P.1 

OAR Box 1111 

Prepped by RyanDugan 

Document Number: 

1£5)ll-A-1a 

-t&±? 

Docket Number: 

A-83-22 

Printed 4/15/2008 1:25:18 PM Sheet 105 of 118 
P.2 

REVIEW OF THE NATIONAL AMBIENT AIR QUALITY STANDARDS FOR LEAD: 

ASSESSMENT OF SCIENTIFIC AND TECHNICAL INFORMATION 

OAQPS DRAFT STAFF PAPER 

Strategies and Air Standards Division 

Office of Air Quality Planning and Standards 

U.S. Environmental Protection Agency 

Research Triangle Park, N.C. 27711 

April, 1985 
P.3 

11 

This document is an OAQPS staff draft that is being 

circulated for technical review and comment. It has not 

been fully reviewed within EPA and does not represent 

Agency policy. 
P.4 

111 

TABLE OF CONTENTS 

Page 

List of Figures v 

List of Tables vi 

I . Purpose 1-1 

II . Background II-l 

III . Approach III-l 

IV. Lead Exposure: Multimedia Considerations IV-1 

A. Airborne Lead IV-3 

B. Lead in Soil I V-6 

C. Lead in Dust I V-8 

D. Lead in the Diet I V-10 

E. Lead in Water I V-12 

V. Estimating Lead Exposure and Blood Lead Levels V-l 

A. Integrated Lead Uptake/Metabolic Model V-2 

B. Statistical Relationships between Blood Lead and 

Airborne Lead V-10 

V I . Critical Elements in the Review of the Primary Standard . . . VI-1 

A. Mechanisms of Toxicity VI-1 

B. Effects of Concern VI-5 

C. Sensitive Population Groups VI-6 

VII. Factors to be Considered in Selecting a Primary Standard 

for Lead VII-1 

A. Averaging Time VII-1 

B. Form of the Standard VII-7 

C. Level of the Standard VII-9 

D. Summary of Staff Conclusions and Recommendations VII-50 
PJ5 

IV 

VIII. Critical Elements in the Review of the Secondary Standard. 

A. Terrestrial Ecosystems 

B. Aquatic Ecosystems , 

C. Staff Conclusions and Recommendations 

Appendix A. Lead Metabolism and Physiological Measurement. .. . 

Appendix B. Estimates of Lead Uptake 

Appendix C. Lead Uptake and Blood Lead Concentrations 

Appendix D. Health Effects of Lead 

References 

Page 

VIII 

VIII 

VIII* 

VIII* 

A-1 

B-l 

C-l 

D-l 

-1 

-1 

-12 

-14 
P.6 

V 

LI ST "OF FIGURES 

Number Title Page 

4-1 Principal Pathways of Human Exposure to Lead IV-2 

4-2 Trends in Maximum Quarterly Lead Concentration for 

Various Monitor Types IV-5 

5-1 Summary of Relationships Between Lead Uptake and 

Blood Lead V-8 

C-l Relationship Between Daily Lead Uptake and Blood Lead 

in Adult Men C-3 

C-2 Schematic Models of Lead Metabolism in Adult Men C-5 

D-l Lead Effects on Heme Biosynthesis D-2 
P.7 

VI 

LIST OF TABLES 

Number Title Page 

4-1 Typical Lead Concentrations in Various Exposure Media ... . IV-2 

4-2 Frequency Distributions of Maximum Quarterly Lead 

Concentrations by Type of Site I V-5 

5-1 Model Balance Schemes for Average Lead Intake and Uptake 

in Children Under Alternative Air Lead Levels V-4 

5-2 Summary of Experimental Lead Inhalation Studies V-11 

5-3 Summary of Epidemiological Studies on Lead-Exposed Children . V-18 

5-4 Blood Lead/Air Lead Slopes in Children for Different Ages 

and Exposures V-20 

7-1 Monthly-to-Quarterly Average Concentration Ratios for 

Different Sites VII-5 

7-2 Summary of Lowest Observed Effect Levels for Key LeadInduced Health Effects in Children VII-10 

7-3 Summary of Lead's Effects on the Nervous System VII-12 

7-4 Summary of Lead's Effects on Heme Biosynthesis and 

Related Systems in Children VII-17 

7-5 Staff Assessment of Key Health Effects of Lead VII-22 

7-6 Population Mean Blood Lead Levels Required to Prevent 99.5% 

of Children from Exceeding Specified Blood Lead Levels . . . VII-28 

7-7 Average Blood Lead Levels for Children Under Different 

Air Lead Levels Estimated Using Integrated Lead Uptake/ 

Biokinetic Model VII-29 

7-8 Air Lead Levels Required to Protect 99.5% of Children from 

Exceeding Alternative Maximum Acceptable Blood Lead Levels, 

According to Aggregate Epidemiological Model; GSD for 

Population Assumed to be 1 .39 VII-37 

7-9 Air Lead Levels Required to Protect 99.5% of Children from 

Exceeding Alternative Maximum Acceptable Blood Lead Levels, 

According to Aggregate Epidemiological Model; GSD for 

Population Assumed to be 1.34 .. . .- VII-37 

7-10 Contributions from Various Media to Blood Lead Levels of U.S. 

Children (CD Disaggregate Model) VII-39 
P.8 

VII 

Page 

7-11 Maximum Individual Blood Lead Levels for 99.5% of Children 

Under Different Air Lead Levels, Based on Mean PbB Predictions 

from CD Disaggregate Model VII-41 

7-12 Summary of Estimated Blood Lead Levels Under Different Air Lead 

Levels Using Three Modeling Approaches VII-42 

7-13 Results of Logistic Regression Analysis of NHANES II Data . . . VII-48 

7-14 Population Mean Blood Lead Levels Required to Prevent 99.5% 

of U.S. Children from Exceeding Specified Blood Lead Levels 

Estimated from Alternate Techniques VII-48 

8-1 Lead-Induced Effects in Hydroponically Grown Vascular Plants . . VI11 -5 

8-2 Experimental Evidence of Lead-Induced Effects Relating to 

Soil Microbial Activity VIII-8 

8-3 Effects of Waterborne Lead in Aquatic Vertebrates (Fish) ... . VIII-15 

B-l Summary of Environmental Lead Measurements from Various 

Locations B-7 

B-2 Generalized Relationships Between Lead Concentrations in 

Air and in Dusts and Soil B-10 

C-2 Predicted Equilibrated Blood Lead Levels Over Time Among 

Children with Constant Lead Uptakes C-9 

C-3 Studies Relating Blood Lead Levels to Dietary Intakes C-ll 

C-4 Estimates of the Contribution of Soil Lead to Blood Lead ... . C-12 

C-5 Estimates of the Contribution of Housedust to Blood Lead 

in Children C-12 
P.9 

REVIEW OF THE NATIONAL AMBIENT AIR QUALITY STANDARDS FOR LEAD: 

ASSESSMENT OF SCIENTIFIC AND TECHNICAL INFORMATION 

OAQPS STAFF PAPER 

I. PURPOSE 

This paper evaluates and interprets the most relevant scientific 

and technical information reviewed in the draft EPA document "Air Quality 

Criteria for Lead" (EPA, 1984) in order to better specify the critical 

elements that EPA staff believes should be considered in the possible 

revision of the primary and secondary National Ambient Air Quality Standards 

(NAAQS) for lead. This assessment is intended to help bridge the gap 

between the scientific review contained in the criteria document and the 

judgments required of the Administrator in setting ambient standards for 

lead. As such, particular emphasis is placed on identifying those conclusions 

and uncertainties in the available scientific literature that the staff 

believes should be considered in selecting the averaging times, forms, and 

levels for the primary and secondary standards. While the paper should be 

of use to all parties interested in the standards review, it is written 

for those decision makers, scientists, and staff who have some familiarity 

with the technical discussions contained in the criteria document (hereafter 

referenced as "CD"). 

II. BACKGROUND 

Since 1970 the Clean Air Act, as amended, has provided authority 

and guidance for the listing of certain ambient air pollutants that may 

endanger public health or welfare and the setting and revising of NAAQS 

for those pollutants. Primary standards must be based on health effects 
P.10 

11*. 2 

criteria and provide an adequate margin of safety to ensure protection 

of public health. As several recent judicial decisions have made clear, 

the economic and technological feasibility of attaining primary standards 

are not to be considered in setting them, although such factors may be 

considered to a degree in the development of state plans to implement the 

standards (D.C. Cir., 1980, 1981). Further guidance provided in the 

legislative history of the Act indicates that the standards should be set 

at "the maximum permissible ambient air level . . . which will protect 

the health of any [sensitive] group of the population." Also, margins of 

safety are to be provided such that the standards will afford "a reasonable 

degree of protection . . . against hazards which research has not yet 

identified" (Committee on Public Works, 1974). In the final analysis, 

the EPA Administrator must make a policy decision in setting the primary 

standard, based on his judgment regarding the implications of all the 

health effects evidence and on the requirement that an adequate margin of 

safety be provided. 

Secondary ambient air quality standards must be adequate to protect 

the public welfare from any known or anticipated adverse effects 

associated with the presence of a listed ambient air pollutant. Welfare 

effects, which are defined in section 302(h) of the Act, include effects 

on vegetation, visibility, water, crops, man-made materials, animals, 

economic values and personal comfort and well-being. In specifying a 

level or levels for secondary standards the Administrator must determine 

at which point the effects become "adverse" and base his judgment on the 

welfare effects criteria. 

The current primary standard for lead (to protect public health) is 

1.5 micrograms per cubic meter (ug/m^), maximum arithmetic mean 
P.11 

III-l 

averaged over a calendar quarter. The current secondary standard for 

lead (to protect public welfare) is identical to the primary standard. 

For both primary and secondary standards, lead and its compounds are 

measured as elemental lead and collected using a high volume air sampler. 

In addition to the lead NAAQS, several other federal regulations have 

been adopted in order to control human exposures to lead. These include 

EPA's schedule for the phased reduction of the allowable lead content in 

gasoline and the national primary drinking water standard for lead (50 pg/ 

liter), as well as the Department of Housing and Urban Development's 

goals to eliminate lead-based paint hazards in federally-funded housing, 

the Food and Drug Administration's regulations on the lead content of 

foods and ceramic products, the Consumer Product Safety Commission's 

limit on lead content in paints, toys, and furniture, and the Occupational 

Safety and Health Administration's standards for occupational exposure to 

lead. In addition, the Centers for Disease Control have established 

criteria for health classification of children screened by lead poisoning 

prevention programs. 

III. APPROACH 

The approach used in this paper is to assess and integrate information 

derived from the criteria review in the context of those critical elements that the staff believes should be considered in the review of the 

primary and secondary standards. Particular attention is drawn to those 

judgments that must be based on the careful interpretation of incomplete 

or uncertain evidence. In such instances, the paper states the staff's 

evaluation of the evidence as it relates to a specific judgment, sets 

forth appropriate alternatives that should be considered, and recommends 

a course of action. 
P.12 

III-2 

The principal focus of this paper is on the effects of inorganic 

lead either airborne or deposited from the air onto dusts, soils, vegetation, 

food, and water. The impact that lead from non-atmospheric sources, such 

as paint and solder, has on human exposure is also considered. The 

effects of organic lead vapors which are not commonly found in the atmosphere 

(see Section I V.A) will not be addressed. 

Section IV presents relevant features of human exposure to atmospheric 

and non-atmospheric sources of lead through various pathways. Section V 

presents different approaches to estimate the impact of alternative air lead 

levels on lead body burdens as indicated by blood lead levels. Section 

VI addresses other essential elements with regard to the primary standards; 

these include the following: 

1) identification of possible mechanisms of toxicity; 

2) description of health effects and their relation to exposure levels; 

and 

3) identification of the most sensitive population groups; 

Drawing from the analyses in Sections IV, V, and VI of the criteria 

document information, and the associated appendices, Section VII identifies 

and assesses the factors the staff believes should be considered in selecting 

an averaging time, form, and level of the primary standard. Selecting an 

appropriate standard level includes a determination of an acceptable blood 

lead level and the impact a given air standard would have on the distribution of 

blood lead levels in the population of concern. Preliminary staff conclusions 

regarding alternative policy options in each of these areas are also presented. 

Section VIII contains an examination of information in the criteria 

document the staff believes is most relevant with respect to the secondary 

standard. This discussion includes: 
P.13 

III-3 

1) identification of the levels at which lead-induced changes in 

terrestrial and aquatic ecosystems have been demonstrated; 

2) assessment of the available data base (laboratory and field studies) 

to identify quantitative relationships necessary for the prediction of 

environmental impact; and 

3) preliminary staff recommendations concerning a secondary standard. 
P.14 

IV. LEAD EXPOSURE: MULTIMEDIA CONSIDERATIONS 

In order to assess the risks associated with alternate lead NAAQS, 

it is necessary to understand the influence exerted by atmospheric lead on 

the total lead exposure of the population(s) of concern through the various 

exposure pathways. Relevant data on these pathways and the relationships 

between air lead and lead in other media are summarized in this section. 

Section V presents methodologies to estimate blood lead levels associated 

with alternative air lead levels. 

The sources and pathways of human lead exposure are diagrammed in 

Figure 4-1 and typical levels of lead in different media to which U.S. 

populations are exposed are presented in Table 4-1. Between 85-90% of 

airborne lead in the U.S. originates from gasoline combustion with the 

remainder from stationary industrial processes such as primary and secondary 

lead smelting, battery plants, lead alkyl production, iron and steel production, ore pulverizing, copper smelting, and combustion of oil, coal, and 

waste oil. Atmospheric emissions can influence human exposure through 

direct inhalation of lead-containing particles and through ingestion of 

lead which deposits onto soil, dusts, vegetation, and other environmental 

surfaces. This deposition can occur by either or both of two mechanisms: 

1) continuous dry deposition due to various mechanisms which may include 

gravitational settling or wind-related deposition; and 2) episodic wet 

depostion due to either washout of coarse mode particles (>2.5 micrometers 

in diameter) which are found mainly near emission sources, or the "rainout" 

(precipitation scavenging) of smaller particles which are more widely 

dispersed. Human exposure to lead can also be traced to lead in paint 

pigments and solder in canned foods and plumbing. 
P.15 

IV-2 

SURFACE ANO 

GROUND WATER 

MAN 

Figure 4-1. Principal pathways of human exposure to lead. Heavy arrows are those 

pathways discussed in greatest detail. From CD, Figure 7-1. 

Table 4-1. Typical Lead Concentrations in Various Exposure Media 

Medium 

Ambient Air (ug/m3)b 

I ndoor Ai r (ug/m3)c 

Soil (ppm) 

Street Oust (ppm)d 

House Dust (ppm)d 

Typical Foods (ppm) 

Water (pg/1 ) 

Painte 

Rural Area 

0.01 - 0.3 

0.003 - 0.2 

5 - 30 

80 - 130 

(90) 

50 - 500 

(300) 

0.002 - 0.98 

<1 - 180 pg/1 

<1 - >5 mg/cm2 

Urban Area 

0.03 - 4.4 

0.01 - 0.4 

30 - 4500 

100 - 5,000 

(1500) 

50 - 3,000 

(1000) 

Same 

Same 

Same 

Near Point Source(s)a 

0.2 - 10.2 

0.07 - 3.1 

150 - 15,000 

(25,000) 

70 - 100,000 

(25,000) 

Same 

Same 

Same 

References 

Tyler, 1984; Yarn, 

1984 

Yocum, 1982; Cohen and 

Cohen, 1980; Rabinowitz 

et al., 1984b 

CD, Table 7-11; Mielke 

et al .; 1983; See Tables 

C-l and C-2 

Nriagu, 1978; CD, 

Table 7-26 

U.S. EPA, 1977; 

Landrigan et al., 1975 

Angle and Mclntire (1 _>7y) 

CD, Table 7D-1 

Sharrett et al., 1982; 

EPA, 1985a 

Billick and Gray, 1978 

aWithin 2-5 km of sources including primary and secondary lead smelters, battery plants. 

^Represents quarterly averages monitored between July 1982 and July 1984. 

cRange of indoor/outdoor ratios used (0.3 - 0.8) from Yocum, 1982 except near point sources where large particles predominate and infiltration into homes is low, ratio appears to be closer to 0.3 (Cohen and Cohen, 1980). 

^Values in parentheses represent estimates provided in CD (Tables 7-24 and 7-26) as typical averages. 

eSince there may be several layers of lead-based paint on a given surface, absolute concentration of lead is less 

useful than mg/cm2. Surveys by HUD in Pittsburgh showed that more than 70% of pre-1940 dwelling units and 20% of post1960 units had at least one surface with more than 1.5 mg/cm2 lead paint (NAS, 1980). 
P.16 

IV-3 

A. Airborne Lead 

1. Physical, Chemical and Spatial Characteristics 

In general, about 50% of automotive lead emissions deposits within a 

few hundred meters of major roadways (Daines et al., 1970; Huntzicker et 

al., 1975; Ingalls and Garbe, 1982) while the remaining particles are small 

enough to remain airborne and travel hundreds or thousands of kilometers. 

This likely accounts for the surface contamination of polar glaciers, 

oceans, and other remote locations around the globe (Murozomi et al., 1969; 

Duce et al., 1975; Davidson et al., 1981b,c, 1982; Settle and Patterson, 

1982). In general, U.S. urban and rural airborne lead particles have a 

mass median aerodynamic diameter* (MMAD) consistently between 0.3 and 0.7 

micrometers (pm) with most of the mass associated with submicron particles, 

although a distinct peak is seen in the upper end of many of the particle 

size distributions between 5 and 10 pm (Davidson and Osborn, 1984). 

Inorganic lead is emitted from automobiles as lead halides, hydroxides, 

and oxides and reacts with atmospheric ammonia and acid sulfates to form 

principally lead sulfate (e.g., [NH ^ SO^'PbSO^) with minor amounts of lead 

carbonates and halides remaining (Habibi, 1970; Ter Haar and Bayard, 1971; 

Dzubay and Stevens, 1973; Biggins and Harrison, 1978, 1979). Small amounts 

of lead additives used in gasoline (tetraethyl- and tetramethyl-lead) may 

escape to the atmosphere by evaporation from fuel systems or storage facilities. 

Relatively low concentrations of these organic lead compounds have been 

typically found in atmospheric samples (1 - 6% of total lead) except in 

special situations such as gasoline stations or garages (Skogerboe, 1975; 

Harrison et al., 1979). Because these organic lead compounds decompose by 

*MMAD is used as an indicator of particle size of a lognormally distributed 

aerosol such that half the mass lies on either side of the MMAD. 
P.17 

IV-4 

photoreaction (Huntzicker et al., 1975) and are readily adsorbed onto 

atmospheric particles (Edwards et al., 1975), their presence in the 

atmosphere is transitory. Therefore, any health hazards associated with 

organic lead exposure are most likely to occur in an occupational setting 

and will not be assessed here. 

In contrast to automobile exhaust, atmospheric lead emissions from 

industrial plants processing lead and its products contribute little to the 

overall pollution load across large, regional areas although fallout from 

these sources can be severe on a local scale. The high concentration levels 

which are found around lead smelters in particular result mainly from 

fugitive emissions predominately made up of large (>7 pm) lead particles 

resulting from materials handling, furnace upsets, and furnace charging 

and tapping operations (Landrigan et al., 1975; Jennett et al., 1977; 

GCA, 1984). Beyond the immediate area (0.25-1 km) of lead stationary 

sources, process emissions from stacks, predominately as lead sulfates 

and oxides with a size range between 2 and 10 pm, become the major 

source of lead in soils and air near these sources (Dorn et al., 1976; 

Roels et al., 1980; Davidson and Osborn, 1984). 

2. Ambient Concentrations 

As indicated in the CD (Section 7.2.1), lead levels in urban areas 

and near point sources have been markedly reduced since 1977 by the use 

of unleaded gasoline in new cars equipped with catalytic converters, the 

lead-in-gasoline phasedown program, and steady reductions in emissions 

from all types of industrial and commercial sources in compliance with the 

1978 lead NAAQS. Recent (1980-1983) air quality data for 414 stationary source 

sites, micro-scale roadside sites, middle scale roadside sites, neighborhood 

scale roadside sites, and other non-classified sites are summarized in Table 

4-2 (Battye, 1985). The monitoring sites located near stationary sources 
P.18 

IV-5 

Table 4-2. FREQUENCY DISTRIBUTIONS OF MAXIMUM QUARTERLY LEAD CONCENTRATIONS BY TYPE OF SITE* 

Site type/time frame 

1980 through 1983 

All monitors0 

Stationary source 

Microscale roadside'*' 

Middle scale 

Neighborhood scale 

1983 only 

All monitors0 

Statlonary source 

Microscale roads1ded 

Middle scale 

Neighborhood scale 

Percent 

<0.5 

69 

62 

17 

39 

61 

71 

53 

16 

53 

72 

of site 

0.5-1.0 

22 

16 

40 

42 

32 

19 

24 

47 

33 

28 

years in 

1.0-1. 

5 

8 

27 

18 

5 

5 

9 

32 

13 

0 

concentration 

5 1.5-2.0 

2 

3 

13 

0 

0 

1 

2 

5 

0 

0 

ranges0 

>2.0 

2 

11 

3 

0 

2 

3 

11 

0 

0 

0 

Mean 

0.53 

0.95 

0.99 

0.68 

0.51 

0.51 

0.88 

0.83 

0.60 

0.40 

Total 

siteyears 

1189 

159 

30 

33 

62 

360 

45 

19 

15 

29 

Total 

number 

of sites 

414 

56 

18 

15 

29 

360 

45 

19 

15 

29 

aData are from the SAROAD system and represent the numbers of site-years for which the maximum quarterly concentrations 

fall within the designated concentration ranges. To be included, a site-year must have four valid quarters of data. 

•""Concentration ranges are 1n units of ug/m3. 

•"•Includes sites previously classified into categories (e.g., urban) that do not meet any of the current definitions. 

•"•Microscale sites are within 5-15 meters from a major roadway and 2-7 meters above the ground. 

Source: Battye, 1984 

P 

_*> 

'"' 

cy 

cj 

-— i 

ri*. .'ARTE 

O 

*•*=: 

^? 

T-T"' 

"2 

§ 

1 .9 

1 .8 

1 .7 

1 .6 

1 .5 

1 .4-

1 .3 

1 .2 

1 ,1 

1 ,0 

O.9 

0.8 

0.7 

0.6 

0.5 

0.4-

0.5 

0.2 -

0,1 -

MICROSCALE 

\ 

+- \ 

STATIONARY "SOURCES 

^ > 

\ 

--*>-. 

...MElG.yeOFLHOOD SCALE •IIDDLc buALEs*.... 

ALL MONlTT_>R**£>^ _^ -V*^ . 

1980 1981 1982 T5iT 

Year 

Figure 4-2. Trends in maximum quarterly lead concentration for 

various monitor types. Source: Battye,1984 
P.19 

IV-6 

and major roadways (i.e., microscale) reported the majority of concentrations 

over 1.5 ug/m^. Only one population-oriented or neighborhood site had a 

quarterly average greater than 1.5 ug/m*-* between 1980 and 1983, whereas 

14% and 16% of quarterly averages in source-oriented and microscale site-years, 

respectively, exceeded this value. 

Trends in maximum quarterly averages between 1980 and 1983 are illustrated 

in Figure 4-2. Because of recent changes in lead monitor siting guidelines, 

the lead monitor network currently is being expanded and changed. In order 

to avoid biases relating to changes in the monitoring network, the trends 

analysis included only sites where valid data were available for three of the 

four years studied (Battye, 1985a). It should be noted, therefore, that these 

trends data, with the exception of those for "all" monitoring sites which 

include currently unclassified site-types, are based on a limited number of 

available monitoring sites that remained in service since 1980 (e.g., 27 

stationary source sites, 9 neighborhood scale sites). Despite the new 

siting guidelines implemented in 1982 that added sites closer to traffic 

emissions, microscale readings have been declining, corresponding to the 

phasedown of the lead content in gasoline and reductions in leaded gasoline 

usage due to the gradual phase-out of older lead-burning cars. Similarly, 

annual and maximum quarterly average lead levels near point sources have 

also decreased since 1980, partly due to increased controls by lead-emitting 

sources in compliance with state implementation plans as well as to decreased 

industrial production at lead-emitting facilities (Silvasi, 1985). 

B. Lead in Soil 

The natural occurrence of lead in the earth's crust averages 

5-50 pg lead/g soil [one ug/g is equivalent to one part per million or 

1 ppm] lead in various soils (Shacklette et al., 1971; McKeague and Wolynetz, 

1980). Much of the lead in the atmosphere deposits on terrestrial surfaces 
P.20 

IV -7 

where it is retained in organic complexes near the soil surface (CD, p. 

7-28). The ability of soil to immobilize lead largely depends on soil pH 

and organic content (i.e., fulvic and humic substances). Many U.S. soils 

appear to have a large capacity to bind lead with only a small fraction 

dissolved in soil moisture where it is available for plant uptake (see 

Section VIII). The environmental impact of lead on the biota of terrestrial 

and aquatic ecosystems is discussed in Section VIII. 

The upper layer of roadside soils may contain atmospheric lead from 

30 to 2000 ppm in excess of natural levels within 25 meters of the roadbed 

beyond which concentrations decline abruptly in relation to traffic density 

and vehicle speed (Page and Ganje, 1970; Quarles et al, 1974; Wheeler and 

Rolfe, 1979; Pierson and Brachaczek, 1976). In contrast, soil lead concentrations 

around various lead point sources generally decrease exponentially within 

a 3-10 km radius from 100-60,000 ppm down to background levels (CD, Appendix 

7-C). However, elevated soil lead levels have even been found at distances 

exceeding 20-25 km from some smelters (Wixson, 1978). Limited data indicate 

that lead in soil near primary and secondary lead smelters occurs as lead 

oxides, sulfide, sulfate, and elemental lead (Olson and Skogerboe, 1975; 

Corrin and Natusch, 1977). 

Urban soils are contaminated by lead from a combination of automotive 

and point source deposition as well as from paint chips from indoor and 

outdoor surfaces. Elevated soil concentrations (as high as 2000 ppm) 

have been found within 10 feet of wood frame houses painted with lead-based 

paint (Ter Haar and Aronow, 1974). Accumulations of lead in soils (and 

dusts) around brick or stone structures have also been found, and can be 

partially attributed to washoff lead collected on roofs, ledges, and exterior 

walls (Wheeler and Rolfe, 1979). Vegetable garden soil samples collected 
P.21 

IV-8 

in a 30-mile radius of downtown Baltimore had lead levels up to 10,900 ppm 

with a median value of 100 ppm (Mielke et al., 1983). Much of this lead 

was attributed to automotive exhaust and industrial emissions because of 

the near absence of lead painted houses and the clustered pattern of lead 

levels around downtown. Soil lead concentrations in a sample of city parks 

have also been reported to be quite high, ranging from 200 to 3300 ppm 

(Chow et al., 1975; Zimdahl and Hassett, 1977). 

The contribution that lead in soil can make to total lead exposure 

under alternative air lead levels is addressed in the modeling approaches 

presented in Section V. 

C. Lead in Dust 

Dust is a normal component of the home (i.e., "house dust") as well as 

the outdoor environment where it can be found on sidewalks, playgrounds, 

driveways, and other hard surfaces. Anthropogenic materials deposited on 

these outdoor surfaces will be referred to as "street dusts". In addition, 

the very top layer of soils (including leaf litter) to which people, particlarly 

children, come in direct contact, are considered in the criteria document 

to be "soil dusts". 

Both house dust and street/soil dust contain lead from atmospheric 

deposition, "natural" soil, and paint chips. As with roadside soil, significant 

correlations between lead concentrations in street dust and the proximity 

and density of traffic have been found (Rolfe et al., 1977; Lau and Wong, 

1982). As summarized by Nriagu (1978), street dusts from different U.S. 

cities contained between 300 and 18,000 ppm lead. A survey of street dusts 

in 77 midwestern cities showed an average lead content of 1,636 ppm in 

residential neighborhoods and 2,413 ppm in commercial and industrial areas 

(NAS, 1980). Limited chemical analyses of roadside soils and dusts from 
P.22 

IV-9 

U.S. cities found lead predominately as sulfate, along with minor amounts 

of oxide and halide salts (Olson and Skogerboe, 1975; Corrin and Natusch, 

1977). Gutter debris in Dearborn, Michigan contained mostly large lead 

particles ranging between 40 and 1000 pm (Pierson and Brachaczek, 1976). 

Airborne lead deposited on streets, sidewalks and driveways is subject 

to further distribution by wind and water. Windblown particles associated 

with dust are apt to be redeposited within the urban environment because of 

the complex wind currents caused by buildings and street canyons. There is 

somewhat conflicting evidence on the persistence of lead in street dust. 

Laxen and Harrison (1977) found that only a light rainfall (2 to 3 mm) is 

sufficient to remove 90 percent of the lead from the road surface, mainly 

to surrounding soil and to waterways. A survey of rainwashed areas in the 

U.K. and New Zealand concluded, however, that the acidity of rain (pH between 

4 and 5) was insufficient to completely dissolve and transport lead particles, 

and that residue near streets pose a health hazard to children who are 

prone to ingest street dusts (Day et al., 1979). The rate of removal of 

lead from dusts is also dependent on the frequency and efficiency of street 

cleaning operations. In the absence of empirical data regarding this 

mechanism, it i.s reasonable to assume that lead concentrations in urban 

street, curb, and sidewalk dust will rise between precipitation and street 

cleaning episodes, and drop thereafter. 

Lead levels in house dust can be expected to vary considerably depending 

on house cleaning practices, the presence and condition of lead-based 

paint, the presence of cigarette smoke, the amount of dust and soil blown 

into or carried into the house on clothing and shoes, (especially on those 

occupationally exposed to lead), indoor sources of lead other than paint 

(e.g., soldering), the permeability of the home to outdoor air (which can 
P.23 

IVrlO 

vary with season), and the outdoor concentrations of air lead. Surveys of 

a diverse set of homes indicate a wide range of house dust lead levels 

between 18 and 16,000 ppm (EPA, 1977; Harrison, 1979; Angle and Mclntire, 1979) 

and as high as 100,000 ppm within 2 km of smelter (Landrigan et al., 1975). 

It is well established that children who play in dust and soil, especially 

in urban areas and on sites polluted by long-term fallout from industrial 

emissions, ingest lead in these media through normal mouthing behavior. 

Significant correlations have been found between blood lead levels and lead 

in soil, household and street dusts, and on children's hands (Lepow et al., 

1975; Sayre et al., 1974; Angle and Mclntire, 1982; Quah et al., 1982; 

Brunekreef et al., 1983). 

In order to assess the impact of atmospheric lead on children's total 

exposure, it is necessary to estimate the contributions of different air lead 

levels to outdoor and indoor soil/dust lead levels as well as the amount 

of dirt a child may ingest, both inadvertantly and deliberately. These 

issues are addressed in the modeling approaches presented in Section V. 

D. Lead in the Diet 

The ingestion of food appears to be a major component of most individuals' 

total lead uptake, although the exact amount is a function of the size and 

type of diet. The occurrence of lead in the diet may be a result of a) natural 

sources of lead; b) deposition of airborne lead particles onto vegetation, 

soils, and water; and c) the harvesting, processing, transportation, packaging, 

preparation, and storage of food during which lead can be introduced at every 

stage either by atmospheric deposition or through metallic contamination, 

particularly from solder. 

As would be expected from the differences in the handling of various 
P.24 

IV-11 

foods, lead contents vary considerably, ranging from 0.002 to 0.98 ppm (CD, 

Table 7D-1). Lead in unprocessed foods such as fresh fruits and vegetables 

comes from atmospheric deposition on vegetation surfaces and uptake from 

soil through roots (Schuck and Locke, 1970; Motto et al., 1970). The 

potential for lead uptake through the roots is determined primarily by 

the soil's organic content and pH; at normal soil pH levels (4.5 to 8) and 

with sufficient organic content, lead is bound to organic complexes in 

preference to other metals that are plant nutrients, e.g., zinc, calcium, 

manganese, magnesium (CD, p. 6-32). With changes in soil properties such 

as reduced organic content and lower pH, a greater fraction of total soil 

lead may become mobilized and its potential for uptake by plant roots 

enhanced (CD, p. 6-38). 

Several studies have shown that lead on the surface of leaves (and 

bark) is closely related to traffic density and distance from the highway, 

(or more specifically to air lead concentration and particle size distribution), and that not all of the lead particles deposited on plant surfaces 

can be washed off (Motto et al., 1970; Schuck and Locke, 1970; Lagerwerff 

et al., 1973; Pilegaard, 1978; Garty and Fuchs, 1982; Tanaka and Ichikuni, 

1982). Leafy aboveground vegetables whose edible portions are exposed to 

atmospheric lead (e.g., spinach, lettuce) tend to have the highest lead 

levels (Spittler and Feder, 1978) while for many crops, the edible internal 

portions (e.g., corn and wheat kernels) have considerably less lead than 

the outer exposed parts such as stems, leaves, and husks (Ter Haar, 1970). 

Belowground crops such as potatoes and onions are only partially protected 

from atmospheric deposition since their roots accumulate lead from the soil 

(CD, p. 7-34). Meat products that enter our food chain may also be affected 

by atmospheric lead via the deposition and accumulation of lead on forage 
P.25 

IV-12 

subsequently eaten by livestock (Graham and Kalman, 1974; Crump and Barlow, 

1982). 

Recent studies on lead content of various foods exposed to and protected 

from atmospheric lead and lead solder, and on dietary patterns in the U.S., 

provide information on dietary lead intakes for different populations 

(Wolnik et al., 1983; National Food Processors Associations, 1982; Pennington, 

1983; U.S. FDA, 1983, 1984). Based on these data, the CD has apportioned 

lead in "typical" child and adult diets' to four sources: natural lead, 

atmospheric lead, lead in solder, and lead whose origin cannot be determined 

at present. These estimates and their associated uncertainties are discussed 

in terms of their application to estimating lead exposure discussed in 

in Section V. 

E. Lead in Water 

Lead is a natural, usually minor, constituent of surface and ground 

waters. Atmospheric lead can enter the aquatic system through direct 

fallout or in surface runoff as suspended particles or adsorbed to soil 

particles. Under most conditions (pH, temperature, alkalinity), lead forms 

insoluble salts and precipitates to sediments, which probably accounts for 

the low lead content of U.S. source water supplies; the average concentration 

ranging between 3 and 4 micrograms Pb per liter water (pg/1). 

In contrast, lead levels in household drinking water can be much 

higher due to plumbing corrosion and subsequent leaching of lead, ranging 

between 10 and 30 pg/1 on average. The combination of corrosive (i.e., 

soft or acidic) water and lead pipes or soldered joints in distribution 

systems create localized zones of high lead concentrations (Worth et al., 

1981) as high as 380 pg/1. In general, levels are highest in samples of 

hot and/or stagnant "first draw" water. 
P.26 

IV-13 

Drinking water is a major source of lead exposure among many infants 

while they are dependent on baby formulas during their first year. EPA's 

Office of Drinking Water is currently reviewing the degree of protection 

afforded by the existing lead standard of 50 pg/1 against health risks 

in this sensitive population. 

The CD's estimates of the contributions that atmospheric and solder 

lead make to young children's total lead exposure via drinking water are 

addressed in the modeling approaches presented in Section V. 
P.27 

V. ESTIMATING LEAD EXPOSURES AND BLOOD LEAD LEVELS 

In order to assess the health risks associated with alternative air 

lead levels, it is necessary to estimate the blood lead (PbB) levels that 

would be distributed in the population(s) of concern under various air lead 

concentrations. [The amount of lead measured in whole blood is an index of 

lead absorption and is generally used as the dosage, or index of exposure, 

in investigating the various human health effects associated with lead.] 

Three approaches are examined that can be used to estimate or predict the 

impact of inhaled and ingested lead aerosols and compounds on the body 

burden of lead as indexed by blood lead. These approaches are presented 

for consideration in possibly using one, two, or all three (with any necessary 

modifications using improved data) in assessing the protection afforded by 

alternative lead NAAQS. 

The first approach is to use measured rates of "uptake" of lead through 

different pathways (e.g., inhalation, ingestion) from experimental studies 

together with available mathematical models from lead balance studies to 

project either total body burden or the amount of lead in any of the presumed 

"physiological" kinetic compartments (e.g., blood, soft tissue, bone) at 

any time (Hammond et al., 1981). This "uptake/biokinetic" modeling approach 

attempts to account for the following: a) the amount of lead in the body at 

any one time is the product of dynamic interactions of partially offsetting 

processes of absorption, distribution, storage, mobilization, and excretion; 

b) these processes vary with the route and rate of exposure, a person's 

age, nutritional and health status, and baseline exposure; and c) uptake 

from all sources by all absorption routes can be modeled, thus providing an 

estimate of the relative importance of atmospheric lead exposure, either 

directly or indirectly, to total body burden. 
P.28 

V-2 

The level of lead in one tissue (e.g., blood) and its relationship to 

levels of lead in other tissues responds to many external and internal 

factors. A discussion of lead's absorption, excretion, retention, and 

distribution within a child's body under different exposure and physiological 

conditions is provided in Appendix A. Any application of this model's outputs, 

should however, recognize the limitations of the data and the significant 

variability among populations in their behavioral, exposure, and physiological 

characteristics. 

The second modeling approach is to estimate separate empirical relationships 

between average levels of lead in air, food, water, dust, soil and in blood, 

which are available from experimental exposure and observational, or epidemiological, studies of different populations (i.e., "disaggregate" approach) 

(CD, Section 11.4). The third is referred to as the "aggregate" approach 

whereby a relationship between blood lead and air lead is derived that 

reflects both direct inhalation exposure and indirect exposures via secondary 

deposition processes. The validity of these latter two approaches, which 

rely primarily on epidemiological data, requires that the input of lead 

from all sources must have been reasonably constant long enough for virtual 

equilibration to occur between blood lead and environmental lead levels 

(Hammond et al., 1981). The nature of the relationships detected between 

lead concentrations in blood and various environmental media, and the merits 

and limitations in using empirical relationships to represent lead exposure 

through multiple pathways, will be discussed in Section V.B. 

A. Integrated Lead Uptake/Biokinetic Model 

There have been several studies measuring the intake, uptake, and 

metabolism of lead in volunteers, from which balance schemes have been 

constructed (Kehoe, 1961; Chamberlain et al., 1978, Rabinowitz et al., 
P.29 

V-3 

1976, 1977). These balance schemes are derived from limited data obtained 

under experimental conditions and their application thus far has been 

restricted to adult males. It is also possible to construct balance schemes 

by making estimates about lead intakes and various metabolic factors. This 

approach suffers from the fact that the data and assumptions employed 

are based on the results of many separate pieces of research, and therefore 

important variables may be omitted. However, provided the data exist, 

balance schemes can be constructed for different groups with different 

exposures to lead, and for assessing the importance of specific exposure 

factors under variable conditions (e.g., alternative lead NAAQS, phaseout 

of lead in soldered cans and in gasoline). 

The staff has attempted to devise model balance schemes for U.S. children 

at and under 6 years of age under alternative air lead levels. Because the 

analysis assumes that the various air lead levels are maintained constantly, 

averaging time (considered in Section VII) will not affect the uptake 

estimates. The reasons for specifying this age group are discussed in 

Section VI.C. The results summarized in Table 5-1 give a broad outline of 

the actual and relative magnitudes of average intakes and uptakes of lead 

by different pathways and from different sources. It is important to recognize 

the limitations of this exercise, which involves many uncertainties and 

assumptions due to a lack of sufficient data. These limitations along with 

details of the available data and calculations are provided in Appendix B. 

The groups of children considered in the model do not include the whole 

U.S. population; they comprise groups with different exposures to lead, 

some of them extreme, in order to illustrate the variations in lead exposure 

and absorption in different situations. Section V.A.2 presents methodologies 

to relate estimates of average lead uptake under alternative air lead levels 
Table 5-1. Model Balance Schemes for Average Lead Intake and Uptake in Children Under Alternative Air Lead Levels1 

1. Outdoor air lead (pg/m**) 

2. Indoor air lead (pg/m-*) 

3. Time spent outdoors (hours/day) 

4. Time weighted average (pg/m3) 

5. Volume of air respired (m3/day) 

6. Lead Intake from air (pg/day) 

7. % deposition/absorption in lungs 

8. Total lead uptake from lungs 

(pg/day) 

9. Dietary Lead Consumption (pg/day) 

a) from solder, undetermined sources 

b) atmospheric lead 

10. % absorption in gut 

11. Dietary lead uptake (pg/day) 

12. Street dust/soil lead (pg/g) 

13. Indoor dust lead (pg/g) 

14. Time weighted average (pg/g) 

15. Amount of dirt ingested (g/day) 

16. Lead intake from dirt (pg/day) 

17. % dirt lead absorption in gut 

18. Lead uptake from dirt (pg/day) 

19. Total lead uptake from lung and 

gut (pg/day) 

0.5 ug/ 

General*^ 

0.5 

0.15-0.4 

2-4 

.18-.42 

5-10 

0.9-4.2 

25-50 

0.23-2.1 

m

3 

Point 

Source3 

0.5 

0.15 

2-4 

.18-.21 

5-10 

0.9-2.1 

45-75 

0.41-1.6 

0.75 pg/m3 1.0 pg/m3 

General 

0.75 

0.23-0.6 

2-4 

.27-.63 

5-10 

1.4-6.3 

25-50 

0.35-3.2 

Point 

Source 

0.75 

0.23 

2-4 

.27-.32 

5-10 

1.4-3.2 

45-75 

0.63-2.4 

General 

1.0 

0.3-0.8 

2-4 

.36-.83 

5-10 

1.8-8.3 

25-50 

0.45-.42 

Point 

Source 

1.0 

0.3 

2-4 

.36-.42 

5-10 

1.8-4.2 

45-75 

0.81-3.1 

10.1 

1.0 

42-53 

2.7-5.9 

100-450 

220-300 

210-325 

0.1 

21.0-32.5 

30 

6.3-9.8 

9.2-17.8 

10.1 

1.0 

42-53 

2.7-5.9 

350-800 

450-700 

442-716 

0.1 

44.2-71. 

30 

13.2-21. 

16.3-29 

6 

5 

0 

10.1 

1.0 

42-53 

2.7-5.9 

275-800 

375-650 

366-675 

0.1 

36.6-67. 

30 

11.0-20. 

14.1-29. 

5 

3 

4 

10.1 

1.0 

42-53 

2.7-5.9 

600-1250 

625-850 

623-917 

0.1 

62.3-91.7 

30 

18.7-27.5 

22.0-35.8 

10.1 

1.0 

42-53 

2.7-5.9 

500-1150 

525-875 

523-921 

0.1 

52.3-92.1 

30 

15.7-27.6 

18.9-33.9 

10.1 

1.0 

42-53 

2.7-5.9 

750-1450 

800-1150 

796-1200 

0.1 

79.6-120.0 

30 

23.9-36.0 

27.4-45.0 

^Assumptions and calculations are described in Appendix B by row number. 

^Refers to children living in typical urban or rural environments. 

3Refers to children living near one or more lead point sources. 
Table 5-1. Model Balance Schemes for Average Lead Intake and Uptake in Children Under Alternative Air Lead Levels1 

(Continued) 

1. Outdoor air lead (pg/m3) 

2. Indoor air lead (pg/m3) 

3. Time spent outdoors (hours/day) 

4. Time weighted average (pg/m3) 

5. Volume of air respired (m3/day) 

6. Lead Intake from air (pg/m3) 

7. % deposition/absorption in lungs 

8. Total lead uptake from lungs 

(Mg/day) 

9. Dietary Lead Consumption (pg/day) 

a) from solder, undetermined sources 

b) atmospheric lead 

10. % absorption in gut 

11. Dietary lead uptake (pg/day) 

12. Street dust/soil lead (pg/g) 

13. Indoor dust lead (pg/g) 

14. Time weighted average (pg/g) 

15. Amount of dirt ingested (g/day) 

16. Lead intake from dirt (pg/day) 

17. % dirt lead absorption in gut 

18. Lead uptake from dirt (pg/day) 

19. Total lead uptake from lung and 

gut (pg/day) 

1.25 

General 

1.25 

0.38-1.0 

2-4 

0.45-1.0 

5-10 

2.3-10.0 

25-50 

0.58-5.2 

wg/ m

3 

Point 

Source 

1.25 

0.38 

2-4 

.45-.54 

5-10 

2.3-5.3 

45-75 

1.0-3.9 

1.5 

General 

1.5 

.45-1.2 

2-4 

0.54-1.25 

5-10 

2.7-12.5 

25-50 

0.68-6.3 

pg/m3 

Point 

Source 

1.5 

0.45 

2-4 

.54-.63 

5-10 

2.7-6.3 

45-75 

1.2-4.7 

1.75 

General 

1.75 

.53-1.4 

2-4 

0.63-1.46 

5-10 

3.2-14.6 

25-50 

0.8-7.3 

yg/ m

3 

Point 

Source 

1.75 

0.53 

2-4 

.63-.73 

5-10 

3.2-7.3 

45-75 

1.4-5.5 

10.1 

2.0 

42-53 

5.1-6.4 

600-1250 

625-1000 

623-1041 

0.1 

62.3-104.1 

30 

18.7-31.2 

24.4-42.8 

10.1 

2.0 

42-53 

5.1-6.4 

850-1000 

1050-1400 

1033-1333 

0.1 

103.3-133.3 

30 

31.0-40.0 

37.1-50.3 

10.1 

2.0 

42-53 

5.1-6.4 

700-1400 

750-1150 

746-1192 

0.1 

74.6-119.2 

30 

22.4-35.7 

28.2-48.4 

10.1 

2.0 

42-53 

5.1-6.4 

1000-1750 

1200-1700 

1183-1708 

0.1 

118.3-170.8 

30 

35.5-51.2 

41.8-62.3 

10.1 

2.0 

42-53 

5.1-6.4 

775-1450 

800-1200 

798-1241 

0.1 

79.8-124.1 

30 

23.9-37.2 

29.8-50.9 

10.1 

2.0 

42-53 

5.1-6.4 

1075-1950 

1350-1900 

1327-1908 

0.1 

132.7-190.8 

30 

39.8-57.2 

46.3-69.1 

Assumptions and calculations are described in Appendix B by row number. 

^Refers to children living in typical urban or rural environments. 

3Refers to children living near one or more lead point sources. 

CO 
P.32 

V-6 

to blood lead levels. Although this approach predicts hypothetical outcomes 

and the absolute numbers should not be used uncritically, the model does 

strive to use the available data, with all its limitations, to the fullest 

extent possible and to provide a useful tool in eventually distinguishing 

the health impacts of alternative lead NAAQS. 

1. Estimates of Lead Uptake 

The method employed to estimate the degree to which each environmental 

source of lead contributes to a child's total daily lead uptake is based 

on the maximum ambient air lead level allowable for each level considered, 

probable exposure conditions with respect to other exposure media such as 

food and dust, and average biological absorption rates for each exposure 

route. The method consists of a four-step process: 

1) definition of ambient concentrations of lead for major exposure 

sources (i.e., air, food, soil, dust); 

2) determination of daily lead intake according to the relationship: 

Ii = Ci • CPb]i 

where Ii is the daily lead intake from source i, Ci is the consumption per 

day of each lead source i and [Pb]i is the concentration of lead in each 

source i'i; 

3) calculation of the amount of lead absorbed from each exposure 

source i: 

^ =Ii ' Ai 

where U-j is lead uptake for each exposure source i, li is the daily lead 

intake from each source i, and A^ is the percent absorption of lead, via 

the appropriate exposure route for the particular source; and 

4) calculation of the total lead uptake from all sources, Uu: 

Uu = Z (1^ ' Ai) 
P.33 

V-7 

Certain assumptions are required to calculate the average daily intake and 

uptake of lead for children living in the two general areas specified --

urban/rural and near (within 2-5 km) one or more point sources. The assumptions 

and estimates used in the calculations presented in Table 5-1 are discussed 

in Appendix B. 

2. Uptake and Blood Lead Concentration 

To estimate children's blood lead (PbB) levels under different exposure 

scenarios, several different kinds of studies can be used to derive a 

relationship between absorbed lead (or lead uptake) and blood lead. Available 

studies include population surveys in which the blood lead concentration of 

individuals or groups is correlated with measured lead concentrations in 

air, food, water, soil, or dust; experiments in which volunteers are exposed 

to controlled air lead concentrations and their PbB levels measured; and 

lead balance studies of individuals with measured lead intakes. The most 

relevant of these studies are discussed in Appendix C along with descriptions 

of the analyses used to derive uptake/PbB relationships. Data on children 

from population surveys are discussed in Section V.B. Because of significant 

metabolic differences, experimental data on adults are used for comparative 

purposes only. 

Figure 5-1 compares the relationships derived from the Ryu et al. 

(1983) dietary intake study on infants, the Chamberlain and Heard (1981) 

analysis of the adult epidemiological data, and the metabolic lead balance/ 

compartmental models of Rabinowitz et al. (1976) and Harley and Kneip (1985). 

Despite the diverse nature of the populations, study designs, and methodologies, 

there is a fair degree of consistency in the relationships. Each study 

found that a linear function provided as good a fit, if not better, than 

other non-linear forms at the relatively low exposure levels investigated. 

Some experimental and epidemiological evidence suggests however, that the 
V-8 

P.34 

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P.35 

V-9 

relationship between lead concentrations in tissue and cumulative lead 

intake is only approximately linear at low levels of intake, and that 

successive increments in intake or exposure result in progressively smaller 

contributions to blood lead concentrations (Azar et al., 1975; Moore, 1977; 

Gross, 1981; DeSilva 1981; Sherlock et al., 1982). This curvilinear relationship 

may be due to increased renal clearance with higher blood lead (Gross, 

1981), distributional non-linearities due to differences in lead binding 

sites in different tissues (Hammond et al., 1981), and/or to a sizeable 

pool of mobile lead in bone maintained more or less independently of uptake 

(Rabinowitz et al., 1977; Chamberlain, 1983). It appears however, that 

none of the mechanisms introduce significant non-linearities at blood lead 

levels below 30 pg/dl (Marcus, 1984, 1985; Chamberlain, 1983) and that a 

linear mathematical model is valid for relatively low to moderate lead 

exposures (CD, p. 10-31, Appdx. 11A-2). As discussed in Appendix A, above 

30-40 pg/dl, blood lead may be an inadequate index for tissue lead burdens 

in many children (Piomelli et al., 1984) and linear models are likely to 

lose their predictive power. For this reason, the relationships depicted 

in Figure 5-1 are truncated at 30 pg/dl. To estimate PbB levels above 

30 pg/dl, which is now above the maximum PbB level of health-related 

concern for children (see Section VII.C), would require use of non-linear 

models which are discussed in the criteria document (Appendix II.B). 

The compartmental biokinetic model of lead metabolism developed by Mallon 

(1983) and Kneip et al. (1983) and revised for children by Harley and Kneip 

(1985) relied on a broad array of experimental and observational measurements 

of mammalian metabolism and growth patterns, and has been successfully 

validated using available human experimental and autopsy data. As is the 

case for any mathematical model, there are inherent limitations and un-
P.36 

V-10 

certainties associated with it. Because this model however is based on the 

most comprehensive data available and has been developed specifically to 

predict organ lead concentrations over time in young children with continuous 

lead uptake, it appears that the outputs of the Harley and Kneip (1985) 

biokinetic model may be the most appropriate to predict PbB levels in 

children using the integrated lead uptake estimates presented in Table 5-1 

and Appendix B. PbB levels calculated from the conjunction of the integrated 

lead uptake and biokinetic models are presented in Section VII.C.2 

(along with estimates using other modeling approaches that are discussed 

later) in order to estimate potential health impacts among children under 

alternative air lead levels. 

B. Statistical Relationships between Blood Lead and Airborne Lead 

This section addresses two other methods of determining the 

contribution of air lead to total exposure and the potential health impacts 

associated with alternative air lead levels. The previous section examined 

the relationships between blood lead in children and estimated levels of 

lead uptake from the air, housedust, outdoor soil and dust, and diet. The 

approaches presented here will be to develop a direct relationship between 

air lead and blood lead in children and to 1) consider how air lead alone 

can serve as an index for lead exposure through other media affected by 

atmospheric lead deposition as well (i.e., "aggregate" modeling approach), 

and 2) how these other environmental media can be taken into account 

separately (i.e., "disaggregate" modeling approach). 

Various experimental and community studies provide quantitative relationships between air lead and blood lead. Experimental studies, summarized in 

Table 5-2, include those in which adult volunteers have been exposed to controlled levels of laboratory generated lead aerosols, in some cases with 
Table 5-2. SUMMARY OF EXPERIMENTAL LEAD INHALATION STUDIES 

Study/Subjects Exposure 

Other 

Controlled 

Lead Exposures 

Source of 

Analysis 

Estimated Mean 

Inhalation Slope 

(ug/dl per pg/m3) 

Griffin et al., 1975 

14 adult males 

17 adult males 

6 adult males 

(controls) 

3.2 Mg/m3 - Diet 

10.9 pg/m3 - Diet 

submicron lead oxide aerosol 

for 4-14 weeks, 23 hrs/day 

Ambient air (0.1-0.2 .g/m3) Diet 

CD 

Snee, 1981 

Hammond et al, 

1981 

CD 

CO 

3.00 

2.3 

1.9 

0.65-2.17 

mean >* 1.57 _+ 0.26 

0.20 + 1.48 

Rabinowitz et al., 1977 

5 adult males Ambient air ( • 4 pg/m3 ) !, 

room with unfiltered air, 

(0.4-2.1 ug/m3 ), and 

room with filtered air 

Diet supplemented 

with Isotopic lead 

tracer 

Ambient air (2.1 pg/m3 )

2 

Other exposures identical 

CD 

Snee, 1981 

CD 

1.59-3.56 

mean «• 2.14 

1.7-3.9 

2.63-5.88 

mean = 3.51 

Chamberlain et al., 1978 

10 adult males Pb labeled submicron car 

exhaust, lead oxide, and 

lead nitrate aerosols for 

several minutes 

CD 2.2-2.73 

3.0-3.54 

Kehoe, 1961 

6 adult males 

9 adult males 

0.6-0.9 ug/m3 submicron Diet 

lead sesquioxide aerosol for 

various daily intervals over 

three-five years 

0.6-3.6 pg/m3 over similar Diet 

period 

CD 

Gross, 1981 

Hammond et al., 

1981 

-0.34 to 2.60 

mean » 1.25 

0.57 

0.59 

ifiased on stationary monitor readings not representative of personal exposures while outside (10 hrs/day) 

(CD, p. 11-47). 

2CD (p. 11-48) estimates outdoor exposure most likely to be 2.1 pg/m3 resulting in estimated lead intake and p 

to be significantly different. 

3Depends on assumptions regarding residence time of lead and volume of blood (CD, p. 11-49 to 11-50). 

'"'After adjustment for long-term bone resorption of lead with chronic exposure (Chamberlain et al., 1978). 

co 
P.38 

V-12 

isotopic lead tracer. Data from the most relevant studies have been re-analyzed 

in the CD to yield blood lead-air lead "slopes" (B), where g measures 

the change in blood lead that is expected for a unit change in air lead. 

Because intake of air lead through the diet and dust was probably minimal 

for the adult subjects in these experiments, these studies may underestimate 

the dose response that would be seen among children to environmental changes 

in air lead (Angle et al., 1985). 

Epidemiological (i.e., community) studies provide correlations between air 

lead and blood lead in different populations of children and adults under 

varying conditions of lead, from current or previous atmospheric fall out 

and other sources, and may yield estimates of dose response that are biologically more relevant. Two modeling approaches using the best available epidemiological data can be applied to estimate quantitatively the relationship between 

air lead and blood lead in children: 1) a disaggregate model in which total 

exposure to air lead is assessed by separately analyzing the relationship 

between blood lead and inhaled air lead versus the associated changes in 

blood lead as a result of surface deposition of lead onto soil, dust, food, 

and water; and 2) an aggregate model in which blood lead/air lead relationships 

are analyzed such that integrated environmental lead exposure is represented 

by a single variable. Before discussing these approaches, several important 

limitations in interpreting the epidemiological studies should be noted. 

a) Measurements of lead in the environment were generally limited 

and taken from samples separated in time and space from actual population 

exposures (as indexed by blood lead). Consequently, reported air lead 

concentrations in outdoor air (measured at centralized, stationary monitors), 

for example, have different relationships to the true personal airborne 

lead exposure of the target population in different studies; 
P.39 

VT1 3 

b) In order for the relationships between blood lead and environmental 

lead to have general predictive value for other populations, steady state 

or near steady state conditions must have prevailed wherein the amount of 

lead inhaled and ingested per unit time was reasonably constant long enough 

for virtual equilibration to occur between lead in air, food, dust, etc., 

and blood lead (Hammond et al., 1981). As discussed below, in situations 

where lead concentrations in different media are only moderately correlated, 

environmental exposure cannot simply be characterized by the lead concentration 

in one medium, like air or dust. (Brunekreef, 1984); 

c) The blood/air lead relationships generally are limited in that 

at most two or three, but frequently, only one environmental source of lead 

is measured in each study. Because of the simultaneous presence of lead in 

multiple media, such relationships underestimate or otherwise confound air 

lead's effect on total exposure unless lead intake from the other sources 

remains approximately constant and lead concentrations in different media 

are well correlated. In situations where the latter condition does not 

hold, environmental exposure cannot be simply characterized by the lead 

levels in air (for example, near point sources where the accumulation of 

lead in soil is related more to historical, rather than present, emissions, 

especially when control measures are being or have been taken). These 

difficulties can be partly overcome but unfortunately, longitudinal assessments 

of simultaneous exposure to all media have not been made and only limited 

information exists from studies measuring lead isotope ratios in blood and 

in the environment, a method which has emerged as a valuable tool to apportion 

lead exposure among different sources (Facchetti and Geiss, 1982; Yaffe et 

al., 1983); 

d) As with the uptake/biokinetic approach, the importance of specific 
P.40 

V-14 

sources of exposure varies widely from one individual to the next, and 

reliance on a blood/air relationship from an "average" case may be inappropriate to predict different individual risks but can provide reasonable 

estimates of possible population-wide impacts. 

e) Again, similar to the uptake/biokinetic approach, environmental 

and blood lead sampling, analytical techniques, and quality control (if 

any) differ among studies and may explain part of the variability of the 

results; and 

f) Possible confounding variables that influence PbB levels but 

which are not related to air lead measurements (e.g., lead in paint, canned 

food and plumbing, socioeconomic status, parental care, housing and play 

conditions, calcium intake) cannot always be disentangled. Control for 

confounders can be achieved by comparing populations that differ only in 

their exposure to airborne-derived lead. However, identifying such groups 

has been difficult. Another possibility is to perform a multivariate 

statistical analysis in which adjustments are made for some or all of the 

confounders before calculating the blood lead/air lead relationship. This 

requires information on the value of each confounder for each individual, 

which is also very difficult to estimate. In the case of lead, several 

confounders tend to work in the same direction as air lead. For example, 

elevated exposure and unfavorable social conditions often are both concentrated 

in central cities. Consequently, when statistical adjustment is incomplete, 

the relationship between air lead and blood lead will likely be inflated. 

The situation is complicated when more than one exposure variable besides 

air lead is entered into the analysis. Adjustment for a confounding variable 

usually implies that all of the shared variance between confounder and exposure 
P.41 

V-15 

variable is attributed to the confounder; this can inevitably lead to 

underestimation of the "true" impact of the exposure variable (Rutter, 

1983). Thus, adjusting for environmental exposures such as soil or 

dust lead, which are determined to a large extent by air lead levels, can 

result in an underestimation of the total impact of airborne-derived lead 

on blood lead (Brunekreef, 1984). 

1. Blood/Air Lead Relationship Using Disaggregate Model 

The CD concludes that experimental inhalation studies (see Table 5-2) 

and epidemiological studies on adults (Azar et al., 1975) exposed to relatively 

low air lead levels (<3.0 pg/m*-*) produce linear inhalation blood lead/air 

lead slopes of 1.64 and in the range of 1.08-2.57 respectively (CD, Tables 

11-38, 11-40). Inhalation slopes for children were estimated in the CD 

from the population studies of Angle and Mclntire (1.92 +_ .60), Roels et 

al . (2.46 +_ 0.58), and Yankel et al. (1.53 +_ 0.064), yielding an unweighted 

mean slope of 1.97 +^0.39 (CD, p. 11-76). These studies were chosen for 

analysis and emphasis in the CD because they were judged to address several 

key factors sufficiently well to establish meaningful relationships. These 

factors include a well-defined study population, a good measure of individual 

exposure, measurement of blood lead with adequate quality control, a statistical 

analysis model that is biologically plausible and consistent with the data, 

and control or measurement of important covariates (CD, p. 11-63). In 

addition, they were selected so that, with the exception of some children 

in the Yankel et al. study, attention can be restricted "to those individuals 

without known excessive occupational or personal exposures" (CD, p. 11-65). 
P.42 

V-16 

The relationship between blood lead and direct inhalation of airborne 

lead provides information useful for changes in air lead on a time scale of 

only several months (CD, p. 11-186). Over time, suspended lead deposits and 

is incorporated into soil, dust, and water, and enters the food chain. Since 

prior and current atmospheric fallout directly modify the daily burden of 

ingested lead, larger changes in blood lead would be predicted by the 

associated changes in the surface deposition of lead (Angle et al., 1985). 

To account for the simultaneous presence of lead in multiple environmental 

media, the CD has analyzed the separate relationships between children's 

blood lead and dietary, soil, and dust lead. These analyses are summarized 

in the tables included in Appendix C and are described in detail in 

Chapter 11.4 of the CD. A set of the most reliable relationships derived 

from these analyses are applied in a further analysis presented in the 

CD (CD, Table 13-6) and reproduced in this paper (Table 7-10) as a way 

to characterize average total lead exposure among U.S. children under 

alternative air lead levels. A similar disaggregate model was developed 

by Angle and Mclntire (1979) and Angle et al. (1985) in forming an integrated 

lead exposure function from measurements of lead in air, soil, and house dust 

and relating that to PbB levels of children living in various areas of Omaha. 

2. Blood/Air Lead Relationship Using Aggregate Model 

In the disaggregate modeling approach, "inhalation" lead slopes are 

derived by statistically adjusting blood lead/air lead slopes by whatever 

non-air exposure variables (e.g., house dust lead) that were measured in 

the individual epidemiological studies, and then combining separate slopes 

available for other exposure media (e.g., dust, food, water) to arrive 

at an integrated lead exposure function. With the exception of Angle and 

Mclntire (1979), the community studies from which inhalation slopes have 
P.43 

V-17 

been derived have not simultaneously measured lead in more than two or three 

media and consequently, the integrated lead exposure function is necessarily 

based on data from multiple studies involving different populations, 

exposure conditions, measurement techniques, etc. An alternative method of 

calculating the effect of changes in air lead on children's blood lead is 

to analyze individual community studies in which reliable "unadjusted" 

blood lead/air lead relationships can be derived such that the impact of 

both direct (inhaled) and indirect (via dust, soil, etc.) contributions of 

air lead are combined, or aggregated, in one variable (i.e., air lead) 

at a time. To simply use an "adjusted" blood lead/air lead slope (i.e., 

inhalation slope) would be to underestimate the impact of atmospheric 

lead on children's total exposure since air lead levels, in general, are 

significantly correlated with other important exposure variables such as 

hand and household dust lead (Brunekreef, 1984). 

The population studies with identifiable air monitoring methods and 

reliable blood lead data are summarized in Table 5-3. As is the case for 

the data in each of the experimental studies, different statistical analyses 

of the studies have resulted in a range of possible values for the blood 

lead/air lead relationship (p). Unadjusted (i.e., aggregate) relationships 

are presented in addition to adjusted relationships derived from regression 

analyses, the latter which refer to the blood lead/air lead relationships 

due to direct inhalation exposure. Note that in the majority of these 

studies adjustment for confounding factors has been absent or incomplete. 

In Table 5-4, the calculated 6 values listed in Table 5-3 for each study 

are presented according to the blood lead levels, ages, and type of location 

of the investigated children. Relatively wide ranges of 3 values are 

observed for industrial and urban areas at low and high PbB levels and for 
Table b-3. SUMMARY OF EPIDEMIOLOGICAL STUDIES UN LEAD-EXPOSED CHILDREN 

Study 

Roels et al., 

1976,1978,1980 

Population3 

Air Lead0 

(pg/m3) 

Blood Lead 

(pg/dl) 

Statistical Model 

(Analyst) 

Covariates 

Measured 

blood Lead/ 

Air Lead Slope 

<lkin: 10-15 yrs n=214 

2.5km: 10-13 yrs n=168 

Urban: 10-14 yrs n=55 

Rural: 10-13 yrs n=223 

Living near lead smelter 

(Antwerp, Belgium) 

2.68-4.06 24.6-30.1 

0.54-1.00 13.3-21.1 

0.45-0.56 10.4-12.7 

0.29-0.37 9.0-10.7 

(9 month avgs; 

low volume sampler)0 

Multiple regressions: 

Roels et al., 1980 

(8 group means) 

CD (148 subjects) 

Age, drinking water, income 5.3 

plus hand dust Pb adjustment 0.007 

-plus hand dust Pb adjustment 2.46 

Yankel et al., 

1977; Walter 

et al., 1980 

1-9 yrs n=1149 (1974) 

1-10 yrs n=781 (1975) 

living at varying 

distances from lead 

smelter (Kellogg) 

0-1.6km 

1.6-4km 

4-10km 

10-24km 

24-32km 

» 75km: 

18.0 

14.0 

6.7 

3.1 

1.5 

1.2 

(monthly avgs. 

65.9 

47.7 

33.8 

32.2 

27.5 

21.2 

21.2 

Multiple regressions: 

Yankel et al. (1977) 

Snee (1982b) 

Snee (1982a) 

CD (linear) 

CD (non-linear) 

Walter et al. (1980) 

Group comparisons 

(Brunekreef, 1984) 

Aye, drinking water, paint, 

SES, house dust 

-plus soil « dust Pb 

occupation adjustment 

-plus soil Pb, occupation, 

cleanliness, pica adjustment 

-same as above 

-same as above 

-same as above 

No adjustment for soil 

or dust Pb 

Angle and 

Mclntire, 

1979 

1-18 yrs n=831 

living in industrial 

urban, suburban 

areas of Omaha 

industrial: 0;37-1.66 24.8 

urban: 0.32-1.44 22.0 

suburban: 0.22-0.73 18.0 

(annual avgs. 1970-

1977) 

Regression Analyses: 

Angle and Mclntire 

(1979) (6-18yr. olds) 

CD (Table 11-33) 

(1-18 yr. olds) 

CD-(Table 11-33) 

Brunkreef, 1984; 

(all children) 

(1-5 yr. olds) 

(6-18 yr. olds) 

Age, drinking water, food 

-plus soil & house dust 

Pb adjustment 

-same as above 

-same as above 

No adjustment for 

soil or dust lead 

At 1.0 py/ 

1974 data 

1.16 

1.13 

1.U7 

l.bi! 

1.1b 

1.26 

2.4-3.3 

dependiny 

1.4 

0.6 

1.92 

4.40 

O.bb 

2.63 

2.10 

m-*; 

\ 

on aye 

< 

i 

00 

Brunekreef 

et al., 1981; 

Zielhuis et 

al., 1979 

1976:2-3 yrs n=108 

1977:1-7 yrs n=690 

1978:1-3 yrs n=95 

living <2km and 2-5km 

from secondary smelter 

(Arnheim) 

0.5-2.5(0.4km) 

0.4-1.6(0.4km) 

0.28-0.51(<lkm) 

(2 month avg.) 

11.8(2-5km)-19.7(.4-lkm) 

14.6(l-2km)-18.2(.4-lkm) 

16.1(.4-lkm) 

Group comparison 

(Brunekreef, 1984) 

Multiple regression 

(Brunekreef, 1984) 

Age, parental education 

and exposure, drinking water, 

food, age of home, mouthing 

behavior/hand dirt, house dust 

- plus adjustment for parental 

education 

4.0 (1976) 

3.6 (1977) 

3.6 (1976) 

Landrigan 1972:1-18 yrs n=259 (exposed) 

et al., 1975; 1977:1-18 yrs n=499 (control) 

Morse et al. 1-18 yrs n=140 (exposed) 

1977 living near primary 

smelter (El Paso) 

<.8km ,8-1.6km 

10.0 6. o a — 

5.5 3.0d 

(4 month avg.) 

<.8km 

41.4 

17.7e 

.8-1.6km 

31.2 

20.2 

Group comparison 

(Brunekreef, 1984) 

Aye, drinkiny water, milk 2.6 (1972) 

consumption, parental income, 3./ (1977) 

home paint status 
Table b-3. SUMMARY OF EPIDEMIOLOGICAL STUDIES ON LEAD-EXPOSED CHILDREN (CONTINUED) 

Study Population3 

Air Lead0 

(py/m3) 

Blood Lead 

(py/dl) 

Statistical Model 

(Analyst) Covariates Measured 

Billick et al., 0-6 yrs n=178,533 

1979, 1980; living in NYC 

Nathanson & 

Nudleman, 1980 

0.8-2.5 

(quarterly averages, 

1970-1974) 

20-33 Regression analysis 

(Brunekreef, 1984) 

Blood Lead/ 

Air Lead Slope 

Season, location, plus 

adjustment for age 4 race 

2.9 

Brunekreef 

et al., 1983 

4-6 yrs n=195 

living in city center 

or in suburban area 

(Rotterdam) 

.25 city 

.13 suburban 

(6-month avg., 

low volume sampler0) 

13.1 

8.2 

Group mean comparisons 

Regression analysis 

(Brunekreef, 1984) 

Regression analysis 

(Brunekreef et al., 

1983, 1984) 

Age, drinkiny water, house 

paint, SES, parental exposure, 

location 

-plus adjustment for Pb 

deposition outdoors, age of 

home, milk consumption, number 

of rooms, hand dirt, mouthing 

behavior, pets 

24.5 

18.b 

3.0-8.5 

aRefers to age of children sampled and sample sizes (n). 

DRepresents average levels measured either at various locations specified in "population" column or at various 

distances from specified point sources. 

cAir lead levels sampled by low volume methods likely underestimated levels that would have been measured by hi-volume samplers used in other studies, especially near smelter where larger lead particles predominate. This could result in inflated blood/air lead ratios. 

Estimated by interpolation of air quality data presented. 

eBased on only 3 samples - blood/air lead slope for 1977 based on reduction of air and blood lead at 0.8-1,6km from 

source. 

i 

t — A 

UD 
Table 5-4. BLOOD LEAO/AIR LEAD SLOPES1 IN CHILDREN FOR DIFFERENT AGES AND EXPOSURES 

Blood Lead (ug/dl)/ 

Age (years) _ 

<25/0-9 

Type of Location (Study) 

Urban Near Point Source(s) 

8.5a>

D (Brunekreef et al., 1983) 3.6-4.0a (Zielhuis et al., 1979; Brunekreef 

et al., 1981) 

<25/0-9, 10+ 0.6 (Angle and 

1.4a Mclntire; 

1.92 1979, CD) 

4.40 

0.66a (Brunekreef, 1984 

-2.63a from Angle and 

2.10a and Mclntire, 1979) 

<25/10+ 

>25/0-9 

2.46 (CD from Roels et al. 1976) 

5.3a (Roels et al. 1980) 

« 5.9-9.8a»

b Brunekreef, 1984 from Roels 

et al., 1976, 1978, 1980) 

2.9 (Bi Hick et al., 1979, 1980; 

Nathanson and Nudleman, 1980) 

1.07-1.52 (Yankel et al., 1977; Walter et al., 

1980; Snee, 1982b; CD) 

2.4-3.3a (Brunekreef, 1984 from Yankel et al., 

1977) 

i 

ro 

o 

>25/0-9, 10+ 2.6-3.7a (Landrigan et al. 1975; Morse et al., 

1977) 

4.6a (Brunekreef, 1984 from Roels et al., 1976, 

1978, 1980) 

^Slopes are in units of pg lead/dl blood per pg lead/m*-* air. 

a"Aggregate" slopes derived from group comparisons or multiple regression analyses that were unadjusted for soil or 

dust lead, thereby attempting to account for influence of deposited atmospheric lead through these exposure routes. 

Remaining slopes represent relationships between blood lead and air lead due solely to direct inhalation which have 

been calculated by adjusting for the influence of soil and/or dust lead. 

DUse of low-volume particulate samplers likely underestimated air lead exposures, and overestimated the 

3 value, especially near point source where large particles predominate. 
P.47 

V-21 

all ages of children. The apparent trend towards lower slopes with increasing 

PbB levels is consistent with findings within some studies (Angle and 

Mclntire, 1979; Roels et al., 1980) and other observations of curvilinear 

blood lead/exposure relationships (Azar et al., 1975; Moore et al., 1977; 

Gross, 1981; DeSilva, 1981; Sherlock et al., 1982; Hammond et al., 1981). 

As discussed, the CD determined that the inhalation slopes derived 

from the studies by Angle and Mclntire, Roels et al., and Yankel et al. 

are the most reliable given their overall quality. It is important to note 

several additional studies and analyses that may provide equally relevant 

and useful information for purposes of estimating an aggregate blood lead/air 

lead slope. Tables 5-3 and 5-4 identify surveys besides those of Angle and 

Mclntire and Roels et al. which studied children (0-10 yrs) whose blood 

lead levels were below 25 pg/dl. These studies (Brunekreef et al., 1983; 

Zielhuis et al. 1979; Brunekreef et al., 1981) reported well-defined study 

populations, employed available quality control procedures for blood lead 

analysis, and measured or controlled for important covariates (see Table 

5-3). Several specific comments should be made regarding these studies: 

1. The series of studies reported by Zielhuis et al. (1979) and 

Brunekreef et al. (1981) included many environmental measurements (lead in 

ambient and indoor air, lead in dustfall indoors and outdoors, soil, 

streetdust, floordust, tapwater, and dustiness of homes) and regression 

analyses to determine the impact on PbB levels of different variables 

(i.e., the above environmental indices as well as distance from the smelter, 

parental education, age of the child, mouthing activity, cleanliness of the 

child). Venous blood lead samples were analyzed by standard techniques and 

although information on interlaboratory comparisons is not given in the 

original study, quality control participation is reported by one of the 
P.48 

V-22 

investigators in a subsequent review (Brunekreef, 1984). Air lead was 

measured at two sites in 1976, and presumably in 1977, 0.2 and 0.4 km from 

the smelter. The levels in Table 5-3 were taken from Brunekreef (1984) and 

represent those measured at 0.4 km from the smelter. Six monitors measured 

air lead at 6 sites continuously for 2 months in 1978. Brunekreef (1984) 

estimates 3 for 1976 by assuming a difference of 2.0 ug/m^ in average air 

lead exposure levels between the 2-3 year old children with the highest and 

lowest PbB levels. The blood lead difference of about 8 ug/dl decreased 

to 7.2 ug/dl after adjustment for parental education, resulting in a 

slightly lower 3 estimate (3.6). For 1977, a difference of 1.0 yg/m^ was 

assumed for air lead exposure levels between exposed and control children 

of 2-3 years who had PbB levels of 18.2 and 14.6 yg/dl, respectively, again 

resulting in a 3 of 3.6. In 1978, only children living between 0.4 and 1.0 

km of the smelter were sampled and air levels did not correlate with blood 

lead within this population. Thus, no direct estimate of 3 can be derived, 

although soil lead and indoor and outdoor dust lead, and therefore, accumulated 

lead deposition, accounted for a significant fraction of the variance in 

PbB levels (Brunekreef et al., 1981). Based on the aforementioned criteria 

used to determine key studies in the CD (p. 11-63), it appears that this 

series of studies near Arnheim and the subsequent analyses in Brunekreef 

(1984) is of sufficient quality to provide reliable aggregate relationships 

between blood lead and air lead. 

2. The more recent study by Brunekreef et al. (1983) on Dutch city and 

suburban children also measured venous blood (which was analyzed as part of 

the European Community laboratory quality control program) and many 

environmental and social variables and potential confounders (lead in 

drinking water, soil, street and playground dust, hand dust, indoor dust, 
P.49 

V-23 

mouthing behavior, dietary intakes, parental education and occupation, age 

of home, etc). The very high 3 value (8.5) derived by Brunekreef (1984) 

even after adjustment in a multiple regression analysis for six of the 

confounders, may be related to an underestimation of ambient air lead 

levels due to the fact that low volume British Smoke air monitors were 

employed, in contrast to the hi-vol samplers used in most other studies. 

The extent of inflation in the estimated slope as a result of any underestimated 

air lead level is uncertain. Brunekreef (1984) notes however that even if 

this bias is accounted for, the difference in urban and suburban air lead 

levels was probably not larger than 0.2 ug/m-*. The contrast in lead 

deposition between the areas was significant (i.e., 643 vs. 220 ug/m^/day), 

indicating that ongoing lead pollution accounted for a good deal of the 

differences in PbB levels, although variations in historical emissions can 

not be entirely ruled out. The relatively low PbB levels in this study 

(

a

 8-13 ug/dl) could be another partial explanation of the high 3 estimates, 

given that other studies used to derive 3 included children with PbB levels 

on average closer to, and above, 30 ug/dl, at which point the blood 

lead/lead intake relationship is estimated to be non-linear and levels off; 

below 30 ug/dl, this relationship appears to be approximately linear (CD, 

p. 11-104). 

Despite the uncertainties in the air monitoring data, this study 

appears to have been carefully designed and conducted and though the precise 

value of the blood lead/air lead relationship is not certain, the estimated 

3 value appears to be significantly higher than the mean inhalation slope 

derived from other studies of comparable quality and relevance. 

In addition to these studies, the available statistical aggregate 

analyses on the criteria document's three "key inhalation slope" studies 
P.50 

Vr.24 

on children require brief discussion. 

3. The three inhalation 3 values (0.6, 1.92, and 4.40) attributed to 

regression analyses performed by Angle and Mclntire (1979) (CD, Table 

11-39) all included adjustments for soil and house dust lead. An unadjusted 

regression analysis found a 3 of 1.4 for 6-18 year olds (Angle and Mclntire, 

1979). Unadjusted coefficients of 0.66 (all children), -2.63 (1-5 yr olds) 

and 2.10 (6-18 year olds) were obtained by Brunekreef (1984). The surprising 3 

for the 1-5 year olds could be due to the fact that this age group was only 

sampled during one year, whereas sampling of older children was performed 

over 6 years. Brunekreef's reanalysis illustrates two points: 1) any slope 

derived for all children in the study (1-18 yrs) likely is deflated by 

including the discrepant results of the 1-5 year olds; and 2) by adjusting 

for soil and house dust lead in the analysis, the slope for air lead decreased 

three-fold from 2.10 to 0.69 in the 6-18 year olds. 

4. The inhalation 3 value of 2.46 from Roels et al . (1976) was estimated 

in the CD by adjusting for dust lead levels measured on the children's 

hands. An unadjusted regression analysis by the authors of the combined 

data (1976 through 1980) yielded a 3 value of 5.3 (Roels et al., 1980). 

Brunekreef (1984) segregated the data and compared groups with large differences 

in exposure (i.e., <1 km from smelter vs. urban/rural; 3 » 5.9) groups with 

small differences in exposure at high exposure levels (i.e., <1 km vs. 2.5 

km from smelter; 3 =* 4.6) and groups with small differences in exposures 

at low levels (i.e., 2.5 km from smelter/urban vs. urban/rural; 3 •**•* 13.7). 

The high estimate at the lower exposure level is influenced by two extreme 

values; removing them leaves a slope of approximately 9.8. As in the 

Brunekreef et al. (1983) study, the use of low-volume samplers likely 

underestimated air lead exposures, and overestimated the 3 value, especially 
P.51 

V.25 

for those children near the smelter where large particles predominate. The 

slope may be underestimated for young children, however, since this study 

only sampled children older than 10. Given these different factors and 

analyses, it is difficult to estimate a "true" aggregate slope from Roels 

et al. (1976, 1980). It is clear that a range of possible slopes for this 

study has been calculated that are dependent on exposure levels and adjustments 

for dust lead, and which are all greater than the slope for inhaled air 

lead alone (2.46) cited in the criteria document. 

5. Similarly, analyses of the Yankel et al. (1977) data adjusted for 

soil lead, cleanliness, dust, education, and/or pica have yielded inhalation 

3estimates ranging between 1.01 and 1.53 at an air lead level of 1.0 pg/m** 

(Yankel et al., 1977; Snee, 1982; Walter et al., 1980; CD, Table 11-39). 

Brunekreef (1984) estimated 3 values between 2.4 and 3.3 depending on age after 

comparing the highest and lowest exposed children's unadjusted PbB levels 

from 1974. 

The remaining slopes listed in Table 5-4 are based on data from children 

whose PbB levels, as some in Yankel et al. (1977), exceeded 25 pg/dl. As 

discussed in the CD, the relationship between lead uptake and PbB levels 

above about 30 pg/dl appears to be non-linear (CD, p. 10-31; Marcus, 1985). 

Because PbB levels above 25-30 pg/dl are above the maximum PbB level of 

health-related concern (see Section VII.C), however, these slopes are less 

relevant to the present review. 

In summary, the above analyses using the aggregate approach assume the 

same source for most lead in air, soil, and housedust, and that adjustment 

of PbB levels for soil or dust lead that yields an inhalation slope underestimates the "true" impact of atmospheric lead on PbB levels. A range of 

values can be estimated from a) additional, and apparently relevant, studies 
V-26 

not used to derive inhalation slopes (i.e., Zielhuis et al., 1979; Brunekreef 

et al., 1981, 1983) and b) aggregate analyses that include both direct 

(inhalation) and indirect (via soil, dust, etc.) air lead contributions in 

the key "inhalation slope" studies cited in the criteria document. Although 

far from conclusive, these studies and analyses suggest a range of possible 

blood lead/air lead aggregate slopes in the range of 2 to 10 for young, 

moderately exposed children with the most reliable slopes falling between 3 

and 5 (CD, p. 11-104). 

Because the blood/air lead relationships were derived from studies 

which measured air lead concentrations averaged over periods ranging between 

one month and one year (See Table 5-3), and because long-term averages 

(e.g., annual) may not reflect short-term (e.g., monthly) peak averages, it 

is possible that applying these slopes to estimate the impacts of different 

air lead levels would yield overestimates of PbB levels if the air lead 

standard considered is a one-month average (See Section VII.A). Any 

overestimation, however, is likely to be small given the long-term pattern 

of lead accumulation in the environmental media to which children are 

predominantly exposed (i.e., soils, dust, food) and the resulting modulation 

by the environment of potential short-term peak exposure levels. Therefore, 

it can be assumed that these slopes are applicable in estimating PbB levels 

associated with different monthly, as well as calendar quarterly, average 

air lead levels. 

It is important to add, as discussed in Appendix A, that some of the 

absorbed lead that accumulates in the skeleton deposits in the spongy 

trabecular bones (e.g., rib, vertebrae) where it may be resorbed into the 

blood stream. Because air-blood slopes are derived from epidemiological 

studies in which exposure to air lead was assessed over days, weeks, or 
P.53 

V-27 • 

months, an additional factor must be allowed for possible re-entry of lead 

into the blood transferred from bone or other long-term storage (Chamberlain, 

1983). Based on isotopic ratio and radiolabel tracer studies on adults, 

Chamberlain et al. (1978) estimated this factor to be 1.3, although it is 

likely to be higher in children because of the rapid growth and high rate 

of turnover in their skeletal systems. Applying this factor to the blood 

lead/air lead aggregate slope range discussed above (3-5 pg/m**) yields a 

range of about 4 to 6. Use of these slopes to evaluate alternative air 

lead levels is discussed in Section VII.C.2 along with the two other modeling 

approaches introduced in this section. 
P.54 

V I . CRITICAL ELEMENTS IN THE REVIEW OF THE PRIMARY STANDARD 

A. Mechanisms of Toxicity 

The toxicological impact of environmental lead can either be the 

cumulative product of continuous low-level exposure, or of single or repeated 

acute exposures. Adverse effects are due essentially to the mobile fraction 

of absorbed lead within the body. Thus, a major determinant of toxicit y 

is the distribution of lead among binding proteins and compartments that 

contain susceptible enzyme systems or other target sites (Raghavan et al. , 

1981; Silbergeld, 1983). The effects of lead on subcellular structures and 

processes result in biochemical derangements common to and affecting, 

many tissues and organ systems. These biochemical alterations can be 

linked to the diverse types of lead-based functional disruptions of organ 

systems that operate in a coordinated, interdependent way. 

The major molecular basis underlying lead's toxicit y in various 

human organ systems and tissues is believed to be it s abilit y as a metallic 

cation to bind with specific biochemical ligands, such as sulfhydryl, amino, 

and carboxyl groups, present in biomolecular substances crucial to normal 

physiological functions (Moore et al. , 1980). This binding interferes with 

physiological processes through the following mechanisms: 

1. Inhibition of enzyme activit y 

Lead inhibit s at least two enzymes in the heme biosynthetic pathway, 

delta-aminolevulinate dehydrase (ALA-D) and ferrochelatase (Chisolm, 1981), 

as well as enzymes and cofactors involved in maintaining the structural 

integrit y of red blood cel l and protecting them against oxidation — 

Na+, K+-activated adenosine triphosphatase (Na+, K+ - ATPase), pyrimidine5'-nucleotidase (Py-5-N), superoxide dismutase, and glutathione (Hasan et 

al. , 1967; Secchi et al. , 1973; Raghavan et al. , 1981; Paglia et al. , 1975; 
P.55 

VI-2 

Valentine et al., 1976; Levander et al., 1980; Gelman et al., 1978). The 

synthesis of tetrahydrobiopterin (a cofactor in brain neurochemistry; see 

below) and the activity of brain adenyl cyclase (associated with neurochemical 

receptors) are also inhibited by lead in vitro and in vivo at low concentrations 

(Purdy et al., 1981; Sauerhoff and Michaelson, 1973; Nathanson and Bloom, 

1975). It is important to note that although catalytic activity of these 

susceptible enzymes may be diminished across a wide range of lead exposure 

down to very low levels, sometimes without an observable threshold, the 

physiological or functional consequences of such inhibitions depend on the 

reserve capacity of the enzymes, the health and nutritional status of the 

individual, and subsequent exposures to lead and other environmental stress 

factors. These issues as well as dose-response relationships are addressed 

in Section VII.C. and Appendix D. 

2. Altered cellular energy metabolism and ion transport 

Energy metabolism occupies a central position in all biologic 

processes and substantial interference with one or more steps in cellular 

energetics can have immediate and severe effects on the usual functional 

outputs of a cell, tissue, or organ. Mitochondrial structure and a variety 

of its functions in energy metabolism are very sensitive to lead, particularly 

in rapidly developing tissues in the young (Holtzman and Shen Hsu, 1976; 

Bull et al., 1979; Holtzman et al., 1978). Effects including uncoupled 

oxidative phosphorylation (Goyer and Moore, 1974), inhibited substrate 

oxidation (Bull et al., 1975), and changes in mitochondrial membrane permeability 

and transport of ions, especially calcium (Ca++) (Holtzman et al. 1977; Bull, 

1980), occur at levels as low as 10 micromoles (p moles) in intact cellular 

systems. Because of the pervasive role calcium plays in regulating cellular 
P.56 

VI-3 

function, a wide range of linkages between lead's impacts on Ca+ + and 

energy metabolism, and altered functional activity and developmental delays 

in the kidney, liver, brain and smooth muscle have been proposed (Bull et 

al., 1975, 1979; Bull, 1980; McCauley et al., 1979; Silbergeld, 1983; 

Pounds et al., 1982) and are discussed below. 

3. Competition with ions for essential binding sites and altered 

neurochemistry 

Lead absorption, distribution, and retention is known to vary 

depending on dietary intake of calcium, iron, copper, and zinc, as well as 

other nutrients (e.g., protein, fat, vitamin D) (Mahaffey and Michaelson, 

1980). In addition, increased susceptibility to the toxic effects of lead 

on heme synthesis and on neurological function has been associated with 

deficiencies in calcium, iron, copper, and zinc (Mahaffey-Six and Goyer, 

1970, 1972; Klauder and Petering, 1977; Cerklewski and Forbes, 1976). 

These metabolic interactions can be expected 'among elements that share 

common chemical properties and compete for common metabolic binding sites, 

such as the mucosal proteins responsible for absorption and transport 

across the intestinal wall, and on specific intracellular enzymes. 

Lead-induced alteration of cellular calcium homeostasis, at levels as 

low as 10 p moles, either by direct competition at receptor binding 

sites (Barton et al., 1978; Ong and Lee, 1980; Habermann et al., 1983) or 

indirectly by reducing energy production and impairing mitochondrial and 

cell membrane transport "pumps" (Pounds et al., 1982a) could disturb multiple 

cell functions of different tissues that depend upon calcium as a messenger 

of hormonal and electrical stimuli or as a modulator of cyclic nucleotide 

metabolism (Rasmussen and Waisman, 1983; Rosen, 1983). For example, low 

levels of lead inhibit the calcium-mediated regulation of pyruvate kinase 

activity essential to hepatic glycolysis (Pounds et al., 1982b), and some 
VI-4 

calcium-dependent neurotransmission that regulates the propagation of 

nerve impulses in the brain (Silbergeld et al., 1977; Silbergeld and Adler, 

1978). 

Besides competition with calcium at synaptic binding sites, other 

mechanisms by which lead at low doses may alter the functioning of neurotransmitter pathways (see CD, Table 12-7) include: 1) inhibition in the brain 

of the enzymes (Na,K)-ATPase which helps maintain the ion distribution about 

the cellular membrane required for neuronal activity (Vallee and Ulmer, 

1972), and adenyl cyclase, which regulates cyclic AMP metabolism and synaptic 

transmission (Nathanson and Bloom, 1975); 2) inhibition of sodium-dependent 

neurotransmitter uptake (Silbergeld and Goldberg, 1975); 3) impairment of 

cerebellar and cerebral energy metabolism (Holtzman et al., 1978; Bull et 

al., 1979); 4) inhibition of tetrahydrobiopterin, which helps control the 

synthesis of the neurotransmitters dopamine and norepinephrine (Purdy et al., 

1981); and 5) inhibition of heme synthesis resulting in a) an accumulation of 

ALA in the brain that disrupts the synthesis and function of the neurotransmitter 

GABA (Sassa et al., 1979; Silbergeld and Lamon, 1980), and b) reduced heme 

levels in the liver that appear to alter the activity in the brain of the 

amino acid, tryptophan, and the transmitter to which it contributes, serotonin 

(Litman and Correia, 1983). 

In addition to the above mechanisms, lead may exert its toxicity by its 

ability to rapidly cleave messenger RNA (at concentrations in solution as 

low as 0.001 millimoles) and disrupt protein synthesis (Farkas, 1975; Brown 

et al., 1983). 

It is uncertain whether a common underlying mechanism is involved in 

the diverse functional impairments produced by lead. It does appear however, 

that lead affects biological systems directly rather than through metabolic 

transformation, and that there may be no biological threshold for its 
P.58 

VI-5 

effects at subcellular or cellular sites of action. External exposure levels 

or internal circulating levels (blood lead concentrations) of lead sufficient 

to achieve subcellular or cellular concentrations associated with the biochemical changes described above remain to be defined. 

B. Effects of Concern 

Lead may produce physiological, and ultimately, pathological effects 

in a variety of tissue and organ systems across a broad range of exposure 

levels. Evidence for such effects is drawn from in vitro, animal toxicological, 

and human clinical and epidemiological studies; Based on these data, 

summarized in the CD (Chapter 12), effects in the following areas are of 

primary interest: 

1) heme biosynthesis and related functions 

2) neurobehavioral function 

3) cardiovascular function 

4) kidney function 

5) reproduction and development 

6) possible carcinogenesis/mutagenesis 

7) immunological function 

8) liver, gastrointestinal, and endocrine function 

The major implications of the available literature related to each of these 

effect areas are discussed in Appendix D and summarized in Section VII.C. 

as they relate to assessing the risks associated with alternative lead 

NAAQS. 

C. Sensitive Population Groups 

Two populations, pre-school age children (_< 6 years old) and pregnant 

women, are defined in the CD as particularly sensitive to lead. Several 

factors predispose young children to lead-related risks: 1) greater lead 
P.59 

VI-6 

content of their diets which include large portions of processed foods, 

canned milk, and drinking water; 2) normal mouthing behavior (e.g., finger 

licking and immature dietary habits) which can transfer lead-contaminated 

soil and dust from their hands into the gastrointestinal (GI) tract; 

3) greater lead intake into the respiratory and GI tracts on a body weight 

basis; 4) greater lead absorption and retention rates; 5) greater prevalence 

of nutrient deficiencies which enhance lead GI absorption rates and toxicological 

effects; 6) relatively greater proportion of their lead body burden in soft 

tissues and other labile pools rather than in slow exchange pools (e.g., 

dense bone matrix) as compared to adults; 7) a less developed blood-brain 

barrier that can allow greater entry of lead into the brain; and 8) an 

inherently greater physiological sensitivity of developing tissues and 

organs, as indicated by lower thresholds, and greater severity for lead-induced 

effects in the hematological and neurological systems. 

In addition, dietary and metabolic imbalances, and periods of physiological 

stress, not unusual in young children, can cause variations in the level of 

toxicologically active lead through bone-lead mobilization and changes in 

lead absorption rates (Chisolm and Harrison, 1956; Rosen and Markowitz, 

1980; Araki and Ushio, 1982). 

Physiological sensitivity to lead may be at a maximun during fetal 

development when the central nervous system is undergoing its most pronounced 

growth. Persistent effects on neurological function have been observed 

following in utero lead exposure in experimental animals and have been 

suggested by some preliminary results from human longitudinal studies. The 

pregnant woman is considered sensitive insofar as she is the exposure 

vehicle for her unborn child, since lead is transferred across the placenta. 

However, there is some evidence that indicates a greater risk of maternal 
P.60 

VI-7 

delivery complications at relatively low PbB levels as well (Appendix D.5). 

There were about 23.3 million pre-schoolage children in the U.S. in 

1982 (U.S. Bureau of the Census, 1982); some 14.2 million lived in urban 

areas and approximately 240,000 live near point sources where lead exposure 

is generally higher (CD, Table 13-10; Battye, 1985c). The CD estimates 

that about 4.4 million children between ages 3 and 5 years are particularly 

sensitive to lead because of iron deficiency (CD, p. 13-47). The total 

number of women of child-bearing age (between 15 and 44 years) is estimated 

to be about 54 million, with about 33 million living in urban areas (CD, 

Table 13-10); of these, approximately 7 percent are pregnant at any given 

time (CD, p. 13-47). Levels of risk are not uniform throughout these 

populations but are likely to be distributed according to individual exposure 

conditions, behavioral patterns, and physiological sensitivity to lead. 
P.61 

VII. FACTORS TO BE CONSIDERED IN SELECTING A PRIMARY STANDARD FOR LEAD 

This section, drawing upon the previous evaluation of scientific 

information from the criteria document, outlines the key factors that 

should be considered by the Administrator in designating an appropriate 

averaging time and sampling frequency criteria and in establishing the 

level of the lead primary standard. Preliminary staff conclusions and 

recommendations regarding the most appropriate policy options in each of 

these areas are presented. 

A. Averaging Time 

To be protective of human health, the averaging period for the lead 

standard should be chosen such that variations of exposure that could 

result in adverse effects do not occur unless the standard is exceeded. 

The current averaging time for the lead primary NAAQS is a calendar quarter 

(3 months). When the lead standard was proposed in 1977, the averaging 

time for the primary lead NAAQS was specified as a calendar month which is 

somewhat shorter than the approximately 60 days before steady state PbB 

levels in adults adjust to changes in air lead concentration (Rabinowitz et 

al., 1973; Griffin et al., 1975). A month averaging time was considered 

appropriate because of the greater risk of exposure of young children (42 

FR 63076). Subsequently, EPA promulgated the current NAAQS with a calendar 

quarter averaging time based on the conclusion that an air level of 1.5 ug/m** 

as a ceiling would be safe for indefinite exposure of young children and 

that the slightly greater possibility of elevated air lead levels within 

the quarterly period was not significant for health (43 FR 46246). The 

following assessment of additional health and exposure information available 

since 1978 and other evidence suggests, however, that a shorter averaging 

time than a calendar quarter may be more appropriate. 
P.62 

VIIr2 

1. Equilibration Period for Blood Lead in Children 

No direct measurements have been made on this parameter, 

although the higher metabolic rates in children would be expected to produce 

a more rapid turnover rate of red blood cells, along with lead, in their 

blood compared to adults (Chamberlain et al., 1978). Duggan (1983), based 

on limited lead balance data in infants, has preliminarily estimated a 

considerably shorter half-life of blood lead in children (< 1 week) than in 

adults (18-28 days; Griffin et al., 1975; Rabinowitz et al., 1976; Chamberlain 

et al., 1978). It is of interest to note that regression analyses of NHANES 

II and national gasoline consumption data found that average blood lead 

levels in children were most closely correlated with gasoline lead use when 

a month lag was introduced (EPA, 1985c). 

Perhaps a more important consideration is the time it takes for the very 

small fraction of "active" lead to be transported in plasma and extracellular 

fluid to the various target body organs and tissues. It appears that lead 

levels in plasma rise with levels in whole blood (PbB) in adults (Everson 

and Patterson, 1980; DeSilva, 1981; Cavalleri et al., 1978) and that lead 

is removed from plasma with a half-life of less than one hour; indeed, 

ingested lead appears within urine in less than an hour (Chamberlain et 

al., 1978). These findings suggest that the rate by which lead is transferred 

to soft tissues via the plasma is fast enough that excess lead entering the 

blood stream would be rapidly transported via plasma to tissues. In addition, 

as illustrated in Figure 10-2 of the CD (p. 10-18; Manton and Cook, 1984), 

the relationship between plasma lead and blood lead is curvilinear upwards 

suggesting that transient shifts in blood lead would result in plasma 

values greater than that predicted on the basis of equilibrated percentages 

at lower PbB values. This curvilinearity becomes manifest in adult subjects 
P.63 

VII-3 

at 50-60 ug/dl (DeSilva, 1981; Manton and Cook, 1984), but may well apply 

at relatively lower PbB levels in children. 

Further support comes from data on experimental animals whose levels 

of lead in brain, kidney, and femur followed more of a direct proportionality 

with the level of dosing than with blood lead, which may relate to the fact that 

plasma lead rises proportionally faster than whole blood lead (Azar et al., 

1973; Grant et al., 1980). 

Based on these data, it appears reasonable to assume that increased 

lead exposure may produce increases in steady state PbB levels in children 

sooner than the 60 days observed in adults, and that such changes may not 

reflect those occurring in the levels of toxicologically active, or mobile, 

lead throughout the body, particularly if exposure is in the form of 

intermittent pulses. 

2. Health Impacts Associated with Short-term Peaks in Lead 

Concentrations 

Most animal and human studies of lead toxicity use measures of 

lead exposure which reflect accumulations over time (such as blood and 

tooth lead) and thus do not readily allow effects of different exposure 

patterns to be distinguished. It is generally accepted, however, that 

acute exposures to very high lead levels can result in immediate changes in 

blood lead and overt toxicity. 

Little information is available on the effects of acute exposures to 

lower levels of lead that are relevant to ambient air conditions although 

there may be some cause for concern. For example, consistent with the fact 

that lead is rapidly transported via blood plasma into target tissues such 

as bone marrow, single experimental lead exposures were followed by a rapid 

(<2 weeks) alteration in the heme production cycle, as indicated by 
P.64 

VII-4 

significantly elevated EP in adult men and women (Stuik, 1974; Cools et 

al., 1976). 

Despite limited quantitative health effects data on humans, it appears 

appropriate in deciding whether to retain the calendar quarter averaging time 

to consider the extent of short-term peaks in air lead levels that can be 

anticipated as a result of the implementation of such a standard. The risks 

of shorter term exposures to lead elevated above a quarterly-averaged standard 

that might go undetected were considered in the 1978 standard decision to be 

minimized because 1) based on the ambient data available at that time, the 

possibilities for significant, sustained excursions were considered small, 

and 2) it was determined that direct inhalation of air lead is a relatively 

small component of total airborne lead exposure (43 FR 46246). More recent 

data on short-term air lead levels are considered below. 

Air quality analyses were performed on all available SAROAD data (10,712 

monitor-quarters) collected from stationary source, microscale (for mobile 

source emissions), and neighborhood scale monitors between 1980 and 1984 

(Battye, 1984). Maximum monthly average lead concentrations were higher than 

quarterly averages by an average factor of 1.35. Monthly-to-quarterly average 

concentration ratios for point source monitors were higher than roadside and 

neighborhood monitors with peak ratios for point source sites as high as 2.86 

(See Table 7-1). These ratios were largely independent of average lead 

concentration. These results suggest that in order to protect against maximum 

monthly average concentrations of 1.5 pg/rn^, for example, a quarterly average 

of approximately 1.1 pg/m** would be required, while a quarterly average of 

1.5 pg/m** would allow monthly maximum averages as high as 2.1 pg/rn*^. Daily 

maximum levels were greater than quarterly and monthly averages by an average 

factor of 2.08 and 1.47, respectively. Daily to quarterly and daily to 

monthly ratios near point sources were 2.59 and 1.72, respectively; at 
TABLE 7-1. MONTHLY-TO-QUARTERLY AVERAGE CONCENTRATION RATIOS FOR DIFFERENT SITES 

Distribution 

property 

All 

monitors 

1.35 

1 .28 

1.20 

Point 

source 

monitors 

1.40 

1 .31 

1.25 

Microscale 

roadside 

monitors 

1.27 

1.23 

1.20 

Neighborhood 

scale 

roadside 

monitors 

1.27 

1.2b 

1.20 

Mean ratio 

Median 

Distribution peak 

Upper limits (one tailed) 

80 percent 

90 percent 

95 percent 

98 percent 

99 percent 

1.50 

1.68 

1.89 

2.24 

2.62 

1.60 

1.82 

2.09 

2.43 

2.86 

1.30 

1.56 

1.79 

1.80 

2.00 

1.39 

1.50 

1.67 

1.89 

2.09 

I 

cn 

Source: Battye (1984) 
P.66 

VII-6 

microscale and neighborhood scale sites these ratios were 2.08 to 2.15, 

and 1.57 to 1.61, respectively. 

The magnitude of such excursions in air lead levels over a given quarterly 

average standard are clearly of concern, especially if they are repeated. 

The health significance of these variations, however, is difficult to determine 

at present. 

In summary, although the frequency and health risks associated with 

repeated, short-term increases in children's lead exposure above that allowed 

under any given standard is difficult to quantify at this time, there does 

appear to be some cause for concern given that: 1) lead accumulates in the 

body and is only slowly removed, therefore repeated exposures to small amounts 

over many months may produce elevated PbB levels (CDC, 1985); 2) the mean-life 

of lead in blood is approximately 30 days and the toxicologically active 

fraction of blood lead appears to respond quickly to changes in exposure; and 

3)' based on limited studies, short-term increases to moderate levels of lead 

exposure may result in significant interference in heme biosynthesis. Effects 

on other physiological processes associated with similar short-term exposures 

remain to be studied. 

Based on the above discussion, the staff recommends that consideration 

be given to a monthly average since it would be more protective of children's 

health than the current quarterly standard, especially around point sources 

where emissions may be more sporadic. Guidance is requested from CASAC on 

whether the added protection provided by a change to a monthly standard 

would warrant a revision of the current quarterly averaging period. The 

staff also requests comment on whether the available information suggests 

the need for an averaging time less than a month. 

Given the normal operation of the one in six day lead sampling schedule, 

the number of samples that are collected in the course of a month would 
P.67 

VII-7 

not provide a statistically valid estimate of the actual air quality for 

the period (Thrall et al., 1984). Consequently, should a monthly average 

lead NAAQS be chosen, it would be necessary to increase the air lead sampling 

from one in six days, especially during periods and in areas of maximum 

concentration. Analyses are underway to determine the most appropriate 

sampling schedules under a monthly standard. 

B. Form of the Standard 

The staff recommends that the primary lead NAAQS be stated in a statistical form rather than the current deterministic form. Under the current 

standard, the maximum arithmetic mean average over a calendar quarter is 

not to exceed 1.5 pg/m**. 

The statistical form can offer a more stable target for control programs 

and, with reasonably complete data, is less sensitive to truly unusual 

meteorological conditions than is the deterministic form. In general, 

monthly or quarterly mean concentrations of lead will vary from one month 

or quarter to the next, even if emissions remain constant, due to the 

random nature of meteorological conditions that affect the dispersion 

of lead particles in the atmosphere. Thus, under a deterministic form, 

compliance with the standard, and consequently emission control requirements, 

may be determined on the basis of a month or quarter with unusually 

adverse weather conditions. The general limitations of the deterministic 

form are discussed more fully elsewhere (Biller and Feagans, 1981). 

Recognition of these limitations has most recently led EPA to propose 

statistical forms for the particulate matter standards. 

Conceptually, assuming either a monthly or quarterly averaging time, 

a simple approach would be to express the statistical form as an expected 

maximum monthly or quarterly arithmetic mean determined by averaging the 

annual maximum monthly or quarterly arithmetic averages over a 3-year 
P.68 

VII-8 

period. Specific adjustments to the computations necessary for analyzing 

lead data may be required to account for possible changes in the frequency 

of sampling. 

An alternative approach would be to directly recognize the statistical 

variability associated with the estimated maximum monthly or quarterly 

average and develop a tolerance interval so that a site would not be 

classified as in attainment unless the estimated exceedance rate is below 

the standard level by more than this tolerance interval. Similarly, 

the tolerance interval approach might also.be applied in the other 

direction, so that a site would not be considered as non-attainment 

unless the maximum monthly or quarterly average plus the tolerance 

limit is greater than the standard level. The magnitude of this 

tolerance interval could be determined by developing a statistical 

model to account for the underlying variability of the data and could 

incorporate factors such as autocorrelation. 

The Agency has solicited comments on this general type of statistical 

standard in the proposal for the particulate matter NAAQS issued on 

March 20, 1984 (49 FR 10408). These comments will be examined by staff 

as it assesses these alternative statistical forms. 

Because the level of protection afforded by a standard varies 

significantly with the averaging period, form, and sampling frequency, 

these interactions must be explicitly considered in setting the standard 

level. Rather than attempting to address these variables simultaneously, 

it may be easier to first select an acceptable standard level under one 

set of conditions, and then adjust the level so as to provide roughly 

equivalent protection under alternative averaging periods, forms, and 

sampling schedules. 
P.69 

VII-9 

For purposes of this paper, alternative air lead levels presented 

later will assume a constant average (regardless of averaging period), 

deterministic form, with 1 in 6 day sampling. Analyses are underway to 

better characterize the distribution of quarterly or monthly ambient lead 

concentrations and to examine whether adjustments would be necessary under 

the alternative statistical form approaches, with possibly more frequent 

sampling, to provide equivalent protection. 

C. Level of the Standard 

To assess the degree of health protection that would be afforded by 

alternative lead NAAQS, it is necessary to predict the blood lead (PbB) 

levels associated with various concentrations of air lead for the 

sensitive populations and to determine the toxicological consequences 

associated with different PbB levels among young children. 

1. Summary of Health Risks Associated with Different PbB Levels 

Table 7-2 summarizes the lowest observed effect levels (in terms of 

PbB levels) that the CD concludes to be thus far credibly associated with 

"unacceptable risk" for particular health effects of concern occurring 

among at least some children (CD, p. 13-32). Many other individuals may 

not experience the stated effect until distinctly higher PbB levels are 

reached (CD, p. 13-32), or conversely respond to even lower PbB levels 

due to wide ranges of individual biological susceptibility, variations 

in nutritional status, and other factors. 

It is clear, as discussed in Section VI and in Appendix D, that lead 

affects many different organ systems and biochemical/physiological processes 

across a wide range of exposure levels. These effects range from biochemical 

changes in energy metabolism and synaptic neurotransmission, with no apparent 

threshold on a subcellular molecular level, as well as alterations in blood 
P.70 

VII-1 0 

Tabl e 7-2 . SUMMARY OF LOWEST OBSERVED EFFECT LEVELS FOR KEY LEAD-INDUCED HEALTH EFFECTS IN CHILDREN 

Lowest Observed 

Effect Level (PbB) 

Heme Synthesis and 

Hematological Effects 

Neurological 

Effects 

Renal System 

Effects 

Gastrointestinal 

Effects 

80-100 pg/dl 

70 pg/dl 

60 pg/dl 

50 pg/dl 

40 pg/dl 

Frank anemia 

Reduced hemoglobin 

synthesis 

Elevated coproporphyrin 

Increased urinary ALA 

30 pg/dl 

IS pg/dl 

10 pg/dl 

Erythrocyte protoporphyin A 

elevation 

ALA-0 inhibition 

1 

Py-5-N activity 

inhibition 

1 

•> 

Encephalopathy 

signs and symptoms 

Peripheral neuropathies 

4* •> 

CNS cognitive effects 

(IQ deficits, etc.) 

Peripheral nerve dysfunction 

(slowed NCV's) 

Altered CNS'electrophysiological 

responses 

Chronic nephropathy Colic, other overt 

(aminoaciduria, etc.) gastrointestinal symptoms 

Vitamin 0 metabolism 

interference 

Abbreviations: PbB = blood lead concentrations; Py-S-N = pyrimidine-5'-nucleotidase. 

Source: CD, Table 13-8. 
P.71 

VII-11 

enzyme activity detectable at PbB levels at or below 10-15 ug/dl (e.g., 

ALA-D, pyrimidine-5-nucleotidase) (CD, Table 12-9; Angle et al., 1982) to 

severe, irreversible central nervous system damage manifested by mental 

retardation, encephalopathy (degenerative brain disease), and possibly, death 

at PbB levels starting between 80 and 100 ug/dl (CD, p. 12-62). Other 

overt neurological damage such as peripheral neuropathies have been observed 

at PbB levels as low as 40-60 ug/dl (CD, p. 12-95). Clearly adverse 

effects occur in other organ systems at these elevated levels (60-100 pg/dl) 

including chronic nephropathy, gastrointestinal symptoms, and frank anemia, 

representing an extreme manisfestation of reduced hemoglobin synthesis 

which has been observed at PbB levels as low as 40 ug/dl (CD, p. 12-47). 

Less severe but important signs of impairment in normal physiological 

function are evident at similar and lower exposure levels than those associated 

with overt intoxication. The nervous system is a critical target for low-level 

lead effects, which are summarized in Table 7-3. Indications of sensory and 

peripheral motor nerve dysfunction, such as slowed nerve conduction velocities 

(NCV), have been observed in adults with PbB levels as low as 30-50 ug/dl 

(CD, p. 12-61). Significant delays in neurological development and persistent 

alterations in neurobehavior have been found in young animals exposed to 

relatively low levels of lead (See Appendix D.2). Determining the subtle 

interactive effects of low level lead exposure on children's neuropsychological 

development in relation to social (especially caregiving), genetic, nutritional, 

and other influential variables over time and controlling for experimental 

and analytical biases has proved to be difficult, however, and has generated 

contrasting interpretations. Problems encountered in the conduct and 

interpretation of childhood lead studies are discussed in the criteria 

document and in Appendix D.2. 
Effect 

Biochemical 

Table 7-3. SUMMARY UF LEAD'S EFFtas UN THE NERVOUS SYSTEM 

_ Exposure Reference 

In vitro impairment of: synthesis of tetrahydrobiopterin U.l - 5 pM lead 

Tneurotransmitter cofactor) in rat brain; adenyl cyclase solution 

and Na,K-ATPase activity in rat brain homogenates; 

eneryy metabolism in rat brain mitochondria 

Purdy et al., 1981; Godard and Robinson, 1976; Taylor et al., 1978; Umerek et 

al., 1981; Holtzman et al., 1978 

Delayed development of rat brain energy metabolism 

and respiration (in vivo) 

Altered synthesis, release, and/or uptake of several 

neurotransmitters in vivo (dopamine, norepinephrine, 

serotonin, GABA) 

0.02% lead salt 

in drinking water 

0.004 - 2.0% lead 

salt in drinking water 

McCauley et al., 1979; Bull et al. 

Bull, 1983 

1979, 

Morphological and Functional Development 

Impaired myelin, glial cell development in rat brain 0.1 - 4.0% lead in diet 

Govonl et al., 1978, 1984; Memo et al., 

1980a,b, 1981; Lucchi et al., 1981; Silbergeld et al., 1979; 1980a; Dubas 

et al., 1978; Goldman et al., 1980; Litman and Correia, 1983 

Delayed synaptogenesis and neuronal development in 

young, rat brain 

Delayed development of exploratory and locomotor 

activity; persistent learning and behavior 

deficits in animals exposed jm utero or since 

birth 

0.2 - 4.0% lead in diet 

>0.005% lead in diet 

Reyners et al., 1979; Windebank et al., 

1980; Stephens and Gerber, 1981 

McCauley et al., 1979, 1982; Petit and 

LeBoutillier, 1979; Averill and Needleman, 1980; Campbell et al., 1982; Alfano and Petit, 1982; Petit et al., 

1983; Costa and Fox, 1983 

Brown, 1976; Overmann, 1977; Overmann et 

al., 1981; Winneke et al., 1977; Hastings 

et al., 1979; Bull et al., 1979, 1983; 

McCauley et al., 1979, 1982; Bushnell and 

Bowman, 1979; Rice and Milles. 1979; 

Crofton et al., 1980; Jason and Kellogg, 

1981; Gross-Selbeck and Gross-Selbeck, 

1981; Petit et al., 1983; Levin and Bowman, 1983 

Conflicting preliminary findings; possible small 

deficits in early sensorimotor and mental 

development in infants 

<15 pg/dl 

PbB 

Dietrich et al. 

et al., 1984 

1984; Bellinger 

Electrophysiological 

Altered electrical activity of isolated 

neurons (i_n_ vitro) 

Altered visual and electrical evoked responses, 

visual acuity, and spatial resolution in 

young rats, monkeys 

Subtle, persistent alterations of brain electrical 

activity (EEG patterns, brainstem and auditory 

evoked potentials) in young children 

Depressed conduction velocities in sensory and motor 

nerves of adults and children 

>1 pm lead solution 

>1% lead in drinking 

water 

0.2% lead in diet 

No apparent threshold 

down to 15-30 pg/dl 

PbB and possibly below 

>30-S0 pg/dl PbB 

Fox and Sillman, 1979; Sillman et al. 

1982; Taylor et al., 1978; Palmer et al., 

1981; Olson et al., 1981 

Bushnell et al., 1977; Fox et al., 1977, 

1979, 1982; Winneke, 1980; Cooper et al., 

1980; Impelman et al., 1982 

Otto et al., 1981, 1982, 1984; Beningnus 

et al., 1981; Burchfiel et al., 1980 

Seppalainen et a\., 197S; Araki and 

Honma, 1976; Melgaard et al., 197b, 

Ashby, 1980; Bordo et al., 1982; Johnson et al., 1980; Seppalainen and Hernberg, 1980, 1982; Singer et al., 1983; 

Triebig and Nottbohm, 1983; Feldman et 

al., 1977 

i 

ro 

ro 
Table 7-3. SUMMARY OF LEAD'S EFFECTS ON THE NERVOUS SYSTEM (CONTINUED) 

EJ_fect 

Motor Nerve Function 

Exposure Reference 

Small deficits in perceptual-motor integration and 

fine motor coordination in youny children 

Conflicting results at similar exposure levels 

5U-60 pg/dl PbB, 

possibly as low as 30-

40 pg/dl or lower 

de la Burde and Choate, 1972, 1975; 

Landrigan et al., 1975; McBride et al., 

1982; Needleman et al., 1979; 1984; 

Winneke et al., 1982a, 1983 

Rummo, 1974; Rummo et al.,1979; Perino 

and Ernhart, 1974; Kotok et al., 1977; 

Winneke et al., 1984 

Behavioral Disorders 

Symptoms associated with hyperactivity in children 

Attention (reaction time) deficits and distractability 

in young children 

Effect level not 

adequately defined 

>30-60 pg/dl PbB 

and possibly as low 

as 15-20 pg/dl 

Baloh et al., 1975; Gittleman and Eskenazi, 1983; David et al., 1976, 1983 

Winneke et al., 1983, 1984; Needleman 

et al., 1979, 1984; Yule and Landsdown, 

1983; Hunter et al., 1983 

Auditory and Language Processing 

Deficits in motor speech behavior, language comprehension, formulation behaviors, auditory processing >30-50 pg/dl PbB de la Burde and Choate, 1975; Needleman 

et al., 1979, 1984 

Cognitive Function 

Small deficits in IQ scores on verbal performance, 

visual-motor perception, short-term memory, 

general intelligence among young children 

Conflicting results at similar exposure levels 

>30-50 pg/dl PbB; 

[possibly as low as 

15-30 pg/dl in 

socially disadvantaged 

children] 

Overt Toxicity 

Peripheral nerve damage among chronically exposed 

adults and children 

Encephalopathy, mental retardation, possibly death 

among children 

>40 pg/dl 

>80-100 pg/dl 

de la Burde and Choate, 1972, 

1975; Rummo, 1974; Rummo et al., 1979; 

Perino and Ernhart, 1974; Ernhart et 

al., 1981; Ernhart, 1983, 1984; Needleman et al., 1979, 1984; [Smith et al., 

1983; Harvey et al., 1983, 1984; Yule 

et al., 1984; Winneke et al., 1983, 1984J 

Yule et al., 1983; Yule and Landsdown, 

1983, Winneke et al., 1983, 1984 

Lillis et al., 1977; Spivey et al., 

1979, Haenninen et al., 1979; ZimmermanTansella et al., 1983; Erenberg et al., 

1974 

Gant et al., 1938; Smith et al., 1938; 

Bradley et al., 1956; Chisolm and Harrison, 1966; Chisolm, 1965; 

Bradley and Baumgartner, 1958; Cumings, 

1959; Rummo et al., 1979 

i 

co 
P.74 

VII-14 

The criteria document concludes that: 

"none of the available studies on the subject, individually, can be 

said to prove conclusively that significant cognitive (IQ) or behavioral 

effects occur in children at PbB levels < 30 ug/dl. Rather, the 

collective neurobehavioral studies can probably now be most reasonably 

interpreted as being clearly indicative of likely associations between 

neuropsychologic deficits and low level lead exposures in young children 

resulting in PbB levels ranging to as low as 30-50 ug/dl. The 

magnitude of average observed IQ deficits appears to be approximately 

5 points at mean PbB levels of 50-70 ug/dl and about 4 points at 

mean PbB levels of 30-50 ug/dl (CD, p. 13-35). Although such IQ 

deficits are relatively small on average, such shifts in the mean can 

make a substantial difference in the percentage of children with IQ's 

in the extremes of the population distribution (i.e., below 80 and 

above 125) and may impact the intellectual development, school achievement, 

and social development of the affected children sufficiently so as to 

be regarded as adverse" (CD, p. 13-36). 

In children estimated to have PbB levels between 15 and 30 ug/dl, 

small deficits in IQ and attentiveness have been observed, although no 

consistent statistically significant associations have been found (Smith et 

al., 1983; Harvey et al., 1983, 1984; Yule et al., 1984; Hunter et al., 

1984; Winneke et al., 1983, 1984). Because the most reliable of these 

studies found 1-2 point IQ deficits remaining after correction for confounding 

factors, the criteria document concludes that "lead cannot be totally ruled 

out as a possible etiological factor contributing to the induction of such 

effects in the 15-30 ug/dl range, based on existing published studies" 

(CD, p. 13-36). 

In addition to IQ decrements, PbB levels in the 30-50 ug/dl range 

may be associated with deficits in auditory and language processing, motor 

coordination, appropriate social behavior, and the ability to focus attention 

(ae la Burde and Choate, 1972, 1975; Needleman et al., 1979; Winneke et 

al., 1983). The degree to which lead's effects on neuropsychological performance 

at these levels persist into later life remains to be established. 

Altered electrical activity in the brain has also been associated with 

PbB levels in children (along with IQ decrements; Burchfiel et al., 1980) 
P.75 

VII-15 

in the range of 30-50 ug/dl, with no evident threshold down to 15 ug/dl 

or somewhat lower (Benignus et al., 1981; Otto et al., 1981, 1982, 1984). 

The functional significance of many of the electrophysiological changes 

observed below 30 ug/dl (i.e., slow wave potentials, synchronized EEG 

amplitudes, visual evoked potentials) has not been established, although 

some changes persisted for at least two years (Otto et al., 1982). However, 

slowed nerve conduction in the auditory pathway has been related to 

pathological lesions and to non-specific demyelinating diseases such as 

multiple sclerosis; thus the effects on auditory brainstem evoked potentials 

observed across the range of PbB levels between 6 and 59 ug/dl may be 

indicative of subtle neurological impairment (Otto et al., 1984). 

Alterations in neurochemistry (e.g., neurotransmission, brain mitochondrial 

function) are evident within minutes of exposure to submicromolar concentrations 

of lead in vitro and in vivo. Although the functional significance is 

difficult to assess and no estimates can be made of PbB levels at which such 

effects occur in humans, these neurochemical changes (e.g., inhibition of 

acetylcholine release and Na,K-ATPase activity) exhibit continuous doseresponse relationships which may form the bases of delayed brain development 

and disrupted neurobehavioral function (Silbergeld, 1983). For example, 

effects have been found on certain behavioral (e.g., reaction time deficits), 

and electrophysiological (e.g., altered EEG patterns, nerve conduction 

velocities) measures indicative of CNS and peripheral nerve function perturbations, supporting a continuous dose-effect gradient between lead and 

neurotoxicity down to exposure levels as low as 15-30 ug/dl PbB, or 

perhaps, somewhat lower (CD, p. 12-137). 

In summary, although there have been inconclusive findings and contrasting 

interpretations regarding lead's effects on specific neurobehavioral indicators 
P.76 

VII-16 

and functions (e.g., verbal performance, emotional reactivity, perceptual-motor 

integration, short-term memory, attention electrical activity in the brain) 

and the mechanisms involved, the overall evidence indicates that lead is 

associated with neurological impairment in some children with PbB levels 

between 30 and 50 ug/dl and that possibly lower levels of exposure (i.e., 

down to 15 ug/dl) may have some small, but potentially important and 

persistent effects on neurological function. 

The impacts of lead on heme synthesis and related systems are summarized 

in Table 7-4. Because heme synthesis is a continuous process, most of these 

effects are reversible upon removal or reduction of lead from the organism or 

cellular systems involved. However, given: a) that there may be long-term 

effects of even transitory changes in developing tissues in,children; 

b) heme's pervasive role in many organ systems and physiological processes; 

and c) the sensitivity of heme production to lead, lead's .interference in 

the heme synthetic pathway must be carefully considered. 

As discussed in Appendix D, lead interferes with heme synthesis at 

several points in its metabolic pathway: 

1) Activity of the enzyme ALA-D, which catalyzes the conversion of ALA 

to porphobilinogen, is inhibited in red blood cells at PbB levels below 

10-15 ug/dl with no clear threshold. ALA-D activity in soft tissues such 

as liver, brain, and kidney, appears to be inhibited to the same degree at 

similar PbB levels; 

2) Accumulations of ALA, which result from inhibited ALA-D activity, 

have been noted in plasma and urine at PbB levels of 40 ug/dl, and possibly 

as low as 18 ug/dl. Increases in non-utilized ALA likely occur in brain, 

kidney, and other tissues at roughly the same PbB levels associated with 

ALA accumulations in plasma; 
PbB 

(ug/dl)1 

<10 

>12 

«15 

>20 

25 - 30 

>33 

18 - 40 

»40 

Effect 

Table 7-4. SUMMARY OF LEAD'S EFFECTS ON HEME BIOSYNTHESIS AND 

RELATED SYSTEMS IN CHILDREN 

References 

Inhibition of ALA-D, Py-5-N, red 

cell ATPase activity 

Reduction in vitamin D hormone 

synthesis 

Accumulation of EP indicating 

impaired heme synthesis 

Impaired globin synthesis 

Significant EP elevation above 

normal 

Significant interference with vitamin 

D hormone synthesis comparable to that 

seen in renal diseases 

Accumulation of underutilized ALA; 

possible interference with neurotransmission 

Significant reduction in hemoglobin levels (anemia) 

Impairment of cytochrome synthesis 

and function (e.g., drug metabolism, 

cellular energy metabolism) 

Alterations in heme-based 

neurochemical synthesis and 

neurological tissue development 

Hernberg and Nikkanen, 1970; Secchi et al., 1973; 

Wada et al., 1976; Angle and Mclntire, 1978; 

Valentine and Paglia, 1980 

Rosen et al., 1980 

Roels et al., 1976; Piomelli et al., 1977;, 1982; 

Hammond et al., 1984; Rabinowitz et al., 1985 

White and Harvey, 1972; Dresner et al., 1982 

Roels et al., 1976; Piomelli et al., 1982 

Rosen and Chesney, 1983; Chesney et al., 1983 

Meredith et al., 1978; O'Flaherty et al., 1980; 

Nicoll, 1976; Brennan and Cantrill, 1979; Silbergeld et al., 1980, 1982 

Betts et al., 1973; Rosen et al., 1974; Adenbojo, 

1974; Pueschel et al., 1972 

Alvares et al., 1975; 1976, Meredith et al., 

1977; Saenger et al., 1984; Holtzman and Shen 

Hsu, 1976; Bull et al., 1979 

Litman and Correia, 1983; Whetsell and Kappas, 

1981; Whetsell et al., 1984 

i 

•~J 

1 These levels represent lowest observed effect levels in a significant fraction of children studied. In some 

cases, no threshold has been detected, as noted by < or > signs. 
P_78^ 

VII-18 

(3) Lead impairs the transmitochondrial transport of iron and instead 

of producing heme, the mitochondria accumulate its precursor, protoporphyrin 

which, lacking iron, is incapable of performing its essential respiratory 

function. As a result of lead intoxication in newly forming erythrocytes, 

protoporphyrin (referred to as erythrocyte protoporphyrin or EP) takes the 

place of heme in the specific pocket of the hemoglobin molecule. As the 

red cells remain in the circulation, zinc is rapidly chelated at the center 

of the molecule in the site normally occupied by iron (Piomelli et al., 1982). 

The resulting zinc protoporphyrin (ZPP) is tightly bound in the available 

heme pocket for the life of the erythrocyte, normally 120-130 days (Lamola 

et al., 1975). The PbB threshold for elevated EP in children is approximately 

15 ug/dl in children with significant elevations (>1 and 2 standard 

deviations above normal EP mean levels) occurring in 50 percent of children 

studied at PbB levels of between 25 and 35 pg/dl (Roels et al., 1976; 

Piomelli et al., 1982). 

The health significance of EP or ZPP accumulation is that it indicates 

that heme or hemoprotein synthesis in many tissues has been impaired as a 

result of lead's entry into mitochondria (CD, p. 12-46). Previously, EP 

elevations at PbB levels around 30 ug/dl were of concern based on functional 

disruptions in hemoglobin synthesis at 40 ug/dl and neurobehavioral 

effects above 50 ug/dl (EPA, 1977). In setting the current lead NAAQS in 

1978, 30 ug/dl was adopted as a maximum safe PbB, allowing some margin of 

safety relative to levels associated with inhibitions of hemoglobin synthesis 

or neuropsychological deficits. This PbB level was identical to the Center 

for Disease Control's (CDC) previous criteria level for undue lead exposure 

for young children. 

Recent data, however, have provided more information on the extensive 

impact of lead on the body heme pool and associated disruptions of many 
P.79 

VII-19 

physiological processes (see Figure 7-1). With increasing lead exposure, 

impairment of heme and hemoprotein synthesis intensifies in different 

organ systems resulting in reductions in oxygen transport, changes in 

cellular energetics, neurotransmitter function, and in detoxification of drugs 

and other foreign agents, and impairments in the biosynthesis of important 

substances such as 1,25-dihydroxyvitamin D (1,25-0H2~D). Inspection of 

Figure 7-1 reveals effects that can be viewed as intrinsically adverse as 

well as those that reduce the body's ability to cope with other forms of 

toxic stress, e.g., reduced hepatic detoxification of certain drugs and 

other xenobiotics (as a result of lead-induced impairment of hepatic enzyme 

systems), and possibly impairment of the immune system (CD, p. 13-30). 

Of the functional consequences associated with heme reductions and 

lead's interaction with those processes, perhaps the best quantitative data 

is available on the negative correlation between PbB levels (beginning at 

12 ug/dl) and circulating levels of the vitamin D hormone, 1,25(0H)2 D 

(Rosen et al., 1980). Highly significant and profound depressions in 

circulating 1,25(0H)g D levels were found in children whose PbB levels 

ranged from 33 to 120 pg/dl, with the most striking decreases above 

62 pg/dl. The criteria document concludes that it appears likely that 

lead-induced reductions in heme underlie this association, and that impaired 

production of 1,25(0H)2 D can have profound and pervasive effects on tissues 

and cells of diverse type and function throughout the body (CD, p. 12-49): 

(1) Altered levels of 1,25(0H)2 D may impact calcium homeostasis and 

thus calcium-dependent processes essential to several enzyme systems, the 

transport of and response to various hormonal and electrical stimuli, and 

cyclic nucleotide metabolism. In addition, lead may directly affect the role 

of 1,25(0H)2 D in cell differentiation/maturation, immunoregulation, pancreatic 
P.80 

VII-20 

function (e.g., insulin secretion), and mediation of tumorigenesis (See Appendix 

D.l(c); CD, pp. 12-40 to 12-42); 

(2) The effect of lead on 1,25(0H)2 D is a particularly robust 

one, with PbB levels of 30-50 pg/dl resulting in decreases in the hormone 

that overlap comparable decreases observed in children with severe kidney 

injury lacking two-thirds of normal renal function, as well as in those 

with various genetic disorders such as vitamin D-dependent rickets and 

hypoparathyroidism (Rosen et al., 1980; Rosen and Chesney, 1983; Chesney 

et al., 1983). 

At higher levels, lead's interference with heme synthesis and other red 

blood cell functions (e.g., inhibition of Py-5-N activity which affects 

membrane stability) may result in anemia. Although this is a serious clinical 

manifestation, the inhibition of heme synthesis at lower lead levels has 

much wider implications for a multitude of organs and systems, as described 

above, especially in the growing child. 

The CD concludes that: 

"Given the available evidence indicative of significant effects on 

neurological functioning and other important physiological processes as 

PbB levels increase above 15-20 pg/dl and approach or exceed 30-40 pg/dl, 

the rationale for continuing to view 30 pg/dl as a "maximum safe" PbB 

level is called into question and substantial impetus is provided for 

revising the criteria level downward, i.e., to some PbB below 30 pg/dl. 

At this time, it is difficult to identify specifically what blood-Pb 

criteria level would be appropriate in view of the existing medical 

information. Clearly, 30 pg/dl can no longer be seen as affording 

any margin of safety before PbB levels are reached that are associated 

with unacceptable risk of notable adverse health effects occurring in 

some children. This is based on at least two grounds: (1) PbB levels 

in the 30-40 pg/dl range are now known to "mask" for some children 

markedly elevated chelatable body lead burdens that are comparable to 

lead burdens seen in other children displaying overt signs and symptoms 

of lead intoxication; and (2) PbB levels in the 30-40 pg/dl range 

are also associated with the onset of deleterious effects in several 

organ systems which are either individually or collectively seen as 

being adverse. 
P.81 

VII-21 

"At levels below 30 ug/dl, many of the different smaller effects 

reported as being associated with lead exposure might be argued as 

separately not being of clear medical significance, although each is 

indicative of interference by lead with normal physiological processes. 

On the other hand, the collective impact of all of the observed effects 

(representing potentially impaired functioning and depleted reserve 

capacities of many different tissues and organs) may, at some point 

distinctly below 30 ug/dl, be seen as representing an adverse pattern 

of effects worthy of avoidance with some added margin of safety. The 

onset of signs of detectable heme synthesis impairment in many different 

organ systems at PbB levels starting around 10-15 ug/dl, along with 

indications of increasing degrees of pyrimidine metabolism interference 

and signs of altered nervous system activity, could be viewed as such 

a point. Or, alternatively, the collective impact of such effects 

might be argued as becoming sufficiently adverse to warrant avoidance 

(with a margin of safety) only when the various effects come to represent 

marked deviations from normal as PbB levels exceed 20-25 ug/dl and 

begin to approach the more -clearly adverse 30 ug/dl level. Lastly, 

other arguments have been advanced to the effect that any deviation 

from normal biochemical levels or physiological functioning in any 

organ system should be viewed as adverse health effects to be avoided, 

even at PbB levels below 10 ug/dl." (CD, p. 13-40) 

Table 7-5 presents a preliminary staff assessment of the data in the 

CD that are most useful in determining a safe PbB for protection of the 

sensitive populations. The table focuses on those effects associated 

with PbB levels at and below 40 ug/dl. The clearly adverse effects at 

higher exposures are listed in Table 7-2. 

Based on the above discussion, the staff concludes that multi-organ 

effects resulting from impairments in heme synthesis and vitamin D metabolism 

are likely between 25-30 ug/dl, and that potentially significant effects 

on these processes, as well as on the central nervous system may be 

possible at the lower PbB levels indicated, but the evidence and risks 

are less certain. In evaluating the health effects in the context of 

decision-making on an appropriate PbB level of concern, the following 

considerations are important. 

1) There is considerable uncertainty and controversy regarding the 

nature and degree of lead's impact on neuropsychological function although 

the weight of the evidence suggests a small but significant association 
P.82 

Table 7-5. 

VII-22 

STAFF ASSESSMENT OF KEY HEALTH EFFECTS OF LEAD 

PbB Observed Effects Implications 

40 pg/dl Reduced hemoglobin synthesis; anemia in some children1 

Possible IQ (4-5 point avg.) and behavioral deficits2 

Significant reductions in vitamin D hormone synthesis3 

Possible slowed nerve conduction velocities4 

Subtle alterations 1n brain electrophysiology' 

Strong evidence for significant 

and persistent effects on hematological, neurological, 

immunological and detoxification systems. 

3U yg/dl Significantly elevated EP6 

Possible IQ (4 point avg.) and attentional deficits7 

Significant reductions in vitamin D hormone synthesis3 

Possible slowed NCVs3 

Subtle alterations in brain electrophysiology^ 

Significant Py-5-N activity inhibition8 

Likely multi-organ effects 

resulting from heme and vitamin 

D impairment. Some risk of 

behavioral/sensory disturbance and 

effect on cognitive function or 

academic capacity. 

25 ug/dl Significantly elevated EP5 

Possible IQ (1-2 point avg.) and attentional deficits9 

Reduced vitamin D hormone synthesis3 

Subtle alterations in brain electrophysiology1" 

Likely multi-organ effects 

resulting from heme and vitamin 

D impairment. Some risk of 

behavioral/sensory disturbance 

and effect on cognitive function 

or academic capacity. 

2U pg/dl Elevated EP6 

Possible IQ (1-2 point avg) and attentional deficits9 

Reduced vitamin D hormone synthesis3 

Subtle alterations in brain electrophysiology1^ 

Some risk of multi-organ effects 

resulting from heme and vitamin D 

impairment. Some risk of behavioral/sensory disturbance and effect 

on cognitive function or academic 

capacity. 

15 pg/dl Lowest level of elevated EP6 

Possible IQ and attentional deficits9 

Reduced vitamin D hormone synthesis3 

Subtle alterations in brain electrophysiology10 

Reduced ALA-D activity11 

Small risk of multi-organ impairments resulting from heme and vitamin D impairment, behavioral/sensory disturbance and effect on 

cognitive function or academic 

capacity. 

5-10 pg/dl Reduced ALA-D activity,11 Py-5-N synthesis8 

Subtle alterations in brain electrophysiology1^ 

Significant functional effects 

unlikely. 

Experimental alterations in neurochemistry and cellular 

energy metabolism12 

Effects detectable at low in vitro 

levels or experimental dosages; 

corresponding human PbB levels and 

functional significance difficult to 

determine 

ibetts et al., 1973; Rosen et al., 1974; Adenbojo, 1974; Pueschel et al., 1972 

2 De la Burde and Choate, 1972, 1975; Perino and Ernhart, 1974; Ernhart et al., 1981; Ernhart, 1983; Needleman et al., 197yNeedleman, 1984 

3Rosen et al., Iy80; Mahaffey et al., 1982; Rosen and Chesney, 1983 

4Seppalainen et al., 1979; Seppalainen and Hemberg 1980, 1982; Feldman et al., 1977 

5Otto et al., 1981, 1982, 1984; Beningnus et al., 1981; Burchfiel et al., 1980 

6Piomelli et al., 1977; 1982; Roels et al., 1976; Hammond et al., 1984; Rabinowitz et al., 1985 

7Needleman et al., 1979, 1982; Needleman, 1982 

8Valentine and Paglia, 1980; Angle and Mclntire, 1978; Angle et al., 1982 

9Smith et al., 1983; Harvey et al., 1983, 1984; Yule et al., 1984; Hunter et al., 1983; Winneke et al., 1983, 1984 

1 00tto et al., 1982, 1984 

^Hernberg and Nikkanen, 1970; Granick et al., 1973; Roels et al., l»75b; Wada et al., 1976 

126ull et al., 1975, 1979; Holtzman and Shen Hsu, 1976; McCauley et al., 1979; Holtzman et al., 1978; Silbergeld and 

Adler, 1978; Silbergeld et al., 1979, 1982; Purdy et al., 1981; Litman and Correia, 1983 
P.83 

VII-23 

between lead, IQ, and disturbances in sensory/attention processes at levels 

between 30 and 50 pg/dl and possibly down to 15 ug/dl. It is hoped 

that improved information will result from ongoing research as well as 

from the ongoing EPA "risk assessment" that will elicit probabilistic 

expert judgment on the existing data base regarding lead's relationship 

to IQ in children. 

2) Similarly, there is incomplete information on the medical significance 

of elevations in EP and the dose-response relationship between lead and 

hemoglobin decrements. The ongoing risk assessment will hopefully provide 

useful information on these issues as well. 

3) The risks associated with reductions in vitamin D hormone synthesis 

and altered brain wave activity at PbB levels _< 30 ug/dl are difficult 

to determine at present. It is felt that the collective impact of these 

changes along with other lead-induced effects at low PbB levels should be 

considered sufficiently important to warrant avoidance. 

4) As part of their lead poisoning screening program, the CDC has 

revised their definition of lead toxicity for individual children from 

30 ug/dl to 25 ug/dl PbB, accompanied by an elevated EP level (>_ 35 pg/ 

dl) (CDC, 1985). Detecting these levels identifies a child as 

requiring immediate medical and environmental intervention. The revisions 

were based on the recent evidence of neurobehavioral, hematological, and 

vitamin D metabolism effects of lead cited above, and on evidence that a 

blood lead concentration may underestimate the body burden of lead in a 

child. CDC argued that 30 ug/dl provides little or no margin of safety, 

and that the biologic threshold for lead toxicity as indicated by increasing 

EP levels, is below 20 ug/dl (CDC, 1985). However, CDC acknowledges 

that practical considerations must be taken into account in setting this 

level. An intervention level of 25 ug/dl therefore represents an 
P.84 

VII-24 

accommodation based on a pragmatic decision on the limits of effectively 

implementing the existing screening program and how much risk is tolerable. 

5) The Clean Air Act requires that the air standard be precautionary 

in nature and that the level should not be based on economic or technological 

considerations. While the lead NAAQS and CDC's program share the common 

goal of reducing children's lead exposure, there is an important distinction. 

The screening program is a form of secondary prevention and is necessary 

to prevent lead toxicity among susceptible children, but is based in 

part, on practical, technological, and cost considerations. In contrast, 

the lead NAAQS is a form of primary prevention to control lead emissions 

at the source, before opportunities for human uptake and undue risks 

arise, and is not to be based on cost. 

The staff concludes on the basis of the above considerations that the 

CDC intervention level is not directly an appropriate surrogate for the 

lead NAAQS and that a PbB level of 25 ug/dl contains little or no 

margin of safety from potentially adverse effects on heme synthesis, 

vitamin D metabolism, and possibly neurological and behavioral functions. 

2. Predicting Blood Lead Levels under Alternative Air Lead Levels 

Three approaches are examined here that can be used to estimate the 

impact of alternative air lead levels on PbB levels among children. The 

first is to combine the estimates of daily lead uptake from all routes of 

exposure for given air lead concentrations with the derived lead uptake-toblood lead relationships, as presented in Section V.A. The second approach 

is to directly apply mathematical relationships between air lead and 

blood lead derived from population studies and appropriate statistical 

analyses that account for children's exposure to atmospheric lead through 

pathways other than inhalation such as ingestion of dust and soil (Section 
P.85 

VII-25 

V.B.2). Finally, a hybrid of the first two approaches is provided in the 

criteria document in which mathematical relationships derived from population 

studies are applied to estimates of lead concentration in individual 

media (Section V.B.I). These three modeling approaches are discussed 

below and the results are presented (in Table 7-12) for consideration in 

the possible use of one, two, or all three approaches (with any necessary 

modifications using improved data) in assessing the protection afforded 

by alternative lead NAAQS. 

All three models estimate PbB levels in terms of population mean 

levels. For purposes of setting a lead NAAQS, it is necessary to determine 

the blood lead distribution corresponding to a given mean PbB for the 

population of children such that a specified percentage is protected from 

exceeding a maximum acceptable PbB level. In determining such a distribution, 

it is important to recognize that there is significant biological variability 

within any population, and it is those individuals with the greatest 

adverse response to any given lead exposure that are of greatest concern 

in establishing a primary lead NAAQS. A method to consider the most 

susceptible segment of the population of children is discussed here. 

Several epidemiological studies have indicated that the log values of 

measured individual PbB levels in a uniformly exposed population are 

normally distributed with a variation, including analytical variation, 

ranging between 1.3 and 1.4, when expressed as a geometric standard 

deviation (GSD) (Tepper and Levin, 1975; Azar et al., 1975; Billick et 

al., 1979). Using standard statistical techniques, it is possible to use 

the geometric standard deviation to calculate the mean population blood 

lead level that would place a given percentage of the population below 

an acceptable maximum PbB for an individual child. The NHANES II study, 

which provides the best available data in terms of quality control and 
P.86 

VII-26 

sample size, yields estimates of GSDs in the range of 1.34 to 1.39, uncorrected for analytical variation, for various subgroups of young children 

with comparable sex, age, income, and place of residence (i.e., degree of 

urbanization) (CD, p. 11-29 to 11-30). By using these GSDs for separate 

homogeneous populations identified in the NHANES II survey, it is possible 

that the most sensitive segment (i.e., highly exposed) of the population 

is not being accurately characterized since for that group there is 

likely to be a different distribution of exposures from the homogenous 

NHANES II subgroups. This is indicated by the fact that the GSD for all 

black children living in central cities was 1.46 and for all children sampled 

in NHANES II, the GSD was 1.47, not adjusted for age, income, or degree of 

urbanization (DHHS, 1984). The range of GSDs presented above which are 

assumed to be constant for the entire distribution should therefore be 

interpreted as preliminary attempts to characterize the most appropriate 

sub-populations of children given the available data in the CD. The 

calculations of blood lead distributions under various air lead levels 

using the three models presented below should also be considered as 

preliminary until further comment and CASAC guidance is received on 

this issue. 

Analytical variation which exists in any measurement has an impact 

on the bias and precision of statistical estimates such as the GSDs 

derived from NHANES II. For this reason, it is important to recognize 

the magnitude of analytical variation in blood lead measurements due to 

measurement variation (i.e., between measurements run at the same time) 

and variation created by analyzing blood samples at different times 

(CD, p. 11-26). Correcting these GSDs for the overall estimate of analytical 

variation for the NHANES II study (0.02083) yields estimated GSDs in the 

range of 1.29 to 1.34. Using GSDs corrected in such a way, although providing 
VII-27 

a more accurate characterization of a given blood lead distribution, may 

not be appropriate for this assessment because the health effects studies used 

to define a maximum acceptable PbB did not correct their PbB measurements 

for analytical variance. These studies, like NHANES II, generally employed 

the best available measurement techniques and quality control. Using 

"corrected" GSDs on one hand to predict percentages of children with various 

PbB levels given a target mean population PbB, and then matching those 

predicted PbB levels with "uncorrected" PbB levels derived from health 

studies in order to assess the risks associated with that population mean 

PbB, would result in a somewhat biased assessment. Therefore, the range 

of GSDs presented in the CD from NHANES II that are not corrected for 

analytical variance will be used in further calculations. The staff 

encourages any comment or additional information on this issue. 

In setting the current lead NAAQS in 1978, EPA estimated that in 

order to protect 99.5% of U.S. children from attaining a PbB of 30 ug/dl, 

a target population mean PbB would be approximately 15 ug/dl assuming a 

GSD of 1.3. Similar calculations can be made for other percentages of 

the population, e.g., 99.9 or 99.0%. There are approximately 25 million 

children under 7 years of age in the U.S., some 14 million in urban 

areas, and approximately 240,000 living near point sources where atmospheric 

lead exposures may be high (CD, p. 13-47; Battye, 1985c). 

Table 7-6 presents the population mean PbB levels that would be 

required to protect 99.5% of U.S. children from reaching various PbB levels 

given the range of uncorrected GSDs derived from NHANES II for homogeneous 

subpopulations. (Mean PbB levels necessary to provide 99.9% protection 

would be somewhat lower; conversely, they would be higher for 99.0% 

protection). 

These values were calculated using the formula given to describe a 
P.88 

VII-28 

lognormal distribution (Yankel et al., 1977): Mg • GSDn = Dn 

where 

Mg = geometric mean PbB 

GSD = geometric standard deviation 

n = the number of standard deviations 

Dn = value of PbB at a standard deviation. 

Table 7-6. POPULATION MEAN BLOOD LEAD LEVELS (pg/dl) REQUIRED TO 

PREVENT 99.5% OF U.S. CHILDREN FROM EXCEEDING SPECIFIED BLOOD LEAD LEVELS 

(Assuming GSDs of 1.34 - 1.39) 

GSD 

1.39 

1.34 

Maximum Acceptable Blood Lead Level (pg/dl) 

25 20 15 10 

10.7 

11.8 

8.6 

9.4 

6.4 

7.1 

4.3 

4.7 

It should be noted that if the GSD of 1.47 calculated for all children 

sampled by NHANES II (not adjusted for age, sex, income, or degree of 

urbanization) is used, the population mean PbB levels required to protect 

99.5% of children from exceeding 25, 20, 15, and 10 pg/dl would be 9.3, 7.4, 

5.5, and 3.7 pg/dl, respectively. 

a) Integrated Lead Uptake/Biokinetic Model 

Table 7-7 presents the upper and lower bound estimates of average 

daily lead uptake derived in the Integrated Lead Uptake Model in Section 

V.A.I for point sources and general urban/rural areas under different 

average air lead concentrations, along with the corresponding PbB levels 

predicted for 2 year old children by the biokinetic model presented in 

Section V.A.2 (Harley and Kneip, 1985). 

Several uncertainties associated with these estimates are discussed 

in Section V.A.I and Appendix B. It is important to emphasize that because 

air lead (and associated dietary, soil, and dust lead) levels were assumed 

to be constant at whatever air level was analyzed, the upper ends of 
P.89 

VII-29 

Table 7-7. AVERAGE BLOOD LEAD LEVELS FOR CHILDREN UNDER DIFFERENT AIR LEAD LEVELS 

(ESTIMATED USING INTEGRATED LEAD UPTAKE/BIOKINETIC MODEL) 

Average Average Average 

Air Lead Lead Uptake Blood Lead 

(ug/m3)

1 Type of Area (ug/day)? (ug/dl )3 

0.25 

0.50 

0.75 

1.0 

1.25 

1.5 

1.75 

General 4.8-11.1 1.9-4.4 

Pt. Source 7.0 - 21.3 2.8 - 8.6 

General 9.2 - 17.8 3.7 - 7.2 

Pt. Source 16.3 - 29.0 6.6 - 9.3 

General 14.1 - 29.4 5.7 - 11.9 

Pt. Source 22.0 - 35.8 8.9 - 14.5 

General 18.9 - 33.9 7.7 - 13.7 

Pt. Source 27.4 - 45.0 11.1 - 18.2 

General 24.4 - 42.8 9.9 - 17.3 

Pt. Source 37.1 - 50.3 15.0 - 20.3 

General 28.2 - 48.4 11.4 - 19.6 

Pt. Source 41.8 - 62.3 16.9 - 25.2 

General 29.8 - 50.9 12.0 - 20.6 

Pt. Source 46.3 - 69.1 18.7 - 27.9 

*Air lead levels that were used to calculate daily uptake levels were assumed 

to be constant and therefore can represent either monthly or calendar quarterly 

averages. 

^Uptake estimates derived in Table 5-1. Range under each air lead level and 

location reflects upper and lower bound sets of estimates used to calculate 

uptake levels. 

3PbB levels for 2 year old children derived from lead biokinetic model 

(Harley and Kneip, 1985) discussed in Section V.A.2. Range under each air 

lead level and location reflects uncertainties in uptake estimates. 
P.90 

VII-30 

these ranges in particular may represent "worst case" population mean 

uptake and PbB estimates for each air lead concentration. Furthermore, 

estimated PbB levels at 2 years of age were selected in order to predict 

the maximum impacts on young children. At this age, PbB levels would be 

highest, assuming constant exposure, according to the biokinetic model 

(consistent with the NHANES II data). The staff believes, therefore, 

that given the available data and necessary assumptions used in this 

model, the lower ends of the ranges of PbB levels for the different 

air lead levels reflect the best estimates of lead exposure, uptake, and 

metabolism among individuals in different locations within the population. 

The lower bound estimates for 2 year old children will thus be used as 

the predicted mean PbB levels under each air level in later calculations. 

Finally, using standard statistical techniques and identified characteristics of the PbB distribution within the population (discussed previously), 

it is possible to calculate for any mean PbB, the individual PbB at a 

specified standard deviation. This calculation is illustrated below for 

the other two modeling approaches and the results are later summarized in 

Table 7-12. 

b) Application of "Aggregate" Blood Lead/Air Lead Relationships 

from Epidemiological Studies 

i) Blood/Air Lead Slope 

The epidemiological studies discussed in Section V.B. provide 

quantitative estimates of the relationship between air lead exposures 

and PbB levels in various populations of children. In assessing the 

total impact that atmospheric lead makes on total exposure, the aggregate 

modeling approach discussed in Section V.B.2 attempts to recognize the 

simultaneous presence of lead in multiple environmental media. Thus, the 

median blood/air lead inhalation slope for children (s) is estimated 

in the CD to be 1.92 from three major studies (Yankel et al., 1977; Roels 
P.91 

VII-31 

et al., 1980; Angle and Mclntire, 1979), and aggregate slopes that include 

both direct (inhalation) and indirect (via soil, dust, etc.) air lead 

contributions typically yield values in the range 3-5 (CD, p. 11-108). 

To acount for possible re-entry of lead into the blood transferred 

from bone or other long-term storage, Chamberlain (1983) estimates 

that blood/air lead relationships for adults must be multiplied by a 

factor of 1.3, yielding a range of aggregate slopes between 4 and 6 for 

total air lead exposure. It is possible that the rapid growth and high 

rate of turnover in children's skeletal systems would require an even 

higher adjustment. 

Assuming that these slopes are reasonably accurate, and that at lower 

levels of exposure (< 30 ug/dl) a linear relationship applies (Chamberlain, 

1983; CD, p. 11-64), a 1 ug/m3 change in the average air lead concentration 

would produce a corresponding increase of between 4 and 6 ug/dl in the 

average equilibrated blood lead level of young children. 

"ii) Contributions from Non-Air Sources of Lead 

To predict PbB levels associated with alternative air lead levels using 

these aggregate slopes, it is necessary to estimate the contribution to 

total lead exposure from emission sources not subject to control by implementing an air quality standard. These sources may include lead-soldered 

food cans, lead plumbing, lead-based paint, and indirect occupational 

exposures (i.e., from clothing and shoes of parents who work in lead-related 

industries). It should be noted that by using observed lead concentrations 

in dust from a wide range of locations and conditions, the integrated 

uptake model discussed in the previous section attempted to implicitly 

account for average contributions to total exposure from lead-based paint. 

In addition, the estimates provided in the criteria document based on 
P.92 

VII-32 

recent FDA and industry data directly provide estimates for non-air sources 

of lead in the diet which were used in the model. 

In attempting to explicitly estimate exposures from non-air sources 

of lead, which is necessary in applying the aggregate blood/air lead 

slopes to determine an appropriate lead NAAQS, several difficulties arise: 

1) With the exception of non-air lead in diet, few studies provide 

detailed information on the relative contribution of various sources to 

children's PbB levels in the U.S. Estimates must be made by inference 

from earlier survey data and theoretical calculations; and 

2) Because non-air contributions to PbB levels probably vary widely 

in space and time among children, a single estimate for the average case 

may result in a lead NAAQS that is not protective for all children. This 

can be expected, for example, for children who regularly ingest lead-based 

paint. Conversely, the air standard will be overprotective in areas 

where lead from non-air sources is below the average. 

In setting the 1978 lead NAAQS, the Agency estimated that non-air 

sources of lead contributed on average, 12 ug/dl to children's PbB levels. 

Since then, significant reductions in PbB levels have occurred, attributable 

not only to declines in atmospheric lead emissions but to the gradual 

conversion by manufacturers to non-lead soldered cans, the reduction of 

old, lead-painted homes, cleaner working conditions, as well as efforts 

by parents and public health agencies to minimize children's lead exposure. 

It is not surprising, therefore, that the non-air lead contribution to 

average PbB levels appears to be lower today. In children sampled in 

NHANES II between 1976 and 1980 living in rural areas where air emissions 

can be expected to be minimal, the measured geometric mean PbB was approximately 

12 ug/dl (Mahaffey et al., 1982). After three adjustments are made to 

the NHANES II data, a true "non-air" PbB in the range of 5.9 to 6.6 ug/dl 
P.93 

VII-33 

is estimated for children living in the U.S. today. The rationale for 

the adjusted value is described below. 

1) Although automobile and industrial emissions may be low, 

rural populations in the U.S. are still exposed to atmospheric 

lead through long-range transport from urban and point source 

areas and indirectly from atmospheric deposition of lead on 

crops grown around the country that enters their diet. No data 

are available on U.S. children, although preliminary analyses 

of the Isotopic Lead Experiment, which manipulated the isotopic 

composition of gasoline sold in and around Turin, Italy, found 

that between 11 and 14% of the blood lead in adult men living in the 

countryside can be directly and indirectly traced to gasoline lead 

locally consumed over 7 years (Facchetti and Geiss, 1982; Colombo 

and Fantechi; 1983). It can be reasonably assumed that the contribution 

of total atmospheric (not only gasoline) lead to active children who 

are regularly exposed to dirt and dust is likely to be significantly 

higher compared to adults. In the absence of direct data, the range 

of 11-14% for rural Turin men is multiplied by two, yielding a range 

of 20-30% for PbB related to gasoline lead and industrial sources in 

rural U.S. children. Thus, the remaining 70-80% of children's blood 

lead is assumed to be attributable to non-atmospheric sources. 

2) The NHANES II data are based on blood lead measurements made 

between 1976 and 1980. Since then, in addition to the phasedown of 

gasoline lead, efforts by the food industry to remove sources of 

lead consumed by young children have continued. The use of lead-soldered 

cans in the canning industry has decreased from 90% in 1979 to 63% 

in 1982 and as the switchover continues, lead in canned foods for 

children should decrease by as much as 70% (CD, p. 7-48). Since 
P.94 

VII-34 

lead from solder and other metals is estimated to account for approximately 21% of a typical child's background lead exposure (Table 7-25), 

it is estimated that the average child's total PbB levels will 

decline by (0.21 x 0.7) or 14%. 

3) The staff estimates that ongoing efforts to reduce occupational 

exposures and to prevent childhood lead poisoning, and the gradual 

reduction of lead exposure to lead-based paint in old homes have 

resulted in a 20% reduction in the average PbB level in U.S. children 

since the 1976-1980 time period. 

Based on these three considerations, the NHANES II mean value of 

12 ug/dl for rural children sampled between 1976 and 1980 is adjusted 

in the following calculation: 

12 ug/dl x (0.7 to 0.8) x (0.86) x (0.8) = 5.8 to 6.6 ug/dl 

This range represents the mean PbB levels that would be expected today 

in U.S. children not exposed to atmospheric lead directly or indirectly, 

based on the data and assumptions presented above. 

Another method to estimate children's mean "non-air" PbB is to use 

available data on typical background levels of lead in food, water, dust, 

and soil ingested by U.S. children and the relationship between lead 

taken up through these media and children's PbB levels. Table 13-6 of 

the criteria document uses such data in calculating a mean PbB of 4.42 ug/dl 

to be expected at an air lead level of zero. Because this estimate is 

based on observations limited to a few studies not necessarily representative 

of all U.S. children, it will be used with and added to the estimates 

derived from the NHANES II survey to construct a range of PbB levels (4.4 

to 6.6 pg/dl) predicted for U.S. children not exposed to atmospheric 

lead emissions, either directly or indirectly. 
P.95 

VII-35 

It must be emphasized that these estimates for non-air contributions 

to average PbB levels represent average values. Many children may be at 

risk for significantly higher lead exposures that cannot be prevented 

by atmospheric emission controls. In particular, these include children 

who ingest paint chips and other non-food items containing leaded paint, 

children exposed to high drinking water lead levels from eroding lead 

pipes or solders in plumbing or distribution systems, those living in 

deteriorated or recently resurfaced lead-painted housing who inadvertantly 

take up paint dust through normal mouthing activities, children of parents 

with high occupational exposures to lead dust that is carried home on 

clothing, or children living near lead smelters and other point sources where 

historical soil and dust lead accumulations are excessive. The staff 

urges that other regulatory agencies and public health programs, including 

other EPA components, responsible for minimizing children's lead exposures 

from non-air sources, or from historical atmospheric lead deposition, 

maintain or increase, where necessary, their efforts. ' 

iii) Calculation of Alternative Lead NAAQS 

Based on the conclusions reached in the preceeding sections, alternative 

target air lead levels can be derived using the "aggregate" modeling 

approach by: 

1) determining a maximum acceptable PbB level for individual children 

(no greater than 25 ug/dl) to protect against effects discussed in 

Sections V.B and VI.A.l with an adequate margin of safety; 

2) calculating a target geometric mean PbB level for U.S. children 

based on placing a specified percentage of them below the maximum 

acceptable PbB: for purposes of the present discussion the goal is 

assumed to be 99.5% (Table 7-6); 
P.96 

VII-36 

3) estimating the PbB level attributed to non-air sources suclras 

leaded paint and canned food (4.4 -6.6 ug/dl). 

4) subtracting the non-air contributions from the target geometric 

mean PbB level; and 

5) dividing the remaining allowable contribution to blood lead from 

air sources by the aggregate blood lead/air lead slopes (4-6 ug/dl 

per ug/m3) discussed in Section V.B. 

Tables 7-8 and 7-9 present the alternative air lead levels derived 

from these calculations assuming a goal of protecting 99.5% of the population 

and GSDs of 1.39 and 1.34 respectively. For purposes of this analysis, no 

distinction is made between monthly or quarterly averaging times because 

each air lead level is assumed to be constant. For each possible PbB 

that could be accepted as the level of concern, different target air lead 

values arise depending on which blood/air lead slope, which non-air blood 

lead contribution, and which GSD is ultimately taken. For example, in 

order to protect 99.5% of the population of children from exceeding a PbB 

level of 20 ug/dl, and assuming a GSD of 1.34, a non-air blood contribution 

of 4.4, and a blood lead/air lead slope of 5, an air lead level of 1.0 ug/m3 

would be adequate. At this time, the staff does not attempt to distinguish 

the validity of the values presented for either of these parameters (i.e., 

GSD, blood/air lead slope, non-air PbB) and awaits comment on these issues 

before discussing the margins of safety associated with alternative lead 

NAAQS. It is clear, however, that unless 25 ug/dl is determined to be an 

acceptable PbB for an individual child, and the non-air contribution to 

blood lead is taken as 4.4 ug/dl and the aggregate blood/air lead slope 

is assumed to be less than 5, all of the air lead alternatives predicted by 

the aggregate epidemiological model are below the current standard level of 
Table 7-8. Air Lead Levels (ug/m3, monthly or quarterly average) Required to Protect 99.5% of Children 

from Exceeding Alternative Maximum Acceptable Blood Lead Levels,According to Aggregate Epidemiological Model, 

for Different Non-Air Lead Contributions and Blood/Air Lead Slopes; GSD for Population Assumed to be 1.39 

Blood/Air Lead 

Slope 

4 

5 

6 

10 ug/dl 

Non-Air PbB 

4.4 6.6 

-

-

Maximum 1nd 

15 ug/dl 

Non-Air PbB 

4.4 6.6 

0.5 

0.4 

0.3 

ividual 

20 

Non4.4 

1.1 

0.8 

0.7 

PbB 

ug/dl 

Air PbB 

6.6 

0.5 

0.4 

0.3 

25 

Non 

4.4 

1.6 

1.3 

1.1 

ug/dl 

-Air PbB 

6.6 

1.0 

0.8 

0.7 

Table 7-9. Air Lead Levels (pg/m3, monthly or quarterly average) Required to Protect 99.5% of Children from 

Exceeding Alternative Maximum Acceptable Blood Lead Levels, According to Aggregate Epidemiological Model, 

for Different Non-Air Lead Contributions and Blood/Air Lead Slopes; GSD for Population Assumed to be 1.34 

i 

00 

Bl ood/Ai r 

Slope 

4 

5 

6 

Lead 

10 

Non4.4 

0.08 

0.06 

0.05 

ug/dl 

Air PbB 

6.6 

-

-

-

15 

Non4.4 

0.7 

0.5 

0.5 

Maximum 

ug/dl 

-Air PbB 

6.6 

0.1 

0.1 

0.08 

Individual 

20 

Non4.4 

1.25 

1.0 

0.8 

PbB 

yg/dl 

Air PbB 

6.6 

0.7 

0.6 

0.5 

25 

Non4.4 

1.85 

1.5 

1.2 

ug/dl 

•Air PbB 

6.6 

1.3 

1.0 

0.9 
VII-38 

1.5 ug/m3. It is also clear that according to this model, even an air 

lead level close to zero would not be fully protective for children from 

exceeding PbB levels of 10 ug/dl, and assuming a non-air contribution of 

6.6 ug/dl, from exceeding 15 ug/dl. These results are compared in 

Table 7-12 with PbB levels predicted under various air lead levels by the 

other two models. 

In addition, it once again should be noted that none of these air lead 

levels can fully protect children who are excessively exposed to non-air 

sources of lead, such as paint chips and heavily contaminated soils and dusts. 

c) Predicting Blood Lead Levels Using "Disaggregated" Slopes for Individual 

Media 

Just as mathematical relationships have been derived between blood lead 

and air lead levels among different populations, various studies have 

investigated the relationship between blood lead levels in children and 

concentrations of lead in food, water, soil, and dust to which they are 

exposed. The CD has applied the most reliable and relevant of these 

relationships to currently representative concentrations of lead in these 

individual media in order to estimate proportional inputs to total PbB 

levels in U.S. children (CD, Section 13.4.3). 

Table 7-10 (CD, Table 13-6) presents estimates for the direct and 

indirect contributions of air lead to 2-year old children's blood lead at 

different air lead levels and typical background levels of lead in food, 

water and dust. Calculations and assumptions used in deriving the estimates 

are summarized in footnotes to the table and are referenced to specific 

sections of the criteria document. 

This disaggregated analysis shares similarities to both approaches 

presented earlier in this paper that were used to estimate PbB levels under 

alternative air lead levels. For example, the integrated lead uptake/bio-
P.99 

VII-39 

TABLE 7-10. CONTRIBUTIONS FROM VARIOUS MEOIA TO BLOOD LEAD LEVELS (pg/dl) OF 

U.S. CHILDREN (AGE = 2 YEARS): BACKGROUND LEVELS AND INCREMENTAL CONTRIBUTIONS FROM AIR 

Source 

Background-non air 

Food1 

Water2 

Dust3 

Subtotal 

Background-air 

Food4 

Water5 

Subtotal 

Ingested Dust (with Pb 

deposited from air)6 

Inhaled air7 

Total 

0 

1.55 

.94 

.30 

2.79 

1.47 

.16 

1.63 

0.00 

0.00 

4.42 

.25 

1.55 

.94 

.30 

2.79 

1.47 

.16 

1.63 

1.57 

.50 

6.49 

.50 

1.55 

.94 

.30 

2.79 

1.47 

.16 

1.63 

3.09 

1.00 

8.51 

Air Lead 

.75 

1.55 

.94 

.30 

2.79 

1.47 

.16 

1.63 

4.70 

1.50 

10.62 

(ug/m3) 

1.0 

1.55 

.94 

.30 

2.79 

1.47 

.16 

1.63 

6.27 

2.00 

12.69 

1.25 

1.55 

.94 

.30 

2.79 

1.47 

.16 

1.63 

7.84 

2.50 

14.76 

1.5 

1.55 

.94 

.30 

2.79 

1.47 

.16 

1.63 

9.40 

3.00 

16.82 

"•From Table 7-25, (18.9 - 9.2) pg/day x (0.16 from Ryu et al., 1983) = 1.55 ug/dl. 

2From Table 7-25, (6.9 - 1.0) pg/day x (0.16 from Ryu et al., 1983) = 0.94 pg/dl. 

Alternatively, Tables 7-20, 7-21 give a weighted mean concentration of liquids as 

0.012 pg/g. 1/7 is atmospheric, leaving 0.01 pg/g (10 pg/1) non-atmospheric. 10 x 

(0.06 from Pocock et al., 1983) =0.6 pg/dl. 

3From Chapter 7, 1/10 dust not atmospheric. Using Angle et al. (1984) low area (Area S) 

for soil and house dust and their regression equation, we have: (1/10) x (97 pg/g x 

0.00681 + 324 pg/g x 0.00718) = 0.30 pg/dl. Alternatively, the consumption from non air 

would be (1/10) x (97 pg/g soil dust + 324 pg/g house dust) x 0.05 grams ingested of 

each = 2.1 pg ingested. Using Ryu et al. (1983), 2.1 x 0.16 = 0.34 pg/dl added to blood. 

4As in 1 above, but using 9.2 instead of (18.9 - 9.2) yields 1.47 pg/dl. Values are derived 

for component of background Pb in food from past deposition from air onto soil and into other 

media leading into human food chain (not expected to change much except over long-term). 

sAs in 2 above, but using 1.0 instead of (6.9 - 1.0) yields 0.16 pg/dl. Values are derived 

for component of background Pb in food from past deposition from air onto soil and into other 

media leading into human food chain (not expected to change much except.over long-term). 

6The regression equations of Angle et al. (1984) are used, as well as levels of soil dust 

and house dust in the low area (S) and high area (C) of that study. For example, the 

increase at 1.0 pg/m3 in air would result in increases in soil as follows: 

orHrU

 X (519

 •97) = 526 M9/9 

Similarly the increase in house dust would be: 

0;86 - gill * (625-324) = 374 pg/g 

ThThee effec effectt o onn bloo bloodd lea leadd woul wouldd b bee (52 (5266 x x 0.00681 0.00681)) + + (37 (3744 x x 0.00718 0.00718) ) = 6.27 pg/dl. 

7Using the 2.0 slope from Angle et al. (1984), i.e., 1.93 rounded up. 

Source: CD, Table 13-6. 
P.100 

VII-40 

kinetic model estimated the range of contributions that both atmospheric 

and non-atmospheric lead make to total exposure, directly and indirectly, 

via the individual media pathways. The second "aggregate" blood lead/air 

lead approach relied on mathematical relationships derived from some of the 

same population studies between blood lead and lead in the environment. 

It is of interest to note that after adjusting the estimated PbB in 

Table 7-10 for children exposed to 1.25 ug/m3 air lead to a level that 

would be expected given the dietary and background lead conditions during 

1976-1980 when NHANES II was conducted, the result is roughly comparable to 

the mean PbB measured by the NHANES II survey for children living in U.S. 

urban areas which then had an average air level of approximately 1.20 ug/m3 

(15.6 vs. 16.8 ug/dl) (CD, p. 13-26 to 13-28). 

The PbB levels listed under each air lead level in Table 7-10 represent 

the predicted population mean PbB levels for 2-year olds. Using the 

equation presented previously in this section, it is possible to estimate, 

given a geometric mean PbB level and known distribution characteristics of 

the population, the individual PbB at a specified standard deviation. 

Table 7-6 for example, indicates that given a geometric mean PbB level 

between 8.6 and 9.4 ug/dl, 99.5% of the population would have PbB levels 

below 20 ug/dl (depending on which geometric standard deviation is chosen). 

Similarly, a population mean PbB of 8.51 for example (predicted under an 

air lead level of 0.50 ug/m3 in Table 7-10), would prevent 99.5% of the 

population from exceeding a PbB of either 18.1 or 19.8 ug/dl (for GSD's of 

1.34 and 1.39, respectively). Table 7-11 lists the maximum individual PbB 

predicted in 99.5% of the population for each estimate of mean PbB predicted 

by the criteria document in Table 7-10. These results are presented in 

Table 7-12 for comparison with those of the other two modeling approaches.