o 

. 1,,, , 1 

1 1 1 

0 

J. 1 1 

1 1 ' 

o 

1 1 . 

-rr 

o 

-LXJ 

1 ' ' 

J -

1 -

0 / — 

joX -

j -

l°-

-

-

— 

1 1 1 

I 1 1 r 

- O - LEAD SMELTED IN NORTHERN HEMISPHERE 

D - LEAD SMELTED IN SOUTHERN HEMISPHERE 

& - LEAD BURNED AS ALKYLS IN NORTHERN HEMISPHERE 

800 

h«-B,C, »| « 

1800 1850 

A. D. 

AGE OF SAMPLES 

Figure 6-12. Lead concentration profile in snow strata of 

Northern Greenland.41 

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 

0.06 

Lead 

aerosols 

produced 

from smelteries.. 

103 tons'yr 

2 

4 

8 

2 

Lead burned 

as alkyls. 

103 lons/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. 

/ig/kg snow 

0.01 

0.03 

0.07 

0.2 

aValues corrected. 

cent ice layers were extremely high (148 fig/kg). 

Jaworowski et al.45 also studied stable and radioactive pollutants from ice samples from Storbreen 

glaciers in Norway. The mean stable lead concentration in Storbreen glacier ice in the 12th century was 

2.13 figlkg. The mean for more recent samples was 

9.88 /u.g/kg. Around 1870, the average lead concentration in Norwegian glacier ice was 5.86 figlkg, 

whereas that for glaciers in Poland was 5.0 figlkg. A 

century later, the mean concentration in the Norwegian glacier was 9.88 Mg/kg, whereas the mean 

concentration in the Polish glacier reached 148 

Mg/kg. Jaworowski et al.45 attributed the large increase of lead concentrations in the Polish glacier to 

local sources. 

Jaworowski et al.45 also measured

 2,0Pb in the 

glacier ice. The values found in the Storbreen glacier 

ice are shown graphically in Figure 6-14. The highest 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 

^

10Pb concentrations in the investigations suggest 

that part of the atmospheric

 2l0Pb may have originated 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 57 56 5S 54 

4 0.5 

z 

2 0.4 H < -210 CONCENT 

o o 

Q 

m 0.1 

-i 

l l I l I l I 1 I I I l I 

r -IT 

— 

-

__ 

. 

-

-

I 1IIII I I I I I 

1 2 3 4 ,5 6 7 8 9 10 11 

DEPTH, meters 

Figure 6-14.

 210Pb In Storbreen, Norway, glacier Ice, 

1954-1966, 

45 

6-11 
"*r*~ 

P.76 

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 input 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 inorganic lead particulate from the atmosphere are 

dry deposition and precipitation. Detailed discussions 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 significantly, 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 sedimentation, 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 acceleration. When a particle is of a size comparable to 

the mean free path of the gas molecules, bombardment by the molecules results in a random or 

Brownian motion that is superimposed on its downward motion. If a particle is very small and its motion is observed for only a short period of time, its 

fall may be completely masked by the Brownian motion. 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 settling velocity of spherical particles of the same 

volume. The aerodynamic particle size, conventionally used when discussing airborne particulate, 

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 fim), large nuclei (particle radius 0.1 to 1 

fim), and giant nuclei (particle radius > 1 fim). Extremely small particles (radius < 0.001 fim) tend to 

coagulate rapidly to form larger ( ~ 0.05 to 0.5 

fim), 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 /Am 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.\fimandn= 103/cm3, 50 percent reduction was calculated to require 500 hr. The size distributions of large and giant nuclei are not significantly affected by coagulation. 

Settling or terminal velocities of spherical, particles, 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. 

/un 

0.01 

0.05 

0.1 

0.2 

0.5 

1.0 

2.0 

5.0 

10.0 

20.0 

50.0 

Terminal velocity 

Israel and Israel 

1.43 x10"5 

— 

2.32 X10-4 

— 

— 

1.32 x10"2 

— 

— 

1.23x10° 

— 

— 

cm/sec 

Green ond Lane 

8.71 x 10"5 

2.27 X10-4 

6.85 x 10"4 

3.49 x10"3 

1.29 x10"2 

5.00 x10'2 

3.03 x10"1 

1.20x10° 

4.71 

24.7 

Airborne particles are also removed from the atmosphere by inertial mechanisms. In turbulent inertial deposition, turbulent wind fluctuations perpendicular to a horizontal surface impart sufficient 

inertia to propel the particles through the boundary 

layer and onto the surface. This mechanism is important for both smooth and rough surfaces. When 

the roughness elements on a surface protrude sufficiently far into the windstream, inertial impaction 

may become important. The mean horizontal flow of 

the wind, rather than turbulent fluctuations, controls impaction. This mechanism occurs when particles cannot follow the air streamlines as they pass 

around a roughness element. In this case, the mean 

windflow supplies the inertia that drives the particles onto the surface. 

Inertial mechanisms are dependent on atmospheric 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 excreted by the leaves. Impaction of submicrometersized 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 particulate matter. Therefore, pine 

trees near a surface source of lead particulate pollution 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, respectively, than soil lead concentrations at corresponding 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 concentration 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|_ c 

(6-1) 

where K is the deposition velocity, N is the deposition 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 particle eddy diffusivity can be determined, that the 

effect of gravity can be described by the terminal settling velocity, that agglomeration does not occur, 

and that particles are completely retained on the 

surface. The model was designed to predict deposition 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 assumptions, Sehmel and Hodgson55

 write the equation for 

deposition flux as: 

N = -(e + D) — -v.C (6-2) 

dz 

where vt is the absolute value of the terminal settling 

velocity, € is the particle eddy diffusivity, D is the 

Brownian diffusivity, C is the airborne concentration, and z is the reference height. For small particles, the sedimentation term (-v,C) is negligible so 

that deposition velocity is a function of the Brownian and eddy diffusivity term only. For large particles, the diffusivity term is negligible, and the 

deposition velocity is equal to the terminal velocity. 

Incorporating the concepts of friction velocity: 

u.= -^—L — (6-3) 

K lm(z/z 0 ) 

where k is von Karman's constant, u is the 

windspeed, z is height, and zo is the roughness 

height. Roughness height is defined as a measure of 

the roughness of a surface over which fluid is flowing: 

z

o=H/3 0 (6 . 4 ) 

where H is the average height of surface irregularities. Sehmel and Hodgson55 developed prediction deposition velocity curves for a range of 

roughness heights and friction velocities. Representative curves are shown in Figures 6-15 through 

6-17. Deposition velocities are shown to be a function of particle diameter and have their smallest 

values in the 0.1 to 1 fim particle diameter range. 

The mean diameter of lead-containing particles in 

the atmosphere, remote from major sources, falls approximately in this range. In the case of larger particles, both increased effective eddy diffusion in surface 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 predicted 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-Mm 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-Mm particlediameter range, the deposition velocities are controlled by atmospheric diffusion in the layers immediately above the canopy. As indicated by Sehmel 

and Hodgson,55 the model should predict reasonably well the deposition velocities for simple surfaces, 

assuming the wind direction is persistent over sufficient 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 
P.78 

particle size. 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.10found a deposition velocity of 1.80 cm/sec on 

a Teflon plate placed on the shoulder of a Los 

Angeles freeway. 

£ 10 

E 

* 

> ELOC OSITION V 

EL 

o 

• •i yi T 

1 cm\ 

- 1 0 cm 

~"^, v 

IIMI | rii i IIIT | T—r t»1111f i v 

TYPICAL: / 

UPPER BOUND; UNSTABLE, L - 10 meters/ 

. /LOWER BOUND;STABLE, L »10meters/ A YJ 7 J 

•--'••:-iL 'k\ / S .'S"7l 

l 10 meters 

i l i 

*"'*- —-"* /*~u„- 0 

1 mi l »l l 1 l/lUl L 1 L 

_ i 

Jz 

' z 

-

' 

1 1 1 Illll 

10'' 1 10 

PARTICLE DIAMETER, micrometers 

Figure 6-15. Predicted deposition velocity of particles at indicated height for u. = 20 cm/sec and ZQ = 3.0 cm.55 

—I 1 I I Mill I—I I I I IM | I I I I 11II | I—Illl l 

.UNSTABLE, L =-10 meters 

..f STABLE. L - 10 meters 

-"••'*-„ 

S • -^^ **-. u. . cm/sec - S \ I /:: 

— ^ >. > • . ' 

V - * 

"•^ 10 , ' 

I I I I 11 u l J iL 

10 1 10 

PARTICLE DIAMETER, micrometers 

Figure 6-16. Predicted deposition velocities of particles at 1-m 

height for z 0 = 3.0 cm, 55 

Johnson57 sampled particles with an instrumented 

aircraft flying at 300 m altitude in the vicinty of St. 

Louis, Missouri. Particles were collected by exposing a small (1.0- 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 from photographs. 

Samples were obtained upwind and downwind of St. 

I I I I Illll 1—I I I I lll| 

^UNSTABLE, L » -10 meters 

„STABLE,L" 

I I I Illll 

10 1 10 

PARTICLE DIAMETER, micrometers 

10 

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 l 

through July 18, 1975. The results indicated typical 

number concentrations of airborne particles larger 

than 10 fim in diameter of 7,500 particles/m3 upwind and 11,000 particles/m3

 downwind. Particles 

larger than 30 fim in diameter were found in concentrations of 200 particles/m3

 upwind and 425 particles/m3

 downwind of the city. For the downwind 

particle number densities of > 10 Mm and >30 Mm 

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 indicate that particles >30 fim 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 fimdiameter 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 carbon monoxide and lead from an expressway (1-75, 

north of Cincinnati, Ohio). The significant results 

are shown in Figures 6-18 through 6-20. Approximately 50 percent of the lead emitted from the automobile traffic was removed from the atmosphere by 

6-14 
dry deposition within 640 ft of the edge of the roadway (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. Assuming 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 Mg/m3 at 20 ft to about 1.5 

Mg/m3 at 640 ft, a decrease by a factor of about 5. 

The data were not sufficient to determine the relative 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. 

1—I Illl l 

% LEAD REMOVED = 

_ R = 0.68 

i—r i i 11 

i IIII I 

40 60 80 100 150 200 400 600 

TRAVEL DISTANCE, feet 

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 contamination 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 processes include rainout and washout. Rainout occurs 

8 

b 

4 

2 

1.0 

0.8 

0.6 

0.4 

0.2 

-

-

-

. 

-

1 1 

—0— 

--•--

1 1 

1 Illl l 

SAMPLING STATION 

20 ft FROM EDGE 

OF EXPRESSWAY 

SAMPLING STATION 

640 ft FROM EDGE 

OF EXPRESSWAY 

1 Illl l 

l 1 /A 

1 

1 

ifa 

1 

a 

aJ 

1 

1 1 

DO | | 

1 

. 

-

-

-

-

-

.. 

-

— 

-

-

-

1 

10 20 50 70 90 95 98 99 

Pb PARTICULATES <STATE D SIZE, percent 

Figure 6-19. Comparison of size distribution of lead particulates collected at 20 and 640 ft from an expressway north of 

Cincinnati. Ohio. Determined by seven-stage Andersen 

sampler.58 

- | 1—|—i i i i | | 1—i—|— r 

Pb CONC. = 12.1147667 - 3.8993135 X LOG DISTANCE 

R " -0.7 8 

CO CONC. - 6.51989 - 1.7138467 X LOG DISTANCE 

R = -0.6 0 

_ i _ _ i _ _L _i_ JL50 100 200 

DISTANCE FROM EDGE OF HIGHWAY, feet 

Figure 6-20. Atmospheric concentration of lead and carbon 

monoxide as a function of log of distance from edge of highway (R = correlation coefficient).58 

when particulate matter is present in the supersaturated environment of a growing' cloud. The 

small particles (0.1 to 0.2 fim) act as nuclei for the 

formation of small droplets, which grow into 

raindrops.49 Droplets also collect particles under 

0.1 Mm by Brownian motion and by the water-vapor 

gradient. The nucleation process may also occur on 

particulate matter present below cloud level, producing droplets large enough to be affected by sedimentation. These processes are referred to as 

rainout. A second process (washout) occurs when 

falling raindrops collect particles by diffusion and 

impaction on the way to the ground. Rainout and 

6-15 
•Ill PI I ••••• • 

P.80 

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 ajid 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 precipitation as in water supplies, inferring the existence of a process by which lead is depleted after 

precipitation reaches the ground. Russian studies61 

point to the insolubility of lead compounds in surface 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 tfoat showers 

had lower concentrations than slow, even rainfall. 

Data presented by Jaworowski44 show tbat in recent 

years, the lead content in rainwater ranged from 0 to 

1858 Mg/l'ter. 

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 percent.63 

Concentrations of

 210Pb in rainwater have also 

been reported by Jaworowski44 as highly variable (as 

much as two orders of magnitude im the same 

locality) and not related to season or amiount of precipitation. Values ranged from 0.2 to 300 

pCi/liter.44 High concentrations were found in samples collected from northern continental localities, 

and low concentrations were found in samples from 

oceanic and Antarctic locations. Jaworowski suggests that the differences might be attributed in part 

to artificial contamination by nuclear esxplosions. 

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 primarily during the late fall and winter months. Airborne concentrations at a freeway site varied from 

0.3 Mg/m3to a maximum of 19 Mg/m3 iffl t*he fall and 

winter seasons, and were a maximum of'9.3 Mg/m3 in 

the spring. During periods of light rawfall in the 

spring, the maximum concentration observed was 

7.4 Mg/m3- A typical daily concentration profile observed is shown in Figure 6-21. More than 90 percent of the lead pollutants reaching the surface during 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.* Approximately 1 percent of the total dry fallout collected 

near the expressway was lead. Wet deposition (approximately 33 cm or 13 in of rain per year) accounted 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. 

E 

•5 15 

MID- 2 

NIGHT 

4 6 8 10 NOON 2 

TIME OF DAY 

4 6 8 10 MIDNIGHT 

Figure 6-21. Atmospheric lead concentration at freeway site 

in Palo Alto, California, on August 15,1966.63 

? 1.0 

N 

en 

E 

1 v ] I I I II I I I 

— ^ V l=STD . DEV. 

1 N . X.9.0x10VB06L 

N . (SEE FOOTNOTE IN TEXTI 

-

-

-

-

1 • 1 1 1 I t I I 

1 

-

-

-

-

-

'x -

IN 

100 200 500 1000 2000 500010,000 50.000 100,000 

DISTANCE FROM FREEWAY {X), foot 

Figure 6-22. Average lead in dry fallout as a function of distance from the freeway.63 

'Figure 6-22 is a semi-log plot of the three average lead values as a function nf distance from the freeway. The data appear to fall along a straight line, suggesting that 

the relationship hetween lead in fall out. I., and distance from the freeway. X. can 

he described by X = aeh l- where a and b are constants. From the semi-plot, the appropriate values for a and b are a = 9.0 x I0 4

; b o -8.06. if L is expressed in 

mgm2-wtc and X is expressed in feet. Therefore X = 9.0 x IO4 e**- 0ft k The area 

under this curve, from X , = 50 ft to X3 = 26,900 ft, should represent the total 

amount of lead deposited in the Palo Alto area for each l-fi section of freeway. This 

value is 7.85 g/ft. The area under the curve from L = 0.95 mg/ft^-wk to L • 0 

should represent the total amount of lead that was removed hy sedimentation, 

assuming that the data can be extrapolated past 26,900 ft. This value is I I.I g/ft. 

This indicated that an average of 70 percent o f the lead that was removed hy sedimentation was removed within 5 miles of the source. 

6-16 
P.81 

TABLE 6-10. SUMMARY OF FIELD DATA FROM PALO ALTO, 

CALIFORNIA' 64 

Freeway3 

{Bayshore) 

Residential Foothills 

Lead in dry fallout: 

Average, mg/fr-wk 

Amount removed, mg/ft -yr 

Lead in rainfall: 

Average, mg/liter 

Amount removed, mg/ft -yr 

Average air concentration, 

Mg/m3 

Pb/total solids in air 

Pb/nonvolatile solids 

in dry fallout 

0.92 

49.4 

0.181 

3.25 

7.30 

0.042 

0.24 

11.7 

0.149 

3.66 

2.28 

0.018 

0.153 

8.3 

0.035 

0.92 

1.90 

0.016 

0.0112 0.0102 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 precipitation 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 ferroalloy 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 presented 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 (g/ha) 

Dry 

January 

February 

March 

April 

May 

June 

Total 

Average 

34.1 

6.7 

21.6 

15.4 

26.5 

11.1 

115.4 

19.2 

< 16.7 

3.3 

10.6 

7.5 

13.0 

5.4 

56.5 

9.4 

a

Total deposition — 172 g/ha. Wet deposition — 67 percent ol total. 

yuntzicker et al.10 estimated the flow of automobile-emitted lead in the Los Angeles Basin based on 

measurements of particle size, atmospheric concentrations, 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 automobile 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 deposition), 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 

25% 

t 

REMOVED 

BY STREET 

CLEANING 6% 

SEWAGE 

40% J 

NEAR DEPOSITION 

STREET 

8% 

LAND 

32% 

RUNOFF 2% V 

0.64 metric 

tons Pb/day 

I 10% 

FAR 

DEPOSITION 

LAND 

T ^ 

COASTAL WATERS 

Figure 6-23. Fate of lead contributed from automotive traffic 

in Los Angeles Basin.03 

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 originated 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 distance of 300m. 

1000 

500 

I I 1 

SMELTER A: 

\ SMELTER B: 

1 1 1 

Y = 6,100 -2.560 log X 

R = -0.8 1 

p < 0.001 

96 SAMPLES AT 16 SITES 

— 

Y = 896 - 340 log X 

R - -0.63 

p <0.001 

34 SAMPLES AT 6 SITES 

-

U 

200 300 400 500 

DISTANCE FROM STACK, meters 

Rgure 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 
P.82 

Studies such as those described above clearly indicate that lead is effectively removed from the atmosphere by dry and wet deposition processes, and 

that atmospheric concentrations are significantly influenced 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 characteristics of the deposition surfaces, airborne concentrations, 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 particles, whereas the smaller particles will remain airborne 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 deposition, although there are few data available to quantify 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 potential human lead-exposure patterns — both inhalation 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 sedimentation 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 particles are removed primarily by diffusion and inertial 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 deposition. 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 occupational environments where fugitive dust emissions 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 leaddust 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 involved and of the temporal and spatial variations 

occurring, it is not possible to quantify human exposure in uncontrolled cases without the use of personal 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 resuspension. 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 resuspension 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"". (The resuspension 

factor, in m1, 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 increased as a function of vehicle speed and was independent 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 resuspension of lead from roadways may play a significant role in the overall transport of lead away from 

automotive sources. This may be important considering the conclusions of Huntzicker et al.10

 that a 

considerable fraction of the emitted lead deposits 

directly on the roadways. 

In another experiment, Sehmel and Lloyd70 examined the resuspension of \0-fim monodisperse 

uranine particles from a smooth surface in the 

laboratory. They found that the fraction of material 

resuspended per second varied from IO"6 to 10"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 second ranged from 2 x 10 l 0 t o 2.2 x 108

for 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 surface.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 excessive 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 

350 

300 

250 

200 

150 

100 

50 

1 1 

-

-

-

-

1 1 

! 

/ 

_ 

-

> 

\ 

1 °^U 

20 

Pb DEPOSITION, ng/cm'-day 

Figure 6-25. Total deposition of lead on Teflon plates at 

various heights above the roof of Keck Laboratories, California Institute of Technology, Pasadena.71 

Baum et al.74 sampled airborne particulate for a 

period of about 2 years at several locations in Portland, 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 elemental 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 quantitative conclusions about this mechanism. Size distribution measurements of ambient lead presented here 

and elsewhere in the literature represent airborne 

data that have been influenced by the combined factors of atmospheric transport, deposition, and 

resuspension. 

6.3.3 Models 

There is an extensive body of literature on at6-19 
P.84 

mospheric transport and diffusion models.75'

79

 A 

detailed discussion is beyond the scope of this document. 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 excellent review of air quality modeling techniques for 

both rural and urban modeling situations. Experimental data describing the pollutant concentrations 

from point sources show that, in spite of wide variations, 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 vertical 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 contamination of soils by the emission of lead from 

mobile and stationary sources and through the disposal 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.2029 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 impact of lead on human health and ecosystems. Information 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 techniques have been developed and used by the Colorado State University research group to determine 

lead compounds in soil and plants.10 

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 incomplete.81

 Early work indicates that lead probably 

reacts with soil anions, e.g., S0 4

=

, P0 4

=

, or C0 3

=

, 

or with some organic or clay complex.82 These reactions would tend to make the Pb insoluble, thus inhibiting 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 increased with decreasing pH and concentration of 

NaCl. Furthermore, absorption of soil lead by hydrous oxides of iron and manganese, and its consequent immobilization, has been reported by Gadde 

and Laitinen.84 

Studies have identified cation exchange capacity, 

organic matter content, pH, soil type, and soil drainage 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(P0)4)2, Pb4 0(P04 ) 2 , 

Pb5 (P04 ) 3 0H, and even PbC03 , 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 present 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 consistent.87 

Olson and Skogerboe29 preconcentrated lead 

compounds in roadside soil samples and used X-ray 

powder diffraction techniques for compound identification. The lead compounds in each soil fraction 

examined are shown in Table 6-12. The most abundant 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 contained in the dense fractions and that the majority 

(>5 0 percent) of this lead was present as sulfate. 

The results indicate that oxides present in the soil 

6-20 
were minor constituents compared to the sulfate 

concentrations. Since lead bromochloride compounds are the principal constituents of fresh automobile 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 S02 in the atmosphere or at the soil 

interface may react with the lead particulate 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 composition 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 reported, (Table 6-12). Analytical data confirming the 

other compounds mentioned above are not available. 

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 carbonate or sulfate ions to (1) form insoluble lead carbonate 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 hydroxide, 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 fig/\iter and about 500 ^tg/liter in soft water (pH 

<5.4). 8 9 Lead sulfate (PbS04) is present in soft 

water and limits the lead concentration in solution. 

Above pH 5.4, PbC03 and Pb2 (OH) 2C03 limit the 

TABLE 6-12. LEAD COMPOUNDS IDENTIFIED IN ROADSIDE 

SOILS BY X-RAY POWDER DIFFRACTION TECHNIQUES29 

Location and 

soil fraction 

Fort Collins: 

Magnetic 

Nonmagnetic 

Denver: 

Magnetic 

Nonmagnetic 

Chicago: 

Magnetic 

Nonmagnetic 

Chicago: 

Magnetic 

Nonmagnetic 

Missouri: 

Magnetic 

Nonmagnetic 

Compounds 

found 

PbS04 

PbS04 

PbOPbS04 

Pb02 

PbO° 

PbS04 

PbS04 

PbS04 

PbO 

PbS04 

PbS04 

PbS04 

Nonec 

PbS 

PbS04 

Estimated 

concentrations8 

Major 

Major 

Minor 

Trace 

Trace 

Major 

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 lo approximately 1 to 10 percent ol the lead in the respective fractions. Trace quantities are 

less than approximately 1 percent of the total in each fraction. 

DAssignment is based on the presence of only the most intense d-spacing and is 

therefore questionable. 

cComplex d-spacing pattern obtained with all intensities low; positive assignment of any one compound or group of compounds is questionable. 

concentration. The carbonate concentration is in 

turn dependent on the partial pressure of C0 2 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 

C 0 2 species. Because the influence of changing temperature 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 /txg/liter could be stable in water with pH 

near 6.5 and an alkalinity of about 25 ng bicarbonate ion/liter of water. Water having these properties 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 

/ug/liter of lead could be retained in solutions at 

equilibrium.87 

6-21 
P.86 

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 incorporated in other components of particulate 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 cation exchange indicated that a major part of the lead 

in stream water may be adsorbed on suspended sediment. Figure 6-26 illustrates the distribution of lead 

outputs between filtrate and solids in stream water 

from both urban and rural compartments, as reported by Rolfe and Jennett.91

 The majority of lead 

output is associated with suspended solids in both 

urban and rural compartments with very little dissolved 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. 

100 

so 

0 

_ 

-

SHWll SUSPENDED SOLIDS 

^-^ j FILTRATE 

,,,II, I ,ii ' f ^ 

-

/V/ ^ 

^ 

Figure 6-26. Lead distribution between filtrate and suspended 

solids In stream water from urban and rural compartments."0 

The concentration of lead usually reported represents 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 acidification 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 particulate, and thus it will be necessary to obtain more information on the amounts of lead transported in 

nonsolute form87 before a valid estimate can be obtained 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 includes carbohydrates, amino acids, phenolic and 

quinonic compounds, organic acids, nucleic acids, 

enzymes, porphyrins, and humic materials.87 In addition 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 compounds found in living systems. In addition, oils, 

plasticizers, polymers, and many other organic compounds are discharged to natural waterways by manufacturing 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 Appendix 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.8792 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 precipitated. At initial pH values of about 10, the leadfulvic 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 complexes. 

In summary, the complexing of lead by most of the 

common sulfur-, phosphorus-, oxygen-, and 

nitrogen-containing ligands means that lead will accumulate in living and nonliving organic components of soil-water and sediment-water systems. The 

living and nonliving organic components are not independent, 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 sediment 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 introduced. 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 tetramethyl 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 intermediate, (Me3Pb)2S.95

 Using a system containing no 

sulfides, however, other workers showed the production 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, Me3PbCI, 

Me2PbCl2, and Pb(N03)2 were substituted for inorganic 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 oxide (Pb304) in an aqueous medium results in partial 

demethylation of the corrinoid. This chemical 

demethylation of MeB12 by Pb3 04 was shown to be 

highly pH dependent, with no demethylation occurring at pH 7, and 61 percent occurring at pH 2. 

Trace r studie s with [ 14C]-methyl-labeled 

methylcobalamin indicated that demethylation of 

MeB12 by Pb(IV) was accompanied by a proportional volatilization of the label. These results 

are in agreement with the known instability of 

monoalkyl lead compounds in aqueous media as described by Wood.97 

The alkylation of lead, then, unlike that of mercury, 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 environment by dry and wet deposition. Considerable attention 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 better to soluble rather than total lead in soils. Wilson 

and Cline99 concluded that only 0.003 to 0.005 percent 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 addition 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 PbS04, Pb3(P04)2, and 

PbC03 as possible controlling mechanisms for the 

amount of lead in soils.44 If PbC03 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 associated with plant surfaces in nature may be largely 

lead phosphate. Zimdahl,102 citing studies conducted at Colorado State University and the University of Illinois, reported the identification of lead 

pyrophosphate in bean roots and lead orthophosphate 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,85103 is favored under conditions of low soil pH.104

 MacLean et al.105 have suggested that soil management practices such as the addition 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 
P.88 

with pH and organic matter, and that addition of 

phosphate reduced the uptake of lead; they suggested 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 proportional to soil lead content and is greatest under 

conditions of low pH and low phosphorus. The binding 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 Illinois107

 (cited by Zimdahl102), it was shown that the 

roots of hydroponically grown corn acquired a surface lead precipitate and slowly accumulated 

crystalline lead in the cell walls. The surface precipitate formed quickly and independently of plant activity. Two compounds were postulated but not 

identified. The lead entering the root was concentrated in some but not all dictyosome vesicles. After 

precipitation had occurred in the dictyosome vesicle, 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 eventually 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.32108109 Several studies have shown that plants near roadways 

exhibit considerably higher levels of lead than those 

farther away. In most instances, the higher concentrations 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.IOS.I 10,111 

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 particularly effective means of removing the deposited particles.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 investigators to stipulate that lead may enter plants 

through the leaves. This would typically require, 

however, that the lead particles be dissolved by constituents 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 experiments 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 treatment 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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7/5(6):455-460, 1973. 

6-28 
7. ENVIRONMENTAL CONCENTRATIONS 

AND POTENTIAL EXPOSURES 

7.1 AMBIENT AIR EXPOSURES 

Several studies on concentrations of lead in the 

ambient air have been undertaken. These studies 

were generally intended to survey the levels and distributions of lead in the general air environment and 

around sources. They usually were not designed in 

conjunction with epidemiological studies of the concurrent 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 exception 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 particles has been questioned; this subject is discussed in 

Chapter 4. The studies show that: 

1. Lead typically occurs in urban airborne suspended particles 0.5 fim or less in mass median equivalent diameter at annual average 

concentrations ranging from <0.1 to 5 

/xg/m3, with an overall average of 1 to 2 

Mg/m3. 

2. Urban concentrations of lead have declined 

somewhat since 1970. 

3. Suspended particles in rural air samples contain lead at concentrations ranging from 

<0.01 to 1.4 /ug/m3, with an overall average 

of about 0.2 /j.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 Appendix C. 

7.1.1 National Air Surveillance Network (NASN) 

Data 

Since 1957, samples of suspended particulate matter collected at some 300 urban and 30 nonurban 

NASN sites have been analyzed for trace metals, including lead. Only data beginning with 1966 are 

summarized here, however, because the procedure 

used before 1966 was found to recover only about 50 

percent of the lead actually present. The emission 

spectrograph^ 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 (91 percent 

of the site-years) reported annual averages below 2.0 

Mg/m3, and the majority of nonurban sites (86 percent of the site-years) reported annual averages 

below 0.2 ,y,g/m3. 

Samples collected by the NASN from 1970 

through 1974 were combined for analysis into quarterly 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 concentrations have been 3.0 figlm3

 or greater are listed 

in Table 7-5. 1 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 
P.94 

TABLE 7-1. NUMBER OF NASN URBAN STATIONS WHOSE 

DATA FALL WITHIN SELECTED ANNUAL AVERAGE LEAD 

CONCENTRATION INTERVALS, 1966-19741 •* 

TABLE 7-2. NUMBER OF NASN NONURBAN STATIONS 

WHOSE DATA FALL WITHIN SELECTED ANNUAL AVERAGE 

LEAD CONCENTRATION INTERVALS, 1966-197412 

Year 

1966: 

No. stations 

Percent 

1967: 

No. stations 

Percent 

1968: 

No. stations 

Percent 

1969: 

No. stations 

Percent 

1970: 

No. stations 

Percent 

1971: 

No. stations 

Percent 

1972: 

No. stations 

Percent 

1973: 

No. stations 

Percent 

1974: 

No. stations 

Percent 

1966-1974: 

No. stations 

Total percent 

< 0.5 

9 

9 

4 

3 

14 

9 

5 

2 

9 

5 

— 

16 

9 

20 

15 

19 

15 

96 

8 

Concentration interval, ug 

0.5-0.99 

40 

42 

37 

32 

67 

45 

46 

25 

54 

33 

23 

21 

67 

37 

76 

55 

69 

53 

479 

38 

1.0-1.9 

40 

42 

63 

55 

54 

36 

103 

57 

80 

50 

64 

58 

84 

47 

36 

26 

38 

29 

562 

45 

2.0-3.9 

6 

6 

9 

7 

10 

6 

23 

12 

15 

9 

21 

19 

12 

7 

4 

3 

4 

3 

104 

8 

/m3 

4.0-5.3 

— 

— 

— 

0 

0 

0 

6 

1 

Total 

95 

100 

113 

100 

146 

100 

178 

100 

159 

100 

109 

o o o O 00 o 

137 

100 

130 

100 

1247 

100 

Year 

1966: 

No. stations 

Percent 

1967: 

No. stations 

Percent 

1968: 

No. stations 

Percent 

1969: 

No. stations 

Percent 

1970-1971: 

No. stations 

Percent 

1972: 

No. stations 

Percent 

1973: 

No. stations 

Percent 

1974: 

No. stations 

Percent 

1966-1974: 

No. stations 

Total percent 

< 0.03 

— 

1 

5 

1 

5 

— 

— 

— 

10 

29 

9 

39 

3 

19 

24 

15 

Concentration interval 

0.03-0.099 

10 

52 

7 

35 

15 

75 

11 

52 

— 

— 

4 

12 

7 

31 

5 

31 

59 

36 

0.10-0.19 

6 

32 

10 

50 

4 

20 

9 

43 

7 

70 

9 

26 

6 

26 

6 

38 

57 

35 

ng'm3 

0.20-0.45 

3 

16 

2 

10 

— 

— 

1 

5 

3 

30 

11 

33 

1 

4 

2 

12 

23 

14 

Total 

19 

100 

20 

100 

20 

100 

21 

100 

10 

100 

34 

100 

23 

100 

16 

100 

163 

100 

TABLE 7-3. CUMULATIVE FREQUENCY DISTRIBUTIONS OF QUARTERLY LEAD MEASUREMENTS 

AT URBAN STATIONS BY YEAR, 1970 THROUGH 1974' 

(/u.g/m3) 

Year 

1970 

1971 

1972 

1973 

1974 

No. 

quarterly 

composites 

797 

717 

708 

559 

594 

Min 

LD" 

LDa 

LD» 

LDa 

0.08 

10 

0.47 

0.42 

0.46 

0.35 

0.36 

30 

0.75 

0.71 

0.72 

0.58 

0.57 

50 

1.05 

1.01 

0.97 

0.77 

0.75 

Percentile 

70 

1.37 

1.42 

1.25 

1.05 

1.00 

90 

2.01 

2.21 

1.93 

1.62 

1.61 

95 

2.59 

2.86 

2.57 

2.08 

1.97 

99 

4.14 

4.38 

3.69 

3.03 

3.16 

Max. 

5.83 

6.31 

6.88 

5.83 

4.09 

Arithmetic 

Mean 

1.19 

1.23 

1.13 

0.92 

0.89 

Std. 

dev. 

0.80 

0.87 

0.78 

0.64 

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 

a

 LD = limit of detection. 

TABLE 7-4. CUMULATIVE FREQUENCY DISTRIBUTIONS OF QUARTERLY LEAD MEASUREMENTS 

AT NONURBAN STATIONS BY YEAR, 1970 THROUGH 1974' 

(ng/m3) 

1970 

1971 

1972 

1973 

1974 

124 

85 

137 

100 

79 

0.003 

0.003 

0.007 

0.015 

0.007 

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 0.107 0.166 0.294 0.392 0.950 

0.015 0.015 0.058 0.132 0.233 0.392 0.698 

0.007 0.053 0.087 0.141 0.221 0.317 0.496 

1.471 

1.134 

1.048 

0.939 

0.534 

0.088 0.190 

0.047 0.155 

0.139 0.169 

0.110 0.149 

0.111 0.111 

Year 

No 

quarterly 

composites Min 10 30 50 

Percentile 

70 90 95 99 Max. 

Arithmetic 

Std. 

Mean dev. 

Geometric 

Std. 

Mean aev. 

0.040 3.72 

0.008 4.80 

0.090 2.59 

0.068 2.77 

0.083 2.30 

7-2 
TABLE 7-5. NASN STATIONS WITH ANNUAL AVERAGE LEAD 

CONCENTRATIONS 23.0 Mg/m31<

2 

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 

3.2 

3.7 

3.6 

3.6 

3.1 

4.4 

3.0 

3.3 

3.9 

3.5 

3.2 

3.1 

3.5 

3.1 

4.6 

3.8 

3.0 

4.9 

3.5 

4.5 

3.7 

3.2 

3.3 

5.3 

3.5 

4.6 

3.2 

3.5 

3.1 

5.0 

4.0 

Maximum 

Quarterly 

composite 

8.1 

6.0 

11.0 

4.3 

5.4 

— 

— 

— 

— 

— 

4.8 

7.1 

4.7 

4.5 

5.7 

4.2 

5.2 

5.8 

4.2 

5.6 

4.1 

3.8 

4.0 

6.2 

4.6 

6.3 

6.7 

5.2 

4.8 

6.9 

5-2 

24-hr 

— 

'' — 

— 

— 

— 

14.0 

7.5 

12.0 

10.0 

8.3 

— 

— 

— 

— 

— 

— 

— 

— 

— 

— 

— 

— 

— 

— 

— 

— 

— 

— 

— 

— 

— 

apparently because of location, topography, and 

meteorological conditions that favor retention of 

pollutants in the air over the area. 

Ambient particulate 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 from 1965 until 1971 and 

then declined from about 1.1 ,ug/m3 to 0.84 

/xg/m3 — 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 particulate matter measured also follow this 

pattern, which indicates that the trends in lead are 

not just a result of general particulate controls but 

are a direct result of decreases in lead emissions. 

E 

•a 

\—i—i—i—i—i—r 

90TH PERCENTILE 

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 highest 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: (l) 

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. Evidently summertime meteorological conditions expedite 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 
P.96 

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 responsible for the observed decrease in ambient lead concentrations 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 probably does not proportionately affect many urban 

monitoring sites (which are chiefly center-city locations) because their neighborhoods are generally at 

or near traffic saturation. There may even be instances 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. 

O 30 

Iz 

UJ 

U 

F. 20 

I I I I I I I I I I I I I I I I 

REGULAR GAS SALES 1%) 

f 

PREMIUM GAS SALES 1%) 

UNLEADED GAS SALES (%l _ 

62 64 66 68 70 72 74 76 

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 established 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 

I l I I I l l 

60 62 64 66 70 72 74 76 

Figure 7-3. Nationwide trends In lead content ot 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 jLtg/m3 in Chicago to a low quarter of 1.3 

/ng/m3 in Washington, D.C. The average mass median diameter for lead particles ranged from 0.69 

fim in St. Louis to 0.42 fim in Washington, D.C. 

Fifty-nine to 74 percent of the lead was associated 

with particles smaller than I fim in diameter. Quarterly and annual particle size distribution data are 

presented in Table 7-6. 

7.1.3 Vertical Gradients of Lead in the Atmosphere 

Very few studies have been conducted to determine the variation of lead concentrations with height 

above the ground. Of those that were found, all contained the premise, either explicitly or implicitly, 

that the concentrations being studied derived principally from automotive emissions. Of the studies 

found in the literature, none were adequately 

designed to establish the lead concentration versus 

height relationship. Such a study would require 

simultaneous measurement (preferably continuous) 

at given height intervals over a long period of time 

(a minimum of l year). Even then, the results would 

be valid only for a location having the same characteristics and experiencing the same atmospheric conditions. A single set of concentration values obtained over short and variable time intervals is not 

sufficient to draw conclusions regarding general exposure conditions. 

7-4 
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 12and 13,1972»« 

(ng/m3) 

City and 

quarter 

of year 

Average 

concentration. 

jj.g/m3 

Average 

mass 

median 

diameter. 

utr\ 

Chicago, III.: 

1 2.9 

2 3.5 

3 3.5 

4 2.9 

Total year 3.2 

Cincinnati, O.: 

1 1.0 

2 2.2 

3 1.9 

4 2.1 

Total year 1.8 

Denver, Colo.: 

1 2.0 

2 1.1 

3 1.4 

4 3.0 

Total year 1.8 

Philadelphia, Penn.: 

1 1.5 

2 1.2 

3 1.8 

4 1.9 

Total year 1.6 

St. Louis, Mo.: 

1 1.9 

2 1.6 

3 1.8 

4 1.8 

Total year 1.8 

Washington, D.C: 

1 1.3 

2 1.0 

3 1.3 

4 1.8 

Total year 1.3 

1.43 

0.51 

0.56 

0.54 

0.68 

0.25 

0.41 

0.54 

0.65 

0.48 

0.43 

0.58 

0.52 

0.56 

0.50 

0.36 

0.38 

0.70 

0.45 

0.47 

0.46 

0.63 

0.78 

0.95 

0.69 

0.36 

0.39 

0.41 

0.54 

0.42 

Percentage 

of particles 

5//.m 

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 concentrations at eight heights above street level in Brattleboro, 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 investigators 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 relationship of concentrations versus height cannot be 

drawn from these data. 

Height Sampling times 

above 8:36a.m. 10:20 a.m. 1:20p.m. 

street, ft 10:15 a.m. 12:00 noon 3:00 p.m. 

3:25 p.m. 4:35 p.m. 9/12 

4:25 p.m. 1:02 p.m. 9/13 

1" 

2 

3 

4 

5

C 

7 

8 

30 

8.94 

8.22 

7.15 

7.84 

4.40 

8.15 

3.85 

5.31 

7.56 

17.38 

21.11 

2.40 

3.01 

4.25 

a

 Average air lead value for 54.38 m3 air = 8.54 ^ g Pb/m3. 

D

 1-. 2-, 3-. and 4-ft heights: Average air lead values lor 13.53 m3 air = 8.01 M 9 

Pb/m3. 

c

 5-. 7-, 8-, 30-ft heights: Average air lead values for 40.85 m3 air = 3.96 n g Pb/m3. 

Edwards7 has reported measurements made in 

downtown Fort Collins, Colo. Measurements were 

made in a street canyon formed by two- and threestory 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 11.3 /i,g/m3 at street 

level to 4.0 /u,g/m3 at roof level. On the west side of 

the street, concentrations ranged from 0.9 /ug/m3 at 

street level to 1.3 /xg/m3 at roof level. Values for two 

additional sampling points above the rooftops on 

each side of the street were 0.4 ttg/m3 (east side) and 

0.9 /xg/m3 (west side). Lead concentrations 2 to 5 

blocks away ranged from 0.1 to 0.3 Mg/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 configuration, and different stability conditions, the distribution of concentration values would also be 

different. 

Barltrop and Strelow8 conducted an air sampling 

program at a proposed nursery site under an elevated 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 /xg/m3. The 12-month mean ranged from 1.51 

Mg/m3 to 1.35 /xg/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-Environmental9 measured lead concentrations at heights of 5 and 20 ft at sites near streets in 

7-5 
P.98 

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 residential 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 LEVEL* 

(Mg/m3) 

Location Range 

Kansas City 0.8-4.0 

Cincinnati 0.1-4.6 

East side of street 

20 ft 5 ft Did. 

1.7 2.0 0.3 

0.9 1.4 0.5 

Averages 

West side of street 

20 It 5 ft Diff. 

1.5 1.7 0.2 

0.6 0.8 0.2 

These data reflect the strong influence of the 

geometry of the boundary layer, wind, and atmospheric stability conditions on the vertical gradient of lead resulting from automobile emissions. 

The varability 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 atmospheric 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 stationary lead source. Among the most intensive of 

these studies was the Los Angeles Catalyst Study of 

1974-1975, undertaken by EPA to measure the impact of the catalytic converter on air quality near a 

major traffic lead source.10 , 

Table 7-9 summarizes the 24-hr ambient concentrations 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-freeway differences is shown in the righthand column. 

The favorable wind direction interval is approximately 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 

Site A. 

Mg/m3 

SiteC. 

jjg/mJ 

Difference. 

C-A 

Ratio. 

C/A 

% 

Favorable 

wind 

direction8 

January 

February 

March 

April 

May 

June 

July 

August 

September 

October 

November 

6.0 

4.1 

3.2 

2.8 

1.8 

1.4 

1.9 

2.8 

3.7 

4.2 

4.8 

6.2 

4.8 

5.2 

6.0 

7.4 

8.1 

8.0 

8.4 

8.5 

7.3 

6.6 

0.2 

0.5 

2.0 

3.3 

5.6 

6.8 

6.1 

5.7 

5.0 

3.3 

1.7 

1.03 

1.18 

1.63 

2.14 

4.06 

5.68 

4.27 

3.00 

2.30 

1.74 

1.37 

28.2 

35.2 

43.3 

47.6 

65.6 

71.2 

68.0 

61.6 

59.5 

49.4 

31.6 

8

 From A to C (S + SW + W winds). 

A very strong seasonal effect is observed in the 

data, with concentrations at Site C exceeding those 

at Site A by only 3 percent in January, increasing to 

a maximum difference of over 400 percent in June, 

and subsequently decreasing during the fall months 

(no data were collected during the month of December). As expected, there is a strong linear relationship between the occurrence of favorable wind 

direction and the observed cross-freeway difference 

in lead concentration. The correlation coefficient 

between the two variables is 0.96, indicating that 

almost all of the variation in the cross-freeway concentration of lead may be accounted for by the 

seasonal variation in the occurrence of favorable 

wind direction. 

In a study conducted in London, England,11 ambient air levels of organic lead were measured at urban sites. Concentrations of 0.04 to 0.11 Mg organic 

Pb/m3 were found on streets of varying widths and 

traffic flow. These values were 0.3 to 2.6 percent of 

total airborne lead. The level of organic lead inside 

a busy tunnel was 0.02 figlm3, or 0.1 percent of the 

total airborne lead. Not surprisingly, organic lead 

concentrations measured at a busy service station 

7-6 
ranged from 0.21 to 0.59 figlm3

, or 3.9 to 9.7 percent of total airborne lead at that site. At a less busy 

service station, the concentration of organic lead 

was 0.07 Mg/m3.

 o r

 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 Tables 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 people who live or work (e.g., traffic policemen, service 

station and garage attendants) in these areas are exposed 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 investigate 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 

Sampling site 

Washington, DC : 

Busy intersection 

Many sites 

Chicago: 

Near expressway 

Philadelphia: 

Near expressway 

Brooklyn: 

Near expressway 

New York City: 

Near expressway 

Detroit: 

Street dust 

PhiladelphiaGutter (low exposure) 

Gutter (low exposure) 

Gutter (high exposure) 

Gutter (high exposure) 

Miscellaneous U.S. Cities: 

Highways and tunnels 

Netherlands: 

Heavily traveled roads 

Concentration 

jig Pb/g 

12820 

(4000-8000)12 

6600 

(3000-8000)13 

(900-4900)1" 

200015 

(966-1213)16 

1507 

(270-2626)" 

3262 

(280-8201)1' 

(10000-20000)18 

500019 

TABLE 7-11. LEAD CONTENT IN OR ON ROADSIDE SOIL AND GRASS 

AS A FUNCTION OF DISTANCE FROM TRAFFIC AND GRASS DEPTH IN PROFILE* 

Site and distance 

from road, m 

Lead content, iig/g dry weight 

Grass 

0-5 cm 

soil death 

5-10 cm 

soil deDth 

10-15 cm 

soil denth 

West ot U.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 

47.5 

26.3 

522 

378 

164 

460 

260 

108 

416 

104 

69 

51.3 

30.0 

18.5 

21.3 

12.5 

7.5 

31.3 

26.0 

7.6 

540 

202 

140 

242 

140 

61 

150 

101 

55 

300 

105 

60 

112 

104 

55 

29 

14 

10 

98 

60 

38 

95 

66 

60 

11 

8.2 

6.1 

a

 Adapted from Lagerwerff and Specht (cited in Reference 20). 

7-7 
P.100 

TABLE 7-12. LEAD DUST IN RESIDENTIAL AREAS 

Sampling site 

Concentration, 

M9 Pn/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 

17501? 

(1000-2000)21 

(500-900)6 

50001" 

(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 highvolume samplers stationed throughout the Silver 

Valley. A highly significant relationship between 

distance from the smelter and ambient air lead concentration was found, and this relationship was used 

to estimate the ambient air lead level for any location 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 mechanism involved. One result of this pivotal study was 

that some specific emergency measures were taken in 

E 

"a 

l~~l AUG. 1974 

ES3 AUG. 1976 

1.5 T 1.8 

JLM 1 2 3 4 5 6 7 

BY AREA ISEE TEXT! 

Figure 7-4. Annual ambient air lead concentration near a 

smelter, by area, before the August 1974 and August 1975 surveys.24

 Area 1 Is within 1 mile of smelter; Area 2 Is 1 to 1-1/2 

miles from smelter; Area 3, 2-1/2 to 6 miles; Area 4, 6 to 15 

miles; and Area 5,15 to 20 miles. 

7-8 
P.1 

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 ofthe 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 ofa major industrial source of lead (e.g., a smelter) are exposed 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 ofthe daily dietary lead intake 

for adult males ranging from 100 to 500 /Ag/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.2733 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 ofthe 

effects of species diversity on the routes of lead accumulation, 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 

ofthe lead associated with oat tops was directly attributable to automobile (aerosol) emissions, but it 

did not distinguish between lead in the edible portion (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 between 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.2729 An FDA survey34 shows 

that grains contain approximately 20 percent as 

much lead as the leafy vegetables. It cannot be concluded, 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 ofthe 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 exceptions 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 
P.2 

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 these 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 intake oflead by children has been shown to be two or 

three times that of adults. This additional dietary intake 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 concentrations 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 comprise 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 major 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 examined, 37 percent contained 200 /xg Pb/liter or 

more; 12 percent contained 400 /xg Pb/liter or more. 

These levels are markedly above the potable water 

standard of 50 tig 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/liter),40 and 18 products averaged 2.7 ppm (approximately 2700 /xg/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 infants and young children. The FDA survey37

 found 

lead concentrations in whole milk ranging from 10 

to 70 tig/liter and averaging about 20 pig/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 /xg/kg (range 15 to 20) in formula and 

10 /xg/kg (range 7 to 15) in milk (1 /xg/kg is approximately 1 /xg/liter). Lead concentration in infant 

fruit juices ranged from 23 to 327 /xg/kg; in five 

varieties of strained fruits, it ranged from 13 to 131 

/xg/kg; and in seven varieties of strained vegetables, 

lead concentration was 14 to 73 /xg/kg. Tolan and 

Elton38 reported 30 /xg Pb/liter in fresh milk in 

Great Britain and 50 /xg Pb/liter in canned (evaporated) milk. Michell and Aldous39

 reported a comparable average for fresh whole milk purchased in 

New York State —40 /xg Pb/liter. But their results 

for evaporated milk averaged 202 /xg 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 predominantly 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 concentrations are attributed to lead-containing inks. 

No related illnesses were identified, nor was contamination of the food implied; but the eating of 

foods from such wrappers and the licking or chewing 

ofthe 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 apparent 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 example 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 in7-10 
P.3 

eluding fatalities, have involved other relatively 

acidic beverages such as fruit juices and soft drinks 

and have been documented by other workers.4445 

Recent reports on lead in European wines46-

47 

show concentrations typically averaging from 130 to 

190 /xg/liter (0.13 to 0.19 ppm) and ranging as high 

as 299 /xg/liter (0.299 ppm). Measurements of lead 

in domestic wines have not been undertaken; but if 

the European data are indicative, wines could contain 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 detectable amounts of lead in untreated public water supplies was shown by Durum48

 to be widespread, but 

only a few samples contained amounts above the 50 

/xg/liter standard. Durfor and Becker49 analyzed 

untreated and treated water for the largest U.S. 

cities, and almost all pairs of samples showed a substantial decrease in lead that was ascribable to treatment provided. A maximum lead concentration of 

62 /xg/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 /xg/liter in the treated water before entering the 

distribution system. Eight of the water supplies distributed water with a pH of less than 7, which could 

be corrosive to the distribution piping; most ofthese 

were in the Northwest. A chemical analysis of 592 

interstate carrier water supplies in 1975 showed only 

0.3 percent to exceed the 50 /xg/liter standard.50 

These samples were collected after treatment but 

before distribution, and they represent both suspended and dissolved lead. Interstate carrier water 

supplies serve planes, trains, buses, and vessels in interstate commerce, and they include almost all of 

the largest U.S. water supplies. 

The presence of lead in drinking water may result 

from contamination ofthe water source or from the 

use of lead materials in the water distribution 

system. Although lead is a relatively minor constituent 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 contamination 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 problem. The extensive use of lead compounds as 

gasoline additives has greatly increased the 

availability of lead for solution in ground and surface waters. For example, in a study in east-central 

Illinois,51 the urban portion of an 86-square-mile 

watershed, which constituted 14 percent ofthe 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 reported for 1 month (June 1972) show that drainage 

waters from this urban portion contained an average 

total lead concentration of 69.5 /xg/liter, including 

6.3 /xg/liter of soluble lead. The rural portion 

yielded an average of lead concentration of 7.4 

/xg/liter of drainage water, including 2.1 /xg/liter of 

soluble lead. 

The major source of lead contamination of drinking 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 urban 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 /xg/liter standard.52 The 

maximum concentration found was 640 /xg/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 population 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 environmental sources may be an important contribution in 

certain areas, depending on the chemical composition ofthe runoff water. Above pH 8.0, the solubility 

of lead is below 10 /xg/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 /xg/liter. 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 /xg/liter after filtering the sam7-11 
P.4 

pies. Samples of rainfall at Menlo Park, Calif., during 1971 showed a wide range of lead concentrations, from a few /xg/liter to more than 100 

/xg/liter.53 Hem and Durum53 hypothesize that higher lead concentrations should be anticipated in 

runoff water and impounded raw water supplies in 

the Northeast, certain urban areas ofthe South, and 

along the Pacific Coast because of low pH and 

alkalinity in waters. However, in much ofthe rest of 

the United States, lead fallout rates and the chemical 

composition of the runoft (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 conducted, 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 

/xg/liter) were found in 63 percent of the samples, 

but only three samples contained more than 50 

/xg/liter. A large proportion of the samples for the 

northeastern and southeastern states contained lead 

above the detection limit, and quite a few ofthe samples showed levels above 10 /xg/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 /xg/liter. The highest concentration was detected on the Ohio River at 

Evansville, Indiana. Twenty-seven of their samples 

exceeded 50 /xg/liter. Observed mean observations 

of >30 /xg/liter dissolved lead were found in the 

following river basins: Ohio, Lake Erie, Upper 

Mississippi, Missouri, Lower Mississippi, and Colorado. 

7.5 OCCUPATIONAL EXPOSURES 

The highest and most prolonged exposures to lead 

are found among workers in the lead smelting, refining, and manufacturing industries.56

 In the work 

areas, the major route of lead exposure is by inhalation 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 engineering or housekeeping practices and worker education. 

7.5.1 Exposures in Lead Mining, Smelting, and 

Refining 

The greatest potential for high-level exposure exists 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 temperatures, 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 concentration may be greater in the vicinity of ore-proportioning 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 primary smelters was obtained in a study of three typical installations in Utah.56

 Air lead concentrations 

near all major operations, as determined using personal monitors worn by the workers, were found to 

vary from about 100 to more than 4000 /xg/m3. Obviously, the hazard to these workers would be extremely 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 exposures in secondary smelters, which are found in or 

near most large cities, the nature oftheir 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 neighborhood or even backyard melting operations for extracting and reclaiming lead. These operations can 

contribute substantially to local airborne lead 

levels. 

7-12 
P.5 

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 subsequently reduced to 30 to 40 /xg/m3

 with the installation 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 ofthe lead 

from the ores. The lead sulfide (PbS) in galena is insoluble, 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 silicate-coated steel (determined to contain some 29 mg 

Pb/in2 of coating) produced breathing-zone concentrations oflead reaching 15,000 /xg/m3

, far in excess of 450 /xg/m3

, the current occupational shortterm 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, breathingzone concentrations of lead averaged 1200 /xg/m3 

and ranged as high as 2400 /xg/m3.

60 

7.5.3 Exposures in the Electric Storage Battery Industry 

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 /xg/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 frequent cleanup is necessary to prevent the accumulation of dust. In the pasting ofthe plates, whether by 

hand or machine, the danger again is from dust 

which accumulates as the paste dries. Also the forming 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 Reichenbach61 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 /xg/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 correlation 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 probably 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 ofthe use of lead 

stearate as a stabilizer in the manufacture of polyvinyl chloride was noted in the 1971 Annual Re7-13 
P.6 

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 ofthe 

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 averaging 58 /xg/m3

 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 Commission 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 /xg 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 /xg 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 nontoxic paints. 

Lead in paint constitutes a potential health problem 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 leadcontaining 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 definitive 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 approximately 2.54 times IO9

 kg of PVC plastic waste 

to be disposed of annually, of which about 0.59 

times IO9 kg would probably be incinerated.70 

Assuming that lead will be emitted from the uncontrolled 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 105 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 fugitive dust and the potential contamination of soil, 

surface waters, and groundwaters through leaching 

from landfill operations. 

Lead is present in other products that may constitute sources of lead exposure when used or disposed of. Lead may be found in color newsprint, 

craft and hobby materials, toothpaste tubes, cosmetic 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) exceeded the allowable limit for painted toys, which is 

0.06 percent. 

7.5.8 Historical Changes 

Perhaps the most impressive data on the magnitude 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 ofthe 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 Greenland, and the 10-fold increase through the last century 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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wrappers of specialty foods as a potential hazard for 

children. Clinical Pediatrics. /5(12):1064-I065. 1974. 

43. Block, J. L. The accident that saved five lives. Good 

Housekeeping, November 1969. 

44. Klein. M., R. Namer, E. Harpur. and R. Corbin. Earthenware containers as a source of fatal lead poisoning. New 

England J. Med. 283( 13):669-672. 1970. 

45. Harris. R. W. and W. R. Elsen. Ceramic glaze as a source 

of lead poisoning. J. Am. Med. Assoc. 202(6):208-210. 

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 Communities. 1973. p. 93-98. 

47. Boudene, C . F. Arsac, and J. Meininger. Study ofair and 

population lead levels in France. Arch. Hig. Rada. 

Tekisol. 26(Suppl.):179-189, 1975. 

48. Durum, W. H. Reconnaissance of Selected Minor Elements in Surface Waters of the U.S. U.S. Dept. of Interior. 

Geologic Survey, Washington, D.C. 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, N.C. Pub. No. EPA 430/9-75-005. 1975. 88 

P51. Rolfe, G. L. and A. Haney. An Ecosystem Analysis of Environmental Contamination by Lead. Inst, for Env. 

Studies, U. of Illinois, at Urbana-Champaign, III. Res. 

Rept. No. 1. 1975. p. 22-34. 

52. McCabe, L. J. et al. Survey of community water supply 

systems. J. Amer. Water Works Assn. 62(11):670, 1'970. 

53. Hem, J. D. and W. H. Durum. Solubility and occurrence 

of lead in surface water. J. Amer. Water Works Assn. 

65(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 ofthe Untied States (Oct. 1, 1962 -

Sept. 30, 1967). U.S. Dept. of Interior, Federal Water 

Pollution Control Administration, Cincinnati, Ohio. 

1967. 218 p. 

56. Environmental Health Criteria. Vol. 3., Lead. United Nations Environment Program/World Health Organization, 

Geneva. Switzerland. 1977. p. 59-65. 

57. Berg, B. A., and C. Zenz. Environmental and clinical control 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 . 

79:521-539, 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):181-186, 

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/(2):l70-179, 1970. 

64. H. M. Chief Insp. of Factories. H. M. Great Britain Dept. 

of Employment. Annual Report, 1971. London, Her Majesty's Stationery Office. 1972. p. 60, 95. 

65. Scarlato. G.. S. Smirne. and A. E. Poloni. L'encefalopatia 

satumina acuta dell adulto. Acta Neurol. 24:578-580. 

1969. 

66. Maljkovic, 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 exposure. 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. Ifeadi, 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 Contract No. 68-02-1375, Cincinnati, Ohio. October 1976. 

424 p. 

7-16 
P.9 

72. Hankin, L., G. H. Heichel, and R. A. Botsford. Lead on 

painted handles of kitchen utensils. Clin. Pediat. 

/5(7):635-636, 1976. 

73. Murozumi, M., T. J. Chow, and C. C. Patterson. Chemical 

concentrations of pollutant lead aerosols, terrestrial dusts, 

and sea salts in Greenland and Antarctic snow strata. 

Geochim. Cosmochim. Acta. (London). 55:1247-1294, 

1969. 

74. Jaworowski, Z. Stable lead in fossil ice and bones. Nature. 

2/7:152-153. January 13, 1968. 

75. Ruhling. A. and G. Tyler. An ecological approach to the 

lead problem. Bot. Notis. (Stockholme) /2/:32l-342, 

1968. 

7-17 
P.10 

8. EFFECTS OF LEAD ON ECOSYSTEMS 

It has been substantiated that lead is a natural 

constituent of the environment, but natural, background 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 oftheir inherent value to ecosystem stability 

and because ofthe ultimate impact that effects of the 

ecosystem would have on man. Figure 8-1 depicts 

the environmental flow of lead and the possible exposure routes for plants and animals in the 

ecosystem.1 

FOOD 

PROCESSING 

:•:•: PLANTS :•:•:• 

LC 

:

:

:

:

:

:

:

:

:

:

:

:

:

:

:

:

:

 _ " I SMELTERS :,,,,,,,:J—^IJ— 

•EARTH 

:

 (SOIL) 

»i:-4 

w&8$. -t-f 

MINING 

OPERATIONS 

J AUTOMOBILES I 

3zm 

:t£ 

WATER 

SUPPLIES 

hr 

>':*AN'IMALS": 

: ATMOSPHERE > 

I (LEAD AEROSOL:; 

: AN D :; 

: ORGANIC LEAD)> 

OTHER LEAD 

CONTAINING 

PRODUCTS 

AND WASTES 

F4LLOUT 

AND RAINOUT 

OCEANS 

Z3ZI 

I- LAKES AND RIVERS;. 

- » :;ESTUARIES; 

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 include 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 emitted 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 concern, 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 inhalation 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 southeastern Missouri.6

 Deaths from lead poisoning of 

lambs and sheep in Britain7 and of horses, sheep, 

and goats in continental Europe have been reported.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 leadcontaminated 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 
P.11 

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 

oflead 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 poisoning 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 estimated 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 oflead 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 stertorously, or to roar. When severe, this paralysis can 

produce suffocation and death. In addition, the 

faulty action of the epiglottis v which 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 weakness, stiffness of joints, and harsh, dry coats. Distortion ofthe 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 

zinc 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, blindness, swelling at the epiphyseal 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 intake16

 relative to that of cattle grazing the same 

pasture. 

Lead poisoning in all domestic animals produces 

various degrees of derangement of the central nervous 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 observed. The animals may become blind and may 

grind their teeth, move in a circle, push against objects, and lose their muscle coordination. Mature 

cattle display fewer overt symptoms, although the 

syndrome of maniacal excitement is not uncommon. 

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 extremities, 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 abortion 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, subcellular, 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. 
P.12 

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 exposed 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 first 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 breeding 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 oftheir 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 grinding 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 superficial 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, weakness, flaccid paralysis, emaciation, anemia, greenish 

diarrhea, impaction of the proventriculus, and distention ofthe 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 appears to be associated with the inhibition of 

8-aminolevulinic acid dehydrase (ALAD) by 

lead.23-

24

 In instances where insufficient lead is ingested to cause death, sterility may result.1 

In an attempt to prevent the deaths of waterfowl 

through the ingestion oflead 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 containing 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 concentrate lead through the food chain (Table 8-1). 

The authors were not able, however, to associate observed 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 Approximate accumulation tactors 

Metal 

Mercury 

Lead 

Cadmium 

Copper 

Zinc 

Seawater 

0.00003 

0.00003 

0.00011 

0.003 

0.01 

Fish 

0.037 

< 0.002 

0.309 

1.74 

53 

Puffin 

0.79 

0.36 

1.67 

4.49 

95 

Fish/ 

seawater 

1,230 

<67 

2,800 

580 

5,300 

Puffin/ 

fish 

21 

>180 

5.4 

2.6 

1.8 

Puffin/ 

seawater 

26,300 

12,000 

15,000 

1,500 

9,500 

8-3 
P.13 

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 exposure, 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, tl.." 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 (ISSUES FROM AREAS OF HIGH-LEAD AND LOW-LEAD ENVIRONMENTS 

(ppm, dry weight) 

Species and lead level8 

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(10) 

Feathers 

26.5 

66.8 

27.0 

158.3 

6.4 

225.1 

36.0 

81.4 

25.3 

.79.7 

Gut 

2.1" 

2.6d 

2.3 

26.2 

1.3 

6.0 

1.4 

10.2 

3.2 

24.5 

Liver 

5.8 

1.2 

0.6 

12.0 

4.0 

16.1 

2.5 

12.1 

2.4 

10.5 

Lung 

0.4 

4.1 

0.9 

6.9 

2.8" 

5.2*1 

2.3" 

2.7« 

2.2 

10.3 

Kidney 

2.1d 

4.1« 

3.5 

33.9 

3.6 

98.5 

3.5 

13.5 

7.3 

25.0 

Boneb 

6.9 

9.1 

16.9 

130.4 

12.8 

213.0 

21.5 

62.8 

41.3 

133.7 

Musclec 

0.8d 

0.6« 

0.9 

2.1 

0.8*1 

2.4" 

0.8 

1.4 

1.0d 

1.2d 

a

 High-lead and low-lead environments are urban and rural areas respectively: high-lead area for red-winged blackbirds is 10 m from an interstate highway. Sample size in 

parentheses. 

b

 Femur. 

c

 Pectoral. 

d

 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. Braham31 

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 ofthe 

study. The exposure of small mammals and selected 

invertebrates near roadways has also been 

studied.32*

38

 In general, gradients in body lead concentrations declined with increasing distance from 

the road. The body lead gradients usually were similar 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 ofthese 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 roadsides.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 insects. The range of food for Clethrionomys encompasses 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 ac8-4 
P.14 

count for the differences in lead concentrations in 

the three species. 

FIELD MOLES 

(Microtus) 

BANK VOLES 

(Clethrionomys) 

FIELD MICE 

(Apodemus) 

D-MEA N OF SPECIES 

306.7 ppm dry wt. 

MEA N Pb ON VEGETATION 

42.5 ppm dry wt. 33.4 ppm dry wt. 

TYPE OF SITE 

Figure 8-2. Concentration of lead In three species of small 

mammals trapped beside major and minor roads and at arable and woodland sites.33 

In a study in central Illinois, samples of small 

mammals were obtained from a range of environments including those within 10 m ofa high-trafficvolume 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 vehicles/24 hr), and those in urban areas (approximately 

100,000 inhabitants).38 

All species except the white-footed mouse 

(Peromyscus leucopus), showed higher concentrations of lead in habitats adjacent to high-trafficvolume 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 considerable 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 requirements and lead concentrations in small mammals captured near high-traffic roadways. Species 

requiring dense vegetation—the prairie vole 

(Microtus ochrogaster), the short-tailed shrew 

(Blarina brevicauda), the least shrew (Cryptotis parva), 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, reflecting the fact that lead concentrations in seed tissue 

are usually extremely low (< 1 ppm). 

It is highly doubtful that the very low concentrations 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 adjacent 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 hightraffic roadways (Figure 8-3). Chewing insects probably 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 (feeding-level) system.39 

Definitive studies correlating toxicity with environmental 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 appears 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 
P.15 

TABLE 8-3. MEAN LEAD CONCENTRATIONS IN ORGANS AND TISSUES OF SMALL MAMMALS FROM 

INDICATED AREAS OF ENVIRONMENTAL LEAD EXPOSURE3' 

(ppm, dry weight) 

Species and 

exposure area 

Blarina brevicauda: 

High 

Medium 

Low 

Microtus ochrogaster: 

High 

Medium 

Low 

Peromyscus maniculatus: 

High 

Medium 

Low 

Control0 

Mus musculus: 

High 

Medium 

Low 

Control0 

Reithrodontomys megalotis: 

High 

Medium 

Low 

Total 

body 

18.4 

6.7 

5.7 

5.1 

5.9 

1.9 

6.3 

4.3 

3.3 

3.1 

6.8 

6.0 

6.7 

2.0 

12.3 

3.0 

2.7± 

Gut 

24.0 

7.0 

3.1 

11.0 

18.4 

2.8 

19.2 

6.0 

4.5 

4.3 

18.6 

8.8 

4.8 

2.7 

17.8 

6.2 

3.5 

Spleen 

4.5 

3.6 

2.3 

5.3 

2.2 

2.4 

19.4 

3.0 

6.5 

3.7 

12.1 

3.1 

5.1 

2.1 

145 

9.2 

5.6 

Liver 

4.6 

2.0 

1.0 

1.6 

1.2 

1.0 

3.5 

1.7 

1.8 

1.1 

2.9 

1.6 

1.6 

1.9 

4.7 

1.1 

2.3 

Lung 

16.9 

5.6 

7.8 

2.8 

1.8 

1.3 

6.4 

2.4 

6.1 

1.5 

2.8 

3.4 

1.7 

3.4 

20.9 

4.2 

4.7 

Kidney 

12.4 

5.8 

3.9 

8.1 

7.6 

2.8 

7.9 

9.0 

3.0 

1.8 

8.1 

6.6 

3.1 

3.4 

— 

2.1 

4.8 

Bone8 

67.1 

19.9 

12.2 

16.6 

23.2 

4.6 

24.6 

8.0 

6.4 

5.7 

19.2 

21.0 

23.5 

9.3 

109.5 

— 

18.4 

Muscle6 

9.7 

5.7 

5.4 

8.2 

3.0 

2.0 

6.8 

7.4 

1.8 

2.1 

5.9 

3.9 

3.4 

3.8 

27.5 

4.4 

— 

a

 Femur. 

"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)3" 

(ppm) 

Feeding type 

Sucking 

Chewing 

Predatory 

Mean 

0 to 7 m from 

pavement 

15.7 

27.3 

31.0 

24.7 

13 to 20 m from 

pavement 

9.8 

10.4 

20.0 

13.4 

area. Analysis of this mucus has revealed the presence 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. 

Symptoms of chronic lead poisoning in fish include 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 Vermilion River showed that lead appears to be taken 

up by aquatic organisms by means of external contact 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 concentrations 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 concentrations of lead varying from 0 to 15 mg/liter of 

water (ppm), and suspended solids in the water contained 15 to 200 ppm lead. The highest levels occurred in the urban stream. The upper 10 cm of sediments 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 
P.16 

I STD. ERROR 

D LOW Pb EMISSIONS AREA 

CD HIGH Pb EMISSIONS AREA 

ii 

CHEWING PREDATORY 

INSECT FEEDING TYPES 

Figure 8-3. Mean lead content In grouped Insect samples 

taken from low- and hlgh-lead-emlsslon areas for 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 invertebrates 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 accumulation by freshwater fish. Ionic lead (as Pb

 + + ) 

was concentrated threefold when the pH ofthe lake 

water was lowered. Lead toxicity in fish was not reported. 

Toxicity varies with pH, temperature, hardness, 

and other water properties.40 The concentrations of 

lead injurious to fich and other aquatic and marine 

life may be found in Water Quality Criteria, 1972.4(l 

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 macrochlrus) 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 

""""") URBAN COMPARTMENT 

*"*""* COMBINED COMPARTMENT 

I I MARGINAL COMPARTMENT 

" • RURAL MAIN CHANNEL 

I"""*" RURAL TRIBUTARIES 

SEDIMENTS CLADOPHORACEAE 

TUBIFICIDAE CHIRONOMIDAE 

SEDIMENTS ANO 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 occur 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 /xg 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 fig 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 fontinalis) indicated that all second generation trout exposed to 235 and 474 fig Pb/liter developed severe 

spinal deformities (scoliosis), and 34 percent of 

those exposed to 119 fig Pb/liter developed 

scoliosis. Of the newly hatched third generation 

alevins exposed to 119 fig 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 
P.17 

TABLE 8-5. LEAD CONCENTRATIONS OF PREDOMINANT 

ORGANISMS FROM THE RURAL, URBAN, AND COMBINED 

COMPARTMENTS OF THE DRAINAGE BASIN OF THE 

SALINE BRANCH OF THE VERMILION RIVER, ILL." 

(ppm, dry weight) 

Arithmetic Number of Standard 

Compartment and organism mean samples deviation 

TABLE 8-6. SUMMARY OF GOLDFISH TOXICITY DATA") 

Rural: 

Plants: 

Cladophora 

Potarrrgeton 

. InvertebrtiTf 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 

(Redfin shiner) 

Pimephales notatus 

(Bluntnose minnow) 

Semotilus atromaculatus 

(Creek chub) 

Urban: 

Plants: 

Claoophoi . 

Invertebrates. 

Tub' cidae 

Chironomidae 

Decapoda 

Combined: 

Plants: 

Elodea 

Cladophora 

Invertebrates: 

Tubificidae 

Chironomidae 

Physa 

Psv,chodidae 

20.1 

30.0 

12.6 

13.2 

16.0 

5.5 

7.6 

10.4 

6.6 

20.1 

4.7 

2.4 

4.1 

1.8 

1.9 

2.7 

1.4 

347 

11 

15 

12 

7 

13 

11 

5 

15 

6 

12 

23 

19 

9 

29 

29 

83 

35 

5.1 

5.4 

14.8 

7.6 

11.8 

3.1 

3.4 

9.7 

2.4 

18.2 

5.2 

1.6 

2.4 

0.9 

0.6 

2.7 

0.6 

139 

367 

153 

11 

89.9 

34.9 

48.6 

42.7 

41.7 

32.3 

29 

5 

4 

22 

7 

71 

12 

10 

4 

373 

106 

93.3 

7.5 

33.9 

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 concentrations of lead nitrate (Table 8-6). The lowest 

concentration that gave significant impairment was 

0.07 ppm. 

Shellfish have been reported to concentrate lead.1 

Ion 

Arsenic 

Lead 

Lead (without 

calcium carbonate) 

Mercury 

Selenium 

LC50. ppm a b 

32.0 (41.6 to 24.6) 

110.0(121.0 to 100.0) 

6.6 (9.2 to 4.7) 

0.82 (0.90 to 0.75) 

12.0 (17.0 to 7.9) 

LCi.ppmh 

1.5 

60.0 

1.5 

0.36 

1.0 

Slope 

1.4 

1.2 

1.6 

1.2 

2.5 

a

 Based on a 7-day survival time. 

^Lowest concentrations of ions that significantly impaired conditioned avoidance 

responses and their fractions of the 50- and 1-percent lethal concentrations. 

Two species of marine gastropods were shown to 

concentrate lead in their shells.51 However, Valiela 

et al.5'

2

 reported that three species of estuarine 

bivalves showed no increase in lead when sludge fertilizer containing lead was added to experimental 

plots in a salt marsh. Furthermore, the lead apparently was trapped by the marsh surface sediments, since no increases were recorded downstream 

in the detritus on creek bottoms or in filter-feeding 

bivalves. Lead uptake by the cordgrass Spartina 

alterniflora reduces by a small amount the quantity 

of lead in the sediments.53 

Aquatic lead concentrations of 0.5 mg/liter have 

been shown to be toxic to flagellates and infusoria, 

the microscopic animals that frequently develop in 

decaying organic matter. Bacterial decomposition of 

organic matter is inhibited by lead concentrations of 

0.1 to 0.5 mg/liter.54 

8.2 EFFECTS ON PLANTS 

8.2.1 Routes of Plant Exposures 

Plants may be exposed to lead through the leaves, 

stems, bark, or roots. The extent of exposure depends on the amount of lead in the immediate environment and the form and availability of that lead. 

8.2.1.1 LEAVES, STEMS, AND BARK 

Particulate substances in the air, including lead, 

are deposited on plant surfaces by fallout, impaction, and precipitation.55

 Precipitation may, in addition to depositing material, wash off or leach out 

material from the plant surface or tissue. Wind and 

sloughing of the cuticle wax may also remove 

deposited material. Thus, meteorological factors are 

important in determining the fate of compounds that 

come into contact with plant surfaces. The 

morphology ofthe plant surface, however, plays the 

major role in determining the type and quantity of 

mateiial that will be retained by that plant surface.5657

 Epidermal cellsof the aerial parts of plants 

are usually coated with a waxy substance, cutin, and 

often form unicellular or multicellular hairs, spines, 

or glands. In addition, secretions from glandular 
hairs may make leaf surfaces sticky; thus, particulate 

material can accumulate on the plant surface, particularly the leaves. However, particulate matter must 

enter the internal plant tissues to affect the plant.56 

Franke58 suggests that the cutin is penetrable via intermolecular 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, adsorbability, and radius. 

Vascular plants have small surface openings, 

called stomata and lenticels, that function in gas exchange. 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 compounds on the leaves are probably of little consequence to a plant. The most important factor in 

determining foliar penetration is the solubility ofthe 

individual metal.5658 The insolubility oflead is undoubtedly 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 exposure. Increased penetration of some cuticles occurred 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 

(Pisum 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 capable 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 entered 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 increase 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 increase or decrease in lead in the tree rings.65 

10-year AVERAGE, 

1963 - 1973 

Figure 8-5. Tree ring analysis of lead concentrations in urban 

and rural trees.63 

8.2.1.2 ROOTS 

The root system is the major pathway of plant exposure to lead, as lead in the soil may be absorbed by 

the roots and moved into the plant.6066"

77

 But the 

total lead content ofthe soil is only one of several in8-9 
P.19 

teracting factors determining plant uptake. These 

factors are not well understood, but uptake is known 

to be influenced by plant species and by the available lead pool in soils.66

-

7174

 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*8

' 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 percentage of soluble lead in soil decreases with time as 

sorption occurs. Soil phosphate60-

75

-

77

-

78

 and liming,60

-

75

-

83

-

84

 as well as cadmium85 in soil, reduce the 

uptake of lead by plant roots. Olson and Skogerboe86

 have identified the primary lead species in 

their soil tests as lead sulfate (Chapter 6). At present, 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 deficiency 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-

72

-

77

 Plant age 

and season of the year also affect internal distribution.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 themselves 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. Little 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 

ofthe lead that enters the root is concentrated in dictyosome 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 processes as photosynthesis,60

-

91-93

 mitosis,'-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 

photosystem 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 indistinguishable 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 

nicotinamid e adenine diphosphonucleotid e 

monohydrogen (NADH). The lead levels used in 

this study approximated the levels found near 

heavily traveled highways. The form of lead used, 

PbC 12, and the isolated mitochondria were not typical of field conditions, but lead in plants does associate with mitochondri a and chloroplast 

membranes.60-

66

-

75 

The presence of lead in plants has also been shown 

to have indirect effects on plant growth. For example, 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 ofthe studies reporting lead toxicity 

have been conducted with plants grown in artificial 

nutrient culture. As a result of the studies, the concept has emerged that the effects of lead, whether 

stimulatory or inhibitory, depend on a variety of environmental factors, including associated anions and 

cations within the plant and in the growth media, 

and the physical and chemical characteristics ofthe 

soil itself. Because lead interacts with so many environmental 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 concentrations 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 important effects may be those resulting from ingestion of 

topical and internal plant lead by grazing animals 

(the next trophic level). From the standpoint of economic consequences, evidence developed on the 

effects of lead in agroecosystems indicates that topical 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 mosses 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.99100 Accumulation of heavy metal ions 

in mosses is generally from precipitation, which is a 

very dilute solution of metals and water. The accumulation occurs because ofthe chemical complexes formed between these heavy metal ions in precipitation and negatively charged organic growth.101 

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 extensive as that in mosses.I01 

8.2.3.2 ALGAE 

Trollope and Evans,102 in a study of algal blooms 

in the Lower Swansea Valley, Wales, noted the sensitivity 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: Coccomyxa, Mougeotia, Tribonema, and Zygnema. Less 

tolerant were Microspora, Oscillatoria and Ulothrix, 

and the least tolerant were Cladophora, Oedogonium, 

and Spirogyra. All ofthese algae were subject to contamination 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 conducted to determine whether the algae found in the 

least polluted waters would grow in more polluted 

ponds. 

Observations in the New Lead Belt of southeastern Missouri103

 have shown that relatively high 

concentrations of lead in stream bottom sediments 

do not have much effect on algal growth in these relatively hard natural waters. Under these conditions, 

the dissolved lead salts are in very low concentrations and well below the limits of tolerance of most 

8-11 
P.21 

TABLE 8-7. CONCENTRATIONS OF SELECTED HEAVY METALS IN FRESH WATER AND IN FRESHWATER ALGAL BLOOMS"" 

Concentrations in fresh waters. \i g 'ml Concentrations in freshwater algal blooms, M 9'mg 

Area of water Fe Ni Pb Algal bloom Cu Fe Ni Pb Zn 

Water adjacent to 

zinc smelting waste: 

1 0-03 0-24 0-15 0-31 34-1 

2 

3 

4 

Mean 

0-02 0-11 0-1 1-24 19-61 

0-01 0-25 0-12 0-1 11-44 

0-02 0-28 0-15 0-1 1-96 

0-02 0-22 0-13 0-44 16-78 

Mougeotia 

Tribonemaa 

Tribonema b 

Tribonemac 

Tribonema d 

Coccomyxa 

Zygnema 

Mean 

Water near zinc 

smelting 

5 

6 

7 

Mean 

waste: 

Water distant from 

zincsme 

8 

9 

10 

11 

12 

Mean 

Iting waste: 

0-02 

0-05 

0-06 

0-04 

0-03 

0-02 

0-01 

0-02 

0-02 

0-02 

0-27 

0-56 

0-56 

0-46 

0-39 

0-1 

0-39 

0-39 

0-11 

0-28 

0-12 

2-2 

2-94 

1-75 

0-07 

0-06 

0-12 

0-12 

0-12 

0-1 

0-1 

0-31 

2-91 

1-11 

0-1 

0-1 

0-1 

0-1 

0-1 

0-1 

1-96 

4-9 

4-9 

3-92 

0-21 

0-08 

0-08 

0-16 

0-05 

0-12 

Oscillatoria 

Ulothrix 

Microspora 

Mean 

Cladophora a 

Spirogyra a 

Spirogyrab 

Oedogonium 

Cladophora b 

Spirogyra c 

Spirogyra d 

Mean 

0-38 

0-4 

0-7 

0-67 

1-33 

0-65 

0-46 

17-61 

9-97 

33-92 

23-37 

30-6 

49-51 

39-85 

0-24 

0-16 

0-26 

0-29 

0-24 

0-15 

0-7 

6-19 

5-45 

4-94 

3-68 

14-19 

3-23 

2-6 

44-94 

19-93 

17-61 

21-11 

17-44 

19-05 

45-89 

0-66 29-26 0-29 5-75 26-57 

0-34 

0-48 

1-02 

0-61 

0-06 

0-22 

0-29 

0-11 

0-05 

0-23 

0-05 

0-14 

2-8 

7-78 

42-31 

17-63 

3-94 

3-03 

7-66 

0-7 

2-91 

0-46 

8-93 

3-95 

1-07 

0-3 

0-11 

0-49 

0-03 

0-13 

0-12 

0-07 

0-1 

0-09 

0-03 

0-08 

0-58 

2-38 

2-16 

1-70 

0-23 

0-4 

0-11 

0-06 

0-09 

0-13 

0-04 

0-15 

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 exceeded 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.104105 Micrococcus luteus and Azotobacter sp., when grown in leadcontaining media under experimental conditions, 

were able to take up substantial quantities of lead 

with no apparent effects on cell viability. Most ofthe 

lead became associated with the cell membrane. Several studies106107

 indicate that bacteria in lake sediments under anaerobic conditions react differently. 

Methylation of mercury and arsenic by microorganisms is a well-known phenomenon,108109

 but the 

methylation of lead is not. The first evidence for the 

methylation of lead was demonstrated experimentally by Wong et al.110

 Microorganisms in lake sediments 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 acetate (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 tha t Pseudomonas, Alcaligenes, 

Acinetobacter, Flavobacterium, and Aeromonas sp. 

growing in a chemically defined medium could 

transform lead nitrate, lead chloride, and trimethyl 

lead acetate (Me3PbAc) into volatile tetramethyl 

lead (Me4Pb). None ofthe bacteria were able to convert 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.' 0 4 "

0

 However, there 

is wide variation in effects. For example, lead has 

been shown to stimulate growth ofa bacterium iden8-12 
tified as Micrococcusflava Strevisan,"' producing an 

insoluble lead metabolite; but lead has also been 

shown to be widely inhibitory to aerobic activated 

sludge bacteria,"2 aerobic river water bacteria,"3 

and marine sulfate-reducing bacteria."4 These reports 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 sediments 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 during aerobic incubation of soil alone and after treatment with straw were studied.115

 Carbon dioxide release during incubation from soils without added 

straw was decreased by all metallic elements. Carbon djoxide release from soil plus straw was 

decreased by lead. The toxic effects ofthe high concentration 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 inhibitory than copper and zinc.115 

Cole'16 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, amylaseproducing bacteria, whereas recovery of synthesis 

(usually in 24 to 48 hr) was associated with an increase in the number of amylase-producing bacteria, 

presumably lead-resistant forms. The results indicated that lead is a potent but somewhat selective inhibitor of enzyme synthesis in soil and that highly insoluble lead compounds such as PbS may be potent 

modifiers of soil biological activity. 

8.3 EFFECTS ON RELATIONSHIPS BETWEEN ARTHROPODS AN D LITTER 

DECOMPOSITION 

A study"7 of the impact of a lead smelting complex in southeastern Missouri focused on forestfloor 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 contributed 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 characterize the arthropod food base. Arthropods were 

removed from litter by Von Tullgren funnel extraction. The arthropods were taxonomically classified 

according to their feeding habits or levels: 

detritivore, fungivore, littergrazer, omnivore, and 

predator. Level refers to the sequential location ofa 

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 cycling were reflected in the population dynamics of 

litter arthropods and macronutrient pools. Reduced 

arthropod density, biomass, and richness (an estimate 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 significantly 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 fragmented 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, heavymetal 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 processes are seriously disturbed near these lead 

smeltering complexes. 

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1975. 

111. Devigne, J. P. Precipitation of lead sulfide by a soil 

micrococcus. C. R. Hebd. Seances Acad. Sci. Ser. D. 

267(10):935-937, 1968. 

112. Hass, W. R. and S. Miller. Effects of Various Metals on 

Aerobic Organisms. IIT Research Institute, Chicago, Illinois. Rep. No. IITR1-C82I3-2. 1971. 

113. Deason, W. D. Effects of Heavy Metal Ions on Bacteria 

Isolated from a Mine Polluted River. Ph.D. Dissertation. 

Colorado State Univ., Ft. Collins. 1970. 

114. Hata, T. In Norinsho Sulsan Koshusko Kenkyo Hokoku. 

(In Japanese.) 9:363, 1960. 

115. Bhuiya, M. R. H. and A. H. Cornfield. Effects of addition 

of 1000 ppm CU, NI, Pb, and Zn on carbon dioxide 

release during incubation of soil alone and after treatment 

with straw. Environ. Poll. 5:173-177, 1972. 

116. Cole, M. A. Lead inhibition of enzyme synthesis in soil. 

Appl. Environ. Microbiol. 55(2):262-268, 1977. 

117. Watson, A. P., R. I. Van Hook, D. R. Jackson, and D. E. 

Reichle. Impact of a Lead Mining-Smelting Complex on 

the Forest-Floor Litter Arthropod Fauna in the New 

Lead-Belt Region of Southeast Missouri. Environmental 

Sciences Division, Oak Ridge National Laboratory, Oak 

Ridge, Tenn. ESD Pub. No. 881, ORNL/NSF/EATC-30. 

July 1976. 

8-16 
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 interlaboratory 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 document. 

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 precautions 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 biological indicators of exposure have been reviewed in the 

clinical literature.2 

In blood studies it is often desirable to use capillary blood by finger prick instead of venous 

puncture, especially when young children are involved. A number of studies have shown that capillary 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 contamination of capillary tubes and syringe is avoided. 

A number of workers have used filter paper discs 

for blood sample collection as an alternative to handling discrete blood volumes. The paper for this 

purpose must be selected for uniformity of manufacture, 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 correlate well with blood obtained by venous puncture. 

Joselow and Bogden6 have employed a micromethod 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 procedure of Hessel.7 

Cook et al.,8 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.' 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. 

Furthe r precaution s 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 
P.27 

Hard- and soft-tissue gathering from laboratory 

animals or human sources entail surface debridement of ambient lead encountered in the process of 

sampling. Hair cleaning before analysis may be carried out via the method of Hammer et al.;10

 bone 

and teeth may be given a quick rinse in EDTA solution. 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 sample 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 measuring lead in blood and other biological media involved 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 ofthe 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, mixedcolor procedure having bismuth as the chief interferent. Blood (and urine) samples are wet-ashed 

using concentrated nitric acid certified as to lowlead content. After digest treatment with hydroxylamine and sodium citrate, the pH is adjusted to 9 

to 10, and cyanide ion is added. Formation and extraction of lead dithizonate is carried out using a 

chloroform solution of dithizone. Lead is then re-extracted into dilute nitric acid (1:99 water), and the 

aqueous layer is treated with ammonia-cyanide solution and re-extracted with dithizone-containing 

chloroform. The organic extracts are read in a 

spectrophotometer at 510 nm. Although bismuth interferes, this element is encountered infrequently in 

biological media. 

The APHA procedure" varies from that described 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). 

Ofthese two analytical approaches, the more technically 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 Feldman12 

and by L'Vov,'3however. 

Macro-scale AA analysis involves direct aspiration of suitably treated lead-containing samples into 

a flame for lead-atom generation and excitation. 

Micro-AA, which is being used more widely as accessories and instrument refinements become commercially available, is of two types: flame and flameless, with the latter employing thermoelectric 

systems in lieu of a flame. 

Of the flame microtechniques for AA analysis of 

blood samples, the most widely used is Delves 

cup procedure14 in which small volumes of blood, 

10 to 100 fi\, are placed in lead-free nickel crucibles. 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 maximally occupied by the lead atom population originally present in the sample. Destruction of the 

organic matrix in blood may be either partial, using 

hydrogen peroxide, or total, with pre-ignition ofthe 

organic matter caused by placing the cups near the 

flame.15 

Increasing use is being made of flameless A A, particularly the heated graphite furnace accessory, 

whereby volumes of blood are reduced to —- 1 /nl, 

and also whereby in-situ destruction of organic matter 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 predetermined 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 
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 permit multiple-element analysis, a feature that will be 

of increasing importance as more is unveiled about 

the complex interactions oflead with other metals in 

man and other organisms. 

9.3 URINE LEAD 

Precautions to be taken for urine sample collection were noted earlier. Because ofthe considerable 

amount of ionic matter in urine, it is usually necessary 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 accommodate 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 ofthe nature of this medium, it is usually 

necessary either to ash or to solubilize tissue samples. 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 ofthe element in refractory 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 elevated temperature in a sealed inert vessel. 

A newer method of tissue handling, solubilization, 

entails the treatment of samples with quaternary ammonium compounds and analysis of aliquots, chiefly 

by AA spectrometry.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 hairlead 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 ofthe former are dyes, shampoos, 

sweat, and dust. Pre-analysis hair washing with 

detergent and EDTA removes most ofthe 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 internal 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 encountered 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 obtained from experimental animal studies. Bone samples must first be debrided of muscle and connective 

tissue and chemically rid of surface lead contamination 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 ofthe 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 ofthe 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 content and to which known amounts of lead from a 

stock solution are then added. Matrix standards prepared in this fashion are assumed to reflect the influence of mineral content on all of the samples. 

9-3 
P.29 

9.7 COMPARATIVE STUDIES OF METHODS 

FOR MEASUREMENT OF LEAD IN BIOLOGICAL MEDIA 

In an interlaboratory study of the USPHS colorimetric method for lead in blood and urine, 

Keenan et al.18 reported the results from 10 participating laboratories. For blood, a mean lead value of 

26 ± 0.82 /ig/dl 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 

/xg/liter. 

Microscale A A techniques for whole-blood lead 

have been found to show good correspondence with 

results obtained using conventional flame procedures.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 somewhat disappointing results.23*

25

 In a recent study involving 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 samples.26

 The criterion used by CDC for assessing unsatisfactory performance is: greater than 15 percent 

relative deviation at levels of 40 figld\ or above and 

greater than 6 Mg/dl at lower levels. 

In a recent CDC report (Survey 1977I)27 covering 

130 laboratories for testing and 26 reference 

laboratories using three bovine blood samples (cows 

fed lead acetate), 72 percent of the tested laboratories were within the acceptable range for a sample 

having a mean of 16.6/u.g/dl. The acceptable percentage was lower, interestingly, at higher sample 

means of 48.2 and 54.6 /ug/dl (64 and 67 percent, 

respectively). When results were tabulated as a function of method, the Delves cup A A spectrometric 

and ASV methods furnished the smallest coefficients 

of variation. 

A number of other proficiency programs are presently operating in the United States, and the results 

of these have been included, along with the European program, in a recently published monograph 

by Pierce et al.2 These same authors describe the 

state ofthe art critically and offer some recommendations 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 agreements 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 preparation 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 compared well with those of other laboratories using 

other instrumentation with the disc technique. 

9.8 MEASUREMENT OF URINAR Y 

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 collection. 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 approach, ALA-U is condensed with a /3-dicarbonyl 

compound such as acetylacetone or ethyl acetoacetate to yield a substituted pyrrole derivative; this intermediate 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 interference 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 ionexchange 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 
P.30 

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 heating to effect complete condensation is followed by 

treatment of sample aliquots with modified Ehrlich 

reagent (p-dimethylaminobenzaldehyde in perchloric/acetic acid). The resulting chromophoric salt 

is allowed to achieve maximum intensity (ca. 15 

min) after which the sample is read in a spectrophotometer at 553 nm. The detection limit is 3 

^moles/liter urine, and chromophore stability is 

limited to about 15 min. 

A number of modifications to the above basic approach 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 reports.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 correlation of 0.99 was observed with the reference 

technique using samples from 39 lead workers. Doss 

and Schmidt35 report that use of commercially available dual ion-exchange columns offers results that 

compare favorably with the Mauzerall and Granick 

method.31 

The assay has been automated with good correspondence of results to the manual method in the 

laboratories of Grisler et al.36 and Lauwerys et al.37 

In another variation ofthe 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 determined by gas-liquid chromatography, a highly 

specific technique. 

9 9 MEASUREMEN T 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 collection and enzyme assay—no more than 24 hr if samples 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 porphobilinogen being condensed with p-dimethylaminobenzaldehyde to yield a chromophore that is 

measured at 553 nm. Mercury (II) is employed to 

minimize the interference effect of sulfhydryl entities present in the medium. 

The micromethod of Granick and co-workers40 

requires only 5 fi 1 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 ofthe 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 = AOD553(sample-tissue control) 

138,000 nMol 

HCI 

= AOD5 „(t 6 0 '-t 0 ')x 

PBG/ml RBC/hr 

00 

HCL 

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 carried 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 mercuric 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 ALAD 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 unactivated enzyme may be normalized by determination 

ofthe rates of both activities. Hence a person having 

9-5 
P.31 

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 activity ratio will depend less on genetic factors than 

on lead inhibition. Consequently, correlation is 

markedly improved. This study also shows that inhibition by lead is of the noncompetitive type. 

9.10 MEASUREMENT OF FREE ERYTHROCYTE PROTOPORPHYRIN (FEP) 

Another reaction that lead inhibits in the human 

heme biosynthetic pathway is heme formation. As a 

result of blocking this reaction, porphyrins, particularly protoporphyrin IX (actually zinc-protoporphyrin), 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 fluorescence. Spectral methods used, however, must take 

into account the fact that copro- and uroporphyrin 

provide considerable interference in FEP measurement. Although both absorption spectrophotometric 

and fluorometric methods may be employed for FEP 

assessment,4446 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. Addition of ethyl acetate/glacial acetic acid (2:1) is then 

rapidly followed by treatment with 0.5N HCI and 

vigorous shaking. The acidic phase (bottom layer) 

contains the bulk ofthe porphyrins. The cuvettes are 

scanned over the range 560 to 680 nm, using excitation at 400 nm. The ratio ofthe 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 indicates copro- and/or uroporphyrins. In the latter 

case, an extraction with 0.05N HCI on analysis ofa 

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 

HCI 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 fi\ of whole blood is worked up in a 

detergent-phosphate buffer solution (dimethyldodecylamine 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, 2Q-fi\ blood volumes are treated with 

ethyl acetate/acetic acid solution (3:1) and agitated 

for 30 sec. After centrifugation, the layers are extracted with 3N HCI, and the acid layer is diluted 

with more 3N HCI. The acid extracts are analyzed 

spectrofluorometrically with coproporphyrin employed as the quantitating standard. 

A portable hematofluorometer that utilizes frontface optics, internal standards, and built-in computational capabilities permits the assessment of 

erythrocyte zinc protoporphyrin (ZPP). As 

developed by Bell laboratories51 and subsequently 

made available commercially,52 the apparatus permits the analysis of a drop of blood applied to a 

cover slip directly from finger pricking. The ZPP 

level {fig 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.

 53: 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 procedures were satisfactory; the complete extraction of 

FEP makes the former the technique of choice when 

an absolute value rather than technical simplicity is 

of primary concern. 

9.11 REFERENCES FOR CHAPTER 9 

1. Marcus, M., M. Hollander, R. E. Lucas, and N. C. Pfeiffer. 

Micro-scale blood lead determinations in screening: 

Evaluation of factors affecting results. Clin. Chem. 

2/(4):533-536, 1975. 

2. Pierce, J. O., S. R. Koirtyohann, T. E. Clevenger, and F. E. 

Lichte. The Determination of Lead in Blood. International Lead Zinc Research Organization, Inc., New York. 

1976. 

3. Mitchell, D. C, K. M. Aldous, and F. J. Ryan. Mass 

screening for lead poisoning: Capillary blood sampling 

and automated Delves-cup atomic-absorption analysis. 

N.Y. State J. Med. 74:1599-1603, Aug. 1974. 

9-6 
4. Cernik, A. A. arid M. P. H. Sayers. Determination of lead 

in capillary blood using a paper punched disc atomic absorption technique. Applications to the supervision of lead 

workers. Brit. J. Ind. Med. 28:392-398, 1971. 

5. Cernik, A. A. Determination of blood lead using a 4.0 mm 

paper punched disc carbon cup sampling technique. Brit. 

J. Ind. Med. J/:239-244, 1974. 

6. Joselow, M. M. and J. D. Bogden. A simplified micro 

method for collection and determination oflead in blood 

using a paper disk-in-Delves cup technique. At. Absorp. 

Newsletter. 77:99-101, 1972. 

7. Hessel, D. W. A simple and rapid quantitative determination oflead in blood. At. Absorp. Newsletter. 7:55, 1968. 

8. Cooke, R. E., K. L. Glynn, W. W. Ullmann, N. Lurie, and 

M. Lepow. Comparative study of a micro-scale test for 

lead in blood, for use in mass screening programs. Clin. 

Chem. 20(51:582-585, 1974. 

9. Lead: Airborne Lead in Perspective. National Academy of 

Sciences, Washington, DC. 1972. 

10. Hammer, D. I.. J. F. Finklea, R. H. Hendricks. C. M. Shy. 

and R. J. M. Horton. Trace-metal concentrations in 

human hair. In: Helena Valley, Montana. Area Environmental Pollution Study. U.S. Environmental Protection 

Agency. Research Triangle Park, N.C. Pub. No. AP-91. 

1972. p. 125-134. 

11. Methods for Determining Lead in Air and Biological 

Materials. American Public Health Association, New 

York. 1955. 69 p. ' 

12. Christian, G. D. and F. J. Feldman. Atomic Absorption 

Spectroscopy: Applications in Agriculture, Biology and 

Medicine. Wiley-Interscience, New York. 1970. 

13. L'Vov, B. V. Atomic Absorption: Spectrochemical 

Analysis. J. H. Dixon (tr). American Elsevier Publishing 

Co., New York. 1971. 

14. Delves, H. T. A micro-sampling method for the rapid 

determination of lead in blood by atomic-absorption 

spectrophotometry. Analyst. (London) 95:431-438, May 

1970. 

15. Ediger, R. D. and R. L. Coleman. A modified Delves cup 

atomic absorption procedure for the determination of lead 

in blood. At. Abs. Newsletter. 7/(2):33-36, 1972. 

16. Matson, W. R. and D. K. Roe. Trace metal analyses of 

natural media by anodic stripping voltammetry. Anal. Instrum. 4:l'9-22, 1966. 

1 7. Murthy, L., E. E. Menden, P. M. Eller, and H. G. Petering. 

Atomic absorption determination of zinc, copper, cadmium and lead in tissues solubilized by aqueous 

tetramethylammonium hydroxide. Anal. Biochem. 

55(2):365-372, 1973. 

18. Keenan.R.G., D.H. Byers, B. E. Saltzman, and F. L. Hyslop. The "USPHS" method for determining lead in air 

and in biological materials. J. Am. Ind. Hyg. Assoc. 

24(5 ):481-491, 1963. 

19. Kubasik, N. P., M. T. Volosin, and M.H. Murray. Carbon 

rod atomizer applied to measurement of lead in whole 

blood by atomic absorption spectrophotometry. Clin. 

Chem. 7S(5):4I0^I2, 1972. 

20. Hicks, J. M., A. N. Gutierrez, and B. E. Worthy. Evaluation of the Delves micro system for blood lead analysis. 

Clin. Chem. 79(3):322-325, 1973. 

21. Matson, W. R. Rapid sub-nanogram simultaneous 

analyses. Trace Substances in Environ. Health. 

IV:396-406, 1970. 

22. Horiuchi, K., S. Horiguchi, F. Takoda, and K. Teramoto. 

A polarographic method for the determination of a small 

amount of lead in biological materials. Osaka Med. J. 

/4:II3-I18, 1968. 

23. Keppler, J. F.. M. E. Maxfield. W. D. Moss, G. Tietjen. 

and A. L. Linch. Interlaboratory evaluation of the 

reliability of blood lead analyses. J. Am. Ind. Hyg. Assoc. 

57:412-429, 1970. 

24. Donovan, D. T., V. M. Vought, and A. B. Rakow. 

Laboratories which conduct lead analysis on biologic 

specimens. Arch. Environ. Health. 2J(2):1 11-113, 1971. 

25. Berlin, A.. P. Del Castilho, and J. Smeets. European inter 

comparison programmes. In: Environmental Health 

Aspects of Lead. Commission of the European Communities, Centre for Information and Documentation, 

Luxembourg. May 1973. p. 1033-1049. 

26. Blood Lead Proficiency Testing. U.S. Department of 

Health, Education, and Welfare, Center for Disease Control, Atlanta. Ga. 1975. 

27. Blood Lead Proficiency Testing Program. U.S. Department of Health, Education, and Welfare, Center for Disease Control, Atlanta, Ga. Monthly Report for March, 

1977. 

28. Lead: Environmental Health Criteria 3. World Health 

Organization and the United Nations Environment Programme, Geneva. 1977. p. 59-65. 

29. Grimes, H.. M. P. H. Sayers, A. A. Cernik, A. Berlin, P. 

Recht, and J. Smeets. Note on the Lead Exposure of 

Children: Determinations Carried Out on Behalf of the 

Commission in Western Ireland. Commission ofthe European Communities, Luxembourg. Report No. VF-I49I. 

1975. p. 7. 

30. Haeger-Aronsen, B. Studies on urinary excretion of 8-

aminolevulinic acid and other haem precursors in lead 

workers and lead-intoxicated rabbits. Scand. J. Clin. Lab. 

Invest. /2(Suppl. 47>—1-128. 1960. 

31. Mauzerall. D. and S. Granick. The occurrence and determination of 8-aminolevulinic acid and porphobilinogen in 

urine. J. BioTchem. 2/9(0:435-446, 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. /4.-53-60. 1966. 

33. Urata. G. and S. Granick. Biosynthesis of 8-aminoketones 

and the metabolism of aminoacetone. J. Biol. Chem. 

258(2):8ll-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 sequential 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 excretion of urinary porphobilinogen, aminoacetone, and 

delta-aminolevulinic acid. Am. J. Clin. Pathol. 

42:349-354. 1964. 

9-7 
Hr***" 

39. MacGee, J., S. M. Roda. S. V. Elias, A. Lington, M. W. 

Tabor, and P. B. Hammond. Determination of deltaaminolevulinic acid in blood plasma and urine by gasliquid chromatography. Biochem. Med. 77:31-44, 1977. 

40. Granick, J. L., S. Sassa. S. Granick, R. D. Levere, and A. 

Kappas. Studies of lead poisoning. I. Microanalysis of 

erythrocyte protoporphyrin 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-

aminolevulinic acid dehydratase activity in circulatory 

blood cells: A sensitive laboratory test for the detection of 

childhoo d led poisoning . New Eng. J. Med. 

284(ll):565-569. 1971. 

42. Berlin. A. and K. H. Schaller. European standardized 

method for the determination of 8-aminolevulinic acid 

dehydratese activity in blood. Z. Klin. Chem. Klin. 

Biochem. 72:389-390, 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-aminolevulinic 

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. 124):l-78. I960. 

45. Heilmeyer. L. Uber die erythropoetischen porphyrien. 

Wien Med. Wochschr. / 76:12-17. 1966. 

46. Langer, E. E.. R. G. Haining. R. F. Labbe. P. Jacoby. E. F. 

Crosby, and C. A. Finch. Erythrocyte protoporphyrin. 

Blood. 40:112-128. 1972. 

47. Granick, S.. S. Sassa. J. L. Granick. R. D. Levere. and A. 

Kappas. Assays for porphyrins. 8-aminolevulinic-acid 

dehydratase, and porphyrinogen 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. Clin. Med. 87:932-940, 

1973. 

49. Lamola, A. A., M. Joselow, and T. Yamane. Zinc protoporphyrin (ZPP): A simple, sensitive, fluorometric 

screening test for lead poisoning. Clin. Chem. 

27(l):93-97, 1975. 

50. Chisolm, J. J., Jr., and D. H. Brown. Micro-scale photofluorometric determination of "free erythrocyte 

porphyrin " (protoporphyri n IX). Clin. Chem. 

27(11):1669-I682, 1975. 

51. Blumberg, W. E., J. Eisinger. 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 

(ZnP), Erythrocyte Protoporphyrin (EP) and Blood Lead 

(BL) in Pediatric Screenings for Lead Insult. Paper presented 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 oflead 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. Chering. 

Micro-photo fluorometric assay for protoporphyrin in 

acidified acetone extracts of whole blood. Biochem. Med. 

9:113, 1974. 

9-8 
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 population 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 dietary 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 handto-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 environmental 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 expended in day-to-day activity. 

10.2.1 Respiratory Absorption 

The International Radiological Protection Commission (IRPC) Task Group on Lung Dynamics' 

developed a model designed to predict the percentage of inhaled aerosols that would be deposited and 

retained in the lungs. This model predicted that approximately 35 percent of the lead inhaled in 

general ambient air would be deposited in the airways. Since the aerodynamic diameter of lead particles is generally in the range of 0.1 to 1.0 fim, 

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 ofthe emission source. 

The deposition within the respiratory tract of very 

small particles (<0.1 fim) 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 /xm 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 uptake as does the aging of the aerosol (Chapter 6). 

This illustrates the difficulty in choosing the appropriate 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 indicates that the absorption or clearance of lead 

deposited in the airways would vary greatly depending 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 particles in the respiratory tract of man have not been 

extensive, especially in the case of lead. Using an air 

10-1 
P.35 

lead level of 150 /xg/m3, Kehoe57 studied the 

deposition of combusted tetraethyl lead in human 

volunteers. The source of lead was combusted 

tetraethyl lead, which produced lead (III) oxide 

(Pb203) in the air. Subjects breathed air containing 

150 /j.g/m3 lead; the smaller particles averaged 0.05 

/um in diameter and the larger ones averaged 0.9 

fim in diameter, as viewed under the electron 

microscope. This represents a mass median 

equivalent diameter of approximately 0.26 and 2.9 

fim, respectively.8 Thirty-six percent ofthe 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 figlm3 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 fim. At 30 respirations per 

minute, deposition rates were about halved. The 

results, which are similar to those of Kehoe,57 are 

fairly consistent with the IRPC lung deposition 

model.1 

These data suggest that a 30 ± 10-percent deposition rate can be expected in individuals breathing 

ambient air and that deposition may vary considerably, 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 ofthe 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 particles. 

Kehoe57 reported a substantial increase in fecal 

excretion when large-particle lead oxide aerosols 

were inhaled for many weeks at 105 /xg/m3; the increase probably resulted from the swallowing of particles trapped in the nasopharynx. When air with a 

similar lead concentration in small particles was inhaled, 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 exhaust 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 demonstrated a pronounced reduction in the number of 

lung macrophages resulting from inhalation of lead 

oxide at both 10 and 150 figlm*. 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 suspension administered intratracheally to rats (1.5 mg of 

lead oxide per dose on 8 successive days) were retained by the body as completely as were intravenous doses. At one-third the dose, however, retention via the intratracheal route was significantly less. 

Randall and his coworkers17 exposed 4 baboons 

to aerosolized lead (Pb304) of varying particle size 

(mass median diameters of 5.9, 3.2, and 2.0 fim, 

respectively). The air lead concentrations varied 

from approximately 1 to 4 /xg/m3. The exposure 

period lasted 4 weeks, and blood sampling continued for 6 weeks. The rate of absorption of lead 

into blood was faster and reached a higher level for 

coarse (mean diameter = 1.6 fim) particles than for 

fine (mean diameter = 0.8 fim). 

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.1820 Kehoe 5 7 concluded from long-term balance studies that approximately 10 percent ofthe intake of lead from food and beverages was absorbed 

from the gastrointestinal tract since this was the 

amount excreted in the urine. This estimate, however, 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. Absorption and retention were consistent within the age 

range studied. This study, however, has been criticized 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 report, 2 separate series of investigations were conducted. In the first, 3 to 8 balance studies were performed with 9 infants each. In the second, each of 6 

infants consumed randomly allocated diets providing low, intermediate, and moderate amounts of 

lead. When intakes of lead exceeded 5 /ug/kg/day, 

which is a reasonable level given typical dietary patterns, net absorption averaged 42 percent and retention 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 subsequent absorption by root crops. (Internal translocation of lead between roots and aerial parts is apparently small.) In addition, variable fractions of inhaled lead are ingested after deposition in the airways; 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 primary food crops and on animal feed crops); (2) absorption 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 processed foods (excluding frozen foods), it would appear that processing and canning of certain foods 

regularly doubles or triples their average lead concentrations (Table 10-1). 

TABLE 10-1. LEAD CONTENT OF FRESH, PROCESSED, AND CANNED FOODSTUFFS24 

Food 

Lead 

concentration (ppm) Food 

Lead 

concentration (ppm) 

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. 

0.205 

0.130 

0.050 

Canned vegetables 

Beets 

Beans 

Peas 

0.128 

0.052 

0.143 

0.104 

0.107 

0.031 

0.087 

0.446 

0.578 

0.512 

0.120 

0.191 

0.150 

Tomatoes 

Avg. 

Canned juices 

Tomato 

Vegetable 

Orange 

Fruit 

Avg. 

Canned fruits 

Peaches 

Pineapple 

Applesauce 

Avg. 

0.381 

0.318 

0.425 

0.710 

0.458 

0.338 

0.215 

0.135 

0.251 

0.235 

0.417 

0.402 

0.320 

0.380 

0.154 

10-3 
P.37 

The data on lead in foods are not comprehensive 

enough to permit construction of a spectrum of 

levels ranging from fresh to canned and characterization of the resulting lead exposure. It must 

suffice to state at this point that some fraction of dietary lead probably is indirectly of airborne origin. 

10.2.2.2 THE RELATIONSHIP OF ORAL INTAKE TO BLOOD LEAD LEVELS 

It has been demonstrated repeatedly that blood 

lead levels increase when the oral intake of lead increases, 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 

100 fig of lead ingested daily ranges from less than 6 

to more than 18 /ug/dl. 

It is important to point out that the high end of this 

range was gathered using subject groups whose dietary 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 European data are more consistent with a contribution of 

about 6 figld\ to the blood lead level per 100 fig 

daily oral intake of lead; a similar level is reported 

by Kehoe.57 

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 between 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 increases 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 

Diet 

Low protein 

High protein 

Low fat 

High fat 

Low minerals 

High minerals 

Low fiber 

High fiber 

Low vitamins 

High vitamins 

Blood 

. 5.1 

1 

1 

9.6 

17.7 

0.2 

1 

1 

1 

1 

Ratio ol mean retention of lead 

(experimental 

Kidneys 

2.5 

3.7 

1 

7.6 

11.9 

0.2 

1 

1 

1 

1 

control) 

Femur 

2.8 

2.6 

1 

4.8 

13.7 

0.1 

1 

1 

1 

1 

Liver 

2.2 

1 

1 

4.2 

8.8 

0.1 

1 

1 

1 

1 

The absorption of lead in paint chips has received 

attention because ofthe 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-

36

 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/xm) 

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, particularly the lead alkyls and lead naphthenates.38

-

39 

Soon after tetraethyl lead was introduced into commercial use, Eldridge39

 reported that it was absorbed 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 subcutaneous applications on alternate days of lead acetate 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 acetate because of more pronounced skin reactions, 

higher lead accumulation in brain, and the occurrence of a paralytic syndrome before death in two 

animals.42 

The rate of absorption of tetraethyl lead and inorganic 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 oflead 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. Ifthe 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 tetraethyl-lead-contaminated atmospheres, in attempting 

to separate cutaneous exposure from respiratory exposure, the role of cutaneous lead absorption in relation 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, however, whenever short-term high levels oflead intake 

are superimposed on such a long-term ingestion pattern. 

10.3.1 Human Studies 

Autopsy data have shown that lead becomes 

localized and accumulates in bone. This accumulation 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 investigators48

 show that in nonoccupational^ exposed 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 provide 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 concentration 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 considered to represent a risk to health.54

 Plasma lead 

concentrations have been shown to be constant at 2 

to 3 /ug/dl over a range of 10 to 150 /ug/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 disappeared 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 clinical 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 
P.39 

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 consistently and continuously. The second pool comprises other organs and systems and accumulates 

much less. The levels of lead in this pool tend to 

stabilize early in adult life and thereafter demonstrate a turnover rate sufficient to prevent accumulation. 

Since the organs and systems that contain the 

relatively mobile lead pool are of greater toxicological significance, it is clear that a mobilizable or 

exchangeable lead burden is a more important concept 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 concentrations 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 observed 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 frequently 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 noninvasive technique and because teeth provide a record 

of long-term lead exposure. The dentine is particularly 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 exposure. 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 approximately 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 produces high initial concentrations of lead in soft 

tissues which then fall rapidly as the result of excretion and transfer to bone.66

 The distribution characteristics of lead within the animals' bodies were 

found to be independent of the dose over a wide 

range. Castellino and Aloj67 described the rate constants 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.68 reported that the 

rate of elimination of a single dose of lead from rats 

became slower with time, reflecting progressively 

decreasing mobility ofthe residual body burden. 

Goldstein et al.69 sacrificed 21-day-old rats 24 

hr after intravenous injection of various single 

doses (1. 50, 200 fig) of labeled lead (210Pb) and 

found that the concentration of radioactivity in the 

brain was directly proportional to the blood radioactivity. Studies of OTuama et al.70

 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 (2l0Pb) in both subacutely intoxicated 

(155 mg PbCOj/day for 5 days) and control animals. 

Radioactivity in barrier tissues (such as choroid 

plexus and meninges) rose rapidly, with concentrations 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, including species differences, time of sacrifice, or a 

more complex mechanism of distribution. 

Rather striking age-related differences in the distribution and retention of lead in rats have been observed.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 sucklings 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-fractiona10-6 
tion techniques. 7 2

-

7 3

 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 ofthe effect have been 

specifically determined. In particular, direct assessment of lead level in bone marrow is difficult to carry 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 cortex.75 

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 concentrations 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 ofa nonoccupational^ exposed 

human subject. Urinary and fecal excretion of

 204Pb 

from the blood amounted to 38 and 8 fig/day, accounting for 76 and 16 percent, respectively, ofthe 

measured recovery. The crude estimation of lead in 

hair, nails, and sweat yielded a value of 4 fig (8 percent). The urinary excretion was similar to the 

average daily lead excretion of 31 /ug/day reported 

by Teisinger and Srbova.80 Booker et al.81 administered lead(212Pb) 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 important 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 exposure can be precipitated by the addition of agents 

such as oxalate, phosphate, or carbonate, only onethird to two-thirds of the lead in the urine of lead 

workers is available for precipitation.83 These 

results suggest the presence ofa 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 increased the lead concentration of sweat twofold to 

fourfold. Schroeder and Nason85 found the concentration 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 excretion 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 excretion of lead.87

 In contrast, urinary excretion was reported to be two times greater than fecal excretion in 

baboons.89 

There are indications that most ofthe 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 ofa 

gallbladder can explain differences in the rate of appearance ofa 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 
P.41 

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 presence of lead-binding ligands in the tubular cell. 

These observations demonstrate that the renal excretion 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 reduction. 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.93 

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 excretion 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 possible that some of them may be useful. Indeed, Robinson96

 has shown that in industrial workers exposed 

to tetraethyl lead, urinary excretion of ALA is increased, but not to the same degree as in workers exposed 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 inorganic 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 significant implications for the increased risk of children 

exposed to lead. There are, as well, differences between children and adults in the intake, desposition, 

etc., of lead. 

Metabolic, physical, and other differences between 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 onethird the surface area of an adult; this parameter is 

not known to be directly related to the risks associated 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 respects99101 are 

quite different from those of adults; normal hand-tomouth 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 pathways99'

01

 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.I00 '

0 1

 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 

Wexler'02find an increasing resorption oflead in rat 

bone organ culture when calcium in the medium is 

reduced. 

10-8 
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pig brain and in neural barrier tissues in cortical and leadpoisoned animals. Tox. Appl. Pharm. 36:1-9, 1976. 

Momcilovic, B. and K. Kostial. Kinetics of lead retention 

and distribution in suckling and adult rats. Environ. Res. 

8:214-220, 1974. 

Costellino, N. and S. Aloj. Intracellular distribution of 

lead in the liver and kidney ofthe rat. Brit. J. Ind. Med. 

26:139-143, 1969. 

Barltrop, D., A. J. Barret, and J. T. Dingle. Sub-cellular 

distribution of lead in the rat. J. Lab. Clin. Med. 

77:705-712,1971. 

Goyer, R. A., D. L. Leonard, J. F. Moore, B. Rhyne, and 

M. R. Krigman. Lead dosage and the role of the intranuclear inclusion body. Arch. Environ. Hlth. 

20:705-711, 1970. 

Allcroft, R. and K. L. Blaxter. Lead as a nutritional 

hazard to farm livestock. V. The toxicity of lead to cattle 

and sheep and an evaluation ofthe lead hazard under farm 

conditions. J. Comp. Path. Ther. 60:209-218, 1950. 

Friberg, L., M. Piscator, G. Nordberg, and T. Kjellstrom. 

Cadmium in the Environment, 2nd Ed. Ohio, Chemical 

Rubber Co. 1973. 

Kehoe, R. A. Normal metabolism of lead. Arch Environ. 

Hlth. 8:232-235, 1964. 

Kehoe, R. A. Metabolism of lead under abnormal conditions. Arch. Environ. Hlth. 8:235-243, 1964. 

Rabinowitz, M. B., G. W. Wetherill, and J. D. Copple. 

Lead metabolism in the normal human: Stable isotope 

studies. Science. 782:725-727, 1973. 

Teisinger, J. and J. Srbova. The value of mobilization of 

lead by calcium ethylene-diamine-tetraacetate in the diagnosis of lead poisoning. Brit. J. Ind. Med. 76:148-152, 

1959. 

Booker, D. V., A. C. Chamberlain, D. Newton, and A. N. 

B. Stott. Uptake of radioactive lead following inhalation 

and injection. Brit. J. Radiol. 42:457-466, 1969. 

Vostal, J. Study of the renal excretory mechanisms of 

heavy metals. 15th International Congress of Occupational Health, Vienna, 19-24 September, V. 3. 1966. p. 

61-64. 

Dinischiotu, G. T., B. Nestorescu, J. C. Radielescu, C. 

Jonescu, N. Preda, and G. Hutza. Studies on the chemical 

forms of urinary lead. Brit. J. Ind. Med. / 7:141-145. I960. 

Schiels, D. O. Elimination of lead in sweat. Aust. Ann. 

Med. 3:225, 1954. 

85. Schroeder, H. A. and A. P. Nason. Trace element analysis 

in clinical chemistry. Clin. Chem. 7 7:461 -473, 1971. 

86. Costellino, N., P. Lamanna, and B. Grieco. Biliary excretion of lead in the rat. Brit. J. Ind. Med. 23:237-239, 1966. 

87. Blaxter, K. L. and A. T. Cowic. Excretion of lead in the 

bile. Nature. 757:588, 1946. 

88. Cohen, N., M. Eisenbud, and M. E. Wrenn. The Retention 

and Distribution of Lead-210 in the Adult Baboon. Annual 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

 2o*Hg, MCu, 52Mn, 2iopb 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 toxicity of some tetra- and trialkyl lead compounds. Brit. J. 

Ind. Med. /8:277-282, 1961. 

92. Bolonowska, W. Distribution and excretion of triethyl 

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. 77:14-19, 1965. 

94. Gutniak, O., H. Koziolowa, and E. Kowaiski. Free protoporphyrin content of erythrocytes in chronic tetraethyl 

lead poisoning. Lancet. 7:1 I 37-1 I 38, 1964. 

95. Beattie, A. D., M. R. Moore, and A. Goldberg. Tetraethyllead poisoning. Lancet. 2:12-15, 1972. 

96. Robinson, T. R. Delta-amino levulinic acid and lead in 

urine of lead antiknock workers. Arch. Environ. Hlth. 

28:133-139, 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 

oflead 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): 1229-1233, 1973. 

101. Lin-Fu. J. S. Vulnerability of children to lead exposure 

and toxicity. N. Engl. J. Med. II. 289(24):1289-1293, 

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 
11. BIOLOGICAL EFFECTS OF LEAD EXPOSURE 

P.45 

11.1 INTRODUCTION 

As noted in Chapter 2, air-quality criteria documents present the scientific knowledge of the relationship between pollutant concentrations and their 

adverse effects on public health and the environment. This chapter addresses the important human 

health and biological effects of lead exposure. 

Section 11.2 treats the biochemical and pathological basis ofthe various health effects of lead, centering 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, ofthe upper range of exposure to this pollutant regardless of 

its source and to state this in a discrete portion ofthe 

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 interdependent 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 important 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 AN D 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 eamino group of lysine. An effect may be imparted, 

therefore, by binding-site competition with the native 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 exposed human subjects and in vitro and in vivo. 

Clearly, many ofthese studies in the literature are of 

marginal relevance to this particular document and 

are briefly summarized for reference reading without evaluation. 

On the other hand, a number of other enzyme 

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 presented 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 
P.46 

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) i 

Erythrocyte and liver AP 

Acid phosphatase 

Catalase 

Chollnesterase 

a-Mannosidase 

/3-Acetyl glucosaminadase 

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 

5.6.14 

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 

Glutathione 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 interval 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 

mitochondrial fractions, and there was a decrease in 

microsomes. Mitochondrial binding was particularly strong. 

Similarly, Barltrop et al.32 measured

 203Pb in 

heart, liver, kidney, and spleen following intraperitoneal (i.p.) administration. Their results indicated that most of the lead accumulated in the 

mitochondria. 

A detailed study ofthe 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 intranuclear 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 inclusion 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 presence oflead.' 3 8 

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 decreased respiratory rates in mitochondria of rabbit 

tissue under chronic lead challenge using aketoglutarate, succinate, and pyruvate as substrates. 

Phosphorylation was also retarded. 

A marked sensitivity ofthe pyruvate-NAD reductase system in kidney mitochondria of lead-intoxicated rats is suggested by the work of Goyer and 

Krall,40 who note impairment of pyruvate-dependent respiration using ADP/O ratios and respiratory 

control rates (RCR's) as indices. Succinate-mediated 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-dependen t respiratio n in 

11-2 
P.47 

mitochondria of the kidney from lead-intoxicated 

animals may be evidence of decreased succino-oxidase enzyme, which would also be consistent with 

decreased mitochondrial protein. 

Walton42 reported an accumulation of lead in granules 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 preservation of ionic gradients in the membrane; and (2) the 

chemical action of lead would promote ATP hydrolysis, 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 subcellular effects of lead on the renal system were apparent 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 inclusion bodies at 50 and 250 ppm. Furthermore, considerable alteration in the activity of heme biosynthetic pathway enzymes (8-ALA synthetase and 

ferrochelatase) was observed at 50 and 250 ppm. 

The blood lead values for the different dose regimens ranged from 5 figldl for control animals and 

10 figldl for the 5 ppm group to 25 /ig/dl for the 50 

ppm group and 70 figldl 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 mitochondrial 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 indications 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 . Th e discussio n of the 

hematopoietic system in Section 11.4 includes treatment of this relationship. 

In addition, the intramitochondrial stages of heme 

synthesis have been suggested to have an intermediary role in introcellular metabolism and are probably required for the continued transfer of iron from 

extracellula r site s to normoblasts of 

reticulocytes.4546 

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. 474 9 A more detailed discussion of 

erythrocyte-lead relationships is given in the 

hematopoietic section. 

Jandl and coworkers50 demonstrated that the uptake of

 59Fe by human reticulocytes was almost completely inhibited by 5 x IO4

 M lead and that its incorporation 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 ofthe 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 Garro525 3 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 
P.48 

metal. It is possible that the metabolism ofthe capsular cells is impaired, which then causes the 

degeneration of associated neurons and axons and 

has a deleterious effect on the ganglion cells. A common site for intoxication in both the capsular cells 

and the Schwann cells of the peripheral nervous 

system has been suggested to account for both axonal degeneration and segmental demyelination55 

because these two cells have a common embryological origin.56 

Moore et al.,57 in a study ofthe 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, Scotland, there was a significant inhibition of cardiac 

ferrochelatase and 8-aminolevulinic acid dehydratase 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 evaluation ofthe relevance 

of many studies can therefore 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 interruption of the processes involved can be serious. Incorrect 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 process can produce abnormal cells. Such chromosomal 

aberrations can, therefore, be responsible for the 

production of such serious consequences as genetic 

defects in offspring ofthe affected organism. 

In the last few years, a number of reports have 

been published on the chromosomal effects of excessive exposure to lead in animals 3

 and 

humans.5668 Although some of these reports have 

been essentially negative,6365 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.5662 Thus, the 

literature is controversial in regard to chromosomal 

abnormalities induced by exposure to lead. 

O'Riordan and Evans63 did not find any significant increase in chromosomal damage in male 

workers exposed to lead oxide fumes in a shopbreaking yard. These shipbreakers had blood lead values 

ranging from 40 to over 120 figldl. Schmid et al.64 

found no evidence of increased chromosomal aberrations in peripheral lymphocytes, studied both in 

vivo and in vitro, in lead manufacturing workers. 

Furthermore, Bauchinger et al.65 found no abnormalities in the chromosomes of policemen with elevated 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 figldl has been reported, 

however, by Forni and Secchi58 and by Schwanitz 

et al.56 Moreover, Deknudt et al. 6 0 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 considered 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 ofthe 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 increased in a group of 24 male workers occupied in 

zinc electrolysis and exposed to zinc, lead, and cadmium. The workers had clearly elevated blood lead 

and blood cadmium levels in comparison with a control 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 Deknudt et al.60

 in regard to exposure to a combination 

of lead, zinc, and cadmium. Referring to studies indicating the mutagenicity of cadmium, Bauchinger 

11-4 
P.49 

and his colleagues66 were inclined to consider cadmium as being mainly responsible for aberrations; 

but Deknudt et al.60 concluded that the abnormalities found were caused mainly by lead rather 

than by combinations of the three metals. 

The question of whether chromosomal abnormalities occur in humans as a result of lead exposure, either alone or in combination with other 

pollutants, remains unanswered.67 Furthermore, the 

human health significance of chromosomal abnormalities 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-carcinogenic 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 ofthe 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 following 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.707273 

Swiss mice fed diets containing 0.1 percent basic 

lead acetate i"Pb(C2H302)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,7074 and the incidence and size were related 

to the duration of lead feeding.74 In male SpragueDawley 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 

containin g 1 percen t lea d acetat e 

[Pb(C2H3 02 ) 2 -3H2 0], 7 6 and Goyer and Rhyne77 reported that 60 to 80 percent of rats on a diet containing 1 percent lead acetate for more than 1 year 

developed renal adenomas or carcinomas with an increase in both size and incidence of carcinomas related 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 administered varied between 120 and 680 mg lead in 

the animals developing the tumors.7178 

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 oxide 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 adenocarcinoma 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 increased carcinogenicity. 

Tetraethyl lead (TEL) [Pb(C2H5)4] is an important, widely used, antiknock additive for motor 

fuels. Epstein and Mantel81 reported that subcutaneous 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 established from human studies. In 1963, DingwallFordyce 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 nonexposed population.83

 This seems to support the 

11-5 
P.50 

conclusion ofa Working Group ofthe 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 supported 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 nonspecific 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 encephalopathy occurs in less than a week. Periods of 

vomiting and apathy progressing to stupor are interspersed with periods of hyperirritability, poor 

memory, inability to concentrate, mental depression, persistent headache, and tremor. Several reports8586

 indicate that children with acute encephalopathy 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 disorders, including loss of motor skills and speech. 

They may also exhibit convulsive disorders; 

however, there are no clinical features that distinguish lead-induced convulsions from other 

seizure disorders. These findings are usually associated with blood lead levels in excess of 60 /ug/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 encephalopathy, 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 centers 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 sometimes hyperuricemia are noted. Late lead nephropathy 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 poisoning 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 discussion ofthe hematopoietic effects is contained in Section 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 observations, 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.9294 Two 

studies9293 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 encephalopathy may be followed by cortical atrophy, hydrocephalus ex vacuo, severe convulsive disorder, 

mental incompetence, and blindness. These results 

are becoming rare, however, and subtle neurological 

deficits and mental impairment are the more common outcomes. 

Many children with documented prior attacks of 

symptomatic lead poisoning develop aggressive, 

11-6 
P.51 

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 observed in children 1 to 6 years old and of lower 

socioeconomic status; in both these groups the prevalence of iron deficiency is quite high. A combination 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 demonstrated 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 established. In lead workers, Sakurai97

 could not demonstrate any difference in hemoglobin level up to a 

blood lead level of 50 figldl. Tola et al.98 reported 

an effect of blood lead level on hemoglobin in a 

study of 33 workers at the beginning of their exposure 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 figldl, the 

average hemoglobin level had decreased to 13.4 g/dl 

from the initial value of 14.4 g/dl (p = < 0.001). 

Pueschel99 observed a negative correlation between 

hemoglobin level and blood lead level in 40 

children with blood lead levels ranging between 30 

and 120 figldl. In this study, however, the ages ofthe 

individual children are not stated. A number of 

other studies also bear out the above observation.100102

 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 irf the youngest 

children. 

The mechanism of anemia in lead poisoning appears to be a combination of decreased erythrocyte 

production as a result ofthe interference oflead 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 erythrocytes103104 as the lead is rapidly 

transferred from plasma to erythrocytes. Rosen et 

al.100 have shown that plasma lead levels are a constant 2 to 3 figldl over a range of 10 to 150 figldl 

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 exposure. It would appear, then, that the whole blood 

content of lead is relatively independent of 

hematocrit. 

11.4.2 Effects of Lead on Erythrocyt e 

Morphology and Survival 

In lead poisoning, even in absence of iron deficiency, the erythrocytes are microcytic and hypochromic. Basophilic stippling is a frequent but inconstant 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-5'-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. 

Detreased 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-5'-

nucleotidase.108 

Osmotic fragility is decreased in lead poisoning. 

This is a common feature of many microcytic 

anemias, as it expresses the increased surface-to11-7 
P.52 

volume ratio that results from the reduced 

hemoglobin content of individual erythrocytes. In 

lead poisoning, however, an increased osmotic resistance also results from a direct effect of lead on the 

erythrocyte membrane because increased osmotic 

resistance may be produced by lead in vitro.-09 Increased 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-dependent membrane ATPase, which is indispensably 

coupled to active cation transport.111 Shortening of 

erythrocyte survival has been shown by Hernberg et 

al." 2 using tritium-labeled difluorophosphonate 

and by Berk et al." 3 using detailed isotopic studies 

ofa patient with severe acute lead poisoning. Leikin 

and Eng114 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 important role. 

An additional factor is a large component of ineffective erythropoiesis. This was demonstrated by 

the detailed study ofthe patient of Berk et al." 3 in 

whom a marked increase of labeled stercobilin was 

observed after administration of labeled

 14Cglycine, a heme precursor. The presence of increased 

amounts of this heme catabolite in the urine demonstrates 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 synthesis 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 proteins in the body, heme is the prosthetic group of 

MITOCHONDRIAL MEMBRANE 

MITOCHONDRION 

FERROCHELATASE 

SUCCINYLCoA if \ 

" 

6-ALA 

Fo + PROTOPORPHYRIN 

S-ALA SYNTHETASE 

(INCREASEI 

Pb (DIRECTLY OR BY 

DEREPRESSION! t 

6-ALA 

DEHYDRASE 

(DECREASEI 

COPROPORPHYRIN 

(INCREASE! 

I 

PORPHOBILINOGEN (PBG! 

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 l kg of hemoglobin, approximately 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 protoporphyrin IX (catalyzed by the enzyme, ferrochelatase). 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-AMINOLEVULINIC 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 ofthe SH group in vitro by reducing 

compound s such as mercaptoetheno l and 

dithiothreitol. The observation that 8-ALAD is inhibited by lead was first reported by Nakao et al." 5 

and DeBruin"6 in 1968. Hernberg et al." 7 demonstrated that the logarithm ofthe activity of 8-ALAD 

was negatively correlated with blood lead level over 

11-8 
a range from 5 figldl (the lowest value observed) to 

95 figldl. In a detailed study of 25 healthy individuals with blood lead levels below 16 figldl, 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 figldl and 90 

percent inactivated at a blood lead level of 55 figldl. 

These observations have been confirmed by several 

other laboratories119123 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 

figldl), 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 figldl (range 5 to 10), (2) 10 families from 

central Tokyo with average blood lead of 12.8 figldl 

(range 9 to 17), and (3) 10 male workers with 

average blood lead of 26.5 figldl (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 demonstrated. 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 

figldl) 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 figldl. By regression 

analysis, they estimated in this series that a ratio of 

reactivated/nonreactivated 8-ALAD of 1 (corresponding to no inhibition) would occur at a blood 

lead level of 15 figldl. Because ofthe 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 figldl, whereas the 

lowest blood lead level studied by Granick et al.126 

was 20 figldl. For these reasons, the observations of 

Granick et al.126 do not contradict the evidence by 

Hernberg et al.118that 8-ALAD is already inhibited 

at the lowest levels of blood lead observed in 

humans in industrialized countries. Because the inhibition of this enzyme is a direct effect oflead in the 

blood, its correlation with blood lead is not surprising, and 8-ALAD activity may be used to estimate 

blood lead with a good degree of accuracy. The inhibition of 8-ALAD in erythrocytes reflects a similar 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 figldl, 

there was a clear correlation between erythrocyte 

and liver 8-ALAD and an expected negative correlation between blood lead and 8-ALAD in 

erythrocytes. Millar et al."9showed that when suckling 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 following 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 activity were found in the 10 and 100 ppm groups but 

no differences in hematocrit, hemoglobin, or FEP 

were observed. Lead storage in the kidney ofthe 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 increased 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 exposure 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 excretion observed in some studies130131

 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 figldl. Their observations have been confirmed by other studies123124133

 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 
P.54 

into two groups, those with blood lead levels below 

and above 40 figldl, two different linear correlation 

slopes could be derived, although with a lesser 

degree of correlation than the exponential relationship 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 ranging between 25 and 75 figldl. In 55 adolescents with 

blood lead levels ranging from 8 to 40 figldl, 

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 figldl), all other studies reported show a 

clear exponential increase in 8-ALA urinary excretion with increase in blood lead. These observations 

parallel the reported exponential inhibition of the 

enzyme 8-ALAD and indicate that this is one ofthe 

earliest effects of lead on heme synthesis. 

The urinary excretion of 8-ALA does not exceed 

the normal range (0.6 figldl) until the blood lead 

level reaches 40 figldl. The normal range, however, 

is derived from values obtained from individuals 

with blood lead levels up to 40 figldl. 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 figldl 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 figldl, the correlation between blood 

lead and 8-ALAD was much greater than with urinary 8-ALA. For these reasons and because ofthe uncertainty of defining a normal range, it is generally 

accepted that urinary 8-ALA becomes clearly abnormal at blood lead levels greater than 40 figldl. It 

has been postulated that there may be an excess of 8-

ALAD activity, so that normal 8-ALA metabolism 

is still sustained by even 50-percent-inhibited 

enzyme at blood lead levels near 40 figldl. Above 

this value, however, the inhibition results in functional impairment and clear accumulation of 8-

ALA, and increased urinary excretion may be observed. A recent study suggests that ALA may, in 

fact, be toxic systemically. The relative contributions from decreased utilization of ALA, as a result 

of ALAD inhibition and the derepression of ALAsynthetase, to urinary levels of ALA at blood levels 

at which excretion is significant cannot be determined 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 indicator 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, combining 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 manipulation of the blood sample. 

Accumulatio n of protoporphyri n 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, protoporphyrin, 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 disorder in which excess protoporphyrin is produced 

after heme synthesis is complete. In that case, the excess of protoporphyrin formed (as a result of a congenital defect in ferrochelatase) is attached to the 

surface of hemoglobin at a site that bridges the aand f3-chains of hemoglobin.137138

 Because this type 

of bond to hemoglobin is very loose in 

erythropoietic protoporphyria, protoporphyrin 

diffuses through the plasma into the skin where it induces 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 photosensitivity is observed, despite extremely elevated 

erythrocyte protoporphyrin levels. 

An additional important difference between the 

increased protoporphyrin level in the erythrocytes 

11-10 
of persons with lead intoxication and erythropoietic 

protoporphyria is the fact that only in the former is 

the center ofthe protoporphyrin molecule occupied 

by zinc.'39 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 increased level of protoporphyrin is observed in the 

erythrocytes. 

Accumulatio n of protoporphyri n 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 substrates of ferrochelatase, less available to enzyme action, with subsequent accumulation ofthe 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 completely inhibited; (2) lead is deposited on the 

mitochondrial membrane, where it produces profound ultrastructural changes; (3) iron transport 

through the mitochondrial membrane is accomplished by both energy-dependent and energyindependent mechanisms that are impaired by 

lead;141 and (4) in iron deficiency (when ferrochelatase activity is normal but iron is scarce) zinc 

protoporphyrin bound in the heme pocket is accumulated, whereas in erythropoietic protoporphyria (when iron is normal but ferrochelatase activity is decreased142143 ) free protoporphyrin 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 protoporphyrin is not limited to the normoblast and/or 

to the hematopoietic system. Formation ofthe hemecontaining protein, cytochrome P450, which is an integral part of the liver mixed-function oxidase 

system, may also be inhibited by lead.144 Accumulation 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 function, 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 increased 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 implication of the impairment of mitochondrial function, 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 Piomelli in a study of 90 children, 

covering the blood lead level range from 5 to 90 

/ig/dl.147 In a later study of 1038 children, 568 of 

whom had blood lead levels greater than 40 

/tg/dl,148 this correlation was confirmed, and it was 

clearly shown that all children with blood lead 

levels greater than 60 figldl had erythrocyte protoporphyrin greater than 250 figldl red blood cells 

(RBC's). Kamholtz et al.149 and Sassa et al.150 also 

showed a similar degree of correlation and indicated 

that a value of 140 fig FEP/dl RBC's would appear 

to be a more appropriate cut-off point for screening 

children for lead poisoning. This value, also suggested 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 
P.56 

49 figldl have erythrocyte protoporphyrin in excess 

of this value. Several additional studies have confirmed the exponential correlation between blood 

lead and erythrocyte protoporphyrin in childreni40,i53-i56anciinleadworkers.123'

133'140'157

.

158 

Sassa et al.150 demonstrated that a better correlation was observed between blood lead and 

erythrocyte protoporphyrin in children with a steady 

blood lead level. This finding suggested that a significant part ofthe 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 error. 

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 protoporphyrin 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 deficiency, but to a lesser degree. Several studies have 

indicated that erythrocyte protoporphyrin levels are 

an excellent indicator of the body iron store164165 

and that these levels may also be used to discriminate between the microcytic anemia of iron deficiency (where they are elevated) and of thalassemia trait 

(where they are normal).166"

168 

These observations and the data collected on over 

300,000 children screened by both erythrocyte protoporphyrin 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 figldl of whole blood in 

the presence of a blood lead level above 30 figldl 

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 figldl, Sassa et al.150 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 figldl, indicate a threshold 

effect at blood lead levels between 15 and 20 figldl. 

In a study by Piomelli et al.169 of 1816 children aged 

2 to 12 years (median age 4.7 years), the threshold 

for no effect of blood lead on erythrocyte protoporphyrin was estimated to be 15.5 figldl, using both 

probit analysis and segmental curve-fitting techniques. 

Because an elevation of erythrocyte protoporphyrin is caused also by iron deficiency, it is 

important to take into consideration the iron state of 

the population under study in any evaluation ofthe 

relationship of this hematological index to lead exposure. 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 ofthe 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 influence the EP response. Moreover, in the same 

study, the iron stores were measured in children with 

blood lead levels < 15 figldl and in children with 

blood lead levels of 15 to 28 figldl and no difference 

11-12 
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 

figldl. 

These studies consistently demonstrate that an 

elevation of erythrocyte protoporphyrin, which indicates 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 procedures. 

11.4.4 Other Hematological Effects 

The effects of lead on 8-ALAD and on iron incorporation in protoporphyrin are the best known. In 

lead intoxication, however, other abnormalities of 

heme synthesis are observed. These include an increased 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 rabbits'72 

and inhibition of uroporphyrinogen I synthetase173 

have been reported. On the other hand, no accumulation 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 protoporphyrin, 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 IO6 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 numbe r 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 burdens 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 fid Pb/dl, whereas the corresponding value for 

adults is about 50 fig Pb/dl. 

Lead interferes with hemoglobin synthesis by inhibiting 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-activated enzyme that mediates the conversion of two 

molecules of 8-ALA into prophobilinogen. Inhibition of this enzyme results in increased plasma levels 

and urinary excretion of 8-ALA. Lead also inhibits 

the last step (incorporation of iron into protoporphyrin), 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 protoporphyrin, 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/ig/dl. The resultant increased 

urinary 8-ALA excretion also starts at a very low 

blood lead level and becomes pronounced at a blood 

lead level 240/ig/dl. 

The precise threshold for coproporphyrin excretion 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 

/ig/dl in children. In adult females, the threshold is 

11-13 
P.58 

probably similar. In adult males, the threshold is 

probably slightly higher (20 to 25 /ig/dl). The 

threshold for increase in 8-ALA synthetase is not established, but increases have been noticed at blood 

lead levels of 240 /ig/dl. 

Although doubt exists as to the health-effects significance of 8-ALAD inhibition, increased urinary 

8-ALA excretion above 40 figldl is accepted as an 

effect probably reflecting physiological impairment.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 considered of greater physiological relevance.177

 For 

these reasons, the consensus of clinicians who participated in the preparation ofthe 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 NEUROPHYSIOLOGY AND BEHAVIOR 

Neurological and behavioral deficits have long 

been recognized as some of the more severe consequences of toxic exposure to lead.178182

 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 debated since the early 1900's. M uch 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 irreversible neural damage or death. The risk involved is unacceptable because of the unpredictability ofthe symptoms observed at high blood lead 

levels. Based on the literature reviewed below, 

it now also appears that lower levels of lead exposure, yielding blood levels below 80 /ig/dl, produce much less well-defined but medically significant neurobehavioral deficits in apparently 

asymptomatic adults and children, that is, in the absence of the neurological symptoms or other signs 

that typify acute lead intoxication requiring immediate 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 /ig/dl, whereas certain other negative findings suggest the lack of neurobehavioral effects at 

blood lead levels less than 80 /ig/dl. In an effort to 

estimate the exposure levels necessary for manifestation 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 exposure 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 approaches, 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 ofthese 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 , thes e 

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 
used to provide most nonhuman data. Although 

epidemiological studies have immediate environmental 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 correlated 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. Nevertheless, the contribution of lead exposure to any 

neurobehavioral deficit(s) can be reasonably estimated 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 laboratory. Unfortunately, however, appropriate experimental designs are frequently lacking. In addition, environmental 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 establishment of dose-response curves, and it is well 

known that a large species difference exists in sensitivity to lead,52

 so that adequate nonhuman exposure 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 exposure 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 maternal 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 

abov e difficulties, useful dat a 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 attention 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.I83186 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 convulsions, 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. I8518 7 

Symptoms of encephalopathy similar to those that 

occur in adults have been reported to occur in infants and young children, 8590 '

8518818 9

 with a 

markedl y higher incidenc e of severe encephalopathic 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 percent; Agerty,192

 20 to 30 percent; McKhann and 

Vogt,189 24 percent; Mellins and Jenkins,193 24 percent; 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 indi11-15 
P.60 

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*'99 On macroscopic examination the brains are often found to be 

edematous and congested. Microscopic findings of 

cerebral edema, altered capillaries (endothelial hypertrophy 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 encephalopathy is considered by some to be primarily a 

vasculopathy, with the encephalopathy reflecting 

perturbed blood-brain barrier function;198199 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 ofthe capillaries with swelling ofthe endothelial 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 permeability of the blood-brain barrier (dysoria). 

Concurrent with the dysoric alterations were 

change s tha t Pentschew1 9 8 attribute d to 

hemodynamic disorders. These ischemic changes 

were manifested as cell necrosis, perineuronal incrustations, or neuronophagia (loss of neurons). The 

isocortex and the basal ganglia were areas of predilection for the ischemic changes. Pentschew concluded 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 predilection 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 involve 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 observed 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 characteristically 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 occurrence of fatalities are the neurological sequelae that 

occur in cases of severe or prolonged nonfatal 

episode s of lead encephalopath y 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. 859019 3 The most 

severe sequelae in children are cortical atrophy, hydrocephalus, convulsive seizures, and severe mental 

retardation.8590193 More subtle sequelae also occur, 

such as impaired motor coordination, altered sensory 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.85T

86

-

9

''203 Of historical interest here in relation to the extremely slow progress 

in recognizing the full consequences of lead intoxication is the fact that, although many cases of childhood lead poisoning had been reported since the 

early 1900's,'80*'82 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 exposures necessary to produce the above acute intoxication symptoms or sequelae in humans is difficult 

in view ofthe usual inaccessability of extensive data 

on environmental lead levels contacted by the victim, the period of exposure, or the body burdens of 

lead existing prior to the manifestation of clinically 

significant symptoms. Nevertheless, enough information 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 Kehoe204206 blood lead 

levels well in excess of 120 /ig/dl are usually necessary to produce such deleterious irreversible effects 

for adults. Recurrent bouts of lead intoxication in 

11-16 
P.61 

the absence of acute encephalopathy may also lead 

to progressive mental deterioration. Other data exist, however,187

 that suggest that acute lead intoxication, including severe gastrointestinal symptoms or 

signs of encephalopathy or both, can occur in adults 

at lead levels somewhat less than 100 /ig/dl; but ambiguities in these data make interpretation difficult. 

The data on threshold levels for children indicate that lower blood lead levels have been associated 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 

Chisholm84207 and Chisholm and Harrison.90 That 

data compilation relates the occurrence of acute encephalopathy 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 associated with asymptomatic cases or less severe signs of 

acute lead poisoning were also tabulated. 

Asymptomatic increased lead absorption was observed at blood levels ranging from 60 to 300 /ig/dl 

(mean = 105 figldl). Acute lead poisoning 

symptoms, other than signs of encephalopathy, were 

observed from approximately 60 to 450 /ig/dl (mean 

= 178 /ig/dl). Signs of mild encephalopathy (hyperirritability, ataxia, convulsions) and severe encephalopathy (stupor, coma, convulsions repeated 

over a 24-hr period or longer) were associated with 

blood lead levels of approximately 90 to 700 or 800 

/ig/dl, respectively (means = 328 and 336 /ig/dl, 

respectively). The distribution of blood lead levels 

associated with death (mean = 327 /ig/dl) was essentially 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 encephalopathy and that such effects are manifested in children 

starting at blood lead levels of approximately 100 

/ig/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 /ig/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 encephalopathy 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 ofthe reports purportedly demonstrated acute encephalopathy in children at blood lead levels even down to 30 

to 50 /ig/dl. Detailed analyses of the articles 

referenced, however, indicate that the actual data 

reported in most did not clearly associate such lowlevel exposures to the occurrence of acute encephalopathy 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 /ig/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 /ig/dl, as well as 

190, 240, and 320 /ig/dl, were obtained for the 

different children upon first admission to the hospital. 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 /ig/dl reading was obtained 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 figldl. Eight children who had 

been previously classified as asymptomatic and who 

had blood lead levels of 50 to 80 /ig/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 reported2

" 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 possible long-term neurobehavioral deficits resulting 

from earlier acute encephalopathy episodes. Blood 

lead assays obtained at the time of the initial hospitalization of the children because of acute encephalopathy symptoms (4 out of 10 had convulsions, 8 out of 10 had ataxia, 7 out of 10 had drowsiness, and 6 out of 10 had irritability) yielded maximum blood lead values that averaged 88 ± S.D. 41 

/ig/dl. Because individual cases were not described, 

however, no clear association between particular 

lead intoxication symptoms and specific blood lead 

11-17 
P.62 

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 /ig/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 /ig/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 /ig/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 determinations of blood lead. In any case, in attempting 

to estimate exposure levels for adverse health effects 

of lead, the range of exposure levels yielding damaging 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 appear that the most susceptible individuals do not exhibit acute encephalopathy symptoms until blood 

lead levels of 100 /ig/dl are reached or, more 

typically, are substantially exceeded. In regard to 

children, the majority of cases showing acute encephalopathic symptoms have blood lead levels of 

100 /ig/dl or more. For a very few cases, levels as 

low as 80 /ig/dl have been reported. 

11.5.1.2 EFFECTS OF LOW-LEVEL LEAD EXPOSURES 

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 /ig/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 occupationally 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 physicians. No correlation between elevated blood lead 

levels and sickness rates or types of symptoms reported were found212

 for groups of workers in a lead 

storage battery factory from high-, medium-, and 

low-exposure areas versus control workers in nonexposure 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 /ig/dl, 

respectively, compared with 45 /ig/dl for the socalled 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 /ig/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 /ig/dl). In 68 percent of the subjects, 

blood lead was <80 /ig/dl. The majority ofthe subjects 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 handeye coordination. This study, therefore, suggested 

that below a blood lead level of 80 /ig/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 exposure. Unfortunately, aspects of the Morgan and 

Repko work can be criticized because of 

methodological problems, including reported ap11-18 
P.63 

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-exposed workers on a number of psychometric and 

other performance tests. 

In addition to the above study213 suggesting possible CNS dysfunctions, numerous investigations have 

provided electrophysiological data indicating that 

peripheral neuropathy symptoms are associated at 

times with blood lead values < 80 /ig/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.217219 More recently, such peripheral 

nerve deficits were established by Seppalainen220 for 

lead workers whose blood lead levels were as low as 

50 /ig/dl and had never exceeded 70 /ig/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 automobile mechanics exposed to TEL and other lead 

compounds in lubricating and high-pressure oils. 

Results ofa multielemental analysis ofthe 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 peripheral neuropathy effects were reported for leadindustry workers with blood lead values of 29 to 70 

/ig/dl. The very low blood lead levels, below 50 

/ig/dl, reported in some of the above studies, 

however, should probably be viewed with caution 

until further confirmatory data are reported on samples of larger size using well verified blood assay 

results. 

In summary, the above studies, when taken 

together, appear to provide reasonably strong evidence that subclinical peripheral neuropathies occur 

in some adults having blood lead levels in the 50 to 

70 /ig/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 always below 70 /ig/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 assessment 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 collectively with the data from other studies reviewed 

above, strong evidence appears to exist for peripheral neuropathies occurring in adults at blood lead 

levels of 50 to 70 /ig/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 exposures producing blood lead levels of 40 to 80 

/xg/dl (or even less) in children may induce subtle 

neurological damage, especially to the very young 

developing CNS. This issue has attracted much attention and generated considerable controversy during 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 ofthe 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 control 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 investigators in an effort to assess whether indications 

of continuing neurobehavioral impairment still existed. 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,223224 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 
P.64 

results. Two other studies, one by Landrigan et al.231 

and one by Kotok et al.,232 although not reporting 

clearly statistically 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 figldl are the work of de la Burde et 

a l 223,224 an(- pe r i n o and Ernhart.225De la Burde et 

al.223 observed dysfunctions ofthe 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 /ig/dl, mean = 59 /ig/dl) in comparison 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 neurological 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.223224 studies appear 

to be methodologically sound, having many features 

that strengthen the case for the validity oftheir findings. 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 initial 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 inappropriate use of multiple chi-square statistical analyses in 

the manner employed to analyze the results of the 

study. Upon recomputation ofthe statistical significance of observed differences, by means ofthe more 

appropriate Fisher's exact probability test and accounting for the number of tests conducted, several 

measures originally reported to be statistically significant 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 ofthe results obtained. Because it is 

stated that the lead-exposed group included 

children with blood lead levels of 40 to 100 /ig/dl, 

or of at least 30 /ig/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 

Betts etal.101 indicates that lead lines are usually not 

seen unless blood levels exceed 60 /ig/dl 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 /ig/dl. Virtually none have lead lines at levels below 40 /ig/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 /ig/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 ranging from 40 to 70 /ig/dl in a group of 80 inner-city 

preschool black children. One of the more interesting aspects ofthe findings, is that the normal correlation 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 ofthe methodological 

virtues of the de la Burde studies223224 were also 

present in the Perino and Ernhart225 work, and 

blood lead determinations and statistical analyses 

appeared sound. About the only alternative explanation for these results might be differences in the 

educational backgrounds of the parents of the control subjects when compared with lead-exposed subjects, 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 
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 studies233235 

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 /ig/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 limitations. Albert et al.226

 found that asymptomatic 

children (5 to 15 years old) whose blood lead levels 

at an earlier age were elevated ( > 60 /ig/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. Unfortunately, however, no assay ofthe 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 /ig/dl. Also, another major criticism is that some 

children in the control group had relatively high 

blood lead levels ( > 40 /ig/dl). In another study, 

Landrigan et al.227 found that asymptomatic, leadexposed children living near a smelter scored significantly lower than matched controls on measures of 

performance I.Q. and finger-wrist tapping. The control 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 remained statistically significant even after appropriate adjustments were made for age differences. 

In another relevant study, presented in a doctoral 

dissertatio n by Rummo, 2 1 1 significan t 

neurobehavioral deficits were found (hyperactivity, 

lower scores on McCarthy scales of cognitive function, etc.) for children who had previously experienced high levels of lead exposure that had produced acute lead encephalopathy. Mean maximum 

blood lead levels for those children at the time of encephalopathy were 88 ± S.D. 40 /ig/dl. Children 

with moderate degrees of blood lead elevation, 

however, were not significantly different from controls on any measure of cognitive functioning, psychomotor 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 

arid duration of lead exposure becomes apparent. 

95 

90 

85 

80 

75 

1 1 

ki 

1 1 

V -

\ -

\ -

* — 

1 1 

CONTROLS 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 T 

MOTOR 

PERCEPTUAL 

VERBAL 

MEMORY 

QUANTITATIVE 

CONTROLS 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-exposure 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 significant 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 shortterm and long-term exposure subjects were all >4 0 

11-21 
P.66 

/ig/dl (means = 61 ± S.D. 7 and 68 ± S.D. 13 

/ig/dl, respectively), whereas control subjects all 

had blood lead levels below 40 /ig/dl (mean = 23 ± 

S.D. 8 /ig/dl); and (2) the control and lead-exposed 

subjects were inner-city (Providence, Rhode Island) 

children well matched for socioeconomic background, 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 /ig/dl were compared 

with 31 asymptomatic children having distinctly elevated blood lead levels (61 to 200 /ig/dl). Both 

groups were well matched on important background 

factors, including, notably, their propensity to exhibit 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 ofthe control-group children were consistently higher than those ofthe lead-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 cognitive or educational deficiencies." They also indicated 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 controlled evaluation of asymptomatic children residing 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 

studies223224 and others reviewed above that report 

results linking low to moderate levels of lead exposure to significant behavioral impairments. 

Other studies have produced mixed or negative 

results in attempts to determine whether a relationship exists between lead exposure and CNS deficits 

TABLE 11-3. COMPARISON OF TEST RESULTS IN LEAD 

AND CONTROL GROUPS232 

Ability class 

Social maturity 

Spatial 

Spoken vocabulary 

Informationcomprehension 

Visual attention 

Auditory memory 

Group 

Lead 

Control 

Lead 

Control 

Lead 

Control 

Lead 

Control 

Lead 

Control 

Lead 

Control 

Mean I.Q. ± S.D. 

123.5 ± 22.7 

126.3 ± 17.7 

92.0 ± 18.0 

100.8 ± 18.7 

91.7 ± 13.9 

92.9 ± 13.7 

94.5 ± 14.9 

96.3 ± 16.6 

89.7 ± 18.3 

93.3 ± 23.0 

93.0 ± 24.0 

99.9 + 32.0 

Significance 

p>.10 

.10 >p >.05 

p>.10 

p>.10 

p>.10 

p >.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 development) in a group of asymptomatic children having 

elevated lead levels (58 to 137 /ig/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 figldl). 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 /ig/dl, whereas some 

of the controls had blood lead levels as high as 55 

/ig/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 versus 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 relationship between blood lead level and mental functioning was found. Only a minority of the lead-exposed sample had blood lead levels over 40 /ig/dl, 

however, one would not expect a striking relationship between mental functioning and lead levels below such a level. 

In an extensive, generally thorough study, McNeil 

et al.230 found that a sample of children living near a 

lead smelter in El Paso was comparable,medically 

11-22 
and psychologically to matched controls living 

elsewhere in the same city other than in the direct 

effects of lead (blood lead level, free erythrocyte 

protoporphyrin levels, and X-ray findings). Leadexposed children in the group living near the smelter 

did, however, have significantly different personality 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 ofthe smelter. Considerable 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 associated 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 information. The personality test results ofthe 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 between lead and age of subjects (p <.10) were reported 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 concluded that no evidence was found for the occurrence of neurobehavioral effects at subclinical lead 

exposure levels in their studies. Perhaps that conclusion could be generalized to suggest that no significant 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 figldl, 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 neuropathies for both populations of children at low to 

moderate lead exposure levels, as described, may indicate 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 significant neurobehavioral deficits. This approach consists of identifying populations of children with diagnosed 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 example, efforts have been made to implicate moderate 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 exposures induce hyperactivity has gained credence 

through the well documented87203 fact that hyperactivity is one of the frequent neurobehavioral sequelae observed in children who survive episodes of 

acute encephalopathy resulting from high-level lead 

exposures. The evidence for and against the hypothesis that low-level lead exposures produce hyperactivity has been accumulating at a rapid rate 

during the past few years and has generated considerable 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 hyperactive children with a possible cause; (4) a group 

of children who had recovered from lead poisoning; 

and (5) a nonhyperactive control group. Pure hyperactive children had statistically significantly 

higher blood lead levels (mean = 26.2 ± 8 figldl) 

than controls (mean = 22.2 ± 9.6 /ig/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 relationship 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 demonstrating alterations in motor activity following lead administrations, 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 
P.68 

author's conclusion6 can be questioned on several 

bases. In that study, for example, the closeness ofthe 

match of subjects in the five groups oij 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 #ie least of 

which is the fact that such levels are probably not 

very accurate indices of long-past lead exposures 

that presumably occurred during presclhool 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 subjects. 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 predispose the affected child toward more lead ingestion by virtue ofthe habit's presence. Indteed, 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 modterately elevated blood lead.238

 Last, it should be noted that a 

number of other investigators,2".227,229.230,239 wn o 

expressly looked for evidence of lead-induced hyperactivity as part of their screening for 

neurobehavioral deficits associated with blood lead 

levels as low as 40 figldl, failed to find any significant 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 associated with low or moderate lead exposures. 

In addition to the above data bearing on possible 

links between subclinical lead exposures and the induction of hyperactivity, certain recently reported 

data 2 4 0 provide evidence implicating increased 

heavy metal absorption, including lead uptake, in 

the etiology of learning disabilities. More 

specifically, children identified for other classification 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 discrimin»ant function 

analysis yielded 98 percent accuracy im classifying 

children as normal or learning disabled based on a 

combined factor of cadmium, cobalt, manganese, 

chromium, and lithium levels. Lead was not included in this five-metal discriminant function, since 

its predictive value was well served by cobalt and 

cadmium because of a significant negative correlation 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 ofthe 

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 /ig/liter), whereas 11 of the 

64 retarded children came from homes served with 

water containing high lead levels. The authors conclude 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 

/iMol/liter (25.5 ± 8.9 /ig/dl) and for normals was 

1.0 ± 0.38 /iMol/liter (20.9 ± 7.9 figldl). The 

difterence 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 intrauterine exposure to lead. Insufficient information 

exists, however, to allow estimation ofthe 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 

11-24 
possible induction of peripheral neuropathies by 

low-to-moderate lead exposures. It is generally accepted 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-induced peripheral neuropathies, as indexed by 

electromyography, assessments of nerve conduction 

velocity, and observations of other overt neurological 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 /ig/dl,245 and in other cases peripheral 

neuropathy was associated with blood lead values of 

30 /ig/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 

/ig/dl and probably in excess of 60 /ig/dl (based on 

the data of Betts et al.101). In each ofthe 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 childhood lead exposure. Most of the cases reported involved inner-city black children, several with sickle 

cell trait. In summary, it appears that (1) evidence 

for frank peripheral neuropathy in children certainly exists; (2) such neuropathy can be associated 

rather well with blood lead levels at least as low as 

60 /ig/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. 

> 62.00 

z 

O 

o 56.80 -

° 51.60 -

lll l 

YICONDUCTION VELOCITYI = 

_ Ir •= • 0.381 In = 202) 

— • 

• 

• 

— • 

• • 

_•••• • • 

— •• •V . # • amI a • • 

«••..•• •"# • •• • 

—*!%*&*+ : 

• mzTr9—*"y!-»-jL • 

• • a a a a • 

. • * 

• • 

. • • 

1 1 1* 1 

lll l 

54.8 - .045 x (BLOOD LEAD) 

• 

**. 

• 

• • 

1 1 1 1 

" 

-

— 

0 15 30 45 60 75 90 105 120 135 150 

BLOOD LEAD, <rg/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 functions. Among the key points to be addressed are: (1) 

the internal exposure levels, as indexed by blood 

lead levels, at which variou s advers e 

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 occurrence 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 /xg/dl are reached. Evidence does exist, 

however, for the occurrence of acute encephalopathy and death in some adults at blood lead levels 

somewhat below 120 figldl. For children, the effective blood lead levels for producing encephalopathy 

or death are lower, typically starting at approximately 100 /ig/dl. Again, however, good evidence 

exists for the occurrence of encephalopathy in some 

at lower levels, i.e., 80 to 100 /ig/dl. 

11-25 
P.70 

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, certain diagnostic or treatment procedures themselves 

tend to exacerbate matters and push the outcome 

toward fatality ifthe nature and severity ofthe problem 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 obvious encephalopathic symptoms. This tends to be 

borne out by studies showing that children having 

high blood lead levels (over 80 to 100 /ig/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 summarized in Table 11-4, present overall a rather impressive array of data pointing to that conclusion. 

Several well-controlled studies have found effects 

that are clearly statistically significant, whereas 

others have found nonsignificant but borderline 

effects. Even some studies reporting generally nonsignificant findings at times contain data confirming 

statistically significant effects, which the authors attribute 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 /ig/dl. Great uncertainties remain, 

however, as to whether these exposure levels (observed blood lead levels) represent the levels that 

were responsible for the behavioral deficits observed. 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 reported 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, primarily 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 ofthe 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 penetrates 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,247 and 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 
P.71 

Reference 

De la Burde and 

Choate (1972)2*3 

Oe la Burde and 

Choate (1974)22* 

Perino and 

Ernhart (1974)225 

Pueschel etal. 

(1972)99 

Landrigan et al. 

(1975)22? 

Rummo (1974)2" 

' 

TABLE 11-4. SUMMARY OF RESULTS OF HUMAN STUDIES ON NEUROBEHAVIORAL EFFECTS 

Population 

studied 

Inner city 

(Richmond, VA) 

Followup 

same subjects 

Inner city 

(New York, NY) 

Inner city 

(Boston, MA) 

Smelter area 

(El Paso, TX) 

Inner city 

(Providence, Rl) 

AT MODERATE BLOOD LEAD LEVELS 

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 

Age at 

testing, yr 

4 

4 

7 

7 

3-6 

3-6 

? 

? 

3-15 (x= 9.3) 

3-15 (x= 8.3) 

4-8 (5=5.8) 

4-8 (x**= 5.6) 

4-8 (x = 5.6) 

Blood lead. 

mm 

Not assayed' 

40-100" 

See above" 

See above" 

10-30 

40-70 

<40 

>40 

<40 

40-68 

x= 23± 8 

7= 61± 7 

x= 68± 13 

Psychometric 

tests employed 

Stanford Binet IQ 

Other measures 

WISC Full Scale IQ 

Neurologic exam 

Other measures 

McCarthy General 

Cognitive 

McCarthy Subscales 

Stanford-Binet IQ 

Neurologic exam 

WISC Full Scale IQ< 

WPPSI Full Scale 

IQWISC + WPPSI 

Combined 

WISC + WPPI 

Subscales 

Neurologic testing 

McCarthy General 

Cognitive 

McCarthy Subscales 

Neurologic exam 

rating 

Summary of results 

( C= control; Pb= lead)3 

C= 94 Pb= 89 

C >Pb on 3/4 tests 

C=90Pb=87 

C better than Pb 

C >Pbon9/10 

tests 

C= 90 Pb= 80 

OPbo n 5/5 scales 

C= ?Pb= 86 

C better than Pb 

C=93Pb=87 

C= 91 Pb= 86 

C= 93 Pb= 88 

OPbo n 

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 

TT'TTT- '- - - " 

Levels of 

significance" 

p <.05 

N.S.-P <.01 

p <.01 

p<.01 

N.S.p <.001 

p <.01 

N.S.p <.01 

— 

p<.001 

N.S. 

N.S. 

p <.01 

N.S.p <,01 

N.S.p <.001 

N.S.p <,01 

(pvsC) 

N.S.p <.01 . 

(pvsC) 

N.S. 

Kotok et al. 

(1977)232 

Inner city 

(Rochester, NY) 

Post enceph Pb= 10 4-8 (x= 5.3) 

Control=36 1.9-5.6 (x= 3.6) 

Lead=31 1.7-5.4 (x= 3.6) 

x= 88 ± 40 

11-40 

61-200 

Kotok (1972)228 

Lansdown et al. 

(1974)229 

McNeil etal. 

(1975)230 

Inner city 

(New Haven, CT) 

Control = 25 

Lead= 24 

1.1-5.5 (x= 2.7) 

1.0-5.8 (x= 2.8) 

Inner city Control = 172 616 

(London, England) Lead= 43 616 

Smelter area Control= 61-152 1.5-1.8(Mdn= 9) 

(El Paso, TX) 

Lead= 23-161 1.5-1.8(Mdn= 9) 

20-55 

58-137 

<40 

40-60+ 

<40 

>40 

Objective neurologic tests 

IQEfor six ability 

classes: 

Social maturity; 

Spatial relations; 

Spoken vocab; Info, 

comprehension; 

Visual attention; 

Auditory memory 

Denver 

Developmental 

Scale 

WISC 

WAIS 

McCarthy General 

Cognitive 

WISCWAIS Full 

Scale IQ 

Oseretsky 

Motor Level 

California Personality 

Frostig Perceptual 

Quotient 

Finger-Thumb 

Apposition 

C+S>L>Pon 

3/12 tests 

IQ Equivalent for 

each: 

C= 126Pb=124 

C= 101 Pb= 92; 

C= 93 Pb= 92; 

C= 96 Pb= 95; 

C= 93 Pb= 90 

C= 100 Pb= 93 

OPbon 1/3 

Subscales 

C= 100 

Pb= 101105 

C=82Pb=8 1 

C=89Pb=8 7 

C= 101 Pb= 97 

C= 80 Pb= 72 

C= 100 Pb= 103 

C= 27 Pb= 29 

N.S.p <.01 

(pvsC) 

p <.10for 

spatial 

p > . 10for all 

other ability 

classes 

N.S. 

N.S. 

N.S. 

N.S. 

N.S. 

N.S. 

N.S. 

N.S. 

a

 Mean test scores obtained for control children are indicated by C = T; mean scores for respective lead-exposed groups are indicated by Pb = x (except for Rummo'--' study where C = control, S = short-term lead-exposed subjects; L = long term lead-exposed group and P = postencephalopathy lead group). 

bN.S. = nonsignificant, i.e. p >.05. Note exception of p <.05. Note exception of p < . 10 listed for spatial ability results in Kotok et al. 2 3 2

 study. 

^Urinary coproporphyrin levels were not elated. 

<

- Or 30 /xg/dl or above with positive radiologic findings. The latter suggest earlier exposure in excess of 50-60 Mg/dl. 

e

 Assays for lead in teeth showed the Pb-exposed group to be approximately twice as high as controls (202 /ig/g vs. 112 /ig/g, respectively). 

Used for children over 5 years of age. 

8 Used for children under 5 years of age. 

11-27 
P.72 

astrocytosis and glial nodules were found in white 

matter along with perivascular exudate. 

Lead encephalopathy in the mouse was first described 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 concluded that no cerebral edema and focal destructive 

lesions were found in the mouse brains. Therefore, 

the histological response of the suckling mouse exposed 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, making the external exposures roughly equivalent. 

Wells et al.251 have recently reported on experimental 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 ofthe brains 

of exposed animals revealed focal vacuolation ofthe 

neuropil, neuronal necrosis, and changes in the 

capillary walls in the cerebral cortex and in subcortical 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 associated with lead encephalopathy vary among 

species and are characterized by their relative involvement of neuronal degeneration and vasculopathy. 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.253 reported that lead interferes 

with potassium-stimulated respiration of rat 

cerebral cortex slices, and Nathanson et al.17 reported that lead inhibited brain adenyl cyclase in 

vitro. No distinction can be made in these studies, 

however, between neuronal 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 encephalopathy in adult guinea pigs with no cerebral 

edema or increased capillary permeability, whereas 

the suckling rat shows these effects almost exclusively. 

Since the initial description of lead encephalopathy in the rat by Pentschew and Garro,52

 considerable 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 organism. The interpretation ofa large number of experU 

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 undernutrition in experimental animals. Changes in nutritional 

status during early brain development are known to 

produce changes in behavior.254255 Castellano and 

Oliverio,256 for example, reported a marked delay in 

neurological development, an increase in exploratory locomotor activity, and a lowered avoidance performance 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 reported 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, nutritional 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 contribution 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-

-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 toxicity of lead. Additional research is needed in this 

area, and until further data are available on the influence of varying degrees of overnutrition, variation 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, reproductive, and neurological development.247250260261

 Unfortunately, in a number of studies either no control 

was provided for undernutrition,250260262 or undernourished pair-fed controls showed similar developmental 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 experiment, 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 pairfed litters, however, differed in the relative reduction 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 ofthe 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 exposed 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 ofthe 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 opening, 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-related delay in vaginal opening in female rats exposed 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 secondary to body weight changes. 

Der et al.266 reported on the combined effect of 

parenteral administration of lead acetate and low 

protein diet (100 fig 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 fig 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 administration (5 mg/ml in the drinking water at parturition) on sexual maturation in the mouse. Vaginal 

opening was delayed about 4 days in lead-treated 

animals. No delay in development was seen in pairfed 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 related 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, locomotor activity is influenced by a variety of factors that 

11-29 
P.74 

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 examined the effects of various brain lesions on ambulation 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 activity 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 measurements do not represent a unitary behavior; careful 

consideration must be given to the particular experimental methods employed. In addition, attempts to 

extrapolate the results of an activity measurement in 

animals directly to the clinical situation are unwarranted. 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.*'* 

Bornschein etal. 2 7 0 

Brown"" 

Driscoll and 

Stegner"" 

Gray and Reiter"'1 

Hastings etal."'* 

Kostas etal." " 

Species 

Monkey 

Mouse, (Charles 

River) CD-I 

Rat(Bar F • 

Rabbitry) 

Rat (Simonsen) 

Mouse, (Charles 

River) CD-I 

Rat, (LongEvans, 

Charles 

River) 

Rat(Long-Evans) 

Blue Spruce 

Exposure 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.O. to dams 

from parturition to 21 

days 

10* and 10" 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 

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 

Lead concentration. ^1 % 

Blood Brain 

160-400 

120-190 200-306 

Control 

= 11±4 

0.2 mg/ml 

= 29±5 

1.0 mg/ml 

= 42±4 

Test conditions, in order o 

presentation: 

1. Method 

2. Length of testing 

3. Group size 

4. Aje 

Observed locomotor 

activity 

Proximity counter 

3 hours 

Individual 

35 days 

Photoactometer 

20 min 

Individual 

49 days 

Open-field 

2 min 

Individual 

31 days 

Residential maze 

90-240 min 

Individual 

30, 50,130 days 

Running wheel 

3 weeks 

Individual 

30-51 days 

Shuttle box, activity 

wheel 

1 hr 

Individual 

75-77 days; 90-93 

days 

Nutritional 

status 

Normal 

Undernourished 

Undernourished 

Undernourished 

Normal 

Results 

Hyperactivity 

(qualitative measures) 

Normal 

Normal 

Hypoactive (61% of 

control) 

Hypoactive (75-80% of 

control) 

Normal 

Normal - 0.05% group Hyperactivity in shuttle 

undernourished in box (182% of control). 

5-5.0% Normal in activity 

wheel. 

11-30 
TABLE 11-5 (continued). 

Reference 

Overman275 

Reiter"'" 

Reiter etal."76 

Reiter et al.2'

4 

Cahill etal.27' 

Reiter etal.2"' 

Sauerhoff and 

Michaelson278 

Sauerhoff27' 

Silbergeld and 

Goldberg262.280.28i 

Species 

Rat, (LongEvans 

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 

Sobotka and Cook2"

2

 Rat, Sprague 

and Sobotka et al.283 Dawley (Charles 

River) 

Sobotka etal.284 

Winneke etal.28' 

Zenicketal.2"" 

Dog (Beagle) 

Rat (Wistar) 

Rat, Sprague 

Exposure conditions 

10, 30, 90/mg/kg/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 concentration. fig% 

Blood 

21 days 

90 mg/kg 

= 226± 21 

35 days 

90 mg/kg 

= 56±5 

180 day 

males 

0= 5± 0.5 

5= 6+ 0.4 

50= 10± 

0.6 

22 days 

81 mg/kg 

= 71±12 

35 days 

81 mg/kg 

= 23±1.4 

16 days 

26.6 

190 days • 

28.5 

Brain 

180 day 

males 

0=18+ 

50= 20± 

50= 27± 

29 days 

88± 1.1 

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 min; 14 days 

Individual; group of 3 

13-44 days; 120-160 

days 

Residential maze 

5 days 

Groups of 3 

2 120 days 

2 

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 

30 min 

Individual 

24-28 days 

Open field 

Individual 

3-4 months 

Open field 

3 min, on consecutive 

days 

Individual 

90-140 days 

Open field 

3 min, on 10 

consecutive days 

Individual 

22-32 days 

Nutritional 

status 

Normal 

Undernourished 

Normal 

Undernourished 

Undernourished 

Undernourished 

Normal 

Not indicated 

Normal 

Undernourished 

Results 

Hyperactive 

Transient hyperactivity 

(200% of control at 13 

days). Normal at 44 

days. Normal levels in 

adults; but disrupted 

ultradian rhythms. 

Hypoactivity (53-78% of 

controls) 

Normal 

Hyperactive at 29 days 

(140190% of control) 

Normal at 50 days 

Hyperactivity (300-400% 

of control) 

Normal 

Hypoactive 

Hyperactive (129% of 

control) 

Initial hypoactivity in 

100 mg/kg group (days 

1 and 2) Hyperactive by 

the 7th test day. 

11-31 
P.76 

The data to be reviewed here suggest that 

perinatal lead exposure produces an altered reactivity of an animal to a novel environment. Reactivity is increased in the young animal, but this increased reactivity disappears as the animal matures. 

In the adult animal, on the other hand, the lead exposure results in a reduced reactivity. As will be 

seen, the exact nature ofthe change in locomotor activity brought about by this altered responsiveness 

will depend heavily on the structure of the test environment. 

Sauerhoff and Michaelson278 and Sauerhoff279 exposed 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 

ofa 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 stationary 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 impairment. 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 observed increase in activity was consistent with a 

lead-induced change in locomotor reactivity. In this 

experiment, pups were directly exposed by daily intubation ranging from 10 to 90 mg/kg/day. This exposure 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 activity in a photoactometer. 

One striking difference between these two experiments was in the reported blood lead levels, shown 

in Table 11-6. Therefore, the higher internal exposure seen in Overmann's experiment may have accounted for the difference in the observed 

behavioral effects, although differences in experimental 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 lead.ug/dl 

Experiment 21 to 22 days 35 days 

Sobotka and Cook

 282 

and Sobotka etal. 2" 

(81 mg/kg/day) 

Overmann275 

(90 mg/kg/day) 

71 ± 12.4 23 ± 1.4 

226.1 ± 21.1 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 reported 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 ambulating at a higher level than controls. These data can 

also be interpreted as an increased locomotor reactivity in lead-treated animals that is initially 

manifested in an open field as decreased ambulation. 

With repeated exposure, the animals show an elevated activity similar to that in previously reported 

studies. The difference in the direction of lead-induced change in initial activity levels in these open 

field experiments as compared to the jiggle platform 

experiments 25827 5 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 exposed to lead by suckling with mothers receiving 1 

mg/ml lead in the drinking water. This exposure 

resulted in blood lead values of 42 figldl 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. 2 7 6 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 exposure to lead may produce a decreased reactivity in 

the adult animals. Kostas et al.274 measured locomotor activity in adult rats exposed to either 0.05, 0.5, 

or 5.0 percent lead carbonate in the chow from parturition until weaning and to 0.25, 2.5, or 25 ppm 

from weaning until 35 days of age. Two measurements 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-induced changes in activity is consistent with the finding 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 indicated 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, including exploratory, diurnal, and nocturnal activity. Exploratory activity was initially suppressed in leadtreated animals, but this difference disappeared as 

the animals became established in the environment. 

On the other hand, activity levels remained suppressed during the nocturnal period. 

In a second study, Reiter et al.276 reported no 

difference in residential-maze activity of adult leadtreated animals. They speculated that the lack of a 

lead effect on locomotor activity in the second experiment 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 exposure, 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 reactivity which disappears as the animal matures. This 

effect could result from a delay in normal maturation of forebrain inhibitory systems.287

 As the leadtreated 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 ambulation 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 hyperactivity 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

-

28' reported lead-induced hyperactivity in mice. Lactating females were exposed to 

lead acetate in the drinking water, starting at parturition, 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 ofa control for the growth retardation found in the ieadtreated groups makes interpretation of these data 

difficult. As previously indicated, Castellano and 

Oliverio256 reported that early undernutrition produces hyperactivity in mice. Therefore, the observed 

hyperactivity may have resulted from the undernutrition, independent ofa lead effect. Greater concern, however, stems from the subsequent failure of 

11-33 
P.78 

two different laboratories261-

270289

 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

 They 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 demonstrate 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 notably, they reported that their lead-treated, hyperactive mice responded paradoxically to the stimulants 

amphetamine and methylphenidate. Examination of 

the activity data following administration of 

methylphenidate28' 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 ofthe leadtreated 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 characteristically 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 contribution of early undernutrition to these results must be 

considered. Bornschein et al.270 found this paradoxical lowering of activity in undernourished mice 

following 10 mg/kg of d-amphetamine, but only during the second hour following drug administration. 

In the first hour, activity showed the expected increase, 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 paradoxical 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.264 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 exposure in young children can produce overt 

manifestations of neurotoxicity.182-

203

 Mental retardation is an established sequela of lead-induced encephalopathy 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 previously, 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 unsatisfactory control groups.291 

In an attempt to overcome some of these limitations, 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 ofthe pertinent studies, including 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 exposure conditions and (2) the stage of learning during 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 
P.79 

utilized to quantify the process are numbers of days of the quantitative nature of the behavior after the 

and trials or problem presentations required to desired criterion has been attained. The reversal/exreach some predetermined level of performance. 

The percentage of the test population attaining the 

defined criterion per unit time is also a common 

tinction column contains studies of behavior observed following the removal of (extinction) or 

alteration of (reversal) the conditions that produce 

measure. The performance column includes studies reinforcement. 

TABLE 11-7. PROTOCOLS USED FOR THE STUDY OF ANIMAL LEARNING 

Reference 

Brady 

et al.»" 

Brown, D.271 

Brown, S. 

et al." " 

Driscoll and 

Stegner?"" 

Overmann29* 

Snowdon"95 

Sobotka 

etal.2«3 

Species 

Rat 

Rat 

Rat 

Rat 

Rat 

Rat 

Rat 

Behavioral tasl 

Apparatus 

water 

T-maze 

T-maze 

T-maze 

Tmaze 

T-maze 

Tmaze 

T-maze 

T-maze 

water 

Tmaze 

Shuttlebox 

Y-maze 

Shuttlebox 

Shuttlebox 

Shuttlebox 

E-maze 

E-maze 

E-maze 

2-compart 

ment chamber 

2-compartment chamber 

Operant 

CF maze 

CF maze 

Shuttlebox 

Reward 

neg. 

pos. 

pos. 

pos. 

pos. 

pos. 

pos. 

pos. 

neg. 

neg. 

pos. 

neg. 

neg. 

neg. 

pos. 

pos. 

pos. 

neg. 

neg. 

pos. 

pos. 

pos. 

neg. 

Task" 

Simult. 

BD. 

Succ. 

B.D. 

Succ. 

B.D. 

Succ. 

B.D. 

Succ. 

B.D. 

Succ. 

B.D. 

Succ. 

B.D. 

Succ. 

B.D. 

Spatial 

discrim. 

2-way 

Simult. 

B.D. 

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 

Periodb 

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 

t 

L 

L 

L 

Adult 

exposure 

andPW 

L 

3-21 days 

postpartum 

exposure 

Level" 

500 GAV 

100 W 

25 GAV' 

35 GAV 

35 GAV" 

70 GAV 

140 GAV 

5 IP" 

100 IP* 

100 IP" 

2070 DT< 

2070 DT' 

2070 DT' 

2070 DT' 

5,16,49 

GAV 

5,16,49 

GAV 

5,16,49 

GAV 

5,16,49 

GAV 

* 5,16,49 

GAV 

5,16,49 

GAV 

2.7,4.4 

6.6 IP" 

4.4 IP« 

5.15,44 

GAV 

Number 

Litter 

per test 

group 

4 

? 

7 

7 

7 

7 

7 

7 

7 

7 

7 

7 

7 

7 

7 

7 

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 

Grow1hd 

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 

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 

Mg/dl 

Attest 

7 

7 

7 

7 

7 

7 

7 

23 

7 

7 

7 

7 

7 

7 

15,23, 

56 

7 

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 

11-35 

(continued) 
P.80 

TABLE 11-7 (continued). 

Lead exposure 

Number 

Reference Species Apparatus Reward Task" Penodb 

Litter Subjects 

per test per test Growth 

Level" group group rate 

Blood lead, fig/d! 

Learning 

Peak At lest performance 

Sobotka and Rat 

Cook"2 

Carson 

et al.30i.302 

and VanGelder 

et al.soo 

Sheep 

Bowman and Monkey 

Bushnell~43 

2-

compartment 

chamber 

Shuttlebox 

Shuttlebox 

Operant 

Slecta«6 

Shapiro 

etal. 2" 

Hastings 

etal. 2" 

Winneke 

et al.285 

Bornschein298 

Bornschein2'" 

Sobotka 

etal.284 

VanGelder 

etal.300 

Rat 

Rat 

Rat 

Rat 

Mouse 

Mouse 

Dog 

Sheep 

Operant 

Operant 

Shock 

grid 

Shock 

grid 

Operant 

Lashley 

jumping 

stand 

Operant 

Operant 

Tmaze 

Operant 

Operant 

Operant 

CF maze 

CF maze 

Operant 

WGTA 

neg. 

neg. 

neg. 

neg. 

pos. 

pos. 

neg. 

neg. 

pos. 

pos. 

pos. 

pos. 

pos. 

pos. 

pos. 

pos. 

pos. 

pos. 

pos. 

pos. 

passive 

avoid 

1-way 

2-way 

Spatial 

discrim. 

Fl 

schedule 

VI 30 

schedule 

Flinch 

SEA 

Succ. 

B.D. 

Simult. 

PD&SD 

Simult. 

B.D. 

Simult. 

B.D. 

Simult. 

R.O. 

Auditory 

discrim. 

Fl 

schedule 

Fl 

schedule 

Maze 

learning 

Maze 

learning 

Simult. 

FD&SD 

3-21 days 

postpartum 

PW (day 

22-57) 

PW (day 

90126) 

PG.G.L 

PW 

2-week5 month 

postpartum 

Adult exposure 

9 weeks 

5 days12 weeks 

post partum 

G 

L.PL 

5,15,44" ? 

GAV 

7 

50,300 — 

1000 W' 

.09 • 52 — 

IP« 

109, 

546 W' 

109, 

546 W' 

109, 

546 W' 

745 OT' — 

103,546 5 

2730 W' 

109,546 7 

W' 

1.4 W' — 

100 GAV — 

1000 DT' — 

530 DT' — 

2.3,4.5" — 

DT 

2,4,8,16" — 

DT 

2,3,4,5" — 

DT 

0.3,1.0 — 

5-8 

5-8 

5-8 

5-8 

3 

10 

10 

10 

10 

15 A 

14 N 

10 N 

18,61,71 

18,61,71 

18,61,71 

18,61,71 

9,28,40 

29,42 

29,42 

29,42 

29 

79 

-190 

80 

180 

85 

No effect 

No effect 

Impaired 

Impaired 

reversal 

Altered 

Altered 

No effect 

5,9 

Less 

5,9 aggressive 

5,9 No effect 

29 Impaired 

29,120 Impaired 

29 Impaired 

reversal 

— Impaired 

Impaired 

5 

5 

6-8 

4 

6-8 

4 

7 

7 

7 

7 

7 

— 

30 

17 

17-25 

57,81 

123,162 

17,25 

50,85 

30 

17 

914 

— 

9,14 

50,85 

No effect 

No effect 

No effect 

No effect 

Impaired 

Impaired 

reversal 

"Succ. B.D. = Successive brightness discrimination. 

Simult. 8.D. = Simultaneous brightness discrimination. 

1-way = One-way avoidance. 

2-way = Two-way avoidance. 

FD = Form discrimination. 

SD = Siie discrimination. 

Flinch T= Tail-flinch test. 

SEA = Shock elicited aggression. 

CF mue = Close-field male. 

Operant = Operant chamber. 

WGTA = Wisconsin General Test Apparatus. 

bPG= Pregestation period, external exposure to dam. 

G= Gestation period, external exposure to dam. 

L= Lactation period, external exposure to dam. 

P W - Post weaning period, external exposure to pup. 

C DT= Diet 

GAV° Gavage 

I P= Intraperitoneal 

W = Drinking water 

% = (formal 

A= Altered 

"mg/kg/day 

'ppm 

11-36 
P.81 

A review ofthe studies listed in Table 1 1-7 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 experimental designs, several design deficiencies frequently 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 application 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 interpretation 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 

11-8. 

TABLE 11-8. STAGE OF LEARNING 

Treatment 

effects 

Present 

Absent 

> 

Acquisition 

Brady etal.292.a 

Brown304,b 

Carson etal.soi.b 

Driscoll and Stegner272.a.b 

Hastings etal.273b 

Overmann294.a 

Snowdon295-

b 

Sobotka et al.283.a 

Winneke etal.285b 

Miller etal.sos.b 

Bornschein et al.298•*> 

Carson et al.soo.b 

Hastings et al.273.b 

Overmann29i a.b 

Sobotka et al.283.a 

Winneke etal.285.b 

Performance 

Shapiro etal.29TM 

Slecta296.b 

Bornschein et al.298-

b 

Reversal 'extinction 

Overmann294.a.b 

Sobotka etal.283.a 

Bornschein et al.298-

1

" 

Bowman303.b 

Overmann294.a 

Sobotka etal.283.a 

Miller etal.305.b 

aNegative reinforcer. 

bPosit ive reinforcer. 

Although learning paradigms are being used to 

demonstrate effects of lead on CNS function, the 

present data do not permit a clear distinction between the effects of lead exposure on cognitive function (learning/memory) and effects on sensorymotor function, arousal, or motivation, which in 

turn can produce performance differences. 

Therefore, some of the studies appearing in the column titled "Acquisition" (Table 11-8) 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 reinforcers 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 effects 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 experimenter-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 immediate exposure period with behavioral disruption 

1-37 
P.82 

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 pertaining 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 exposure. 285,294,301 Other forms of visual discrimination such as size285

-

301

 and brightness272-

292

-

304

-

306

 appear to be particularly sensitive. The two reports of 

altered size discrimination285-

301

 may in fact be 

special cases of brightness discrimination since the 

different size stimuli (white pattern on a black background) also reflect different amounts of light. 

Further testing will be necessary to resolve this issue. 

Active-avoidance tasks are also being used successfully to examine effects obtained following lead 

exposure. Both one-way avoidance294-

306

 and twoway, shuttle-avoidance tasks272

-

283

 reflect a disruption in normal behavior. The one exception is a 

negative finding by Sobotka et al.283 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 presented 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 exposed to lead following weaning.296

-

297

 These reports are contrary to the generally held opinion that 

adult or post-weaning rats are insensitive to lead exposure. 293.295.30i 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 increased 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 observed on litter-mate males housed together." 

Sauerhoff and Michaelson278 also referred to an increased 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 al.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 aggressive 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 quantitative examination of aggressive behavior suggests 

that lead can cause a decrease rather than an increase 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 
system. Much ofthe 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 exposure are hindered by the same problems in experimental design as those discussed in the section on 

behavioral studies. 

Research on neurotransmitter systems has concentrated primarily on the effects of lead exposure 

on cholinergic and monoaminergic functions, probably because of the extensive background literature 

that exists on the basic neurochemistry of those 

transmitters and because of the documentation extant 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 transmitter substances in brain tissue;277

-

283

-

288

-

307"315

 (2) 

assessment of synthesis and turnover rates;309-

315

 (3) 

measurement of the activity of enzymes responsible 

for transmitte r synthesis or degrada -

t

jon;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 

Species Exposure 

Nutritional 

status 

Blood. 

Ittlil 

Brain. 

Mil Neurochemical parameter 

Silbergeld and 

Goldberg308 

Mouse 

Silbergeld etal.309 Mouse 

Carroll etal.3i* Mouse 

Brown et al.318 

Goiter and 

Michaelson*"' 

Rat 

Rat 

Michaelson and 

Sauerhoff*'* 

Sauerhoff and 

Michaelson"8 

Grant et al."'" 

Rat 

Rat 

Rat 

5 mg/ml lead acetate in 

drinking water starting at 

parturition 

5 mg/ml lead acetate in 

drinking water starting at 

parturition 

2,5,10 mg/ml lead acetate 

in drinking water starting 

at parturition 

7.5 mg/kg (IP) from birth 

to 10 days of age 

5% lead acetate in 

mother's diet from parturition to 16 days post 

partum, 40 ppm in drinking water 

Intubated with 1.0 mg/day 

from parturition to 16 

days post partum, 40 ppm 

in drinking water 

Undernourished 

Undernourished 

Undernourished 

Normal 

Undernourished 

1) High affinity transport of 

phenylalanine, glycine, 

leucine, NE, 5HT, GABA, 

DA, choline, and tyrosine 

2) Steady-state ACh NEDA 

1) ACh release 

2) Steady state NE, HVA, 

VMA 

3) MAO 

4) Choline transport 

1)K+ -induced release of 

ACh and choline 

2) Spontaneous release of 

ACh 

3) Steady-state levels of ACh, 

choline 

4) CAT CBK AChE 

AChE 

(regional brain analysis) 

Steady-state NE, DA 

1) Decreased high affinity 

transport of dopamine 

and choline 

Increased high affinity 

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 choline 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 

5% lead acetate in 

mother's diet from parturition until day 16, 25 

ppm in drinking water 

4% lead carbonate in 

mother's diet from parturition until 16 days, 40 

ppm in diet 

0, 25, 100 or 200 

mg/kg/day by gavage on 

postnatal days 3-25 

Undernourished 

Undernourished 

? 

? 

0 = 

25 = 

100 = 

200 = 

Control = 0.1 

4% = 0.88 

, 

16 

26 

43 

63 

0.15 

0.38 

0.51 

0.68 

1) Steady-state DA 

2) Steady-state 5HT, GABA, 

and NE 

Steady-state NE, DA 

Steady-state NE, DA 

(regional brain analysis) 

1) Decreased DA (20%) 

2) No change 

Decreased DA (20%) 

No change 

(continued) 

11-39 
P.84 

• r * • 

TABLE 11-9 (continued). 

Reference 

Hrdina3l3 

Modak etal.3n 

Sobotka etal."8" 

ShihandHanin3i5 

Cahill etal."" 

Silbergeld and 

Chisolm3i9 

Gerber et al.312 

Bhatnagar3i7 

Bull etal."" 

Species 

Rat 

Rat 

Rat 

Rat 

Rat 

Mouse 

Mouse 

Rat 

(200-

250 

g) 

Rat 

(200-

400 

g) 

Holtzman and Hsu"""1 Rat 

Abbreviations: 

ACh • Acetylcholine 

CAT • Choline acetyltranferase 

AChE • Acetylcholinesterase 

NE - Norepinephrine 

DA - Dopamine 

5NT • 5-riydroiytrypta 

Exposure 

0.2 and 1.0 mg/kg IP 

(lOOg)for 45 days 

1% lead acetate in drinking 

water at parturition 

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

4% lead carbonate in 

mother's chow from parturition to 21 days, 40 

ppm in diet 

5, 50 ppm in drinking 

water. 40 day pretreatment of parents continued 

from conception through 

adulthood 

5 mg/ml lead acetate in 

drinking water starting at 

parturition 

0.1-1000 mg/l lead acetate 

in drinking water for one 

year 

0,1,2% lead acetate for 70 

days 

1) 67 /xM in vitro lead 

chloride 

2)3,12, 60 mg/Pb/Kg total 

dose over 2 weeks 

4% lead carbonate at 2 

weeks postpartum 

mine (serotonin) 

GABA • Gamma aminobutyric acid 

CPK - Choline phosphokinase 

Nutritional 

status 

7 

Lead concentration 

Blood. 

nW 

7 

Brain stem NE 

5HT 

Under- Control = 0 

nourished 

Normal 

Undernourished 

Normal 

Undernourished 

? 

•> 

— 

Impaired 

growth in 60 

mg/kg group 

Undernourished, 

reduced 

brain weights 

1%= 245 

8 71 

? 

180 day 

0 = 5 

5 = 6 

50 = 10 

7 

? 

7 

— 

Control = 0.08 

3= 13.2 

12= 72.6 

60= 380 

7 

Brain, 

Hill 

7 

7 

— 

7 

180 day 

0 = 18 

5 = 20 

5 0 = 27 

7 

7 

7 

— 

0.06 

0.17 

0.41 

1.02 

7 

Neurochemical parameter 

Cerebrocorticol 

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, choline 

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 

mitochondrial respiration 

Results 

ACh = 32-48% increase 

AChE - No significant 

change 

1)Increased ACh in diencephalon (12%) 

2) Increased in medullapons, hippicampus and 

cerebral cortex (11-12%) 

3) Lower in medulla-pans, 

midbrain and diencephalon (10-20%) 

1) No change 

2) Decreased (marginal) 

1) No change in ACh, increased choline 

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 
Several studies utilizing high levels of lead exposure have reported inhibition of cholinergic function. In a series of experiments on the mouse, 

Silbergeld et al.308-

309

 and Carroll et al.316 reported 

decrease d potassium-induce d releas e of 

acetylcholine (ACh) and decreased high-affinity 

transport of choline. Unfortunately, no control for 

growth retardation was provided in these experiments 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.311 

and Shih and Hanin.315 At lower levels of external 

exposure, with no accompanying growth retardation, no consistent effects on cholinergic function 

have been reported (cf. 283 and 318). Thus, if impaired cholinergic function during in vivo lead exposure is also found in the absence of undernutrition, and/or growth retardation, which is probable in 

view ofthe 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. Findings have been reported of increased steady-state 

levels of norepinephrine,277-

307

-

308

 increased activity 

of monamine oxidase (MAO),309 increased synaptosomal 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 However, inconsistencies within a given laboratory (cf. 

278 vs. 307), absence of similar findings in different 

laboratories (cf. 283 and 310), and findings of decreased 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 exposure (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 indices of CNS monoamine turnover rates. Although 

initial studies on catecholamine excretion have suggested a lead effect, ah 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 investigations of low-level toxicity. Also, as indicated 

by Wender et al.,321 urinary metabolites reflect primarily 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 function. 283,308,312-314 

The reasons for the inconsistencies of lead-induced 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 suggest that some subpopulations of rats or mice might 

be resistant to lead effects on monoamine transmitters 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 inhibits adenyl cyclase activity (I50 = 2.4 fiM). 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 mechanism of action of a number of hormones, including 

neurotransmitters. The effects of lead exposure on 

adenyl cyclase and the resultant effects on neurotransmitter systems warrant further investigation. 

Several recent reports have dealt with the effects 

pf lead exposure on brain-energy metabolism. Bull 

et al.253 reported that both in vivo and in vitro lead 

exposure inhibited potassium-stimulated respiration. Of interest was the finding that lower brain 

levels of lead (approximately 1 /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 reported 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 
P.86 

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 fiM lead nitrate 

depressed or blocked nerve transmission. Contraction of the nictitating membrane during 

acetylcholine perfusion was unaltered. Also, perfusion 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 presynaptic terminals. 

Manalis and Cooper 3 2 6 and Cooper and 

Manalis327 showed that lead can influence both preand postsynaptic events. Using the frog (Rana ippiens) 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 ofthe postsynaptic membrane 

to released acetylcholine in quantities that are insufficient 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 preparation from mice exposed to lead from birth 

through 60 days of age. The nerve-muscle preparation from these lead-exposed animals showed a 

reduction in force of contraction with nerve stimulation. Also, a reduced force of contraction was reported 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 importance 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 contraction force of the rabbit saphenous artery following 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 demonstrated that lead interferes with synaptic transmission in the peripheral nervous system. This effect appears to be related to a competitive inhibition 

of calcium-mediated, evoked release of the 

neurotransmitters. Further, lead was shown to increase 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 cortical 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-induced 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 fig % at 20 days of 

age to 584 /ug % 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 reported 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 indicate that encephalopathy is produced by high-level 

perinatal exposure to lead. This encephalopathy occurs 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 attributable to a greater sensitivity or to a greater 

susceptibility of the developing organism will require 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 exposure to lead even at moderate exposure levels will 

produce delays in both neurological and sexual 

development. Because these effects have been demonstrated to occur in the absence of either undernutrition or growth retardation, it has been suggested 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. Ifthe test conditions are appropriate, this increased reactivity will 

be manifested as increased locomotor activity, 

although some text situations will show reduced activity. Therefore, the altered activity levels per se 

are merely reflective ofa 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 exposure 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 figldl. 

Sobotka and Cook, using a similar exposure regimen, found normal activity levels with 22-day blood 

lead levels of 71 figldl. 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 moderate and low levels of lead may disrupt this behavior. 

Thus, external exposures that result in blood lead 

levels ranging from 30 to 80 figldl have been reported to disrupt cognitive function (see Table 

11-5). As is true with the clinical data, this area requires 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 experiments including: 

1. Better documentation of internal exposure, 

not only with respect to lead levels but also 

with respect to correlative indices of lead toxicity, e.g., ALAD, protoporphyrin, etc. 

2. The use of exposure protocols that do not produce confounding variables such as undernutrition, 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 corre11-43 
P.88 

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 nephropathy. Acute renal effects of lead are seen in persons 

dying of acute lead poisoning or suffering from leadinduced 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 proximal tubules, rather than the vascular changes often 

referred to in earlier studies, are primary evidence 

of injury to the kidney in lead poisoning. Many subsequent studies have shown at least three pathological 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 ultrastructural 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 normal, 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 observation 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 /ig/dl.99 It should be noted that the 

children reported to have aminoaciduria in the study 

of Pueschel99 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 ug/dl 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 ug/dl, the minimum was 71 ug/dl, and 

all had strikingly high urinary ALA excretion. Some 

with very long exposures were reported to have interstitial 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 degeneration of these vessels. This is a progressive disease, 

sometimes resulting in renal failure. It seems to occur sporadically, primarily in industrially exposed 

workers and in older adults who have been diagnosed 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 acidfast intranuclear inclusions within the cells of the 

kidney tubules and liver. Ball and Jorenson339 reported a high frequency of saturnine gout resulting 

from the consumption of lead-contaminated 

whiskey, convincingly demonstrating reduced renal 

uric acid clearance associated with plumbism. 

11-44 
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 ug/dl, with a range of 42 to 141 ug/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 ug/dl. In the studies 

of Albahary et al.,342 blood lead levels were not reported 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 occupational 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 increased 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 ofthe subjects showed proximal tubule abnormalities via biopsy. In eight subjects, lead-induced 

nephropathy was established by exclusion. The 

blood lead values ofthe individuals ranged from 48 

ug/dl, for the subject having asymptomatic renal 

failure, to 98 ug/dl. The lead levels ofthe other two 

subjects in the preclinical renal dysfunction category 

were 51 and 66 ug/dl. All subjects showed glomerular filtration rates of less than 87 ml/min/1.73m2

. 

The authors suggest on the basis ofthese 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. Ofthese 401 subjects, 165 had died, 108 from nephritis or hypertension. This is greatly in excess of expectation. Information was obtained from 101 ofthe 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 attributable to lead poisoning had similarly elevated 

excretion of lead. The presence of intranuclear inclusion bodies is very helpful in establishing a relationship 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 nephropathy 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-documented history of childhood plumbism 20 to 35 

years earlier at the Boston Children's Hospital. 

Likewise, Chisolm347 found no evidence of renal disease in 62 adolescents known to have had lead intoxication 11 to 16 years earlier. An important distinction 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 adverse 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 poisoning. Extensive evidence for adverse effects of lead on 

reproduction and development has also been accumulating 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 preand postnatal survival and development ofthe fetus 

and newborn, respectively. In addition, it appears 

that the viability and development ofthe fetus may 

also be markedly affected by lead indirectly via ad11 -45 
P.90 

verse effects on various health parameters, e.g., 

nutritional state or blood chemistry, ofthe 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 regarding 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, miscarriages 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 ofthe 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"" 

Sample 

Housewives 

Female workers (mill work) 

Females exposed to lead 

premaritally 

Females exposed to lead 

after marriage 

Number of 

abonions and 

stillbirths per 

1000 females 

43.2 

47.6 

86.0 

133.5 

Number of 

neonatal deaths 

(first year) per 

1000 females 

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 exposure 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 ug/m3 were examined for effects 

on reproduction. Longitudinal data on 15 pregnancies 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 ug/liter. 

In a more recent study351 ofthe 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 pregnancy 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 incidence 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 correlation 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 function 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 ug 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 

11-46 
P.91 

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 significance, 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 disturbed 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., hormonal 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 conclusively 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 century.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 potential, but as yet not clearly defined, threat for subtle teratogenic and other deleterious health effects. 

The placental transfer of lead has been established, 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 occurring in bone, kidney, and liver, and lesser, but significant, amounts occurring in blood, brain, and 

heart. Barltrop has also pointed out that the distribution 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. Placental levels were greater 

than 1.5 ug/g in only 7 percent ofthe 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 maternal blood. For example, in the study of Gershanik et 

a l 360,361 98 cord-blood samples matched with 

maternal blood samples showed a high correlation 

between lead levels in infants (mean = 10.1 ug/dl) 

and their mothers (mean = 10.3 figldl), 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 

ug/dl) was significantly different (p <0.05) from the 

mean rural value (8.3 ug/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 urban value was 22.1 figldl (10 to 37 ug/dl), whereas 

the corresponding suburban level was 18.3 ug/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 ug/dl and a mean maternal 

blood level of 13.2 ug/dl. 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 cordblood 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 
P.92 

lead levels as well as for the corresponding urinary 

ALA levels. The maternal blood mean was 16.89 

figldl 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 <0.0I). 

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 synthesis. 

In a study of Fahim365 on cord-blood lead levels, 

blood lead values in pregnant women having preterm 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 percentage of women having preterm deliveries and premature 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, respectively. 

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 urinary excretion of lead was observed, indicating intrauterine 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 conceived 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. 3 6 8 have reported that 

moderately increased lead absorption (blood lead 

mean = 52.8 ug/dl) resulted in gonadal impairment. The effects on the testes were shown to be 

direct in that tests for hypothalamopituitary influence 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: leadpoisoned workmen (74.5 ug/dl) and those showing 

moderate (52.8 figldl), slight (41 figldl), and 

physiologic (23 ug/dl) absorption of lead. Semen 

analysis revealed asthenospermia, hypospermia, and 

teratospermia in lead-poisoned workers and those 

with moderately increased absorption oflead (blood 

lead levels = 50 to 80 ug/dl for the latter). The abnorma l spermatozoa included binucleated , 

bicephalus, amorphous, and tapered forms. In contrast, 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 number 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 significant adverse health effects on reproductive functions. Most studies, however, have typically looked 

at the effects of prolonged moderate-to-high exposures 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 interfered 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 deficient. No effects were found in animals with normal 

diets. The combined effect of maternal and paternal 

oral lead intoxication upon reproductive performance was studied in rats by Morris et al.372

 who reported significant reduction in weaning percentage 

among offspring of rats fed 512 ppm lead. Stowe and 

Goyer373 assessed the relative paternal and maternal 

11-48 
P.93 

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, SpragueDawley 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), leadtoxic female to control male (PbF-CM), and leadtoxic female to lead-toxic male (PbF-PbM). The 

results identifying specific deleterious paternal and 

maternal effects of lead toxicity upon rat reproduction are shown in Table 11-11. 

TABLE 11-11. REPRODUCTIVE PERFORMANCE OF F, LEAD-TOXIC RATS***-** 

Parameter 

Type of mating 

CF-CM CF-PbM PbF-CM PbF-PbM 

Litters observed 

Pups/litter 

Pup birth weight, g 

Weaned rats/litter 

Survival rate, % 

22 

11.90 ± 0.40a 

6.74 ± 0.15 

9.84 ± 0.50 

89.80 ± 3.20 

Litter birth weight/Dam breeding weight, % 28.04 ± 1.30 

Litter birth weight/Dam whelping weight, % 19.09 ± 0.80 

Gestation gain/Pups per litter, g 11.54 ± 0.60 

Nonfetal gestational/Gain/fetus, g 3.93 ± 0.38 

24 

10.10 ± 0.50 

5.92 ± 0.13c 

7.04 ± 0.77<= 

73.70 ± 7.90 

22.30 ± 0.90= 

15.97 ± 0.58= 

11.20± 0.74 

4.83 ± 0.47 

36 

8.78 ± 0.30b 

5.44 ± 0.13=."" 

5.41 ± 0.74C1 

52.60 ± 7.20 

19.35 ± 1.00c 

14.28 ± 0.66c 

11.17 ± 0.54 

4.15 ± 0.42 

16 

7.75 ± 0.50= 

4.80 ± 0.19C-MJ 

2.72 ± 0.70cd.e 

30.00 ± 8.20C.-U 

15.38 ± 1.10C-U 

11.58 ± 0.78=--".' 

12.34 ± 1.24 

3.96 ± 0.46 

aMean ± S.E.M. 

bSignificantly (p <0.05) less than mean for CF-CM. 

^Significantly (p <0.01) less than mean for CF-CM. 

-"Significantly (p <0.01) less than mean for CF-PbM. 

eSignificantly (p <0.01) less than mean for PbF-CM. 

'Significantly (p <0.05) less than mean for PbF-CM. 

The paternal effects of lead included a 15 percent 

reduction in the number of pups born per litter, a 12 

percent reduction in the mean pup birth weight, and 

an 18 percent reduction in pup survival rate. The 

maternal effects oflead included a 26 percent reduction in litter size, 19 percent reduction in mean pup 

birth weights, and 41 percent reduction in pup survival. The combined male and female effects of lead 

toxicity resulted in 35 percent reduction in the number of pups per litter, 29 percent reduction in the 

pup birth weights, and 67 percent reduction in pup 

survival to weaning. Stowe and Goyer373 classified 

the effect of lead upon reproduction as gametotoxic, 

intrauterine, and extrauterine. The gametotoxic 

effects of lead appear to be irreversible and had additive male and female components. The intrauterine effects resulted from the transmammary 

passage of lead from the dam to the suckling pup 

adding insult to the gametotoxic and uterine environmental effects. 

The effects of lead on the reproduction of sexually 

mature male and female Sesco rats were reported by 

Hildebrand et al.374 The animals were orally fed 

lead acetate at doses of 5 and 100 ug for 30 days. 

Control females possessed the same levels of lead 

concentration in their blood as those for male controls. However, for the treated animals the blood 

lead levels for the females were higher than those for 

the males: 30 figldl versus 19 ug/dl at 5 ug lead acetate, and 53 ug/dl versus 30 ug/dl at 100 ug lead 

acetate. They noted impotence and prostatic hyperplasia in the males at the lower dose, progressing 

to testicular damage with inhibition of spermatogenesis in those reaching blood levels of 50 

ug/dl. In the females, they noted irregularity ofthe 

estrus cycle at both doses. When lead levels reached 

50 ug/dl, the female rats developed ovarian follicular cysts with a reduction in the number of corpora 

lutea. A subsequent study employing SpragueDawley rats was unable to replicate these findings.375 

A number of other studies have focused more 

specifically on either maternal or paternal lead exposure effects. For example, in reference to maternal 

effects, histopathological changes in ovaries in leadpoisoned Rhesus monkeys have been demon11-49 
P.94 

strated.376 Most other animal studies have utilized 

rodents. 

Kennedy et al.377 administered an aqueous solution oflead 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 pregnancies decreased and the number of embryos succumbing 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 middle dosage, pregnancy incidence decreased, the 

number of embryos dying before implantation increased, 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 demonstrated 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 incidence 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 ofthe 

treated males was reduced to 50 percent. They 

calculated the mutagenicity index (number of early 

fetal deaths/total implants) to be 10.4 for leadtreated mice versus 2.9 for controls (X2

 = 10.4, p < 

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 ug/kg 6 times over a 10-day period and 

observed damage to testes and spermatozoa. Stofen 

also reported that Golubova et al. found morphological 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 pregnant rats on days 8 through 17 of gestation. A 

urorectocaudal syndrom of malformations was produced when lead was administered on the 9th day of 

gestation. The lead nitrate was increasingly embryoand fetotoxic when administered on later days of 

gestation (days 10 to 15) but not teratogenic. Ferm 

and Carpenter386 as well as Ferm and Ferm387 reported increased embryonic resorption and malformation rates when various lead salts were administered to pregnant hamsters on the 8th day of 

gestation. The teratogenic effect of lead was almost 

completely restricted to the tail region. Malformations ofthe sacral and caudal vertebrae, resulting in 

absent or stunted tails, were observed. 

The reasons for the localization ofthe teratogenic 

effects of lead are unknown at this time. Ferm and 

Ferm387 have suggested that the specificity could be 

explained by an interference with specific enzymatic 

events during early development. Lead alters 

mitochondrial function and enhances or inhibits a 

variety of enzymes,388 any or all of which could interfere with normal development. Ferm389

 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 
P.95 

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, ruptured brain, shortened beak, twisted neck and limbs, 

and everted viscera.391 The most common developmental 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 ug/g) from weaning through mating, 

gestation, and lactation. No teratogenic effects were 

observed, although exposure to 250 ug/g lead acetate caused a slight but nonsignificant increase in 

fetal resorptions. The lead-treated animals produced litters of normal numbers, but the offspring 

from the 50- and 250-ug/g groups weighed less at 

weaning and showed delays in physical development. Reiter et al.264

 have also observed delays in 

the development of the nervous system in offspring 

exposed to 50 ug/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 involved, these studies suggest that low-level, chronic 

exposure to lead may induce postnatal developmental delays in rats. 

It should be noted that the above reports on normal 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 concentrations of lead of approximately 170 ug/dl 

whole blood can inhibit 8-ALAD activity in both 

blood and brain of suckling rats. Although brain 

tissue was not purged of residual blood. ALAD contribution to brain ALAD activity would not be expected 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 

ofthe 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 experimental 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 plumbism in a house painter. Monaenkova395

 in 1957 observed impaired concentration of

 131I by thyroids in 

10 out of 41 patients with industrial plumbism. Subsequently, Zel'tser396

 showed that in vivo 13II 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 poisoning, can be offset by treatment with thyroid-stimulating hormone (TSH).397

-

398

 Lead may act to depress 

thyroid function by inhibiting SH groups or by displacing 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 impair thyroid function. 

Sandstead et al.399 studied the effects of lead intoxication 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 hypopituitarism 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 synthesis of Cortisol. 

Excessive oral ingestion of lead in man has 

resulted in pathological changes in the pituitaryadrenal 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-hydroxycorticosteroids 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 ofthe adrenal 

cortex has also been suggested.403 

There also is some evidence suggesting that lead 

11-51 
P.96 

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 recently, however, Schiele et al.,405

 using a different 

analytical method, were unable to find any significant 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 oxalacetic transaminase (SGOT) activity at an increased value of 11.5 percent in subjects with blood 

lead levels below 70 ug/dl, 20 percent in those with 

a blood lead level of about 70 ug/dl, and 50 percent 

in workers with a blood lead level of about 100 

ug/dl. The correlation between blood lead levels 

and SGOT was not statistically significant. In the absence of information on the possible influence of 

diet, infection, or personal habits, however, the 

authors were unable to draw any definite conclusions concerning the etiology of these changes. 

The liver is the major organ for the detoxification 

of drugs. In acute lead poisoning, the mixed-function 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 ofthe 

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 impairment ofthe mixed-function oxidase system.409

 Drugmetabolizing activities were significantly decreased 

in the lead-poisoned animals. Intensity and duration 

of these changes were dose dependent. In vivo experiments, based on the duration of pentobarbital 

sleeping time, provided further evidence for the inhibition of drug metabolism in lead-poisoned rats. 

These data would suggest than an enhanced sensitivity to xenobiotics (drugs, pesticides, food additives, etc.) should be expected to occur in leadpoisoned animals. Alvarez et al.410

 studied the effect 

oflead exposure on drug metabolism in children and 

adults. There were no differences between two normal children and eight lead-poisoned children in 

their capacities to metabolize two test drugs, antipyrine 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 figldl, antipyrine half-lives were significantly 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 

chelation therapy. In seven of eight subjects, chelation therapy shortened the antipyrine half-lives, but 

the effect was minimal. The two authors concluded 

that chronic lead exposure results in significant inhibition 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-Fordyce and Lane82

 reported a marked increase in the 

cerebrovascular mortality rate among heavily exposed 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 smelting industry between 1947 and 1970. Many were 

found to have blood lead concentrations in excess of 

80 ug/dl. The authors concluded that there was excess mortality associated with only two categories of 

illness, chronic nephritis and hypertension. The increased 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 hypertension in a population of 364 industrially exposed men, 273 of whom had a long-term exposure 

to lead. They subdivided the workers into leadaffected 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 expected for nonexposed men in the general population. Other reports on the question do not show hypertension 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 lesions in rabbits. 

Structural and functional changes of the myocardium 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 encephalopathy is present, the electrocardiographic abnormalities disappeared with chelation therapy, suggesting that lead may have been the original etiological factor.419421

 Silver and Rodriguez-Torres421 

noted abnormal electrocardiograms in 21 of 30 

children (70 percent) having symptoms of lead toxicity. After chelation therapy, the electrocardiograms remained abnormal in only four (13 percent) 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 percent 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, increased permeability; second, decreased permeability) in rats, rabbits; and dogs that received a 

solution of lead acetate. A phase change in the content of catecholamines in the myocardium and in the 

blood vessels was observed in subacute lead poisoning in dogs.425

 This effect appears to be a link in the 

complex mechanism ofthe 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 injection 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 producing 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, particularly 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 ug/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 particulate lead 

oxide (200 ug/m3) for 14 days revealed ultrastruc11-53 
P.98 

tural damage (mitochondria and endoplasmic 

reticulum) to the alveolar macrophages and the type 

I alveolar epithelial cells. Biochemically, a considerable loss in the activity ofthe benzopyrene hydroxylating 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 elevated free erythrocyte protoporphyrin and blood 

levels 2 40 figldl and seven nonlead-burdened 

children for evidence of impairment of their immunological responses. They found no differences 

between the control group and the lead-exposed 

group with reference to complement levels, to immunoglobulins, or to anamnestic response to the 

tetanus toxoid antigen. 

Hicks435 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 relationship 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 industrial 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 constipation. They had blood lead levels ranging from a 

little less than 40 to 80 ug/dl as determined by 

polarography, a technique which tends to yield 

values lower than the actual blood levels. The diagnosis 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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The growth and reproduction of rats fed diets containing 

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373. Stowe, H. D. and R. A. Goyer. The reproductive ability 

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Teratogenic evaluation of lead compounds in mice and 

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on the reproductive organs and the embryos. Economic 

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380. Jacquet, P., A. Leonard, and G. B. Gerber. Progress report 

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the developing brain and on cytogenetics of post meiotic 

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382. Weller, C. V. The blastrophthoric effect of chronic lead 

poisoning. J. Med. Res. 55:271, 1915. 

383. Der, R., Z. Fahim, M. Yousef, and M. Fahim. Environmental interaction of lead and cadmium on reproduction 

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384. Verma, M . M., Joshi, S. R., and A. O. Adeyemi. 

Mutagenicity and infertility following administration of 

lead sub-acetate to Swiss male mice. Experientia. 

50(5):486-487, 1974. 

385. McClain, R. M. and B. A. Becker. Teratogenicity, fetal 

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386. Ferm, V. H. and S. J. Carpenter. Developmental malformations resulting from the administration of lead salts. 

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388. Vallee, B. L. and D. D. Ulmer. Biochemical effects of mercury, cadmium and lead. Ann. Rev. Biochem. 47:91-128, 

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390. Giliani, S. H. Congenital cardiac anomalies in lead 

poisoning. Pathol. Microbiol. (Basel). 59:85-90, 1973. 

391. Giliani, S. H. Congenital anomalies in lead poisoning. 

Obstet. Gynecol. 47:265-269, 1973. 

392. Millar, J. A „ V. Battistini, R. L. C. Cumming, F. Carswell, 

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dehydratase levels in mentally retarded children and in 

lead poisoned suckling rats. Lancet. 2:695, 1970. 

393. Porritt, N. Cumulative effects of infinitesimal doses of 

lead. Brit. Med. J, 2:92-94, 1931. 

394. Kremer, H. U. and M. N. Frank. Coexisting myxedema 

and chronic plumbism. Ann. Intern. Med. 42:1130-1 136, 

1955. 

395. Monaenkova, A. M. Functional state of the thyroid in 

chronic intoxication with some industrial poisons. Gig. 

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396. Zel'tser, M. E. The functional state of the thyroid gland in 

lead poisoning. Tr. Inst. Kraevoi. Patol. Akad., Nank, Kaz 

SSR. 70:116-120, 1962. 

397. Sandstead, H. H. and R. Galloway. Effect of chronic lead 

intoxication on in vivo I" 1 uptake by the rat thyroid. Proc. 

Fed. Soc. Exp. Biol. Med. /24:l8-20, 1967. 

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R. T. Terry'. Lead intoxication and the thyroid. Arch. Int. 

Med. 725:632-635, 1969. 

399. Sandstead, H. H., D. N. Orth, K. Abe, and J. Stiel. Lead intoxication: Effect on pituitary and adrenal function in 

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Zabol. 70:46-47, 1966. 

401. Pines, A. G. Indexes of general reactivity in saturnine toxicity. Vroch. Delo. 5:93-96, 1965. 

402. Makotchenko, V. M. The functional condition of supra 

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403. Sandstead, H. H., A. M. Michelakis, and T. E. Temple. 

Lead intoxication. Its effects on the renin-aldosterase 

response to sodium deprivation. Arch. Environ. Health. 

20:356-363, 1970. 

404. Urbanowicz, H., J. Grabecki, and J. Kozielska. The urinary excretion of 5-hydroxyindoleacetic acid in industrial 

lead exposure. Med. Lav. 60:582-586, 1969. 

405. Schiele, R., K. H. Schalle, and H. Valentin. The influence 

of lead upon the tryptophan metabolism. Klin. Wschr. 

52:401-404, 1974. 

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methyl mercury: Effects of acute exposure on cytochrome 

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408. Remmer, H., J. Schenkman, R. W. Estabrook, H. Sasame, 

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drug metabolizing activity in lead-poisoned rats. Experientia. 29:970-972, 1973. 

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411. Alvares, A. P., A. Fishbein, S. Sassa, K. E. Anderson, and 

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poisons (lead, carbon disulphide, benzene). Git. Tr. Prof. 

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415. Cramer, K. and L. Dahlberg. Incidence of hypertension 

among lead workers. Brit. J. Ind. Med. 25:101-104, 1966. 

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control of lead hazard in the storage battery industry. 

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Effect of experimental lead poisoning on the development 

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418. Prerovska, J. Einfluss von Blei auf biochemische Veranderungen im Serum und Veranderungen in der Aderwant 

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419. Myerson, R. M. and J. H. Eisenhauer. Atrioventricular 

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420. Freeman, R reversible myocarditis due to chronic lead 

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in experimental lead intoxication. Izv. Akad..Nauk 

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426. Hemphill, F., M. L. Kaerberle, and W. B. Buck. Lead suppression of mouse resistance to Salmonella typhimurium. 

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428. Gainer, J. H. Activation of Rauscher leukemia virus by 

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Alveolar macrophages: Reduced number in rats after 

prolonged inhalation of lead sesquioxide. Science. 

762:1297-1299, 1968. 

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Aspects of Lead, Amsterdam, October 2-6, 1972. Luxembourg, Commission of the European Communities, p. 

221-230. 

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1976. 

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25:289-291, 1971. 

11-65 
P.10 

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 exposures directly to human health effects in various 

population groups. Unfortunately, few such studies 

exist. Standards setting, then, must rely on constructing (1) the linkage between exposures to environmental 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 considerations 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 addition, 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 exposures 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 implications. 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 investigators' 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 distribution 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.13 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 littleknown 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 acceptance that homogeneous populations have a lognormal distribution of blood lead values. 

The lognormal distribution and its application to 

biological measurements are discussed by several 

authors.48-

9

 A variable is said to have a lognormal 

distribution if the logarithm of the variable-is normally distributed. Because of the skewed nature of 

the lognormal distribution, the median (50th percentile) is a more meaningful estimate of central tendency than the arithmetic mean. For the normal distribution, the best estimate of the median is X, the 

simple arithmetic mean. Forthe lognormal distribution, the best estimate of the median is the geometric 

mean (GM): 

12-1 
' *"*•*"" ' 

P.11 

GM = Exp[S (In(Xi))/n]. (12-1) 

i= 1 

The standard deviation of the logarithms is: 

S = [1 (ln(X;)- ln(GM))2/n-l]"2. (12-2) 

i= 1 

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 standard deviation, SD, are given, then the geometric 

mean and the geometric standard deviation can be 

estimated by:10 

GM = X/(l + SD2/X2)''2 (12-3) 

and 

GSD Exp[(ln(SD2

/X2 + l))'/2]. (12-4) 

The geometric standard deviation must be interpreted 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)'

 % and (20)(1.3)'-96

 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 

X p = (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 

p 

-2.326 

-1.960 

-1.645 

-1.282 

25 

50 

75 

90 

p 

-.674 

0.000 

0.674 

1.282 

95 

97.5 

99 

99.9 

p 

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 distribution. Figure 12-1, for example, is drawn with an 

assumed geometric standard deviation of 1.3. 

Q 20 — 

GM-GEOMETRIC MEAN 

GSD - GEOMETRIC STANDARD DEVIATION 

Illl l ! I 1 I I I I 

95 50 

PERCENT OF POPULATION WITH BLOOD.LEAD LEVELS 

EXCEEDING GIVEN VALUE 

Figure 12-1. Estimated cumulative distribution of blood lead 

levels lor populations in which the geometric mean level is 15, 

25, or 40 M9/dl. 

From this description of the distribution, estimates 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 example, (Figure 12-1) in the populations with 

geometric mean blood lead levels of 15, 25, and 40 

Aig/dl whole blood, 0.1, 10, and 68 percent, respectively, will have blood lead levels exceeding 35 

Mg/dl. 

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 

100 

80 ; I I 1 

1 Illl l 

^ 1 1 1 

1 1 1 1 1 1 1 1 1 1 1 1 I 1 1 IK -

GM = GEOMETRIC MEAN — 

GSD •= GEOMETRIC STANDARD DEVIATION — 

1 MINI -

O 10 

S 8 

PERCENT OF POPULATION WITH BLOOD-LEAD LEVELS 

EXCEEDING GIVEN VALUE 

Figure 12-2. Estimated cumulative distribution ol blood lead 

levels lor populations having a geometric mean blood lead 

level of 25 Mg/dl, but geometric standard deviations ol 1.2, 

1.3, or 1.5. 

12-2 
P.12 

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 provided. 

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 Study? 

Southern California-Males7 

Southern California-Females7 

Houston6 

Azar3 

Population 

size 

879 

1908 

64 

107 

189 

149 

Replicates 

per 

observation 

3 

1 

2 

2 

2 

2-8 

Number 

ol 

duplicates 

16b 

171 

64 

107 

189 

NAC 

Population 

variance3 

0.190 

(1.55) 

0.090 

(1.35) 

0.224 

(1.60) 

0.183 

(1.53) 

0.182 

(1.53) 

0.148 

(1.47) 

Within group 

variance3 

0.072 

(1.31) 

0.082 

(1.33) 

0.181 

(1.53) 

0.167 

(1.51) 

0.069 

(1.30) 

0.099 

(1.37) 

Measurement 

variance 

0.01-2" 

(1.12) 

0.063 

(1.28) 

0.216 

(1.59) 

0.141 

(1.45) 

0.094 

(1.36) 

0.049 

(1.25) 

a

 Includes measurement variation. 

D

 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.1 The 

estimates of population and within group variance come from the original study. 

c

 Not available. 

12.2.1.3 VARIATIO N 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 individuals with the same exposure as well as 

demographic differences in age, sex, race, 

socioeconomic status, and environmental background 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 exposure 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 interpreted 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 calculations 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, except 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 includes both biologic and measurement variation. It 

is possible for the measurement variation to exceed 

12-3 
P.13 

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 

Lucas11 has described a problem that he terms 

"false exceedences." For example, a lognormal distribution 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 hypothetical 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 variation. In such cases, the estimated percentage of the 

distribution above a fixed level will be an overestimate as shown in the previous paragraph. It is extremely difficult to obtain more accurate estimates 

because the appropriate variance can only be estimated 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 observed 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 throughout the world establishing mean blood lead concentrations 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 improved. Also, sometimes neither the methods of 

analysis nor the sampling scheme used have been reported. 

Studies of remote populations have been used to 

estimate the natural background blood lead level for 

humans.1215 Likewise, studies comparing either 

rural or suburban populations have been used to establish 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 studies1215 have focused on remote 

populations. Goldwater and Hoover12 conducted an 

international study of urban and rural populations 

in which investigators from 14 countries participated; 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 /ug/dl, respectively. 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 /ig/dl and a standard deviation of 5 

Mg/dl. 

Stopps13-

14

 reported data on remote populations. 

Table 12-2 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,1314 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 figldl 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 /ug/dl; SD, 5.7), 

but still are low in comparison with the values reported 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. 

ug/100 g 

23 

23 

18 

17.5 

16 

13 

12 

A number of studies have specifically contrasted 

blood lead results between rural, suburban, and urban populations.21621

 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 urban12-4 
P.14 

suburan comparison groups. Table 12-3 displays the 

results of the contrasts between those groups as calculated 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 

Cily 

Chicago, IL 

Philadelphia, PA 

New York. NY 

Three cities together 

Urban 

17.55 

20.12 

16.47 

18.05 

Blood Lead, ug % 

Suburban 

14.02 

17.88 

15.24 

15.71 

Urban excess 

3.53 

2.24 

1.23 

2.34 

Significant 

>0.01 

>0.01 

>0.01 

>0.01 

Nordman16 studied a series of populations in Finland 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 policemen, streetsweepers, downtown Helsinki residents, 

and rural controls, had a mean blood lead level that 

exceeded 13.5 figldl. 

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 urban survey sites, the mean blood lead level was significantly 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. ol 

samples 

130 

97 

112 

137 

128 

131 

162 

Mean 

blood lead. 

jjg/100g 

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 figldl 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 /ug/dl 

compared with 18.3 /ug/dl for the suburban 

newborn. This difference was not statistically significant. 

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 /xg/dl, respectively. 

Cohen et al.21 reported on a rural-urban comparison 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 standard 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.121417 In the Goldwater and 

Hoover study,12 urban population mean blood lead 

levels were found to range from 7 to 25 figld\, 

whereas the mean for rural areas ranged from 9 to 

32 /xg/dl. The wide range of means in both population 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 /ug/dl." Exceptions to this general range are found, however. 

Lower-than-usual blood lead levels have been reported 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.2427 Zurlo et al.,24 in particular, 

reported very high blood lead levels for adults in the 

Milan area, urban mean of 30 /xg/dl for males and 

23.7 figldl for females. 

Data obtained from adults within the United 

States follow a similar pattern. 2172 8 In data from 

Tepper and Levin,2 differences were noted in the 

geometric mean blood lead among the 11 populations 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 
P.15 

Philadelphia —GM and GSD of 20.6 and 1.33, 

respectively. 

In the 1960 Hofreuter et al. study,17 blood samples were collected from people in six metropolitan 

areas and one rural control site. The mean blood 

lead values varied from 14 to 22 /ug/100 g. The maximum observed values ranged from 38 to 60 

Mg/100 g. 

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 

figldl in Jacksonville, Florida. The highest reported 

value, 109.27 /xg/dl, occurred in Fargo, North 

Dakota. A wide range in values was reported for 

each city, the largest being 5.91 to 109.27 /xg/dl in 

Fargo. Further, the authors report three cities with 

mean blood lead levels below 8.00 /ug/dl, namely 

Lubbock, Texas, 7.95; Geneva, New York, 7.65; 

and Lafayette, Louisiana, 7.25 /xg/dl. These low 

values approximate those found in parts of Scandinavia.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 /ug/100 g for the Ashland, Wisconsin, plant to a 

high of 21.6 /ug/100g at the Los Angeles, California, 

plant. The overall geometric mean for the 23 locations was 18.2 /ug/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 information. 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 determined by an atomic absorption technique. Mean 

values for cities ranged from 19.8 to 32.9 figldl; the 

mean for all 14 cities was 25.5 /ug/dl. These values 

are indicative of sources of lead in the children's environment. 

Baker et al.31 determined blood lead values for 

1672 children aged 1 to 5 living in 19 towns containing smelters and 3 control towns. The smelter communities were selected for study because they had 

not previously been subject to thorough investigation. Blood lead values were determined by an 

atomic absorption technique. 

The mean blood lead levels for the lead and copper 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. Ol 

children 

screened 

449 

670 

387 

376 

793 

383 

285 

298 

226 

172 

537 

103 

264 

1,208 

6,151 

% ol 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 

7.31 

6.14 

Mean blood 

lead value, 

ug/dl 

28.2 

31.5 

32.9 

28.6 

21.5 

27.8 

25.0 

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 /ug/dl, was 

found in children for McGill, Nevada, whereas the 

highest mean value was found for Bartlesville, 

Oklahoma, with 28.60 /ug/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 /ug/dl, considerably higher than that found in Honolulu 

children, 17 /xg/dl. 

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 setting. 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 

/xg/dl, and 14 percent exceeded 60 /ug/dl. In 

children 5 to 9 years old, 45 percent exceeded 40 

figldl, as did 31 percent of measurements in individuals 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 
P.16 

TABLE 12-6. BLOOD LEAD LEVELS (WHOLE BLOOD) IN CHILDREN IN U.S. SMELTER AND COMPARISON TOWNS, 197531 

City 

No. ol 

samples Mean SEa GM GSD 

Percent 

exceeding 

35 ug/dl 

Comparison towns 

Albuquerque, NM 

Perryville, MO 

Safford, AZ 

Total 

Lead smelter towns 

Bixby, MO 

Glover, MO 

Herculaneum, MO 

Total 

Copper smelter towns 

Ajo. AZ 

Anaconda, MT 

Copper Hill, TN 

Douglas, AZ 

Hayden, AZ 

Hurley, MN 

McGill, NV 

Miami, AZ 

Morenci, AZ 

San Manuel, AZ 

White Pine. Ml 

Total 

Zinc smelter towns 

Amarillo. TX 

Bartlesville, OK 

Corpus Christi. TX 

Monaco, PA 

Palmerton, PA 

Total 

81 

85 

92 

258 

48 

23 

87 

158 

105 

64 

86 

97 

100 

42 

50 

94 

100 

101 

70 

909 

84 

87 

12 

62 

102 

347 

17.70 

16.88 

15.26 

16.56 

13.76 

12.05 

18.80 

16.34 

12.55 

13.38 

16.63 

20.47 

21.24 

14.33 

9.15 

17.00 

13.87 

18.01 

18.62 

16.36 

22.34 

28.60 

19.02 

14.84 

17.51 

21.04 

0.63 

0.74 

0.71 

0.41 

0.96 

1.19 

0.94 

0.66 

0.46 

0.95 

0.74 

0.86 

0.85 

1.23 

0.52 

0.74 

0.56 

0.55 

0.74 

0.25 

1.16 

1.91 

1.42 

0.82 

0.60 

0.66 

16.8 

15.8 

13.8 

15.4 

12.4 

11.1 

17.2 

14.6 

11.7 

11.6 

15.4 

18.9 

19.9 

12.8 

8.9 

15.5 

12.9 

17.2 

17.8 

14.8 

20.9 

23.6 

18.4 

13.7 

16.5 

18.6 

1.39 

1.42 

1.57 

1.57 

1.66 

1.58 

1.54 

1.64 

1.45 

1.77 

1.47 

1.49 

1.42 

1.60 

1.45 

1.59 

1.47 

1.37 

1.34 

1.58 

1.41 

1.92 

1.32 

1.49 

1.42 

1.63 

0.0 

2.4 

1.1 

1.2 

0.0 

0.0 

8.0 

4.4 

0.0 

1.6 

1.2 

3.1 

5.0 

4.8 

0.0 

3.2 

0.0 

1.0 

2.9 

2.0 

4.8 

31.0 

0.0 

1.6 

1.0 

9.5 

SE = standard error. 

TABLE 12-7. GEOMETRIC MEAN AND GEOMETRIC 

STANDARD DEVIATIONS (IN PARENTHESES) OF BLOOD 

LEAD LEVELS BY AGE AND STUDY SECTOR (-ug/dl) 

Study 

sector 

I 

II 

III 

<10 

66(1.33) 

47(1.30) 

34(1.26) 

Age. years 

10-19 

39(1.26) 

33(1.23) 

28(1.40) 

>20 

38(1.32) 

33(1.33) 

30(1.35) 

Likewise, a study of traffic exposure in Dallas, 

Texas,34 found mean blood lead concentrations of 

12 to 18 /xg/dl in children as contrasted with 9 to 14 

figldl 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 summer 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 2 40.0 /xg/dl, 

whereas 31.4 percent of those 3 years of age or older 

had values240.0/xg/dl. 

Elam et al.36 studied pediatric patients in a 

Chicago outpatient service. The proportion of 

children (Table 12-8) with blood lead values 2 50 

figldl varied with age; the proportion over 50 figldl 

peaked at 18 to 30 months of age. 

TABLE 12-8. PROPORTION OF CHILDREN WITH BLOOD 

LEAD VALUES BETWEEN 50 AND 99 /xg/dl, BY AGE, 

CHICAG01971-197536 

Age. months 

% Blood lead 

50lo99/jg/dl 

6-17 

18-30 

31-42 

43-52 

55-66 

24 

40 

16 

12 

7 

A study of Philadelphia ghetto children37 conducted 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 
P.17 

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 1 year of age 

and those 1 to 3 years old. Blood lead levels 

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, 

TABLE 12-9. MEAN BLOOD LEAD (/xg%) BY AGE, SEX, AND G6PD STATUS IN 1559 URBAN BLACK CHILDREN37 

Age, years Sex Number 

G6PD 

normal 

G6PD 

deficient 

<1 

1-3 

4-8 

9-13 

14-18 

Both 

Males 

Females 

Both 

Males 

Females 

Both 

Males 

Females 

Both 

Males 

Females 

Both 

Males 

Females 

61 

32 

29 

289 

133 

156 

404 

177 

227 

394 

189 

205 

242 

94 

148 

19.1 ± 

19.5 ± 

19.2 + 

29.1 ± 

30.5 ± 

28.8 ± 

25.0 ± 

24.6 ± 

25.1 ± 

21.3 ± 

20.4 ± 

21.7 ± 

18.7 ± 

18.5 ± 

18.8 ± 

9.5 

9.0 

9.2 

14.6 

15.1 

11.0 

12.6 

13.2 

11.1 

10.4 

10.9 

9.7 

9.7 

10.1 

8.9 

9 

6 

3 

40 

30 

10 

55 

38 

17 

44 

29 

15 

21 

13 

8 

18.3 ± 8.2 

18.8 ± 8.2 

17.3 ± 8.4 

33.2 ± 15.5 

33.1 ± 15.5 

33.6 ± 13.5 

25.7 ± 13.4 

25.2 ± 12.9 

26.1 ± 13.5 

23.0 ± 12.5 

22.1 ±11.8 

24.8 ± 13.9 

19.1 ± 9.9 

18.9 ± 9.3 

19.5 ± 10.1 

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 

25.2 

22.3 

22.6 

22.2 

20.5 

18.1 

21.5 

19.9 

18.7 

20.1 

19.7 

17.4 

17.9 

21.0 

19.9 

17.1 

20.3 

18.6 

19.1 

20.7 

13-24 

31.2 

29.7 

26.3 

26.9 

25.7 

22.9 

20.7 

24.9 

22.9 

20.6 

21.8 

21.4 

19.6 

18.6 

23.9 

22.8 

20.2 

21.5 

20.5 

20.0 

17.2 

25-36 

31.2 

30.4 

26.7 

26.3 

25.5 

22.9 

21.2 

25.5 

25.0 

22.1 

22.5 

23.0 

20.6 

19.2 

24.7 

22.9 

22.0 

21.9 

20.0 

19.0 

19.1 

Age. months 

37-48 

28.4 

29.8 

25.8 

25.6 

24.4 

22.3 

20.9 

23.9 

24.9 

22.6 

23.1 

22.6 

20.9 

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 

24.1 

24.4 

22.1 

22.2 

22.1 

20.6 

19.2 

23.7 

23.9 

21.2 

20.6 

21.4 

19.8 

18.4 

61-72 

22.9 

27.7 

24.3 

24.1 

22.2 

21.8 

19.2 

24.5 

23.9 

22.0 

21.6 

20.1 

20.0 

18.2 

24.9 

21.9 

21.4 

21.6 

21.3 

18.0 

17.7 

73^ 

25.7 

27.0 

23.8 

23.1 

22.1 

19.6 

19.3 

24.0 

23.9 

21.3 

21.7 

20.3 

18.5 

18.4 

22.5 

21.7 

20.6 

21.1 

19.6 

17.3 

17.5 

12-8 
P.18 

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 /xg/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 

1 

i 

-

Illl l 

/ BLACK 

/ HISPANIC "*•— . . 

/ ^^ \ 

/ WHITE ^ v 

Illl l 

^ 

-

 T 

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 substantial 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, 1970-19773* 

Year White Black Hispanic 

1970 

1971 

1972 

1973 

1974 

1975 

1976 

1,282 

2,796 

1,350 

823 

601 

656 

491 

8,839 

23,174 

16,730 

9,722 

4,139 

4,585 

3,755 

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 figldl in the first year 

of life, increasing with each year to a mean of 11.5 ± 

4.9 figldl 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

.

4

0-4' 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.4243 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. 18.25,38,44,45 The 

earlier studies1844 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 higher 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 (/ug/dl)18 IN MILITARY 

RECRUITS, BY RACE AND PLACE 

Place Number 

Urban 58 

Suburban 4 

Outstate 15 

Mean 

38 

80 

59 

90th 

percentile 

85 

124 

105 

Number 

203 

218 

406 

Mean 

31 

27 

39 

90th 

percentile 

69 

54 

71 

It is of interest to note that the age-associated pattern 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.16254046 In general, these data support the 

conclusion that workers exposed to automobile exhaust, lead fumes, or dust in manufacturing carry 

higher lead burdens than those who do not. 

12-9 
P.19 

TABLE 12-13. GEOMETRIC MEAN BLOOD LEAD LEVELS 

(Mg/dl) IN NEW YORK LEAD SCREENING PROGRAM, 

1970-1976, FOR CHILDREN UP TO 72 MONTHS OF AGE, BY 

RACE AND YEAR" 

Year 

1970 

1971 

1972 

1973 

1974 

1975 

1976 

Black 

28.6 

28.5 

25.0 

25.0 

23.9 

22.0 

20.0 

Hispanic 

24.0 

23.4 

21.3 

21.9 

21.6 

19.8 

18.7 

While 

23.8 

22.4 

20.4 

21.3 

20.8 

19.0 

18.6 

12.3 RELATIONSHIPS BETWEEN EXTERNAL 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. automobile 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 primary 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 importance of combustion of leaded gasoline to total 

lead burden in humans have only recently been initiated. 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 contribution 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 exposed 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 stationary 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 discussed. 

Clinical studies have the advantage of permitting 

precise control over the levels of exposure but have 

the disadvantages of studying people under somewhat 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 successful; traffic policemen had less education than 

their controls and the garage employees were 

younger than their controls. Females were matched 

12-10 
P.20 

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. 

jjg'd l 

23.1 

18.4 

28.3 

21.3 

12.9 

11.9 

SD 

9.21 

7.38 

10.33 

9.70 

4.47 

4.28 

Sample 

size 

141 

150 

119 

95 

120 

117 

P = 0.05 

P= 0.05 

P > 0.05 

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 residents studied were individuals living in the vicinity 

of heavily traveled freeways within the city. They included males and females, aged 1 through 16, 17 

through 34, and 35 and over. The persons selected 

from Lancaster represented similar age and sex distributions. 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 subjects. 

Lead in ambient air along the Los Angeles freeway averaged 6.3 ± 0.71 /xg/m3

, and in the Lancaster area the average was 0.6 ± 0.21 /ig/m3

. The 

mean soil lead in Los Angeles was 3633 figlg, 

whereas that found in Lancaster was 66.9 figlg. 

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 (Mg/dl) 

FOR LOS ANGELES AND LANCASTER, CA, BY SEX AND AGE7 

Groups by sex 

and age. years 

Total 

Males 

1-16 

17-34 

35-

Females 

1-16 

17-34 

35-

N 

126 

56 

20 

29 

7 

70 

18 

41 

11 

Los Angeles 

Mean 

16.4 

19.3 

23.5 

16.6 

18.5 

14.2 

16.7 

12.9 

14.7 

SEa 

0.7 

1.1 

2.5 

1.1 

2.0 

0.7 

1.8 

0.6 

1.5 

Geometric 

mean 

14.6 

17.2 

20.8 

15.1 

17.1 

12.8 

14.9 

11.8 

13.4 

N 

119 

50 

21 

18 

11 

69 

25 

16 

28 

Lancaster 

Mean 

10.5 

11.8 

11.1 

11.8 

13.0 

9.6 

10.2 

9.1 

9.3 

SE 

0.4 

0.6 

0.8 

0.9 

2.0 

0.4 

0.7 

1.2 

0.5 

Geometric 

mean 

9.6 

10.8 

10.4 

10.9 

11.1 

8.8 

9.6 

8.0 

8.7 

Significance 

of difference 

P b 

«.00 1 

«.00 1 

«00 1 

.003 

.09 

«00 1 

•C001 

<001 

<001 

a

 Standard error. 

b

 I test. 

It has been pointed out by Snee that, in the hightraffic-density area, the reported 29 percent of samples in children 1 through 16 years old exceeding 40 

figldl represented 5 individuals.50 For 3 of these a 

second blood sample showed approximately 20 

figldl; 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 
P.21 

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 residents. 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 DENSITY" 

-

-

o 

•r-" 

D 

I 

O 

I 

o 

I 

o 

1 

O 

! "1 

0 

o o^^^ ^ 

O 

O 

" " 

1 1 T 1 

0 

Y =• 0.6598 + 0.0263 X 

X = cars/day 

1 1 1 1 

-

-

_] 0 4,000 8.000 12.000 16.000 20.000 24.000 28.000 32.000 36,000 38.000 

TRAFFIC VOLUME, cars/day 

Figure 12-4. Arithmetic mean of air lead levels by traffic 

count, Dallas, 1976.3" 

In addition, during this phase, data for indooroutdoor comparisons of air lead levels were collected. 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 between indoor-outdoor values in both locations. It 

has been postulated that at least part of this 

difference is the result of using air conditioners. 

TABLE 12-16. MEAN AIR LEAD LEVELS (fj.g/m3) INDOORS 

AND OUTDOORS AT TWO TRAFFIC DENSITIES, DALLAS, 

TEX. 1976*" 

10.000 cars'day 20.000 cars day 

Outdoor Indoor Outdoor 

Mean 

N 

0.182 

9 

0.918 

9 

0.199 

5 

2.105 

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 concentrations were about 55 percent of the street concentration; at 100 ft concentrations were less than 40 

percent of the street concentrations. In air lead collections from 5 to 100 ft from the street, approximately 50 percent of the airborne lead was in the 

respirable range ( < 1 fim) 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 12-17). The maximum 

soil level obtained was 730 figlg. 

Traffic density, 

vehicles/day 

Soil lead levels. 

II gig 

<1.000 

1,000-13,499 

13.500-19,499 

>19,500 

73.6 

92.2 

110.9 

105.9 

Dustfall samples for 28 days from 9 locations 

showed no relationship to traffic densities, but outdoor levels were at least 10 times the indoor concentration in nearby residences. 

In the second phase, three groups of subjects, 1 to 

6 years old, 18 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 figldl, than in adults, 9 

to 14 figldl. 

-

-

~ 

1 1 1 1 

A. 

f ' \ FEMALES < 9 

* / \ \ MALES < 9 

** -VfC—'" MALES >49 

°~~ ^ j ^ _Q _ FEMALES19-49 

ef " .Q_ 5 

FEMALES >4 9 

1 1 1 1 

< 1,000 1,000-13.500 13,500-

19,500 

19,500-

38.000 

TRAFFIC DENSITY, cars/day 

Figure 12-5. Blood lead concentration and traffic density by 

sex and age, Dallas, 1976.34 

Galke et al.43 studied blood lead levels in 187 

South Carolina children l 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 
P.22 

TABLE 12-18. BLOOD LEAD CONCENTRATIONS IN 

RELATION TO SOIL LEAD CONCENTRATIONS AND TRAFFIC 

DENSITY** 

(MQ/dl) 

Soil lead 

concentrations. 

uglg 

<585 

>585 

Total 

Low mean 

(951-1677 

cars/day) 

32 (7)a 

36(10) 

34(9) 

Automobile traffic density 

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, reported 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 figldl. 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 figldl. 

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, 1971" 

(M9/dl) 

Distance of residence 

from roadway, ft 

<100 

100-200 

>200 

number 

Percent blood lead levels 

<40 

42.6 

72.4 

68.4 

3401 

40-59 

49.3 

24.2 

26.9 

1562 

>60 

8.1 

3.4 

4.7 

263 

Number 

758 

507 

3961 

5226 

No other sources of lead were considered in this 

study. Data from other studies on mobile sources indicate, 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 subjects lived in houses on streets paralleling the highway 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 /ttg/m3, respectively, for the 3 distances. 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 significantly 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 fig/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 highway were 33.5 and 457 meters and where the subjects 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, reaching background air lead levels at 250 ft, the explanation 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 figldl for women. These 

concentrations were higher than for control subjects 

living near the ocean: 16.0 ± 8.4 figldl for men and 

9.9 ± 4.9 figldl 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 12.25 ± 

2.70 jag/m3 at a location 30 ft from the San Bernardino freeway; 13.25 ± 1.90 /u.g/m3

 at another location 40 ft from the same freeway; 6.40 ±2.1 5 /Lig/m3 

at a fourth floor location 300 ft from the freeway; 

and 4.60 ± 1.92 /u.g/m3 1 mile from the nearest freeway. The investigators concluded that the 

differences observed were consistent with coastal-inland 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 demonstrated. 

12.3.1.1.2 British studies. In a Birmingham, England, study, mean blood lead levels in 41 males and 

58 females living within 800 m of a highway interchange were 14.41 and 10.93 figldl, respectively, 

just prior to the opening of the interchange in May 

1972.54 prom October 1972 to February 1973 the 

respective values for the same individuals were 

18.95 and 14.93 fig/dl. In October 1973 they were 

12-13 
P.23 

23.73 and 19.21 figldl. 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 samples. To interpret the significance of the change in 

blood collection method, some individuals gave 

both capillary and venous blood at the second collection. 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 figldl, 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 ,ug/dl and that for the females to 

18.7 figldl. These adjusted means still show an increase 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 following the model of Knelson et al.56

 because air lead 

values near the road were approximately 1 ,u.g/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 inhaled 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,5758 

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 produce 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 nonindustry-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 between environmental exposure and human response. 

12.3.1.2.1.1 El Paso, Texas. In 1972, the Center for 

Disease Control, formerly the Communicable Disease 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 1971,33 

These figures, however, include only stack emissions; the quantities in fugitive emissions via ventilation, windows, etc., are unknown. Daily highvolume samples collected on 86 days between 

February and June 1972 averaged 6.6 /ig/m3 of lead. 

Concentrations ranged from 0.49 to 75 /ig/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 highest levels occurring near the smelter. The geometric 

means of 82 soil and 106 dust samples from the sector closest to the smelter were 1791 and 4022 figlg, 

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 living near the smelter had blood lead levels > 40 

/xg/dl, and 14 percent had blood lead levels that 

exceeded 60 figldl. Concentrations in older individuals were lower; nevertheless, 45 percent of the 

children 5 to 9 years old, 31 percent of the individuals 10 to 19 years old, and 16 percent of the 

individuals above 19 had blood lead levels all exceeding 40 figldl. 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 >4 0 figldl, 

the geometric mean concentration of lead in soil at 

their homes was 2587 figlg, whereas for those with a 

blood lead concentration <40 figldl, home soils had 

a geometric mean of 1419 figlg. For housedust, the 

respective geometric means were 6447 and 2067 

Mg/gAnalysis 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 figldl, 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 con12-14 
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 attendance, or employment of a parent at the smelter. The 

reported prevalence of pica also was minimal. 

It was concluded that the primary factor associated 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 particulate, and suspended sulfates, singly and in combination 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 environmental 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 atmosphere averaged 8.3 metric tons per month from 

1955 to 1964, 11.7 metric tons from 1965 to September 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 figldl 

were found in 385 (41.9 percent) of 919 children less 

than 10 years old who were examined. About 99 percent of the 172 children living within 1.6 km of the 

smelter had blood lead values 240 figldl. 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 active ingestion of lead-containing material (pica), 

with lower socioeconomic status, and with parental 

employment at the smelter or at a lead mine. A significant 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)" 

GM 

blood lead. 

ug/dl 

65.9 

47.7 

33.8 

32.2 

27.5 

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. 

/xg/mJ 

18.0 

14.0 

6.7 

3.1 

1.5 

1.2 

Distance from 

smelter. 

km 

0- 1.6 

•1.6- 4.0 

4.0-10.0 

10.0-24.0 

24.0-32.0 

about 75 

a

 EPA analysis of data from Yankel et al.1 

level and hematocrit value was found. Seven of 41 

children (17 percent) with blood lead levels 280 

figldl were diagnosed by the investigators as being 

anemic on the basis of hematocrit less than 33 percent, whereas only 16 of 1006 children (1.6 percent) 

with blood lead levels < 80 figldl were so diagnosed. 

Although no overt neurologic disease was observed 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 correlation was found between the estimates and the 

measured blood lead levels (r + 0.72). 

12-15 
P.25 

Figure 12-6. Monthly ambient air lead 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.' The 

follow-up was undertaken to determine the effectiveness 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 distance from the smelter, the concentrations in the two 

years were 18.0 to 10.3 /Ag/m3, 14.0 to 8.5 /ng/m3, 

6.7 to 4.9 jug/m3, and, finally, 3.1 to 2.5/ig/m3 at 10 

to 24 km. Similar reductions were noted in the 

housedust lead concentrations. 

In a separate report, von Lindern and Yankel described 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 complicate any analysis in which they were included. To 

compensate for this, the authors also presented separately 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 reductions 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 figldl. 

The report of Yankel et al.1 showed that there 

I 1 AUG. 1974 

rrrr\ AUG. 1975 

CONTROL 

D_D_n 3 4 5 

BY AREA (SEE TEXT! 

Figure 12-7. Annual ambient air lead concentration, by area, 

before the August 1974 and August 1975 surveys.1 

were reductions in environmental lead contamination between 1974 and 1975, and that the correlations 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 

(Mg/m3). 

2. Concentration of lead in soil (ppm). 

3. Age (years). 

4. Cleanliness of the home (subjective evaluation coded 0, 1, and 2, with 2 signifying 

dirtiest). 

5. General classification of the parents' occupation (dimensionless). 

Although the strongest correlation found was between blood lead level and air lead level, the 

authors concluded that it was unlikely that inhalation of contaminated air alone could explain the elevated 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 
P.26 

TABLE 12-21. MEAN BLOOD LEAD LEVELS IN CHILDREN LIVING IN VICINITY OF A PRIMARY LEAD SMELTER, 1974 and 1975 

Group N H N 

II 

X 

Study area and data set 

III 

N •)( N 

IV 

X N 

V 

X 

Blood levels 

>80,ug/d|a 

in 1974 test 

Retested in 

1975 

Difference 

Blood levels 

>60 but <80 

/ug/dl in 1974 

test 

Retested in 

1975 

Difference 

Blood levels 

<60n.g/dl 

in 1974 test 

Retested in 

1975 

Difference 

90.2 

52.3 

-38.0 

64.5 — 

47.4 8 

-17.2 — 

52.3 — 

80.0 

61.0 

-19.0 

69.6 

50.3 

-19.3 

47.0 45.6 

37.4 23 36.0 20 39.8 

-14.9 — -11.0 — - 5.8 

14 

43.7 

37.4 

- 6.3 

61.0 

51.0 

-10.0 

43.4 

33.5 

- 9.9 

a

 Adapted from von Lindern and Yankel.63 

of the children in this area the regulation of environmental 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 variations in the environmental factors on mean blood 

lead levels in children: 

1 n (Pb-B) =3.1 + 0.041 (Air) + 2.1 x 105 (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 determinations were made for this study. 

12.3.1.2.1.4 Meza Valley, Yugoslavia. A Yugoslavian study in the Meza Valley investigated exposures to lead from a mine and a smelter over a 

period of years.6469 The mine and smelter are located 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-emitting 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 concentrations of up to 60 /ig/m3

 were found as far as 5 

km from the source. Mean particle size in 1968 was 

<0.8 /im. The lead levels were about 25,000 ppm in 

the most contaminated area. Analysis of some common 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 emissions was established at the smelter, weighted 

average weekly exposure was calculated to be 27 

figlm* in the village near the smelter. In contrast to 

this, the city of Zagreb,65 which has no large station12-17 
P.27 

ary source of lead, had an average weekly air lead 

level of 1.1 figlm*. 

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 undertaken.66

 ALA-U decreased significantly from the 

previous year. When the published data were examined closely, there appeared to be some discrepancies in interpretation. The exposure from dust 

and from food might have been affected by the control 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 exposure of 25 ^g/m3

, it is possible that some other explanation should be sought. The author indicated in 

the report that the decrease in ALA-U showed "the 

dependence on meteorologic, topographic, and technologic 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 figldl blood as defined by the 

author).fif> In light of current knowledge, this definition 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 burdens ranging from normal to ten times normal.6668 

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 timeweighted 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 exposures held. In Table 12-22, the estimated timeweighted blood lead values as well as the observed 

mean blood lead levels for these studied populations 

are presented. An increase in blood lead values occurs 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 

Timeweighted 

air lead 

Mg/m3 

0.079 

0.094 

0.146 

1.6 

1.8 

2.1 

3.0 

Mean blood 

lead level, 

jjg/dl 

7.9 

11.4 

10.5 

18.3 

10.4 

24.3 

12.2 

SD 

4.4 

4.8 

4.0 

9.3 

3.3 

10.5 

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 /xg/m3; the maximum 24-hr 

value was found to be 15 figlm*. In the city of 

Helena, the average concentration was 0.1 jig/m3. 

Lead in soil was found to be 4000, 600, and 100 

figlg at distances of 1.6, 3.2, and 6.4 km (1, 2, and 4 

miles), respectively, from the smelting complex. Uncontaminated soil near the Helena Valley showed a 

mean of 16 figlg. Deposited lead (dustfall) was 

found to vary from 3 to 108 mg/m2-month in East 

Helena and from 1 to 7 mg/m^-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 figldl in blood and about 40 and 13 

ppm in hair. The hair values indicated differential 

exposure to lead. However, in the opinion of the investigators, 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.7072 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 
P.28 

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 major strides were taken in improving analytical technology. Hence, the more recent studies are likely, 

but not necessarily, to provide more accurate information. 

Although many of the reports specified that the 

blood lead levels were done in duplicate, this unfortunately does not ensure their accuracy. This problem 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 inner-city area of Omaha, Neb. have been reported by 

Angle et al. in a series of publications.7376 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 techniques 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 pig/m3. 

TABLE 12-23. AIR, DUSTFALL, AND BLOOD LEAD CONCENTRATIONS IN OMAHA, NEB., STUDY, 1970-1977a'

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 

1.48 

0.43 

0.10 

0.52 

1.69 

0.63 

0.10 

0.60 

0.79 

0.29 

0.12 

M9 

± 

l+ 

± 

+ 

+ 

l+ 

+ 

+ 

l+ 

+ 

+ 

Air, 

m

3

 IN)b 

0.14(7:65) 

0.08(8;72) 

0.03(10:72) 

0.07(12:47) 

0.11(7:67) 

0.15(8:74) 

0.03(10:70) 

0.10(12:42) 

0.06(7:65) 

0.04(8:73) 

0.05(10:73) 

— 

Dustfall. 

ng m3 - mo IN)C 

— 

10.6 ± 0.3(6) 

6.0 ± 0.1(4) 

8.8 (7) 

— 

25.9 ± 2.4(5) 

14.3 + 4.1(4) 

33.9 (7) 

— 

4.6 ± 1.1(6) 

2.9 ± 0.9(4) 

— 

Blood. 

Mg'dl (N)d 

31.4 + 0.7(168) 

23.3 ± 0.3(211) 

20.4 ± 0.1(284) 

22.8 ± 0.7(38) 

34.6 ± 1.5(21) 

21.9 ± 0.6(54) 

19.2 + 0.9(17) 

22.8 ± 0.7(38) 

— 

19.6 ± 0.5(81) 

14.4 ± 0.6(31) 

18.2 ± 0.3(185) 

rPb-B» Pb-A= -0.95 (N = 10) 

Pb-B = 10.04 Pb-A + 17.06 

r

lnPb-B» Pb-A= 0.91 (N = 10) 

1n Pb-B = 0.4 Pb-A I 2.86 

Blood lead 1970-71 is by the macro technique, corrected for an established laboratory bias of 3 ng dl, macro-micro; all other values are by Delves micro assay. 

N = Number of months; number of 24-hour samples. 

N = Number of months. 

N = Number ot 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 figldl) 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 fig 

percent versus schoolmates with blood lead levels 

below 20 fig percent.74 The urban versus suburban 

high school children did not differ significantly, 

22.3 ± 1.2 to 20.2 ± 7.0 figldl, respectively, with 

mean values of air lead concentrations of 0.43 and 

0.29 figlm3. For the 15 students who had environmental 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 respectively. 

Suburban 10-to-12-year-olds had lower blood 

lead levels than their urban counterparts, 17.1 ± 

0.7 and 21.7 ± 0.5 figldl, respectively.74 Air lead 

exposures were higher in the urban than in the 

suburban population, although the average exposure 

remained less than 1 /xg/m3. Dustfall lead measurements, 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 significant 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 figldl versus an average 

of 22 figldl in control children.77 For the two study 

populations, the air and soil lead levels were 3.5 and 

1.5 /xg/m3 and 727 and 255 ppm, respectively. 

Direct automobile traffic exposure was not considered. 

In Toronto, Canada, the effects of two secondary 

lead smelters on the blood and hair lead levels of 

nearby residents have been extensively studied.7879 

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 particulate fugitive emissions 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 exponentially with distance. They reached urban background 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.80 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 exponential decrease with distance similar to that observed 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 fim), it was believed that 

the emissions originated mainly from dust-producing operations at low height rather than from stack 

emissions.78 

Lead concentrations in air ranging from 1.0 to 5.3 

/xg/m3 were only twice those found at other Toronto 

urban sites away from the smelter (0.8 to 2.4 /xg/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 /xg/m3, whereas at 220 m 94 

samples varied from <0.5 to 14 /ng/m3. Two groups 

of children living within 300 m of each of the 

smelters had geometric mean blood levels of 27 and 

28 /xg/dl, respectively; the geometric mean for 1231 

controls was 17 figldl. 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 figldl. Only 1 percent of the controls had blood lead levels >40 /xg/dl. 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 figlg in 

the smelter areas and 13 figlg in the control area.78 

Blood lead and hair lead levels were found to be related, thus indicating a fairly constant rate of absorption. 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 figldl; that for 172 females was 14.3 

figldl. 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 

> 4 0 figldl, and none exceeded 50 /xg/dl. 

A weaker correlation was obtained between 

ALAD activity and distance from the smelter, this 

being due almost entirely to the female subjects. Examination 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.8283 Average concentrations of lead in air were as high as 4.1 /xg/m3

 at 

a distance of 1500 m; peak exposures at this distance 

reached 9.7 /ng/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 /xg/liter. 

Studies of the effects of storage battery plants have 

been reported from France and Italy.8485 The 

French study found that children from an industrialized area containing such a plant excreted 

more ALA than those living in a different area.84 Increased urinary excretion of lead and coproporphyria 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 encountered in their vicinities is much larger for daily 

or longer averaging times than in the vicinity of 

mobile sources. Increases of 2 to 3 /xg/m3 in air lead 

concentrations have been associated with higher 

blood lead levels in exposed populations. 

Although the significantly higher air lead concentrations 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'

316

-

41'12

 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 consisted of 30 men in each of 5 city-occupation categories. The subjects included cabdrivers, plant 

employees, and office workers. From two to eight 

blood samples were obtained from each subject during the air monitoring phase. Blood lead determinations were done in duplicate. Table 12-24 presents 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 (/xg/100 g) FOR FIVE CITY-OCCUPATION GROUPS3 

(Data calculated by EPA) 

Group 

Plant employees 

Starke, FL 

Plant employees 

Barksdale, Wl 

Cabdrivers 

Philadelphia. PA 

Office workers 

Los Angeles. CA 

Cabdrivers 

Los Angeles. CA 

Geometric 

mean 

air lead. 

ng/m3 

0.59 

0.61 

2.59 

2.97 

6.02 

GSD 

2.04 

2.39 

1.16 

1.29 

1.18 

Geometric 

mean 

blood lead. 

ug/100 g 

15.4 

12.8 

22.1 

18.4 

24.2 

GSD 

1.41 

1.43 

1.16 

1.24 

1.20 

Sample 

size 

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 surprising. 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 homogeneous. 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 
P.31 

/xg/m3, and geometric mean blood lead values 

ranged from 12.5 (1.31) to 20.6 (1.33) /xg/dl. 

TABLE 12-25. GEOMETRIC MEAN AIR AND BLOOD LEAD 

VALUES FOR 11 STUDY POPULATIONS2 

(Data calculated by EPA) 

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 

Geometric 

mean 

air lead. 

/ig 'm3 

0.17 

0.32 

0.85 

1.13 

1.15 

1.18 

1.19 

1.67 

1.76 

2.08 

3.39 

Blood lead./jg'dl 

GM 

14.9 

15.6 

12.5 

15.4 

18.0 

13.9 

19.2 

20.6 

17.6 

16.6 

17.5 

GSD 

1.28 

1.39 

1.31 

1.28 

1.38 

1.27 

1.26 

1.33 

1.27 

1.28 

1.31 

Sample 

size 

185 

156 

186 

196 

148 

146 

219 

136 

146 

139 

194 

Nordman reported a population study from Finland16

 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 stationary samplers. All levels were comparatively low, 

particularly in the rural environment, where a concentration of 0.025 /xg/m3

 was seen. Urban-suburban levels ranged from 0.43 to 1.32 /ig/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 correlation 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 

Air lead, 

jig'm ^ 

Blood lead. 

ng 100 g 

0.024 

0.198 

0.444 

0.831 

1.157 

17.0 

17.1 

16.8 

18.0 

19.7 

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 /xg/m3. For 

boys in elementary school, blood lead levels ranged 

from 14.3 to 23.3 /xg/dl; those for girls ranged from 

13.8 to 204 figldl for the same range of air lead exposures. 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 /xg/m3 and the 

blood lead range was from 9.0 to 12.1 /xg/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 

STUDIE S IN RELATIO N T O AI R 

LEAD/BLOOD LEAD RATIOS 

Griffin and his colleagues undertook two studies 

using volunteers exposed in a gas chamber to an artificially generated aerosol of submicron-sized particles of lead dioxide.86

 All volunteers were introduced into the chamber 2 weeks prior to the initiation 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 /xg/m3 exposure study. Twenty-one subjects, including 6 controls, participated in the 3.2 /xg/m3

 exposure study. Not all volunteers completed the exposure regimen. Blood lead levels were found to 

stabilize after approximately 12 weeks. Among II 

men exposed to 10.9 /xg/m3 for at least 60 days, a 

stabilized mean level of 34.5 ± 5.1 /xg/dl blood was 

obtained, as compared with an initial level of 19.4 

± 3.3 /xg/dl. AU but 2 of the 14 men exposed at 3.2 

/xg/m3 for at least 60 days showed increases and a 

stabilized level of 25.6 ± 3.9 figldl was found, compared with an initial level of 20.5 ± 4.4 /xg/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 /xg/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 experiment 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, jjg'm 

10.9 

10.9 

10.9 

3.2 

3.2 

3.2 

Avg. baseline 

blood lead 

level, (tig-'dl 

Target 

blood lead 

level, jjg/dl 

25 

30 

35 

25 

30 

35 

Time needed 

to reach 

target level, wk 

1 to 2 

4 

6 

7 

Not reached 

Not reached 

20.0 

20.0 

20.0 

20.8 

20.8 

20.8 

levels with those predicted by Goldsmith and Hexter's equation,87

 that is, log10 blood lead = 1.265 + 

0.2433 log 10 atmospheric exposure. 

In contrast to the study of Griffin et al. that 

approximates the exposure regimen of environmentally exposed persons, Kehoe studied long-term 

exposures under conditions approximating those of 

occupationally exposed individuals.88 Kehoe exposed a subject to an air lead as the sesquioxide first 

at 75 /xg/m3 then at 150 /xg/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 /xg/dl, 0.88 /xg/day, and 2.50 /xg/day, respectively, for each increase of 1 /xg/m3

 in air lead 

levels.89 

The derivation of these estimates is currently unknown 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 approximately 30 /xg/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 /xg/dl. ' 

Rabinowitz and colleagues have conducted 

studies of lead metabolism by stable isotopes that 

permit the determination of blood/air lead relationships.9091

 In one study, a single volunteer was confined 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 compensate 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 decliningblood 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 additional 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 concentration92

 was typically about 6 mg/m3 and the 

total particulate 30 mg/m3. The aggregates of particles about 0.6 fim in diameter were stable: those .5 

0.01 fim 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 percent of the particles was retained, and that 60 percent was exhaled. The lung clearance rate for

 203Pb 

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 highlevel, short-term exposures to longer term ones. The 

following formula and data were used to calculate a 

blood-to-air level ratio: 

12-23 
P.33 

[T|/2 ] [%Deposition] [%Absorption] [Daily 

ventilation] 

[Blood volume] [0.693] 

where: a = blood to air lead ratio 

biological half life 

(12-7) 

1

 1/2 

Data used were: 

1. Airborne level = 1 /xg/m3 

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, Chamberlain 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 /xg/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 depending on whether the air lead exposure is increasing, remaining constant, or decreasing. 

On the first point, only a few studies have sufficiently precise estimates of air lead exposures to permit this calculation, namely Yankel et al.1

 and Azar 

et al.3 EPA used William's

 96

 test on the data from 

both these studies to determine the air lead levels at 

which blood lead levels were found to be significantly 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 concentration for this area was 1.7 /xg/m3

. 

EPA, using this same test for the Azar et al. 

study,3 showed that blood lead values for the Philadelphia 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 exposures were 2.6 and 3.1 /xg/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 /xg/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 ,u.g/m3; the Azar et 

al. data,3 at 2.6 /xg/m3. These results are not inconsistent 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 between 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 concentration. 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 relationship 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, depending on the form of the relationship that was fitted. 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 regression 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 observations on 4 individuals experimentally exposed 

to 10 and 150 /xg/m3 in a pattern equivalent to a normal work exposure were found to fit the equation. 

The slope of this line was not significant below 2 

figlm3 of air exposure, possibly because few observations were available in the Three-City Study below 

that level. The derived slope of the regression line 

suggests an increase of 1.3 /xg/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 /xg/m3 to 0.7 at an air lead of 5.0 

/xg/m3. It is important to note that all four air lead 

concentrations of interest are well within the range 

of the air levels observed. 

40 

20 

10 

-

1 

•' 

_—^—7~* 

*. 

• * • 

l 

1 

L-^-r~ 

• *.. 

9 

• 

1 

1 

•' 

" 

' 

» 

1 

1 1 1 

. ° 

. 

O LOS ANGELES OFFICE WORKERS 

A LOS ANGEt-ES CAB DRIVERS 

• BARKSDALE. WISCONSIN 

7STARKE, FLORIDA 

• PHILADELPHIA CAB DRIVERS 

1 1 1 

TOTAL AIR LEAD, ng/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 

Nordman" 

Fugasb 

Johnsonb 

Johnson^ 

Tsuchiyab 

Goldsmithb 

Goldsmithb 

Yankel-von Linderna 

Chamberlains-Williams 

Dainesb 

Clinical 

Griffin" 

Griffin" 

Rabinowitz" 

Gross0 

Chamberlain0 

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 @10.9 

14® 3.2 

2 

(21,000 person-days) 

7 

5 

1.0 

2.57 

0.87 

1.16 

Ratio at 

air lead concentrations, 

2.0 

1.43 

0.92 

1.21 

u. g/m' 

3.5 

0.89 

1.00 

(0.42)° 

(0.11) 

(2.64) 

(0.80) 

(0.60) 

(3.84) 

(2.30) 

(1.70) 

1.27 

(1.10) 

(2.30) 

(1.40) 

(1.65) 

(1.7,2.5) 

(0.38) 

(1.20) 

(1.10) 

5.0 

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 
P.35 

One of the authors, Snee,50 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 improvement 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 /xg/m3 to 1.4 at an air lead of 5.0 yxg/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 assumption is not correct. Obviously, the monitored air lead 

values are not the exact values inhaled by the subjects 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 estimates could be calculated. 

The Yankel et al. study1 gives sufficient information to estimate the effect of this problem. The 

authors assigned 1 of 33 different estimated exposure 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 

figlm3 and from 1.37 to 1.69 at 5 Mg/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 exposures 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 reported by Hasselblad and Nelson22

 was used to estimate 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 exposure. 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 loglinear model at the four air lead values shown in Table 12-28. These slopes ranged from 0.9 at an air 

lead of 1.0 figlm3 to 1.1 at an air lead of 5.0 /xg/m3. 

The air lead values only ranged from 0.2 to 3.4 

/u.g/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 ievels of black females living in residences 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 presented in Table 12-29. From these values a ratio 

may be calculated as follows: 

23.1-17.6 ratio = A ,,, ~ ~A = 2.3 for the total population. 4.60-2.24 

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 

Area C 

In Yugoslavia, Fugas et al. in the study described 

earlier,69 estimated the weekly time-weighted air 

lead exposures of eight population groups. The estimates were based on air lead values monitored at 

various locations and estimated proportions of time 

the individuals spent at those locations. The timeweighted 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 sample 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 ,ug/m3. The resulting 

slope is 2.64, and is presented in Table 12-28. 

Distance from 

highway, m 

3.7 

38.1 

121.9 

Air lead. 

Mg/m' 

4.60 

2.41 

2.24 

Blood lead 

jjg/l00g 

23.1 

17.4 

17.6 

12-26 
P.36 

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. Unfortunately, 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 gradient that parallels the air lead concentrations. 

Weighted regression analysis was used on the blood 

and air lead data reported in Table 12-26. The estimated slope is 3.8 and is recorded in Table 12-28. 

The observed range in air lead concentrations was 

0.024 to 1.157 Mg/m3. 

From the Johnson et al. study in California,6 estimates of the ratio between blood and air lead levels 

can be derived. Because of analysis problems encountered 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 figldl for Los Angeles and Lancaster, 

respectively. For females, the corresponding values 

are 12.1 and 8.4 figldl. 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 variation 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 Mg/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 STUDYTM 

Group 

Pertummaa 

Pyhajarui 

Suburban 

Downtown 

Policemen 

Street sweepers 

Air lead, 

Mg/m3 

0.025 

0.025 

0.74 

0.90 

1.32 

1.32 

Male blood lead, 

N 

243 

— 

37 

142 

28 

86 

ixg/dl 

Avg 

12.1 

— 

10.6 

11.4 

13.5 

13.3 

SD 

4.5 

— 

2.8 

3.3 

2.8 

4.1 

Female blood lead, 

N 

256 

93 

81 

37 

— 

11 

/jg/di 

Avg 

9.6 

8.6 

9.7 

8.5 

— 

10.4 

SD 

3.5 

2.5 

2.6 

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, respectively (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 nonexposed population. He calculated a slope of 1.1. 

Clinical studies also provide data useful in quantitating 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 

Mg/m3. The study design, it was believed, precludes 

fitting an overall equation to these data, and a separate calculation of a ratio is presented for the two experiments. In both experiments, the background air 

lead levels were estimated to be 0.15 Mg/m3- 1°

 tn e 

3.2 Mg/m3 air lead exposure, the men increased their 

mean blood lead levels from 20.5 to 25.6 figldl. 

This yields a ratio of 1.65 (25.6-20.5)/(3.2-0.15). 

The 10.9 Mg/m3 air lead exposure resulted in an increase of blood lead levels from 19.4 to 34.5 figldl. 

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 

Mg/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 between 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 ex12-27 
P.37 

trapolation of a short-term exposure to a long-term 

one. The calculation involves a number of experimentally 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 increased, 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 determining 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, 

JJ g/m3 

0.91 

0.91 

air lead 

Filtered air, 

li g/m3 

0.072 

0.072 

Blood lead 

Normal air, 

/»g/l00g 

20.2 

16.3 

Filtered air, 

Mg/100 g 

18.8 

14.2 

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 = 

Plog,0 (blood lead) - 1.2257-0.1531 log|0 (air lead)1 

100 f rl( HMSE"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 representative 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* 

Percent exceeding blood lead level ol: 

r lead, 

ig/m3 

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 

20.0 

ug/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 

30.0 

f<g/di 

0.59 

1.67 

2.88 

4.12 

5.35 

6.57 

7.75 

8.90 

10.01 

11.09 

13.16 

15.10 

16.92 

40.0 

Mg/dl 

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 Irom the equation ol Azar et al.3 

The last element in defining the relationship between 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

 9I

 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 Mg/m3 

decrease in air lead levels resulted in a 2 figllOO g 

decrease in blood lead levels. 

Baker98 presented data to the EPA Science Advisory Board showing decreases in blood lead levels 

in the vicinity of an Idaho smelter between 1974 and 

1975 (fable 12-33). Information from all study 

areas combined indicated that blood lead levels had 

decreased by 2.3 figldl for each 1 Mg/m3 reduction 

in air lead. This same investigator provided additional information in a separate communication to 

EPA showing that, when analyses were limited to 

children of nonsmelter workers, blood lead levels 

decreased 2.0 figldl in all study areas for each 

decrease of 1 figlm3 of air lead. If the analyses included only those children of nonsmelter workers 

exposed to air lead levels ranging from 0.5 to 10 

12-28 
Mg/m3

, blood lead levels decreased 1.3 figldl 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) 

Study 

area 

1 

2 

3 

4 

Blood lead levels, 

1974 

69 

49 

36 

33 

II g/dl 

1975 

46 

38 

32 

27 

Diff. 

23 

11 

4 

5 

Ai 

1974 

18 

14 

6.7 

3.1 

lead levels, 

Ii g/m3 

1975 

10.3 

8.6 

4.9 

2.5 

Diff. 

7.7 

5.4 

1.8 

0.6 

Pb-B diff./ 

Pb-A diff. 

3.0 

2.0 

2.2 

8.0 

Data from Angle and Mclntire's studies7376 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 figldl 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 Mg/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 HUD3 8 

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. During 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 HiVol 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 concentrations vary from a minimum of 1.3 to 8 or 10 

figldl. 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 constant 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 exposure encountered (it varies in most studies between 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 decreasing 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 subject of scientific investigation for some time. 7 8 "- 1 0 5 

Duggan and Williams105 have recently published an 

assessment of the risk of increased blood lead resulting from the ingestion of lead in dust. Some of these 

studies have been concerned with the effects of such 

exposures:7899102 others have concentrated on the 

means by which the lead in soil and dust becomes 

available to the body.I03104 

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 compared with soil samples taken from the yards of 

homes where 37 cases of lead poisoning had occurred. The soil lead values obtained had a wide range, 

from 1 to 12,000 ppm, with 75 percent of the samples 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 additional sources of lead, such as paint or air. 

12-29 
P.39 

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 figlg), a 5-Mg/dl difference in blood lead 

levels was obtained. Soil lead exposure for this 

population ranged from 9 to 7890 figlg. 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 significantly related to blood lead levels. 

Barltrop et al.100 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 collected and analyzed for lead. Lead content of the 

suspended particulate 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 Mg/m3 compared with 0.29 Mg/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 preliminary and final form.100101

 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 Table 12-34, children's mean blood lead levels increased correspondingly from 20.7 to 29.0 figldl. 

Mean soil lead levels for the low and high soil exposure groups were 420 and 13,969 ppm, respectively. 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, 

n 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.3378102106 Some of these also 

included measurements of soil lead. 

Lepow et al.,106 for example, studied the lead content of air, housedust, and dirt, as well as the lead 

content of dirt on hands, food, and water, to determine 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 Mg/m3. The mean lead concentration in dirt was 

1,200 figlg and in dust, 11,000 figlg. The mean concentration 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 between 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 compared. Hair lead levels ranged from 12 figlg in the 

low area to 17 figlg in the high. Mean dustfall and 

housedust lead levels ranged from 2 to 16 mg/m2-

month, and from 279 to 766 figlg. 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 contributors to the hair lead levels. The investigators concluded 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 (/3 = 0.0662).34 

Lastly, Shellshear's case report from New Zealand 

ascribes a medically diagnosed case of lead poisoning 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.103104 Sayre et al. in Rochester, New York, 

demonstrated the feasibility of housedust being a 

source of lead for children.103 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 suburban 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 ingestion of dust and dirt. They reasoned that because 

the proportion of the naturally occurring isotope 

210Pb 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 hospitalized 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 criterion 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 hospitalized children, the stable lead mean value was 

22.43 figlg dry excreta, and the eighth child had a 

value of 1640 figlg. The controls' mean for stable 

lead was 4.1 figlg dry excreta. However, the respective means for

 210Pb 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

 210Pb and vastly different in respect to 

stable lead per gram of dry excreta. The hospitalized 

children ingested larger amounts of material containing stable lead. Granting that the hospitalized 

children ingested leaded paint chips and the controls 

did not. does not permit the conclusion that all the 

210Pb 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 summarized the literature on the amounts of lead ingested by ingestion of dust. In their opinion, a quantity of 50 Mg 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 indicate that soil lead exposures, often found in urban 

settings, can contribute between 5 and 8 figldl to the 

blood's lead burden.33101 

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 available 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 
P.41 

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/log (2))] (12-7) 

Study 

Age, 

years 

Regression 

coefficient, 

log-log 

Geom. mean 

blood lead, 

ug/dl 

Geom. mean 

soil level. 

»g/g 

Mean % increase 

in Pb-B for 2 x soil 

level 

Charleston.SC43 

Kellogg, ID1 

Dallas, TX34 

England101 

1-5 

1-9 

1-5 

2-3 

0.0432 

0.0528 

0.0662 

0.0840 

36.4 

37.5 

11.4 

23.2 

451.6 

1518.1 

91.6 

1849.1 

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 involved 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 community that was relatively lead free. It is interesting 

to note that the larger estimates of the percentage increase 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 constitutes 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 dietary intake of lead: duplicate meals, market basket 

surveys, and fecal lead determinations. The estimated 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 fig/day.88 Most of the 

more recent comparable data2109110 have reduced 

that estimate to between 50 and 150 Mg/day. The 

California study of Johnson et al.7 points to a daily 

intake of about 100 to 150 Mg. 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 132 Mg/day, and Barltrop and Killola a value 

of 130Mg-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 nutritional needs is analyzed. The foodstuffs are assembled in accordance with national food sample surveys. One such study111112

 has indicated that the 

lead content of the diet of young adults averages 150 

to 200 Mg/day, and another113 cites a figure of 254 

Mg/day for 15- to 20-year-old males. At least 30 percent 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 foodbased intake of 80 to 100 Mg 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 content, 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 sustained value of 6 figldl for 100 Mg of dietary lead intake. 

Water, itself, can also be a source of significant 

quantities of lead with the metal present in the supply 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 

Mg/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 occur. These cases most frequently involve isolated 

farms or houses in rural areas, but a surprising situation was revealed in 1972 when Beattie et al.114

-

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 association 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 piping, and (3) less than 60 ft of lead piping. The mean 

lead content of the water as supplied by the reservoir 

was 17.9 figlliler; that taken from the faucets of 

groups 1, 2, and 3 was 934, 239, and 108 Mg/l'ter, 

respectively. 

Another English study1 1 6 showed a clear 

difference between the bone lead content of the 

populations of Glasgow and London, the latter having 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.118119 Participants, 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 between water lead and blood lead was apparent (Table 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 Mg/'iter had a blood lead 

value 2 35 figldl. whereas only 17.4 percent of those 

consuming water within the standard had blood lead 

valuesof235 figldl. 

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) 

Blood lead 

levels, /jg/dl 

<50iig Pb/liler f5G>gPb/liter 

No. Percent Percent Total 

<35 

>35 

Total 

622 

61 

683 

91 

9 

100 

68 

20 

88 

77.3 

22.7 

100.0 

690 

81 

771 

x = 14.35; dl = 1. 

P <0.01. 

Greathouse et al. have published an extensive 

regression analysis of these data.119 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 waterborne lead is, therefore, considerably greater. 

12.3.4 Effects of Lead in the Housing Environment: Lead in Paint 

A major source of environmental lead exposure 

for the general population comes from lead contained in both interior and exterior paint on dwellings. The amount of lead present, as well as its accessibility, 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 professionals 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 dwelling is a complex function of history, geography, economics, 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 interior 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 permissible 1 percent level.122

 Later studies by the National 

Bureau of Standards123 and by the Consumer Product Safety Commission124

 showed a continuing 

decrease in the number of interior paints with lead 

levels greater than 1 percent. By 1974, only 2 percent 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 
P.43 

surface as well as the frequency of ingestion. Attempts to set an 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 attempted by local communities through health or 

housing codes and regulations. At the Federal level, 

the Department of Housing and Urban Development has issued regulations for lead hazard abatement 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 dependent more on the sensitivity of field measurement by 

different regulatory bodies (using X-ray fluorescent 

lead detectors) than on direct biological doseresponse relationships. Regulations also require 

lead hazard abatement when the paint is loose, flaking, 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 1940 

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 Pittsburgh, about 20 percent of the residences built after 

1960 have at least one surface with more than 1.5 

mg/cm2 lead. 

The distribution of lead within an individual 

dwelling varies considerably. Figure 12-10 presents 

the distribution of the highest paint lead measurements 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 windows where lead levels greater than 1.5 mg/cm2

 were 

found on 2 percent of the surfaces surveyed, whereas 

Al 

LEAD LEVEL (X). mg/cm 

Figure 12-9. Cumulative distribution of lead levels in dwelling 

units:*" 

only about l 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 Washington. D.C. showed similar results.127 

An attempt was made in the Pittsburgh study to 

obtain information about the correlation between 

12-34 
Al 

10

 r—i—,— 

0.9 

0.8 

0.7 

0.6 

0.5 

0.4 

0.3 

0.2 

0.1 

1 

1 

i 

1'. 

y, 

\\\ 

IM 

M 

" * \ 

1 M 

1 M 

" 1 \\ 

1 *K 1 M - 1 \\ 

I VjW-DOORS 

r- \ A \ U 

\ n 

\ \ 

" i 

i i i 

I i """?"" 

-

_ 

-

-

LEAD LEVEL (X), mg/cm 

Figure 12-10. Cumulative distribution ol lead levels by location in dwelling, all ages.126 

the quantity and condition of lead paint in buildings 

and the blood lead of children who resided there.128 

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 correlation 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 (XI. mg/cm* 

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

children from two lower socioeconomic communities.129

 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 main12-35 
P.45 

5 ioo 

5 80 

"TT" ~n—r—i—i i i i i i i—i—i— i i i i i i -| 

STD. DEV. = 1.39 

MEDIAN =20.7wg/dl 

\ I I I I I I I I I 1 I I I I I 

Figure 12-12. Cumulative frequency distribution of blood lead 

levels found in Pittsburgh housing survey.126 

The findings are presented in order to place in 

proper perspective both the concept of total lead exposure 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.

1

" 

z > 

UJ LJJ 

Q 20 

O 

o 

I I I I I I I I 

SURFACES IN BAD CONDITION, i.e., PEELING 

_ CHALKING, OR POOR SUBSTRATE 

ALL SURFACES 

* • 

I I I I 

• 

'I I I 

o 

I I 

-

— —• — 

I 

Fiscal year8 

Results 1976'" 197513' 1974"' 

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 

FRACTIONS OF SURFACES WITH LEAD > 2 mg/cm2 

Figure 12-13. Correlation of children's blood lead levels with 

fractions of surfaces within a dwelling having lead concentrations 22 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 positive findings defined as paint with more than 1 percent lead.130 

Data published or made available by the Center 

for Disease Control, Department of Health, Education, and Welfare, also show that a significant number of children with undue lead absorption occupy 

buildings that were inspected for lead-based paint 

hazards, but in which no hazard could be demonstrated.131132

 Table 12-37 summarizes the data obtained 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 elevated 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. 

No. children 

screened 

No. children 

with elevated 

lead exposure 

No. dwellings 

inspected 

No. dwellings 

with lead 

hazard 

500,463 440,650 371,955 

69,131" 28,5971= 16,228<= 

50,276 30,227 23,096 

28,333 17,609 13,742 

a

 Fiscal year 1976 includes transition quarter. 

bCDC Classes ll-IV. 

0

 Confirmed blood lead level if"40 ug/dl. 

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 automobile. 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 classical pica, which refers to the intentional ingestion of 

nonfood material rather than to the passive, nonintentional ingestion of dust from a dirty finger or 

piece of candy that has been dropped and thus contaiminated. 

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 figldl, than the 511 children of persons 

in other occupations who lived in the same areas 

whose mean blood lead level was 43.7 figldl. 

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)=* 

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) 

54.5(15) 

36.0(16) 

31.8(29) 

— 

65.8(28) 

43.8(32) 

35.5(39) 

33.0(53) 

27.1(79) 

— 

Zinc smelter 

worker 

66.3(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) 

44.9(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 contaminated 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 protective 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 undergarments 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.135 found blood lead levels >30 figldl 

in 38 of 91 children whose fathers were employed at 

a secondary lead smelter in Memphis, Tenn. Housedust, the only source of lead in the homes of these 

children, contained a mean of 2687 figlg compared 

with 404 figlg 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 figlg, 18 children had a mean blood 

lead level of 21.8 ± 7.8 figldl, whereas in homes 

where lead in dust was >7000 figlg, 6 children had 

a mean blood lead level of 78.3 ± 34.0 figldl. 

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 interviews 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" 

Area 

1 

2 

3 

4 

5 

6 

Distance 

Irom 

smeller, km 

1.6 

1.6 to 4.0 

4.0 to 10.0 

10.0 to 24.0 

24.0 to 32.0 

75. 

Pica 

78.7 

50.2 

33.5 

— 

— 

— 

Lead 

smelter 

worker 

No 

pica 

74.2 

52.2 

33.3 

30.3 

24.5 

— 

Lead/zinc mine 

Pica 

75.3 

57.1 

36.7 

38.0 

31.8 

— 

worker 

No 

pica 

63.9 

46.9 

33.5 

32.5 

27.4 

— 

Zinc smelter 

Pica 

69.7 

62.7 

36.0 

40.9 

— 

— 

worker 

No 

pica 

59.1 

50.3 

39.6 

36.9 

— 

— 

Other 

occupations 

No 

Pica pica 

70.8 59.9 

37.2 46.3 

33.3 32.6 

— 39.4 

28.0 26.4 

17.3 21.4 

12-37 
P.47 

populations living nearest to the smelter, environmental 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 significantly increased by the intentional ingestion of nonfood materials having a high lead content. 

Data on the parents' occupations are, however, 

more reliable. It must be remembered also that the 

stud y area s wer e no t homogeneou s 

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 ranging from 10 to 30 percent. 

12.3.6 Miscellaneous Sources of Lead 

Although no studies are available, it is conceivable 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 poisoning. Domestic and imported earthenware with improperly fired glazes have also been related to clinical 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 Oriental and Indian ethnic groups contain high percentages of lead that sometimes are absorbed by users in 

quantities sufficient to be toxic. 

12.4 SUMMARY 

Blood lead levels in homogeneous human populations have almost invariably been found to be lognormal. 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 standard deviation, it is possible to predict the percentages 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 environmental lead. Coupling these two procedures provides a method by which standards may be chosen to 

protect the health of the population. 

Blood lead levels have been found to exhibit considerable 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 segments of the population, after eliminating occupational exposure in lead workers, males have a higher 

blood lead than females. The published data comparing 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 association of elevated blood lead levels with elevated 

hand lead levels has not yet been established. Quantitatively, blood lead levels have been shown to increase 3 to 6 percent when the soil or dust lead content 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 settings. 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 association 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 quantitative 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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86. Griffin, T. B., F. Coulston. H. Wills, J. C. Russell, and J. 

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90. Rabinowitz, M. B. Lead contamination of the biosphere 

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Kinetic analysis of lead metabolism in healthy humans. J. 

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94. Williams, M. K., E. King, and J. Walford. An investigation 

of lead absorption in an electric accumulator factory with 

the use of personal samplers. Brit. J. Indus. Med. 

26:202-216, 1969. 

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means when several dose levels are compared with a zero 

dose control. Biometrics. 27:103-117. March 1971. 

97. Kendall, M. G. and A. Stuart. The Advanced Theory of 

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Board's Subcommittee on Scientific Criteria for Environmental Lead. Washington, D. C. January 31, 1977. 

99. Fairey, F. S. and J. W. Gray III. Soil lead and pediatric 

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128. Urban, W. D. Statistical Analysis of Blood Lead Levels of 

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lead levels and the in situ analysis of wall paint by X-ray 

fluorescence. Amer. J. Dis. Child. 724:500-502, 1972. 

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Med. 296:260-261, 1977. 

12-43 
P.53 

13. EVALUATION OF HUMAN HEALTH RISKS 

1

 FROM EXPOSURE TO LEAD AND ITS COMPOUNDS 

13.1 INTRODUCTION 

The preceding chapters of this document have described lead production, the eonomics of lead 

utilization, the dispersion of lead in the environment — 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 environment? (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 exposures 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 section 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 component. 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 contaminant 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 gradations 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 function; 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 chemical nor that which ultimately suffers the most 

serious injury. 

Dose-effect relationships will vary among the 

members of a population. Response is the proportion 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 MECHANISMS OF ENTRY 

13.2.1 Sources 

Of the estimated 161,225 metric tons of lead emit13-1 
P.54 

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, precipitation, 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 exposure. The addition of lead to paint makes lead 

directly available by ingestion of paint chips and 

paint-saturated plaster. In addition it becomes indirectly 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. Canned 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 higher 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 primary, secondary, and tertiary sources. Table 13-1 displays these sources. 

TABLE 13-1. SOURCES OF LEAD FOR HUMAN EXPOSURES 

Primary 

exposure 

source 

Air 

Paint 

Water from 

leaded pipes 

Food 

aReentrainment 

Secondary 

exposure 

source 

Dust and 

soil 

Water 

Dust and 

soil 

Tertiary 

exposure 

source 

Food 

Runoff water 

Aira 

Runoff water 

Aira 

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 airborne 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 controlled 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 intake by both routes of entry: inhalation and ingestion. Thus the total internal dose represents the summation 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 exposure 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 
P.55 

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 processing has been studied more thoroughly than contribution 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 airborne lead into blood, and epidemiologic data also 

generally support such a relationship. 

Studies concerned with dust and soil lead exposures will be considered together since in many 

studies the investigators did not attempt to deal with 

these sources separately. Considerable evidence exists that these exposures can be significant determinants of blood lead levels. Furthermore, investigations 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 definition 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 living in old housing. Abatement efforts have frequently 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 relationships 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 determining blood lead levels; this relationship is discussed 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, virtually 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 significance of the racial/ethnic factor cannot be established 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 relevant. 

Socioeconomic variables such as income and 

education have not been examined adequately as independent factors. Associated characteristics such as 

residence in old housing, or proximity to high-density 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 distribution has properties that make it amenable to use in 

the standard-setting process, since it permits an estimate 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. Evidence indicates that a positive relationship exists be13-3 
P.56 

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 consistency, 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 exposure must occur before there is an effect. 

Evidence presented in Chapter 12 indicates that a 

5 figldl increase in blood lead can result from an air 

lead exposure of 3.2 /ug/m3 for a period of 7 weeks. 

Furthermore, FEP levels have been shown to increase within 2 weeks of an increase of blood lead 

levels. Therefore, an air lead exposure of 3.2 figlm3 

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 considered 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 irreversible; 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 concept 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 probability of the person being removed from the exposure setting inducing these effects is slight or nonexistent, for whatever reason, then defacto irreversibility 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 attention in this section will be directed to those biological 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 consequences 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 discussed 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 indicate that statistically significant decreases in 

hemoglobin levels begin to appear at a blood lead 

level of 40 figldl or somewhat below. In adults a significant decrease in hemoglobin level appears to 

become evident at a blood lead level of 50 figldl. 

13.5.1.2 LEAD EFFECTS ON HEME SYNTHESIS 

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 important points of interference are: (1) the condensation of two units of 8-aminolevulinic acid 

dehydratase to form porphobilinogen and (2) the in13-4 
sertion of iron into protoporphyrin IX which is 

catalyzed by the enzyme ferrochelatase. 

13.5.1.3 EFFECT OF LEAD ON 8-AMINOLEVULINATE DEHYDRATASE (8-ALAD) 

AND 8-AMINOLEVULINIC ACID (8-ALA) EXCRETION 

A number of studies have shown the high sensitivity of 8-ALAD to lead and the negative correlation between blood lead and the logarithm of 8-

ALAD activity. These studies are described in Section 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 figldl (Chapter 11). This high degree of 

sensitivity makes application and interpretation of 

the test difficult. ALAD inhibition is virtually complete at blood lead levels of 70 to 90 figldl. 

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 INSERTION INTO PROTOPORPHYRIN 

Accumulation of protoporphyrin in erythrocytes 

in lead exposure is the result of lead-induced inhibition of the intramitochondrial enzyme, ferrochelatase. The inhibitory effect of lead on ferrochelatase may either be direct or may be mediated 

by a disruption in the function of mitochondrial 

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 hemerequiring 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 

mitochondrial 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 clinical 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 /xg/dl in the 

presence of a blood lead level above 30 figldl whole 

blood. 

More recent information relating to threshold of 

lead effects indicates that FEP levels begin to increase at a blood lead value of 15 to 20 fig Pb/dl 

blood in children and women and, at a somewhat 

higher value, 20 to 25 fig Pb/d 1 blood, in adult men. 

13.5.1.5 OTHER EFFECTS ON HEME SYNTHESIS 

There are other abnormalities of heme synthesis 

that are a result of lead exposure. For example, it is 

well known that an increased urinary coproporphyrin 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 pathway. Few data exist to quantitate the health significance 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 figldl. 

13-5 
P.58 

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 doseresponse data exist that might allow external lead 

exposure parameters to be linked directly to the occurrence of particular neurobehavioral effects. In 

contrast, more data exist relating blood lead levels 

to neurobehavioral deficits; major emphasis here 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 irritability, stupor, convulsions, and/or coma, which 

characterize the well-known encephalopathy syndrome. Such symptoms at times occur abruptly during the course of much milder symptomatology or 

even in apparently asymptomatic lead poisoned individuals and may progress to death within 48 hr. 

Even in the absence of death or prolonged unconsciousness, it is now widely accepted that irreversible neural damage typically occurs as one of the sequelae 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 retardation 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 figldl 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 encephalopathy or death may occur in adults at blood 

lead levels under 100 figldl (from 80 to 100 figldl), 

but the rarity of such cases and ambiguities in the reported data render it difficult to accept those reports 

as evidence for encephalopathy in adults at blood 

lead levels below 120 figldl. 

Much better evidence exists for the occurrence of 

lead encephalopathy in children at blood lead levels 

below 120 figldl or even 100/xg/dl. That is, it is well 

documented that such symptoms occur for some 

children beginning at the 100 figldl level; also, 

several scattered reports suggest that somewhat 

lower threshold levels may obtain, i.e., in the 80 to 

100 figldl 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 apparently asymptomatic children experience subtle 

neurobehavioral deficits at low-to-moderate blood 

lead levels in the 40 to 80 /xg/dl range remains a subject 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 figldl are likely 

sufficient to cause significant neurobehavioral impairments for at least some apparently asymptomatic 

children. The impairments consist mainly of cognitive or sensory-motor integration deficits, but do 

not appear to include the occurrence of hyperactivity; that latter effect seems to be much better established as one of the neurological sequelae following 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 intoxication. Recent studies of apparently asymptomatic 

adults, usually occupationally exposed to lead, 

however, present reasonably strong evidence for peripheral neuropathy at more moderate lead exposure levels, i.e., at blood lead levels in the range 

of 50 to 70 figldl. 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 occurrence, in some rare instances, at blood lead levels 

as low as 50 to 60 figldl. 

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 supportive 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 
P.59 

the induction of lead encephalopathy at high exposure 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 figldl 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 encephalopathic effects, i.e., in the 30 to 80 /xg/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 

figldl. 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 questioned. 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 distinction has repeatedly been made between threshold 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 inappropriately convey an impression of such effects occurring in a discrete, step-like fashion as particular 

threshold blood lead levels are reached. It is important 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 

figldl; 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 encephalopathic 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 accurately, 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 observed at blood lead levels of 50 to 80 /xg/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 /xg/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 present at birth. 

Tissue analysis also demonstrates that, in Americans 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 matchings, infant blood levels were highly correlated with 

those of their mothers. A second study showed that 

13-7 
P.60 

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 premature membrane rupture in pregnant women in this 

region compared to a group from a relatively unexposed 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 figldl. Because chronic 

lead nephropathy results only after prolonged or 

repeated exposures, it is impossible to recapitulate 

accurately the exposure history; therefore, determination of an exposure threshold for this condition 

is impossible. 

13.5.4.2 EFFECTS OF LEAD ON THE ENDOCRINOLOGICAL, HEPATIC, CARDIOVASCULAR, 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 relating 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 questions 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 obtained that define a proportion of a population 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 exhibiting health effects at a given blood lead level. 

TABLE 13-2. SUMMARY OF LOWEST OBSERVED EFFECT LEVELS 

Lowest observed 

effect level Population group 

10 

15-20 

25-30 

40 

40 

40 

50 

50-60 

50-60 

80-100 

100-120 

ALAD inhibition 

Erythrocyte protoporphyrin elevation 

Erythrocyte protoporphyrin elevation 

Increased urinary ALA excretion 

Anemia 

Coproporphyrin elevation 

Anemia 

Cognitive (CNS) deficits 

Peripheral neuropathies 

Encephalopathy symptoms 

Encephalopathy symptoms 

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 attempts have been restricted to effects on the 

hematologic system, in particular the elevation of 

FEP, the inhibition of ALAD activity, and the excretion of ALA in the urine. 

In regard to defining dose-response relationships 

for hematological effects, three different assessments 

of such relationships have been carried out46 and 

published. For example, in the approach of 

Zielhuis,4 dose-response relationships were 

developed for ALAD, ALA-U, and FEP as obtained 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 
P.61 

data for FEP in adult males, adult females, and 

children. 

z 

O S« 80 

I- Q 

< UJ 

_l H 

= 2 

SS 60 

">• A 

u. . 

O I ; 40 — 

_ 

— 

1 1 

x J / / 

/ / / 

/ 

/ 

/ 

/ 

/ 

/ 

/ y 

l - V 

/ / 

1 

—(^40 % 

70% / / / / / / / 

/ / 

1 1 

"P 

1 

* - 1 

>40 % 

>70 % 

ADULTS 

CHILDREN 

1 

—. 

_ 

-

If < 

O I 20 

0 10 30 50 70 

BLOOD LEAD LEVEL, ug Pb/dl 

Figure 13-1. Dose-response curve for percent ALAD inhibition for adults and children as a function of blood lead 

level. 

°- < 60 

O w 

uu A 

> 5 mg/liter 

mg/liter 

30 50 

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 inhibition. For example, at 20 /xg/dl blood lead, approximately 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 inhibition in ALAD at 20 figldl blood lead, whereas virtually all of the adult population shows 40 percent 

inhibition at 40 figldl. 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 figldl blood 

lead. At 60 figldl blood lead, the corresponding percentage 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 figldl blood lead, the corresponding percentage of the adult population is approximately 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 A 

< » 

100 

80 

60 

40 

20 

-

-

1 1 1 1 

ADULT FEMALES /* " 

1 /l*""' l 1 

1 1 1 

/ADUL T MALES 

1 / CHILDREN 

1 1 1 

-

-

-

-

-

30 50 

BLOOD LEAD LEVEL, ug Pb/dl 

Figure 13-3. Dose-response curve for FEP as a function of 

blood lead level.4 

Q 

UJ 

K < 

(/> 

A 

ADULT MALES 

20 30 

BLOOD LEAD LEVEL, ug Pb/dl 

Figure 13-4. Dose-response curve for FEP as a function of 

blood lead level.5 

13-9 
.P.62_ 

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 virtually all the children exceed this value at 35 /ug/dl 

blood lead. 

The dose-response data of Piomelli6 are presented 

in Figure 13-5 and consist of composite plots for 

mean plus 1 standard deviation (33 figldl whole 

blood) and the mean plus 2 standard deviations (51 

fig FEP/dl whole blood). In the data presented in 

Figure 13-5. blood lead levels in excess of 28 figldl 

whole blood were not used in tne calculations. It appears from the above that there exists a threshold at 

about 15 figldl whole blood. 

> 98 — 

Q 95 — 

98 

95 

90 

75 

50 

25 

5 

2 

1 

1 

NOTE 

1 

1 1 1 1 1 1 1 

POINTS OUTSIDE THE RANGE OF THE SOLID LINES 

WERE NOT USED IN CALCULATIONS 

0 

r> 

-

s * — 

FEP > MEAN + 1 S.D. (33 ug/dl) ' 

j* y 

Jg rf FEP>MEAN + 2 S.D. 

_ tmJT j f (51 ug/di) ? y* 

S QV J C (NATURAL FREQUENCY) — 

o ° /f^ ^ 

1 " 1 I I I I 1 

? 25 -

° ,„_ = 

< 5 -

0 10 20 30 40 

BLOOD LEAD LEVEL, ug 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 doseresponse curves were plotted for two different cutoff points. These points were the mean values for 

blood lead levels less than 13 figl 100 g, plus 1 standard deviation and plus 2 standard deviations, 

respectively. From the mean plus 2 standard deviations curve, it is readily apparent that the linear portion of the curve is quite steep. At a blood lead level 

of 20 figldl, 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 

figldl, 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. 

4 80 

< 

<so 

s 

Z 50 

o 

MEAN+ 1 S.D. 

MEAN + 2 S.D. 

MEAN ALA-U » 0.32 FOR BLOOD 

LEAD < 13 ug/dl 

J I I I I I 

BLOOD LEAD LEVEL, ug Pb/dl 

Figure 13-6. EPA calculated dose-response curve for ALA-U 

(from Azar et al.7). 

In Table l 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 doseresponse 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 S mg/liter FOR VARIOUS BLOOD 

LEAD LEVELS 

Blood lead levels. 

ijg'dl 

10 

20 

30 

40 

50 

60 

70 

4 

Zielhuis. 

% 

0 

0 

6 

24 

48 

76 

96 

Azar et at.. 

% 

2 

6 

16 

31 

50 

69 

84 

13-10 
TABLE 13-4. ESTIMATED PERCENTAGE OF CHILDREN 

WITH EP EXCEEDING CUT-OFF POINTS FOR VARIOUS 

BLOOD LEAD LEVELS 

Blood lead 

level, ug/dl 

10 

20 

30 

40 

50 

60 

70 

80 

Zielhuisa% 

0 

6 

22 

37 

49 

— 

— 

— ' 

Roels et al,.b% 

3 

27 

73 

100 

— 

— 

— 

— 

Piomelli.c% 

9 

11 

48 

80 

— 

— 

— 

— 

aEP > EP of children with Pb-B < 20 iig/dl. 

bEP >82 ugd l cells. 

CEP >EPo l 33ug'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 condition, illness, or other abnormal status. This high 

risk may result from either greater inherent susceptibility 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 external stimulus or agent. 

In regard to lead, two such populations are 

definable. They are preschool age children, 

especially those living in urban settings, and pregnant 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 metabolism of lead. Also, the behavior of children frequently places them in different relationship to 

sources of lead in the environment, thereby enhancing 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 medical 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 considered that one would expect to predispose children 

to a heightened vulnerability to lead, but also the actual 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 included: (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-contaminated 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 fac13-11 
P.64 

tors appear to emerge as important factors determining 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 example, the few credible reports of lead encephalopathy 

in children at blood lead levels less than 100 ug/dl 

all concern children from inner-city areas. 

Similarly, statistically significant effects or borderline effects indicative of more subtle neurobehavioral deficits in lead-exposed children at 

moderately elevated blood lead levels have been reported 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 experiencing similar elevations in blood lead levels, 

but residing near primary smelter facilities in semirural areas. 

One cannot determine with any certainty the 

specific factors that might contribute to the apparent 

differential sensitivity of inner-city children to the 

neurobehaviora l effects of lead. Several 

possibilities, however, might be reasonably considered, 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 existed 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 contribute to the apparent differential susceptibility of inner-city chilren. 

13.6.1.2 EXPOSURE CONSIDERATIONS 

Children's dietary habits as well as the diets themselves 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 exposure to lead since both those foodstuffs have been 

shown to contain higher amounts of lead than components 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 contribution is added 

Children ordinarily undergo a stage of development 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 indicating that women may in general be at somewhat higher 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, however, the mother herself can also be at somewhat 

greater risk. This section will first describe the 

general evidence for all women and then the evidence 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 
P.65 

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 suggestive evidence that lead exposures may affect maternal complications of delivery. 

With reference to maternal complications at 

delivery, information in the literature suggests the 

incidence of preterm delivery and premature membrane 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 exposure 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 trimester. 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 apparent 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 offspring. The available data are insufficient to state 

with any certainty that such effects occur or to determine 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 EXPOSURES 

In this section estimates are provided of the number of individuals potentially at risk to lead exposures. Unfortunately the latest census data are 

only from 1970,8 although some estimates are available from the National Center for Health Statistics 

for 1975.9 This is unfortunate since some significant 

changes are thought to have occurred in the population 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 potential 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 distribution 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 stations. 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 urban 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 

inn (10°) 

Urban 

Inside urbanized areas 

Central cities 

Urban fringes 

Outside urbanized areas 

Rural 

Total. United States 

128.773(72.4) 

100.952(56.8) 

49.547 (27.9) 

51.405(28.9) 

27.822(15.7) 

48.976 (27.6) 

177.773 

20,552 (80.7) 

17,495 (68.7) 

14,375 (56.5) 

3,120 (12.3) 

3,057 (12.0) 

4,911 (19.3) 

25.463 

149.325(73.5) 

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 nonwhite 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 
TABLE 13-6. NUMBER OF BIRTHS BY RACE AND SIZE OF POPULATION8 

P.66 

Urban areas of given 

size from 1970 census 

Births 

White 

772.230 

286.706 

600.166 

1.432.162 

3.091.264 

Black 

321.412 

37.024 

65.790 

148.136 

572.362 

Births 

Others 

24.394 

4.182 

10.394 

28.790 

67.760 

Total 

1.118.036 

327.912 

676.350 

1,609.088 

3.731,386 

> 100,000 

50-99,999 

10-49,999 

59,999 

Total 

Urban areas of given 

Size from 1975 census White Black Others Total 

> 100,000 

50-99,999 

10-49,999 

59,999 

571.478 

222.735 

478.382 

1.279.401 

276.387 

37.885 

64.481 

132.828 

26.332 

5.921 

13.039 

35.329 

874,197 

266.541 

555.902 

1,447.558 

Total 2.551.996 511.581 80.621 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 comparisons, 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 

figldl 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 programs conducted in this country, is not meant to imply that all of these values resulted from airborne 

lead. They probably do not, since paint lead exposures are an additional important source. But, on 

the other hand, the addition of an airborne component 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 pregnant 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 tabulated 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. Finney, D. J. Statistieal method in biological assay. 

Charles Griffin and Co., London. 1971. p. 5. 

3. Hernberg, S. Biochemical. Subclinical and Clinical 

Responses to Lead and Their Relation to Different Exposure 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 BIS. 

4. Zielhuis, R. L. Dose-response relationships for inorganic 

lead: I. Biochemical and hematological responses. Int. 

Arch. Occup. Hlth. 55:1-18. 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. 

J/:3 10-316, 1976. 

6. Piomelli. S. Reanalysis of data from S. Piomelli. C. Seaman, 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 
7. Azar, A.. R. D. Snee. and K. Habibi. An epidemiological 9. U. S. National Center for Health Statistics, Vital Statistics 

approach to community air lead exposure using personal of the U. S.. 1975, Data for 1975 Births. Unpublished -

air samplers. Environ. Qual. Saf.Suppl. 11:254-290. 1975. provided by NCHS. 

8. 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 

18, Table 19. ' Technical Note 921, September 1976. 

13-1 5 
APPENDIX A 

GLOSSARY* 

Absorption (of lead): Transfer of lead into an organism via intestinal wall, alveolar surface, or skin. 

Accumulation (of lead): Net positive difference between intake and output of lead over an extended 

period. 

Acetyl coenzyme A (CoA): Coenzyme, derived principally from the metabolism of glucose and fatty 

acids, that takes part in many biological acetylation 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 excitabl e 

membranes that inactivates acetylcholine. 

/3-Acetyl glucosaminadase: Enzyme that hydrolyzes 

the terminal glucosaminidic bonds of odd-numbered oligosaccharides to yield N-acetylglucosamine 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 glandular tissue or in which the tumor cells form recognizable 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 composed of adenosine and two molecules of 

phosphoric acid; important in intermediate cellular metabolism; a product of the hydrolysis of 

adenosine triphosphate (ATP). 

Adenosine triphosphate (ATP): Nucleotide occurring 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 + 

H2 0 — ADP + orthophosphate. 

Adenyl cyclase: Enzyme that catalyzes the formation 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 adenosin e 

monophosphate (AMP). 

Adrenaline: See Epinephrine. 

Adrenergic: Describes the chemical activity of 

epinephrine or epinephrine-like substances. 

Adrenergi c synapse : Synaps e 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 question. Thus, particles having the same aerodynamic diameter may have different dimensions 

and shapes. 

Aerodynamic drag: Aerodynamic resistance; retarding force that acts upon a body moving through a 

gaseous fluid and that is parallel with the direction 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 l 2 t o 10 ' fim in 

diameter, dispersed in a gas. 
P.69 

Agglomeration: Process by which precipitation particles 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 atmosphere that serve as condensation nuclei for 

droplet growth during the rapid adiabatic expansion 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 = 

dihydroxyaceton e phosphat e + 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. 

Alveola r macrophages: Rounde d granula r 

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, attached to e, or 5th, carbon atom from the carboxyl 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): COOHCH2-CH2-CO-CH2-NH2; intermediate in the biosynthesis of heme-containing compounds; formed 

from succinyl-coenzyme A and glycine. 

8-Aminolevulinic acid dehydratase (ALAD): 

Enzyme in heme biosynthetic pathway that mediates 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 succinyl-CoA via 2-amino-3-ketoadipate. 

Amphetamine: a-Methylphenethylamine. Drug 

used to stimulate the central nervous system, increase blood pressure, reduce appetite, and 

reduce nasal congestion. Abuse may lead to dependence, characterized by strong psychic dependence associated with an increase in REM (rapideye-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 inadequate perfusion of tissues by blood carrying normal amounts of oxygen or by normal perfusion of 

blood carrying reduced amounts of oxygen. 

Antipyrine (C,,H12ON2): Compound used as an antipyretic, 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 performance. 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 unidirectional 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 element 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 
P.70 

Biosphere: The part of the earth's crust, waters, and 

atmosphere where living organisms can subsist. 

Blood-brain barrier: The barrier created by semipermeable 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 substance (for example, lead) in an organism, including 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 dispersed small particles suspended in a fluid; 

results from random collisions between the 

molecules of the dispersing medium and the particles 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 malignancy. 

Carcinoma: Malignant new growth made up of 

epithelial cells tending to infiltrate the surrounding 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 coordination 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 hydrolysis 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 probabilities or probability distributions (goodness 

of fit), statistical dependence or independence 

(association), and common populatio n 

(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. 

A-3 
P.71 

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 kidneys. 

Coagulation: Process that converts numerous 

droplets into a smaller number of larger precipitation 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 substances, one of which, called the dispersed phase 

(or colloid), is uniformly distributed in a finely 

divided state through the second substance (dispersion 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 evaporation. 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, <a <a2) 

determined from a sample by definite rules so 

chosen that, in repeated random samples from the 

hypothesized population, an arbitarily fixed proportion (1-e) of that range will include the true 

value, x, of an estimated parameter. 

The limits, a, and a2, are called confidence limits; 

the relative frequency (1-e) with which these 

limits include a is called the confidence coefficient; and the complementary probability, e, is 

called the confidence level. As with significance 

levels, confidence levels are commonly chosen as 

.05 or .01, the corresponding confidence coefficients being .95, .99. 

Confidence intervals should not be interpreted as 

implying that the parameter itself has a range of 

values; it has only one value, a. On the other 

hand, the confidence limits (ap a2), being derived 

from a sample, are random variables the values of 

which on a particular sample either do or do not 

include the true value a of the parameter. 

However, in repeated samples, a certain proportion (namely 1-e) of these intervals will include 

a, provided that the actual population satisfied 

the initial hypothesis. 

Contamination: Contact with an admixture of an unnatural agent, with the implication that the 

amount is measurable. 

Convection: Atmospheric motions that are predominantly vertical, resulting in vertical transport and 

mixing of atmospheric properties. 

Convulsions: Violent, involuntary contraction or 

series of contractions of the voluntary muscles. 

Coprogen III: Coproporphyrinogen III, an intermediary metabolite in heme biosynthesis. It is a 

natural precursor of heme. 

Coprogenase: Coproporphyrinogenase, the enzyme 

that converts coproporphyrinogen III to protoporphyrin IX. 

Coproporphyrin: Urinary pigment derived from 

coproporphyrinogen, an intermediate in the biosynthesis of heme. 

Coproporphyrinogen (syn. coprogen): A fully 

reduced colorless tetracarboxylic tetrapyrrole. 

Isomers I and III are found in biologic systems. 

Cortex: See Cerebral cortex. 

Corpus callosum: Band of nerve tissue connecting 

the cerebral hemispheres in man and higher mammals. 

Corpus striatum: A subcortical mass of gray and 

white substance in each cerebral hemisphere, containing the caudate nucleus and the lentiform 

nucleus. 

Cortical atrophy: Wasting away of the outer layer(s), 

e.g., of the brain or kidney. 

Creatinine: C4H2ON3; compound formed by 

dehydration of creatine; found in urine, blood, 

and muscle. 

Cristae: Inner membranes of mitochondria, the surfaces of which are studded with roughly spherical 

particles attached to the cristae by stalks. 

A-4 
P.72 

Cumulative frequency distribution: Proportion of a 

distribution that lies below a given value. 

Curie: Unit of radioactivity; quantity of radionuclide that has 3.7 x IO10

 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 + 0 2 = 4 oxidized 

cytochrome c + 2H2 0. 

Cytochrome c reductase: Enzyme that catalyzes the 

reduction of oxidized cytochrome c: NADH2 + 

oxidized cytochrome c = NAD + reduced 

cytochrome c. 

Cytochrome P-450: a fc-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 cementum on the roots of the teeth. 

Denver Development Screening Test: Rating scales 

employed to assess four areas of child development: (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-deoxyribose, phosphate, and a purine or a pyrimidine; 

carrier of genetic information coded in the sequence of purines or pyrimidines (organic bases). 

Deposition: (1) Deposit of particles from the ambient 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-CSNH»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 

decarboxylatio n of dop a (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 accumulation of excessive fluid in the subcutaneous tissues. 

Electromyographic: Pertaining to electromyography, the recording and study of the intrinsic 

electrical properties of skeletal muscle. 

A-5 
P.73 

Electron microprobe: X-ray method in which 

electrons from a hot-filament source are accelerated electrostatically, then focused to an extremely small point on the surface of a specimen 

by an electromagnetic lens; method for nondestructive 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 determinants 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 peripheral 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 surfaces, 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 protoporphyrin. 

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 characterized 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, particulate matter that falls 

to the surface of the earth through the action of 

gravity; a passive phenomenon unrelated to atr 

mospheric or mechanical motion. 

Fanconi syndrome: In this document, the triad of 

glycosuria, hyperaminoaciduria, and hyr 

pophosphatemi a in the presenc e of hy7 

perphosphaturia that is associated with injury to 

proximal renal tubular cells. 

Flinch/jump thresholds: Behavioral testing procedure used to measure pain threshold by measuring 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 hippocarrij 

pus. 

Free erythrocyte porphyrin (FED): See Free 

erythrocyte protoporphyrin. 

Free erythrocyte protoporphyrin (FEP): Intermeditate in the biosynthesis of heme; specifically, the 

immediate precursor to heme synthesis in which 

one atom of iron is inserted into the protoporphyrin nucleus to form heme. Used interchangeably with erythrocyte protoporphyrin 

and erythrocyte porphyrin. 

Fugitive dust: Dust that escapes from industrial pro* 

cesses, soil surfaces, roadways, etc.; dust that cannot be contained by air pollution control practices. 

/3-Galactosidase: Enzyme that hydrolyzes galacr 

tosides (compounds containing a sugar and a nonsugar 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. 

A-6 
Gastrointestinal mucosa: Mucous membrane of the 

stomach and intestine. 

Geometric mean: An estimate of the median of a lognormal distribution, calculated as the antilogarithm of the mean of the logarithms of the observations. 

Geometric standard deviation: A measure of dispersion for a lognormal distribution; it is the antilogarithm 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 reabsorbed 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 expanded end or capsule of each of the uriniferous 

tubules of the kidney. 

Glucose-6-phosphate dehydrogenase: Enzyme important in maintenance of adequate concentrations of reduced glutathione in red blood cells. 

Deficiency of this enzyme is inherited as a sexlinked trait; it mediates the reaction, Dglucose-6-phosphate + NADP = D-glucono-8-

lactone 6-phosphate + NADPH2. 

/3-Glucuronidase: Enzyme that mediates the hydrolysis 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 dicarboxylic 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 simple 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 organomaghesium 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 radioactive 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 portable 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 marrow, spleen, and lymph nodes concerned with formation of cellular elements of the blood. 

Hemin : Crystallin e chlorid e 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 certain aspects of emotion and behavior. 

Histidine residue: One of the naturally occurring 

peptide linkages in a protein, containing the 

chemical group, imidazole: 

HC = CI I 

N NH V 

C 

H 

A-7 
P.75 

Homovanillic acid: A methylated metabolite of hydroxytyramine: 

CH3 0 

HO CH2-COOH 

Hydrocephalus: Condition characterized by abnormal accumulation of fluid in the cranial vault, accompanied by enlargement of the head, prominence of the forehead, atrophy of the brain, mental deterioration, and convulsions. 

Hyperactivity: Abnormally increased activity. 

Developmental hyperactivity of children is 

characterized by constant motion—exploring, experimenting, 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 increased muscular movement. 

Hyperkinetic-aggressive behavior disorder: A disorder 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 particles 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 enters the sampler. 

Jiggle platform: Apparatus used in behavioral testing 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 metabolism. 

Kilocalorie: Unit of heat energy equal to 1000 calories; also known as large calorie. 

Lactic acid dehydrogenase (LDH): Catalyzes reduction of pyruvic acid by reduced nicotinamide 

adenine dinucleotide; prevents buildup of pyruvate 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 adverse effects of the absorption of lead into the 

system. 

Lead subacetate (syn. lead monosubacetate, 

monobasic lead acetate): Pb(C2H3 02 ) 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 
P.76 

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 distributirin. 

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-mediated immunity. 

Lysosome: Submicroscopic organelle, found by 

electron microscope in many types of cells, that 

contains various hydrolytic enzymes and is normally involved in localized intracellular digestion. 

a-Mannosidase: Enzyme that catalyzes the hydrolysis of a-D-mannoside to an aocohol and Dmannose, a simple sugar. 

Mass median diameter (MMD): Geometric median 

size of a distribution of particles, based on weight. 

Mass median equivalent diameter (MMED): Convenient parameter for characterizing airborne particulates; divides the total mass of aerosol particles 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 intellectual assessment instrument (appropriate for 

ages 2.5 to 8.5 yr), consisting of five subtests 

yielding individual scores in (1) verbal, (2) perceptual-performance, (3) quantitative, (4) memory, 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 complementary to a single strand of DNA; carries information for protein synthesis to the ribosomes. 

Metabolites: End products of metabolic processes 

that transform one compound into another in living 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 proteins. 

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 content 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 expressed in grams). 

Midbrain: Mesencephalon; portions of the adult 

brain derived from the embryonic midbrain. 

Miniature end-plate potentials (MEPP's): Small potential changes in the neighborhood of the end 

plate representing the response of the membrane 

to release of acetylcholine in quantities insufficient 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. 

A-9 
P.77 

Monominergic: Stimulated, activated, or transmitted 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): Networks 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 uncontrollable 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 sympathetic nerve endings and probably in certain 

synapses in the central nervous system. 

Normal distribution (Gaussian distribution): Fundamental frequency distribution of statistical 

analysis. A continuous variate, x , is said to have 

a normal distribution or to be normally distributed if it possesses a density function, f(x), 

that satisfied the equation: 

f (x) =_U-( X- ^ W (-oo< X <oc), 

cr27r ' 

where fi is the arithmetic mean (or first moment) 

and o- is the standard deviation. About two-thirds 

of the total area under the curve is included between x = fi-a and x = fi + o\ 

Normal population: Collection of quantities having 

a normal distribution. 

Normoblast: Nucleated percursor cell intermediate 

in the formation of erythrocytes. 

Nuclear inclusion bodies: Round, oval, or irregularly shaped bodies appearing in the nuclei of 

cells. 

Nucleus: Small mass of differentiated protoplasm 

rich in nucleoproteins and surrounded by a 

membrane; found in most animal and plant cells; 

contains chromosomes and functions in metabolism, growth, and reproduction. 

One-way avoidance tasks: See Avoidance task. 

Optical emission spectrography: Analytical method 

in which the sample is vaporized and decomposed, and the constituent elements excited by an 

electrical arc or a high voltage spark. The light 

emitted as a consequence of the excitation passes 

through a spectrograph and the resulting 

spectrum is recorded photographically. 

Paraplegia: Paralysis of the legs and lower part of 

the body. 

Parenchyma: General term to designate functional 

elements of an organ as distinguished from its 

framework, or stroma. 

Particle eddy diffusivity: The diffusion of particles 

by eddies in a turbulent flow. 

D-penicillamine: Product of penicillin; whitish 

crystalline powder used as a metal complexing 

agent to remove excess metals from the body. 

Peptidergic: Stimulated, activated, or transmitted by 

peptides; applied to those nerve fibers that liberate peptides at a synapse when a nerve impulse 

passes. 

Photolysis: Chemical decomposition by the action of 

light. 

Phrenic nerve: Arising from the third, fourth, and 

fifth cervical segments of the spinal cord, the 

nerve that innervates the diaphragm. 

Pica: Habitual ingestion of nonfood items. 

Pinna: Projecting part of the ear lying outside the 

head. 

Plumbism: Lead poisoning; saturnism. 

A-10 
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 (PBG): Intermediate in the biosynthesis of heme that does not accumulate under 

normal circumstances. 

Porphyrin: Any one of a group of iron-free or magnesium-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 frequently 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 hybridization state required for bonding. 

Protoporphyrin (PP): Porphyrin that is the proteinfree 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, 

Na

 + ,C1 , 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 inorganic 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 intermediate in carbohydrate (Krebs cycle) and protein metabolism. 

Reentrainment: Resuspension of particulate matter, 

especially dust, in the ambient air; see text dicussion of resuspension. 

Reference method: In this document, the official, accepted method for sampling and analysis of an 

element or compound; method to which other 

methods are compared for accuracy and precision, 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 peripheral blood. 

Ribonucleic acid (RNA): Nucleic acid in the form of 

a linear polymer, usually a single strand, composed of repeating units of nucleotides (the 

organic bases; adenine, cytosine, guanine, and 

uracil) conjugated to ribose and kept in sequence 

by phosphodieste r bonds. Involved intracellularly 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 sampling techniques and procedures. 

Sampling train: Pollutant collecting device consisting 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 airborne 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 convulsion. 

A-ll 
P.79 

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 Lglutamic acid to oxaloacetic acid, forming 8-

ketoglutaric acid plus L-aspartic acid. Oxaloacetic and 8-ketoglutaric acids are both major 

intermediates in the citric acid cycle (Krebs cycle), the energy-generating cycle. 

Serum glutamic-pyruvic transaminase (SGPT): 

Enzyme that transfers an amino group from Lglutamic 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 oxaloacetic 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 compartment 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 activity by measuring vertical movement of the 

floor. 

Stack emissions: Effluents released into the atmosphere 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 dispersion of values about a geometric mean; the portion of the frequency distribution that is one standard 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 individual deviations from the mean. 

Stanford-Binet I.Q. Test: A standardized intellectual assessment instrument (appropriate for ages 

2 yr to adult), yielding a general intelligence quotient (I.Q.) score. 

Steady state exposure: Exposure to an environmental pollutant whose concentration remains constant 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 intermediate in carbohydrate (Krebs cycle) and protein metabolism. 

Succinoxidase: Complex enzyme system, containing 

succinic dehydrogenase and cytochromes, that 

catalyzes the conversion of succinate and molecular oxygen to fumarate ( a Krebs cycle intermediate). 

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 
P.80 

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 malformations. 

Teratospermia: Presence of malformed spermatozoa 

in the semen. 

Temperature inversion: Layer of air in which temperature increases with altitude; very little turbulent exchange occurs within it. 

Terminal velocity: See Terminal fall velocity. 

Terminal fall velocity (terminal velocity): Particular 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 air 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-bottom 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 complementary 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 physical 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 instantaneous velocities exhibit irregular and apparently 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, 

CgHnOjN) found in most proteins and synthesized metabolically from phenylalanine. It is a 

precursor of dopamine and of the hormones, 

epinephrine , norepinephrine , an d 

triiodothyronine. 

Ultradian rhythms: Biological rhythm with a frequency higher than circadian (24 hr). 

Uncertainty: Standard deviation of a sufficiently 

large number of measurements of the same quantity by the same instrument or methods; the noncorrectable inaccuracy of the instrument. 

Upwind: Toward the direction from which the wind 

is flowing; counter to the wind. 

Urobilinogen: Colorless compound formed in the intestine by the reduction of bilirubin (a bile pigment 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 normal urine and feces. 

Vacuolization: Formation of vacuoles, any small 

spaces or cavities formed in the protoplasm of a 

cell. 

A-13 
P.81 

Vacutainers: Registered trademark of sealed ampules, maintained under a slight vacuum and containing an anticoagulant, into which blood samples may be drawn directly. 

Vanillyl mandelic acid (vanilmandelic acid): A major 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 subtests designed to yield verbal and performance intellectual scores. 

Wet deposition: Removal of particles from the atmosphere 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 consisting of 10 subtests representing a downward extension 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 sample; 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 correct 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 
P.82 

APPENDIX B 

PHYSICAL/CHEMICAL DATA FOR LEAD COMPOUNDS 

B.l DATA TABLES 

TABLE B-1, PHYSICAL PROPERTIES OF INORGANIC LEAD COMPOUNDS' 

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(C2H302)2 

Pb(N3)2 

Pb(Br03)2-H20 

PbBr2 

PbC03 

2PbC03-Pb(OH)2 

PbCI2 

PbCIBr 

PbCr04 

PbCr04-PbO 

Pb(CN)2 

PbF2 

PbFCI 

Pb(CHO)2 

PbH2 

Pb(OH)2 

Pb(l03)2 

Pbl2 

Pb(N03)2 

Pb(OH)(N03) 

PbC204 

PbO 

Pb02 

Pb304 

Pb3(P04)2 

PbS04 

PbS 

PbS03 

Pb(SCN)2 

glyc - glycol 

i - insoluble 

s - soluble 

M.W. - molecular weight 

S.G. - specific gravity 

MP. - melting point 

M.W. 

207.19 

325.28 

291.23 

481.02 

367.01 

267.20 

775.60 

278.10 

322.56 

323.18 

546.37 

259.23 

245.19 

261.64 

297.23 

209.21 

241.20 

557.00 

461.00 

331.20 

286.20 

295.21 

223.19 

239.19 

685.57 

811.51 

303.25 

239.25 

287.25 

323.35 

S.G. 

11.35 

3.25 

— 

5.53 

6.66 

6.6 

6.14 

5.85 

— 

6.12 

6.63 

— 

8.24 

7.05 

4.63 

— 

— 

6.155 

6.16 

4.53 

5.93 

5.28 

9.53 

9.375 

9.1 

7 

6.2 

7.5 

— 

3.82 

M.P. 

327.5 

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 

Solubility, g/100 

Cold 

water 

i 

44.3 

0.023 

1.38 

0.8441 

0.00011 

i 

0.99 

— 

6x10-6 

i 

si s 

0.064 

0.037 

1.6 

— 

0.0155 

0.0012 

0.063 

37.65 

19.4 

0.00016 

0.0017 

i 

i 

1.4x10-5 

0.00425 

8.6x10-5 

i 

0.05 

Hot 

water 

i 

22150 

0.0970 

Si s 

4.71100 

d 

i 

3.34100 

— 

i 

i 

s 

— 

0.1081 

20 

— 

si s 

0.003 

0.41 

127 

s 

— 

— 

0.0056 

— 

i 

0.2 

ml 

Other 

solvents 

sa 

sglyc 

— 

— 

sa 

sa.alk 

sHN03 

ial 

— 

sa.alk 

sa.alk 

sKCN 

sHN03 

— 

ial 

— 

sa.alk 

sHN03 

s.alk 

s.alk 

sa 

sa 

s.alk 

sa 

sa . 

s.alk 

— 

sa 

sa 

s.alk 

B-l 
P.83 

TABLE B-2. TEMPERATURE VARIATION OF THE VAPOR PRESSURES OF COMMON LEAD COMPOUNDS* 

Name 

Lead 

Lead bromide 

Lead chloride 

Leadflouride 

Lead iodide 

Lead oxide 

Lead sulfide 

Formula 

Pb 

PbBr2 

PbCI2 

PbF2 

Pbl2 

PbO 

PbS 

MP. 

327.4 

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) 

Temperature "C 

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 comparison 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 equations: 

M + BF=^M- B (B-l) 

M-B + Br=^MB 2 (B-2) 

k

d 

The related expressions for the bidentate case are: 

The overall equilibrium constants, therefore, are: 

K

'-k b k d

; K 2 - k2k4 

For a given metal, M, and two ligands, B and B-B, 

which are chemically similar, it is established that k, 

and ka have values similar to each other, as do k2 

and kb, k4 and kd; each of these pairs of terms represents chemically similar processes. The origin of the 

chelate effect lies in the very large value of k3 relative to that of kc. This comes about because k3 represents a unimolecular process, whereas kc is a 

bimolecular rate constant. Consequently, K2 »K, . 

This concept can, of course, be extended to'polydentate ligands; in general, the more extensive the 

chelation, the more stable the metal complex. 

Hence, one would anticipate, correctly, that polydentate chelating agents such as penicillamine or 

EDTA can form extremely stable complexes with 

metal ions. 

M + B-BF=^M-B- B (B-3) B.3 REFERENCES FOR APPENDIX B 

M-B-B =*rvK ) 

L B y 

1. Handbook of Chemistry and Physics. 56th Ed. R.C. Weast 

(ed.). Cleveland, The Chemical Rubber Co. 1975. 

(B-4) 2. Stu.ll. D.R. Vapor pressure of pure substances: Organic compounds. Ind. Eng. Chem. J9(4):5 1 7-540. 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.l GENERA L 

CENTRATIONS 

AMBIEN T AIR CONC.l.1 Seven-City Study 

A special lead study (Seven-City Study) was conducted 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 summarized in Table C-1. 

This study, specifically designed to measure ambient 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 attributable to heavy automotive emissions. 

C.l.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 Birmingham, Alabama, as a part of the Alabama 

Respiratory Disease and Air Pollution Study initiated 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 samples. The lead data are summarized in Table C-2. 

The maximum seasonal lead concentration (3.5 

/ug/m3) occurred at Birmingham site 4 during the 

winter. Only 2 sites showed average concentrations 

> 2 figlm3 for the year, Birmingham site 4 (3.0 

figlm3) and Tarrant (2.3 /Ag/m3). These results are 

typical for a medium-sized industrialized urban 

area. 

C. 1.3 Kanawha Valley, West Virginia3 

A comprehensive air pollution study was conducted in the Kanawha River Valley in the vicinity 

of Charleston, West Virginia (Figure C-1), during 

1964 and 1965. Twenty-four-hour samples of suspended 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 particulates) 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 composite 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 operations, asphalt hot-mix production, and other industrial processes. In most cases, these sources have 

inadequate air pollution control equipment. The 

lead concentrations found are somewhat low when 

C-1 
P.85 

TABLE C-1. SUMMARY OF MONTHLY AVERAGE LEAD 

CONCENTRATIONS FOUND IN SEVEN-CITY STUDY' 

City 

LOS Angeles 

Philadelphia 

Cincinnati 

Los Alamos 

Houston 

Chicago 

Washington, D.C. 

New York 

a

 C - commercial; I - industrial; R 

Site 

type8 

C 

C 

R 

R 

R 

R 

I 

C 

M 

C 

C 

I 

R 

M 

R 

R 

R 

R 

C 

R ' 

I 

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 

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 

12 

7 

12 

12 

12 

7 

12 

12 

12 

12 

12 

12 

11 

12 

12 

12 

12 

12 

12 

12 

12 

Monthly concentration, 

Min. 

2.4 

2.6 

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 

Q1 

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 

6.8 

0.9 

0.9 

0.8 

(i g/m3 

Max. 

5.8 

6.8 

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 

Avg. 

4.2 

4.5 

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 

0.2 

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 

- residential; M - mixed; F - farm; and P - park. 

TABLE C-2. SEASONAL LEAD CONCENTRATIONS IN 

BIRMINGHAM, ALABAMA, AREA, 1964-1965 

(/xg/m') 

Place 

Bessemer 

Birmingham 

Birmingham 

Birmingham 

Birmingham 

Fairfield 

Irondale 

Mt. Brook 

Tarrant 

Vestavia 

Site 

1 

3 

4 

5 

7 

1 

1 

1 

1 

1 

Seasonal average 

Spring 

0.9 

0.7 

3.2 

1.2 

1.2 

0.6 

0.6 

0.5 

1.1 

0.8 

Summer 

0.7 

1.4 

2.8 

1.6 

1.4 

0.5 

0.4 

0.6 

1.8 

0.8 

concentrations 

Fall 

1.1 

1.7 

2.3 

1.8 

1.3 

0.6 

0.9 

1.0 

3.0 

0.5 

Winter 

0.6 

1.4 

3.5 

0.8 

1.8 

0.3 

0.6 

0.5 

3.4 

0.7 

Study period 

average 

concentration 

0.8 

1.3 

3.0 

1.4 

1.4 

0.5 

0.6 

0.6 

2.3 

0.7 

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 midwestern cities from September through December 

1968. Within each city, sites were chosen to represent residential, commercial, and industrial areas. 

The lead content of the settled particulates was 

determined by atomic absorption spectrophotometry, and the depositions were expressed as mg/m2

-

mo. The highest amounts found in residential, commercial, 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); respectively. Maximum readings by month occurred in 

Muncie, Indiana (industrial) (105 mg/m2-mo in September); Nashville, Tennessee (commercial) (346 

mg/m2-mo in October); Omaha, Nebraska (industrial) (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, California3 

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 locations. The evidence strongly suggested that the 

C-2 
TABLE C-3. LEAD DATA FROM KANAWHA VALLEY STUDY' 

Sampling sites. 

location and no. 

Falls View (1) 

Smithers (5) 

Montgomery (6) 

Cedar Grove (7) 

Marmet(11) 

Kanawha City (13) 

Charleston (15) 

West Charleston (17) 

North Charleston-W (19) 

South Charleston-E (20) 

Dunbar (22) 

St. Albans (24) 

Nitro (25) 

Nitro-West (27) 

Fall 

1964 

— 

0.4 

— 

0.5 

— 

2.1 

— 

— 

— 

2.7 

— 

1.3 

1.0 

— 

Winter 

1964-1965 

0.2 

0.3 

0.6 

0.4 

0.5 

0.8 

0.9 

0.7 

0.7 

0.6 

0.4 

0.9 

1.4 

0.1 

Spring 

1965 

— 

0.3 

— 

0.2 

— 

0.6 

— 

— 

— 

0.6 

— 

0.3 

0.2 

— 

Summer 

1965 

0.0 

— 

0.4 

— 

0.5 

— 

— 

— 

1.0 

— 

0.4 

0.3 

— 

Study period 

average 

— 

0.2 

— 

0.4 

— 

1.0 

— 

— 

— 

1.2 

— 

0.7 

0.7 

— 

Lead in settled particulates, 

mg/m^/mo. 

study period 

average 

11.2 

6.7 

4.8 

3.8 

2.8 

— 

8.6 

11.6 

3.0 

3.4 

— 

EASTCHARLESTON 

CHARLESTON 

CREDE 

WEST CHARLESTON 

NORTH CHARLESTON, EAST 

NORTH CHARLESTON. WEST 

SOUTH CHARLESTON. EAST 

SOUTH CHARLESTON, WEST 

DUNBAR 

INSTITUTE 

ST.ALBANS 

NITRO 

WEST OF ST. ALBANS 

WEST QF NITRO 

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 Lead deposition 

Area 

Residential 

Commercial 

Industrial 

Concentration, 

geometric 

5.24 

9.80 

12.78 

mean Month 

September 

October 

November 

December 

Concentration. 

geometric mean 

9.11 

8.71 

9.15 

8.06 

horses died of lead poisoning that was caused by ingestion 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 concluded 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 during the study. Note that the fallout rates are on a 

daily basis. 

Figure C-2. Air sampling sites for Southern Solano County, 

California, study.5 

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 highest concentrations of deposited lead of 22 midwestern cities. Because automobile emissions should 

reflect the relatively low population density, the 

possibility of a significant contribution to air lead 

C-3 
P.87 

TABLE C-5. LEAD CONCENTRATIONS IN AIR DETERMINED 

BY ANALYSIS OF SUSPENDED PARTICULATE, SOUTHERN 

SOLANO COUNTY, CALIFORNIA, MARCH-MAY 1970s 

Site 

Carquinez Bridge 

Elliot Cove 

Babson house 

Braitodump 

Walsh house 

Braito TV transmitter 

site 

Wesner pasture 

Wesner pasture 

Wesner pasture 

Gomez pasture 

Wesner house 

San Francisco" 

Fremont0 

San Rafael" 

Distance 

from 

Selby,a 

km 

1.9 

3.0 

3.7 

5.6 

57 

7.7 

7.8 

8.0 

8.3 

10.0 

10.2 

22.0 

20.0 

19.2 

Lead concentration! 

High 

8.45 

0.93 

0.82 

0.69 

0.62 

1.07 

0.56 

0.66 

0.51 

0.28 

0.22 

3.50 

2.24 

2.04 

Low 

0.35 

0.27 

0.58 

0.07 

0.14 

0.25 

0.40 

0.11 

0.03 

0.03 

0.02 

1.15 

0.59 

0.41 

,/xg/m3 

Mean 

3.49 

0.52 

0.70 

0.64 

0.40 

0.59 

0.42 

0.38 

0.27 

0.11 

0.14 

2.12 

1.04 

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 1970* 

Site 

Distance 

from 

Selby.a 

km 

Sample 

period, 

days 

Total 

solids. 

mg 

Total 

lead, 

n9 

Lead 

fallout. 

mg/m2-day 

Carquinez 

Bridge 

Braito dump 

Braito TV transmitter site 

Wesner 

pasture 

Wesner 

pasture 

Wesner 

pasture 

Wesner 

pasture 

Wesner 

pasture 

Wesner 

pasture 

Wesner 

pasture 

Wesner 

pasture 

Gomez 

pasture 

Drachman 

pasture 

1.9 30 49.2 

5.6 30 58.7 

7.7 60 101.7 

8.0 31 370 

8.0 31 162 

8.0 31 171.4 

8.0 31 109.8 

8.0 31 351.7 

8.0 31 220.2 

8.0 30 83.5 

8.3 30 163.6 

10.0 32 45.0 

13.4 30 26.5 

1435 

195 

2.78 

0.38 

520 

185 

155 

195 

255 

210 

4535 

430 

705 

150 

75 

0.50 

0.35 

0.29 

0.37 

0.48 

0.39 

8.51 

0.83 

1.37 

0.27 

0.15 

from other sources (two battery plants, one refinery) 

in the central city area was considered. Consequently, 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 similar 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. 

ATMOSPHERIC LEAD - OMAHA 

MONTHLY COMPOSITE 

MAY - NOVEMBER 1970 

RESIDENTIAL 

a

 Location of suspected lead emissions source. See text. 

MAY JUN JUL AUG SEP OCT NOV 

TIME, months 

Figure C-3. Omaha, Nebraska study: mean monthly composite atmospheric lead at Industrial, commercial, mixed, 

and two residential sites. Mean is that of representative 24-

hour samples collected three times weekly. The autumnal 

peak at all but the industrial site parallels the usual Omqha 

pattern for particulates.6 

C.2.3 El Paso, Texas7'

8 

The El Paso, Texas, study was initiated in 1971 as 

a result of the discovery of increased lead deposition 

in the 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 particulate 

sampling network. Particulate' samples were collected 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 figlm3 and averaged 6.6 jixg/m3 over 

86 days. Average concentrations of 3.6 and 6.5 

/ug/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 

km 

12.8 E 

16 NE 

15.2 NW 

8NW 

4.8 SE 

21.6 SE 

4.8 N 

2.4E 

1.6 NE 

samples 

84 

73 

45 

75 

70 

71 

94 

26 

65 

Suspended atmospheric 

lead concentration 

Range 

0.38 to 5.82 

0.12 to 3.68 

0.10 to 1.50 

0.18 to 4.51 

0.02 to 22.16 

0.18 to 4.81 

0.08 to 8.62 

0.12 to 7.28 

0.26 to 6.67 

./jg/m3 

Average 

0.96 

0.76 

0.46 

1.03 

2.69 

1.39 

0.83 

2.72 

1.16 

C.2.4 Helena Valley, Montana9 

During the summer and fall of 1969, a sourceoriented 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 figlm3, with maximum concentrations of up to 0.7 /ug/m3

. The residents of the East Helena area were exposed to an 

average daily concentration of 0.4 to 4.0 /ug/m3, depending upon proximity to the source, with maximum daily exposures of up to 15 figlm3

. Within a 1-

mile radius of the East Helena smelter, settled particulate lead values ranged from 30 to 108 mg/m2

/ 

mo. Table C-8 summarizes the dustfall and suspended particulate data acquired during this study, 

and Figure C-4 shows the deposition of lead 

(dustfall) in the area. 

SCALC. kitamM*? 

L 

HTTLIAUI 

••ARTICULATC Lf AD. 

g^>10TO<3 0 

1)111 >JO TO < MO 

Figure C-4. Settleable particulate 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 atmospheric pollutants from lead mining and smelting 

operations. This industrial district has become one 

of the world's largest lead-producing areas by mining more than 392,277 MT of lead, or 75 percent of 

the entire U.S. lead production, during 1970. Settleable 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 collected in Glover, Mo. (Site 43, southeastern Iron 

County), by high-volume sampler were 3.4 /ng/m3 

(20 samples) in 1970, 5.3 /xg/m3 (32 samples) in 

1971, and 5.6 Mg/m3 (28 samples) in 1972. 

TABLE C-8. PARTICULATE DATA SUMMARY FROM HELENA VALLEY, MONT., ENVIRONMENTAL POLLUTION STUDY" 

Settleable particulate lead. mg/m2/mo 

Suspended particulate lead 

in glass fiber filter sample, iig/rrfl 

Station 

1 

2 

3 

4 

6 

Location3 

0.8 mi; 34° 

2.5 mi; 105° 

0.4 mi; 112° 

4.5 mi; 274° 

0.5 mi; 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 

76 

87 

85 

82 

34 

Max. 

5.3 

2.5 

16.0 

7.0 

15.0 

Min. 

< md° 

< md 

< md 

< md 

0.2 

Average 

0.45 

0.24 

1.25 

0.10 

3.89 

a

 Distance and compass direction from smelter stack, 

b Minimum detectable. 

C-5 
BUICK TOWtR # 0«3 

Figure C-5. Annual average of settleable particulate lead at 

sites near Missouri lead mine and smelter, g/mJ/Tno.10 

C.2.6 Helsinki, Finland" 

Investigators for the Agricultural Research 

Center in Tikkurila, Finland, an industrial and residential area near Helsinki, found high lead levels in 

soil. To clarify the origin of this excess lead, the Institute of Occupational Health conducted a dustfall 

lead survey in the area. Eighty collectors were located 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 increased deposited lead values fortyfold in some 

areas. The deposited lead values ranged from background 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 MISSOURITM 

1971 

Station 

no. 

Wind 

direction Distance, m 

Lead deposition rate, 

mg/m^/mo 

Wind frequency, % 

prevailing direction 

May-June 

July 

August 

September 

October 

November 

6 

7 

10 

7 

7 

3 

E 

SSE 

NE 

SSE 

SSE 

WNW 

81 

91 

633 

91 

91 

61 

5.88 

5.54 

4.57 

7.76 

5.10 

2.01 

18(S). 12(WNW) 

14(SSE), 13(S). 10(SSW) 

14ISSE). 1KS). 10ISSW) 

22IS). 12ISSE). 121SSW) 

10(N). 10(W). 10ISE). 11 (ESE) 

26(S). 12ISSW). 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 annually; until 1969 the stack emitted lead oxides 

without control by filters or other devices. Five sampling sites with high-volume samplers operating on a 

24-hr basis were established in the four principal settlements 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 CrnaW); 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 proportions. 

C.2.8 Ontario,Canada1* 

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 industrial sources. Emissions of lead from the smelter 

were estimated to be 17 tons per year; from the battery plant, 6 tons per year. Averages and ranges of 

C-6 
flIVERS 

rrfflflp SETTLEMENTS 

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 

Site 

Mezica 

Zerjav 

Rudarjevo 

CrnaSE 

CrnaW 

Minimum 

0.1 

0.3 

0.5 

0.1 

0.1 

Pb concentration jjg/m^ 

Maximum 

236.0 

216.5 

328.0 

258.5 

222.0 

Average 

24.2 

29.5 

38.4 

33.7 

28.4 

lead concentrations are summarized in Table C-11. 

Both soil and foliage samples showed definite trends 

toward reduced concentrations with increasing distance 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 measurements 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 figlcm2/yr from precipitation 

and 0.2 /ig/cm2/yr from dustfall14 in areas remote 

from intensive human activity. These small additions 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 concentrated 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 decomposition usually shows an increase in the concentration 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 roadways. 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 to 21.200 

1.996 

95 to 17.300 

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 

16 to 387 

43 

10»o124 

Air, /ig/m^ 

(24-hour samples) 

3.87* 

Max1 74.4 

2.21° 

Max-31.0. 

1.02c 

Max: 4.0 

aApril 1973 to May 1974. 

bNovember 1973 to May 1974. 

c

January 1974 to April 1974. 

C-7 
P.91 

studied in recent years.19 An example of this 

phenomenon is taken from a study of the Saline 

Branch watershed, which includes Champaign, Illinois. One facet of this comprehensive study20

 consisted of analyses for lead in soil at increasing distances from a low-traffic-volume street (400 vehicles/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 exterior 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 highvolume 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. 

E 1000 — 

a 

o. 

_• 20 0 

DISTANCE FROM STREET, meters 

Figure C-7. Soil transects by two streets: Curve A = lowtraffic-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.21 Similar data, compiled from a 3-yearold Russian lead smelter, 2 2

 are shown in 

Table C-12. The concentration decrease with both 

depth and distance is also apparent here. Information on soluble lead levels in soil near a similar complex in Great Britian is presented in a report by Little and Martin.23

 Barltrop reported values up to 

30,000 ,u.g/g in villages in the eastern half of Derbyshire County, England.24

 In this instance, the soil 

included lead contamination from old mine tailings 

and possible natural mineralization, i.e., the concentrations were not exclusively atmospheric in 

origin. 

DON * ANACOUN 

UMTE D STATU! 

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)a 

Distance trom Surface Soil depth 

source, m 

500 

1.000 

2.000 

3.000 

5.000 

16.000 

layer 

23.9711 

9.0163 

1.4207 

1.2192 

0.1031 

0.0943 

25 cm 

4.1747 

1.8368 

0.7432 

0.5991 

0.0649 

0.0778 

75 to 100 cm 

0.0748 

— 

0.0545 

0.0474 

0.0233 

0.0292 

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 preparation 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 Poland. Soil analyses were made in several areas prior 

to operation of the factory and after 1 year of operation. 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'S 

from 

km 

On grounds 

0.5 

1.0 

1.5 

2.0 

3.0 

5.0 

40.0 

Number 

of 

samples 

12 

10 

20 

6 

6 

4 

4 

4 

Maximum 

11.170.0 

2.420.0 

1:170.0 

720.0 

1.070.0 

340.0 

97.0 

3.0 

0 to 1 cm depth 

Minimum 

1.300.0 

470.0 

130.0 

170.0 

250.0 

130.0 

80.0 

2.5 

Lead content ot soi 

Average 

5.546.0 

1.156.0 

613.0 

369.0 

530.0 

235.0 

88.5 

2.7 

, mg/100 g a 

Maximum 

6.800.0 

650.0 

990.0 

720.0 

610.0 

260.0 

46.0 

Trace 

25 cm depth 

Minimum 

510.0 

130.0 

200.0 

70:0 

70.0 

100.0 

40.0 

Trace 

Average 

3.143.0 

458.0 

430.0 

340.0 

260.0 

180.0 

43.0 

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 fertilization, 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 population lead levels in selected american communities. Prepared by University of Cincinnati, Cincinnati, Ohio, under 

Contract No. PH-22-68-28. U. S. Environmental Protection Agency. Washington, D.C. Publication No. EPARI-73-005. 1973. 

2. Hauser, 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. Publication No. APTD-70-l. March 1970. 

4. Hunt, W. F., C. Pinkerton, O. McNulty, and J. Creason. 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 of Missouri Press. 

1971. p. 56-58. 

5. Maga. J.A.. F.B. Hodges, C.B. Christenson, 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 PasoSmelter Briefing 

Paper. Environmental Monitoring and Support Laboratory, 

U.S. Environmental Protection Agency. Research Triangle 

Park, N.C. May 1972. 

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Study. U.S. Environmental Protection Agency. Research 

Triangle Park, N.C. Publication AP-91. January 1972. 

10. Purushothaman, K. Air Quality Studies of a Developing 

Lead Smelter Industry. Rolla. University of Missouri Press. 

1972. 13 p. 

11. Laamanen, A. and A. Ryhanen. Aerial distribution of 

dustfall lead in the neighborhood of some lead emitters. 

Suomen Kemistilehti. (Helsinki). 44:367-371, 1971. 

12. Fugas, M., D. Majic, R. Paukovic, B. Wilder, and Z. Skaric. 

Biological Significance of Some Metals as Air Pollutants. 

Final Report. Part I: Lead. U. S. Department of Health, 

Education, and Welfare, Consumer Protection and Environmental Health Service. Washington, D.C. January 1974. 

Linzon, S. N., B. L. Chai, P. J. Temple, R. G. Pearson, and 

M. L. Smith. Lead contamination of urban soils and vegetation by emissions from secondary lead industries. J. Air 

Pollut. Control Assoc. 26(7): 650-654, 1976. 

Lead: Airborne Lead in Perspective. Washington, D.C,National Academy of Sciences. 1972. p. 28. 

15. Swaine, D. J. and R. L. Mitchell. Trace element distribution 

in soil profiles. J. Soil Sci. //(2):347-368, 1960. 

Goldschmidt, V. M. The principles of distribution of chemical elements in minerals and rocks. J. Chem. Soc. (London.) 

655-673. 1937. 

13 

14. 

16 

I 7. Tyler. G. Heavy metals pollute nature, may reduce productivity. 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. London 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 of Environmental Contamination by Lead. Institute for Environmental Studies, University of Illinois at Urbana-Champaign. 

Research Report No. I. August 1975. p. 53-56. 

21. Human Lead Absorption - Texas. U.S. Department of 

Health, Education, and Welfare. Atlanta, Georgia. Morbidity and Mortality Weekly Report. 22(49):405-407, 1973. 

C-9 
P.93 

22. Pakhotina, N.S. Sanitary hygienic evaluation of industrial 

emissions by a zinc-lead combine. In: Survey of USSR 

Literature on Air Pollution and Related Occupational Diseases. U. S. Public Health Service. Washington, D.C. 

J.-93-97, I960. 

23. Little, P. and M. H. Martin. A survey of zinc, lead and cadmium in soil and natural vegetation around a smelting complex. Environ. Pollut. 5:241-254, July 1972. 

24. Barltrop, D. Significance of lead-contaminated soils and 

25. 

26 

dusts for human populations. Arh. Hig. Rada Toksikol. 

(Yugoslavia.) 26:81-93, 1975. 

Smokotnina, T. N. Hygienic evaluation of air pollution with 

wastes from a lead plant. Hig. Sanit. (USSR). 27(6):87-90, 

1962. 

Paluch; J. and S. Karweta. The accumulation of zinc and 

lead in soil and plants. In: Lectures of 6th Int'l Congress of 

Forestry Specialists for Smoke Damage. Katowice. (Poland.) 

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 always familiarly translatable from one to the other, 

even when expressed in metric units. There are also 

two distinct categories of measurements: concentrations 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.l CONCENTRATIONS 

Airborne lead concentrations are customarily reported in units of mass per volume: micrograms of 

lead per cubic meter of air (fig/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 (figlg), or as parts per million 

(ppm). When ppm refers to mass, the expression is 

interchangeable with figlg. 

Concentrations of lead in water (dissolved or suspended) 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 lOOOg, and units 

of jag/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 

(figlg). or milligrams per kilogram (mg/kg), all of 

which are interchangeable. 

Concentrations of lead in blood may be reported 

in micrograms per deciliter (figldl) or in 

micrograms per 100 grams (figll00 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 production 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 (lb/ton), 

pounds per thousand gallons (lb/103 gal), 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, involving the human body, through inhalation and ingestion 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-l 
P.95 

D.3 UNITS D.4 CONCENTRATION CONVERSION 

FACTORS 

1 m = lOVm = 102cm = 10"3km = 3.281 ft = 

39.37 j n 1 PPb (mass) = 1 ng/g = Ifiglkg 

1 ppm (mass) = 1 figlg = 1 mg/kg 

1 m2= 104cm2= 10-6km2= 10.76 ft2 = ] mg/liter (water) » 1 ppm » I figlg 

1550 in2 1 Mg/liter (water) *£* 1 ppb 

lm3 = 106cm3 = 999.97 liters = 35.31 ft3 = ' ^8 / d l (blood) « 0.95 fig/l00 g (blood) 

6.1 x 104 in3 = 264.2 gal D.5 TRANSFER RATE CONVERSION 

l g = 10* ug= 103mg= 103kg= 0.035 oz = FACTORS 

0 0022 1b 1 mg/m2/mo= 2.85x10-3 tons (short)/mr2/mo 

1 tonne/yr - 2.74 kg/day = 

1 tonne (metric) = 1000 kg = 106g= 1.1023 tons (short )/yr 

1.1023 tons (short) 1 fig/day = 3.53 x 108oz (av.)/day 

D-2 
P.96 

APPENDIX E 

ABSTRACT OF A REVIEW OF THREE STUDIES 

ON THE EFFECTS OF LEAD SMELTER 

EMISSIONS IN EL PASO, TEXAS 

Presented by Warren R. IVluir 

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 conclusions of other investigations under different conditions and those in which clinical effects have been confirmed. However, because of inherent problems of study design and the limitations in the tests used, this finding 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 committee report. 

E l 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 airborne wastes in a series of baghouses; remaining emissions contain approximately 40 lb of lead per day. 

The El 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 medical 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 reported. 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 requested 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 

figllOO ml) of 46 and a control group (< 40 /xg/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 /i.g/100 ml 

were eventually involved in litigation, most of them took part in the studies. However, on the recommendation 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. Residence, 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 
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 discontinued), 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 impression that the effects of lead itself are being studied in a homogeneous population. However, since exposure 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 figllOO 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 administered. 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 figllOO 

ml and 15 with blood lead levels less than 40 figllOO ml) 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 onetailed tests. Significant differences between lead and control groups are reported in this study for the performance 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 functions in the CDC study were clouded by potentially important methodological difficulties. These included 

E-3 
P.99 

age differences between case and control groups, limited statistical treatment of the psychometric data collected, 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 Smeltertown, 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 predispose 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 conclusions of other investigations under different conditions and those in which clinical effects have been confirmed. However, because of inherent problems of study design and the limitations in the tests used, this finding should not lead to a conclusion that low levels of lead have no effects on neuropsychological performance. 

£ -4 * US- GOVERNMENT PRINTING OFFICE; 1978— 757-140/668 1