UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON D.C. 20460
OFFICE OF THE ADMINISTRATOR
SCIENCE ADVISORY BOARD
July 26, 2006
EPA-CASAC-06-008
Honorable Stephen L. Johnson
Administrator
U.S. Environmental Protection Agency
1200 Pennsylvania Avenue, NW
Washington, DC 20460
Subject: Clean Air Scientific Advisory Committee's (CASAC) Peer Review of the
Agency's Air Quality Criteria for Lead (Second External Review Draft),
Volumes I and II (EPA/600/R-05/144aB-bB, May 2006)
Dear Administrator Johnson:
EPA's Clean Air Scientific Advisory Committee (CASAC), supplemented by subject-
matter-expert Panelists — collectively referred to as the CASAC Lead Review Panel (CASAC
Panel) — met in a public meeting held in Durham, NC, on June 28-29, 2006, to conduct a peer
review of the Agency ' s Air Quality Criteria for Lead (Second External Review Draft), Volumes I
and //(EPA/600/R-05/144aB-bB, May 2006). The Clean Air Scientific Advisory Committee
roster is found in Appendix A of this report, and the CASAC Panel roster is attached as
Appendix B. The charge questions provided to the CASAC Panel by EPA staff are contained in
Appendix C to this report, and CASAC Panelists' individual review comments are provided in
Appendix D.
EPA is in the process of updating the Lead Air Quality Criteria Document (AQCD). The
purpose of the revised AQCD is to provide an assessment of the latest scientific information on
the effects of ambient lead on the public health and welfare, for use in the Agency's current
review of the National Ambient Air Quality Standard (NAAQS) for lead. On December 1, 2005,
EPA's National Center for Environmental Assessment, Research Triangle Park (NCEA-RTP),
within the Agency's Office of Research and Development (ORD), made the 1st draft Lead
AQCD available for public review and comment. Detailed summary information on the 1st draft
Lead AQCD is contained in a Federal Register notice (70 FR 72300, December 2, 2005). On
February 28-March 1, 2006, the CASAC Panel met in a public meeting to conduct its initial peer
review of the 1st draft Lead AQCD. The CASAC report from that meeting (EPA-CASAC-06-
005, dated April 26, 2006), is posted at URL: http://www.epa.gov/sab/pdf/casac-06-005.pdf
The CASAC Panel's June 28-29, 2006 meeting focused on the peer review of the 2nd draft Lead
AQCD.
-------
The CASAC Panel was pleased that the 2nd draft Lead AQCD is a substantial
improvement from the first draft. However, the CASAC has requested to review an updated
version of the integrative synthesis (Chapter 7), which was only available as a first draft in the
2nd draft Lead AQCD. The CASAC Panel noted that, in a January 1990 letter to the EPA
Administrator (please see Appendix E), the CASAC recommended that a monthly standard,
rather than a 90-day standard should be set for lead. The same letter also stated the following:
"The Committee believes you should consider a revised standard with a wide margin of
safety, because of the risk posed by lead exposures, particularly in the very young whose
developing nervous system may be compromised by even low level exposures. At the upper level
of the staff paper range (1.0-1.5 (ig/m3) there is relatively little, if any, margin of safety. There-
fore the Committee recommends that in reaching a decision on the level of the standard, greater
consideration be given to air lead values below 1.0 |ig/m3."
Despite this advice, neither the level of the standard nor the averaging time was changed. Now,
16 years later, the same concerns still exist. Also, a huge disparity now exists between the U.S.
NAAQS standards for lead and the guidelines for lead pollution developed by the World Health
Organization. Thus, the current CASAC Lead Review Panel wishes to emphasize in the
strongest manner possible that the updated air quality criteria document needs to provide a clear
scientific basis for the Agency to consider revising the Lead NAAQS to lower levels over shorter
averaging times. The CASAC Panel provides this advice in anticipation of its review of the 1st
draft Lead Staff Paper, which is currently under development by the EPA Office of Air Quality
Planning and Standards (OAQPS), within the Office of Air and Radiation (OAR).
Another major concern of the Panel was that Lead is a multimedia pollutant and the
current NAAQS process does not lend itself to protecting either public health or the environment
from the adverse effects of such a pollutant. Consideration must be given to all sources of lead
— in air, water and soil — to obtain a better idea of the most pertinent sources of lead exposure
that need to be controlled. In particular, the contributions of airborne lead to non-
inhalation pathways need more emphasis. In addition, estimates of exposure impacts for any
given exposure pathway cannot ignore exposure from other sources, but rather should consider
an expected distribution of those exposures, and should at least consider whether some
populations may have unusually high exposures from other sources. The current Lead AQCD
does not adequately discuss this problem, nor does it define the various sources of lead emissions
well. Finally, the Panel recommends that Chapters 7 and 8 be reversed, so that the material in
the welfare chapter (Chapter 8) can also be included in the integrative synthesis (Chapter 7).
The following comments relate to individual chapters on the 2nd draft Lead AQCD.
Detailed comments of individual Panel members are provided as an attachment (Appendix D).
Overall, the second draft of Chapter 2, "Chemistry, Sources, and Transport of Lead,"
represents a substantial improvement from the 1st draft Lead AQCD in both content and
presentation. The chemistry and physical properties of lead, and its transport and transformation
processes that affect migration, deposition and behavior in environmental reservoirs, are
described satisfactorily. However, there remains a scarcity of data with respect to emissions,
production, use, environmental release, and fate of lead. There are still numerous references
-------
throughout the Section 2.2 (Sources of Lead) that relate to pre-1990 data. The authors should
acknowledge the lack of current information in these areas (if indeed the data are not available)
and present critical evaluation of the available emission data to provide an adequate and
appropriate basis for the lead analysis and risk assessment activities proposed by OAQPS.
Chapter 3 on "Routes of Human Exposure to Lead and Observed Environmental
Concentrations" has been improved considerably since the first draft. The coverage for the
contribution of airborne lead to total body lead burden has been significantly enhanced. This
chapter still would benefit by incorporating a framework to describe the relative contribution of
various lead sources to dust lead loading. Specifically, it remains important to understand the
contribution of airborne lead on deposition of lead on surfaces and the existing burden of lead in
the environment in contributing to lead exposures, particularly for at-risk populations. More
clearly identifying the primary sources of lead exposure and the interactions between airborne
and oral lead intake would strengthen the presentation of data in this chapter. Although the
existing levels of airborne lead are relatively low by contemporary standards, they are still high
compared with pre-industrial standards. Lead-based paint remains a major source of lead
exposure in at-risk populations and needs greater weight in this chapter. It is also important to
describe factors that modify lead absorption such as iron status and fasting to complete an overall
understanding of the importance of human exposures to lead.
For Chapter 4, "Lead Toxicokinetics and Measurements/Modeling of Human
Exposure Impacts on Internal Tissue Distribution of Lead," the authors have significantly
improved the 2nd draft in response to CAS AC Panel members' comments on the 1st draft Lead
AQCD. Material from other chapters was moved to Chapter 4, and the discussion of lead
kinetics provides the reader with a better understanding of how these kinetics impact the
assessment of internal dose and thus the risk assessment. Also, descriptions of the models for
predicting blood lead levels were expanded to cover some case studies and more aspects of the
strengths and weaknesses of the various dosimetry models. However, making all of these
changes has led to a chapter title that is unwieldy in its length and needs to be changed.
Across the various sections, there is a need to check for consistency in terminology,
numbers, and discussions. A chapter summary section is needed wherein the major points that
should be carried forward to the integrative synthesis chapter are clearly articulated. Some
terminology can be tightened. For example, elemental lead and inorganic lead compounds are
not technically metabolized. In addition, lead "metabolism" in the chapter is really addressing
lead "binding kinetics."
Treatment of uptake by the route of inhalation is still not adequate. The deposition
fractions cited in the chapter differ by two- to three-fold from what current particulate dosimetry
models predict for children. EPA should be using the latest International Commission for
Radiation Protection (ICRP) or the multiple-path particle dosimetry (MPPD) model to obtain
deposition fractions for different sizes of lead particles.
Conclusions about model uncertainties should be explicitly included in the chapter. The
confidence intervals for mean blood estimates vary by at least a factor of two above and below
the mean in all instances, reflecting significant uncertainty in one's ability to predict accurately
-------
blood lead levels at current ambient exposures. There is also no discussion of how EPA would
use the slope factor models compared to the biokinetic ones. A recent combined analysis of
multiple studies has the potential to allow slopes to vary by population characteristics, but there
is no discussion of how this could be used. Because the biokinetic models rely on numerous
assumptions, it is critical to compare the predictions of the biokinetic models for specific
locations where the slope factor models were developed with epidemiologic data. It is also
important to note that some of the parameters in the biokinetic models are based on data from
small and non-representative populations, yielding uncertainty that also needs to be addressed.
The Panel agrees that this draft of Chapter 5, "lexicological Effects of Lead in
Laboratory Animals, Humans, and In Vitro Test Systems," is significantly improved over the
first draft in terms of defining its purpose, organization and inclusion of relevant materials. The
style of the summaries and the conclusions after each section is generally consistent, except for
the inclusion of human data in section 5.3 (neurotoxicology). Such data are appropriate for
Chapter 6 concerning human effects. The Introduction, section 5.1, might more strongly define
the purpose of chapter 5 as providing experimental and animal data in support of Chapter 6
concerning human health effects. Sections 5.2, 5.3 and 5.11 are all improved over the first draft.
The diagram, (5-2.1) on Effects of Lead on Heme Synthesis is complex and might be more clearly
described in the introductory paragraph to section 5.2, pp. 5-8. There are some redundancies in
Section 5.11 The organization according to organ systems may seem appropriate based on the
literature reports, but it is likely that many of the specific proteins are common to more than one
organ system, e.g., ALA-D. All figures in section 5.11 may be deleted since these are redundant
to the text and not needed in this document.
Chapter 6, "Epidemiologic Studies of Human Health Effects Associated with Lead
Exposure," does a thorough job of reviewing the epidemiological health-related literature. It is
logically presented in both providing historical background information and updating the current
findings. Lead has many proven health effects, and the chapter systematically goes through the
organ systems in a logical fashion, stressing the most important findings first as related to neuro-
cognitive function in children and then moving on to the findings in cardiovascular and renal
function in adults. Other organ system findings are presented, generally in a summarized fashion
with cross-referencing to the annex tables that contain the detailed findings.
The summary sections of the chapter provide a useful conclusion to each section and the
overall summary in section 6.10 brings all of the findings together. The CAS AC Panel believes
that it would be useful to add to the summary a discussion of the results of Patterson and Flegal,
showing that bone lead concentrations in the 1970s were three orders of magnitude higher than
background concentrations, as it put the findings in the newer studies (at an order of magnitude
lower exposure, but still two orders of magnitude above background) in context. In particular, it
helps clarify why studies have failed to find thresholds for effects in people with blood levels of
lead in the range of 1-10 |ig/dL.
-------
Clearly, there are significant neurocognitive effects in young children with lead blood
levels in the range of 1-10 |ig/dL, and when flexible functions such as penalized splines were
used to model these associations, they showed, if anything, steeper slopes at the lower end of the
range. While a smaller number of studies of children with blood lead levels below 4-5 |ig/dL
means that the magnitude of the slope is more uncertain in that range, the weight of the evidence
suggests, although less definitive, that a negative association with lead continues down to 1-2
Hg/dL.
The effects in adults on blood pressure, while small, are highly-consistent across the
epidemiologic studies and in the meta-analyses, and coupled with the mechanistic results from
the animal studies, should be treated as causal. As noted by Pirkle et al. (Am JEpidemiol. 1985
Feb;121(2):246-58), the cardiovascular epidemiology literature indicates that a national
reduction of 1 mm Hg of blood pressure can result in several thousand fewer cardiovascular
deaths per year, which is large compared to the risk assessments for most environmental agents.
Results for renal function are more difficult to quantify as they in large part reflect lifetime
accumulations, with release from endogenous stores (bone) as well as multimedia ongoing
exposures.
Chapter 7, "Integrative Synthesis of Lead Exposure/Health Effects Information," is
concise and well-written. The CASAC recommends that the chapter be amended to include an
evaluation of welfare effects of lead as well as health effects. With the inclusion of material
from Chapter 8, the integrative synthesis the chapter is then more appropriately placed following
after the chapter on environmental effects (Chapter 8).
The chapter could be further improved by better standardizing the format in which the
data are presented, i.e., including a discussion of human data first, followed by animal data that
support or extend the conclusions from the human studies; and by maintaining a consistent focus
on biologic effects that occur at relatively low lead levels. It is important to note that even
today's much-reduced lead exposures are still substantially above historical background levels.
Chapter 7 would also benefit from including tables that summarize the multi-exposure sources of
lead and its multi-organ system effects. As currently written, Chapter 7 tabulates the neuro-
cognitive results and provides figures for dose-response relationships in this area that are useful.
An additional table focused on the key lead contamination and lead exposure issues and a second
additional table focused on key dose-response relationships across various systems are also
recommended.
The neurotoxic effects of lead are appropriately identified as the area of major concern at
the lower lead exposure levels and total burdens commonly experienced today. The assumptions
made in estimating neurotoxic lead effects for children need to be clearly identified, particularly
those that could lead to an underestimation of the adverse consequences of childhood lead
exposure on intellectual abilities. A substantial portion of this chapter is directed at identifying
effects of lead on organ systems where adverse outcomes have not been shown to occur at low
lead levels. These include effects on the immune system, blood and heme synthesis, liver and
gastrointestinal system effects, reproductive and developmental effects, bone and teeth effects,
and genotoxi city /carcinogen! city. The chapter should more clearly integrate effects of lead in
these organ systems with assessment of their relative importance at low levels of exposure.
-------
The information in Chapter 8, "Environmental Effects of Lead," needs to be presented
in a way that is more directly relevant to the issue of whether the EPA Administrator should alter
the present primary (human health-related) and secondary (environmental- or welfare-based)
NAAQS for lead. Since secondary standards are often (and in the CASAC Panel's judgment,
neglectfully) set equal to primary standards, a key question is whether there are environmental
effects that occur at lead concentrations lower than — or for indicators, forms, or averaging
times different from — those that affect human health.
In the case of both the 2nd draft Lead AQCD and OAQPS' associated draft Analysis Plan
for Human Health and Ecological Risk Assessment for the Review of the Lead National Ambient
Air Quality Standards (draft Lead Risk Analysis Plan, May 2006), it seems clear that it is not just
the present ambient concentration of lead that is emitted into the air by contemporary lead
emissions sources that is hazardous to the present and future health and productivity of terrestrial
and aquatic ecosystems but rather, in very large part, the fraction of the historically deposited
lead that is redistributed. Contemporary loadings to terrestrial ecosystems are now about 1-2
mg/m2 per year — about three orders of magnitude smaller than the cumulative loading from all
atmospheric sources during the past century.
Thus, with rare exceptions in the immediate vicinity of some lead processing facilities,
most contemporary exposures of living organisms (and consequent risks to the health and
productivity of natural and managed ecosystems in the U.S.) are not caused by contemporary air
concentrations and exposures to airborne lead compounds, but rather are caused primarily by
redistribution of environmentally persistent lead compounds deposited in soils, sediments, and
surface waters during the past century. Therefore, maintaining a secondary lead NAAQS that is
equivalent to the primary NAAQS — and thus aiming only to manage current air concentrations
of lead by decreasing contemporary emissions of lead instead of processes and procedures that
decrease the redistribution of historically deposited — will not provide satisfactory protection of
terrestrial and aquatic ecosystems from risks of exposure to lead.
At a minimum, the Lead AQCD should allow decisions about changes to the present
primary and secondary NAAQS to be able to take into account the large reservoir of lead
currently stored in soils and sediments in terrestrial ecosystems of the U.S. Furthermore, the
document should strongly suggest that these reservoirs must be periodically evaluated and
considered as significant sources of lead. To that end, Chapter 8 still does not adequately
consider monitoring needs and the implications of dietary exposure for such future activities. It
continues to understate the uncertainties in regulatory applications of equilibrium partitioning in
sediments and the biotic ligand model.
The CASAC was pleased that the 2nd draft Lead AQCD contained a revised discussion of
the "Critical Loads" concept and its strengths and limitations.
Finally, the CASAC has reached a consensus that, pending incorporation of the CASAC
Panel's advice as reflected herein, the science in the 2nd draft Lead AQCD is adequate for
regulatory purposes. However, the CASAC has requested to review an updated version of the
integrative synthesis (Chapter 7), which was only available as a first draft in the 2nd draft Lead
AQCD. This review is scheduled for August 15, 2006 via a public teleconference.
-------
As always, the Clean Air Scientific Advisory Committee and the CASAC Panel are
pleased to continue to provide scientific advice to the Agency during the NAAQS review
process. The Committee looks forward to reviewing the 1st draft of the Agency's Lead Staff
Paper. We wish Agency staff well in this important task.
Sincerely,
/Signed/
Dr. Rogene Henderson, Chair
Clean Air Scientific Advisory Committee
Appendix A - Roster of the Clean Air Scientific Advisory Committee
Appendix B - Roster of the CASAC Lead Review Panel
Appendix C - Agency Charge to the CASAC Lead Review Panel
Appendix D - Review Comments from Individual CASAC Lead Review Panel Members
Appendix E - CASAC Letter re: NAAQS for Lead (EPA-SAB-CASAC-90-002) dated January
3, 1990
-------
Appendix A - Roster of the Clean Air Scientific Advisory Committee
U.S. Environmental Protection Agency
Science Advisory Board (SAB) Staff Office
Clean Air Scientific Advisory Committee (CASAC)
CHAIR
Dr. Rogene Henderson, Scientist Emeritus, Lovelace Respiratory Research Institute,
Albuquerque, NM
MEMBERS
Dr. Ellis Cowling, University Distinguished Professor-at-Large, North Carolina State
University, Colleges of Natural Resources and Agriculture and Life Sciences, North Carolina
State University, Raleigh, NC
Dr. James D. Crapo, Professor, Department of Medicine, National Jewish Medical and
Research Center, Denver, CO
Dr. Frederick J. Miller, Consultant, Cary, NC
Mr. Richard L. Poirot, Environmental Analyst, Air Pollution Control Division, Department of
Environmental Conservation, Vermont Agency of Natural Resources, Waterbury, VT
Dr. Frank Speizer, Edward Kass Professor of Medicine, Channing Laboratory, Harvard
Medical School, Boston, MA
Dr. Barbara Zielinska, Research Professor, Division of Atmospheric Science, Desert Research
Institute, Reno, NV
SCIENCE ADVISORY BOARD STAFF
Mr. Fred Butterfield, CASAC Designated Federal Officer, 1200 Pennsylvania Avenue, N.W.,
Washington, DC, 20460, Phone: 202-343-9994, Fax: 202-233-0643 (butterfield.fred@epa.gov)
(Physical/Courier/FedEx Address: Fred A. Butterfield, III, EPA Science Advisory Board Staff
Office (Mail Code 1400F), Woodies Building, 1025 F Street, N.W., Room 3604, Washington,
DC 20004, Telephone: 202-343-9994)
A-l
-------
Appendix B - Roster of the CASAC Lead Review Panel
U.S. Environmental Protection Agency
Science Advisory Board (SAB) Staff Office
Clean Air Scientific Advisory Committee (CASAC)
CASAC Lead Review Panel
CHAIR
Dr. Rogene Henderson*, Scientist Emeritus, Lovelace Respiratory Research Institute,
Albuquerque, NM
MEMBERS
Dr. Joshua Cohen, Faculty, Center for the Evaluation of Value and Risk, Institute for Clinical
Research and Health Policy Studies, Tufts New England Medical Center, Boston, MA
Dr. Deborah Cory-Slechta, Director, University of Medicine and Dentistry of New Jersey and
Rutgers State University, Piscataway, NJ
Dr. Ellis Cowling*, University Distinguished Professor-at-Large, North Carolina State
University, Colleges of Natural Resources and Agriculture and Life Sciences, North Carolina
State University, Raleigh, NC
Dr. James D. Crapo [M.D.]*, Professor, Department of Medicine, National Jewish Medical and
Research Center, Denver, CO
Dr. Bruce Fowler, Assistant Director for Science, Division of Toxicology and Environmental
Medicine, Office of the Director, Agency for Toxic Substances and Disease Registry, U.S.
Centers for Disease Control and Prevention (ATSDR/CDC), Chamblee, GA
Dr. Andrew Friedland, Professor and Chair, Environmental Studies Program, Dartmouth
College, Hanover, NH
Dr. Robert Goyer [M.D.], Emeritus Professor of Pathology, Faculty of Medicine, University of
Western Ontario (Canada), Chapel Hill, NC
Mr. Sean Hays, President, Summit Toxicology, Allenspark, CO
Dr. Bruce Lanphear [M.D.], Sloan Professor of Children's Environmental Health, and the
Director of the Cincinnati Children's Environmental Health Center at Cincinnati Children's
Hospital Medical Center and the University of Cincinnati, Cincinnati, OH
Dr. Samuel Luoma, Senior Research Hydrologist, U.S. Geological Survey (USGS), Menlo
Park, CA
B-l
-------
Dr. Frederick J. Miller*, Consultant, Cary, NC
Dr. Paul Mushak, Principal, PB Associates, and Visiting Professor, Albert Einstein College of
Medicine (New York, NY), Durham, NC
Dr. Michael Newman, Professor of Marine Science, School of Marine Sciences, Virginia
Institute of Marine Science, College of William & Mary, Gloucester Point, VA
Mr. Richard L. Poirot*, Environmental Analyst, Air Pollution Control Division, Department of
Environmental Conservation, Vermont Agency of Natural Resources, Waterbury, VT
Dr. Michael Rabinowitz, Geochemist, Marine Biological Laboratory, Woods Hole, MA
Dr. Joel Schwartz, Professor, Environmental Health, Harvard University School of Public
Health, Boston, MA
Dr. Frank Speizer [M.D.]*, Edward Kass Professor of Medicine, Channing Laboratory,
Harvard Medical School, Boston, MA
Dr. Ian von Lindern, Senior Scientist, TerraGraphics Environmental Engineering, Inc.,
Moscow, ID
Dr. Barbara Zielinska*, Research Professor, Division of Atmospheric Science, Desert Research
Institute, Reno, NV
SCIENCE ADVISORY BOARD STAFF
Mr. Fred Butterfield, CASAC Designated Federal Officer, 1200 Pennsylvania Avenue, N.W.,
Washington, DC, 20460, Phone: 202-343-9994, Fax: 202-233-0643 (butterfield.fred@epa.gov)
* Members of the statutory Clean Air Scientific Advisory Committee (CASAC) appointed by the EPA
Administrator
B-2
-------
Appendix C - Agency Charge to the CASAC Lead Review Panel
SUMMARY OF SALIENT REVISIONS INCORPORATED INTO THE MAY 2006
SECOND EXTERNAL REVIEW DRAFT OF EPA's LEAD AQCD AND ASSOCIATED
CHARGE QUESTIONS FOR JUNE 2006 CASAC PUBLIC MEETING
A. GENERAL REVISIONS
Addition of an Executive Summary. A newly-developed Executive Summary has been added
to the 2n Draft Lead AQCD at the beginning of Volume I. That summary consists of concise
bullets characterizing key findings and conclusions drawn from various main chapters of the
document.
Charge Question - Executive Summary:
What are the CASAC Lead Panel's views with regard to the format of the newly-
provided Executive Summary and the soundness of its scientific content, including
consistency of the restatement of key findings and conclusions stated in the main chapters
of the document?
B. REVISIONS TO SPECIFIC CHAPTERS
Chapter 2 - Chemistry, Sources and Transport of Lead. This chapter has been revised to
update and clarify information on atmospheric chemistry of Lead (Pb) and various sources of Pb
in the environment. Discussion of data available from EPA's National Emissions Inventory has
been added to Section 2.3, including estimated Pb emissions for 1990 and 2003 for the larger
source categories.
Charge Questions - Chapter 2:
(a) Overall, does this revised chapter adequately characterize various important sources
of Pb in the environment?
(b) Are salient data from EPA and other sources, in addition to the peer-reviewed
literature, now adequately incorporated into the chapter?
(c) Are any further improvements necessary?
Chapter 3 - Routes of Human Exposure to Lead. Revisions have been made to more clearly
delineate sources of Pb exposure from different media. Section 3.1 has been expanded to discuss
data from EPA's current monitoring networks that measure airborne Pb and to provide summary
data on ambient Pb concentrations from recent years. The evidence related to Pb exposure via
soil or dust sources is also more thoroughly discussed in this 2nd Draft AQCD.
C-l
-------
Charge Questions - Chapter 3:
(a) Overall, does the revised chapter adequately discuss available information on routes
of Pb exposure via air, drinking water, soil, dust and food?
(b) Are any further revisions needed to address issues regarding Pb exposure in dust and
soil that were earlier identified by the Panel?
Chapter 4 - Lead Toxicokinetics and Measurement / Modeling of Human Exposure
Impacts on Internal Tissue Distribution of Lead. The scientific rationale underlying most
lead-related regulatory or remedial action decisions typically include estimation of the impact of
exposures to Pb in air, water, food, soil/dust or other media on internal Pb body burden. Blood
lead concentration is extensively used as an index of exposure and body burden relative to other
potential dose indicators (e.g., lead in kidney, plasma, urine, or bone) in epidemiologic studies.
Chapter 4 addresses the relationship between Pb exposure and the resulting Pb burden and
distribution in the body.
Charge Questions - Chapter 4:
(a) An overview of Pb toxicokinetics (absorption, distribution, and elimination) was
added to the chapter in Section 4.2. Particular attention was accorded to describing
factors recognized to affect Pb absorption. The distribution of Pb between body
compartments and the role of Pb in bone as an internal Pb source for the blood was
briefly introduced since an extensive discussion of Pb in blood and bone appears in
Section 4.3. Does the current discussion provide sufficient information on the routes of
Pb exposure and toxicokinetics?
(b) Biological markers of Pb exposure and body burden are discussed in Section 4.3.
Higher blood Pb concentrations are interpreted as indicating higher exposures (or Pb
uptakes), but are not necessarily predictive of overall body burden. Bone Pb is more so
considered an indicator of cumulative Pb exposure and is a potential internal source of Pb
exposure for other tissues. Are the discussions of various biomarkers adequate to
elucidate for present purposes their usefulness for assessing human health effects of Pb
exposure?
(c) Section 4.4 characterizes key information on available approaches to the modeling of
external Pb exposures and their impacts on internal Pb body burdens. Does this section
sufficiently characterize the ability of different models to handle key factors related to Pb
exposure modeling, including temporal variation in external exposure profiles, low-level
Pb exposure, multi-pathway Pb exposure and the contribution of historical Pb exposure in
influencing blood Pb levels? Are the strengths and weaknesses of the currently available
models adequately discussed?
C-2
-------
Chapter 5 - Toxicologic Effects of Lead in Laboratory Animals, Humans and In Vitro Test
Systems. The CASAC Panel expressed major concerns with section 5.3, which discusses
neurological and neurobehavioral effects of Pb. Section 5.3.1 has been extensively revised to
include: expanded summaries of the pre-1986 literature; less emphasis on neurochemical and
electrophysiological effects of lead; the addition of- 24 pages of new information on
neurobehavioral effects (i.e., effects on learning, memory, attention, motor activity, social
behavior); and expanded discussions regarding the blood brain barrier, Pb accumulation in brain,
susceptibility and vulnerability factors (such as gender, stress, aging, of period of exposure) and
lack of evident threshold. Additionally, for all studies discussed, blood Pb levels at which effects
occur are included. Section 5.3.2 has been shortened by moving previous epidemiology
discussions to Chapter 6 and biomarker discussions to Chapter 4. Overall, the chapter has a
more consistent format, with bulleted summaries at the end of each major section.
Charge Questions - Chapter 5:
(a) Does the revised neurobehavioral material adequately cover the large and extensive
literature to provide a solid basis for comparison with human Pb-induced neurobehavioral
dysfunction, as presented in the following chapter?
(b) Do the neurochemical and electrophysiological studies provide adequate information
about Pb mechanisms of action observed in animals and humans?
(c) Do the expanded discussions of pre-1986 data adequately provide context for more
recent literature, including the observation that advances in animal toxicology data
continue to point to adverse effects occurring at lower and lower Pb exposure levels?
(d) Also, are the discussions of susceptibility and vulnerability factors sufficient and
clearly presented?
Chapter 6 - Epidemiologic Studies of Human Health Effects Associated with Lead
Exposure. Chapter 6 examines the extensive epidemiologic evidence base for human health
effects associated with Pb exposure. The epidemiologic literature base is assessed to address the
issue of adverse health effects observed at or near ambient Pb levels, or more specifically, at
blood lead levels of 10 |ig/dL and lower. Key adverse health outcomes seen at low blood lead
levels (< 10 |ig/dL) are discussed in terms of Pb effects on a number of different types of health
endpoints. Particular emphasis has been placed in the 2nd Draft Pb AQCD materials on:
(1) neurotoxic effects of lead in children,
(2) cardiovascular system effects in adults, and
(3) renal effects in adults.
C-3
-------
Charge Questions - Chapter 6:
(a) Does the presentation in chapter 6 with regard to neurotoxic effects of Pb exposure
on children substantiate an adverse effect at blood Pb levels <10 |ig/dL? Is the potential
public health significance adequately discussed? Does the evaluation of available data in
regard to model selection provide an adequate basis for model selection and use in risk
analysis? If so, which models are recommended for this endpoint? Are there aspects of
the above that are not adequately addressed?
(b) Does the Chapter 6 presentation regarding cardiovascular effects in adults of Pb
exposure substantiate adverse effects at blood Pb levels <10|ig/dL? Is the potential public
health significance adequately discussed? Does the evaluation of available data in regard
to model selection provide an adequate basis for model selection and use in risk analysis?
If so, which models are recommended for this endpoint?
(c) Does the Chapter 6 presentation on Pb renal effects in adults substantiate an adverse
effect at blood Pb levels <10|ig/dL? Is the potential public health significance adequately
discussed? Does the evaluation of available data in regard to model selection provide an
adequate basis for model selection and use in risk analysis? If so, which models are
recommended for this endpoint?
(d) Has Chapter 6 omitted any important newly available key Pb epidemiology studies
that should be considered? If so, please provide copies of any missed studies and
comment as to what aspects of these studies warrant review.
Chapter 7 - Integrated Synthesis of Lead Exposure and Health Effects. The first draft of
Chapter 7 (Integrated Synthesis of Lead Exposure and Health Effects) has been incorporated into
the AQCD along with second drafts of other chapters. The purpose of Chapter 7 is to provide a
coherent framework for assessment of health risks associated with human exposures to ambient
airborne Pb. The chapter first discusses Pb sources, emissions, and ambient concentrations. This
is followed by discussions of Pb toxicokinetics and measurement and modeling of Pb exposure
to estimate internal Pb levels. This is also followed by a more extended integrative discussion of
toxicologic and epidemiologic evidence for Pb health effects. A key topic addressed is
characterization of dose-response relationships, including the nonlinear nature of Pb effects seen
for a number of endpoints. Discussions of persistence/reversibility of Pb-induced health effects
and susceptibility and vulnerability to Pb are additional important components of the chapter,
with certain human population groups being identified as likely being at increased risk for Pb
effects.
Charge Questions - Chapter 7:
(a) Has NCEA staff adequately integrated the toxicologic and epidemiologic evidence to
provide biologic plausibility for Pb effects on cognitive function, blood pressure,
renal function, and other key endpoints?
(b) Has the proper focus been placed on relevant low-level exposures?
(c) Does the chapter capture the unique properties of Pb in the context of exposure and
health effects (e.g., the multimedia nature of exposures, the nonlinear dose functions,
C-4
-------
and the apparent lack of threshold for effects)?
(d) Does the chapter adequately describe the important considerations for identifying
populations that are especially susceptible or vulnerable to Pb?
Chapter 8 - Environmental Effects of Lead. The terrestrial and aquatic ecosystem summary
sections (Sections 8.1.1 and 8.2.1) have been moved to the main body of the AQCD and serve as
the main chapter. More detailed information is contained in the Chapter 8 Annex. The section
numbers in the main chapter correspond to the same section numbers in the Annex, to facilitate
locating of more detailed information in the Annex while reviewing the main chapter. The
relatively brief main chapter includes: (1) a concise summary of "Key findings/conclusions"
from earlier assessment documents, and (2) carefully prepared descriptions of advances in
scientific understanding that have been made since the time of the last review and published in
more recent scientific literature.
Charge Questions - Chapter 8:
(a) Has NCEA staff adequately resolved previous inconsistencies across the sections that
comprise Chapter 8 and its Annex? Have the redundancies been reduced to an
acceptable level?
(b) Are limitations with use of the biotic ligand model adequately addressed?
(c) Are there any further improvements that need to be made in Chapter 8?
C-5
-------
Appendix D - Review Comments from
Individual CASAC Lead Review Panel Members
This appendix contains the preliminary and/or final written review comments of
the individual members of the Clean Air Scientific Advisory Committee (CASAC) Lead
Review Panel who submitted such comments electronically. The comments are included
here to provide both a full perspective and a range of individual views expressed by
Panel members during the review process. These comments do not represent the views
of the CASAC Lead Review Panel, the CASAC, the EPA Science Advisory Board, or
the EPA itself. The views of the CASAC Lead Review Panel and the CASAC as a
whole are contained in the text of the report to which this appendix is attached. Panelists
providing review comments are listed on the next page, and their individual comments
follow.
D-l
-------
Panelist Page#
Dr. Joshua Cohen D-3
Dr. Deborah Cory-Slechta D-5
Dr. Ellis Cowling D-9
Dr. Bruce Fowler D-15
Dr. Andrew Friedland D-17
Dr. Robert Goyer D-19
Mr. Sean Hays D-21
Dr. Bruce Lanphear D-23
Dr. Samuel Luoma D-27
Dr. Frederick J. Miller D-30
Dr. Paul Mushak D-34
Dr. Michael Newman D-53
Dr. Michael Rabinowitz D-55
Dr. Joel Schwartz D-60
Dr. Frank Speizer D-64
Dr. Ian von Lindern D-67
Dr. Barbara Zielinska D-75
D-2
-------
Dr. Joshua Cohen
Comments on Chapter 4
Joshua Cohen
These comments do not address in depth Section 4.2 (Toxicokinetics), or Section 4.3 (Biological
Markers), as these issues are outside my area of expertise and are better addressed by other
members of the CAS AC. Overall, I think that the revised chapter is a substantial improvement
on the December 2005 version. Nonetheless, I am troubled that some of my comments appear
not to have been addressed, and I do not know why.
(1) The introduction to Section 4.4, which corresponds to the introduction to Chapter 4 in the
December 2005 version, nicely describes the characteristics, advantages, and
disadvantages of regression models and mechanistic models. The revised introduction
addresses the concerns I outlined in my original comments for Section 4.1 in the
December 2005 version of the report.
(2) My original comment pertaining to Section 4.3 in the December 2005 version of the
report does not appear to have been addressed. I include the comment here for the sake
of convenience:
This section does a good job at describing the components of the IEUBK model (Section 4.3.1).
The discussion of the model's calibration and evaluation (Section 4.3.2) is inadequate. Page 4-
16, line 30-32 states that the IEUBK model has been evaluated by Hogan et al. (1998). It then
goes on to describe the reasonable agreement that Hogan et al. reported between observed and
lEUBK-predicted blood lead levels. EPA does not mention that another evaluation (Bowers and
Mattuck, 2001) that found that "the IEUBK Model reproduces blood lead levels in children well
for some communities, but poorly for others" (p. 1706). EPA does mention this paper (p. 4-17,
line 17) but only in the context of stating that empirical comparisons have shown that numerous
factors influence agreement between the model and observed blood lead values. EPA does not
mention that, at least according to Bowers and Mattuck, these factors can be so idiosyncratic that
it is impossible to account for them unless empirical blood lead measurements are available for
the community in question (p. 1708), something that would obviate use of the model.
Even if the IEUBK model predicts GM blood lead levels without bias, I am concerned about the
way in which the model is used to predict the probability that a child's blood lead level will
exceed a specified level of concern (in particular, 10 jUg/dL). Because the model's predictions
are imperfectly correlated with actual blood lead levels, its low predictions will tend to be
underestimates, while its high predictions will tend to be overestimates. It follows that the model
will overpredict the probability that blood lead levels will exceed a specified level of concern at
higher levels of environmental lead exposure (and likewise underpredict this probability at lower
levels of environmental lead exposure). Even if the residual GSD (as estimated by Griffin et. al.
(1999b) is reasonably correct), and hence the aggregate predicted risk of exceeding 10 /ug/dL is
close to observed values (i.e., summed over all individuals in the population), the model will tend
to overestimate this risk at higher levels of environmental lead exposure (and underestimate it at
lower levels of environmental lead exposure). These discrepancies can have ramifications for the
use of such models to identify appropriate regulatory limits for exposure to lead.
D-3
-------
Section 4.4.4.2 in the current version of the report still states that the IEUBK model has
been evaluated and that its predictions were close to empirical measurements. The
Bowers and Mattuck (2001) article is cited, but the findings in that article have been
ignored. It is critical that EPA acknowledge these less favorable findings and explain
why they are or are not relevant.
(3) EPA has addressed my original comment regarding the use of the term "average" at page
4-31, line 13. That comment asked if "average" referred to the arithmetic or geometric
mean. The most recent version of the report indicates that EPA intends for the inputs to
the IEUBK model to represent arithmetic average values (see line 23 on p. 4-92). The
text, though, reads "Exposure inputs that represent the average (e.g., arithmetic mean)
daily value..." Why does EPA use "e.g.," in this context (meaning, "for example")?
Does the Agency mean that one could use the arithmetic mean, for example, or
alternatively the geometric mean? Although it appears that EPA has addressed my point,
the text could be clarified further. Should "i.e." ("that is") be used in place of "e.g."?
(4) It appears that EPA has addressed my comment pertaining to Section 4.6 in the
December 2005 version of the report regarding the prediction that AALM predictions
will probably agree with the IEUBK model. That text seems to have been removed.
(5) EPA has not fully addressed my comment pertaining to Section 4.9 in the December
2005 version of the report. That comment stated that from a regulatory perspective, the
differences between various mechanistic models are not minor. My original comment
read,
Page 4-42, lines 5-7. The suggestion that remaining differences between the major
models are "minor discrepancies" does not seem appropriate. As noted above, the
impact of lead uptake on blood lead levels predicted by the Leggett model (and hence the
AALM) exceeds the corresponding IEUBK model prediction by a factor of two.
Nonetheless, EPA has retained the text, now at lines 5-7 on p. 4-123, that reads,
A fourth model, the All Ages Lead Model (AALM), is still under development and may
resolve some of the issues regarding minor discrepancies between other models...
(6) I agree with Fred Miller's general comments. The chapter still does not reach a
conclusion or make recommendations as to how lead body burden is best estimated given
the available tools. As it now stands, the chapter represents a tremendously valuable
literature summary. It does not, however, offer as much guidance as it should for EPA's
need to evaluate the public health implications of population exposure to lead.
D-4
-------
Dr. Deborah Cory-Slechta
Chapter 5 Comments
General Comments
The revised version of this chapter is in general significantly improved, in terms of
defining its purpose, chapter organization, and inclusion of relevant materials. The one exception
to this is the inclusion of the human data related to neurotoxicology. The introduction here
doesn't as clearly define what the purpose of having this section in chapter 5, especially since it
is supposed to be to provide conclusions for chapter 6. This still needs better integration,
particularly if it is to be presented prior to the material from which these conclusions are to be
drawn.
Specific Comments
p. 5-5, line 6, add V to 'concentration'
p. 5-18, lines 26-27'. It is not clear where this conclusion comes from re: gender. It doesn't seem
at all clear from either the experimental or human literature where the literature is minimal and
inconsistent.
p. 5-23, line 22, add 't' to 'he'
p. 5-23, line 25, 'Nonetheless' does not seem to be the correct word for this sentence.
p. 5-27, line 6, insert space after Pb2+.
p. 5-28, line 29. This paragraph should probably include a statement about the relative
importance of chronic exposure rather than simply early developmental exposure.
p. 5-32, line 21, why is the visual system 'especially' sensitive? Not clear from blood Pb levels
of exposure at which such effects are seen that it stands out.
p. 5-33, lines 9-10. Its not clear that this interpretation applies, since these monkeys were likely
to have very high bone Pb levels feeding back to blood and thus there technically is 'current
exposure'.
p. 5-33, line 12, is the value of 109 |ig/dL correct?
p. 5-35, lines 23-28, these two sentences appear to be inconsistent
p. 5-36, lines 12-13, it isn't clear why the statement that there was a high degree of response
variability is included here; what is the reference to that for rats?
D-5
-------
p. 5-41, lines 1-2, change 'during acquisition of to 'on'; delete 'and during steady state'.
p. 5-41, lines 3-4, change 'the acquisition and steady state' to 'on'; change 'in the FF to 'on the
FF.
p. 5-41, lines 1-12. Text should be included here that states that the enhanced sensitivity of the
FR schedule in this case probably resides in the fact that it requires a fixed number of responses
for reinforcement, whereas the FI schedule reinforces only a single response for reinforcement.
p. 5-41, lines 20-27. In addition to the two potential interpretations suggested, the phrase 'or an
alteration in timing capabilities' should be added.
p. 5-46, lines 6-8. The definition of a concurrent discrimination is incorrect.
p. 5-49, line 4, it should be indicated as to whether these are wet weight (presumably) values or
not.
p. 5-49, lines 16-18, The last sentence seems inconsistent with the evidence. It is clear that
learning deficits can be produced by Pb exposure at virtually all stages of the life cycle; there is
no particular window of vulnerability.
p. 5-54, lines 23-31. It should be indicated that the lack of an effect on sustained attention was
seen despite broad modifications of virtually all parameters of the task.
p. 5-58, line 4, certainly not a mechanism for all of Pb's neurobehavioral effects?
p. 5-58, lines 17-20, units should be added to the concentration values listed.
p. 5-61, lines 1-2. . It is not clear why this task is singled out for what should be indicated in
future studies as to its limitations, since this is certainly not done across all of the assays used in
neurotoxicology as described here. It appears to be singled out. The statement and interpretation
also fails to apparently understand that whatever its deficiencies, differential changes in drug
discrimination does indeed make clear where there are differences in underlying functions of the
neurotransmitter system under study; what can happen is that with repeated drug dosing, the
nature of the effects produced can change differentially in Pb and control animals.
p. 5-69, lines 5-7, insert 'either' before 'exposure'; insert 'alone or' before 'maternal stress;
insert 'alone' after 'maternal stress'.
p. 5-74, lines 6-7; should also indicate that these levels appear to be homogenous across regions.
p. 5-78, lines 1-5, references?
p. 5-78, lines 8-13, references?
p. 5-81, lines 14-16, references?
D-6
-------
p. 5-121, lines 10-14. It seems surprising that no mention is made of the exposure concentrations
and associated blood Pb values associated with the Tsao et al study, since they seem to bring the
hypertension effects to extremely low Pb exposure levels, lower than any (?) other study. This
omission also occurs in the executive summary.
p. 5-184, lines 2-9, Still missing is what may be an interesting interaction described between Pb
and arsenic, with As exposure increasing Pb concentrations in brain. There is a study by Meja et
al. (Neurotoxicology and Teratology, 1997, vol 6:489-497) examining combined effects of Pb
and As that reports that Pb levels in brain are increased by this co-exposure.
p. 5-281 The section on lead-binding proteins is overlapping with what has been previously
described.
Chapter 7 Comments
p. 7-20, lines 25-31. The statement about control of exposure in animal models requires
clarification. While one can terminate external exposure sources, there is still the problem of
residual bone Pb concentrations that will feed back into blood and continue exposure. This is
acknowledged appropriately in the executive summary but is not the black and white that the text
in chapter 7 suggests.
p. 7-24, lines 16-29, no references for the studies described are cited.
p. 7-26, lines 11-19 suggests that is a critical period of vulnerability for memory and NMDA
receptor changes produced by Pb. I don't think this is consistent with the literature.
p. 7-62, lines 11-12. Text could be added here to strengthen this argument. Increases in fixed
interval response rate are never 'beneficial' in that they always unnecessarily increase the
number of response required per reinforcer. In addition, increases in response rate are always
context specific. If it is responses that are inappropriate in context, then it can hardly be
considered beneficial, as is alluded to in the text.
Executive Summary Comments
E-9, line 7, reads strangely, perhaps change the word 'well' to 'consistently'
E-9, line 15-22, as noted for chapter 5, it is not clear that the lowest levels of exposure associated
with Pb-related hypertension have been reported. While the executive summary states levels of
20-30 |ig/dl in normal animals, the study of Tsao et al. (2000) seems to indicate increases in
blood pressure down to blood Pb levels of 2 |ig/dl in rats.
D-7
-------
E-12, Effects of Lead on Other Organ Systems, the impact of Pb on corticosterone deserves
mention as well as future research. If it turns out to be a broadly based effect, as suggested by
current studies, it has broad implications for a potential mechanism of Pb-induced hypertension,
but also a potential role for Pb in other diseases and disorders as yet unstudied in relation to Pb,
including diabetes, obesity and others.
D-8
-------
Dr. Ellis Cowling
Please note that pages 1 and 2 of these Individual Comments were prepared on June 25, 2006,
prior to the CASAC Peer Review and Consultation on June 28-29, 2006, and that
pages 3-6 of these comments were prepared on July 6-11, 2006 in light of the very valuable
discussions during the CASAC Peer Review and Consultation on June 28 and 29, 2006.
Individual Comments prepared before the
CASAC Peer Review of the Second External Review Draft Criteria Document on Lead
and the CASAC Consultation on the Analysis Plan for Human Health and Ecological Risk
Assessment for the Review of the Lead National Ambient Air Quality Standards
The most impressive general conclusion in the First and Second External Review Drafts of
the Lead Criteria Document is the very substantial decreases in air concentrations and
atmospheric deposition of lead into the environment that were achieved in recent decades -
especially as the result of the phase-out and almost complete discontinued use of lead as a motor
fuel additive. The amounts of lead that were emitted into the air by human activities, transported
through the atmosphere, and deposited onto vegetation, surface waters, soils, and accumulated
into sediments during the past century earlier decades were very substantial indeed.
Total lead cumulative deposition of lead in the United States during the 20th Century is
estimated to be 1-3 grams per square meter of land and water surface area - depending on
elevation and proximity to urban areas and lead smelting and processing facilities.
Contemporary loadings to terrestrial ecosystems are now about 1-2 milligrams per square
meter per year - about three orders of magnitude smaller than the cumulative loading from all
atmospheric sources during the past century.
Thus, with rare exceptions in the immediate vicinity of some lead processing facilities, most
contemporary exposures of living organisms (and consequent risks to the health and productivity
of natural and managed ecosystems in the United States) are not caused by contemporary air
concentrations and exposures to airborne lead compounds, but rather are caused primarily by
redistribution of environmentally persistent lead compounds deposited in soils, sediments, and
surface waters during the past century.
Recognizing this reality, the consensus statement regarding Environmental Effects of Lead
prepared by CASAC Members Cowling and Poirot and by CASAC Lead Panelist Friedland,
Luoma, and Newman for inclusion in the CASAC Letter to EPA Administrator Johnson
regarding Chapter 8 in the First External Review Draft for Lead recommended that:
"The information in chapter 8 needs to be presented in a way that is more directly
relevant to the issue of whether the Administrator of EPA should retain, increase, or decrease
the present primary and secondary National Ambient Air Quality Standards for lead. Since
secondary standards are often (neglectfully) set equal to primary standards, a key question is
whether there are environmental effects that occur at lead concentrations lower than, or for
indicators, forms, or averaging times different from, those that effect human health."
D-9
-------
In my opinion, this same general comment applies equally well to the revision of Chapter 8
in the Second External Review Draft and also to the "Ecological Risk Assessment" part of the
"Analysis Plan ... for the Review of the Lead National Ambient Air Quality Standards."
The newly prepared Executive Summary in the Second External Review Draft, and Chapter 8
in both the Second as well as the First External Review Draft of the Criteria Document for Lead,
needs to more clearly indicate how any continuing environmental effects of lead might respond
to changes in current and future atmospheric lead emissions, concentrations, or deposition. A
further revised Chapter 8 would better help USEPA prepare for such changes if it included a
more complete and/or balanced analysis of the status of new advances in the science relevant to
environmental management of lead. For example, consideration of monitoring needs and the
implications of dietary exposure and trophic transfer are needed, as is more balance in
considering equilibrium partitioning in sediments. Some improvement in the discussion and
suggested uses of the biotic ligand model are evident in the revision of Chapter 8 for the Second
External Review Draft. But it also would be useful if this Chapter were to consider how
environmental effects of historically deposited lead or future increases in deposition (if current
laws are relaxed) might be modified by land-use changes, or soil amendment treatments, or
interactions with other pollutants including other metals or acidifying pollutants, or with changes
in climate and climate processes."
Members of CASAC were especially pleased to see the relatively thorough discussion at the
end of Chapter 8 in the First External Review Draft regarding the alternative concepts of critical
loads, critical limits, target loads, and target times that have been developed in European and
Canadian scientific literature to guide the processes of decision making regarding both
environmental and public health effects of airborne chemicals. Although these alternative
concepts and processes of analysis of multiple pollutant/multiple effects have not been carefully
considered for use in the United States, we believe, together with the authors of the National
Research Council/National Academy of Sciences 2004 report on "Air Quality Management in
the United States," that these alternatives should be considered very carefully as air quality
management tools for use in this country as well.
The further revised discussion of the Critical Loads concept and its strengths and limitations
in Chapter 8 in the Second External Review Draft indicates that progress in American thought
about these aspects of environmental management are moving in constructive directions.
In summary, many of us in CASAC continue to believe that:
"The principal goal of the NAAQS review process is to answer the following policy
question: 'What scientific evidence is there since the last review to indicate if the current
NAAQS standards are satisfactory or need to be revised or if additional standards needs to be
implemented to protect public health and public welfare and the environment.'"
In the case of the current Criteria Document and the associated "Analysis Plan" document for
lead, it seems clear that it is not just the present ambient concentration of lead that is emitted into
the air by contemporary lead emissions sources that is hazardous to the present and future health
and productivity of terrestrial and aquatic ecosystems, but rather, in very large part, the fraction
of the historically deposited lead that is redistributed. Thus, maintaining a Secondary (public-
D-10
-------
welfare based) NAAQS that is equivalent to the Primary (public-health based) NAAQS, and thus
aims only to manage current air concentrations of lead by decreasing contemporary emissions of
lead instead of processes and procedures that decrease the redistribution of historically deposited
will not provide satisfactory protection of terrestrial and aquatic ecosystems from risks of
exposure to lead.
Individual Comments prepared on July 6 and 7 in light of valuable discussions during the
CAS AC Peer Review of the Second External Review Draft Criteria Document on Lead
and CASAC Consultation on the Analysis Plan for Human Health and Ecological Risk
Assessment for the Lead National Ambient Air Quality Standards on June 28-29, 2006
The most impressive result of the valuable discussions that occurred during the CASAC Peer
Review of the Criteria Document and the Consultation on the Staff Paper on lead is the almost
complete absence of discussion in both the Second External Review Draft of the Criteria
Document (including the Integrative Synthesis Chapter and the Executive Summary) and the
Analysis Plan for Human Health and Ecological Risk Assessment for the Lead National Ambient
Air Quality Standard about the following four science and policy-relevant issues:
1) The many unique features of lead as a Criteria Pollutant compared to the other gaseous
pollutants for which air concentrations and exposures are the primary mode of action in
inducing both human health and human welfare effects,
2) How the Identical Primary and Secondary National Ambient Air Quality Standards for
lead established very early (in 1977) by the USEPA have remained unchanged since 1977
despite the significant review of the NAAQS for lead that occurred in 1990 and 1991,
3) How different the contemporary standards or targets for lead pollution established by the
World Health Organization and some other countries of the world are from those
established by the USEPA for use in the United States, and
4) How many members of CASAC are coming to realize that continuing to adopt identical
Primary and Secondary National Ambient Air Quality Standards for Criteria Pollutant
involves a (usually unstated) assumption regarding policies and procedures appropriate
for protection of human health and the environment. In fact, policies and procedures
appropriate for protection of human health and human welfare (the latter including both
ecological and other welfare effects such as visibility) may not be as effective (or even
well-justified scientifically) for protection of the environment (including ecological,
visibility, and other human welfare effects.
This last statement often is true either because:
a) There are ecologically important living organisms that are even more sensitive to
some criteria pollutants than human beings, and/or
b) The mode of ingestion, mechanism of action, or other features of some pollutants
may be sufficiently different from that of other pollutants that a different level (air
concentration), indicator, form, or averaging time for a National Ambient Air
Quality Standards - or even an entirely different approach (such as critical loads
or levels) may be important and thus should be considered even more thoroughly
D-ll
-------
in the Criteria Documents and policy-focused Staff Papers prepared by the
USEPA.
In summary, I hope that these four limitations of the Ecological Effects Chapter (Chapter 8),
the Integrative Synthesis Chapter, and the Executive Summary in the Second External Review
Draft of the Criteria Document, and the initial Analysis Plan for Human Health and Ecological
Risk Assessment for the Lead National Ambient Air Quality Standards will be considered in
preparing the final drafts of these important documents - even in the limited time that is
available before the court-ordered deadline for completion of these documents - but especially in
the future in developing other Criteria Documents and Staff Papers or other scientific assessment
and policy assessment documents for other Criteria Pollutants.
With regard to the second and third issues listed above, it was very encouraging to see the
following statements prepared by my CASAC colleagues, Jim Crapo and Paul Mushak, in their
individual comments after the CASAC meeting on the lead Criteria Document and Staff Paper:
Jim Crapo's very brief statement was as follows:
"It is recommended that the introduction include a more detailed discussion of the history of
EPA Lead NAAQS revisions including recommendations of previous CASAC groups. It is
recommended that this section also include the chronology of international policies on lead
air quality standards."
Paul Mushak's more detailed statement was as follows:
"CASAC member Dr. Cowling recommended acceptance of the document but only so
long as the history of past efforts by EPA and others, post-1978, to evaluate and make
recommendations on air lead standards or guidelines be included. Similar sentiment was
expressed by others. I agree. I particularly agree with the need for inclusion of discussion
of past CASAC actions, post-1978, as part of the review record.
Members of the current CASAC Panel may or may not be aware that, in the 1989-
90 timeframe, a former CASAC Panel presented a set of quite clear recommendations to
Administrator William K. Reilly regarding that Panel's review, conclusions and
recommendations for the EPA/OAQPS Staff Paper on NAAQS evaluation dated March,
1989.1 was a member of the CASAC Panel preparing the 1/90 report (and also a member
of the two WHO-Europe panels noted below who presented WHO-Europe air lead
guidance values in 1987 and again in 2000).
The 1990 CASAC Report on the NAAQS
The most significant parts of EPA's former SAB/CAS AC Committee on NAAQS
review for Pb, in its January 3, 1990 transmittals to EPA Administrator Reilly, were
specific conclusions and recommendations deriving from its review of the OAQPS
March, 1989 Staff Paper. I would urge that the current CASAC Chair include, in any
near-future transmittals to Administrator Johnson, complete copies of both the January 3,
1990 transmittals and the March, 1989 OAQPS/EPA Staff Paper as part of the
Administrative Record.
D-12
-------
The subject 1/90 CASAC transmittal to Administrator Reilly included two
paragraphs among the conclusions and recommendations that captured the essence of the
CASAC Panel's efforts. I strongly recommend that these two paragraphs be quoted in the
current AQCD and any new OAQPS Staff Paper so as to provide important context.
These two paragraphs are presented verbatim below:
[1990 CASAC Report, p. 1, 2nd Par.] "In discussing blood lead levels used to
assess alternative standards, it is the consensus of CASAC that blood lead levels
above 10 |ig/dl clearly warrant avoidance, especially for development of adverse
health effects in sensitive populations. The value of 10 |ig/dl refers to the
maximum blood-lead level permissible for all members of these sensitive groups,
and not mean or median values. The Committee concluded that the Agency
should seek to establish an air quality standard which minimizes the number of
children with blood lead levels above a target value of 10 |ig/dl. In reaching this
conclusion, the Committee recognizes there is no discernible threshold for several
lead effects and that biological effects can occur at lower levels. In setting a target
value for blood lead (matched ultimately to air lead level) the Committee
emphasized the importance of always being mindful that blood lead levels and
health outcome measures are best characterized as a distribution of values about
mean or median values. The importance of considering the distribution of values
about the mean or median is apparent from consideration of the influence of lead
exposure on I.Q. A seemingly modest decrease in the mean or median I.Q. may
result in significant changes at the outer limits of the distribution with both a
reduction in the number of bright children (I.Q. > 125) and an increase in the
number of children with I.Q. < 80."
[1990 CASAC Report, p. 3,1st Par.] "The EPA Staff recommended in the Staff
Position Paper that the lead NAAQS be expressed as a monthly standard in the
range of 0.5 to 1.5 |ig/m3 not to be exceeded more than once in three years. The
Committee concurs with the EPA Staff recommendation to express the lead
NAAQS as a monthly standard not to be exceeded more than once in three years.
The Committee strongly recommends that in selecting the level of the standard
you take into account, the significance and persistence of the effects associated
with lead as well as those sensitive population groups for which valid quantitative
exposure/risk estimates could not be made at this time. The Committee believes
you should consider a revised standard with a wide margin of safety, because of
the risk posed by lead exposures, particularly to the very young whose developing
nervous system may be compromised by even low level exposures. At the upper
level of the staff paper range (1.0-1.5 |ig/m3) there is relatively little, if any,
margin of safety. Therefore, the Committee recommends that in reaching a
decision on the level of the standard, greater consideration be given to air lead
values below 1.0 |ig/m3. To provide perspective in setting the NAAQS for lead it
would be appropriate to have the EPA Staff compute the distribution of blood-
lead levels resulting from a monthly standard of 0.25 |ig/m3 for comparison with
the values already computed for higher levels. In setting the NAAQS for lead it is
D-13
-------
important to recognize that airborne lead serves not only as a source of inhalation
exposures, but that lead in air deposits on soil and plants becoming a potential
source for intake into the body."
The WHO-Europe Air Lead Guidelines
The 1987 (first edition) WHO-Europe "Air Quality Guidelines for Europe"
developed an air lead guideline for Europe consisting of a level in the range of 0.5 to 1.0
|ig/m3. The process for development of the 1987 air Pb guideline is contained in Chapter
23. The key elements in that development included, but were not limited to, the fact that
both adults and very young children are affected; children are affected at lower exposures
than adults; and air lead enters the body directly through inhalation but also subsequently
via ingestion of dusts and soils produced from air lead fallout.
World Health Organization. 1987. Air Quality Guidelines for Europe. Lead. Ch.
23. WHO Regional Bureau for Europe, Copenhagen, pp. 242-261.
The 2000 (second edition) WHO-Europe "Air Quality Guidelines for Europe"
took an even more quantitative approach, which permitted a single, low air lead guideline
to be selected, a guideline value at the lower end of the previous range given in 1987.
Elements of the recommendation in the Guidelines update for air lead included 1)
derivation of a guideline value based on a Pb-B level of 10 |ig/dl in young children; 2)
lead ingestion as well as lead inhalation are important for young children; 3) an air lead
value of 1.0 |ig/m3 translates via direct and indirect (dust/soil/diet) pathways to a Pb-B of
at least 5 |ig/dl; 4) 98% of young children should have a Pb-B that does not exceed 10
Hg/dl; 4) this translates to the median Pb-B not exceeding 5.4 |ig/dl. All of this, plus
factoring in the non-air inputs to children's Pb-B levels, works out to the air lead not
exceeding 0.5 |ig/m3 and this value was the recommended Guideline.
World Health Organization. 2000. Air Quality Guidelines for Europe. Second
Edition. Lead. Ch. 6.7. WHO Regional Bureau for Europe, Bilthoven, The
Netherlands, pp. 149-153.
If CAS AC wishes the relevant sections of these two WHO documents, they
presumably are in the EPA docket for the current process. Otherwise, I would be happy
to provide them.
D-14
-------
Dr. Bruce Fowler
BAF 6/22/06
Bruce A. Fowler
Comments on Chapter 5 Second Draft of EPA AQCD for Lead
General Comments
This is a much improved draft of Chapter 5 with an improved organizational structure and clarity
of discussion and completeness of references. One general suggestion for improvement would
be to further integrate mechanistic information wherever possible between interactive cellular /
biochemical systems in the chapter. In particular, the effects of lead on the heme biosynthetic
pathway, mitochondrial respiration, generation of reactive oxygen species and apoptosis are
treated as isolated consequences of lead exposure. These effects are, in fact, integrally related to
each other. It might be useful for a reader, new to the field, to also receive some understanding
that observed individual effects of lead discussed in the document are frequently connected to
each other. This type of integration occurs in the discussion for the neurotoxic, immunotoxic
effects of lead but it would helpful for this approach to be expanded wherever possible to other
organ systems such as the hematopoietic, renal and reproductive. Please see specific comments
below for individual organ systems.
Hematopoietic System
Section 5.2 Effects of Lead on Heme Synthesis
This section is largely a discussion of the effects of lead on the erythrocyte structure and
function with respect to ALAD. Figure 5-2.1 is a nice schematic of the heme biosynthetic
pathway but omits the fact that mature erythrocytes do not contain mitochondria. This aspect of
erythrocyte heme biosynthesis actually occurs in the bone marrow progenitor cells not
erythrocytes in circulation. This figure also notes Zn protoporphyrin but this section does not
discuss the importance of this molecule for lead biomonitoring at elevated exposure levels (other
countries in the world still have sub- populations with blood leads above 20 ugPb/dl). Zn
protoporphyrin is also useful as an index for iron deficiency which may be useful to the
discussion of iron/lead interactions that should also be taken up later in the document (see
below). A short paragraph on Zn protoporphyrin and the bone marrow progenitor cell
localization of the mitochondria would add some clarity. The other aspect which should be
discussed in this section is concerns lead inhibition of mitochondrial respiration which would
lead to increased formation of H2O2 and reactive oxygen species (ROS) and attenuated
reduction of Fe+3 to Fe+2 by the mitochondrial electron transport chain which is necessary for
incorporation of Fe2+ into the protoporphyrin ring by ferrochelatase to form heme. If this
reduction does not occur, Zn is inserted resulting in formation of Zn-protoporphyrin. It is worth
noting here that porphyrins are also toxic and capable of catalyzing formation of ROS which
may stimulate apoptosis and cause the release of more Fe from the Fe-S clusters of aconitase to
catalyze Fenton chemistry. The overall point here is that all these processes are related and
D-15
-------
capable of building on each other. These relationships hence have implications for mechanism of
action (MO A) based - low dose extrapolations of lead toxicity in a number of target tissues. The
heme pathway deserves a more complete discussion here if for no other reason than to explain
why it is so important as a sensitive metabolomic biomarker system for lead.
Populations at Risk
It has been appreciated for many years that great variability in sensitivity to lead toxicity exists
in human populations exposed to lead. In order to improve assessments for populations at special
risk, it is important to have a better understanding of the factors which contribute to defining a
sensitive sub-population. The document currently takes up a number of these factors in various
sections of Chapter 5 and perhaps it might be useful to gather up those which are well-
documented into one section to address this evolving issue. Nutritional status (Ca2+ and Fe),
concomitant exposure to other metals such as Cd, genetic polymorphisms (ALAD), metal
binding proteins (MTs) / lead-binding proteins, age, gender etc are clearly potentially important
modulators of susceptibility for lead toxicity and a discussion of these factors at one place in the
document should be helpful. There has been a great increase in knowledge in recent years
regarding the role of these factors in mediating susceptibility to lead toxicity and it would seem
prudent to make sure this information is summarized in Chapter 5 to some degree as well as in
Chapter 7.
Specific Page Comments
P 5-16 First Bullet - that the activity of erythrocyte ALAD appeared...
Page 5- 155 Section 5.7.1 - consider adding the following reference regarding the mechanisms
of lead uptake in the kidney:
Victery WW, Miller CR, Fowler BA. Lead accumulation by rat renal brush border membrane vesicles.
J Pharmacol Exp Therap 231:589-596, 1984.
Page 5-179 Consider adding the J Lab. Clin Med papers from the 1970s by Mahaffey and Goyer
on Pb-Ca interactions (currently not cited) interactions here. It is the primary study on this
interaction.
Page 5- 180 Pb x Cd Interactions
The study by Mahaffey et al (1981) cited on page 184 was a factorial design study which
contained a PbxCd group and found marked reduction in the blood lead concentration vs the
increase reported here. The reason may be dose / duration dependent.
Page 5-182 Pb x Fe Interactions - J Lab Clin Med paper from the 1970s by Mahaffey and
Goyer should be cited here. A primary study on this interaction.
Page 5-187 - second to last bullet - delete or modify statement that cadmium increases Pb in
blood when both are given...
D-16
-------
Dr. Andrew Friedland
Andy Friedland, Dartmouth College
22 June 2006
Preliminary Individual Review Comments on Second External Review Draft Lead Air Quality
Criteria Document (Dated May 2006)
In general, the overall document is much improved. Most of my comments refer to Chapter 8:
Environmental Effects of Lead; a few comments refer to the Executive Summary, Chapter 7 and
Chapter 2
The second draft of Chapter 8 reflects small but effective changes relative to the first draft. I
believe the authors have done a very good job of improving the document and responding to
comments from the CAS AC and Lead Panel.
The most significant comment I have refers to the fact that there still does not appear to be any
detailed information within Chapter 8 on the present-day sources of Pb to terrestrial ecosystems.
There is general discussion of the sources of Pb at the beginning of Chapter 8, so it does appear
that the authors agree this is a valuable subject. And there are mentions of sources in Chapter 2,
7 and elsewhere. However, none give a present-day picture of the sources of Pb emissions in the
US. Figure 2-2, page 2-17, gives the most detailed analysis of the sources of Pb in emissions.
Unfortunately, the data are from 1990. The observation that Pb emissions have decreased
significantly is discussed repeatedly throughout the document but this does not reduce the need
for knowing exactly current Pb deposition sources.
It is possible that this topic can be addressed, at least in New England, through careful
extrapolation from Polissar et al. 2001 (Atmospheric aerosol over Vermont: chemical
composition and sources). However, it is more likely that the data are simply not available in the
peer-reviewed literature for emissions in Year 2000 and beyond. I think that it is important for
the lack of data and the need for the collection of these data to be stated at the beginning of
Chapter 8 and elsewhere.
Other, more minor comments follow:
Page 8-1, lines 10-11. I still think it is incorrect to list waste incineration as the first item in a list
of sources of atmospheric lead pollution. Surely the other two items on the list—metal smelting
and production and combustion of fossil fuels—are larger sources. Fig. 2-2, which is nearly
inscrutable, suggests that waste incineration was not a major source of Pb in 1990. If the authors
have newer and different information, they should present it.
Pages 8-12 line 23 through 8-13 line 11. I do not understand the distinction that is made between
"disruption of the organic matter cycle in forests" under the section "Influence of Forest
Harvesting" and soil carbon mobilization and loss leading to Pb loss in the section "Influence of
D-17
-------
Land Use and Industry." These two very brief sections should probably be merged or the
distinction between these similar topics should be made clearer.
Page 8-15, line 3 through 8. I hope this doesn't seem arbitrary, but I think this sentence needs to
be made more active and should start with the phrase at the end of this very long sentence. The
sentence should begin with "In acid- and metal-contaminated soils or soils treated with Pb" and
then go into the way the sentence currently begins "numerous investigators have documented
significant declines in litter decomposition rates " This way, all the references come at the
end of the sentence rather than separating two very important clauses.
The aquatic and critical load sections are satisfactory as drafted here.
The Executive Summary is quite good. I noted that page E-15 lines 34-37 contains an
inconsistency relative to Chapter 8, page 8-1. The Executive Summary states lead in the
atmosphere "results largely from waste incineration, metal smelting, metal production, and coal-
fired power plants." Chapter 8 refers to the last source as "combustion of fossil fuels." I suspect
that Chapter 8 is correct but I don't know and I can't learn this from the current document, which
further reinforces my request for a figure containing recent data on Pb sources in atmospheric
deposition.
D-18
-------
Dr. Robert Goyer
COMMENTS: 2ND DRAFT AQCD FOR LEAD
Chapter 5 Toxicological Effects
Robert A. Goyer, M.D.
This draft of Chapter 5 is much improved over the earlier version. It is now quite well organized
with few redundancies and is clearly written. The style of the summaries and conclusions after
each section are consistent, and as far as I could determine, accurately reflect the text.
I have only a few comments and minor criticisms. I tried to see how well the report of the
toxicological studies supported Chapter 6, the results of epidemiological studies
Section, 5.2, Heme, The Chapter is well written and the conclusions fit the text as in the first
draft. Minor comment on the diagram 5-2.1. This diagram on Effects of Lead on Heme Synthesis
is more complex than the diagram that appeared in the 1986 criteria document reflecting new
details. Studies supporting the diagram are described in the text but it took some effort on my
part to fully understand the diagram. I interpreted the numbers 1 thru 6 as identifying enzymatic
steps in heme synthesis but it might help the reader if there was a comment to this effect,
(identification of steps in heme synthesis) in the introductory paragraph to section 5.2, p5-8. The
sites for lead effect are clearly marked.
Section 5.6 Cancer p. 5-134 Line 14 —The statement, "The assessment of carcinogenicity of
epidemiologic studies remains ambiguous". I agree. However, IARC and the NTP have recently
upgraded Lead to a 2A classification —probable human carcinogen and this is discussed in
Chapter 6, Section 6.7.2.1 suggest deleting 'ambiguous' and add a reference to discussion in
Chapter 6.
Section 5. 7 Kidney-conclusions are well-done, reflect the text. In support of the debate in
chapter 6 section about newer epidemiological studies on effects of chelation on renal function,
(section 6.4), experimental studies on effects of EDTA might be expanded to provide studies on
mechanism. I want to bring attention to two earlier studies from my laboratory many years ago
that compliment the discussion of the Sanchez-Fructoso et al. (2002b) study.
One study shows the effects of EDTA on removal of lead from kidneys, (inclusion bodies) by
EDTA.
Goyer, R.A., Wilson, M., Lead-induced inclusion bodies: results of EDTA treatment. Lab Invest
32:149-156, 1975.
A second study showed the effects of EDTA on removal of lead and restoration of oxidative-
phosphorylation from mitochondria from renal tubular cells from lead exposed rats.
D-19
-------
Goyer, R.A., Krall, A., Kimball, J.P. The real tubule in lead poisoning: in-vitro studies on
mitochondrial structure and function. Lab Invest 19:78-83, 1968.
The section on lead binding proteins was greatly improved in terms of clarity and organization.
The organization according to organ systems is appropriate. I don't believe enough is known yet
to identify relations between Pb-binding proteins from different organs systems —maybe in the
future. The text regarding potential role of metallothionein has been revised to reflect
conclusions of research reports.
I have no comments regarding other sections of chapter 5.
D-20
-------
Mr. Sean Hays
Comments on Air Quality Criteria for Lead (Second External Review Draft)
Provided by: Sean Hays
Date: June 27, 2006
Comments on Chapter 4: Lead Toxicokinetics and Measurement/Modeling of Human Exposure
Impacts on Internal Tissue Distribution of Lead
• EPA has done a good j ob of summarizing the understanding of lead kinetics. This new
section helps the reader and risk manager understand how the kinetics of lead impact the
assessment of internal dose and thus the risk assessment. This new sections also provides
a nice backdrop to then judge the lead kinetic models.
• The example simulations of case studies provided in Figures 4-4 through 4-7 are very
helpful. It might be additionally insightful to redo Figure 4-7 to show the predicted
relationship between lead intake blood lead concentrations in adults and children at blood
lead levels ranging from about 0.1 to 5 |ig/dL (a more relevant range of blood lead levels
in the U.S.).
• A major factor in this risk assessment will be how certain can we predict a blood lead
level for a given level of lead in our environment (dust, soil, water, air, etc.). To this
degree, it would be helpful if the authors would discuss explicitly this topic in a section
of its own. To provide a little context, it is useful to look at Table 4-10 (page 4-76) and
observe the 90% confidence intervals for blood lead levels associated with the various
dust and soil loading scenarios from Lanphear 1998. Even for the lowest soil and dust
concentrations, the mean (and 90% CI) are 2.3 (0.9, 5.7) |ig/dL. This is an incredibly
variable estimate.. .based on actual monitoring data and their regression modeling.
Furthermore, a quick glance at Table 4-10 indicates that the coefficient of variation in
predicted/observed blood lead levels increases with decreasing exposures. Albeit, Table
4-10 only reports two exposure media factors, but given that dust and soil are the largest
contributors to blood lead levels today in the U.S., it is not expected that the certainty in
blood lead predictions will improve significantly by including additional exposure terms.
This issue will have to be carefully considered in designing the risk assessment. A
conclusion about uncertainty in model predictions should be explicitly included in this
chapter. In particular, the authors should discuss uncertainty in blood lead level
predictions at current background levels. I think the following quote from Chapter 4 is
very insightful and the individuals conducting the risk assessment for this AQCD should
take heed from this quote.
(Quote taken from pages 4-65 to 4-66): Modeling of human lead exposures and biokinetics has advanced
considerably during the past several decades. Among the most important new advances are development,
evaluation, and extensive application of the Integrated Exposure Uptake Biokinetic (IEUBK) Model for
Lead in Children (U.S. Environmental Protection Agency, 1994a) and the development of models that
simulate lead biokinetics in humans from birth through adulthood (Leggett, 1993; O'Flaherty 1993,
1995). While these developments represent important conceptual advances, several challenges remain for
further advancements in modeling and applications to risk assessment. The greatest challenge derives
D-21
-------
from the complexity of the models. Human exposure-biokinetics models include large numbers of
parameters, which are required to describe the many processes that contribute to lead intake, absorption,
distribution, and excretion. The large number of parameters complicates the assessment of confidence in
parameter values, many of which cannot be directly measured. Statistical procedures can be used to
evaluate the degree to which model outputs conform to "real-world" observations and values of
influential parameters can be statistically estimated to achieve good agreement with observations. Still,
large uncertainty can be expected to remain about many, or even most, parameters in complex exposure-
biokinetic models such as those described below. Such uncertainties need to be identified and their
impacts on model predictions quantified (i.e., through use of sensitivity analysis, probabilistic methods).
Given the difficulty in quantitatively assessing uncertainty in values of all of the individual parameters in
an exposure-biokinetics model, assurance that the model accurately represents the real-world in all
aspects is virtually impossible. As consequence of this, Oreskes (1998) noted, "... the goals of scientists
working in a regulatory context should be not validation but evaluation, and where necessary,
modification and even rejection. Evaluation implies an assessment in which both positive and negative
results are possible, and where the grounds on which a model is declared, good enough are clearly
articulated. " In this context, evaluation of confidence in a given exposure-intake or intake-biokinetics
model rests largely on assessment of the degree to which model predictions, based on model inputs
appropriate for a situation, conform to observations and/or expectations; and, most importantly, the
degree to which this conformity does or does not satisfy requirements of model application to a specific
context. Because of limitations in observations of predicted outcomes, it may be possible to evaluate
confidence in some uses of a model, but not others. Similarly, it is possible for confidence in a model to
be judged acceptable for a given use, but not for others. The concept of validation of highly complex
mechanistic models, outside of the context of a specific use of the model, has little meaning.
There is considerable uncertainty associated with using the available models for predicting blood
lead levels associated with environmental exposures, and this uncertainty is even larger when
trying to predict blood lead levels at the very low blood lead levels encountered in the U.S.
today. The models are better at estimating the relative change in blood lead levels associated
with a relative difference in exposures. The risk assessors who will be conducting the lead risk
assessor should consider this factor and consider providing a relative risk assessment rather than
an absolute risk assessment. An absolute risk assessment will be fraught with uncertainty. If a
risk assessment contains too much uncertainty, paralysis will rule the day when it comes to
making a decision about how to change the NAAQS for lead.
Response to Charge Questions:
4a) Yes, Chapter 4 provides sufficient information on the routes of Pb exposure and
toxicokinetics.
4b) Yes, the current discussion of the various lead biomarkers is adequate for assessing their
usefulness for assessing human health effects of Pb exposure.
4c) Yes, the strengths and weaknesses of the currently available models are adequately
discussed. A discussion of model uncertainty, as discussed above, should be added for the
biokinetic models and the slope factor models.
D-22
-------
Dr. Bruce Lanphear
Comments on "Routes of Human Exposure to Lead and Observed Environmental
Concentrations" (Chapter 3)
General Comments:
The Chapter on "Routes of Human Exposure to Lead" has been improved considerably since the
first draft, but there are several modifications that would further enhance the Chapter.
The Chapter needs considerable re-organization. As written, it reads like a litany of exposures
without any framework to help the reader understand the relative contribution of various sources
of lead or their pathways of exposure. In some cases, the authors' conclusions about the relative
contribution of various sources of lead was not justified.
As requested in the first review, an introduction that describes the outline of the Chapter would
be useful. As written, the chapter meanders through various sources of exposure without a
logical format or outline. The existing introduction should be revised. The revised introduction
should include a perspective on the primary sources of lead (leaded gasoline, other airborne
emissions, lead-based paint, and plumbing) and a description of the various pathways. This
introduction should serve as a framework for the Chapter.
If the authors are unclear about what I mean by this statement, they should review the
introduction in Chapter 6, which was beautifully written.
Charge Question 1. Does the revised chapter adequately discuss available information on
routes of lead exposure via air, drinking water, soil, dust, and food?
The coverage of the contribution from airborne lead has been considerably enhanced, but it
would be helpful if the authors provided a description and context for the relative contribution
and pathways of various sources of lead exposure. The revised chapter should include a
perspective on the primary sources of lead (leaded gasoline, other airborne emissions, lead-based
paint, and plumbing) and a description of the various pathways. This should be located before
the description of the specific sources and pathways (e.g., page 3-2, line 1), and provide a
context for the chapter.
Charge Question 2: Are there any further revisions needed to address issues regarding
lead exposure in dust and soil that were earlier identified by the panel?
Page 3-15, line 28-31: As I indicated in the last review, the authors either need to provide greater
justification to conclude "The dominant source of lead to soil is atmospheric deposition" or modify
this statement to indicate that "The dominant sources of lead to soil are atmospheric deposition and
lead-based paints".
D-23
-------
Page 3-16, lines 29-31; Page 3-17, lines 1-13: The authors should not provide equal weight to studies
without careful consideration of the quality of the research. For example, the authors cite Mielke to
argue that lead-based paint is not an important source of lead-contaminated soil. Mielke's study is
based on small sample size and did not measure the lead-content of house paint; instead, the authors
used the age of house as a proxy for lead-based paint. In contrast, Jacobs et al. conducted a nationally
representative sample of over 800 housing units and quantified the lead content of paint. The authors
should therefore provide greater weight to the Jacobs study because it had a larger sample size, was
representative of US housing, and it measured lead concentration in house paint. This perspective
would change the conclusion (cited above) to read: "The dominant sources of lead to soil are
atmospheric deposition and lead-based paints".
Page 3-24, line 19: The authors need to change the title to incorporate "dust lead loading". It is
disconcerting to read about dust lead loading when it is described as dust lead concentration (see, for
example, page 3-27, lines 7 and 30). It is also disconcerting that the authors provide limited
interpretation of why they focus on concentration when there is evidence that dust lead loading is a
better predictor and the basis of the US EPA residential lead standard.
Page 3-45, lines 13-31, Page 3-46, lines 1-9: I still find it odd that lead-based paint is mentioned
as an afterthought when it is arguably the major source of lead exposure for contemporary
children, especially those whose blood lead concentrations exceed 10 |j,g/dL. This should be
described as an important source of lead exposure.
Page 3-48: The authors briefly reviewed the types of laboratory analyses used for lead, but there
was still no mention of soil sampling or dust sampling in the section on measurement methods as
requested in the last review. It is well recognized that dust lead loading varies considerably by
the surface sampled and the sampling methods used (Lanphear, 1995). Dust lead loading
collected from troughs is oftentimes 1000-fold greater than floors samples. The levels of lead in
house dust collected from the midpoint of a room tends to be lower than those found under a
window or in the perimeter of a room (Sayre, 1974). Finally, soil lead concentration can vary by
location (perimeter of foundation versus yard samples), by the sieve size used, and the depth of
collection.
Lanphear BP, Emond M, Jacobs DE, Weitzman M, Winter NL, Tanner M, Yakir B, Eberly S. A
side-by-side comparison of dust collection methods for sampling lead-contaminated house-dust.
Environmental Research 1995;68:114-123.
Sayre JW, Katzel MD. Household surface lead dust: its accumulation in vacant homes. Environ
Health Perspect. 1979;29:179-82.
Page 3-38: It is important to describe factors that modify lead absorption, such as iron status and
fasting. In the experimental setting, for example, fasting has been shown to modify lead
absorption in adults. There was a 10-fold increase in lead absorption among fasting volunteers
who ingested lead compared with those who had recently eaten (Rabinowitz 1980; Maddaloni
1998).
D-24
-------
Maddaloni M, Lolacono N, Manton W, Blum C, Drexler J, Graziano J. Bioavailability of soilborne lead
in adults, by stable isotope dilution. Environ Health Perspect 1998;106:Suppl:1589-1594.
Rabinowitz MB, Kopple JD, Wetherill GW. Effect of food intake and fasting on gastrointestinal lead
absorption in humans. Am JClinNutr 1980;33:1784-1788.
Comments on "Epidemiologic Studies of Human Health Effects associated with Lead
Exposure" (Chapter 6)
General Comments:
Overall, Chapter 6 is well organized and clearly written. It is an outstanding review of the
literature. In the future, I will use it as a desk reference and suggest it as a comprehensive review
of lead epidemiology. I only had a few comments or questions of clarification.
Page 6-61, lines 7-8: This sentences could be rewritten to indicate "Other blood lead indices,
including concurrent or lifetime average, appear to be stronger predictors of lead-associated IQ
effects than peak blood lead concentration." because it introduces the paragraph more accurately.
Table 6-2.2: It wasn't clear why some, but not other studies were selected from this table to be
included in Table 7-3, Chapter 7. The presentation of these two tables should either be
consistent or reasons for the differences more obvious.
Page 6-69, lines 12-14: My conclusion of the review was somewhat different. The authors
should consider modifying their statement to read something like: "Therefore recent evidence
indicates that there are adverse effects of lead on neurocognitive deficits at blood lead levels of 5
Hg/dL. These data also suggest that there are adverse effects below 5 ng/dL, but the evidence is
less definitive."
Comments on "Integrative Synthesis: Lead Exposure and Health Effects" (Chapter 7)
General Comments:
Overall, Chapter 7 is concise and well written. I only had a few comments or questions of
clarification.
Page 7-17, lines 8-10: I was not familiar with the meta-analysis that concluded "the most
common pathway ... was exterior soil, operating through its effect on interior dust lead and hand
lead". It would be helpful if this and all other factual statements were referenced.
D-25
-------
Page 7-34, lines 10-12: This sentence is confusing and potentially misleading. What
epidemiologic studies? I am only aware of one particular study. The newer studies from Mexico
studies are of questionable relevance because they have only published results for children
through 24 months of age. What are the other studies? These studies should be referenced.
Page 7-76, lines 10-17 (and Table 7-3): The assumptions made in this paragraph and table
underestimate the effects of lead exposure on children's intellectual abilities.
It is not clear how the "average" was calculated, but it is clearly an underestimate of the lead-
associated IQ effects for children who have blood lead levels <10 |j,g/dL. Using the "10th to the
90th percentile" will underestimate the size of the effects because the IQ decrements are steepest
at the lowest levels of blood lead. Using Cincinnati and Port Pirie - which had few (Cincinnati)
or no children (Port Pirie) with maximum blood lead levels below 10 |j,g/dL - will lead to an
underestimate of the effects <10 |j,g/dL. (In fact, I am not even sure how they were able to be
calculated.) It is critical that the assumptions EPA makes about the IQ-associated lead effects
are clear and easily understandable because these studies are central to the standard setting
process.
The Table and its contents should be modified. First, because the pooled analysis includes 7 of
the prospective cohorts (including the studies by Bellinger, Dietrich, Baghurst, Wasserman,
Ernhart, Rothenberg and Canfield) and provides estimates of the effects at blood lead levels
below 10 ng/dL, it should be made clear that these studies are in the pooled analysis for the
summary column to estimate the slope below 10 |j,g/dL. (They should not be listed separately or
they are being counted twice.) Second, using the Tellez-Rojo, et al study, and the Kordas et al.
study, both of which are of high-quality, is reasonable. If we used the pooled analysis, the
Tellez-Rojo, et al study, and the Kordas et al. study, the average is probably somewhere between
-0.5 and -1.0, not -0.4 IQ points per 1 |j,g/dL. (I also couldn't tell if the -0.4 was an "eyeball"
average or a more careful calculation. How was that value "calculated?)
Page 7-76, Table 7-3: It was also unclear whether the estimated slope in IQ decrements for
blood lead levels < 10 |j,g/dL (last column) were based on the 5th to 95th percentile, the 10th to the
90th percentile, or the total sample. It was also not clear whether these were based on linear or
non-linear analyses. If we use the non-linear analyses, which is reasonable, it would also tend to
underestimate the adverse consequences of childhood lead exposure on intellectual abilities.
The consequence of all of these assumptions will tend to underestimate the lead effects for
children with maximal blood lead levels < 10 |j,g/dL. It is worth repeating that it is critical that
all of the assumptions EPA makes about the IQ-associated lead effects are obvious because these
studies are central to the standard setting process.
The article by Silva et al. (1988) was not described in Chapter 6 or Chapter 7. This is an
important omission because it is described in Table 7-3 as an important study used to generate an
"average" IQ effect at blood lead levels <10 |j,g/dL. Given the vintage of this study (1980s), it
would be a surprise to me that they examined effects <10 ng/dL. (But I may be wrong.)
D-26
-------
Dr. Samuel Luoma
Review comments from Sam Luoma:
Sam Luoma Review comments on 2nd draft of lead air quality criteria document.
Charge Questions - Chapter 8:
(a) Has NCEA staff adequately resolved previous inconsistencies across the sections that
comprise Chapter 8 and its Annex? Have the redundancies been reduced to an acceptable level?
Most inconsistencies seem to be improved, although all are not eliminated (see comments on
BLM below). If different sections were written by different authors, it might be worthwhile to
for authors to read sections they did not write. The redundancies are still significant in the soils
section, as are some contractions (e.g. extractions). The aquatic section seems much improved. I
believe the sediment quality criteria section is an example of an improved section.
(b) Are limitations with use of the biotic ligand model adequately addressed?
The BLM is mentioned in many places in this report. Some limitations are mentioned, in the
aquatic section; but in a rather cursory manner, again with the implication that this new tool is
somehow the final answer to implementing consideration of bioavailability. The most
extensive aquatic section ends with statements that suggest there are not going to be serious
impediments to implementing the BLM as a regulatory tool for lead. The executive summary
ends with a statement about the important issue of dietary exposure, but states nothing about
other contradictions and limitations. For that reason it is worth a few sentences to clarify what
the report does not adequately address in this regard:
1. It is not adequately emphasized that the BLM is based upon acute toxicity tests, with a
few minor (one paper?) exceptions. That one paper on correlations with chronic toxicity
(which is not about Pb) concludes that there are important difficulties in using the present
BLM approach with chronic toxicity tests. The implication of using the BLM site-
specifically is that EPA is satisfied with reverting to acute toxicity (48 - 96 h) as the
standard by which ecosystems are protected. This is not acceptable, of course; with no
correction factors. It is also unclear that there are adequate "chronic" tests with Pb that
can be correlated with the BLM (how robust are the data sets?).
2. Exposure to lead via routes other than dissolved metal is treated unevenly in the report.
The BLM section minimizes the importance of this factor, citing papers from 1977 and
1978 as the authority that lead exposure to fish is via solution. The executive summary
section emphasizes the importance of dietary exposure, building from citation, primarily,
of a 2005 report in the aquatic exposure section. The agency must explicitly consider that
dietary exposure and dietary toxicity are not known for Pb, but what evidence is available
suggests it cannot be ignored in at least some circumstances (e.g. chronic toxicity). The
BLM could under-estimate Pb effects in those circumstances (under protect). Again, the
agency must answer the question, if it implements a BLM-based regulatory approach is it
resorting to uncorrected acute toxicity via a single route of exposure to protect aquatic
ecosystems.
D-27
-------
3. The uncertainties about metal reactions with dissolved organic matter require correction
factors in the modeling, no matter what metal is used. If it is assumed that all organic
matter is equivalent to fulvic acids, for example (a common assumption), the model
consistently is under-protective. Most studies therefore adjust the model to the specific
toxicity test species to get the correlation. Pb is very reactive with organic matter, so this
will be extremely important.
4. (more minor) The report presents statements about critical loads without conclusions
about future consideration of this approach. If the issues with the BLM can be improved,
isn't the critical load concept a way to link inputs/outputs and bioavailability?
In summary, the BLM is a nice way to link speciation models and toxicity tests; in particular
taking into account competition with major ions and pH. Strong correlations are shown with
toxicity tests when individual data sets are considered, then adjusted for factors like organic
complexation. But isn't the BLM only as useful as a regulatory tool as the toxicity tests and the
models it is built upon? Don't they all have important limitations? Acute toxicity tests need
correction factors to apply to nature. How to adjust it to chronic toxicity has not yet been
resolved, satisfactorily for any metal. Models need site specific adjustments typically.
Transparency in discussing this new tool could be critical to its future credibility. The BLM is a
new way to consider bioavailability, but don't the caveats stated above need to be carefully
considered before applying it?
(c) Are there any further improvements that need to be made in Chapter 8?
A few are mentioned below.
1. pg. 8-4. The definition of bioaccessibility is unclear; and it is unclear how this is
different from bioavailability. Why did the authors bother to include this term? The
NRC committee on Bioavailability of Contaminants from Soils and Sediments found 90
different definitions of bioavailability in the literature, some of which attempted to
include bioaccessibility. The only solution to this is be explicit in what processes this
specific document is going to include in the definition of bioavailability and state them
here. This is attempted in the next paragraph, somewhat implicitly, but then this
document reverses itself and states the NRC definition (which is more inclusive). Start
with EPA's definition in italics, and adhere to that in this discussion. There is no value to
adding a redundant term.
2. Both in the executive summary and the report, it might be worth mentioning how robust
the data is for chronic lead toxicity. The report states that full life cycle tests are required
for chronic toxicity, but it is unclear how much of such data there is. Lack of adequately
robust data sets is often the reason that AWQCr resort to Acute-to-chronic ratios; making
this an important consideration.
3. Page 8-27 and 8-16 are somewhat contradictory and redundant with regard to "indirect
methods" and extractions. Both sections consider the operational semi-selectivity of
extractions. On page 8-16 it is stated that no extractable fraction has been correlated
with Pb bioavailability. This issue is not mentioned in the pages surrounding 8-27, for
example. As an aside, it is interesting that Tessier is credited with developing the
sequential extraction techniques. Indeed this is true for aquatic sediments. But those
D-28
-------
techniques were taken from decades of work by soil scientists, as Tessier himself would
mention I am sure.
In general fate of atmospheric lead in soils is a more comprehensive and scholarly section
than the section on soils alone. They are quite redundant however. The inputs/outputs
section is particularly interesting. But it could benefit from consideration of the "critical
load" concept as currently being developed by Ed Tipping in Britain and colleagues
elsewhere in Europe (as mentioned later). Modeling trends in the long term as the soil
equilibrates with atmospheric inputs/outputs could be extremely interesting and relevant
for an atmospheric lead standard.
D-29
-------
Dr. Frederick J. Miller
Chapter 4. Lead Toxicokinetics and measurement/modeling of human exposure impacts on
internal tissue distribution of lead
General Comments
The size of the 2nd draft of this chapter has approximately tripled compared to the 1st draft,
mostly in accord with a response to the CASAC Panel's comments and criticisms. While much
of the new material is informative, the Chapter still lacks a 'bottom line" position on a number of
fronts. For example,
• Which models are considered the most appropriate to use in predicting blood lead levels
in children? In adults?
• Which is the best method to use for measuring bone lead?
• How would EPA use the slope factor models compared to the biokinetic ones?
• There is no Summary section for the chapter where the most important and salient points
are reiterated relative to the task at hand.
• How does the chapter contribute to answering the question "Is the current NAAQS for Pb
protective of public health or are revisions in order?"
There is a need to be consistent in terminology in the various sections as the current wording
reflects the fact that multiple authors were involved. The new chapter title is a "mouthful' and
should be changed.
Treatment of uptake by the route of inhalation is still not adequate. For example, as noted in my
specific comments, the deposition fractions contained in Table 4-14 for children need updating.
Current particulate dosimetry models have predictions that are 2 to 3-fold different from those
cited in the table, and I have included a table and plot for a 3 year-old child that illustrate these
differences. EPA should be using the latest ICRP model or the MPPD model to obtain deposition
fractions for different sizes of Pb particles.
Specific Comments
p. 4-2,1. 18
Change "which" to "that"
p. 4-3,1. 16
While the authors are correct in that lead particles have only been studied
in adults, there are a number of studies for particulate deposition in
children that are useful because the aerodynamic properties of particles
not their speciation determine where they are deposited in the respiratory
tract. Examples of particulate deposition studies in children are:
Becquemin, M.H., Roy, M., Bouchikhi, A., and Teillac, A. (1987).
Deposition of inhaled particles in children. In: Deposition and clearance
of aerosols in the human respiratory tract (W. Hofmann, ed.), pp 22-27.
D-30
-------
Facultas, Vienna.
Becquemin, M.H., Yu, C.P., Roy, M., and Bouchikhi, A. (1990). Total
deposition of inhaled particles related to age: comparison with age-
dependent model calculations Third International Workshop on
Respiratory Tract Dosimetry, July 1-3, Albuquerque, New Mexico.
Becquemin, M.H., Swift, D.L., Bouchikhi, A., Roy, M., and Teillac, A.
(1991a). Particle deposition and resistance in the noses of adults and
children. Eur. Respir. J. 4:694-702.
Becquemin, M.H., Yu, C.P., Roy, M., and Bouchikhi, A. (1991b). Total
deposition of inhaled particles related to age: comparison with age-
dependent model calculations Radiation Protection Dosimetry 38:23-28.
Bennett, WD, and Zeman KL (2004). Deposition of fine particles in
children spontaneously breathing at rest Inhalation Toxicology 10:831-
842.
Bennett WD, Zeman KL. Deposition of fine particles in children
spontaneously breathing at rest. Inhal Toxicol 1998; 10(9):831-842.
Bennett WD, Zeman, KL, Jarabek AM. Nasal contribution to breathing
with exercise: effect of race and gender. J ApplPhysiol 2003;95:497-
503.
Bennett WD, Zeman KL, Kang CW, Schechter MS. Extrathoracic
deposition of inhaled, coarse particles (4.5 mm) in children versus adults.
Ann OccupHyg 1997;41(suppl. 1):497-502.
Schiller-Scotland, Ch.F., Hlawa, R., and Gebhart, J. (1994).
Experimental data for total deposition in the respiratory tract of children
Toxicology Letters 72:137-144.
Schiller-Scotland, Ch.F., Hlawa, R., Gebhart, J., Wonne, R., and Heyder,
J. (1992). Total deposition of aerosol particles in the respiratory tract of
children during spontaneous and controlled mouth breathing J. aerosol
Sci. 23(Supplement 1):S457-S460.
Section 4.2.2
This section rambles on quoting blood levels all over the world for
different populations. The information is of little value in its current
form. It would be better to cut drastically this material and include some
of the representative numbers in a table. Alternatively, I could see a
series of bullets stating facts about lead distributions and ratios with a
few citations provided to support the statements being made.
p. 4-16,1. 19
Since a2|i is a protein unique to the rat, the metabolism discussion here is
not particularly useful. The authors should so note these findings.
D-31
-------
p. 4-24, 1. 7
p. 4-42, 1. 18
p. 4-48, 1. 4
p. 4-57, 1. 27
p. 4-65, 1. 5
p. 4-66, 1.31
p. 4-68, 1. 18
Table 4-5
p. 4-13, 1.30
p. 4-69, 1. 13
Table 4-7
Table 4- 10
p. 4-85, 1. 5
Fig. 4-22
Table 4- 14
p. 4-96
p. 4-111,1. 6
Data that produce half life estimates from 3 to 30 years do not give one
much confidence in their usefulness.
Change "which" to "that"
The speculation from the Gulson et al study about mobilization of Pb
from the mother's skeleton could not be answered if Pb levels in breast
milk were not determined to establish that the children were receiving
comparable amounts of lead via the milk and thus differences might be
due to maternal skeletal transfer during pregnancy This is particularly
true given that later on 7 to 39% is quoted as the range of maternal
burden transfer of Pb from her skeleton to the fetus..
The authors should define what IC1 stands for in Eq. (4-2).
"outside of should be "outside the"
Insert "are" before "appropriate"
While an R2 of 0.23 is significantly different from zero, I do not consider
this an acceptable R2 to have confidence in the model's use for prediction
Explain P>F in this table or use a better expression for what is being
conveyed
A reference should be provided for the reasonableness of the assumption
that blood lead concentration at birth is 0.85 of the maternal blood lead.
Should "and" be "a"?
The lead sources can not contribute more than 100% yet the table shows
104%
Does footnote b apply to all exterior lead column values or only to the 72
ppm number? If to all, place the footnote after "(ppm)".
Are these t s for the slow compartments expressed correctly?
Why isn't there an arrow going from the respiratory tract to the G.I. tract
in each of the first two panels?
This table of deposition fractions is out of date. Some entries differ by 2
to 3 -fold from what current parti culate dosimetry models such as the
MPPD model predicts. For example, see the table and figure at the end of
my specific comments that give deposition fractions for a 3 yr old child.
Save a leaf- delete Eq. (4-9) as it adds nothing over what Eq. (4-8)
shows.
"other" should be "mother"
D-32
-------
Particle Size
(um)
0.5
1
2
2.5
3
5
7.5
10
12.5
15
20
Regional Deposition Fraction for a 3 Yr-Old Child
Head
0.208
0.243
0.264
0.27
0.243
0.332
0.443
0.562
0.647
0.686
0.649
TB
0.047
0.047
0.064
0.077
0.047
0.178
0.317
0.324
0.245
0.167
0.074
P
0.164
0.167
0.269
0.312
0.167
0.313
0.133
0.027
0.0027
1.5E-4
7.0 E-7
Total
0.419
0.457
0.597
0.659
0.457
0.824
0.894
0.912
0.895
0.853
0.723
D-33
-------
Dr. Paul Mushak
PRE-MEETING COMMENTS: INTEGRATIVE SYNTHESIS
CHAPTER 7 OF THE LEAD AQCDCHAPTER 7 OF THE LEAD AQCD
Panel Reviewer: Paul Mushak, Ph.D.
I have both general and specific comments.
GENERAL COMMENTS
Overall, this Chapter does a reasonably good job of capturing the key points of each of the
main chapters. This is particularly welcome, given the short turn-around time. The thoroughness
and crispness across chapters, however, is somewhat uneven. This may reflect collective writings by
different section authors for the Chapter. In some cases, there is no mention of parts of the sections
of the main chapters.
In other cases, there appears to be no standardized way the main chapters are summarized
and integrated. Some Chapter 7 sections discuss human data, followed by those parts of the animal
data that support or extend the conclusions about the human studies. That, I believe, is the desirable
format and it is the format used in earlier documents and documents of other Agencies, e.g., the
Environmental Health Criteria reports of the World Health Organization. It is more confusing and
distracting to scramble human and animal data together with variable logic behind the choice of the
animal data. That occurred in some sections.
NCEA apparently is sticking to the format of the first draft of the AQCD-Pb, using Chapter
7 as the wrap chapter for human studies and associated data. This is followed by a stand-alone
Chapter 8. It makes no more sense to keep to this now than it was to propose it the first time. The
cover note for the changes in the second draft provides no explanation why the original sequencing
was retained.
Chapter 7 lacks some multi-exposure source and multi-effect summarizing Tables that
would capture the sense of the synthesis. These should be added. Currently, Ch. 7 tabulates the
neurocognitive results and provides some figures for dose-response relationships which are quite
useful. One Table should be on the key lead contamination and lead exposure issues facing health
science and the reviewers at OAQPS preparing the Staff Paper for the Administrator. The second
Table should capture the key dose-response relationships. These could follow the format of earlier
Pb criteria documents.
The section on societal and other consequences of pervasive and historical/ongoing lead
exposure (Section 7.5) and its toxic effects should be expanded. A table could be added noting the
distribution of Pb-Bs currently in the U.S. population and the associated low-level lead effects that
are reported in the AQCD for Pb-B thresholds or range of thresholds.
D-34
-------
Much of the developmental neurotoxicity section in Chapter 6 and supporting experimental
data in Chapter 5 deals with cognitive psychometrics. That reflects the focus of attention by the
field for decades. But an equally or even more consistent adverse finding is attention deficits.
The consequence of this effect for the personal economic security of large numbers of
disadvantaged segments of the population, and also for the national economy, would be
significant. That specifically applies to those low-income workers employed in highly repetitive
work tasks that require high, not impaired, attention to detail.
SPECIFIC COMMENTS
Section 7.2
Section 7.2 should be broken into Sections 7.2 and 7.3, representing the Emissions, Fate,
Transport and the media lead levels sections respectively. The present mixing is confusing to follow
and discordant in parts. As one example, ambient air Pb levels appear before the transport and
dispersal sections that provide the basis for the air levels and why they are what they are. Also, other
media with lead are separated from air lead levels. Compare 7.2.2 with 7.2.4.
The Intro to Section 7.2 mentions organometallic lead as a major form. This is technically
misleading, to the extent that implying presence in ambient air of a lead form also assumes chemical
stability to that form. Organometallic lead, particularly the lower aliphatic forms, has a very short
photochemical half-life and is therefore quite unstable. Conversion to other forms occurs rapidly.
This paragraph should be tightened and clarified.
The statement "there are more than 200 known organolead compounds" is a statement that
conveys little of environmental relevance. There are not 200 forms typically emitted, whatever their
ambient stability. There may be 200 forms listed in a chemical handbook or some specialty
chemical manufacturer's catalog. This can be dropped.
Chapter 7 in current section 7.2 (and also the Executive Summary) should include the well-
known environmental cycling figure that has appeared in all other EPA lead documents and other
treatises using the figure. This Figure will be very helpful to the general reader and/or policy maker.
This suggested Figure would show soil lead is (/') a receiving medium for lead, (/'/') a contact
medium for such exposure populations as young children, and (//'/') a generating medium for exterior
and interior dusts. The current Section 7.2 needs to show and describe the close linkage between
soils and dusts. At present, dust is treated in isolation.
Is there any particular reason why there is little or no mention in Sections 7.23 and 7.2.4 of
direct exterior and interior deposition onto surfaces of leaded particles as dusts in and around
residences due to stack emissions of operating facilities nearby? These deposition levels and
loadings can be much larger compared to fugitive dust re-entrainment rates. For historic
perspective, the authors should review the huge literature on the matter for the Bunker Hill
Superfund site. For ongoing contamination, the authors should also check the available data
gathered by EPA Region 7 and the MO Department of Natural Resources for the currently operating
Herculaneum, MO facility.
D-35
-------
Section 7.2.4 needs to differentiate between idiosyncratic sources and significant sources,
depending on the exposure scenario. Merely enumerating potential sources does not make them
scenario-specific significant sources. The first paragraph leaves the reader with the impression that
hair dyes or Ca supplements can be as important as lead paint. This surely was not the intent of the
authors. Please revise.
In the last par., p. 7-8, the authors should attempt to break out food lead intakes from the
food and beverages fraction (30-50% of 50 ug/day), 15 to 25 ug/day. This is useful with regard to
the use of dietary lead intakes in the IEUBK and various other biokinetic models described in Ch. 4
of the draft.
Section 7.3 Biokinetics, Measurement, and Modeling of Pb Exposures
In Section 7.3.1, add the role of lactation in maintaining bone lead releases. These releases
have been studied and discussed in the various papers of Gulson et al. Dr. Gulson is a contributor to
the writing in the AQCD, so that should tend to that.
There are some typos or garbling of the ALA-D lead binding capacities and rates in whole
blood. Pb at 850 ug/dL erythrocytes computes to 340 ug/dL whole blood.
The last par. of p. 7-12, Sec. 7.3 should be updated to indicate that earlier literature
suggestions about biokinetic and biochemical distinctions existing between endogenous (bone lead
resorption) and exogenous lead in terms of potential internal dosimetry do not appear to be so.
Chettle and coworkers retracted some earlier comments while Gulson et al. have excretion data for
lead stable isotopes studied by TI-MS that do not indicate differences.
The authors need to clarify and differentiate in Sec. 7.3.2, p. 7-13, top, that it is spontaneous
lead excretion into urine that has (but not always) been found to be problematic. Plumburesis in
response to Succimer or other approved chelant challenge has been shown to be reliable in both
pediatric clinical and occupational settings for ascertaining a history of excessive lead exposure.
The discussion of 7.3.3, the NHANES data sets, is generally OK, but some further
discussions of the linkage of national socioeconomic and demographic strata with the Pb-B
snapshots should be included. The reason for this is to assist the OAQPS staff in integrating
NHANES data and to point out to OAQPS the uses and limits of NHANES data. There is only the
briefest discussion of these. We know that Pb-Bs are declining differentially as a function of
income, race, and such demographic indicators as housing age.
This section should point out that, given the statistical nature of the NHANES surveys, it is
not statistically permissible to disaggregate national mean Pb-Bs or strata-classified national mean
Pb-Bs into what one should or should not see in specific regions or communities. This is a common
mistake among the somewhat statistically challenged. The OAQPS Plan text makes the erroneous
assumption that local use of national figures can be made or applied in the various scenarios.
D-36
-------
The 1988 ATSDR Report to Congress on U.S. childhood lead poisoning points out this
statistical no-no. The caveats therein were inserted at the insistence of contributing staff comments
from the National Center for Health Statistics. The Executive Summary of the ATSDR report notes
on p. 4:
"Valid estimates of the total number of lead-exposed children according to SMS As or some
other...geographic unit smaller than the Nation...cannot be made...The NHANES II statistical
sampling plan...does not permit valid estimates to be made for geographic subsets of the total data
base."
Page 7-17, 1st full par., has misleading information about uses of structural equation
modeling (STEM) that should be corrected. The 1998 Succop et al. STEM studies in EHP covered
both urban (heavy on lead paint impact) and extractive industry sites. The Succop et al., 1998 report
provides the detailed structural equation coefficient tables for soil lead and paint lead vis-D-vis
relative contributions to dust lead and eventually hand lead. In Table 3 of Succop et al., 1998,
interior and exterior paint was less a significant contributor to children's Pb-B than soil lead at
Western extractive industry sites. Secondly, dust lead was more significantly linked to soil lead than
it was to lead paint at these Western sites.
Succop P, Bornschein R, Brown K, Tseng C-Y. 1998. An empirical comparison of lead
exposure pathway models. Environ Health Perspect 106 (Suppl 6): 1577- 1583.
The Malcoe, Lynch et al. studies using inferential statistical analysis for Pb-B versus
environmental lead data sets, a study done in the Picher, OK, mining communities (part of the Tri-
State mining district), clearly showed lead paint in such settings to be a less robust link to interior
dusts than soil lead and soil lead-related dusts.
Lynch PA, Malcoe LH, Skaggs VJ, Kegler MC. 2000. The relationship between residential
lead exposures and elevated blood lead levels in a rural mining community. J. Environ.
Health 63:9-15.
Malcoe LH, Lynch RA, Kegler MC, Skaggs VJ. 2002. Lead sources, behaviors, and
socioeconomic factors in relation to blood lead of Native American and White children: A
community-based assessment of a former mining area. Environ. Health Perspect. 110: 221-
231.
Section 7.4
This is generally a good summary. However, I would make the language about associations
between lead and toxic effects stronger, since such is justified by the wealth of new data. The last
par., 7-19, can add a bit more cement than just "pointing to."
The section on neurotoxicity, 7.4.2, does a good job of integrating animal and human data. It
might be a good idea, as noted in general comments, to have the 7.4 subsections headed as human
or animal data. Mixing the two in a running discussion is OK, but only so long as the comparative
information can flow smoothly and with the most relevant animal data interwoven into human data.
D-37
-------
The subsection 7.4.2.1 is particularly good.
Regarding Sec. 7.4.2.8, is there some reason why the multi-center TLC study, on Succimer
use and the issue of reversibility of deficits summarized in Rogan et al., 2001 in the NEJM, is not
mentioned? The gist of the TLC study, whatever the discussions about study design, is that medical
interventions in the form of chelation therapy do not seem to reverse cognitive deficits associated
with early lead exposures. The Rogan et al. paper is in the list of cited papers for Ch. 7.
Section 7.4.5, immunotoxic effects of lead, has a good summary of the field, although the
mixing of the animal and human data in the text makes the material hard to follow.
Section 7.4.6, hematotoxic effects, is one of the sections that would benefit from separation
of the text into human and animal subsections.
The placement of hepatic and GI text is unusual. Given the (appropriate) emphasis in this
Chapter on effects at low doses, it's unclear why the hepatic and GI effects are placed before the
carcinogenesis and genotoxicity sections.
Discussion here on tumor promotion and proliferative activity would seem better placed in
the carcinogenesis section. The carcinogenic potential of lead salts is most clearly expressed in
kidney cells and that is appropriately held for Sec. 7.4.10, the cancer and genotoxicity section.
Sections 7.4.8 and 7.4.10, reproduction and development and carcinogenesis/genotoxicity,
mainly discuss animal results, even though there are data sets for human exposures that require
discussion and integration. Was this an oversight with the press of time?
Section 7.5
There is some confusion in this chapter about curvilinear dose-response relationships being
linked to U-shaped or inverse U-shaped dose-response, i.e., hermetic relationships. Curvilinear
dose-response curves, like those for rectilinear relationships, are both examples of monotonic dose-
response (MDR) relationships, while hormetic responses are nonmonotonic dose-response (NMDR)
relationships. Curvilinear relationships still are unidirectional, uniphasic or MDR as to direction and
nature; only the slopes change across the entire dose spectrum. NMDR (e.g., hormetic) responses
entail a reversal of directionality and are considered biphasic or bidirectional across the entire dose
spectrum tested or examined. This is quite apart from the notion of "beneficial" versus "harmful"
characteristics of hormesis, which is an entirely different topic. Numerous recent papers, advancing
the pros and the cons of the phenomenon, are available on the topic and three are cited below:
Calabrese EJ, Baldwin LA. 2002. Defining hormesis. Hum Exp Toxicol 21:91-97.
Crump K. 2001. Evaluating the evidence for hormesis: A statistical perspective. Crit Rev
Toxicol 31:669-679.
D-38
-------
Thayer KA, Melnick R, Burns K, Davis D, Huff J. 2005. Fundamental flaws of hormesis for
public health decisions. Environ Health Perspect 113:1271-1276.
Section 7.5.2 covers a critical topic for risk assessment and regulatory policy, the persistence
or irreversibility of effects. A reasonably good job is done with this, although some clarifying
discussion can be added. First, there is the matter of intrinsic versus de-facto definitions of
irreversibility.
Put differently, persistence of adverse effect can trace to either of two causes. First, organic
damage has occurred and no repair to the underlying cellular or organellar processes can occur. The
second is a persistence of effect because there is persistence of exposure. With persistence of
exposure, it is arguably irrelevant what the intrinsic ability is of the target tissues or organs to
recover. The text notes that endogenous, continuing exposure can occur. That does not vitiate or
prevent the existence of persistence; it merely provides a mechanism for it.
Another example is a biologically reversible effect of lead that is rarely expressed simply
because exogenous lead exposure rarely ceases. This is typified by lead's effects on the blood-
forming system of young children who remain in badly lead-contaminated housing in the inner
cities for virtually all of their childhoods. Hematotoxicity is intrinsically reversible, but continuing
lead exposure prevents that reversal.
Page 7-70, Sec. 7.5.3, should include the studies of Gulson et al. They have been the major
contributors to the topic and their studies are extensive. The studies show actual lead release, not
potential lead release. Furthermore, the extent of skeletal release during pregnancy and lactation is a
function of calcium dietary adequacy.
Section 7.5.4 is a very good treatment of the significance of low-level lead effects to public
health. Discussion includes the important factor of population-wide effects.
The authors need to reinforce the point that IQ decrements are apparently expressed
uniformly across the entire population. One can refer to the well-known population shift dose-
response curve by Needleman et al. in a 1982 issue of the NEJM already cited in the References list.
The authors should also have a look at, with a figure or two, dose-population response
frequency for a given level of some selected effect beyond the relationship shown in Figure 7-7. The
dilemma with dose-response frequency relationships for developmental neurotoxicity and other
effects is the need to deal with truncated data sets. Typically, children above a certain Pb-B level are
removed for medical ethical purposes from study and referred for medical management.
The dose-frequency response curve depicted in figure 7-7 is for quite serious indices of
cognitive deficit. Can the effect index be extended to other IQ cut points stepped upwards from 70?
D-39
-------
CASAC PEER REVIEW OF EPA'S SECOND (5/06) AQCD
EXTERNAL REVIEW DRAFT FOR LEAD: CHAPTER 4
Reviewer: Paul Mushak, Ph.D.
I have both general and specific comments on Chapter 4.
GENERAL COMMENTS
Overall, this chapter is much more comprehensive than the first draft. It is much
improved in its new editorial and technical incarnation and appears much improved in the
writing. It has been greatly expanded, growing about three-fold between drafts.
One clear remaining order of business is to replace the cumbersome and messy title. A
simpler substitute would be:
"4. LEAD EXPOSURE AND BODY BURDEN BIOMARKERS: MEASUREMENT,
MODELING AND TOXICOKINETIC CORRELATES"
Part of the growth in the size of the Chapter is its inheritance of material from elsewhere
in the AQCD draft. That is a good move in part but a problematic move in part. In the first draft,
one had to keep shifting between Chapters 4 and 6 and bits of other chapters to keep things and
thoughts aligned. The change in the title of the Chapter reflects its expanded purpose, including
the topic of toxicokinetics and expansion of the rest to now include both measurements and
modelings for lead exposure in its various aspects.
The current layout of the new Chapter reads reasonably well. One starts with the various
aspects of lead toxicokinetics and proceeds from there to one of the spinoffs of lead
toxicokinetics, biological markers of lead exposure. The one limitation I see in the first part is the
absence of some more recent data or critical discussions of the references cited. Some might
quibble whether Section 4.3 needs to have two subsections, a general treatment of lead in blood
plus a section on measurement issues. Section 4.4, Modeling, is still largely dealing with Pb-B
being the exposure biomarker, although the discussions of the various PB-PK models discuss
lead burdens in other tissues.
One major problem across sections is the appearance of repetition and the editorial need
to cross-check sections for consistency in terminology, numbers and discussions.
Some terminology can be tightened. The element lead and inorganic lead compounds are
not technically metabolized (Sec. 4.2.3), in the typical biochemical/pharmacological sense of, for
example, large molecules being oxidatively catabolized to small molecules or the process of
anabolic metabolism, where small molecules are combined to form large molecules. What's
really meant by lead "metabolism" here is lead "binding toxicokinetics." Perhaps 4.2.3 can be
labeled "Binding Toxicokinetics (Metabolism)" or some such.
D-40
-------
The various subsections of 4.2 do a reasonable job of identifying the various factors that
affect lead toxicokinetics, with animal data being used where appropriate. There are specific
issues, but those are noted later.
Serious Need to Harmonize Sections 4.2 and 4.4
A toxicokinetics section, 4.2, largely dealing with entry of lead into biomarker media via
discussions of uptake, distribution and excretion, is appropriate as a prelude to other sections, but
it needs to be consistent with the toxicokinetic inputs used in the Modeling section, 4.4. The
authors need to compare what's said quantitatively about toxicokinetic parameters in Sec. 4.2
with what's said in Sec. 4.4. One should not have biokinetic, i.e., toxicokinetic, parameters
expressed as one set of numbers in one Section and have different values used elsewhere for the
same purpose. Compare for example, the uses of GI absorption rate in the models for children
and adults versus what's said in Sec. 4.2. for lead uptake.
SPECIFIC COMMENTS
4.2 Toxicokinetics of Lead
Inhalation Uptake
There is surprisingly little in the literature for quantification of respiratory uptake of lead
in humans beyond the literature citations given in the 1986 AQCD. James et al. and the few
others cited in this section appear to be it as far as newer data. There are a number of reports in
the global literature of an epidemiological, not an experimental, nature that deal with alterations
in children's Pb-B levels with phase out or phase down of leaded gasoline or other alterations to
ambient air lead. In these studies, of course, Pb-B impacts are a function of both direct inhalation
and post-depositional exposures via soils and dusts and to some extent, airborne lead
contamination of food crops. Such studies are limited for calculating uptake rates.
The section on organic lead is short, as it should be. Uptake of the organic lead
compounds are principally a problem in occupational settings and principally via dermal
absorption, as the section notes for the dermal route.
Oral Uptake
There are also limited recent human data for exposure via ingestion. Much of the material
in the chapter reflects older material in the 1986 AQCD Ch. 10. The subdividing of the balance
of oral uptake into factors modifying oral uptake is generally O.K. However, portions have to be
revised for accuracy.
The Gulson et al. 1997 data are too limited for purposes of identifying the age band
dependence of GI uptake of lead. It is somewhat suggestive but not determinative. The authors
need to insert a paragraph or two about having to differentiate how much of the uptake
differences in young children versus older children and adults is due to physiology and cellular
D-41
-------
energetics and such factors as diet differences and feeding patterns. If one studies fasting adults,
one gets uptake rates rivaling those of children. My 1991 article (in your cite list) on uptakes of
lead in young organisms also pointed to such factors as the role of milk components in
facilitating uptake through micellar formation and pinocytosis.
Studies in young animals including pre-weanling rodents generally suggest higher
uptakes of lead. However, one caveat in interpretation of these data is that one cannot often
distinguish increased Pb-B from increased uptake from any increase in Pb-B from increased
retention. The usual experimental designs for these studies make it difficult to quantify the two
factors. Inverted sac intestinal uptake studies are compromised by the highly altered condition of
the experimental versus the unaltered systems.
The nonlinear effect of dose on GI uptake is likely a combination of processes. That this
curvilinearity is not a simple reflection of uptake saturation kinetics can be seen from data
reported over the years showing that dose/exposure relationships to organ lead levels are linear,
though Pb-B is non-linear. The first report of this was the two-year feeding study of Azar et al.
from Haskell Laboratories, reported in the early 1970s at the 1973 Amsterdam conference. Later
data cited in this section, such as Casteel et al., 2006 and citations therein, confirmed this. If we
were simply dealing with an attenuating uptake of lead across lead dose we would see curvilinear
organ kinetics for lead.
The subsection on particle size is a reasonable discussion but the studies are dated. This
reflects to some extent the data. Have the authors looked at the more recent aerometry literature
for any information on lead in emitted nanoparticles?
The subsection on lead uptake from ingested soil needs some reworking. The best animal
model surrogate of non-dietary lead uptake in the young child is the young pig. There are many
similarities physiologically, biochemically and behaviorally which justify this and the excellent
article by Weis and LaVelle, 1991 and Weis et al. writings in some later papers enumerate these
in detail.
The rat is an inferior model for lead toxicokinetics, certainly uptake kinetics. There are as
many reasons not to use the young rat as there are good reasons to use young pigs. Authors
should either qualify the discussions or contract the rat discussion.
The list of test materials as part of the legend to Figure 4.1 needs to be better linked to the
Figure or deleted. Also, the authors need to make clear that mineral phases appearing in
mineralogical wastes will greatly weather over time. Galena in milling wastes will undergo
oxidative weathering to more bioavailable forms with time. For example, galenic forms of lead
(the sulfide) are converted to cerussite (Pb carbonate) in tailing piles and in receiving soils. One
has to verify, via chemical speciation and micromineralogical (e.g., BMP A) spectroscopic
techniques, what's in the material.
D-42
-------
Dermal Uptake
This section is O.K. and differentiates among uptakes for inorganic, organic salt and true
organolead dermal uptakes. There appears to be a typo for the label "lead naphthalene." Should
be lead naphthenate, a lead salt of naphthenic acid. Organic lead salts are not higher in dermal
uptake than they might be expected to be from the label "organic salts" for simple chemical
reasons. The carboxylic acid group(s) binding lead rapidly exchange lead with dermal binding
sites.
4.2.2 Distribution
Generally O.K. The 2nd Par. has a typo, i.e., 850 |ig/dL is not equivalent to 40 jig /Dl.
Should be 340 jig/dL.
The use of autopsy data that is older than figures from the Bavarian studies of Drasch and
colleagues or those of Wittmers et al. is problematic for several reasons. Methods were relatively
crude in terms of avoidance of contamination and histories of autopsy subjects often are
unknown in terms of lead contact. Comparisons with more recent data need to keep these
confounders in mind.
The older literature, i.e., the data of Barry, made some erroneous interpretations of the
bone data as a function of age. Those misinterpretations were covered to some extent in the
toxicokinetics section of the 1986 AQCD. Those can be mentioned. For example, when one is
looking at age-stratified bone lead contents from infancy to the teens, one cannot ignore the
enormous relative skeletal system mass increase that co-occurs with lead exposure. That is, over
time, lead is being sequestered into an increasingly larger bone reservoir mass.
Section 4.3 Biomarkers of lead exposure and body lead burdens...
This section is a good one, although what is done here is the discussion of the
measurement of exposure biomarkers, not their modeling. Section 4.3 can be re-titled
"Measurement of Lead Biomarkers of Exposure and Body Lead Burden." The modeling section
still deals with biomarkers of exposure and burden. It does not deal with biomarkers of early
effect.
The IEUBK model simulates the biomarker Pb-B in children 84 months or younger. It
does this through a biokinetic component that is sealed to the user. The PB-PK models in their
biokinetic components presented in Sec. 4.4. reveal the internal lead depositions in target and
other tissues, i.e., internal dose/exposure to in-vivo lead.
The bone, blood and urinary Pb in terms of both their biomarker utility and their
toxicokinetic underpinnings were quite good. Here again, the authors should cross-reference for
consistency of text of the measurements of the biomarkers, Sec. 4.3, and their modeling, Sec.
4.4.
D-43
-------
This Section should be checked for repetition with other sections. The NHANES data sets
over the years (II, Hispanic HANES, Ill-Phases 1 & 2, IV) should mainly be discussed here as
they apply to exposure epidemiology, a main area of application for use of this biomarker.
Comments on NHANES results should be contracted in Sec. 4.2.2, p. 12.
The section can be tightened. Where should the analytical aspects of the biomarkers go?
It probably makes more sense to discuss the biology and toxicokinetics first, and then the
measurement methodologies. We need to know what to measure and when to measure before we
describe how to measure.
The Section begins with several comparative statements as to biomarker utility in the
dimension of time. This needs to be expanded and critically examined to capture the complexity
of the topic. There are much more data in more recent literature post-1986 AQCD dealing with
toxicokinetic/mathematical aspects of changes in external versus internal lead relationships. See
the discussion on some of this in one of my 1998 papers in EHP, which is in the References list
already.
The interplay of multiple body compartments for lead and how one kinetically scales
across these compartments differs with exposure history but also which time period is used to
measure what kinetic component. The extent to which one can tease out, say, half-times or mean
times of different length in exposed subjects differs with the testing design. The more test points,
the more one can differentiate half-lives vis-a-vis compartments. That's the same kind of
situation one finds for any timed typical dosing regimen.
The fast component typically comes into play with use of Pb-B in a diagnostic, case-
driven setting when (i) the exposure history is relatively recent, (ii) testing is relatively time-
concordant, and (Hi) the subjects are typically very young children whose bone lead kinetics and
dynamics have not jelled to produce net bone lead accumulation. The more remote in time the
Pb-B testing from the lead exposure history the more problematic measurement versus modeling
becomes.
Children without an extensive lead exposure history or a large body lead burden, will,
collectively speaking, present with shorter Pb-B half-lives than those with more extensive and
intensive exposure histories. Examples of the latter are seen in the findings for the Cincinnati
prospective study (e.g., Succop et al., 1987) and the data of Manton et al. 2000.
Adults relatively naive as to lead exposure also show very short Pb-B half-times. The
study of Omokhodian and Crockford, 1991, showed that in adult volunteers ingesting low lead
doses, lead was rapidly removed from blood and declined to pre-test levels in a matter of days.
Omokhodion S, Crockford GW. Sweat lead levels in persons with high blood lead levels:
Experimental elevation of blood lead by ingestion of lead chloride. Sci. Total Environ.
108:235-242(1991).
Even lead workers will show a pronounced decline in the fast (largely non-bone tissue
lead) component when their steady-state exposure is altered, i.e., reduced. Nilssen et al. (1991) a
D-44
-------
paper already in the reference list, reported on worker subjects who showed a half-life of the fast
component of about 20-30 days, with one subject having a half-life of 7 days, when occupational
lead exposure ended.
Section 4.3 correctly focuses on the main biological media that serve for measurement of
systemic exposures. However, something should be said about the role of plasma lead, in terms
of its role in lead toxicokinetics and its measurement. If hair lead is discussed, plasma lead
should certainly be at least given summary discussion.
The extremely small levels of lead in plasma, under steady-state lead exposures and body
lead burden maintenance, raises measurement questions and it is the measurement accuracy and
precision, as well as the very sizeable risks to these measurement criteria that limit its use. One
can easily calculate how even modest artifacts such as lead leakage from erythrocytes with even
indiscernible hemolysis would double or triple the true plasma level.
It is also true that absence of dose-response metrics for plasma lead in diagnostic and
epidemiological settings limits its use. But that would resolve if one got around the measurement
question. We have largely solved the measurement question for bone lead and in time routine use
of this measurement in clinical and epidemiological settings may occur. At present, it's still a
research tool.
The authors in the subsection on urine lead, 4.3.4.4., assert plasma lead tells us little
about body lead burden. That is superficially true for ongoing exposures where exogenous lead
dominates endogenous lead releases from the main burden reservoir, bone. It is also
superficially true where one has no serial measurement data with no good (Class 100, super-
clean) lab to do it in. Lead in bone is in equilibrium with lead in the blood compartment, which
means such releases occur through the plasma subcompartment. Under conditions where we see
other compartments changing, as in the section's Figure 4-10 for simulated Pb-U declines, one
would have a comparative Pb-plasma marker of decline in the body lead burden.
The discussions that differentiate measurements of exposure from measurements of body
lead burden should be expanded and made simple for the general or policy reader. Blood lead
versus bone lead and endogenous lead releases to produce exposures versus exogenous lead
intakes to produce exposures should all be clarified.
Bone lead is 90+ % of the body lead burden at any one time in adults, but it also
produces, in many instances of non-occupational lead exposure scenarios, lead exposures in the
form of endogenous releases. Hence, body lead burdens in bone are always simultaneously
virtual or latent exposure sources, whose exposure role grows with age and physiological
disturbances of various types. Even in younger subjects, there is arguably the impact of bone
lead on the slow kinetic compartments that go into estimations of children's Pb-B half-lives. The
long half-life of lead in the blood of quite young children of the order seen by Succop et al. and
Manton et al. is tapping a bone compartment.
The authors should also note that in workers retired from workplace lead exposures, body
lead burdens in bone are the principle determinant of the exposure biomarker lead in blood, and
D-45
-------
from that compartment, lead in diverse target tissues. We would expect this from the known
equilibria. Various studies in the older literature showed this clearly, including the Italian data of
Alessio et al.
Section 4.4, Modeling..
There have been a number of changes in the layout of the current modeling section from
what was previously the lead exposure modeling Chapter. A major change was the addition of
empirical model approaches, i.e., slope factor, ad-hoc, statistical models. The various data sets
that go into the use of structural equation modeling (STEM), those of the Cincinnati group and
studies done for the Coeur d'Alene contamination site in Idaho. Also, slope-factor models are
presented from Lanphear et al., 1998.
Another data set employing STEM that could be added is that analysis done by Alan
Marcus and others for the Superfund site in Madison County, IL (Granite City Site) that entailed
community exposures from a secondary lead smelter and battery-recycling operation. This was
done in 1995. The citation is in my EHP 1998 paper.
It's not clear to me how EPA will use the slope factor section, compared to the biokinetic
model sections. I offered comments on that in earlier submissions.
POST-MEETING COMMENTS: CASAC PANEL REVIEW OF THE SECOND PB
AQCD DRAFT AND CONSULTATION FOR THE OAQPS DRAFT ANALYSIS PLAN
Reviewer: Paul Mushak, Ph.D.
July 3, 2006
Overall Recommendations for Pb AQCD-2.
The second draft of the Pb AQCD, on balance, is of sufficiently good scientific quality
that it can go forward in the overall process for review of the NAAQS. Going forward assumes
attention to recommendations for changes in draft Chapter 7.
CASAC member Dr. Cowling recommended acceptance of the document but only so
long as the history of past efforts by EPA and others, post-1978, to evaluate and make
recommendations on air lead standards or guidelines be included. Similar sentiment was
expressed by others. I agree. I particularly agree with the need for inclusion of discussion of past
CASAC actions, post-1978, as part of the review record.
Members of the current CASAC Panel may or may not be aware that, in the 1989-90 time
frame, a former CASAC Panel presented a set of quite clear recommendations to Administrator
William K. Reilly regarding that Panel's review, conclusions and recommendations for the
EPA/OAQPS Staff Paper on NAAQS evaluation dated March, 1989.1 was a member of the
D-46
-------
CASAC Panel preparing the 1/90 report (and also a member of the two WHO-Europe panels
noted below who presented WHO-Europe air lead guidance values in 1987 and again in 2000).
The 1990 CASAC Report on the NAAQS
The most significant parts of EPA's former SAB/CAS AC Committee on NAAQS review
for Pb, in its January 3, 1990 transmittals to EPA Administrator Reilly, were specific conclusions
and recommendations deriving from its review of the OAQPS March, 1989 Staff Paper. I would
urge that the current CASAC Chair include, in any near-future transmittals to Administrator
Johnson, complete copies of both the January 3, 1990 transmittals and the March, 1989
OAQPS/EPA Staff Paper as part of the Administrative Record.
The subject 1/90 CASAC transmittal to Administrator Reilly included two paragraphs
among the conclusions and recommendations that captured the essence of the CASAC Panel's
efforts. I strongly recommend that these two paragraphs be quoted in the current AQCD and any
new OAQPS Staff Paper so as to provide important context. These two paragraphs are presented
verbatim below:
[1990 CASAC Report, p. 1, 2nd Par.] "In discussing blood lead levels used to assess
alternative standards, it is the consensus of CASAC that blood lead levels above 10 |ig/dl
clearly warrant avoidance, especially for development of adverse health effects in
sensitive populations. The value of 10 |ig/dl refers to the maximum blood-lead level
permissible for all members of these sensitive groups, and not mean or median values.
The Committee concluded that the Agency should seek to establish an air quality
standard which minimizes the number of children with blood lead levels above a target
value of 10 |ig/dl. In reaching this conclusion, the Committee recognizes there is no
discernible threshold for several lead effects and that biological effects can occur at lower
levels. In setting a target value for blood lead (matched ultimately to air lead level) the
Committee emphasized the importance of always being mindful that blood lead levels
and health outcome measures are best characterized as a distribution of values about
mean or median values. The importance of considering the distribution of values about
the mean or median is apparent from consideration of the influence of lead exposure on
I.Q. A seemingly modest decrease in the mean or median I.Q. may result in significant
changes at the outer limits of the distribution with both a reduction in the number of
bright children (I.Q. > 125) and an increase in the number of children with I.Q. < 80."
[1990 CASAC Report, p. 3,1st Par.] "The EPA Staff recommended in the Staff
Position Paper that the lead NAAQS be expressed as a monthly standard in the range of
0.5 to 1.5 |ig/m3 not to be exceeded more than once in three years. The Committee
concurs with the EPA Staff recommendation to express the lead NAAQS as a monthly
standard not to be exceeded more than once in three years. The Committee strongly
recommends that in selecting the level of the standard you take into account, the
significance and persistence of the effects associated with lead as well as those sensitive
population groups for which valid quantitative exposure/risk estimates could not be made
at this time. The Committee believes you should consider a revised standard with a wide
D-47
-------
margin of safety, because of the risk posed by lead exposures, particularly to the very
young whose developing nervous system may be compromised by even low level
exposures. At the upper level of the staff paper range (1.0-1.5 |ig/m3) there is relatively
little, if any, margin of safety. Therefore, the Committee recommends that in reaching a
decision on the level of the standard, greater consideration be given to air lead values
below 1.0 |ig/m3. To provide perspective in setting the NAAQS for lead it would be
appropriate to have the EPA Staff compute the distribution of blood-lead levels resulting
from a monthly standard of 0.25 |ig/m3 for comparison with the values already computed
for higher levels. In setting the NAAQS for lead it is important to recognize that airborne
lead serves not only as a source of inhalation exposures, but that lead in air deposits on
soil and plants becoming a potential source for intake into the body."
The WHO-Europe Air Lead Guidelines
The 1987 (first edition) WHO-Europe "Air Quality Guidelines for Europe" developed an
air lead guideline for Europe consisting of a level in the range of 0.5 to 1.0 |ig/m3. The process
for development of the 1987 air Pb guideline is contained in Chapter 23. The key elements in
that development included, but were not limited to, the fact that both adults and very young
children are affected; children are affected at lower exposures than adults; and air lead enters the
body directly through inhalation but also subsequently via ingestion of dusts and soils produced
from air lead fallout.
World Health Organization. 1987. Air Quality Guidelines for Europe. Lead. Ch. 23.
WHO Regional Bureau for Europe, Copenhagen, pp. 242-261.
The 2000 (second edition) WHO-Europe "Air Quality Guidelines for Europe" took an
even more quantitative approach, which permitted a single, low air lead guideline to be selected,
a guideline value at the lower end of the previous range given in 1987. Elements of the
recommendation in the Guidelines update for air lead included 1) derivation of a guideline value
based on a Pb-B level of 10 |ig/dl in young children; 2) lead ingestion as well as lead inhalation
are important for young children; 3) an air lead value of 1.0 |ig/m3 translates via direct and
indirect (dust/soil/diet) pathways to a Pb-B of at least 5 |ig/dl; 4) 98% of young children should
have a Pb-B that does not exceed 10 |ig/dl; 4) this translates to the median Pb-B not exceeding
5.4 ng/dl. All of this, plus factoring in the non-air inputs to children's Pb-B levels, works out to
the air lead not exceeding 0.5 |ig/m3 and this value was the recommended Guideline.
World Health Organization. 2000. Air Quality Guidelines for Europe. Second Edition.
Lead. Ch. 6.7. WHO Regional Bureau for Europe, Bilthoven, The Netherlands, pp. 149-
153.
If CAS AC wishes the relevant sections of these two WHO documents, they presumably
are in the EPA docket for the current process. Otherwise, I would be happy to provide them.
Overall Consultation Recommendations on the OAQPS Draft Action Plan
D-48
-------
I concur in the recommendations of others regarding elements of the draft OAQPS
Action Plan and add several more. Overall, the Action Plan process should go forward only
within a number of recommendations for prioritization or limitation:
• The Case Study approach appears acceptable in principle, but it will be the details in the
Pilot and Full phases that determine how many devils there are to deal with.
• Concurrence with the blueprint does not translate to acceptance of the results there from,
and results review by the Panel in the future will say what they say.
• The Risk evaluation should be focused on IQ and any other neurobehavioral deficits in
young children as a first priority of business for risk quantification, with further sensitive
population evaluations only proceeding when the first evaluation is finished.
• The most acceptable dose-response data set for assessment of IQ decrement distributions
are contained in the international pooled analysis by Lanphear et al., 2005.
• Lead exposure modeling will necessarily entail the IEUBK model, but use will need to be
in harmony with risk assessment use by EPA sister offices and EPA Regions.
• Comparisons can be made of biokinetic with statistical, slope-factor modeling approaches
as part of the dose-response calculus.
• The development and evaluation/validation of a probabilistic distribution exposure input
module for any biokinetic model at this time is simply not feasible and the use of
exposure inputs to the biokinetic module and its outputs as point estimates will be
necessary.
• I would urge that OAQPS include the full assessment of the impact of even modest air
lead concentrations on significant lead exposures, through dust lead loadings onto interior
and exterior hard surfaces, of very young children; such modest air lead levels are a
combination of both new emissions and reentrained, dust lead movement back to the
atmosphere.
• I recommend that OAQPS take special note of the above fact that air lead levels reflect
both new lead emissions and reentrained lead from already-contaminated surfaces; this
recognition will greatly assist in air lead NAAQS review in that any further direct
emissions from point sources will have to be kept to a minimum, and certainly below 1.5
|ig/m3 .
• Finally, I would especially urge OAQPS to keep in mind that the current low levels of
lead in air in many areas are absolutely no scientific or biomedical rationale for retention
of the current NAAQS of 1.5 air lead units for lead; at the 1.5 current standard, a
significant window of permissible pollution would occur should there be abrupt entry of
new industrial technologies having potentially significant waste streams that include
significant new air lead emissions; re-attainment of typical levels nationally at the 1.5
D-49
-------
current standard would be a major source of, and would actually produce, new exposures
and associated toxicity in sensitive populations. To illustrate, Table 4-3 in the OAQPS
3/89 Staff Paper showed that at 1.5 |ig/m3, the fraction of young children with Pb-B > 10
Hg/dl is two-to-three times higher than is the case for Pb-air at 0.5 |ig/m3.
Other Comments
Dr. Crapo correctly noted at the meeting that there is a sizeable accumulated lead burden
in various environmental compartments with which risk populations come in contact. There was
the implication that this accumulated burden would overwhelm new air lead emissions from
point sources. I would like to add further discussion by first noting that, yes, there is an
accumulated burden of lead that contributes to children's Pb-B levels, but no, this complication
does not trivialize the impact of new lead emission inputs to children's Pb-Bs nor does it render
the NAAQS lead regulation approach moot. Past, present and future inputs to air lead all need to
have equal billing.
Dr. Crapo cited lead levels normalized over huge expanses. The localized or "hot spot"
distributions of anthropogenic lead as a fraction of that overall amount is the metric that is
comparatively more at issue for human lead exposures. Areas of soil surfaces receiving
anthropogenic lead input in the form of fallout from point or past mobile emissions will exceed
areas of natural or background crustal origin by many-fold. Compare a natural crustal abundance
of lead at 20-50 ppm versus a 20- to 50-fold higher roadway or point source impact zone soil of
1,000 ppm. There are numerous publications on the topic.
In addition, those areas with the most anthropogenic lead inventories and those most
likely to receive more new lead emissions are also those with the most numbers of children,
either in terms of children near past mobile source emissions or child populations around lead
point sources. Of the U.S. total child population ages 6 months to 6 years of age, the great
majority live in and around areas with elevated soil lead levels from anthropogenic activity and
these figures are to be found in such sources as the Appendix and summary tables in the 1988
U.S. ATSDR report to Congress on childhood lead poisoning in America.
U.S. ATSDR. 1988. The Nature and Extent of Childhood Lead Poisoning in Children in
the United States. Atlanta, GA: Agency for Toxic Substances and Disease Registry, U.S.
Centers for Disease Control.
Equally important, natural or geochemical lead still encased in natural soil matrices, e.g.,
silicates, is quite different from deposited anthropogenic lead, the latter tending to be in smaller
and in more chemically and biochemically available, i.e., more bioavailable, particulate forms.
This means that transport of lead in soils to children's residential interiors via various
mechanisms favors relatively higher inputs to interior dusts from anthropogenic lead in soils than
from naturally derived lead in soils and also favors higher uptake rates of anthropogenic lead in
terms of bioavailability.
The cumulative inputs to the hot-spot subsets of U.S. surfaces of anthropogenic lead can
be estimated in various ways. Our 1988 ATSDR Report to Congress noted the tonnages
D-50
-------
deposited from leaded gasoline combustion and from lead paint use as being cumulatively about
10 million metric tons (MT). Extractive industry wastes from smelters, milling operations, slags,
etc. have been computed by Nriagu and Pacyna, 1988, and are sizable in terms of impact on
nearby communities and are contained in the 1993 NAS/NRC report on lead exposure in
sensitive populations.
NAS/NRC. 1993. Measurement of Lead Exposure in Infants, Children, and Other
Sensitive Populations. National Research Council. Washington, DC: National Academy
Press., Ch. 3: pp. 99-141.
Nriagu JO, Pacyna JM. 1988. Quantitative assessment of worldwide contamination of air,
water and soils by trace metals. Nature 338: 47-49.
One can also calculate U.S. anthropogenic lead dispersals as an upper bound by assuming
that cumulative figures for U.S. lead consumption over the decades eventually translates to
environmental dispersal. Annual figures for U.S. lead use since the 19th C. to the present, as
contained in annual estimates from the U.S. Bureau of Mines or the U.S. Geological Survey, are
available. These can be summed to achieve a tally of around 100 million MT. I suggest Staff do
this. There have been recent summary Tables produced by USGS, as the successor to the U.S.
Bureau of Mines Mineral Yearbook statistics. The Bureau essentially went out of business in
1994-95.
DiFrancesco CA, Smith, GR: U.S. Geological Survey. 2005. Lead Statistics. Last
Modification, December 2003.
Smith GR: U.S. Geological Survey. 2002. Lead. Accessed at URL
http://minerals.usgs.gov/minerals/pubs/commodity/lead/leadmyb02r.pdf.
U.S. Geological Survey, 1901-1927, Mineral Resources of the United States, 1900- 23.
U.S. Geological Survey, 1997-2004, Mineral Commodity Summaries, 1997-2004.
U.S. Geological Survey, 1997-2003, Minerals Yearbook, vol. 1, 1995-2001.
U.S. Geological Survey and U.S. Bureau of Mines, 1996, Mineral Commodity
Summaries, 1996.
U.S. Bureau of Mines, 1927-1934, Mineral Resources of the United States, 1924-1931.
U.S. Bureau of Mines, 1933-1996, Mineral Yearbook, 1932-1994.
U.S. Bureau of Mines, 1978-1995, Mineral Commodity Summaries, 1978-1995.
Whatever the size of the current anthropogenic lead burden in soils and other sources of
dust-sized particles that can be reentrained into risk population environments, the fact remains
that newly deposited dust lead from new emissions can itself add to risks of children's lead
D-51
-------
exposures as per EPA's own calculations and from which I was able to generate Tables submitted
after the first meeting.
To the extent that total but quite low air lead arises from both new air emissions and
reentrained dusts, and that total air lead from both sources even at low concentrations can be
potentially toxic via dust lead loadings onto hard surfaces, there is clearly very little margin for
permissible newly-emitted air lead. The adherence of air lead emissions to this minimal
permissible value obviously requires the continued use of an air lead NAAQS.
D-52
-------
Dr. Michael Newman
Chapter 8 - Newman Comments
Generally, statements and assessments are less clear here than in the other chapters but
this is a consequence of our current state of knowledge, not a specific deficiency of the
chapter.
> Many ecological entities must be considered including individuals, populations,
communities, ecosystems, landscapes, and even higher levels for pollutants influenced
strongly by atmospheric (or hydrologic) movements. Temporal scales of effects shift also
with a change in hierarchical scale/vantage.
> Many new cause-effect models and relationships must be included as higher levels in the
ecological hierarchy are considered. They should be considered in the discussion of
uncertainties if it isn't possible to discuss them throughout the chapter text. Some examples
include the following:
Life history strategy and optimal foraging theory
Community processes and associated theory
Ecosystem processes and the influences of redundancy/interactions
Some issues seem to need more focus to optimally address the goal of this chapter.
> BLM model and AVS-SEM discussion is not completely balanced and is inconsistent in
points. (Sam Luoma also mentions this in his comments.)
The AVS/SEM method focuses only on dissolved metal but Page 8-21 discusses dietary
uptake of lead. The other chapters spend time on dietary uptake. Two publications
demonstrate that the method has issues of concern:
Long, E.R., MacDonald, D.D., Cubbage, J.C., and Ingersoll, C.G. 1998. Predicting the
toxicity of sediment-associated trace metals with simultaneously extracted trace
metal:acid-volatile sulfide concentrations and dry weight-normalized concentrations: A
critical comparison. Environ. Tox. Chem. 17:972-974.
Lee, B., Griscom, S.B., Lee, J., Choi, H.J., Koh, C., Luoma, S.N., Fisher, N.S. 2000.
Influences of Dietary Uptake and Reactive Sulfides on Metal; Bioavailability from
Aquatic Sediments. Science 287: 282-284.
Page 8-17 states that the approach allows accurate predictions.
In fact, the scientific jury is still out on this issue although groups within EPA believe
that it is now time to accept the general context.
Some discussion of recent digestion fluid extraction techniques might also be helpful.
D-53
-------
Mayer, L.M., Chen, Z., Findlay, R.H., Fang, 1, Sampson, S., Self, R.F.L., Jumars, P.A.,
Quetel, C., and Donard, O.F.X., 1996. Bioavailability of sedimentary contaminants
subject to deposit-feeder digestion. Env. Sci. Technol. 30, 2641-2645.
Chen, Z., Mayer, L.M. 1998. Mechanisms of Cu solubilization during deposit feeding,
Env. Sci. Technol., 32, 770-775.
Weston, D. P., Maruya, K. A., 2002, Predicting bioavailability and bioaccumulation with
in vitro digestive fluid extraction, Environ. Toxicol. Chem., 21, 962-971
> Mixtures effects (e.g., page 8-24): The presentation mixes the "similar & independent action"
and "deviations from (concentration or effect) additivity" contexts in ways that produce
invalid statements. Should be reviewed carefully as these contexts and associated
mathematical models are not the same.
Finney, D. J. 1947. The Toxic Action of Mixtures of Poisons. Cambridge at the
University Press, Cambridge, UK, pages 122-159.
> Co-stressors are likely important to consider here and probably should be discussed in more
detail. Immunomodifiers are an example.
> Loadings
The approach comes into the US context from Europe and carries with it default values that
are not changed. More discussion of these kinds of actions and decisions about its use might
engender more confidence for the reader.
The approach treats the issue in an ecosystem/landscape context and attempts to assess a
threshold or tipping point. The current associated ecological theory is very relevant and not
unambiguously supportive of this context.
Redundancy hypothesis - Many species are redundant and their lose will not influence
the community function as long as crucial (e.g., keystone and dominant) species
populations are maintained.
Rivet popper hypothesis - Species in a community are like rivets that hold an airplane
together and contribute to its proper functioning. The loss of each rivet weakens the
structure.
These references give some insights about this issue:
Pratt, J.R., and J. Cairns. Ecotoxicology and the redundancy problem: Understanding
effects on community structure and function, in Ecotoxicology: A Hierarchical
Treatment, Newman, M.C. and C.H. Jagoe, Eds., CRC/Lewis Publishers, Boca Raton,
FL, 1996.
D-54
-------
Tilman, D. and J. A. Downing (1994). Biodiversity and stability in grasslands. Nature
367: 363-365.
Tilman, D., D. Wedin, et al. (1996). Productivity and sustainability influenced by
biodiversity in grassland ecosystems. Nature 379: 718-720.
Tilman, D. (1996). Biodiversity: Population versus ecosystem stability. Ecology 77(2):
350-363.
D-55
-------
Dr. Michael Rabinowitz
Comments on the "Air Quality Criteria for Lead (Second External Review Draft) May
2006
by Michael Rabinowitz, PhD June 2006
Overall, this manuscript is well on its way to being a document which will prove useful for many
years to come.
My comment include some minor wording suggestions, a few additional references which
illustrate some aspects of lead not already included, and identifying a few egregious sentences,
which require removal.
Let me again suggest that Table 2-3 (page 2-6) include two other commercially significant lead
compounds: lead azide and lead stearate. The first is used as a primer in ammunition, and the
second is a so-called lead soap, used as a lubricant and as a stabilizer in plastics. It is the source
of the lead found when mini-blinds deteriorate. An excellent source of information is the New
Jersey Right to Know web site, http://www.state.nj.us/health/eoh/rtkweb (Substances #1100 and
1111), or http://www.scorecard.org.
On the topic of the permanency of lead's effects on child intelligence test scores:
A: Let me suggest you include the following study:
Soong WT, Jang CS, Wang JD (1999) Long term effect of increased lead absorption on
intelligence of children. Arch Env Hlth 54: 297-301
The authors examined 32 children who attended a kindergarten near a lead battery smelter along
with 35 matched for age, gender, sibling order, and parental education, children 5 km away in
Northeast Taiwan. After the initial examination the kindergarten near the smelter was relocated
2 km away. 28 children from each group were followed for 2.5 years. Compared with the initial
examination the exposed children's blood lead dropped by 6.9 |ig/dl and their intelligence
quotient increased by 11.7 points, both highly significant. Meanwhile, the reference group had a
drop of blood lead of 1.7 |ig/dl and an increase in IQ of 4.2 points. Their was a significant
difference between the exposed and reference groups in terms of blood lead and intelligence
during the initial study, but that difference subsequently disappeared during the followup. The
authors concluded that the intelligence impairment caused by subclinical elevations of blood
lead, likely no more than 30|ig/dl) for a period of 1 to 3 years in a 3 to 5 year old may be at least
partially reversed.
It should be noted that these children were well nourished and recovered in an environment with
great emphasis on learning. Individual intelligence and performance on nationwide standardized
tests are the basis for entry into advanced schooling and future roles in society, Taiwan being a
Confucian meritocracy. The families were motivated. These conditions might be more favorable
in contrast, for example, with other societies where one's likelihood of academic advancement
D-56
-------
are viewed as predetermined based on family connections, caste, or predestination, such as
Hindu societies (The Economist, May 27, 2006 p38.).
This topic is revisited in 6.2.11 and AX6-2.10
B: In the Executive Summary:
E-8 line 9, regarding irreversibility of lead's effects on children's intelligence, this statement
("effects appear to be irreversible") is too general. There are cases where reversibility has been
demonstrated (see Soong et al. in Taiwan and Bellinger et al. in Boston on conditions that favor
reversibility of lead's effects). I suggest we need to be consistent with what the authors have
written on page 7-65, line 11. So let's say instead that "...possibly permanent", or "... can be
irreversible, depending on the intensity, duration, and timing of the exposure". Or "...may be
irreversible."
Aside from the scientific veracity of the statement, which perhaps should be our only concern, I
have another objection. Saying that it is permanent may serve to weaken efforts by individuals
and families to overcome the deficit. A child might be written-off with little motivation if told
that the IQ deficit is permanent with such a blanket statement. These children would be better
served, I suggest, not being stigmatized but by being told that efforts to perform better might
pay-off. Sequella may be minimized.
C: In Chapter 7
7.5.2 7-63, lines 21+ contain the following sentence, which deserves to be deleted:
"A rigorous test of reversibility would require that essentially every Pb atom has been cleared
from the body. This being unattainable,..."
Actually, what would be required is only for enough lead atoms to be cleared until the lead level
in the body reaches some background, or pre-exposure level, which is far from "essentially every
atom". The author apparently doesn't appreciate the fact that lead is a naturally occurring
element, and the Earth is sufficiently old that the chemical elements have been so mixed, that
there are trace or ultra-trace amounts of every element in everything (aside from a few laboratory
curiosities).
So, the rest of the paragraph needs to be omitted or rewritten so as not to require the false
premise.
On the topic of pregnancy hypertension
This topic was not touched, sorry if I missed it. So, perhaps add this published study in 6.5.3.3
andAX6-4.1 Page 6-157
Lead appears to have a small but demonstrable association with the diagnosis of pregnancy
hypertension and with blood pressure at the time of delivery. By assessing 3851 Boston women's
cord blood lead level (mean, 7 ± 3 [SD] |ig/dl), demographic, medical, and personal information,
D-57
-------
lead was found to correlate with both systolic (Pearson r— 0.081,/? = 0.0001) and diastolic (r =
0.051, p = 0.002) blood pressures during labor. The incidence of pregnancy hypertension
increased with lead level. Multivariate models of pregnancy hypertension and systolic blood
pressure as a function of maternal age, parity, hematocrit, ponderal index, race, and diabetes
were improved by including lead as a predictor variable.
Rabinowitz M, Bellinger D, Leviton A, Needleman H, Schoenbaum S (1987) Pregnancy
hypertension, blood pressure during labor and cord blood lead levels. Hypertension 10:447 - 451.
On Blood Lead Kinetics:
Here are two studies that should be included. One deals with the very slow dynamics in adults,
dominated by bone turnover and kidney function. The other demonstrates the rapid turnover in
young infants, with increasing stability with age.
A: The time course of blood lead in adults in response to being treated for occupational lead
poisoning illustrates the impact of bone lead stores on maintaining an elevated blood lead over
many years. In a study from Chicago of 65 adults followed for over six years, the blood lead
elimination half-life was about 600 days, even with EDTA treatment. Among the eight subjects
with impaired renal function the median half-life was over 5 years. This illustrates that the major
route of transfer of lead out of blood is into the urine.
Hyrhorczuk D, Rabinowitz M, Hessl S, Hoffman D, Hogan M, Mallin K, Finch H, Orris P, and
Berman E (1985) Elimination kinetics of blood lead in workers with chronic lead intoxication.
American Journal of Industrial Medicine 8:33 - 42.
This might appear in Section 4.3.1.5 line 28 page 4-28. Later in this section, may I suggest for
page 283, line 27 this report on variability.
B: Infants were found to have relatively variable blood lead levels compared to adults. By
examining more than 200 Boston children's blood lead levels semiannually during their first two
years of life (mean 7.2 +5.3 std dev |ig/dL), the average change every 6 months was 4 |ig/dl. Part
of this variability was from changes in the environment associated with changing residences or
home repairs. Only 25% of the children in the highest decile of lead level at birth were also in the
highest third at 2 years of age.
This variability decreased with age, as the child's bone mass grows, which accounts for
increasingly more of their body burden of lead. The correlations of blood lead every six months
consistently increased with age, being 0.10 during the first 6 months, .41 at one year and 0.60 at
2 years of age.
Rabinowitz M, Needleman H, and Leviton A (1984) Variability of blood lead concentrations
during normal infancy. Archives of Environmental Health 39:74-77.
Summary E 8 line 9 "appears to be irreversible" to "reversibility depends on the magnitude,
duration and timing of exposure".
D-58
-------
E-10 line 19, mention that hematological effects (even as far as anemia) are reversible
On Confounding Adjustment and R-squared Estimates
in section 6.10.6.2 on page 6-310
Please remove the offending sentences from line 12 to 19. The proposed doubling of the lead
effect, so as to account for 100 percent of the variance, is specious. Indeed, most studies have
found a modest or small lead effect, of a few percent, while other well-recognized factors
account for large portions, almost half of the variance. However, there is no justification for
doubling the values to make it 100%. This might have been true is there were no other,
unmeasured factors, but indeed there are. We now know genetic make-up and nutrition, labor
and delivery and childhood medical events and head injuries, for example, are influential, but
rarely measured as part of a lead study. So are other pollutants. For example a recent study from
Columbia Medical School has demonstrated that air pollution levels in New York City,
specifically PAH, can account for many IQ points. Incidentally, those authors point out that lead
at the levels currently found (blood lead levels near Ijig/dL) are not associated with intelligence.
In that this pollutant PAH was not previously measured, while lead, previously also a product of
traffic, was measured, it may be that some of what had attributed to lead from automobile
exhaust may have been from this or other pollutants. (Perera, FP, Rauh V, Whyatt RM, et al.
(2006) Effect of Prenatal Exposure to Airborne Poly cyclic Aromatic Hydrocarbons on
Neurodevelopment in the First Three Years of Life Among Inner-City Children, Env Hlth Persp
Online April 24). So, we can not simply double what had been measured, but what accounted for
only 50%.
Yet, another independent reason why blood lead, even if it were the only cause of lowered IQ
would not account for all the variance is based on the fact that blood is not the target organ,
rather the brain is. If we could measure brain lead levels, we would get a higher correlation
with IQ, but, since the ratio of brain lead to blood lead is small and itself variable, we could not
expect blood lead to carry all of the variance. So, we can not simply double the blood lead r-
squared.
Furthermore, I'd also take issue with this paragraph's comments that "means of remediating
inadequate parenting" are not apparent. We do know how to encourage children to be more
well-developed, and those methods are in the realm of educators.
So, for any one of these reasons, these lines need to be stricken. The "scientific" document does
not need that sort of specious extrapolation.
On Soil Lead:
8.1.1 page 1210 line 2 Perhaps add yet another phosphate reference, somewhat earlier than the
others, for historical reasons:
Rabinowitz M (1993) Modifying Soil Lead's Bioavailability by Phosphate Addition. Bulletin of
Environmental Contamination and Toxicology 51:438-444.
D-59
-------
Dr. Joel Schwartz
Comments of Joel Schwartz
Chapter 7
In general, I found this chapter well written, clear, and that it accurately described the state of the
science. I have the following specific comments.
P 7-8. Other sources of lead exposure, please add soil to the list.
P7-17 Please note that the influence of the dust and soil pathways is relevant to air emissions.
That is, a sentence such as:
"Because air emissions eventually deposit, these pathways offer additional opportunity for air
lead emissions to result in lead absorption, resulting in an effective air lead to blood lead ratio
that can be substantially higher than that only incorporating the inhalation pathway".
Otherwise, it appears that you are now talking about a new topic (dust lead), and the implications
for air emissions is lost.
P 7-20 Animal models are also very useful because they are not subject to confounding by SES
or other factors, and hence establish a firm basis that effects can be caused by lead, and not
putative confounders. This allows the coherence of the effects to be compared between the
animal studies and the human studies (whose advantage are that they are in the species of
interest, at the dose of interest).
P 7-21. That the relationship between external dose and blood lead differs between animals and
humans does not mean that external dose must of necessity be the primary exposure of interest,
as suggested in lines 8-10. If the reason monkeys require a higher dose to reach the same blood
lead is that they absorb less from the gut, or move the lead more rapidly to bone, blood lead may
still be the most relevant exposure metric, and not dose. I think we need rather more data to
conclude that the same effects would be seen in humans at higher blood lead levels.
I liked the way the animal and human data were integrated, and think this is a excellent
discussion integrating the two sources of data.
7.4.3 I dislike the characterization of the studies of blood lead and blood pressure showing a
weak association. Weak association is an ambiguous word that may suggest small effect sizes to
some, lack of significance to others. I believe it is useful to resolve the ambiguity. The large
majority of the associations are positive, the meta-analysis is significant, both suggesting a
robust indication that there is an effect. However, the effect sizes are small.
The comments on the paper of Bowers should indicated addition problems with their analysis. In
contrast to normal regression analysis, which assumes that the distribution of the outcome,
conditional on the predictors, is normal, they have chosen to assume that the distribution of the
outcome is normal before regression on the predictors. If some of the predictors have a skewed
distribution, then this assumption (which differs from normal statistical theory for linear
regression) would indeed force the dose-response to be nonlinear, as the difference in
distribution between outcome and exposure cannot be accommodated otherwise. Essentially, in
D-60
-------
order for the outcome to remain normally distributed when the predictor has a long right hand
tail to the distribution, it is necessary for points out on that tail to have progressively less and less
impact. That is, the slope out at the high end of the exposure distribution must be smaller than at
the low exposure end. Otherwise, they would skew the distribution of the outcome, which
Bowers does not allow. However, none of the published papers on lead and IQ (or lead and
blood pressure) make that assumption. Rather, they make the usual assumption that conditional
on the predictors, the IQ scores are normal. It is also important to realize that many other
predictors of children's IQ, such as socio-economic status, have skewed distributions, and it is
unreasonable to make the assumption of raw scores being normal in any case, and this is a matter
of principle, not testing of deviation from normality. In any case, since the lead—IQ studies do
not make the distorting assumption of Bowers, they do not produce the distortion.
To see this better, consider the implication of the published analyses of truncated distributions.
Blood lead has a skewed distribution—the tail extends to the right longer than to the left. As we
truncated the data by e.g. eliminating all lead levels above 20 |ig/dL, or above 10 |ig/dL, the
right hand tail is truncated, and the ability of extremely high lead levels to distort the dose
response relationship is reduced. Hence even if the scenario of Bowers had been true, analyses of
studies that eliminate blood lead concentrations above 10 mg/dL would eliminate the distortion.
And yet the studies restricted to the low end of the dose response relationship continue to show
large slopes. Hence these large slopes are clearly real. Whether the smaller slopes at blood lead
levels above 20 are an artifact of assumption is really irrelevant, as the major concern is what the
dose-response curve looks like at low levels.
The discussion of why the toxicologic assumption of a threshold is not met should incorporate
more of a discussion of the work of Patterson. His findings that non-occupationally exposed
adults with no record of childhood lead poisoning had bone lead concentrations 3 orders of
magnitude above those of pre-industrial Southwest Indians, suggests that even today's much
reduced lead exposures in the 1-20 |ig/dL range are still 2 orders of magnitude above background
levels the human body evolved to deal with. Hence if there were a threshold at say, 5 times
normal background concentrations, that would still be an order of magnitude lower than the
lowest exposures examined in the studies presented in the Criteria Document.
Chapter 6
Page 6-6
I strongly disagree with the statement:
"Also, given that lead-related cognitive deficits in adults tend to be specific, not generalized,
vocabulary and reading ability, which correlate highly with year of education and are predictors
of performance on other specific cognitive tests, also may serve as confounders or modifiers of
lead effects on adult cognitive function. "
It may well be true that in studies of other exposure linked to cognitive decline in the elderly, the
exposures are associated only with specific cognitive tests, and it may therefore be traditional
that control for vocabulary and reading ability be controlled for. However, this is clearly
inappropriate for lead. As this chapter goes on to explain, the extensive literature on lead and
D-61
-------
cognitive ability in children suggest the opposite of what is alleged above—to wit, that lead is
associated with general decrements in cognitive ability, not narrow decrements in only a few
specific tests. In the absence of clear, convincing evidence that this is not the case for adults, this
statement is unjustified, and contradictory to the known literature. Moreover, the specific
recommendation that vocabulary and reading ability be controlled in examining the cognitive
effects of lead is astounding, given the extensive literature associating lead exposure with
reading ability. For example, Needleman, in his follow-up of his cohort into high school,
reported lead associated with reading two or more grades below level, with an odds ratio of 5.8,
and also an negative association with vocabulary. If lead produces reading and vocabulary
deficits in high school students, do we really expect those to resolve post high school? Moreover,
the Lanphear study of NHANES III data reported an association of lead and reading score
(WRAT-R) in teenagers, a result well discussed in this very chapter. Does that not further make
it clear that this is an established effect of lead exposure? What about the studies of Fergusson et
al., 1988a; Fulton et al., 1987; Yule et al., 1981, reporting negative associations between lead and
reading scores? Or the Fergusson 1997 follow-up at age 18 showing a persistent negative
association of lead with reading performance on the Burt reading test?
Given all this, if we are now associating bone lead with cognitive outcomes in adults, would we
not hypothesize that reading ability and vocabulary was a well justified outcome to examine?
And is there not a published paper showing that bone lead is indeed associated with that outcome
in adults? So in what way does this statement not violate the sense of the literature described
elsewhere in the chapter, and the usual statistical rule that variables on the causal pathway
between exposure and other outcomes are inappropriate choices for potential confounders?
P 6-66 States that the cubic regression spline is descriptive and may not be used for inference. In
fact, the linear dose-response curve is nested within the cubic spline, so a test of improvement of
fit for the extra degrees of freedom can be performed. Since this is a specific non-linear term,
rejection of improvement in fit cannot definitively reject the hypothesis of nonlinearity, although
given the flexibility of the spline, it is strong evidence. However, acceptance of the test (i.e. that
the curve is significantly different from linear) is a justifiable inference.
p. 6.69 as above, the discussion of why the toxicologic assumption of a threshold is not met
should incorporate more of a discussion of the work of Patterson. His findings that non-
occupationally exposed adults with no record of childhood lead poisoning had bone lead
concentrations 3 orders of magnitude above those of pre-industrial Southwest Indians, suggests
that even today's much reduced lead exposures in the 1-20 |ig/dL range are still 2 orders of
magnitude above background levels the human body evolved to deal with. Hence if there were a
threshold at say, 5 times normal background concentrations, that would still be an order of
magnitude lower than the lowest exposures examined in the studies presented in the Criteria
Document.
P 6.71-72. states, " It is assumed that measurement errors are essentially random ...." This
should be extended to indicate that in a linear model random measurement error in the outcome
does not bias the estimated effect size for exposure (unlike measurement error in exposure), but
does reduce power to detect a significant effect.
D-62
-------
P 6.78 states, "When administering a neuropsychological battery, it is necessary to include a test
that estimates premorbid ability, such as Vocabulary or a reading test such as the Wide Range
Achievement Testing for Reading (WRAT).."
As noted above, since lead has been associated with decrements in the WRAT, this statement is
inappropriate. Moreover the further statement that "these tests are not affected by exposure to
neurotoxicants unless severe global brain damage .." is obviously contradicted by the studies in
chapter 6.
Further, in a longitudinal study, incorporation of either a random intercept of the baseline
measure, or analysis of differences in cognitive function does control for baseline cognitive
ability.
P 6-80 again expresses shock that lead was associated with educational attainment, and takes that
as an indication of uncontrolled confounding, as opposed to consistent with the literature in high
school students and others showing that lead is associated with educational attainment, which is
well described in the apparently unread sections of this chapter. Again, it is stated that
vocabulary should not be considered an outcome.
In general this section simply asserts that all significant results reported for lead and cognitive
outcomes are confounded, while accepting the studies with no significant findings. This is not a
balanced approach.
Cardiovascular effects of Lead
Please be clear that the meta-analysis of the blood lead studies is highly statistically significant,
although the coefficient is small. The consistency of studies (almost all reported positive effects)
adds to credibility even if the main focus of the chapter switches to the bone lead studies.
D-63
-------
Dr. Frank Speizer
Comments on Chapter 6 Lead Draft 2
Submitted by Frank E. Speizer
Generally, except for its length (is it considerably longer than the first draft?) I found this to be
well written and logically presented. The neurotox section is appropriately the lead off section as
it is clear it seems to be worked through in terms of identifying significant health effects that will
have importance in choosing a standard. However, it does in part seem to go on and on with
some redundancy and repetition is some sections.
Specific Comments:
In terms of cohort studies in children the Rochester study and the Mexico City 2 study appear to
be the only ones relevant to current exposures below 10|ig/l. All of the other studies were of
higher exposure levels at young ages. The meta-analysis discussion does not make this point as
clearly as it might.
The cross sectional studies consistently show a relationship between blood lead levels below
10|ig/Dl and in addition by using retrospective techniques at least one of the meta-analyses
suggests a peaking of effect by exposure measure below age 3, with cognitive effects persisting.
The summary of the academic achievement section suggest an impressive effect, but the
statement in the middle of page 6-41 could be strengthened further by indicating that the effect
was clearly present even when limiting the data to those studies with average levels were below
10|ig/dl. This is clearly a matter of style; it is just that the way it is said suggests that the effects
below 10 are an unusual finding whereas they are the norm.
Page 6-43-44: It is not clear why this study is included as the average levels of exposure are well
over 10|ig/dl. However, having done so the authors spend almost a whole page trying to explain
the null result. Not mentioned is the potential for a selection bias in the population. This study
was done at the same time as several others yet these children seem to have had levels that are
twice as high as others (from other cities). This seems to be more than a city effect and would
need to be explored. The results also suggest a non-linear function of effects with a flattening of
effects at higher levels. This also might reflect as selection bias in follow up.
Page 6.67, Figure 6.-2.5 What is critically important is that whether one uses a log-linear model
or the 5 knot spline model, the lower bound of the 95% c.f. at 90 occurs at 10|ig/dL and below
that level there is an inverse linear non-threshold effect of lead level on the full IQ range. This
will need to come up again in the integrated chapter as well as in the scientific assessment
portion of the staff paper.
Page 6-71 end of section on selection and measurement error. One wonders if it might be worth
adding what the impact of measurement error might be on the findings using full IQ. I think
there are some data in the section that could be used for an example. The difference between the
D-64
-------
IQ scores of 5 and 7 year olds in spite of the drop in lead levels is probably related to
measurement error in the validity of the IQ scores. The point is one sees an important (to my
eye) linear relationship that persists and perhaps if formal measurement error correction were
applied to the 5 year old data might have it match up even better with the 7 year old data.
Page 6-72-74 Section 6.2.15 Confounding, causal inference and effect modification. This is an
interesting section from the standpoint of its importance as being part of the CD. Given that it is
here, it should remain. But going forward with a revised process how important is it to have
such a discussion in a CD document? Does it belong simply in the integrated summary or as part
of the staff paper or not at all, but by reference they are or should be the issues discussed in the
original papers?
Section on Occupational exposures could have been shortened. Much of the exposure is above
the levels of interest. The issue of interest is how cognitive reserve appears to protect against
ravages of lead. Issue is one of measurement error or variance vs real protection. This point
may need to be brought out further.
In the section on renal toxicity there appears to be redundancy between the table 1 and figure 1 in
that the same studies are presented. This was raised on the first draft as having more of the
specific results presented in this section, albeit smaller and probably less important that the
section on neurotoxicity in children and seems, therefore, inappropriate. It is also true that the
table material appears in the appendix tables (I think).
Section on Occupational studies reads like an apology for considering it. It probably would have
been reasonable to simply state in one paragraph why the studies were not considered relevant.
I continue to not see the value of a discussion on chelation in patients as part of this CD. In
contrast I like the section of susceptibility.
Page 6.201, table 6.7.3 Don't find this table particularly useful. It could have been summarized
as saying x number of studies have been done. This is in contrast to table 6.7.4, which suffers
from being mostly occupational studies at relatively high exposure with very high blood levels
that do not related to the task at hand. I would have thought that this table could have been in the
appendix, with the results summarized in a few sentences.
The sections on a number of other systems seem to go on and on and become ponderous to read.
Once again the encyclopedic nature of the data presentations, particularly the review of clinical
studies of clearly lead toxicity that are irrelevant to the task in hand, leads to less than thoughtful
review of the details. In addition consideration of potential misclassification of exposure to
mixtures as being the result of lead exposure leads to some inappropriate suggestions of
associations. See for example the comparison of battery manufactures with hospital workers
comparing lung function. No thought seems to be offered that what is called a lead effect could
relate to other agents in the battery plant that could also explain the results.
Section 6.10 begins to get at the meat of the chapter in trying to pull together much of the
material that has come before. Even here it takes 16 pages before one actually get to
D-65
-------
summarizing health effects of interest. Much of the preamble has already been mentioned in the
chapter and could have summarized as bullets with cross referencing to earlier parts of the
chapter.
It is unclear what figure 6.10.4 is telling us. The discussion on page 6.17 suggests this is a lead
effect but if the average IQ is taken to be 100 with a SD of 15 than one would expect by chance
in any population that 2.5% of the population would have IQ's below 70, and 0.1% would have
IQ's below 50. Isn't that what the figure shows irrespective of lead level? The next paragraph is
true but is not clear that the population shift data has been presented.
D-66
-------
Dr. Ian von Lindern
June 26, 2006
COMMENTS OF IAN VON LINDERN REGARDING SECOND DRAFT OF AIR QUALITY
CRITERIA DOCUMENT FOR LEAD
Charge Question - Executive Summary: What are the CASAC Lead Panel's views with
regard to the newly-provided Executive Summary and the soundness of its scientific content,
including consistency of the restatement of key findings and conclusions stated in the main
chapters of the document?
In general, I believe that the Executive Summary captures and conveys the salient points in the
document, with the exception of some additional discussion regarding Sections 2 and 7 of the
document, as indicated below.
EXECUTIVE SUMMARY
Subsection El appropriately summarizes the main points from Section 1 of the document.
Subsection E2 should add summary discussion of the current production and uses of lead in the
U.S. and globally, provide a contemporaneous estimate of emissions and domestic production
data and compare those to the situation applicable to the last AQCD. It should also note that
relative scarcity of present day emission information. A short description of lead's unique
physical and chemical characteristics as they relate to past and present uses of lead in commerce,
industry and consumer goods would be informative to the reader, as well.
I don't find a Section E3 in the Executive Summary and the subsequent numbering system does
not correspond to Chapters in the main document. This might be inconvenient for the reader that
would like to follow up points made in the main body of the document.
I believe there should be some summary discussion reflective of the conclusions and advice
subsequently offered in Section 7.
Charge Questions Chapter 2: (a) Overall, does this revised chapter adequately characterize
various important sources of Pb in the environment? (b) Are salient data from EPA and other
sources, in addition to the peer-reviewed literature, now adequately incorporated in this chapter?
(c) Are any further improvements necessary?
I have several concerns regarding the adequacy of emissions, production, end use, reuse/recycle
and ultimate sink data provided in this Section. The additions provided from various agencies
sources have added substantially to the document since the previous draft. In many cases, it
seems that this may represent a real unknown and EPA should acknowledge the lack of
information in these areas. There should be some critical evaluation of the data sources and the
results presented to provide reviewers with a sense of the adequacy and appropriateness of the
D-67
-------
state of knowledge in these areas. This is particularly true as it applies to the next step in the
standard setting process. The OAQPS will, likely, need to pursue a case-study approach to risk
assessment and development of a protective standard.
CHAPTER 2 PHYSICAL AND CHEMICAL PROPERTIES OF LEAD
Overall, the AQCD represents a substantial improvement in both content and presentation from
the previous draft. The addition of "gray literature" references has added greatly to the
characterization of lead sources, particularly with respect to present day or, at least, more
contemporaneous data. However, there remains a scarcity of data with respect to emissions,
production, use, environmental release and fate that will likely hamper assessment activities in
the ensuing regulatory efforts. These areas should be pointed out and apparent research and
characterization needs should be stressed. In the ensuing OAQPS effort, much of the data that
will be requisite to the lead analysis plan will be sought from other "gray literature" regulatory
files. It seems appropriate that those same references be provided in the AQCD for scrutiny by
the public and reviewers, as well. With respect to describing the chemistry and physical
properties of lead and those transport and transformation processes that affect migration,
deposition and behavior in environmental reservoirs, the EPA has done a good job in presenting
the state of the art, and the current draft AQCD provides an adequate and appropriate basis for
the lead analysis and risk assessment activities proposed by OAQPS.
P2-1 In 8 states "The chapter does not provide a comprehensive list of all sources of lead, nor
does it provide emission rates or emission factors for all source categories, since such
information is available for only a limited number of sources. " This statement continues to
reflect critical unknowns with respect contemporary lead emissions and environmental releases.
This lack of fundamental data should be pointed out here, in other Sections of the AQCD, and
subsequently in the OAQPS Assessment Plan. It is most important to provide the reader with
sense of where this lack of data is most significant. For example, as other reviewers point out, the
lack of present day emission data hampers the assessment of terrestrial ecosystems; emission
data from soil re-suspension and road dusts, although acknowledged as significant, is scarce and
adds considerable uncertainty to modeling efforts employed quantify its effect, etc.
2.1 PHYSICAL AND CHEMICAL PROPERTIES OF LEAD
The physical and chemical properties of lead are appropriately characterized and I have a minor
comment regarding this section.
P2-1 In 26 states "This aspect of its chemistry made Pb especially convenient for roofing,
containment of corrosive liquids, and until the discovery of its adverse health effects,
construction of water supply systems". It seems natural to cite lead's role in protecting surfaces,
i.e. as paint here.
D-68
-------
2.2 SOURCES OF LEAD
2.2.1 Natural Sources
P2-14 In 4 states "However, many countries around the world have much greater lead emissions
than the U.S. from stationary and mobile sources, including several countries that still use
leaded gasoline. Furthermore, the EPA estimate does not account for emissions of lead in
re suspended soil. Harris and Davidson (2005) estimate that stationary and mobile source
emissions account for only about 10% of the total lead emissions in the South Coast Air Basin of
California; the remaining 90% of the emissions are from resuspended soil. The soil contains
elevated lead levels because of the many decades of leaded gasoline use. Therefore, on a
worldwide basis, the anthropogenic emissions of lead are expected to be much greater than
natural emissions. " Are there some references and examples of data to support these inferences?
P2-15 In 5 states that 90% of natural lead in surface waters is in dissolved form, whereas P2-73
Iin3 points out that PM bound lead and suspended lead are the important forms of lead with
respect to aquatic transport. P2-15 In 11 states "A naturally occurring, radioactive isotope of
210
Pb, Pb, is commonly studied as a tracer to determine how particles are transported through
the environment. " P2-16 1 8 states "Leaching ofPb naturally contained in host rock is a very
210
small source to water (Toner et al, 2003).In surface waters, Pb is primarily in paniculate
form, while dissolved Pb is transported more readily (Joshi et al., 1991). Dissolved Pb is
scavenged by suspended matter (Carvalho, 1997). " This discussion is somewhat confusing. Is
this about natural lead, lead-210 or is it reflective of general transport mechanisms? Some
clarification of the significance of "natural" versus anthropogenic forms of lead as it relates to
chemical form and transport may be in order.
P2-16 through In 16-22 reports ingestion of lead-210 in piC whereas mass per day is much more
informative. This observation should be put into context, is it about low radiologic exposure,
little lead-210 ingestion, the relative significance of natural lead exposure, or something else?
2.2.2 Lead Emission in the U.S.
This section is much more informative with the addition of information from the various EPA
data bases. I believe there is likely more information that could be provided from the regulatory
files for individual facilities that are available in the State Implementation Plans (SIPs), relevant
permits and support documents for qualified facilities in the U.S. These data might be
particularly informative, as it will reflect actual emission measurements for both point and
fugitive emissions and source characteristics that are utilized in modeling efforts to assess
compliance with applicable regulations for stationary sources. It seems particularly appropriate
to cite these data for the single primary smelter operating in the U.S. These are the same data that
will presumably be accessed by OAQPS in developing the pilot risk assessment exercises
proposed in the Lead Analysis Planning Document.
There has been substantial improvement in presenting more contemporaneous data, with the
addition of the "gray literature" sources. The 2002 reference is quite helpful. However, there
D-69
-------
could be more analysis, critical evaluation and discussion of the results, particularly as to
whether the data support the overall theme of large emission reductions over the years. Can these
data tell us what has happened in various source categories, where problems have been
minimized and where emissions remain significant, etc. In a few cases, the cited references and
relative values conflict, and it seems incumbent on EPA to discuss these discrepancies and the
significance in utilizing the information in the context of the overall AQCD.
P2-16 In 25 refers to Figures 2-2 and 2-3. These figures provide much more information to the
reader than was available in the previous draft. However, the figures are quite busy and, perhaps,
the data would be better presented in a Table. I would recommend showing all the data in Tables,
aggregated by sub-groups, and then show the sub-groupings in the Figures. There are also some
inconsistencies among these figures and other data cited in the text that bear some investigation
and explanation of the differences. For example, it is difficult to compare the two years, as the
symbols and categories seem inconsistent. I am confused as the legend does not show primary or
secondary lead smelting in 2002. Assuming the same symbol applies from Figure 2.2, Figure 2.3
does indicate a minor contribution for primary smelting in 2002. However, a later reference on
Pg 2-20 In 9 indicates 14% (or 565 metric tons) of total anthropogenic emission was due to
primary smelting in 2000. How do these numbers compare. Several of the source categories are
similarly discussed later in the Chapter. There needs to be some comparative analysis
accomplished and there should be some discussion in each area as to how the later presentations
comport with the data supporting the estimates in these Figures.
P2-19 Inl I don't understand what is meant by "Complete source category coverage is needed,
and the NEI contains estimates of emissions from stationary point andnonpoint (stationary
sources such as residential heating that are inventoried at the county level) and mobile source
categories. " It may be that the NEI does contain the pertinent information available in the SIP
and permitting files noted above. EPA could likely determine that by contacting the State
authorities where the primary and large secondary smelters are located.
P 2-20 In 24 states "Emissions from smelters have been measured in several cases. A survey of
approximately 50 European Pb smelters had mean emission factors ofO. 1 grams and 0.05 grams
ofPb emitted per kg of Pb processed for primary and secondary Pb smelters respectively
(Baldasano et al, 1997). " Only European data are provided. There should be detailed emission
data available in State Implementation Plans (SIPs) for both the operating primary and
representative secondary smelters in the U.S., as well.
P 2-21 In 1 states "The ambient air concentrations in the immediate vicinity of smelters tend to
be elevated to 2 varying degrees depending on facility operations and meteorological
conditions. " The draft then cites mostly European observations. There are likely U.S.-specific
measurements available in the same references noted above for emission data.
P2-23 In 11 states "Lead mining occurs in 47 countries, although primary Pb production is on
the decline (Dudka andAdriano, 1997). World mine production ofPb is approximately 2.8
million metric tons per year (Wernickand Themelis, 1998). The reserve base ofPb is estimated
to be about 120 million metric tons, which will sustain current rates of mine production for 43
years (Wernick and Themelis, 1998) ". Can the U.S. figures be contrasted here?
D-70
-------
2.2.4 Mobile Sources
This section was quite informative and covered the subject area concisely and adequately.
P2-44 In 19-20 states "Most countries have made a similar move away from leaded fuel, but a
few continue the practice of adding tetraethylPb to automotive gasoline. " Is it possible to list
those countries continuing to use leaded gasoline?
2.3 TRANSPORT WITHIN THE ENVIRONMENT
2.3.1 Atmospheric Transport of Lead Particles
This section is well developed and appropriately presents the basic state of knowledge related to
quantifying atmospheric transport in the context of the types of modeling efforts that will be
required of the OAQPS proposed effort to assess risk associated with lead in the ambient air.
P2-52 In 6 states "Airborne lead tends to be in the form ofsubmicron aerosols (Davidson and
Rabinowitz, 1992; Davidson andOsborn, 1986; Harrison, 1986; Lin et al, 1993)". This
statement may be inaccurate for particular source categories, particularly those associated with
re-entrained soils discussed in the next section.
P2-53 In 10 states "Modeling efforts for an abandoned battery recycling facility using the EPA
Industrial Source Complex Short Term (ISCST) model, based on Gaussian equations, showed
good agreement with measured concentrations (Small et al., 1995). Model predictions at three
sites at distances between 240 and 310 mfrom the stack were between 3.8 and 4.4 jjg/m ,
whereas measured concentrations taken when the plant was in full operation had averages
between 4.1 and 5.2 pg/m . " Was this study pertinent to earlier discussions regarding ambient
concentrations near battery recycling plants?
2.3.2 Deposition of Airborne Particles
Similar to the previous section, this section is well developed and appropriately presents the
basic state of knowledge related to quantifying deposition of ambient particulate in the context of
the types of modeling efforts that will be required of the OAQPS proposed effort to assess risk
associated with lead in the ambient air.
P2-61 In 18 contains a spelling error
2.3.3 Resuspension of Lead-Containing Soil and Dust Particles
This section is well developed and provides balanced coverage of the basic model techniques for
estimating atmospheric contributions from re-entrained sources. It will be important for OAQPS
to utilize these different techniques and compare and contrast results in assessing the risk
associated with these sources.
D-71
-------
2.3.4 Runoff from Impervious Surfaces
2.3.5 Leaching of Soil Lead
P 2-68 In 17 states "Lead can bind to many different surfaces in the heterogeneous soil matrix.
This adsorption greatly affects mobility and is dependent on the characteristics of the soil and
lead compounds. " It would be good to indicate that lead is generally immobile in most soils and
has long residence times.
P2-72 In 21 states "Lead is removed from the water column through flushing, evaporation, or
sedimentation (Schell and Barnes, 1986). " Does this reference show loss from the water column
through evaporation?
2.3.6 Transport in Aquatic Systems
No comments. This sub-section, in combination with Chapter 8, appropriately covers the subject.
2.3.7 Plant Uptake
No comments. This sub-section, in combination with Chapter 8, appropriately covers the subject.
2.3.8 Routes of Exposure for Livestock and Wildlife
No comments. This sub-section, in combination with Chapter 8, appropriately covers the subject.
2.4 METHODS FOR MEASURING ENVIRONMENTAL LEAD
2.5 SUMMARY
P2-79 LN 20 states "Currently, the major use ofPb in the United States is in lead-acid batteries,
for which the demand is increasing (Socolow and Thomas, 1997). Other major uses are for
glass, paints, pigments, and ammunition. United States consumption ofPb by industry is shown
in Figure 2-8. " This is the single discussion of lead production and consumption in the AQCD. It
is an important topic, but is introduced in the summary with little discussion. Can information be
provided to put this in the global context and is there data to support the role of recycling. It
seems important to know if this lead is being released to the environment by routes other than
air, particularly for ecological and environmental pathways. Where is all this lead going?
P2-79 In 9 states "Efforts to develop accurate databases ofPb emissions are needed. " This
statement should be expanded to indicate the potential ramifications of this shortcoming in
impending uses of the AQCD. The OAQPS analysis plan should acknowledge the situation and
indicate possible sources of information that could be used to mitigate those problems.
P2-81 In 7 states "A rigorous comparison ofresuspension, leaching, and plant uptake
"removal" rates for soil lead has not been undertaken. Resuspension of lead-containing
particles is likely the dominant removal mechanism from surface soil when soilpH is high. "
D-72
-------
There are several important summary points included here. The summary should emphasize that
resuspension is both an emission source and a transport mechanism. Resuspension may be one of
the largest and most significant emission sources in this country, although few attempts have
been made to quantify this in other than local settings. In mining areas, resuspension is a major
emission source and a dominant transport problem, even at low pH. In all cases, resuspension
and subsequent deposition is of greatest concern as it contributes to house dust where it can
accumulate and expose children, regardless of current air lead concentrations. Leaching and/or
plant removal are unlikely mechanisms to alleviate resuspension as an emission source in areas
with high soil lead concentrations. Dilution through development of the soil profile and
mechanical processes and adherence to larger particles that don't erode are more likely scenarios
in most situations.
P2-82 In 3 states "On a local scale industrial effluent and urban runoff may dominate'' Erosion
of contaminated soils is often the largest source in rural and suburban areas.
SECTION 4
4.4.2 Empirical Models of Lead Exposure Blood Lead Relationships
Discussions in this Chapter of analyses presented in TerraGraphics 2000 were subsequently
published in the peer-reviewed literature in
Von Lindern, I.; Spalinger, S.; Petroysan, V.; Von Braun, M. (2003b) Assessing remedial
effectiveness through the blood lead soil/dust lead relationship at the Bunker Hill
Superfund site in the Silver Valley of Idaho. Sci. Total Environ. 303: 139-170
SECTION 7 INTEGRATIVE SYNTHESIS: LEAD EXPOSURE AND HEALTH
EFFECTS
7.2 AMBIENT AIRBORNE LEAD, SOURCES, EMISSIONS, AND
CONCENTRATIONS IN THE UNITED STATES
7.2.1 Sources of Lead Emissions into Ambient Air
There is little discussion of lead production and consumption in the AQCD. It is an important
topic, but is introduced only in the Chapter 2 summary with little discussion. Some information
should be provided to summarize what is known regarding emissions and releases associated
with these uses, and the ultimate fate, or sinks of the materials. This should also be put this in the
global context, if possible. It seems important to know if this lead is being released to the
environment by routes other than air, particularly for ecological and environmental pathways.
Section 7 should note that efforts to develop accurate databases of Pb emissions are needed.
This statement should be expanded to indicate the potential ramifications of this shortcoming in
impending uses of the AQCD.
D-73
-------
Section 7 should note that resuspension is both an emission source and a transport mechanism
and that resuspension may be one of the largest and most significant emission sources in this
country, although few attempts have been made to quantify this in other than local settings.
Additionally, erosion of contaminated soils and urban runoff are significant transport
mechanisms.
D-74
-------
Dr. Barbara Zielinska
Comments on the EPA NCEA-RTP Air Quality Criteria Document for Lead, Second
External Review Draft
Chapter 2: Chemistry, Sources and Transport of Lead
Barbara Zielinska
Charge Questions for Chapter 2: (a) Overall, does this revised chapter adequately characterize
various important sources ofPb in the environment? (b) Are salient data from EPA and other
sources, in addition to the peer-reviewed literature, now adequately incorporated in this
chapter? (c) Are any further improvements necessary?
Overall, the second draft of Chapter 2 is substantially improved over the first version.
The sources of lead emissions have been partially updated and the newer inventory data
incorporated into the document. However, there are still numerous references throughout the
Section 2.2 (Sources of Lead) that relate to pre-1990 data. These include, for example Table 2-9
that lists the emissions of lead from non-lead metallurgical processes (data published in 1973,
1986 and 1988) or emission factors from Pb mines (page 2-23) and coal combustion (Table 2-12,
data from Pacyna, 1986). It is confusing to the reader which data are current and which are no
longer valid. The main purpose of the criteria document is to present the new information since
the publication of the last AQCD and its Supplement in 1990, thus repeating the old data is not
necessary, it only makes the document longer. If the more recent data are not available, this
should be clearly stated in the text. Since the OAQPS staff paper intends to focus on the current
sources of Pb emissions to ambient air (as described in the Analysis Plan for Human Health and
Ecological Risk Assessment) the information on the most current emission sources is critical.
In addition, Section 2.2 lists many emission data for Europe, without comparing them
with the US data. NAAQS for lead is relevant to the US only, thus the US data should be
emphasized.
Section 2.2.1 concerning natural sources of lead is somewhat confusing. The authors list
the estimated worldwide natural emissions of lead as 12,000 metric ton/year (data from 1989).
The US data are not given, but the authors conclude that the anthropogenic emissions of lead are
expected to be much grated than natural emissions. Since natural emissions may be important in
relation to the background level of lead, more precise information would be useful. This section
also discusses the natural isotopes of lead, radioactive 210Pb, and various forms of lead in water.
It is not clear what is the relevance of this information to the natural sources of lead.
Section 2.2.2 concerning lead emissions in the US was improved by the addition of the
more recent data, however, the data cited in various places in the text are not consistent with
Figures 2.2 and 2.3 that show lead emission sources and rates for 1990 and 2002, respectively.
For example, on page 2-20 it is stated that 14% (or 565 metric tons) of total anthropogenic
emission was due to primary smelting in 2000, whereas Figure 2-3 doesn't show this category at
all. Also, it is difficult to compare the two figures, as the symbols and categories are inconsistent
and the figures are quite busy. Perhaps it would be better to present the data in a table and/or use
D-75
-------
colors for the figures. Some critical evaluation of the emission data presented in this Section is
needed.
Some specific comments:
1. Table 2-3, page 2-6: the formulas for some lead salts are not correct. What is the
difference between anhydrous lead acetate and lead acetate trihydrate, lead carbonate and
basic lead carbonate, as shown? Also, lead iodide is no longer used for cloud seeding,
Agl is used.
2. Section describing solid waste incineration (p. 35-39), states at the opening paragraph
that the incineration of municipal waste is on the decline in the US, but "locally it is still
a concern in some places". Since the next 4 pages discuss the process in detail, it would
be useful to know how important this Pb source is in the US presently.
3. Page 2-45, lines 6-10. Does a reference of Gillies et al (2001) refer to PM or to lead
emissions?
4. Figures 2-6 and 2-7. page 2-64 and 2-65. The concentration units are not correct (either
kg/m2 or kgm"2, but not kg/m"2).
5. Summary section is confusing. Figure 2-8 that shows US consumption of Pb by industry
should be introduced and discussed much earlier, in Section 2.2. The numbers cited in
lines 19-20 do not agree with those in lines 30-31 (p.2-79) and 1-4 (page 2-80). Also,
lines 27-28 (page 2-79) list the largest current emitters as lead-acid battery plants,
smelters, lead-alloy production facility and this is not what Figure 2-3 shows. Page 2-81,
lines 7-10 lists resuspension as the dominant removal mechanism from soil surfaces, but
fails to mention that this is also the most important emissions source (as discussed on
page 2-58).
D-76
-------
Appendix E - CASAC Letter re: NAAQS for Lead
(EPA-SAB-CASAC-90-002) dated January 3,1990)
J I OMlMBIMftMl
of the Air Scientific
Advisory
Of the
and 1m At
E-l
-------
•UNITED •ST*T«'3 I*« JtPPi.«i*nC , At •
4 !, if If, CJUM! r*Vi*,re-,! •: ,
lt*!f
»r-?a
JOB* IX,
tin* to prwpar*
;* ef ir-,e
and defcnaibL*
foi Invinq t3» CASM1
j ri;---i4ir.q the intcrostcd
ItMiCare reach Lr»iT clDH,ir*i.
EPA ELDc-ozcjitn , aioni| vith t -'i^
upflbllj provide a »ci«intif lc* 1 1 y
«sf •S'Jr ccyrar.t JcnawSaiif* of
E-2
-------
Jk, T.n r*t.,iir. ur revis* primary and jsocor-daiy MAHQs
AM past of tnia review pree***-, the CSRaiittw eona-idarvd and
approved tha CAAAC EafptsftiLf* su£eaHkitC44> »*!«* *C *agu»t 19S8-
EPA doeuunt, *nevlou af ch* ^*tt«i*l U&i«rt«, Air Qoaltty
5*po«yr* Jta*ly&lB HcthodQlo^y and
CamaJ.ly ODflitainail in
-------
it
to wa*«kat« %&• »«.5,i«*5,*ii airtr ifcnrfioo of *fr&— ts ee
it * flv*p. l*v#: of .
H5iil« tPn* Ceoaitt** i* willing to fu-r*b*r *dwi*«i yc»« an,
w* p*« »p n«<»i., in
,, to r*vi«ir arY prc-|.«t'*»
izi tt» 7*3*nl Ptgii»t;iir. Tn* p-uaiilc ccmwnt periad CoLl.avi.ifqr
c,a proved* *Jiy »iia,ttlewii <5Ki***pit: or r*wi«w*-r if
of tha. CXaAC CDIS^*J riljiQ Ltc claeiir* oei thi Criteria
3i&d*si&iSM and th.* EPA Staff taftltion Pwpvt ~<"-r ^Irt^rm?
lead. In CQrtftid*rirY£r ths CAJlAC'ii raaoa»ff»dli.t itmm far -ttiA load
it A* Lnpeet«cit to rwp^nLi« %.(Hl. ftitr a* VJ^t ui^u aecre* ot
a cdnc*ft*d effort t-fs r^Jiai.* L*Ad intaJc* iron all mour cas .
»ppr*eint* opportunity to
iafja ar.d fnmr4 ta yauj" to
T « mi «t: iona- .
, r3#*ri Air Scientific
E-4
-------
la th*
af fefc*
«v of tlu KAti«m«i **.*iL«ftr. Air
f*t t***! jL>i««sxb*f!,'C *f
^4t*4 tt«rcJt l*f'i . de»
, with th» CMBltrt** r«*»ct*ir«i
i or tf.n; tfct it&c-JiSM^r.t.* pr^vig* *n *i$»4puit.* *r i wr.t » e fc i-
fswr tf'Jk tc
E-5
-------
t'<**n witt'iai mm part of t*i* »et ivit.l«ii ry Br.*rd. a public fl.'lvlwory eraup
•vtranuroi BciefitiflO lnfot^iitiC4«h find «d<#lc« 1c ti* ft4ainL-trar c B
and ath»« &ttiaLnlm *r tfc* fen*i.!f not ?i
and palld*« of t,»%« EnvironiMnt*A
ia t^.* rc-i«r*'. sen?*rmwoit« Hcr-i:Son of 1 rn-lfi nniea ut
v .-Fit«rc: J» 1 pirrifbct-a lSo4i« net aorntlCutv a rweosMmln-t Ian for
E-6
-------
0,1* Etwlrarjeantal
Clu
r ft. wcC!ellafe«, t~!i*bi-$*£ imftMtry En*biturt* of Tax L ro
fork, DBiwiriity X*dLGil Cssut^r,
of t.-T.-irznawr.tal M(t»:J icir.«r |f*w ifcric, K
-------
Sr ft, R»rtft* »i*leglc»!
Or, Mire 1, fehenM*?* . Occuput 1 on* 1 and, EnviratHHtntAl Mtaltb. Unit,
it >' e>f Call Corn la, S
If4irhi •? . U^:**.*.*, i*Jl,K;««irf 5L»«***» t^it,, CTiiv»r»itif of
SiBrea.?! V*L>>ii. JL vision, of T,ii .c^-iiiy-- D*J*tr* wwt of
ScfcDD-1 of Mi-'licinB, rr.iv*rPat,y of RzchcHt-r, Rachastar;,
Vork
J.
«af flw^ttJi,, ®&T"x*lmyJ, ct 1 1 Sea
T.
?»
StJIi tilt raff y
Mr, At Robert Fl*»k, noBlgziitfifd P»d»rsi, Offiei»i,
(A-ldiP| . U.S*
"-*, St*ff
jA-lOLF'ij U.S. Ir.virocaint.al trip*" »st ion jyj«ncy,
CC 204IB
-------
cf
CLt&Jf *;p sczfifTiriC
CF IT* XZVICW Sf
waitr* *.;* ar-AJ-m »TApDMiai mm.
CASAG OM Till Ifit All QgfcLJTT
Mil? tit* NktH
* -py*l.ie
Iwld on April IT, lllf, CAJAC ravi*wed
IP* Air Criteria Dac«JB»nt ypnt»t«r tt i : r -n i ^ nr n t ft 3,
CritMil. fat LMd - vcluaa 1
of fie* af Air Quality Planakn? in4 Stdp^1*raii
pyip«r BjtViatf gg tha national Agfalant Air Qja^
for 'Mmtii A.g»»g.«agnt of a-s
ef
aur
of
ill . •
to
to
ii^» of
r
»n»tk
of
In
| f s d ifA
fci * A«TI .
St.aiidana«
far
not.
tlic
ot
;,» 4 J,
it.AHj.aci* ,
if
cf *5 o
-i for all
rte Ceaaitt** crncl i:a#d thut
on air
vlth fclood
ihie cDnci'j»icln, tb*
far
*t i«w«
value for blcod l«ad faat£li*di uLt lf.at*l y to
th« CdBBitt** cnphasiiel tJii inport-anc* of nlw*y
that to-lucid lend It vela and h.g-alth Huur** BE*
Av a diJtrJlmtien of vilue* Jifcitmt MW or
tli* ilpCrtinc* Of ecal*lilltlnf drlfltributiwi of
t.h* mattH -r xedian ia -apparent- f r-?a -"anaLdaratlasi at
, nrLu«n/-4 of l*-*d *l^€idlUf« eft l.-Q. A t«lMAfly d*cr*ai» :r.
tha a«dii ur midica waliai for I,Q. iiay £«-«l,,t In «1 pi If IBM!;
In
and
a
l«v«i]
E-9
-------
at tt*
of th» diiitjr L hut ion vltli fee til t reduction In
cut ; ton fl-Q, > 12SJ uid «n |,r^¥*a«* la
In
ft Wtxxl
ten] it- la-
thm
lr
rr.it
. , 4.1* e^npd, *»*?«r, •!»!! *n?i paint
§r« all c-cwtc il*«ter» to trtal Lwid lat-aka* Aahluvinq m taif«t
° ill r«quiz* An ici* p-ji at*d appiroAc
for »11 rput*i oC erp^wiiJfA, fiot Juat
.it t. * it ««h*ilE«d that A»ii«tii«Mint of ri*kj§
I»t4 blood i
Ln *ir.
aal
or,ly I
y an tli« ai,r !**d
Ln ;•«
Is UriAtrfOlrtf lt« o&if
li-ipainaer.ii
,. tH4 rnNtlttv* cadciir«
AlU.lt p£i £ .1 : a r .
in ti« at,*Ef
a-w^i b*n»fici«l fti
-z at :
v soups du*
tta
Mt
fvtal
-.nildren
f*y» la logi
to
to
In
at
In
iMlQW^ q-iBTst i t Atl V*
%«i»r« not done fdr
CL-TIT. Ittena fizida tJiat t h* a*thcdaioq-iBa ipp', !».J ir,
•t,aff paper &••« ntiMy analynis on yo'-ifig ctalldf^A wit i-J"--^ •#?;
pyat*srcioai at
u««rui ITS
eati«ateis
In »iWlt.lan,
of
wist s
provide BJI
lt«oni!tl
-s!K9«r.iag
should her? to* n
»t
Out*
tn
rg Srs of amfety for
a* natwi by th* CMJUC
*r» not
lack of
a£
aorwt
-------
EPA Stiff f*c.--ma*i''.d*.;3 in tb» ft*ff
tli'* L*ad MUU39 IMI dipt••*•*! ** • •onfjliiy tt,Jir..lird, i.r< tf",« :*,-Kia - r
0.5 fea i.s wfi/ii'1 rxrt to to* *k«*«liM9 »fif* ttyin anc* in «**•»• y»»r*.
rii« ^.-.UBlCt** ,:or*.".ir» wlt*i ti"»# CPA SCAff "T*C«-i«*#f,.l*iE, I->fi t,i»
dfl «
Us*
sf
£X;fu,!.*l- ,OP 9C«M^« f»t vtifc-ll,
it«lr, Lv« *icp Finally, i.h» Cowiitt«« mws&axm wttft UIA flt*rr
«*Mpl*rfi b* pursittftd Ln
** III* hl
l«-id lull no
*^tiv*ly pVirHU* fl puillic htf«l,£k,
E-ll
-------
tint l**a aantap* of blood ta tlw *srt»i»t ptM«ibl«
r*c- qnia Ln^i flat AB a DfttarBlly BuiCtixirli*! *i**in-E, Ltad #iL| !:••
IB «
»,
of A. «tr«togy for guefei lowing th* fa*l
far i**d try ll,iwlf i* rat «ufx icrlcat to ac-ht^B tJ",*
E-12
-------
NOTICE
This report has been written as part of the activities of the U.S. Environmental Protection
Agency's (EPA) Clean Air Scientific Advisory Committee (CASAC), a Federal advisory committee
administratively located under the EPA Science Advisory Board (SAB) Staff Office that is chartered to
provide extramural scientific information and advice to the Administrator and other officials of the
EPA. The CASAC is structured to provide balanced, expert assessment of scientific matters related to
issue and problems facing the Agency. This report has not been reviewed for approval by the Agency
and, hence, the contents of this report do not necessarily represent the views and policies of the EPA,
nor of other agencies in the Executive Branch of the Federal government, nor does mention of trade
names or commercial products constitute a recommendation for use. CASAC reports are posted on the
SAB Web site at: http://www.epa.gov/sab.
E-13
------- |