f • ' " ' '•' United States Office of Water EPA 440/5-80-057
Environmental Protection Regulations and Standards October 1980
Agency Criteria and Standards Division
Washington DC 20460 C • /
&EPA Ambient
Water Quality
Criteria for
Lead
-------
AMBIENT WATER QUALITY CRITERIA FOR
LEAD
Prepared By
U.S. ENVIRONMENTAL PROTECTION AGENCY
Office of Water Regulations and Standards
Criteria and Standards Division
Washington, D.C.
Office of Research and Development
Environmental Criteria and Assessment Office
Cincinnati, Ohio
Carcinogen Assessment Group
Washington, D.C.
Environmental Research Laboratories
Corvalis, Oregon
Duluth, Minnesota
Gulf Breeze, Florida
Narragansett, Rhode Island
Protection Ap»r*r»-
-------
DISCLAIMER
This report has been reviewed by the Environmental Criteria and
Assessment Office, U.S. Environmental Protection Agency, and approved
for publication. Mention of trade names or commercial products does not
constitute endorsement or recommendation for use.
AVAILABILITY NOTICE
This document is available to the public through the National
Technical Information Service, (NTIS), Springfield, Virginia 22161.
ii
-------
FOREWORD
Section 304 (a)(l) of the Clean Water Act of 1977 (P.L. 95-217),
requires the Administrator of the Environmental Protection Agency to
publish criteria for water quality accurately reflecting the latest
scientific knowledge on the kind and extent of all identifiable effects
on health and welfare which may be expected from the presence of
pollutants in any body of water, including ground water. Proposed water
quality criteria for the 65 toxic pollutants listed under section 307
(a)(l) of the Clean Water Act were developed and a notice of their
availability was published for public comment on March 15, 1979 (44 FR
15926), July 25, 1979 (44 FR 43660), and October 1, 1979 (44 FR 56628).
This document is a revision of those proposed criteria based upon a
consideration of comments received from other Federal Agencies, State
agencies, special interest groups, and individual scientists. The
criteria contained in this document replace any previously published EPA
criteria for the 65 pollutants. This criterion document is also
published in satisifaction of paragraph 11 of the Settlement Agreement
in Natural Resources Defense Council, et. al. vs. Train, 8 ERC 2120
(D.D.C. 1976), modified, 12 ERC 1833 (O.D.C. 1979).
The term "water quality criteria" is used in two sections of the
Clean Water Act, section 304 (a)(l) and section 303 (c)(2). The term has
a different program impact in each section. In section 304, the term
represents a non-regulatory, scientific assessment of ecological ef-
fects. The criteria presented in this publication are such scientific
assessments. Such water quality criteria associated with specific
stream uses when adopted as State water quality standards under section
303 become enforceable maximum acceptable levels of a pollutant in
ambient waters. The water quality criteria adopted in the State water
quality standards could have the same numerical limits as the criteria
developed under section 304. However, in many situations States may want
to adjust water quality criteria developed under section.304 to reflect
local environmental conditions and human exposure patterns before
incorporation into water quality standards. It is not until their
adoption as part of the State water quality standards that the criteria
become regulatory.
Guidelines to assist the States in the modification of criteria
presented in this document, in the development of water quality
standards, and in other water-related programs of this Agency, are being
developed by EPA.
STEVEN SCHATZOW
Deputy Assistant Administrator
Office of Water Regulations and Standards
111
-------
ACKNOWLEDGEMENTS
Aquatic Life Toxicology:
Charles E. Stephan, ERL-Duluth
U.S. Environmental Protection Agency
Mammalian Toxicology and Human Health Effects:
Paul B. Hammond (author)
University of Cincinnati
Michael L. Dourson (doc. mgr.) ECAO-Cin
U.S. Environmental Protection Agency
Jerry F. Stara (doc. mgr.) ECAO-Cin
U.S. Environmental Protection Agency
Patrick Durkin
Syracuse Research Corporation
W. Galke, ECAO-RTP
U.S. Environmental Protection Agency
Terri Laird, ECAO-Cin
U.S. Environmental Protection Agency
K. Mahaffey
U.S. Food and Drug Administration
John H. Gentile, ERL-Narragansett
U.S. Environmental Protection Agency
Roy E. Albert*
Carcinogen Assessment Group
U.S. Environmental Protection Agency
R.J. Bull, HERL
U.S. Environmental Protection Agency
Thomas Clarkson
University of Rochester
Robert A. Ewing
BatteUe - Columbus Laboratory
T.J. Haley
National Center for Toxicological Research
P. Landrigan
Center of Disease Control
H. Needleman
Children's Hospital Medical Center
Technical Support Services Staff: D.J. Reisman, M.A. Garlough, B.L. Zwayer,
P.A. Daunt, K.S. Edwards, T.A. Scandura, A.T. Pressley, C.A. Cooper,
M.M. Denessen.
Clerical Staff: C.A. Haynes, S.J. Faehr, L.A. Wade, D. Jones, B.J. Bordicks,
B.J. Quesnell, T. Highland, 8. Gardiner.
*CAG Participating Members: Elizabeth L. Anderson, Larry Anderson, Dolph Arnicar,
Steven Bayard, David L. Bayliss, Chao W. Chen, John R. Fowle III, E5ernard Haberman,
Charalingayya Hiremath, Chang S. Lao, Robert McGaughy, Jeffrey Rosenblatt, Dharm
V. Singh, and Todd W. Thorslund.
IV
-------
TABLE OF CONTENTS
Criteria Summary
Introduction A-l
Aquatic Life Toxicology B-l
Introduction B-l
Effects B-2
Acute Toxicity B-2
Chronic Toxicity B-5
Plant Effects B-8
Residues B-9
Miscellaneous B-9
Summary B-ll
Criteria B-ll
References B-31
Mammalian Toxicology and Human Health Effects C-l
Introduction C-l
Exposure C-2
Natural Background Levels C-2
Man-generated Sources of Lead C-3
Ingestion from Water C-3
Ingestion from Food C-4
Inhalation C-9
Dermal C-9
Miscellaneous Sources C-9
Pharmacokinetics C-15
Absorption C-16
Dermal C-19
Distribution C-19
Metabolism C-21
Excretion C-21
Contributions of Lead from Diet versus Air to PbB C-22
Effects C-35
Careinogenicity C-48
Teratogenicity C-63
Mutagenicity C-66
Reproductive Effects C-66
Renal Effects C-68
Cardiovascular Effects C-70
Miscellaneous Effects C-71
Criterion Formulation C-72
Existing Guidelines and Standards C-72
Current Levels of Exposure C-72
Special Groups at Risk C-73
Basis and Derivation of Criterion C-73
References C-81
Appendix C-104
-------
CRITERIA DOCUMENT
LEAD
CRITERIA
Aouatic Life
For total recoverable lead, the criterion (in ug/1) to protect fresh-
water aauatic life as derived using the Guidelines, is the numerical value
given by e(2'35l>(hardness)]-9.48) as a 24_hour average and the concep_
tration (in ug/1) should not exceed the numerical value given by
e(1.22[ln(hardness)1-0.47) at any time> For example> at hardnesses of 50§
100, and 200 mg/1 as CaC03 the criteria are 0.75, 3.8, and 20 yg/l, re-
spectively, as 24-hour averages, and the concentrations should not exceed
74, 170, and 400 ug/l» respectively, at any time.
The available data for total recoverable lead indicate that acute and
chronic toxicity to saltwater aauatic life occur at concentrations as low as
668 and 25 ug/1, respectively, and would occur at lower concentrations among
species that are more sensitive than those tested.
Human Health
The ambient water duality criterion for lead is recommended to be iden-
tical to the existing water standard which is 50 wg/1. Analysis of the
toxic effects data resulted in a calculated level which is protective of
human health against the ingestion of contaminated water and contaminated
aauatic organisms. The calculated value is comparable to the present stan-
dard. For this reason a selective criterion based on exposure solely from
consumption of 6.5 grams of aauatic organisms was not derived.
VI
-------
INTRODUCTION
Lead (atomic weight 207.2) is a soft gray, acid-soluble metal (Windholz,
1976) and exists in three oxidation states, 0, +2, and +4. Lead is a major
constituent of more than 200 identified minerals. Most of these are rare,
and only three are found in sufficient abundance to form mineral deposits:
galena (PbS) the simple sulfide, angelesite (PbS04) the sulfate, and cer-
rusite (PbC03) the carbonate' (U.S. EPA, 1979). Lead is used in electro-
plating, metallurgy, and the manufacture of construction materials, radia-
tion protective devices, plastics, and electronics eauipment.
Although neither metallic lead nor the common lead minerals are classi-
fied as soluble in water, they can both be solubilized by some acids; in
contrast, some of the lead compounds produced industrially are considered
water soluble. Natural lead compounds are not usually mobile in normal
ground or surface water because the lead leached from ores becomes adsorbed
by ferric hydroxide or tends to combine with carbonate or sulfate ions to
form insoluble compounds (Hem, 1976). The solubility of lead compounds in
water depends heavily on pH and ranges from about 10,000,000 yg/1 of lead at
pH 5.5 to 1 wg/1 at pH 9.0 (Hem and Durum, 1973). Lead does reach the
aauatic environment through precipitation, fallout of lead dust, street run-
off, and both industrial and municipal wastewater discharges (U.S. EPA,
1976). Inorganic lead compounds are most stable in the plus two valence
state, while organolead compounds are more stable in the plus four state
(Standen, 1967).
A-l
-------
REFERENCES
Hem, J.D. 1976. Geochemical controls on lead concentrations in stream
water and sediments. Geochim. Cosmochim. Acta. 40: 599.
Hem, J.D. and W.H. Durum. 1973. Solubility and occurrence of lead in sur-
face water. Jour. Am. Water Works. 65: 562.
Standen, A. (ed.) 1967. Kirk-Othmer Encyclopedia of Chemical Technology.
Interscience Publishers, New York.
U.S. EPA. 1976. Quality criteria for water. Off. Water Plan. Stand., U.S.
Environ. Prot. Agency, Washington, D.C.
U.S. EPA. 1979. Water-related environmental fate of 129 priority pollut-
ants. Off. Water Plan. Stand., U.S. Environ. Prot. Agency, Washington, D.C.
Windholz, M. (ed.) 1976. The Merck Index. 9th ed. Merck and Co., Inc.,
Rahway, New Jersey.
A-2
-------
Aquatic Life Toxicology*
INTRODUCTION
The acute and chronic adverse effects of lead have been studied with a
variety of freshwater organisms. Representative test animals listed in Ta-
bles 1 through 6 include fish from six different families (Salmonidae, Cy-
prinidae, Catostomidas, Ictaluridae, Poeciliidae, and Centrarchidae), and
invertebrate species from the nine groups (rotifers, annelids, snails, clad-
ocerans, copepods, isopods, mayflies, stoneflies, and caddisflies). Tox-
icity tests have also been conducted with freshwater plants from the algal,
desmid and diatom groups, and both fish and invertebrate species have been
used in bioconcentration tests.
Acute toxicity tests have been conducted with lead and a variety of
saltwater invertebrates, but no tests with fish are available. Results in-
dicate a range of acute values from 668 vg/1 for a copepod to 27,000 pg/1
for the adult soft shell clam. A chronic test has been conducted with one
invertebrate species, the mysid shrimp, and the chronic value was 25 yg/1.
Select invertebrate and algal species are good accumulators of lead. Bio-
concentration factors calculated on a wet weight basis ranged from 17.5 for
the hard clam to 2,570 for the mussel.
Of the analytical measurements currently available, a water quality cri-
terion for lead is probably best stated in terms of total recoverable lead,
because of the variety of forms of lead that can exist in bodies of water
and the various chemical and toxicological properties of these forms. The
*The reader is referred to the Guidelines for Deriving Water Quality Cri-
teria for the Protection of Aquatic Life and Its Uses in order to better un-
derstand the following discussion and recommendation. The following tables
contain the appropriate data that were found in the literature, and at the
bottom of each table are calculations for deriving various measures of tox-
icity as described in the Guidelines.
8-1
-------
forms of lead that are commonly found in bodies of water and are not meas-
ured by the total recoverable procedure, such as the lead that is a part of
minerals, clays and sand, probably are forms that are less toxic to aquatic
life and probably will not be converted to the more toxic forms very readily
under natural conditions. On the other hand, forms of lead that are common-
ly found in bodies of water and are measured by the total recoverable proce-
dure, such as the free ion, and the hydroxide, carbonate, and sulfate salts,
probably are forms that are more toxic to aquatic life or can be converted
to the more toxic forms under natural conditions.
Because the criterion is derived on the basis of tests conducted on sol-
uble inorganic salts of lead, the total and total recoverable lead concen-
trations in the tests will probably be about the same, and a variety of an-
alytical procedures will produce about the same results. Except as noted,
all concentrations reported herein are expected to be essentially equivalent
to total recoverable lead concentrations. All concentrations are expressed
as lead, not as the compound tested.
EFFECTS
Acute Toxicity
Table 1 contains six acute values for three freshwater invertebrate spe-
cies. Only one of the tests was flow-through (Spehar, et al. 1978) but in
two, the toxicant concentrations were measured (Spehar, et al. 1978;
Chapman, et al. Manuscript). Acute tests were conducted at three different
levels of water hardness with Daphnia magna (Chapman, et al. Manuscript),
demonstrating that daphnids were three times more sensitive to lead in soft
water than in hard water. This acute value for Daphnia magna in soft water
agrees closely with the value reported earlier for the same species in soft
water by Biesinger' and Christensen (1972). Rotifers tested for 96 hours in
B-2
-------
soft water by Buikema, et al. (1974) were very resistant to lead; however,
scuds were reported by Spehar, et al. (1978) to be more sensitive to lead
than any other invertebrate thus far tested. Interestingly, this same rela-
tionship existed in longer exposures lasting up to 28 days in which the scud
was far more sensitive to lead than a snail, cladoceran, chironomid, mayfly,
stonefly, and caddisfly (Table 6) (Spehar, et al. 1978; Biesinger and Chris-
tensen, 1972; Anderson, et al. 1980; and Nehring, 1976).
Thirteen acute toxicity tests have been conducted on lead with six spe-
cies of fish (Table 1). Of the 13 only three were reported to be
flow-through, and measured toxicant concentrations were reported for only
one (Holcombe, et al. 1976). The results of acute tests conducted by
Oavies, et al. (1976) with rainbow trout in hard water are reported as
unmeasured values in Table 1, because total lead concentrations were not
measured, even though the dissolved lead concentrations were.
The data in Table 1 indicate a relationship between water hardness and
the acute toxicity of lead to rainbow trout (Davies, et al. 1976), fathead
minnows and bluegills (Pickering and Henderson, 1966), because lead was gen-
erally much more toxic in soft water. Another example of the effect of
hardness was reported by Tarzwell and Henderson (1960) who conducted 96-hour
exposures of fathead minnows to lead in soft and hard water (20 and 400 mg/1
as CaCO,, respectively). Results from the soft water test are shown in
Table 1. The hard water exposure is included in Table 6 because an LC^Q
value was not obtained within 96 hours; however, this test did show that the
hard water LC5Q value was greater than 75,000 yg/1 which meant that the
LCcQ in hard water was at least 31 times that in soft water. Hale (1977)
conducted an acute exposure of rainbow trout to lead and obtained an IC™
value of 8,000 yg/1. This value is six times greater than the LC50 value
B-3
-------
obtained for rainbow trout in soft water by Davies, et al. (1976). Hale did
not report water hardness; however, alkalinity and pH were reported to be
105 mg/1 and 7.3, respectively, which suggests that this water was probably
harder than the soft test water used by Davies, et al. (1976). Wallen, et
al. (1957) also reported high acute lead values for the mosquitofish; how-
ever, these authors also did not report water hardness and the test was con-
ducted in turbid water contining suspended clay particles at apporoximately
300,000 wg/1 (Table 6). Pickering and Henderson (1966) found that lead ace-
tate was about as toxic as lead chloride to the fathead minnow in soft water
(Tables 1 and 6).
An exponential equation was used to describe the observed relationship
of the acute toxicity of lead to hardness in fresh water. A least squares
regression of the natural logarithms of the acute values on the natural
logarithms of hardness produced slopes of 1.05, 2,48, 1.60, and 1.01, re-
spectively, for Daphnia magna, rainbow trout, fathead minnow, and bluegill
(Table 1). The slope for Daphnia magna was significant, but that for rain-
bow trout was not. The slopes for the bluegill and fathead minnow were
based on data for two hardnesses each, although four tests are available
with the minnow. An arithmetic mean slope of 1.22 was calculated for the
three species other than the rainbow trout. This mean slope was used with
the geometric mean toxicity value and hardness for each species to obtain a
logarithmic intercept for each of the nine freshwater species for which
acute values are available for lead.
The species mean intercept, calculated as the exponential of the loga-
rithmic intercept, was used to compare the relative acute sensitivities
(Table 3). The Guidelines specify that in order to derive a criterion the
minimum data base should include at least one acute value for a benthic in-
sect. No such value is available for lead. However, 7- to 28-day soft
B-4
-------
water exposures of the mayfly, stonefly, and caddisfly to lead have been re-
ported by Nehring (1976), Warnick and Bell (1969), and Spehar, et al. (1978)
(Table 6). Their results indicate that benthic insects are rather insensi-
tive to lead. Although the data are not really comparable, it appears that
the caddisfly may be the least sensitive of the three and may be slightly
less sensitive than the goldfish. In an attempt to account in some way for
these insensitive species in the derivation of the Final Acute Intercept, a
caddisfly was entered as the least sensitive species in the list of fresh-
water intercepts in Table 3.
A freshwater Final Acute Intercept of 0.623 yg/1 was obtained for lead
using the species mean intercepts listed in Table 3 and the calculation pro-
cedures described in the Guidelines. Thus the Final Acute Equation is
e(1.22[ln(hardness)]-0.47)< '
No standard acute toxicity values for saltwater fish species are availa-
ble but several are available for invertebrate species. The most sensitive
invertebrate species was a copepod Acartia clausi with an LC™ of 668 yg/1
and the least sensitive was the soft shell clam Mya arenaria with an LC™
of 27,000. A value of 2,450 was obtained with oyster larvae Crassostrea
virginica in a static test and a LC5g of 2,960 was recorded for mysid
shrimp Mysidopsis bahia in a flow-through test in which concentrations were
measured (Table 1). Acute values are not available for enough appropriate
kinds of species to allow calculation of a Saltwater Final Acute Value.
Chronic Toxicity
Four tests of the chronic toxicity of lead to freshwater invertebrate
species have been conducted (Table 2). Chapman, et al. (Manuscript) studied
the chronic toxicity of lead to Daphnia magna at three different hardnes-
ses. Results shown in Table 2 demonstrate that daphnids were nearly 11
B-5
-------
times more sensitive to lead in the soft water. For the same species in a
different soft water, a chronic value over four times higher (Table 6) was
obtained by Biesinger and Christensen (1972) in a test in which the concen-
trations of lead were not measured. Use of the comparable acute value of
450 ug/1 (Table 1) results in an acute-chronic ratio of 8.2.
A life cycle test on lead in hard water was conducted by Borgmann, et
al. (1978) with snails. These authors used biomass as their endpoint and
reported that lead concentrations as low as 19 ug/1 significantly decreased
survival but not growth or reproduction. After a thorough review of this
work, however, it was not at all clear how these investigators arrived at
such a low effect concentration. This publication did, however, contain
suitable information for determining a chronic value. Chronic limits were
taken directly from the cumulative percent survival figure which showed no
observed effect on survival at 12 ug/1 and almost complete mortality at 54
ug/1. The chronic value for snails shown in Table 2 was therefore estab-
lished at 25 ug/1, which is somewhat lower than the chronic value reported
for daphnids in hard water.
Seven chronic tests on lead have been conducted with six species of
freshwater fish (Table 2), all of which were in soft water. In addition,
Davies, et al. (1976) described the long-term effects on rainbow trout fry
and finger!ings exposed to various concentrations of lead for 19 months in
hard and soft water (Table 6). Although these experiments were neither life
cycle (no natural reproduction) nor early life stage (no embryos exposed),
they do provide valuable information concerning the relationship between
water hardness and chronic lead toxicity to fish. During these 19-month ex-
posures, most of the trout (60 to 100 percent) developed spinal deformities
in hard water at measured lead concentrations of 850 ug/1 and above.
B-6
-------
However, during the soft water exposure most trout (44 to 97 percent)
developed spinal deformities in measured lead concentrations as low as 31
ug/1 (Table 6). These results strongly demonstrate that lead is more
chronically toxic in soft water than in hard water.
Davies, et al. (1976) also published results of an early life stage test
with rainbow trout in soft water (Table 2). Even through this test was
started with embryos and continued for 19 months after hatch, it could not
be considered a life cycle test because no reproduction occurred. The
chronic limits that these authors chose were somewhat lower than those shown
in Table 2, because they based their results on a very low incidence of
black colored tails and spinal deformities (0.7 and 4.7 percent, respective-
ly). Because this test was not conducted with duplicate exposures, statis-
tically significant differences could not be determined. After careful ex-
amination of their results it was decided that the chronic limits (Table 2)
should be established on the occurrence of spinal curvatures only and at
lead concentrations which caused a substantial increase in these deformi-
ties. Even though the incidence of black tail was apparently related to the
concentration of lead, it could not by itself be considered an important
adverse effect.
Spinal deformities have also been cause by lead in a life cycle test
with brook trout (Holcombe, et al. 1976) and in early life stage tests with
rainbow trout, northern pike and walleye (Sauter, et al. 1976). On the
other hand, Sauter, et al. (1976) did not observe deformities during early
life stage tests with lake trout, channel catfish, white sucker, and blue-
gill. Results of tests by Sauter, et al. (1976) with northern pike and
walleye, however, were not included in Tables 2 and 6 because of excessive
mortality due to cannibalism and feeding problems. The chronic value ob-
tained for rainbow trout by Sauter, et al. (1976) is somewhat higher than
B-7
-------
that chronic value derived from Oavies, et al. (1976). Even though the
hardnesses were about the same, differences could be due to differences in
the length of exposure (2 months vs. 19 months).
As was done with the freshwater acute values, the freshwater chronic
values of Chapman, et al. (Manuscript) were regressed against hardness to
account for the apparent effect of hardness on the chronic toxicity of lead
and a slope of 2.35 was obtained. Even though this slope is not significant
because it is based on only three values, it relects the obvious effect of
hardness on chronic toxicity. In the same manner as for acute toxicity, the
chronic slope was used with the geometric mean chronic toxicity value and
hardness for each species to obtain a logarithmic intercept and a species
mean chronic intercept for each species for which a chronic value is availa-
ble (Table 2). A Freshwater Final Chronic Intercept of 0.000076 wg/l was
then obtained using the calculation procedures described in the Guidelines.
Thus, the Final Chronic Equation is e(2'35f1n(hardness)]-9.48)>
The mysid shrimp Mysidopsis bahia is the only saltwater species with
which a chronic test has been conducted on lead (Table 2). The most sens-
itive observed adverse effect was reduced spawning (U.S. EPA, 1980) and the
resulting chronic value was 25 ug/1. The 96-hour |_C50 for this same spe-
cies in the same study was 2,960 wg/1, producing an acute-chronic ratio of
119.
Plant Effects
Four static tests on three species of algae have been reported by Mona-
han (1976) (Table 4). These exposures were conducted for 7 days and concen-
trations of lead were not measured. Results of short exposures of algae and
diatoms to unmeasured lead concentrations have also been published by Malan-
chuk and Gruendling (1973) (Table 6). The adverse effect concentrations
from these tests ranged from 500 to 28,000 ug/l. It would appear therefore
B-8
-------
that any adverse effects of lead on plants are unlikely at concentrations
protective of chronic effects on freshwater animals.
No saltwater plant species have been exposed to inorganic lead, but one
saltwater algal species Dunaliella tertiolecta has been exposed to both
tetramethyl and tetraethyl lead. The results (Table 6) demonstrate that
this species is more sensitive to tetraethyl lead by a factor greater than
10. No data are available concerning the relative toxicities of inorganic
lead and these organolead compounds.
Residues
Four freshwater invertebrate species have been exposed to lead (Borg-
mann, et al. 1978; Spehar, et al. 1978) and the bioconcentration factors
ranged from 499 to 1,700 (Table 5). Brook trout and bluegills were also ex-
posed to lead (Holcombe, et al. 1976, and Atchison, et al. 1977) and calcu-
lated bioconcentration factors were 42 and 45, respectively (Table 5).
Some species of saltwater bivalve molluscs, diatoms and phytoplankton
are capable of accumulating lead (Table 5). The bioconcentration factors
range from 17.5 with the hard clam to 2,570 with the mussel. Because the
duration of the study may be an important consideration in bioconcentration
studies, this comparison is not entirely valid since the mussel was exposed
for 130 days and the hard clam for only 56 days.
Neither a freshwater nor' a saltwater Final Residue Value can be calcu-
lated because no maximum permissible tissue concentration is available for
lead.
Miscellaneous
Many of the values in Table 6 have already been discussed. Spehar
(1978) found no adverse effects on a freshwater snail, scud, stonefly, and
caddisfly in 28 days at 565 yg/1. Pickering and Henderson (1966) found that
lead chloride and lead acetate are about equally toxic to fathead minnows in
8-9
-------
static tests in soft water (Table 1 and 6), but Wallen, et al. (1957) found
that lead oxide is much less acutely toxic than lead nitrate to the mosqui -
tofish in turbid water.
The 10-day test conducted by Anderson, et al. (1980) (Table 6) showed
that the midge, Tanytarsus dissimilis, is rather insensitive to lead with a
chronic value of 258 yg/1. This test included exposure of the species
during most of its life cycle and several of the presumably sensitive molts,
and so should probably be considered as useful as the early life stage test
with fish.
A variety of other effects on saltwater organisms have been observed.
Gray and Ventilla (1973) observed a reduction in growth rate in a ciliate
protozoan after a 12 hour exposure to a lead concentration of 150 yg/1.
Woolery and Lewin (1976) observed a reduction in photosynthesis and respira-
tion in the diatom Pheodactylum tricornutum at concentrations of lead
ranging from 100 to 10,000 yg/1. However, Hannan and Patouillet (1972)
obtained no growth inhibition with £. tricornutum at a concentration of
1,000 yg/1 after 72 hours. Rivkin (1979) using growth rate to determine
toxicity to the diatom, Skeletonema costatum, reported a 12 day EC50 of
5.1 yg/1. Messier (1974) observed delayed cell division in the phytoplank-
ton, Platymonas subcordiformus, after treatment with 2,500 yg/1 for 72
hours. At 60,000 yg/1, Messier (1974) reported not only growth retardation
but also death. Benijts-Claus and Benijts (1975) observed delayed larval
development in the mud crab, Rhithropanopeus harrisii, after treatment with
lead concentrations of 50 yg/1. In Fundulus heteroclitus, Weis and Weis
(1977) observed depressed axis formation in developing embryos with lead
concentrations of 100 yg/1. Reish and Carr (1978), found that 1,000 yg/1
suppressed reproduction of two polychaete species, Ctenodriluis serratus and
Ophryotrocha disdema, in a 21-day test.
B-10
-------
Summary
Standard acute data for lead are available for nine freshwater fish and
invertebrate species with a range from 124 to 542,000 yg/l. Chronic tests
have been conducted with two invertebrate species and six fish species with
the chronic values ranging from 12 to 174 wg/l. Both the acute and chronic
toxicities of lead to freshwater animals decrease as hardness increases.
Freshwater algae are affected by concentrations of lead above 500 yg/1,
based on data for three species. Bioconcentration factors ranging from 42
to 1,700 are available for four invertebrate and two fish species.
Acute values for five saltwater species ranged from 668 yg/1 for a cope-
pod to 27,000 yg/1 for the soft shell clam. A chronic toxicity test was
conducted for the mysid shrimp and adverse effects were observed at 37 yg/l
but not at 17 yg/1. The acute-chronic ratio for this species is 118.
Delayed embryonic development, suppressed reproduction and inhibition of
growth rate among fish, crab, polychaete worm, and plankton were also caused
by lead.
CRITERIA
For total recoverable lead the criterion (in yg/1) to protect freshwater
aquatic life as derived using the Guidelines is the numerical value given by
e(2.35[ln(hardness)]-9.48) as a 24-hour average and the concentration (in
yg/1) should not exceed the numerical value given by e^1-22[ln(hardness)]
-°-47) at any time. For example, at hardnesses of 50, 100, and 200 mg/1 as
CaC03 the criteria are 0.75, 3.8, and 20 yg/l, respectively, as 24-hour
averages, and the concentrations should not exceed 74, 170, and 400 yg/l,
respectively, at any time.
B-ll
-------
The available data for total recoverable lead indicate that acute and
chronic toxicity to saltwater aquatic life occur at concentrations as low as
668 and 25 yg/1, respectively, and would occur at lower concentrations among
species that are more sensitive than those tested.
B-12
-------
Table 1. Acute values for lead
Species
Method*
Chemical
Hardness Species Mean
(mg/l as LC50/EC50»» Acute Value"
CaOM (ug/l) (ug/|
Reference
FRESHWATER SPECIES
Rotifer,
Ph Medina acutlcornls
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnla maqna
C 1 adoceran,
Daphnla magna
Scud,
B Gammarus pseudol Imnaeus
{-* Rainbow trout.
Sal mo qalrdnerl
Rainbow trout.
Sal mo gairdneri
Rainbow trout.
Sal mo galrdnerl
Rainbow trout (2 mos).
Sal mo gairdneri
Brook trout (18 MOS),
Salvelinus fontlnalis
Fathead minnow,
Plmephales promelas
Fathead minnow,
Plmephales promelas
Fathead minnow,
Pimephales promelas
S, U
S, U
R, M
R, M
R, M
FT, M
S, U
S, U
FT, U
FT, U
FT, M
s, u
S, U
s, u
Lead chloride
Lead chloride
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead chloride
Lead chloride
Lead chloride
25
45
54
110
152
46
290
353
28
-
44
20
20
20
40,800
450
612
952
1,910
124
542,000
47 1 ,000
1,170
8,000
4,100
2.400
5,580
7,330
Bulkema, et al. 1974
Bieslnger &
Christen sen, 1972
- Chapman, et al.
Manuscript
Chapman, et al.
Manuscript
Chapman, et al.
Manuscript
Spehar, et al. 1978
Davles, et al. 1976
Davles, et al. 1976
Davles, et al. 1976
Hale, 1977
Holcombe, et al. 1976
Tarzwel 1 & Henderson,
I960
Pickering &
Henderson, 1966
Pickering &
Henderson, 1966
-------
Table 1. (Continued)
Species Method*
Fathead minnow, S, U
Plmephales promelas
Goldfish, S, U
Carasslus auratus
Guppy (6 mos), S, U
Poeci 1 la reticulata
Bluegil 1, S, U
Lepomis macrochirus
Bluegi II, S, U
Lepomis macrochirus
Oyster, S, U
td Crassostrea vlrginlca
*» Hard clam, S, U
Mercenarla mercenaria
Soft shell clam (adult), S, U
Mya arenarla
Mysid shrimp, FT, M
Mysidopsls bahia
Copepod, S, U
Acartla clausl
Hardness Species Mean
(rng/l as LC50/EC50** Acute Value**
Chemical CaC03> (ug/l) (ug/1 Reference
Lead chloride 360 482,000
Lead chloride 20 31,500
Lead chloride 20 20,600
Lead chloride 20 23,800
Lead chloride 360 442,000
SALTWATER SPECIES
Lead nitrate - 2,450 2,450
Lead nitrate - 780 780
Lead nitrate - 27,000 27,000
Lead nitrate - 2,960 2,960
Lead nitrate - 668 668
Pickering &
Henderson, 1966
Pickering &
Henderson, 1966
Pickering 4
Henderson, 1966
Pickering &
Henderson, 1966
Pickering &
Henderson, 1966
Calabrese, et al.
1973
Calabrese & Nelson,
1974
Elsler, 1977
U.S. EPA, 1980
U.S. EPA, 1980
* S = static, R = renewal, FT = flow-through, M = measured, U = unmeasured
**Results are expressed as lead, not as the compound.
-------
TabU I. (Continued)
I
M
Ln
Freshwater
Acute toxlclty vs. hardness
Daphnla maqna: slope = 1.05. Intercept * 2,13, r * 0.97, p = 0.05, n = 4
Rainbow trout: slope - 2.48, Intercept = -1.16, r = 0.99, not significant, n = 3
Fathead minnow: slope = 1.60, Intercept » 3.62, r = 0.98, p = 0.05, n = 4
BJueglll: slope = 1.01, Intercept = 7.05, r = 1.00, n = 2
Arithmetic mean acute slope = 1.22 (slope for rainbow trout not used)
-------
Table 2. Chronic values for lead
w
I
Species
Test*
Chemical
Hardness
(mg/l as Limits
CaCOr) tug/I)
Chronic Value**
(ug/l) Reference
FRESHWATER SPECIES
C ladoceran,
Daphnla magna
Cladoceran,
Daphnla magna
Cladoceran,
Daphnia magna
Snai 1,
Lynrnea palustris
Rainbow trout,
Sal mo galrdnerl
Rainbow trout,
Sal mo gairdneri
Brook trout,
Salvellnus fontinalis
Lake trout,
Salvelinus namaycush
Channel catfish,
Ictalurus punctatus
White sucker,
Catostomus commersoni
Bluegill,
Lepomis macrochlrus
Mysld shrimp,
Mysidopsls bahia
LC
LC
LC
LC
ELS
ELS
LC
ELS
ELS
ELS
ELS
LC
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
SALTWATER
Lead nitrate
52
102
151
139
28
35
44
33
36
38
41
SPECIES
—
9-17
78-18)
85-193
12-54
13-27
71-146
58-119
48-83
75-136
1 19-253
70-120
17-37
12
119
128
25
19
102
83
63
101
174
92
25
Chapman, et al.
Manuscript
Chapman, et al.
Manuscript
Chapman, et al.
Manuscript
Bor groan n, et al
Davles, et al.
Sauter, et al.
Holcombe, et al
Sauter, et al.
Sauter, et al.
Sauter, et al.
Sauter, et al.
U.S. EPA, 1980
. 1978
1976
1976
. 1976
1976
1976
1976
1976
* LC = life cycle or partial life cycle, ELS = early life stage
•"Results are expressed as lead, not as the compound.
-------
Table 2. (Continued.
Freshwater
Chronic toxiclty vs. hardness
Dafihnla mag,*: slope = 2.35, intercept = -6.60. r = 0.94, not significant, n = 3
Chronic slope = 2.35 (see text)
to
Species
Cladoceran,
Daphnia maqna
Cladoceran,
Daphnia maqna
Cladoceran,
Daphnia magna
Rainbow trout,
Salmo gairdneri
Brook trout,
Salvellnus fontinalis
BluegiI I,
Leponuls macrochlrus
Mysld shrimp,
jfysidopsls
Acute-Chronic Ratios
Acute Value Chronic Value
(ug/D (ug/l)
612
952
1,910
1,170
4,100
23,800
2,960
12
119
128
19
83
92
25
Ratio
51
8
15
62
49
259
118
-------
Table 2. (Continued)
Species Mean
Chronic Intercept
Rank*
8
7
6
5
4
W 3
i
00
2
1
Spec 1 es
White sucker.
Catostomus commersonl
Channel catfish.
1 eta 1 urus punctatus
Lake trout,
Sa 1 ve 1 1 nus namaycush
Bluegill,
Lepomis macrochlrus
Rainbow trout.
Sal mo galrdnerl
Brook trout.
Salvelinus fontlnalis
Cladoceran,
Daphnla magna
Snail,
Lymnea palustrls
-------
Table 3. Species mean acute Intercepts and values and acute-chronic ratios for lead
ra
t->
ID
lank*
10
9
8
7
6
5
4
3
2
1
Species
Caddisf ly,»*
(unspecified)
Goldfish,
Carasslus auratus
Rotifer,
Ph 1 1 od 1 na acut 1 corn 1 s
Guppy,
Poeci 1 la retlculata
Bluegil 1,
Lepomls macrochlrus
Fathead minnow.
Plmephales promelas
Rainbow trout,
Sal mo gairdnerl
Brook trout.
Salvelinus font! nails
Cladoceran,
Daphnla magna
Scud,
Species Mean
Acute Intercept
(yg/l)
FRESHWATER SPECIES
—
815
804
533
455
158
158
40.5
4.02
1.16
Species Mean
Acute-Chronic
Ratio
_
—
.
259
_
62
49
18
_
Gammarus pseudolImnaeus
-------
Table 3. (Continued)
Species Mean Species Mean
Acute Value Acute-Chronic
Rank* Species (U9/D Ratio
w
to
o
5
4
3
2
1
SALTWATER
Soft she! 1 clam,
Mya arenaria
Mysld shrimp,
Mysidopsls bahia
Oyster,
Crassostrea vlrglnlca
Hard clam,
Mercenarla mercenarla
Copepod,
Acart i a c 1 aus 1 1
SPECIES
27,000
2,960
2,450
780
668
118
* Ranked from least sensitive to most sensitive based on species mean
acute Intercept or value.
»» See text.
Freshwater
Final Acute Intercept = 0.623 ug/l
Natural logarithm of 0.623 = -0.47
Acute slope = 1.22 (see Table 1)
Final Acute Equation = e<1.221In(hardness)1-0.47)
-------
Table 4. Plant values for lead
Species
Alga,
Anki strodesmus sp.
Alga,
Chi ore! la sp.
Alga,
Scenedesmus sp.
Alga,
Selenastrum sp.
to
Hardness
(mg/l as Result*
Chemical CaCO,) Effect
-------
Table 5. Residues for lead
BIoconcentrat Ion
Duration
(days) Reference
K)
to
Spec 1 es
Snal 1,
Lymnea jaalustrls
Snail,
Physa Integra
Stonef ly,
Pteronarcys dorsata
Caddisf ly.
Brachycentrus sp.
Brook trout (embryo- 3 mos),
Salvel inus fontinalis
Bluegl 1 1,
Lepotnls macrochlrus
Oyster,
Crassostrea vlrglnlca
Oyster,
Crassostrea vlrglnlca
Oyster,
Crassostrea vlrglnlca
Ouahaug, hard clam,
Mercenaria mercenaria
Soft shel 1 clam.
Mya arenarla
Mussel,
Mytllus edul Is
Mussel,
Mytl lus edul is
T 1 ssue
Whole body
Whole body
Whole body
Whole body
Whole body
Whole body
Soft parts
Soft parts
Soft parts
Soft parts
Soft parts
Soft parts
Soft parts
onemitai
FRESHWATER SPECIES
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
"
SALTWATER SPECIES
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead chloride
1,700*
738*
1,120*
499*
42*
AS*
*v J
536
68*
1,400
17.5*
112*
650*
200*
120 Borgmann, et al. 1978
28 Spehar, et al. 1978
28 Spehar, et al. 1978
28 Spehar, et al. 1978
140 Holcombe, et al. 1976
-** Atchison, et al. 1977
140 Zaroogian, et al.
1979
49 Pringle, et al. 1968
70 Shuster i Pringle,
1969
56 Pringle, et al. 1968
70 Pringle, et al. 1968
40 Schulz-Baldes, 1974
37 Talbot, et al. 1976
-------
Table 5. (Continued)
Species
TIssue
Chemical
BIoconcentratIon Duration
Factor (days)
Reference
Musse 1 ,
Myti lus edul is
Mussel,
Myti lus edul is
Mussel ,
Myti lus edul is
Diatom,
Phaeodacty turn tricornutum
Diatom,
Ditylum brightwel 1 i I
Phytoplankton,
Platymonas subcordiformis
, * B ioconcentrat ion factors
M
Soft parts
Soft parts
Soft parts
Whole body
Cells
Whole body
have been converted
Lead n i trate
Lead nitrate
Lead nitrate
Lead chloride
Lead chloride
Lead chloride
from dry weight
2,570*
2,080*
796*
1,050*
725*
933*
to wet weight.
130 Schu Iz-Baldes,
130 Schu Iz-Baldes,
130 Schu Iz-Baldes,
1/24 Schu Iz-Baldes,
14 Canterford, et
1978
1/24 Schu Iz-Baldes,
1972
1972
1972
1976
at,
1976
analyzed for lead, zinc and cadmium.
-------
Species
Chemical
Table 6. Other data for lead
Hardness
(ing/1 as
CaCOx) Duration
FRESHWATER SPECIES
Effect
Result*
(pg/I) Reference
Alga,
Anabaena sp.
Lead nitrate
24 hrs
50% reduction
of 14C02
fixat ion
15,000 Malanchuk & Gruendling,
1973
Alga,
Anabaena sp.
Lead nitrate
24 hrs
50? reduction
of 14C02
fixation
26,000 Malanchuk & Gruendling,
1973
Alga,
Anabaena sp.
Lead nitrate
24 hrs
50? reduction
of 14C02
fIxatIon
15,000 Malanchuk i Gruend I Ing,
1973
Alga,
Chtamydomonas sp.
Lead nitrate
24 hrs
50? Deduction
of 14C02
fixation
17,000 Malanchuk & Gruendling,
1973
Alga,
Chlamydomonas sp.
Lead nitrate
24 hrs
50? reduction
of 14C02
f Ixat Ion
17,000 Malanchuk i Gruend I ing,
1973
Desmid,
Cosmarlum sp.
Lead nitrate
24 hrs
50? reduction
of 14C02
fixation
5,000 Malanchuk & Gruend I Ing,
1973
Desmid,
Cosmarlum sp.
Lead nitrate
24 hrs
50? reduction
of 14C02
fIxat ion
5,000 Malanchuk & Gruend I ing,
1973
Desmid,
Cosmarlum sp.
Lead nitrate
24 hrs
50? reduction
of 14C02
fixation
5,000 Malanchuk i Gruend I Ing,
1973
D i atom,
Navlcula sp.
Lead nitrate
24 hrs
50? reduction
of 14C02
fixation
17,000 Malanchuk & Gruend I ing,
1973
Diatom,
Navicula sp.
Lead nItrate
24 hrs
50? reduct ion
of 14C02
fixation
28,000 Malanchuk i Gruendl ing,
1973
-------
Table 6. (Continued)
Species
Diatom,
Nay leu la sp.
Sludge worm,
Tublfex sp.
Sludge worm,
Tublfex so.
Snail,
Gonlobasls^ llvescens
Snail,
Lymnaea emarg 1 nata
Snail,
Physa Integra
Cladoceran,
Daphn la magna
Cladoceran,
Daphn la magna
Scud,
Gammarus pseudol Imnaeus
Chironomid
(embryo - 3rd instar),
Tany tarsus disslml Us
Mayfly,
Ephemerel la^ grand Is
May-fly (nymph),
Ephemere 1 1 a_ grand 1 s
Mayfly,
Ephemerel la subvaria
Chemical
Lead nitrate
Lead nitrate
Lead nitrate
Lead acetate
Lead acetate
Lead nitrate
Lead chloride
Lead chloride
Lead nitrate
Lead nitrate
Lead nitrate
Lead nitrate
Lead su 1 fate
Hardness
(«g/l as
CaCOO
-
-
-
154
154
46
45
45
46
47
50
50
44
Duration
24 hrs
24 hrs
24 hrs
48 hrs
48 hrs
28 days
21 days
21 days
28 days
10 days
14 days
14 days
7 days
Effect
50t .reduction
of 44C02
fixation
LC50
LC50
LC50
LC50
No effect on
survival
LC50
Reproducti ve
I mpa Irment
LC50
LC50
LC50
Bloconcentra-
t ion factor =
2,366
LC50
Result*
(uq/l)
17,000
49,000
27,500
71,000
14,000
565
300
30-100
28
258
3,500
-
16,000
Reference
Malanchuk & Gruendling.
1973
Whit ley, 1968
Whit ley, I96S
Cairns, et al. 1976
Cairns, et al. 1976
Spehar, et al. 1978
Blesinger &
Chrlstensen, 1972
B I es 1 nger &
Christensen, 1972
Spehar, et al. 1978
Anderson, et al. 1980
Nehrlng, 1976
Nehrlng, 1976
Warnick & Bel 1, 1969
-------
Table 6. (Continued)
Species
Stonefly,
Pteronarcys californica
Stonef ly.
Pteronarcys dorsata
Caddisf ly.
Brachycentrus sp.
Caddlsfly,
Hydropsyche betteni
Rainbow trout.
Salmo qalrdnerl
Rainbow trout (12 mos).
Salmo qalrdnerl
f Rainbow trout.
M Salmo qalrdneri
Rainbow trout,
jajmo gairdnerl
Rainbow trout.
Salmo gairdnerl
Rainbow trout.
Salmo qalrdneri
Rainbow trout,
Salmo qalrdnerl
Rainbow trout (f ingerl Ing) ,
Salmo qalrdnerl
Chemical
Lead nitrate
Lead nitrate
Lead nitrate
Lead su 1 fate
Lead nitrate
-
Lead nitrate
Lead nitrate
Lead nitrate
Lead chloride
Lead nitrate
Hardness
(mg/l as
CaCO^)_
50
46
46
44
135
135
135
135
135
135
99
353
Durat I on
14 days
28 days
28 days
7 days
28 days
14 days
21 days
32 wks
32 wks
29 wks
28 days
19 mos
Result"
Effect (yg/D
B ioconcentra-
tion factor =
86
No effect on
survival
No effect on
survl val
-
565
565
LC50 32,000
Inhibition of
ALA-D activity
Inhibition of
ALA-D activity
LC50 2
Black-tails in
3 of 10
remaining fish
1 ncrease of RBC
and decreases of
RBL, Iron content,
and ALA-D in blood
Al 1 fish with
black tai Is, and
decrease in ALA-D
In blood
LC50
Lordoscol iosls
13
10
,400
120
13
87
180
850
Reference
Nehring, 1976
Spehar, et al.
Spehar, et al.
Warnick & Bel 1,
Hodson, 1976
Hodson, et al.
Hod son , et a 1 .
Hodson, et al.
Hodson, et al.
Hodson, et al.
Birge, et al.
Da vies, et al.
1978
1978
1969
1977
1978
1978
1978
1980
1978
1976
-------
to
I
Table 6. (Continued)
Species
Rainbow trout (sac fry),
Salmo galrdnerl
Brook trout,
Salve IInus font I nails
Brook trout (12 mos),
Salvellnus fontlnalls
Brook trout
(embryo - 21 day),
Salvellnus fontlnalls
Brook trout (12 mos),
Salvellnus fontinalls
Red shiner,
Notropis lutrensls
Goldfish «12 mos),
Carasslus auratus
Pumpklnseed (>12 mos),
Lepomls glbbosus
Largemouth bass,
Mlcropterus salmoIdes
Fathead minnow,
Plmephales promelas
Fathead minnow,
Plmephales promelas
Mosquitofish (adult),
Gambusla affinls
Mosquitofish (adult),
Gambusla affinls
Marbled salamander,
Ambystoma opacum
Chemical
Lead
Lead
Lead
Lead
Lead
Lead
Lead
Lead
Lead
Lead
Lead
Lead
Lead
nitrate
-
nitrate
chloride
chloride
nitrate
nitrate
nitrate
chloride
chloride
acetate
nl trate
oxide
chloride
Hardness
(«g/l as
CaCOif) Duration
28 19
21
135 14
44 38
44 56
48
135 14
135 14
99 8
400 96
20 96
%
96
99 8
mos
days
days
days
days
hrs
days
days
days
hrs
hrs
hrs
hrs
days
Re-
Effect (JK
Lordoscol losis
Stamina
Inhibition of
ALA-D activity
Elevation of ALP
and ACH activity
Decrease of
hemoglobin and
inhibition of
GOT activity
suit*
l/il
31
14
90
525
58
LC50 630,000
Inhibition of
ALA-D activity
Inhibition of
ALA-0 activity
LC50
LC50 >75,
LC50 7,
LC50 240,
LC50 >56,000,
LC50 1,
470
90
240
000
480
000
000
460
Reference
Davies, et al
Adams, 1975
Hod son, et al
Christens en.
Chrlstensen,
1977
Wai len, et al
Hod son, et al
Hod son, et al
Blrge, et al.
.Tarzwel 1 4 He
1960
Pickering 4 H
1966
Wai len, et al
Wai len, et al
Birge, et al.
. 1976
. 1977
1975
et al.
. 1957
. 1977
. 1977
1978
ndersoi
enders<
. 1957
. 1957
1978
-------
Table 6. (Continued)
Species
Frog (adult).
Rana plplens
Cil late protozoan.
Cr 1 st 1 gera sp.
Cl 1 iate protozoan,
Cr 1st! gera sp.
Polychaete,
Ophrvotrocha labronlca
Polychaete,
Ctenodrllus serratus
Polychaete (trocnopnore).
a Capltella capitata
oo Polychaete,
nphryotrocha diapema
Polychaete,
nphryotrocha dladema
Oyster,
r.rassostrea virgin lea
Aba lone,
Hal lotus rufescens
Mummichog,
Fnndulus heterocl itus
Hardness
img/l as
Chemical CaCO^L- Duration
Lead nitrate - 30 days
SALTWATER SPECIES
Lead nitrate - 12 hrs
Lead nitrate - 12 hrs
Lead nitrate - >«>0 hrs
Lead acetate - 21 days
Lead acetate - » nrs
Lead acetate - * hrs
Lead acetate - 21 days
i 1 vr
Field study ~ ' 'r
Lead chloride - 6 mos
Lead nitrate
Result*
Effecl
Death
Reduced growth
rate by 8.5*
Reduced growth
rate by 11.7?
LC50
Suppressed
reproduction
LC50
LC50
Suppressed
reproduct Ion
Bioconcentra-
tion factor =
326
Accumulated 21
ug/g wet Wt
*hl le being fed
a brown alga
(Egregla laevi-
gata) which was
pretreated with
1 mg/l
30* depressed
axis formation
In embryos
(liq/l)
100
150
300
1..000
1,000
1,200
14,100
1,000
-
-
100
Reference
Kaplan, et al. 1967
Gray i Ventil la, 1973
Gray 4 Ventl 1 la, 1973
Brown 4 Ahsanul lah,
1971
Relsh 4 Carr, 1978
Relsh, et al. 1976
Reish 4 Carr, 1978
Reish 4 Carr, 1978
Kopf ler 4 Mayer, 1973
Steward 4
Schulz-Baldes, 1976
Weis 4 Weis, 1977
-------
Table 6. (Continued)
Species Chemical
Soft shell clam. Lead nitrate
Mya arenarla
Mussel, Lead chloride
Mytllls edulis
Mussel, Lead nitrate
Mytllus edulis
Mud crab. Lead chloride
Rh 1 thropanopeus har 1 s I 1
Fiddler crab, Lead nitrate
Uca pug I lator
Sea urchin. Lead nitrate
Arbacia punctulata
™ Shiner perch. Lead nitrate
to Cymatogaster agqreqata
vo
Alga,
Laminar ia digitata
Diatom, Lead chloride
Phaeodacty 1 um tr I cornutum
Diatom, Lead chloride
Phaeodacty 1 um tr i cornutum
Diatom,
Phaeodacty lum tricornutum
Diatom, Lead nitrate
Skeletonema costatum
Hardness
(mg/l as
CaCO\) Duration
168 hrs
40 days
150 days
2 wks
30-31 days
24 hrs
48-72 hrs
72 hrs
12 days
Effect
LC50
LC50
LT50 for
adults
Delayed larval
development
Bioaccumu la-
tion factor =
20
Few gastru la
developed
21% inhibition
of bra i n
chol inesterase
50-60? reduc-
tion In growth
Completely
inhibited
photosynthesi s
Reduced photo-
synthesis and
respiration by
25-50$
No growth
Inhibition
EC50 for
growth rate
Result*
(ug/l)
8,800
30,000
500
50
100
14
7.8
1,000
10,000
100
1,000
5.1
Reference
Elsler, 1977
Talbot, et at. 1976
Schulz-Baldes, 1972
Beni jts-Claus 4
Benijts, 1975
wels, 1976
Waterman, 1937
Abou-Donia &Menzel,
1967
Bryan, 1976
Woolery 4 Lew in, 1976
Woolery 4 Lew in, 1976
Hannan 4 Patoull let,
1972
Rivkin, 1979
-------
Table 6. (Continued)
w
U)
o
Species Chemical
Diatom, Lead nitrate
Skeletonema costatum
Phytoplankton, Lead chloride
Platymonas subcordlformls
Phytoplankton, Lead chloride
Platymonas subcordlformls
Phytoplankton, Lead chloride
Platymonas subcordlformls
Phytoplankton, Lead chloride
Platymonas subcordlformls
Alga, Tetramethyl lead
Dunaliella tertiolecta
Alga, Tetraethyl lead
Dunaliella tertiolecta
Hardness
(mg/l as Result*
CaC03) Duration Effect
-------
REFERENCES
Abou-Donia, M.B. and D B. Menzel. 1967. Fish brain cholinesterase: Its in-
hibition by carbamates and automatic assay. Comp. Biochem. Physio!. 21: 99.
Adams, E.S. 1975. Effect of lead and hydrocarbons from snowmobile exhaust
on brook trout (Salvelionus fontinalis). Trans. Am. Fish. Soc. 104: 363.
Anderson, R.L. et al. 1980. Survival and growth of Tanytarsus dissimilic
(cheronomidae) exposed to copper, cadmuim, zinc, and lead. Arch. Environ.
Contam. Toxicol. 9: 329.
Atchison, G.J., et al. 1977. Trace metal contamination of bluegill
(Lepomis macrochirus) from two Indiana lakes. Trans. Am. Fish. Soc.
106: 637.
Benijts-Claus, C. and F. Benijts. 1975. J_n_: J.H. Koeman and J.J. Strik
(eds.), Sublethal Effects of Toxic Chemicals on Aquatic Animals. E^lsevier
Pub. Co., Amsterdam, p. 43.
Biesinger, K.E. and G.M. Christensen. 1972. Effect of various metals on
survival, growth, reproduction and metabolism of Daphnia magna. Jour. Fish.
Res. Board Can. 29: 1691.
Birge, W.J., et al. 1978. Embryo-larval Bioassays on Inorganic Coal Ele-
ments and Jji Situ Biomonitoring of Coal-waste Effluents. In: E.E. Samuel,
et al. (eds.), Surface Mining and Fish/Wildlife Needs in the Eastern United
States. U.S. Dept. Int., Fish Wildl. Serv., FWS/OBS-78/81, Dec. 1978.
B-31
-------
Borgman, U., et al. 1978. Rates of mortality, growth, and biomass produc-
tion of Lymnaea palustris during chronic exposure to lead. Jour. Fish. Res.
Board Can. 35: 1109.
Brown, B. and M. Ahsanullah. 1971. Effect of heavy metals on mortality and
growth. Mar. Pollut. Bull. 2: 182.
Bryan, G.W. 1976. Heavy metal contamination in the sea. In; R. Johnson
(ed.)> Marine Pollution. Academic Press.
Buikema, A.L., et al. 1974. Evaluation of Pnilodina acuticornis (Rotifera)
as a bioassay organism for heavy metals. Water Resour. Bull. 10: 648.
Cairns, J., et al. 1976. Invertebrate response to thermal shock following
exposure to acutely sub-lethal concentrations of chemicals. Arch. Hydro-
biol. 77: 164.
Calabrese, A. and D.A. Nelson. 1974. Inhibition of embryonic development
of the hard clam, Mercenaria mercenaria, by heavy metals. Bull. Environ.
Contam. Toxicol. 11: 92.
Calabrese, A., et al. 1973. The toxicity of heavy metals to embryos of the
American oyster Crassostrea virginica. Mar. Biol. 18: 162.
Canterford, G.S., et al. 1978. Accumulation of heavy metals by the marine
.diatom Ditylum brightwellii (West) Grunow. Aust. J. Mar. Freshwater Res.
29: 613.
B-32
-------
Chapman, G.A., et al. 1980. Effects of water hardness on the toxicity of
metals to Daphnia magna. U.S. Environmental Protection Agency. Environ.
Res. Lab., Corvallis, Oregon. (Manuscript)
Christensen, G.M. 1975. Biochemical effects of methylmercuric chloride,
cadmium chloride and lead nitrate on embryos and alevins of the brook
trout. Toxicol. Appl. Pharmacol. 32: 191.
Christensen, G., et al. 1977. The effect of methylmercuric chloride, cad-
mium chloride, and lead nitrate on six biochemical factors of the brook
trout (Salvelinus fontinalis). Toxicol. Appl. Pharmacol. 42: 523.
Oavies, P.M., et al. 1976. Acute and chronic toxicity of lead to rainbow
trout (Salmo gairdneri) in hard and soft water. Water Res. 10: 199.
Eisler, R. 1977. Acute toxicities of selected heavy metals to the soft-
shell clam, Mya arenaria. Bull. Environ. Contam. Toxicol. 17: 137.
Gray, J.S. and R.J. Ventilla. 1973. Growth rates of sediment-living marine
protozoan as a toxicity indicator for heavy metals. Ambio. 2: 118.
Hale, J.G. 1977. Toxicity of metal mining wastes. Bull. Environ. Contam.
Toxicol. 17: 66.
Hannan, P.O. and C. Patouillet. 1972. Effect of mercury on algal growth
rates. Biotech. Bioen. 14: 93.
B-33
-------
Messier, A. 1974. Effects of lead on algae. I. Effects of Pb on viability
and motility of Platymonas subcordiformis (Ch1orophyta:volvocales). Water
Air Soil Pollut. 3: 371.
Hessler, A. 1975. Effects of lead on algae. Mutagenesis experiments on
Platymonas subcordiformis (Chlorophyta:valvocales). Mutat. Res. 31: 43.
Hodson, P.V. 1976. Amion leVulinic acid dehydratase activity of fish blood
as indictor of harmful exposure to lead. Jour. Fish. Res. Board Can.
33: 268.
Hodson, P.V., et al. 1977. Evaluation of erythrocyteamion levulinic acid
dehydratase activity as a short-term indicator in fish of a harmful exposure
to lead. Jour. Fish. Res. Board Can. 34: 501.
Hodson, P.V., et al. 1978. Chronic toxicity of water-borne and dietary
lead to rainbow trout (Salmo gairdnerj) in Lake Ontario water. Water Res.
12: 869.
Hodson, P.V., et al. 1980. Effects of dietary ascorbic acid on chronic
lead toxicity to young rainbow trout (Salmo gairdneri). Can. Jour. Fish.
Aquat. Sci. 37: 170.
Holcombe, G.W., et al. 1976. Long term effects of lead exposure on three
generations of brook trout (Salvelinus fontinalis). Jour. Fish. Res. Board
Can. 33: 1731.
B-34
-------
Kaplan, H.M., et al. 1967. Toxicity of lead nitrate solutions for frogs
(Rana pipins). Lab. Anim. Care. 17: 240.
Kopfler, F.C. and J. Mayer. 1973. Concentration of five trace metals in
the waters and oysters (Crassostrea virginica) of Mobile Bay, Alabama.
Proc. Natl. Shellfish Assoc. 63: 27.
Malanchuk, J.L. and G.K. Gruendling. 1973. Toxicity of lead nitrate to
algae. Water Air and Soil Pollut. 2: 181.
Marchetti, R. 1978. Acute toxicity of alkyl lead to some marine organ-
isms. Mar. Poll. Bull. 9: 206.
Monahan, T.J. 1976. Lead inhibition of chlorophycean microalgae. Jour.
Psycol. 12: 358.
Nehring, R.B. 1976. Aquatic insects as biological monitors of heavy metal
pollution. Bull. Environ. Contam. Toxicol. 15: 147.
Pickering, Q.H. and C. Henderson. 1966. The acute toxicity of some heavy
metals to different species of warmwater fishes. Air Water. Pollut. Int.
Jour. 10: 453.
Pringle, B.H., et al. 1968. Trace metal accumulation by estuarine mol -
lusks. Proc. Am. Soc. Civil. Eng., Jour. San. Eng. Div. SA3, 455-475.
B-35
-------
Reish, D.J. and R.S. Carr. 1978. The effect of heavy metals on the surviv-
al, reproduction, development and life cycles for two species of polychaet-
ous annelids. Mar. Pollut. Bull. 9: 24. (Table 3 available from author.)
Reish, D.J., et al. 1976. The effect of heavy metals on laboratory popula-
tions of two polychaetes with comparisons to the water quality conditions
and standards in Southern California marine waters. Water Res. 10: 299.
Rivkin, R.B. 1979. Effects of lead on growth of the marine diatom Skele-
tonema costatum. Mar. Biol. 239.
Sauter, S., et al. 1976. Effects of exposure to heavy metals on selected
freshwater fish. Ecol. Res. Ser. EPA 600/3-76-105.
Schulz-Baldes, M. 1972. Toxizitat und anreicherung von Blei bei der Mies-
muschel Mytilis edulis im Laborexperiment. Mar. Biol. 16: 266.
Schulz-Baldes, M. 1974. Lead uptake from seawater and food, and lead loss
in the common mussel Mytilis edulis. Mar. Biol. 25: 177.
Schulz-Baldes, M. 1976. Lead uptake in two marine phytoplankton organ-
isms. Biol. Bull. 150: 118.
Shuster, C.N. and B.H. Pringle. 1969. Trace metal accumulation by the
American Eastern oyster, Oassostrea virginica. Proc. Natl. Shellfish
Assoc. 59: 91.
B-36
-------
Spehar, R.L., et al. 1978. Toxicity and bioaccumulation of cadium and lead
in aquatic invertebrates. Environ. Pollut. 15: 195.
Stewart, J. and M. Schulz-Baldes. 1976. Long-term lead accumulation in
Abalone (Haliotus sp.) fed on lead-treated brown algae (Egregia laevigata).
Mar. Biol. 36: 19.
Talbot, V., et al. 1976. Lead in Port Phillip Bay mussels. Mar. Pollut.
Bull. 7: 234.
Tarzwell, C.M. and C. Henderson. 1960. Toxicity of less common metals to
fishes. Ind. Wastes. 5: 12.
U.S. EPA. 1980. Unpublished laboratory data. Environ. Res. Lab.,
Narragansett, Rhode Island.
Wallen, I.E., et al. 1957. Toxicity to Gambusia affinis of certain pure
chemicals in turbid waters. Sewage Ind. Wastes. 29: 695.
Warnick, S.L and H.L. Bell. 1969. The acute toxicity of some heavy metals
to different species of aquatic insects. Jour. Water Pollut. Control Fed.
41: 280.
Waterman, A.J. 1937. Effects of salts of heavy metals on development of
the sea urchin, Arbacia punctulata. Biol. Bull. 73: 401.
B-37
-------
Weis, J.S. 1976. Effects of mercury, cadmium, and lead salts on regenera-
tion and ecdysis in the fiddler crab, Uca pugilator. U.S. Dep. Comm. Natl.
Ocean. Atmos. Admin. Fish. Bull. 74: 464.
Weis, J.S. and P. Weis. 1977. Effect of heavy metals on development of the
killifish, Fundulus heteroclitus. Jour. Fish. Biol. 11: 49.
Whitley, L.S. 1968. The resistance of tubificid worms to three common pol-
lutants. Hydrobiol. 32: 193.
Woolery, M.L. and R.A Lewin. 1976. The effects of lead on algae. IV. Ef-
fects of lead on respiration and photocynthesis of Phaeodactylum tricornutum
(Bacillariophyceae). Water Air Soil Pollut. 6: 25.
Zaroogian, G.E., et al. 1979. Oassostrea virginica as an indicator of
lead pollution. Mar. Biol. 52: 189.
B-38
-------
Mammalian Toxicology and Human Health Effects
INTRODUCTION
The hazards of lead exposure have been under intensive inves-
tigation for many years. Research activities continue for several
reasons. First, industrial production and commercial use continues
at a fairly steady rate. Second, hazardous sources persist in the
environment long after the hazard-generating practice has been cur-
tailed. A good example is the persistence of lead-base paint in
houses long after the elimination of lead-containing pigments from
new household paints. Finally, as biomedical science in general
and toxicology in particular continue to push back the frontiers of
knowledge, indices of toxicity change, generally with a consequent
downward revision of what is considered an acceptable level of
human exposure to environmental pollutants.
Reassessment of acceptable levels of lead exposure have been
fairly numerous in recent years. These have taken the form of cri-
teria documents and of more academically-oriented reviews. Some
have been highly comprehensive, covering effects on the ecosystem
in general, as well as on man [National Academy of Sciences (NAS),
1972; Boggess, 1978]. Others have been mainly concerned with ef-
fects of lead on man [World Health Organization (WTTO) , 1977; U.S.
EPA, 1977; Hammond, 1977].
The purpose of this review is to summarize the literature
which is most relevant to the question of what is an acceptable
level of human exposure to lead via water. In doing so, it is
necessary to consider the consequences to human health of one or
another level of intake assignable to water and to the numerous
other sources.
C-l
-------
EXPOSURE
Natural Background Levels
Lead is ubiquitous in nature, being a natural constituent of
the earth's crust. The usual concentration in rocks and in soils
from natural sources ranges from 10 to 30 mg/kg. Most natural
groundwaters have concentrations ranging from 1 to 10 yg/1. This
is well below the United States' drinking water standard of 50
yg/1. It is much easier to specify natural levels of lead in rocks
and soil than in vegetation since long-range transoort of lead from
man-made sources via the air inevitably contaminates both surface
soil and plants growing thereon. The normal concentration of lead
in rural vegetation, however, ranges from 0.1 to 1.0 mg/kg dry
weight, or 2 to 20 mg/kg ash weight. Thus, nutrient movement from
soil to the organic matter in plants via water does not result in
any noticeable degree of biomagnification. Again, because of the
impact of long-range transport of lead via air from man-generated
sources, it is only possible to specify lowest concentrations found
over areas of the globe most remote from human activity. These are
of the order of 0.0001 to 0.001 yg/m3, mostly measured over Green-
land and over remote oceans.
Areas of abnormally high concentrations of lead occur in natu-
ral ores, usually in conjunction with high concentrations of cad-
mium and zinc. There is essentially no transfer from natural ore
beds into overlying streams; and there is none if the soil, is even
slightly alkaline (Jennett, et al. 1977).
C-2
-------
Man-generated Sources of Lead
Lead consumption in the United States has been fairly stable
from year to year at about 1.3 x 10 metric tons. Approximately
half of that consumption has been for the manufacture of storage
batteries and one-fifth has been for the manufacture of gasoline
antiknock additives, notably tetraethyl lead and tetramethyl lead.
Pigments and ceramics account for about 6 percent of annual pro-
duction. All other major uses are for metallic lead products or
for lead-containing alloys. The consumption of tetraethyl lead and
tetramethyl lead is declining. Other uses that have significant
potential for input into man are for paint pigment and solder.
Paints applied to surfaces will eventually crack, flake or peel.
Children are known to ingest this type of deteriorating paint.
Solder also is a potential source of lead exposure either when used
to seal water pipe joints or for joining seams in metal food and
beverage containers.
Ingestion from Water
Lead does not move readily through stream beds because it
easily forms insoluble lead sulfate and carbonate. Moreover, it
binds avidly to organic ligands of the dead and living flora and
fauna of stream beds. Nonetheless, under special circumstances,
lead does have considerable potential for hazardous exposure to man
via drinking water. In areas where the home water supply is stored
in lead-lined tanks or where it is conveyed to the water tap by lead-
pipes, the concentration may reach several hundred micrograms per
liter or even in excess of 1,000 yg/1 (Beattie, et al. 1972) .
There is a definite positive correlation between the concentration
C-3
-------
of lead in the domestic water supply and the concentration of lead
in the blood. The concentration of lead in the water conveyed
through lead pipes is dependent on a number of factors. The longer
the water has stood in the pipes, the higher the lead concentration
(Wong and Berrang, 1976). The lower the pH of the water and the
lower the concentration of dissolved salts in the water, the great-
er is the solubility of lead in the water. Leaching of lead from
plastic pipes has also been documented (Heusgem and E)e riraeve,
1973). The source of lead was probably lead stearate, which is
used as a stabilizer in the manufacture of polyvinyl plastics. The
magnitude of the problem of excessive lead in tap water is not ade-
quately known. In one recent survey of 969 U.S. water systems, 1.4
percent of all tap water exceeded the 50 ug/1 standard (^cCabe,
1970) . Special attention should be given in water quality surveil-
lance to soft water supplies, especially those with a PH < 6.5.
Future survey work should also indicate whether or not the water
was filtered before analysis. This appears to be a common practice
among water analysts. Since a substantial fraction of the lead in
drinking water probably is in particulate form, filtration prior to
analysis could give deceivingly low analytical values especially if
a substantial fraction of the particulate lead in water is avail-
able for absorption. However, "drinking water" analyses are usual-
ly performed in unfiltered water and hence represent total lead.
Ingestion from Food
It is generally held that food constitutes the major source of
lead ingested by people. Raw fruits and vegetables acquire lead by
surface deposition from rainfall, dust and soil, as well as from
C-4
-------
uptake via the root system. The relative contribution of these two
sources varies greatly depending upon whether the edible portion is
leafy or not. Furthermore, the nature of food processing may
either lower or raise the concentration in the raw product - e.g.,
washing as compared to packing in metal cans with lead solder
seams. There is no evidence of biomagnification in the food chain,
e.g., from aquatic vegetation to the edible portions of fish and
shellfish. Therefore, fish do not constitute an unusually signifi-
cant source of lead in man's diet.
Schroeder, et al. (1961) reported 0 to 1.5 mg/kg of lead for
condiments, 0.2 to 2.5 mg/kg for fish and seafood, 0 to 0.37 mg/kg
for meat and eggs, and 0 to 1.3 mg/kg for vegetables. Other more
recent studies have confirmed this observation. Many foods and
beverages are packed in metal cans which have a lead-soldered side
seam and caps. The concentration of lead in the contents is sub-
stantially higher after packing than before, and is also higher
than the same product packed in glass [Mitchell and Aldous, 1974;
U.S. Food and Drug Administration (U.S. FDA), 1975]. In some
instances, the lead probably leaches from the solder through cracks
or pores in the protective shellac coating applied to the inside of
the can. In many other instances, however, microscopic pellets of
lead splatter inside the can during the soldering process. Their
availability for absorption may differ substantially from that of
lead leached into solution.
Milk has been studied extensively as to lead content because
it constitutes a substantial fraction of the diet of infants and
young children. Whole raw cow milk has a concentration of about 9
C-5
-------
ug/1 (Hammond and Aronson, 1964) whereas market milk has an average
of 40 yg/1 (Mitchell and Aldous, 1974). Evaporated milk has been
variously reported to contain an average of 202 ug/1 (Mitchell and
Aldous, 1974), 110 + 11 yg/1 (Lamm and Rosen, 1974), and 330 to 870
yg/1 (Murthy and Rhea, 1971).
The daily dietary intake of lead has been estimated by numer-
ous investigators, using either the duplicate portions approach or
the composites technique wherein theoretical diets are derived
using nutrition tables. The results are generally consistent, con-
sidering variations in body size and metabolic rates. Thus, Nord-
man (1975) reported an average daily intake of 231 yg Pb for Fin-
nish adult males and 178 yg Pb for adult females. This is consis-
tent with a British study reporting 274 yg Pb/day for young adults
(Thompson, 1971) and with a Japanese study reporting 299 ug Pb/day
for adult males doing medium work (Horiuchi, et al. 1956). The
first two studies (Nordman, 1975; Thompson, 1971) described the
duplicate portions technique whereas the third (Horiuchi, et al.
1956) used the composites approach. Kolbye, et al. (1974) analyzed
the difficulties inherent in applying this approach. Kehoe (1961)
reported an average intake of 218 yg Pb/day for sedentary men.
This is not consistent, however, with two other American studies of
daily fecal lead excretion (Griffin, et al. 1975; Tepper and Levin,
1972) . From the lead balance studies of Kehoe (1961) , it can be
estimated that gastrointestinal absorption of lead approximates 8
percent. Making this adjustment, daily lead intake from the diet
based on fecal lead excretion would be 113 ug in sedentarv adult
males (Griffin, et al. 1975) and 119 yg in women (Tepper and Levin,
1972) .
C-6
-------
Many studies of dietary lead intake are somewhat vague as to
whether water consumption was included in the estimates. Others
specify "food and beverages."
The dietary intake of lead in infants and young children has
not been studied as extensively as it has in adults. Using the
duplicate diet approach, Alexander, et al. (1973) estimated a range
of 40 to 210 yg/day of lead for children ranging in age from three
months to 8.5 years. Horiuchi, et al. (1956) estimated 126 yg/day
of lead for youngsters 10 months old. These seemingly high values
compared to adults are not too surprising considering the high
caloric and fluid requirements of children in proportion to their
weight.
A bioconcentration factor (BCF) relates the concentration of a
chemical in aquatic animals to the concentration in the water in
which they live. An appropriate BCF can be used with data concern-
ing food intake to calculate the amount of lead which might be
ingested from the consumption of fish and shellfish. Residue data
for a variety of inorganic compounds indicate that bioconcentration
factors for the edible portion of most aquatic animals are similar,
except that for some compounds bivalve molluscs (clams, oysters,
scallops, and mussels) should be considered a separate group. An
analysis (U.S. EPA, 1980) of data from a food survey was used to
estimate that the per capita consumption of freshwater and estua-
rine fish and shellfish is 6.5 g/day (Stephan, 1980). The per
capita consumption of bivalve molluscs is 0.8 g/day and that of all
other freshwater and es'tuarine fish and shellfish is 5.7 g/day.
C-7
-------
Several bioconcentration factors are available for the edible
portions of bivalve molluscs:
Species
BCF
Oyster,
Crassostrea virginica
Oyster,
Crassostrea virqinica
Oyster,
Crassostrea virqinica
Auahaug, hard clam,
Mercenar ia mercenaria
Soft shell clam,
Mya arenaria
Mussel,
Mytilus edulis
Mussel,
Mytilus edulis
Mussel,
Mytilus edulis
Mussel,
Mytilus edulis
Mussel,
Mytilus edulis
536
68
1,400
17.5
112
650
200
2,570
2,080
796
Reference
Zarooqian, et al.
1979
Pringle, et al. 1968
Shuster and Pringle,
1969
Pringle, et al. 1968
Pringle, et al. 1968
Schulz-Baldes, 1974
Talbot, et al. 1976
Schulz-Baldes, 1972
Schulz-Baldes, 1972
Schulz-Baldes, 1972
The geometric mean bioconcentration factor for lead in bivalve
molluscs is 375, but no data are available for appropriate tissues
in other aquatic animals. Based on the available data for copper
and cadmium, the mean BCF value for other species is probably about
one percent of that for bivalve molluscs. If the values of 375 and
3.8 are used with the consumption data, the weighted average BCF
for lead and the edible portion of all freshwater and estuarine
aquatic organisms consumed by Americans is calculated to be 49.
C-8
-------
Inhalation
The third major obligatory source of lead in the general popu-
lation is ambient air. A great deal of controversy has been gener-
ated regarding the contribution of air to total daily lead absorp-
tion. Unlike the situation with food and water, general ambient
air lead concentrations vary greatly. In metronolitan areas aver-
age air lead concentrations of 2 ug/m with excursions of 10 ug/m
in areas of heavy traffic or industrial point sources are not un-
common, whereas in nonurban areas, average air lead concentrations
usually are of the order of 0.1 ug/m . In addition, people are so
mobile that static air sampling devices are not very useful for
estimating the integrated air lead exposure of urban populations.
Dermal
Exposure of the skin to lead probably is significant only
under special circumstances such as among workers in contact with
lead-based gear compounds or greases, or blenders of alkyl lead
fuel additives. It is very unlikely that the concentrations of
lead in water or air are sufficient to make dermal contact a sig-
nificant route of exposure.
Miscellaneous Sources
Among adults not occupationally exposed to lead, there are sev-
eral sources of lead which may assume clinically significant pro-
portions. Perhaps the most serious widespread problem is the con-
sumption of illicitly distilled whiskey (moonshine) which is often
heavily contaminated with lead. Many cases of frank lead poisoning
have been documented. The concentration of lead in moonshine whis-
key commonly exceeds 10 rag/1, or 2,000 times the drinking water
C-9
-------
standard. Storage of acidic beverages in improperly glazed earth-
enware has caused severe, sometimes fatal poisoning in the consumer
(Klein, et al. 1970; Harris and Elsea, 1967) .
Occupational exposure to lead may be quite excessive. Thus,
in primary lead smelters, the air lead concentration may exceed
1,000 jjg/m . A similar situation exists in some storage battery
manufacturing plants. Other hazardous occupations include welding
and cutting of lead-painted metal structures, automobile radiator
repair, and production of lead-base paints. In these occupations,
the principal hazard is generally considered to be from inhalation
of lead fumes and dusts. Hand-to-mouth transfer is probably sig-
nificant.
The hazard of lead to children is of considerable concern.
The number of children excessively exposed to lead from miscella-
neous sources is impressive. Thus, federally assisted lead screen-
ing programs reveal that excess lead absorption was found in 11.1
percent of 277,347 children screened in 1973. Blood lead levels
(PbB) were reported to be in excess of 40 yg/dl. The percentage has
fallen since then, being 6.4 percent in 1974 and 6.5 oercent in
1975 (Hopkins and Houk, 1976). By 1976 the problem had not changed
appreciably since 1974 and 1975. In that year, 8.7 percent of
500,463 children screened had PbBs ^ 30 yg/dl and 2.7 percent or
13,604 children had PbBs > 50 yg/dl (Center for Disease Control,
1977) .
It has long been held that the major source of elevated lead
exposure in infants and young children is lead-base paint in the
interior of home and in the soil surrounding the homes. More re-
C-10
-------
cently, the high lead content of soil and street dust attributable
to the fallout of lead from automobile exhaust has become suspect.
Thus, in the 1972 publication Airborne Lead in Perspective (NAS,
1972) , it is pointed out that the daily ingestion of 44 mg of street
dust at 2,000 yg Pb/g would suffice to elevate the PbB of a young
child from 20 yg/dl to 40 yg/dl. In a survey of 77 midwestern
United States cities, it was found that the average lead concentra-
tion in the street dust of residential areas was 1,636 yg/g and
that in commercial and industrial areas the average concentrations
were, respectively, 2,413 yg/g and 1,512 yg/g (Hunt, et al. 1971).
Soil along the shoulder of heavily-traveled roadways also is heavi-
ly contaminated, although most values found have been in the range
of hundreds of micrograms per gram rather than thousands (for exam-
ple, Lagerwerff and Specht, 1970).
The relative contribution of soil, automotive exhaust fallout,
and paint to lead exposure in children remains uncertain. There is
no question that children in the age range of 1 to 5 years, in which
the problem of elevated PbBs exists, do indeed exhibit pica, the
habit of mouthing or ingesting nonedible objects, e.g., pieces of
plastic, gravel, cigarette butts, etc. (Barltrop, 1966). The habit
also appears to be more prevalent among children who have elevated
PbBs than among those who do not (Mooty, et al. 1975) . There is
strong evidence that paint is a major source of lead in children
with pica. Thus, Sachs (1974) reported that 80 percent of patients
seen because of evidence of excessive lead absorption had a history
of eating paint or plaster. Hammond, et al. (1977) reported that
among 29 children with elevated PbBs (_>40 yg/dl) selected at ran-
C-ll
-------
dom from a lead screening program, all but one came from 14 homes
classified as having high hazard for lead-base paint, either exter-
ior or interior (Table 1). High hazard consisted of there being at
least one accessible painted surface with _^_0.5 percent Pb, peeling
or otherwise loose. The medium classification consisted of > 0.5
percent Pb, but the painted surface was generally tight. In this
study there was found to be a highly significant correlation (p =
0.007) between paint hazard classification (low, medium/ high) and
fecal lead excretion, but no correlation between fecal lead excre-
tion and traffic density (vehicles per day) in the vicinity of the
home (p = 0.41). Unfortunately, the correlation between traffic
density and the lead content of soil and dust was not determined.
Thus, the data are merely suggestive.
Ter Haar and Aronow (1974) reported that elevated lead expo-
sure in eight children, hospitalized for excessive lead absorption,
could not be caused by lead from fallout of airborne combusted
automobile exhaust. Six of the eight children had distinctly ele-
vated fecal lead excretion as compared to nine control children,
210
yet their excretion of Pb, a marker for aerosol fallout, was no
different from that of the controls. However, the children in this
study were supposed to have ingested paint. The criteria were one
or all of the following: (1) x-ray showed radio opaque materials
in the gut, (2) history of pica, (3) elevated PbB, and (4) x-ray
showed Pb lines on the long bones.
There is other evidence, however, which sugqests that dust and
soil are, under some circumstances at least, significant sources of
lead for infants and children and that their effect is additive to
C-12
-------
TABLE 1
Classification of Home Environments as to Lead Hazard'
n
i
Family
A
B
C
D
F
G
H
J
L
M
N
P
R
S
Paint, Lead
Hazard Interior
Dust
H
H 20
H
H
II 0.3(1)
M
H
H
H
Mi) ; H(E)
H
M(I) ; H(E)
H
MI) , H(E)
Concentration, %
Exterior
Dust
0
0
-
0
0
0
4
1
-
-
-
-
0
-
.45
.11
• 3(
• 1 (
.!(
.0(
• 9(
.6(
(2)
(2)
D
D
D
D
1)
1)
, c
d . w.
Soil
0.
0.
0.
0.
0.
0.
0.
-
0.
0.
-
-
0
-
12
06
07
3(
1(
2(
9(
05
(
(
(
2
1
3)
2)
D
)
)
D
2
(
1(3
)
D
)
Vehicles -,
per d. x 10
2.
10
2.
= 0
= 0
4
1
2.
0.
1
2.
4
5
5-5
30
- 15
5-5
.5
.5
- 6
- 2
5-5
5-1
- 2
5-5
- 6
- 7.5
Source: Hammond, et al. 1977
H = high; M = medium; L = low; (I) = interior; (E) = exterior. Absence of (I) or (E)
designation means that both conformed to the designated classification of H, M or L.
••
'Numbers in parentheses indicate number of environmental samples.
-------
that produced- by inhalation. The best evidence is orovided in a
study of a population of children residinq in the immediate vicini-
ty of a large secondary lead smelter near El Paso, Texas (Landri-
gan, et al. 1975). Sixty-nine percent of one- to four-year-old
children living within one mile of the El Paso smelter had blood
lead levels greater than or equal to 40 yg/dl, the level then con-
sidered indicative of increased lead absorotion. By contrast, the
prevalence of blood lead levels greater than or equal to 40 yg/dl
among 98 adults living in the same area was 16 percent. The geo-
metric mean lead concentration of soil in that location was 1,791
ppm and that of house dust was 4,022 opm. Lead based paint was not
a problem. Therefore it seems likely that a proportion of the lead
intake in the children living in El Paso was oral rather than by
inhalation and that the net effect of the two routes of exposure
was to place children at a considerably increased risk of lead up-
take than adults. The mere presence of high concentrations of lead
in soil accessible to children is not enough to create a hazard.
Thus, children living in British homes built on soils containing
8,000 yg Pb/g showed a considerably smaller elevation of PbB than
was found in the El Paso study (Barltrop, et al. 1974) . This may be
explained by other factors, e.g. rainfall and soil composition. El
Paso, Texas is a hot, dry, windy town, whereas Britain has consid-
erable rainfall, probably resulting in a heavy protective cover of
vegetation.
Certain miscellaneous sources of lead are unique to children
by virtue of the pica habit. These include colored newsprint
(Joselow and Bogden, 1974) and other items to which lead-base oig-
C-14
-------
ment is applied. In addition, pica is known to occur in some women,
particularly during pregnancy.
PHARMACOKINETICS
In characterizing the accumulation of lead in the body under
various circumstances of exposure, experimental animal data are
useful for establishing relevant principles. The specific rates of
transfer into, within, and outside of the animal system cannot be
relied upon to reflect, with any reliability, the situation in man.
Only human data will serve to indicate how much lead, in what form,
and by what route the accumulation of lead in specific organs and
systems would occur. This restriction has imposed severe limita-
tions on knowledge concerning lead metabolism in man. Only certain
human biological fluids and tissues are accessible for sampling,
except after death. The human cadaver, in turn, has its own limi-
tations, chiefly that the precise history of lead exposure prior to
death is not known. Ante mortem studies of lead metabolism in
human volunteers, on the other hand, have their own limitation.
They provide a substantial amount of knowledae concerning the sub-
ject, but extrapolation of the data to the general population is
tenuous. Population studies materially overcome this restriction,
but at the expense of precision and detail of knowledge. By com-
bining data from a.11 sources, a reasonable understand: ^a of lead
metabolism does emerge, however. The ultimate objective of this
section is to relate contribution of source (water) to total expo-
sure. As will be seen, this can only be achieved by using incre-
mental PbB as an index of water exposure - the approach also used by
the U.S. EPA in assessing air as a source of lead exposure.
C-15
-------
In reviewing the metabolism of lead in man, it is generally
assumed that all inorganic forms once absorbed behave in the same
manner. There is no evidence to suggest that this assumption is
erroneous.
Absorption
The classic studies of lead metabolism in man, conducted by
Kehoe (1961) indicate that, on the average and with considerable
day to day excursions, approximately 8 percent of the normal diet-
ary lead (including beverages) is absorbed. This conclusion was
reached as a result of long-term balance studies in volunteers.
?04
Recent studies using the nonradioactive tracer " Pb have con-
firmed this conclusion (Rabinowitz, et al. 1974). It is; of special
significance that these same workers found that absorption of doses
of lead nitrate, lead cysteine, and lead sulfide eaten after a 6-
hour fast and followed by another 6-hour fast was up to 8-fold
higher than when the lead was taken with meals (Wetherill, et al.
1974). This finding has been confirmed in mice using small doses
of lead (3 yg/kg) but not when using large doses (2,000 ug/kg)
(Garber and Wei, 1974). Thus, lead in water and other beverages
taken between meals may have a far greater impact on total lead
absorption than lead taken with meals.
The gastrointestinal absorption of lead in young children is
considerably greater than in adults. Alexander, et al. (1973)
found that dietary lead absorption was approximately 50 percent in
eight healthy children three months to 8.5 years of age. This
finding has been confirmed using a larger number of subjects less
than 2 years of age (Ziegler, et al. 1978). It is worth noting too
C-16
-------
that the same observation has been made using infant rats, thus
suggesting a similarity in lead absorption characteristics (Forbes
and Reina, 1974; Kostial, et al. 1971).
Numerous factors influence the absorption of lead from the
gastrointestinal tract. Low dietary Ca and Fe and high dietary fat
enhance lead absorption in experimental animals (Sobel, et al,
1938; Six and Goyer, 1970, 1972). Lead absorption has also been
shown to be enhanced in experimental animals by high fat, low pro-
tein, and high protein diets, and to be decreased by high mineral
diets (Barltrop and Khoo, 1975) . There also has been shown to be an
inverse relationship between dietary lead absorption and the cal-
cium content of the diet of infants (Ziegler, et al. 1978). The
chemical nature of the lead also has an influence on the degree of
absorption. Thus, Barltrop and Meek (1975) reported that, in
mature rats in an acute experiment, lead naphthenate, lead octoate,
and lead sulfide were absorbed only two-thirds as well as lead ace-
tate and that elemental lead particles, 180 to 250 ym, were ab-
sorbed only about 14 percent as well. Lead phthalate and lead car-
bonate were absorbed somewhat better than lead acetate. Some
attention has also been given to the availability for absorption of
lead in dried paint. The absorption of lead naphthenate is reduced
50 percent (in rats) as a result of incorporation in paint films
(Gage and Litchfield, 1969). Similarly, it has been found in mon-
keys that lead octoate in dried ground paint is not absorbed to the
same extent as lead octoate not incorporated into paint (Kneip, et
al. 1974) .
C-17
-------
There are serious problems in reqard to assessing the absorp-
tion of lead via the respiratory tract. The fractional deposition
of inhaled aerosols is relatively easy to measure, even in man.
The problem lies in determining the fate of the aerosol Particles.
To varving degrees, depending on their solubility and particle
size, these particles will be absorbed from the respiratory tract
into the systemic circulation, or they will be transferred to the
gastrointestinal tract by swallowing following either retrograde
movement up the pulmonary bed or by drainage into the pharynx from
the nasal passages. Unfortunately, the particle size distribution
and solubility of lead aerosols varies tremendously, depending on
their origin and residence time in the air. All of these diffi-
culties have frustrated previous attempts to assess the impact of
lead inhalation on the body burden of lead. It has always proved
necessary to fall back on a more indirect approach to the Problem,
whereby the impact of air lead concentration on the blood lead con-
centration is measured. In order for this approach to be meaning-
ful, certain conditions and restrictions must apply. First, a
fairly large population of subjects is needed in order to overcome
the background noise resulting from the variable impact, of dietary
lead on the subject's PbBs. Second, it is necessary to monitor the
air breathed by the subjects continuously and for a substantial
period of time. Third, the subjects must have been in the air envi-
ronment being evaluated for at least three months in order to
assure reasonable equilibration of air lead versus PbB. If all
these conditions are achieved, the results are only applicable for
the particular type of lead aerosol under study. Thus, it would
C-18
-------
not be reasonable to extrapolate data obtained in a peculation
breathing city air to a population of industrial workers for whom
the greatest source of input might be lead oxide fumes. Needless
to say, these restrictions are so severe that very few studies have
been performed which would allow one to make a reasonable iudgment
concerning the relative importance of diet versus air as sources of
lead absorption. An assessment of available information is de-
ferred to the end of this section on lead metabolism.
Dermal
Very few studies concerning the dermal absorption of lead in
man or experimental animals are available. Once again, the problem
of the chemical form of lead comes into play. In an early study of
dermal absorption of lead in rats, it was found that tetraethyl
lead was absorbed to a substantially greater degree than lead arse-
nate, lead oleate, or lead acetate (Laug and Kunze, 1948). Differ-
ences in the degree of absorption among the oleate, arsenate, and
acetate were not significant. In a more recent study, absorption
of lead acetate and lead naohthenate through the intact skin was
demonstrated, based on concentrations of lead attained in various
organs as compared to controls (Rastogi and Clausen, 1976). There
seems to be little question that lead can be absorbed through the
intact skin, at least when applied in high concentrations such as
were used in the Rastogi study (0.24M).
Distribution
The general features of lead distribution in the body are
well-known, both from animal studies and from human autopsy data.
Under circumstances of long-term exposure, approximately 95 percent
C-19
-------
of the total 'amount of lead in the body (body burden) is localized
in the skeleton after attainment of maturity. By contrast, in
children, only 72 percent is in bone (Barry, 1975). From animal
studies it also appears that the very young retain lead to a great-
er extent than adults (Jugo, 1977) . The amount in bone increases
with old age but the amount in most soft tissues, including the
blood, attains a steady state early in adulthood (Barry, 1975;
Horiuchi and Takada, 1954). Special note should be made regarding
the kinetics of lead distribution with reference to the blood.
When human volunteers are introduced into a new air environment
containing substantially higher concentration of lead than the ore-
vious one, the concentration of lead in the blood rises rapidly and
attains a new apparent steady state in about 60 to 100 days (T'ola,
et al. 1973; Rabinowitz, et al. 1974; Griffin, et al. 1975). This
is probably only an apparent steady state rather than a true one
because the kinetics of disappearance of lead from the blood differ
depending upon whether the high level was maintained for months or
for years. When men were placed in a high lead environment for 100
days and then returned to a low lead environment, the PbB concen-
tration returned to the pre-exposure level with a disappearance
half-time of only about six weeks. By contrast, the rate of PbB
decrement in workers who retire from the lead trades is much longer
(Haeger-Aronsen, et al. 1974; Prerovska and Teisinger, 1970). This
suggests that true equilibrium between the blood compartment and
bone compartment is only slowly attained under constant state expo-
sure conditions.
C-20
-------
The distribution of lead at the organ and cellular levels has
been studied extensively. In blood, lead is primarily localized in
the erythrocytes. The ratio of the concentration of lead in the
cell to lead in the plasma is approximately 16:1. Lead crosses the
placenta readily. The concentration of lead in the blood of the
newborn is quite similar to the maternal blood concentration. The
approximate ratio of fetal to maternal PbB is somewhat greater than
one (Clark, 1977; Schaller, et al. 1976). Studies of the subcellu-
lar distribution of lead indicate that distribution occurs to all
organelles, suggesting that all cellular functions at least have
the opportunity to interact with lead.
Metabolism
Upon entry into the body, lead compounds occurring in the
environment dissociate. Therefore, no question of metabolism of
the pollutant is involved. The one exception is the family of
alkyl lead compounds, principally tetramethyl lead and tetraethyl
lead. These are dealkylated to form trialkyl and dialkyl metabo-
lites, which are more toxic than the tetraalkyl forms (Bolanowska,
et al. 1967).
Excretion
The numerous studies reported in the literature concerning
routes of excretion in experimental animals indicate wide interspe-
cies differences. In most species, except the baboon, biliary
excretion predominates over urinary excretion (Cohen, 1970). it
also appears that urinary excretion predominates in man (Rabino-
witz, et al. 1973). This conclusion, however, is based on data
from one volunteer.
021
-------
Contributions of Lead from Diet versus Air to PbB
Great concern has developed in recent years regarding the
impact of air lead exposure on human health in the general pooula-
tion. Analysis of the contribution of ambient air to lead intake
by man has taken the form of an analysis of air lead versus PbR for
reasons explained in the section on lead absorption. An analysis
of all available data bearing on this guestion first appeared in
the Environmental Health Criteria 3 Lead published by WHO (1977) .
A more rigorous and detailed analysis was published subsequently in
Air Quality Criteria for Lead (U.S. EPA, 1977) .
Most of the data bearing on the question of air lead versus
PbB are deficient in one of two major respects. The most serious
and frequent deficiency is the lack of continuous air sampling in
the breathing zone of the subjects. An almost equally serious but
less frequent deficiency is the lack of variation in the air lead
concentration over the range of interest. This is, unfortunately,
a problem seen mainly in the clinical studies (as opposed to popu-
lation studies) where the number of subjects is quite limited.
Another problem, also limited to the clinical studies, is the arti-
ficial nature of the lead aerosol utilized. In spite of all these
apparent limitations, calculations from the epidemiologic and labo-
ratory data sources indicate a fairly narrow range of blood Pb to
air Pb ratios, namely 1 to 4 ug/dl for every microgram of air lead
per cubic meter (yg/m ). This blood Pb to air Pb ratio appears to
be higher for children than adults (Table 2) .
Among all the studies, the only one that satisfied all cri-
teria for design was the one by Azar, et al. (1975). It should be
C-22
-------
TANLE 2
Estimated Blood Lead to Mr Lead Ratios for Four Air Lead Concentrations
O
I
NJ
U)
Study
Rpidemio logical
A7.arh
Tepper- Levin0
Nordman
Nordmanc
Fuqasc
Johnson0
Johnson
Tsuchiya°
Goldsmith0
Goldsmith0
Yankel-von Lindern
Chamberlains-Williams
Da inesc
Clinical
Gri ff inc
Griffin0
Rahinowi tzc
Gross
Chamber la in
Chamberlain -Kehoe
Population
Adult males
Adult females
Adult males
Adult females
Adults
Adult males
Adult females
Adult males
Children males
Children females
Children
Adul ts
niack females
Adult males
Adult males
Adult males
Adults
Adults
Adults
Sampl e
Size
149
3 ,008
536
478
330
64
107
591
202
203
879
482
(unknown)
11 P 10.9
14 e 3.2
2
(21,000 person-days)
7
5
Ratio at
Air Lead Concentrations
|iq/rn
1.0 2.0 3.5 5.0
2.57 1.43 0.89 0.66
0.87 0.92 I. 00 1.08
(0.42)
(0.11)a
(2.64)
(0.80)
(0.60)
(3.84)
(2.30)
(1.70)
1.16 1.21 1.27 1.37
(1.10)
(2.30)
(1.40)
(1.65)
(1.7. 2.5)
(0.38)
(1.20)
(1.10)
"Source: U.S. EPA, 1977
Author's regression equation evaluated at specific air lead
°IJ.S. KPA calculation
Author's calculations
°Ratios presented in parentheses are not calculated from regression equation
-------
noted that the regression eauation developed to describe the data
(log PbB = 1.2557 + 0.153 (log ug Pb/m3)) has a slope of less than
one. Thus, the incremental rise in PbB for each 1 ug Pb/m in air
becomes progressively smaller. This relationship is consonant with
experimental animal data showing that over a wide range of dietary
lead levels the incremental rise in PbB decreases progressively
proportional to the rise in dietary lead levels (Prpic-Maiic, et
al. 1973; Azar, et al. 1973). It also is consonant with the World
Health Organization analysis of data on air lead exposure in a bat-
tery plant (WHO, 1977) .
The Azar data have been analyzed as to dose response by the
U.S. EPA (1977) and are presented in Table 3.
So far as the contribution of other sources of lead to PbB is
concerned, a quantitive analysis such as has been done for air lead
is simply not possible using the data currently available. An
estimate of the total dietary contribution to PbB was attempted by
WHO (1977) recently (Table 4).
So far as the specific contribution of water is concerned,
information is even more scarce than for total diet. Estimates of
the contribution of lead in water to PbB have been reported in four
separate studies. The first of these was oublished in 1976 (El-
wood, et al. 1976) . A linear regression was calculated for PbB and
water lead using "first run" morning tap water in 129 houses in
northwest Wales. Blood lead concentrations were determined for an
adult female resident in each house. The regression drawn was as
follows:
PbB (ug/dl) = 19.6 + 7.2 (mg *>b/l water)
C-24
-------
TABLE 3
Estimated Percentaqe of Population
Exceeding a Specific Blood Lead Level in Relation
to Ambient Air Lead Exposure
Air Lead,
yg/m
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
6.0
7.0
8.0
20.0
yg/di
15.22
26.20
34.12
40.23
45.15
49.23
52.69
55.67
58.27
60.57
64.45
67.63
70.28
Percent Exceeding
Blood Lead Level of:
30.0
ug/dl
0.59
1.67
2.88
4.12
5.35
6.57
7.75
8.90
10.01
11.09
13.16
15.10
16.92
40.0
ug/dl
0.02
0.07
0.16
0.26
0.38
0.51
0.66
0.81
0.97
1.14
1.48
1.83
2.20
C-25
-------
TABLE 4
Comparison of Daily Oral Lead Intake With PbB Levels3
Study Design
Fecal
excretion
Duplicate
Duplicate
o
i
Compos
ites
portion
portion
technique
Oral Intake
(yg/day)
119C
230
180
505
(women)
(men)
(women)
(men)
PbBb
(yg/100 ml)
15
12
7
34
.3
.3
.9
.6
PbB
100
oral
13
5
4
6
per
yg
Pb
.0
.4
.4
.8
Reference
Tepper
Nordman
Nordman
and Levin (1972)
(1975)
(1975)
Zurlo and Griffini, 1973d
d
Source: WHO, 1977
Contributions of air to PbB levels are not reported in most of these studies and could not be
subtracted from total PbB levels.
'Calculated from daily faecal excretion of 108 yg of lead assuming gastrointestinal absorption
10 percent
Pb-B levels from Secchi, et al. 1971
-------
The regression selection seems inappropriate from examination of
the scattergram (Figure 1) . A curvilinear model would have been
more appropriate or at least should have been tested, particularly
since the authors' linear model extrapolates to PbB 19.6 ug/dl, a
rather high baseline value for non-occupationally exposed women.
Moore, et al. (1977a) reported a very similar study in which
the interaction of PbB with lead in both "first flush" water and
running water was determined (Moore, et al. 1977a). The study was
conducted in Glasgow, Scotland, where the water is extremely soft.
As in the Elwood study, blood was drawn from adult females of the
household.
The Moore, et al. (1977a) study demonstrated that there is a
curvilinear relationship between PbB and the concentration of lead
in "first flush" water (Figure 2) . The equation for the regression
line was x = 0.533 + 0.675 y, with both values being expressed as
umol/1. Blood lead rose as the cube root of "first flush" water.
Actually, there is an error in the equation. The term x really is
PbB and y is the cube root of the "first flush" water. The authors
point out that the lead concentration in running water probably
reflects the impact of drinking water on PbB better than "first
flush" water. They found that the same relationship held, wherein
mean blood lead rose in proportion to the cube root of running
water lead. The correlation of running water lead to PbB was even
somewhat better than that of "first flush" water to PbB (r = 0.57
vs. 0.52). According to the authors, running water lead concentra-
tions were approximately one-third the "first flush" lead concen-
trations. These data are useful in that they provide an estimate
C-27
-------
450
400
Blood load
(»1 »)
ISO
300
250
200
ISO
• »'
TK< rtqrmion ef bleed Ited
on (merninq ) ««ttr lied in
Ce«rnoriir<
100
0 10 0 ZO 0 30 0 40 0 50 0 60 0 70 0 10 0 90 I 00
W«l«r Itad (»»" )
Rogrttsion o> blood-lead on morning watir lead in Caernarlonshir*.
FIGURE 1
Regression of Blood-lead on Morning Water Lead
in Caernarfonshire
Source: Elwood, et al. 1976
C-28
-------
1,5 —
BLOOD LEAD
0.5
Intervals of
Uater Lead
No. of Samples
Interval
I
.24 .48 1 1.44 2345
First Draw Water Lead C/jmol/l)
FIGURE 2
Mean Blood-lead Values for Nine Grouos at
Intervals of First-flush Water Lead
Source: Moore, et al. 1977a
C-29
-------
of the consequences of changing the concentration of lead in water
from one value to another. The example provided is the PbB conse-
quence of going from a "first flush" concentration of 0,,24 ymol/1
(50 yg/1) to 0.48 ymol/1 (100 yg/1). Such a change results in an
incremental rise in PbB of 0.11 ymol/1, or of 2.3 yg/dl. On a run-
ning water basis, the PbB change would occur going from 24/3 or 8
yg/1 to 48/3 or 16 yg/1. Using the authors' equation, the effect on
PbB of lead in running water can be estimated (Table 5). If this
relationship is correct, the impact of water lead on PbB is ex-
tremely great in the lower ranges of water lead but diminishes rap-
idly in the higher range of water lead (50 to 100 yg/1).
Hubermont, et al. (1978) also reports the interaction of morn-
ing tap water lead to PbB in pregnant women of the household.
Again, as in the study of Moore, et al. (1977a) a curvilinear rela-
tionship is described for the interaction of PbB with water lead:
PbB = 9.62 + 1.74 log morning water Pb, (yg/1).
The correlation was good (r = + 0.37; p = 0.001). The calculated
impact of water Pb on PbB using this equation is considerably less
in the lower range of water lead than in the Moore, et al. (1977a)
study. The data may not be strictly comoarable concerning water
sampling procedure.
One additional set of data is available which bears on the
question of the impact of the concentration of lead in water on
PbB. A study was conducted by the U.S. EPA concerning the rela-
tionship of lead in drinking water to PbB (Greathouse and Craun,
1976). Both early morning and running water samples were analyzed
for lead in a soft water area (Boston, Massachusetts) . In addi-
C-30
-------
TABLE 5
Effect of Running Water Lead on PbB*
Pb in Levels
(ymol/1) (y3)
0
0.
0.
0.
0.
0.
1.
0145
0725
1449
3623
7246
4493
ay
(y ) Pb Levels in
Running Water
(yg/D
0
1
5
10
25
50
100
_ (yg of Pb/1 of running
207
Total
PbB
11.03
14.44
16.86
18.37
20.99
23.58
26.84
water) -,
PbB due to
Water
0
3
5
7
9
12
15
.41
.83
.34
.96
.55
.81
*Source: Moore, et al. 1977a
C-31
-------
tion, blood samples for members of the household were analyzed for
lead. These subjects included both children and adults. Numerous
variables that might have influenced PbB were measured, including
age, sex, traffic density, lead in dust, and socio-economic status.
The data for interaction of PbB and water Pb were re-evaluated by
Dr. Greathouse specifically for the purpose of comparison to the
analyses of Moore, et al. (1977a) and Hubermont, et al. (1978).
This was done subsequent to publication of the 1976 Greathouse and
Craun report. Statistical analyses were performed using both the
Hubermont model (PbB = a + b log Pb in water) and the Moore model
(PbB = a + b Pb water) . These models were tested using (1) all
subjects aged 20 or more, and (2) women 20 to 50. The models were
also tested using running water data and early morning water data.
Interestingly, the relationship of early morning water Pb to run-
ning water Pb was almost identical to the 3:1 relationship reported
by Moore, et al. (1977a). More precisely, the relationship was:
Early morning water Pb = -0.028 + 3.081 running water Pb
r2 = 0.235? p = 0.0001
The cube root model of Moore, et al. (1977a) was more appro-
priate than the log water Pb model of Hubermont, et al. (1978) , and
the correlation of PbB with running water Pb was better than with
morning water Pb. The correspondence between data from all sub-
jects 20 years of age and over and for women age 20 to 50 was
striking:
Females 20 to 50, n = 249
PbB = 13.38 + 2.487 \} running water, Pb, yg/1
p = 0.020
C-32
-------
All subjects 20 yrs + , n = 390
<
PbB = 14.33 + 2.541 3>/running water, Pb, yg/1
p = 0.0065
At this point it is useful to compare the data from the three
studies discussed above. These data constitute the sole firm foun-
dation for assessinq the impact of lead in water on the internal
dose of lead as reflected in PbB. The comparison is presented in
Table 6. Calculations are made as to the PbB due to water over a
range of 1 to 100 yg Pb/1. The comparison is made on the basis of
running water Pb in spite of the fact that the equations for the two
European studies were developed on the basis of "first flush" or
"early morning" water. ^his adjustment seems -justified since the
ratio of these values to running water values has been affirmed to
be 3:1 in two of the three studies and therefore probably is ap-
proximately correct for the third study, the one by Hubermont, et
al. (1978). It is seen that the impact of lead in water on PbB is
quite different among the three studies. Since there is no basis
for rejecting any of the three studies, an estimate of the average
situation is made from an average of the three sets of data. The
reasons for any variation in the relationships can only be left to
speculation. Certainly the calcium, phosphate, and iron concentra-
tions of the waters in the three studies were different and may, to
some extent at least, account for the differences in the impact of
lead in water on PbB.
It is known that calcium profoundly Depresses lead absorption,
even over a relatively narrow range. For example, Ziegler, et al.
(1978) demonstrated that a mere doubling of the dietary calcium
C-33
-------
TABLE 6
PbB Levels due to Water Lead
PbB Due to Water (yq/dl)
Running Water
(yg/D
1
5
10
o
w 25
50
100
Greathouse and
Craun, 1976
2.54
4.35
5.47
7.43
9.36
11.79
Moore, et al.
1977a
3.41
5.82
7.34
9.96
12.55
15.81
Hubermont, et al.
1978
0.83
2.05
2.57
3.26
3.79
4.31
Average,
All 3 Studies
2.26
4.07
5.13
6.88
8.57
10.64
aThese values were all calculated using morning or "first flush" water values which were taken
to be three times the running water levels in the table.
-------
level profoundly depressed lead absorption in infants. Also, ani-
mal studies have shown that nutritional iron deficiency enhances
lead absorption. Attention should be given to the significance of
the variations in calcium and iron content of water against the
background variations of calcium and iron in nonaqueous portions of
the diet. As with calcium, high phosphate levels also tend to de-
press lead absorption.
EFFECTS
The effects of lead on man will be reviewed in a selective
fashion. Greatest emphasis will be placed on those effects which
occur at the lower levels of exposure and those which are properly
viewed with the most concern, namely neurobehavioral effects, car-
cinogenesis, mutagenesis, and teratogenesis. Because of the pauci-
ty of data in man and the seriousness of the effect, some sections
will be specifically subdivided into sections dealing with human
data and animal data. In other cases, that does not seem necessary
because of the wealth of human data available.
There is vast literature concerning the effects of lead on the
formation of hemoglobin and more limited literature on the related
effects on other hemo-proteins. From the standpoint of standard
setting, the effects of lead on this system are particularly impor-
tant since current knowledge suggests that the hematopoietic system
is the "critical organ." That is to say that effects are detect-
able at lower levels of lead exposure than is the case with any
other organ or system. The mechanism whereby lead reduces the cir-
culating concentration of hemoglobin is not thoroughly understood.
Many specific abnormalities exist, some occurring at lower PbBs
C-35
-------
than others. The life span of erythrocytes is shortened in heavy
lead exposure (PbB = 59 to 162) (Hernberg, et al. 1967). The mech-
anism is not well understood, but damage to the erythrocyte mem-
brane is likely. Dose-response and dose-effect relationships have
not been established. It seems unlikely, however, that shortened
cell life results in lead-induced reduction in circulating hemo-
globin. Rather, it is more likely that the synthesis of hemoglobin
is the critical mechanism.
Although there is evidence that lead interferes with globin
synthesis as well as heme synthesis, this effect seems to occur
only secondarily to a deficit in heme production (Piddington and
White, 1974) . Thus, it is the action of lead on heme synthesis that
appears most critical. This action is complex and involves several
enzymes in the synthesis of heme (Figure 3).
Clear evidence exists that lead inhibits both d-aminolevulinic
acid dehydrase (ALAD) and heme synthetase both ir\ vitro and ir± vivo
at relatively low levels of lead exposure. Elevation of the con-
centration of the substrates for these two enzymes in plasma and
urine (ALA) and in erythrocytes (PROTO) increases as PbB increases.
As a matter of fact, rise in PROTO and ALA occur at PbBs somewhat
below those associated with a decrement of hemoglobin. ^hus, in
adults, a decrement in hemoglobin first appears at PbB = 50 (Tola,
et al. 1973) and at PbB = 40 in children (Betts, et al. 1973;
Pueschel, et al. 1972), whereas a distinct elevation in ALA in the
urine (ALAU) first appears at PbB = 40 in men (Selander and Cramer,
1970; Haeger-Aronsen, et al. 1974) and children (NAS, 1972) and
somewhat lower in women (Roels, et al. 1975) . Rises in PROTO first
C-36
-------
(Mitochondrion)
Succinyl-CoA
Glycme
ALA Synthetase (ALAS)
Heme
s Aminolevulinic
Acid (ALA)
Protoporphyrin IX
(Cytoplasm)
ALA Dehydrase (ALAD) CoprophyrinogenUI
Pb
Porphobilinogen
-*- I Irnporphyrinogen TTT
FIGURE 3
Effects of Lead on Heme Metabolism
:-37
-------
appear at PbB = 15 to 30 in women and children and at PbB = 25 in
men (Sassa, et al. 1973; Roels, et al. 1975). The most reasonable
explanation for the rise in PROTO at levels of lead exposure below
the threshold for hemoglobin decrement is that the primary event is
inhibition of the insertion of iron into PROTO IX, whether it is
caused by inhibition of heme synthetase or by inhibited entry of Fe
into the mitochondrion (Jandl, et al. 1959) . Regardless of that
uncertainty, the effect is the same, a potential decrement in hemo-
globin, which leads to feedback depression of ALAS resulting in a
compensatory increase in the production of ALA and other heme pre-
cursors. The evidence for this compensatory adjustment, is to be
found both in laboratory animal studies (Strand, et al. 1972;
Suketa, et al. 1975) and in studies of peoole with elevated lead
exposure (Berk, et al. 1970; Meredith, et al. 1977). The approxi-
mate threshold for ALAD inhibition is ^bB = 10 to 20 for adults
(Tola, 1973) and PbB = 15 in children (Granick, et al. 1973) .
Roughly equivalent inhibition occurs concurrently in the liver of
man (Secchi, et al. 1974) and in the liver and brain of rats (Mil-
lar, et al. 1970). The toxicological implications of ALAD inhibi-
tion have not been studied extensively. However, substantial lead-
induced depression of blood ALAD activity in dogs does not reduce
the blood-regenerating response to acute hemorrhaging in dogs (Max-
field, et. al. 1972).
A few studies have been reported concerning effects of lead on
hemoproteins other than hemoglobin. Thus, the rate of cytochrome
P450-mediated drug metabolism has been found to be depressed in two
cases of lead poisoning (PbB = 60 and 72) but not in 10 cases where
C-38
-------
lead exposure ranged from PbB = 20 to 50 (Alvares, et al. 1975) .
Cytochrome content of kidney mitochondria has also been reported to
be depressed in rats (Rhyne and Goyer, 1971).
The question arises as to whether certain peculations may be
predisposed to the toxic effects of lead as a result of G-6-PD
deficiency or iron deficiency. G-6-PD deficiency is known to be
associated with increased susceptibility of erythrocytes to hemoly-
sis. The possibility' of increased susceptibility of G-6-PD-defi-
cient children to the hematopoietic toxicity of lead has not been
reported. In regard to possible enhancement of hemoglobin defi-
ciency by coexistent iron deficiency, the one study reported to
date was negative. There was no significant difference in the
blood hemoglobin or hematocrit among 29 iron-deficient children
with PbB 20 yg/dl as compared to 17 iron-deficient children with
PbB = 20 to 40 yg/dl (Angle, et al. 1975).
Dose-response relationships for the effect of lead on various
parameters of hematological indices have been developed recently
(Zielhuis, 1975). These are reproduced in tabular form in Table 7.
In considering these data, it is obvious that PEP (essentially
PROTO) elevation is a more sensitive correlate of lead exposure
than ALAU. It should also be noted, however, that an increase in
PEP above normal also occurs in iron deficiency anemia. Thus, the
data must be considered in that light. In a recent study of PEP in
lead-exposed and non-lead-exposed children, Roels, et al. (1978)
were able to study the interaction of PEP and PbB in the absence of
anemia as indicated by serum iron concentration. They proposed a
maximum acceptable limit for PEP at PbB = 25 ug/dl. The maximum
C-39
-------
o
I
TABLE 7
Dose Response Relationships for the Effect of Lead
on Various Parameters of Hemotological Indices
Percentage of adult female subjects
with FEP levels that exceeded those
found in control subjects with
PbB = 20 yg/100 ml
Percentage of children with FEP
levels that exceeded those found
in control subjects with
PbB= 20 yg/100 ml
PbB Level
(yg/100 ml)
11-20
21-30
31-40
41-50
51-60
61-70
No.
28
9
8
4
49
% with FEP Level
Higher than Normal
4
33
90
100
PbB Level
(yg/100 ml)
20
21-30
31-40
41-50
51-60
61-70
No.
87
72
24
14
12
10
219
% with FEP
Higher than
5
21
29
64
Level
Normal
Percentage of adult male subjects
with FEP levels that exceeded those
with PbB = 20 yg/100 ml
Percentage of male adults with ALA-U
levels = 5 mg/1 and = 10 mg/1
according to PbB level
PbB Level
(yg/100 ml)
11-20
21-30
31-40
41-50
51-60
61-70
No.
26
43
32
4
2
2
109
% with FEP Level
Higher than Normal
0
7
19
100
PbB Level
(yg/100 ml)
11-20
21-30
31-40
41-50
51-60
61-70
No.
17
27
36
55
38
34
207
ALA-U Level
= 5
0
0
14
33
74
88
(mg/1)
-10
0
0
j
11
37
50
lSource: Zielhuis, 1975
-------
acceptable point was the mean FEP plus two standard deviations for
rural children, which equalled 79.2 yg FEP/dl erythrocytes. The
PbB of these children was 9.1 ug/dl + 0.5 with serum iron > 50
yg/lOOml. This maximum is very similar to the maximum acceptable
FEP which would be calculated at mean FEP Plus two standard devia-
tions (PbB = 26 ug/dl) cited in the recent "Air Quality for Lead"
(U.S. EPA, 1977). As was indicated earlier, the cooperative effect
of iron deficiency and lead exposure on FEP has not as yet been ade-
quately defined. There is lust the one study by Angle, et al.
(1975), suggesting no interaction at PbB = 20 to 40.
The syndrome of lead encephalopathy has been recognized since
the time of Hippocrates as occurring in workers in the lead trades.
The major features were dullness, irritability, ataxia, headaches,
loss of memory and restlessness. These symptoms often progressed
to delirium, mania, coma, convulsions, and even death. The same
general effects were also described in infants and young children.
Encephalopathy due to lead was probably more frequently fatal in
children than in adults because lead exposure was usually not sus-
pected and because children do not communicate signs and symptoms
as readily as adults. The mortality rate among children has been
variously reported as being from 5 to 40 percent.
The literature concerning the neurological features and the
probable dose of lead involved is far more specific for children
than for adults. This is probably because the problem persisted
longer and hence benefited more from the accumulated sophistication
of disease investigation. Apart from the mortality statistics,
there was a considerable toll recorded among survivors in the form
C-41
-------
of long-term neurological sequelae. Cortical atroohy, convulsive
seizures, and mental retardation were commonly reported (Perlstein
and Attala, 1966; Byers and Lord, 1943).
The minimal level of lead exposure resulting in lead encepha-
lopathy is not clearly known and perhaps never will be in light of
the dramatic decrease in the incidence of the disease, particularly
during the last 10 to 15 years. Drawing mainly from his own experi-
ences, Chisolm (1968) has estimated the minimal PbB associated with
encephalopathy as being 80 pg/dl. There are occasional reports
however of occurrence of encephalopathy at PbBs below 80 ug/dl
(Smith, et al. 1938; Gant, 1938). Although 80 ug/dl may be a rea-
sonable estimate of threshold for encephalopathy in children, the
usual values are much higher, with a mean of approximately 328
according to one source (NAS, 1972).
It has been reasoned that if lead exposure as specified above
can have such severe deleterious effects on the central nervous
system, lower levels of exposure might well result in more subtle
effects. Specifically, the concern has been over whether such
effects occur in children whose PbBs are in the 40 to 80 ug/dl
range. Given the difficulties of study design, it is hardly sur-
prising that all of the relevant studies are ooen to criticism.
The most common deficiencies encountered are overlap of lead expo-
sure in the study groups (Pb versus control), inadequate matching
for socio-economic status and other variable, insensitivity of the
behavioral tests, and poor knowledge of the degree of lead exoo-
sure. In regard to this last-named problem, the index of exposure
has usually been PbBs determined at the time of behavioral testing.
C-42
-------
In some instances record of one earlier Pb3 determination was
available. In spite of these problems, when the various studies
are taken together, subtle neurobehavioral effects do appear to
occur as a result of exposure in the range of PbB = 40 to 80 yg/dl.
Two general approaches have been used in attacking the prob-
lem. The most common approach has been to evaluate two populations
of children closely matched as to age, sex, and socio-economic
status, but differing as to lead exposure. These studies are
retrospective and usually strictly cross-sectional. In only one
instance was a follow-up repeat study of the population performed
(de la Burde and Choate, 1972, 1975). The other general approach
has been to identify children with neurobehavioral deficits of un-
known etiology and to establish whether their lead exposure was
excessive in comparison to appropriate control children. Aside
from the usual specific flaws in experimental design, there has
been the additional question as to which came first, the excessive
lead exposure or the neurobehavioral deficit. Among mentally sub-
normal children whose problems were clearly attributable to etiolo-
gies other than lead, pica incidence and PbBs were both elevated
(Bicknell, et al.'1968) .
Among studies of the first type, those of de la Burde and
Choate (1975) are illustrative of the problems that exist in this
area of toxicology. Fine motor dysfunction, impaired concept for-
mation, and altered behavior profile were observed in 70 preschool
children exhibiting pica and elevated PbBs, all of which were > 30
yg/dl. The mean level was 59 yg/dl. The children were examined at
four years and again at seven vears of age. Both the lead-exposed
C-43
-------
group and the control group had been followed from infancy through
eight years of age as part of a Collaborative Study of Cerebral
Palsy, Mental Retardation, and Neurologic Disorders of Infancy and
Childhood. Unfortunately, the control group did not have blood
lead analyses performed. However, tooth lead and urinary coprooor-
phyrin determinations were ultimately performed. Another problem
was the inference that positive radiographic findings of lead in
long bones and/or intestines were found in subjects with PbBs in
the range of 30 to 40 ug/dl. Lead lines in bones at this level of
exposure are extremely unlikely (Betts, et al. 1973), suggesting
either that the blood lead determinations were spuriously low or
that they had actually been higher at times which did not coincide
with the time of sampling. Thus, it would seem that the minimal PbB
associated with neurobehavioral effects may well have been more on
the order of 50 to 60 ug/dl rather than 30 to 40 ug/dl. Overall,
the experimental design was otherwise generally sound.
Another often-cited study by Perino and Ernhart (1974) was
basically of the same general design as the one reported by de la
Burde and Choate (1972, 1975). It concluded that neurobehavioral
deficits occurred at PbBs as low as 40 yg/dl. The flaw in this
study was that the parents in the control group were better educat-
ed than those of the lead-exposed children. Differences found may
have been due to the fact that more highly educated parents train
their children more on tasks related to the behavioral measures
used. Low lead parent-child intelligence was correlated at 0.52
and high lead at only 0.1. The low correlation in high lead groups
suggests that a factor other than parental influence was operating
and probably was lead exposure.
C-44
-------
Albert, et al. (1974) studied school-age children with a his-
tory of PbBs ) 60 ug/dl early in childhood. Unfortunately, PbBs
for about one half of the control population were not available and
some of the control children previously had PbBs ^40 yg/dl.
The same types of flaws existed in studies which came up with
negative results. Thus, Kotok's study (1972) had a rather wide
overlap between PbBs of control subjects and lead-exposed subjects,
and in another negative study fewer than half of the "lead-exposed"
group had PbBs _>_40 yg/dl (Lansdown, et al. 1974). Another problem
among negative studies has been the study of perhaps inappropriate
populations. Lansdown's population consisted of British children
living in the vicinity of a smelter. In another negative study,
the children were Mexican-Americans also living in the vicinitv of
a smelter (McNeil, et al. 1975) . The problem population we are
dealing with in this country is of an entirely different socio-
economic character; inner city children who are predominantly
socially and economically deprived. The difference in background
may be significant as a determinant of behavioral ability.
In summary, there is sufficient evidence to indicate that
subtle neurobehavioral effects of lead exposure occur in children
exposed to lead at levels which do not result in clinical encepha-
lopathy. The minimal level of lead exposure, the duration of expo-
sure required, and the period of greatest sensitivity cannot be
specified with any degree of certainty. However, the conclusions
of two recent expert groups who have evaluated the literature in
great depth are remarkably similar. The World Health Organization
concluded that the probability of noticeable brain dysfunction
-------
increases in children from PbB levels of approximately 50 ua/dl
(WHO, 1977), and the U.S. EPA Science Advisory Board concurred in
the U.S. EPA conclusion that "the blood lead levels associated with
neurobehavioral deficits in asymptomatic children appear to be in
excess of 50 to 60 yg/dl." Future research may reveal that this
cut-off point is actually lower. Effects of lead exposure on the
peripheral nervous system of both adults and children are also
documented. A number of studies have documented the occurrence of
slowed nerve conduction with an approximate ^bB maximum of 50 ug/dl
(Hernberg, et al. 1967; Lilis, et al. 1977; Landrigan and Baker,
1976). This effect has been noted to occur at this exoosure level
without any overt signs of neuromuscular impairment.
Although generally considered not to be a maior public health
problem today, the potential damage to the brain of the fetus from
lead exposure has received some attention. Beattie, et al. (1975)
identified 77 retarded children and 77 normal children matched for
age, sex, and geography. Of 64 matched pairs, 11 of the retarded
children came from homes in which the concentration of lead in the
"first flush" water exceeded 800 ug/1. By contrast, none of the
control children came from such homes. In a follow-up study, PbBs
from the mental retardates, taken during the second week of life,
were found to be significantly higher than those of control sub-
jects (25.5 yg/dl versus 20.9 ug/dl) (Moore, et al. 1977b). Taken
at face value, those studies are extremely provocative. They sug-
gest that the brain of the fetus is considerably more sensitive to
the toxic effects of lead than the brain of the infant or young
child. Lambs exposed to low levels of lead in utero (PbB = 35)
C-46
-------
developed impaired visual discrimination learning behavior (Car-
son, et al. 1974). In spite of this seemingly low level of expo-
sure, control animals were exposed ir\ utero to lower levels of lead
(PbB = 5) than are generally considered normal for most species.
Bull and coworkers have exposed female rats to Pb from 14 days
prior to breeding through weaning of pups. The normal postnatal
increase in cerebral cytochromes (Bull, et al. 1978) and synapto-
genesis in the cerebral cortex (McCauley, et al. 1979) were delayed
by this treatment. These delays were associated with delays in the
development of exploratory and locomotor behavior during the same
development period (Crofton, et al. 1978). The latter effect was
shown to be entirely due to exposure to Pb _in utero. Blood lead
concentrations on the 18th day of gestation were reported to be
31.9 yg/dl. Further work is urgently needed concerning the neuro-
behavioral effects of low-level lead exposure _in utero.
Final.ly, a few comments are in order regarding neurobehavioral
effects of low-level exposure in adults. A battery of performance
tests were administered to 190 lead-exposed workers, along with a
questionnaire (Morgan and Repko, 1974). PbBs were below 80 ug/dl
in many of the workers. Unfortunately, there were many methodo-
logical problems and equipment failures which rendered the results
difficult to interpret. Further, results of a similar study by
other investigators were essentially negative (Milburn, et al.
1976). Thus, although it seems reasonable to suppose that neuro-
behavioral effects do occur at some level of exposure in workers,
it is extremely difficult to specify the exposure level at which
these effects may occur.
C-47
-------
Carcinogenicity
Three groups of investigators have reported epi^emiological
studies of causes of death among people overly exposed to lead.
The first such study was of causes of death among 184 pensioners
who died between 1926 and 1961 and of 183 men who died between 1946
and 1961 while still employed (Dingwall-Fordyce and Lane, 1963) .
The men were categorized as to lead exposure based on the nature of
their work and, in the case of highly exposed men, on the basis of
urinary lead excretion (100 to 250 yg/dl during the past 20 years
and probably higher than that earlier in the work historv). There
is a correlation between urinary lead and blood lead, wherein 100
yg Pb/1 in urine corresponds roughly to 50 ug/dl in blood (Selander
and Cramer, 1970).
There were 179 men in the high exposure category for which
causes of death were registered, 67 men in the category of negligi-
ble exposure and 91 men with no exposure. Although there was a sig-
nificant excess number of deaths among the men who had been exposed
*
to the greatest lead hazard, this excess could not be attributed to
malignant neoplasms, as the mortality rate from this cause was
actually somewhat less than expected. Furthermore, the incidence
of death from malignant neoplasms in this group has actually in-
creased in the more recent years as working conditions have im-
proved. It seems, rather, that the excess deaths in the heavily-
exposed group was due mainly to vascular lesions of the central
nervous system among men employed in the lead industries; during the
first auarter of this century.
C-48
-------
The second relevant study was of orchardists who at one time
sprayed fruit trees with lead arsenate. A cross-sectional study of
this population was conducted in 1938 by the U.S. Public Health
Service (Nelson, et al. 1973) . The population was classified as to
exposure on the basis of whether they were adult orchard workers,
(orchardists and lesser-exposed "intermediates" as separate cate-
gories) , non-exposed adults of the area, and children in the area.
For all categories blood lead, urine lead, and arsenic concentra-
tions were determined. In addition, the number of years of spray
exposure was recorded for the orchardists and "intermediates."
There was a definite gradation in blood and urine lead concentra-
tion corresponding to the degree of exposure as classified by
nature of orchard-related work or lack thereof. The orchardists
had the highest PbB (x = 44 for males and 43 for females) . Children
of the area were intermediate (PbB = 37 in boys and 36 in girls) and
adult consumers and "intermediates" had PbBs of 22 to 30.
In 1968 a follow-up study of this population was begun. Re-
sults were reported in 1973 (Nelson, et al. 1973). Of the original
1,229 study members, the status of 1,175 could be determined. Four
hundred and fifty-two had died and death certificates were avail-
able for 442. No consistent differences in Standard Mortality
Ratios (SMR) were observed on the basis of either exposure classi-
fication or duration of exposure. The only deviations in SMR from
expected were in the direction of fewer-than-expected deaths. The
mortality records for heart disease, cancer, and stroke were exam-
ined separately. Again, there was no suggestion of a relationship
between lead exposure and death from any of these three maior
causes of death.
C-49
-------
The most recent study of causes of death among lead-exposed
workers was reported by Cooper and Gaffey (1975) and Cooper (1976) .
Since the results were published, the study population has been re-
examined (Cooper, 1978). Results from the updated study will be
discussed, although details as to lead exposure history appear
mainly in the earlier publication. The objective of the study was
to determine what happened to lead workers whose levels of lead
absorption were below those associated with clinically-recogniz-
able illness but above that of the general population. The popula-
tion studied consisted of 2,352 smelter workers and 4,580 battery
workers. Death certificates were available for 1,703 of these men.
A good record of lead exposure history was considered important.
Unfortunately biological monitoring programs (lead in urine or
blood) were not in effect in many of the plants during the period of
employment, particularly so for the deceased. Nevertheless, enough
data were available to indicate that exposure was heavy. Thus, 67
percent of 1,863 workers had PbBs ^ 40 yg/dl and 20 percent had
PbBs y 70 yg/dl. Twenty-six percent of the battery workers and
21.1 percent of the smelter workers had been employed for more than
20 years.
The only causes of death that showed a statistically signifi-
cant elevation were "all malignant neoplasms" in the battery work-
ers, cancers of "other sites" in battery workers and "symptoms,
senility, and ill-defined conditions" in battery workers. In only
one of all the cancer deaths was a renal tumor specified. Only two
tumors of the brain were identified in the follow-up study. (No
specification is made in the original 1975 report as to brain
C-50
-------
tumors.) The author of the 1978 report concludes that the excess
deaths due to neoplasms cannot be attributed to lead "because there
was no consistent association between the incidence of cancer
deaths and either length of employment or estimated exposures to
lead." It is not clear from reading either of the two reports con-
cerning this population as to just how exposure categories were
established.
In a letter to Science, Kang, et al. (1980) questioned the
appropriateness of basing the decision of statistical significance
of the results on confidence limits rather than on calculations of
a more rigorous statistical test. In their reanalysis of the re-
sults of the 1975 report by Cooper and Gaffey, Kang, et al. (1980)
used the test statistic z = - SMR - 100 _ and calculated a sfca_
100 -/I/expected
tistically significant increase in deaths due to all malignant neo-
plasms, cancer of the digestive organs, and cancer of the respira-
tory system for lead smelter workers. For battery plant workers
they calculated a statistically significant increase in cancer of
the digestive organs and cancer of the respiratory system. They
did not calculate an increased incidence of all malignant neoplasms
for these workers. Based on their calculations, the authors state
"observation of a significant excess of cancer in two independent
populations exposed to lead in two different industrial settings
lends credibility to the suggestion that lead is an etiological
factor. "
In their responses to Kang, et al. (1980), Cooper (1980) and
Gaffey (1980) support the methods and conclusions of their previous
work.
C-51
-------
In 1953 a study was published indicating that lead causes
renal tumors in rats (Zollinger, 1953). Since that time, five
other studies have confirmed this finding (Boyland, et al. 1962;
Van Esch, et al. 1962; Roe, et al. 1965; Mao and Molnar, 1967;
Oyasu, et al. 1970). The same observation has also been reported
in mice but could not be elicited in hamsters (Van Esch and Kroes,
1969) . Other studies indicate that lead also causes lung tumors in
hamsters (Kobayshi and Okamoto, 1974) and cerebral gliomas in rats
(Oyasu, et al. 1970). All of these studies were conducted using
levels of lead exposure far in excess of tolerable human doses, but
most were designed to study the mechanism of lead-induced carcino-
genesis.
The first report of lead-induced renal tumors (Zollinger,
1953) was essentially a lifetime study in rats, with administration
of lead beginning at 150 to 180 grams body weight and continuing
for up to 9.5 months. Single weekly doses of 20 mg lead phosphate
were administered subcutaneously. Of the 112 animals on lead that
were examined, many died early in the study. Twenty-one had
tumors. Of the 29 animals remaining after 10 months, 19 had
tumors. The last animals were killed 16.5 months after initiation
of the lead injections. All the tumors were renal and were classi-
fied as adenomas, cystadenomas, or papillary adenomas. Metastases
were evident in only one case. According to the histological cri-
teria for renal toxicity, all the animals receiving lead had severe
lead intoxication. Among 50 control animals, none developed
tumors.
C-52
-------
The next study reported (Boyland, et al. 1962) tested the
hypothesis that renal cancer due to lead was actually caused by the
well-known accumulation of porphyrins associated with lead toxici-
ty. To test the hypothesis, elevated porphyrin excretion was stim-
ulated by administration of allyl-isopropylacetamide (AIA) in the
diet of 20 rats for one year. A like number of rats were fed 1 per-
cent lead acetate in their diet for one year. Both groups of ani-
mals were observed until they became ill or had palpable tumors.
During the period of lead administration the mortality rate in the
two groups was quite similar. Subsequently the lead-fed rats died
earlier than the AIA rats. Subsequent to the 1-year administration
of test compounds all but one of the lead-fed rats had renal tumors
whereas none of the AIA group had tumors of any kind. It is not
clear whether the accelerated mortality among the lead-fed rats was
due to the tumors or to other toxic effects of lead.
Van Esch, et al. (1962) presented the first study in which
tumor mortality was determined at more than one dosage level of
lead. In this case lead was administered in the diet as basic lead
acetate, 0.1 percent in one group and 1.0 percent in the other.
Approximately equal numbers of males and females were used. Each
lead-fed group was compared to its own set of controls, not receiv-
ing lead. Prior to the termination of the experiment, only mori-
bund animals were killed and examined morphologically. At equiva-
lent durations of lead administration, using these guidelines for
tumor assessment, the higher dose of lead was more carcinogenic
than the lower dose. Thus, at the end of 600 days of lead adminis-
tration, 31 percent of the animals which survived to 400 days died
C-53
-------
from renal tumors in the 1.0 percent lead acetate group, whereas
only 14 percent of the animals alive at 400 days in the 0.1 percent
lead acetate group died of renal tumors (Figure 4) . Mortalities
with tumors in the subsequent 200-day period (600 to 800) were not
comparable because in the case of the 1.0 percent lead group all
the animals were killed at 730 days, whereas in the case of the 0.1
percent lead group the animals were allowed to survive until 985
days unless they became moribund. It should also be noted (Table
8) that during the first 600 days of the 0.1 percent basic lead ace-
tate regimen, 10 of the original 26 rats (38 percent) died without
renal tumors as compared to one of the original 26 in the control
group (4 percent), indicating that at this level the lead regimen
was lethal in some manner unrelated to its carcinogenicity. As a
matter of fact, both levels of lead administration caused reduced
body weight gains, suggesting toxicity unrelated to carcinogenesis.
The next study of lead-induced tumors in rats was also de-
signed to shed light on the mechanism of lead carcinogenesis rather
than to define dose-response relationships. Roe, et al. (1965)
sought to establish whether testosterone or xanthopterin would
influence the induction of renal neoplasms by lead in rats. In
this study, the forms of lead, lead orthophosphate, and the mode of
administration were unique. The lead salt was administered subcu-
taneously once weekly for four weeks, then intraperitoneally for
nine weeks; then after a rest period of four or nine weeks, depend-
ing on the particular group of rats, lead administration was re-
sumed for an additional 14 weeks. All the animals were males. The
dosage schedule of lead is presented in Table 9, assuming an aver-
C-54
-------
100 j I
Cumulative %
Mortality (O )
or % Animals c
Tumors at Time
of Death (©)
90
80
70
60
50
40
30
20
10
i r
~ Total n = 29
0.1% PbAc
Total n = 26
1.0% PbAc
JL
0 201 401 601 0 201 401 601
4, 4, > 4. 4- ^ 4- 4-
200 400 600 729 200 400 600 730
TIME INTERVALS,DAYS
FIGURE 4
Cumulative Mortality and Tumor Incidence in Rats
Source: Van Esch, et al. 1962
C-55
-------
TABLE 8
liffect of Lead Exposure on the Incidence of Renal Tumors in Rats
O
I
cn
"n at beginning of interval-
dead, no renal tumors
dead, renal tumors
n at beginning of interval-
dead, no renal tumors
dead, renal tumors
n at beginning of interval-
dead, no renal tumors
dead, renal tumors
n at beginning of interva.1-
dead, no renal tumors
dead, renal tumors
Successive Time
0-200
Cb
15
2
0
14
0
0
0.1C
16
0
0
16
0
0
201-400
C
13
1
0
34
2
0
0.1
16
1
0
16
1
0
401-600
C
12
2
0
12
3
0
0.1
15
1
0
15
6
1
Intervals, Days
601-729
C
10
3
0
9
4
0
0.1
14
1
3
9
4
0
601-800 800-985
C
10
5
0
9
6
0
0.1 C 0.1
1456
651
305
935
331
004
C
13
0
0
13
0
0
1.0d
11
1
0
13
4
0
C
13
0
0
13
0
0
1.0
10
1
2
9
2
1
C
12
1
0
13
0
0
1.0
7
1
1
6
1
3
C
13
0
0
13
0
0
1.0
5
1
2
2
0
2
C
13
12
0
13
13
0
1.0
5
1
4
2
0
2
^Source: Van Esch, et al. 1962
hC = Control
C0.1 = 0.1% basic lead acetate in diet
(11.0 = 1% basic lead acetate in diet
"n = number
-------
TABLE 9
Dosage Schedule used by Roe, et al. (1965) in their study of the Influence of
Testosterone and Xanthopterin on the Induction of Renal Neoplasms by Lead in Rats
o
1
U\
-O
Group
Pb alone
Pb alone
Pb alone
Pb + testosterone
Pb + xanthopterin
Pb + testosterone
Pb + xanthopterin
Xanthopterin
Testosterone
No treatment
Pb,
mg/kg/d
2.63
1.25
0.17
1.25
1.25
0.17
0.17
-
-
-
Days on Pb
242
238
238
238
238
238
238
238
238
238
n*
24
24
24
16
16
16
16
16
24
24
*n = number
-------
age body weight of 400 g, and averaging the dose over the total
treatment period.
In analyzing the cancer data for these groups, it seems rea-
sonable to pool all the groups receiving the same dosage of lead
since neither testosterone nor xanthopterin influenced the tumor
incidence. However, xanthopterin alone seemed to increase the mor-
tality rate whereas testosterone alone did not. Therefore, only
the lead alone, the lead plus testosterone, and the no treatment
and testosterone alone groups are pooled here at equivalent lead
dosages. The results are summarized in Table 10.
It is not possible to establish the slope of the interaction
between dosage of lead and tumor incidence. The highest dose was
so toxic that there were only two survivors by the time the first
tumor appeared in that group (Table 10). The remaining two dosage
levels, by contrast, did not cause death unrelated to tumorigenesis
(Figure 5). However, since only one of these two remaining dosage
levels was tumorigenic, no dose-response relationship in regard to
tumorigenesis is calculable.
Interstitial nephritis occurred in all groups, including con-
trols. Unfortunately, other manifestations of toxicity, e.g.,
anemia, reduced body weight gains, and food consumption were not
reported. In keeping with the observations of Van Esch, et al.
(1962), Boyland, et al. (1962), Mao and Molnar (1967), and Zol-
linger (1953), very few of the affected animals exhibited metasta-
sis and no elevated incidence of other types of tumors was noted.
Neither of the two remaining reports concerning the carcino-
genic effects of lead in rats (Mao and Molnar, 1967; Oyasu, et al.
C-58
-------
TABLE 10
Summary of Mortality Data Resulting Irom Lead Phosphate Administration to Rats
Successive Time Intervals, Days
o
I
01
l£>
0-100 101-200 201-300 301-100 101-500 501-600 601-700
Cb 2.6C I.3C .I7C C 2.6 1.3 .17 C 2.6 1.3 .17 C 2.6 1.3 .17 C 2.6 1.3 .17 C 2.6 1.3 .17 C 2.6 1.3 .17
n at beginning ^ 2() w <,0 ^ 6 37 w M 3 37 38 <,6 2 37 31 11 1 35 25 26 - 11 18 11 - 6
of interval
dead, no renal o 18 3 003022 1012019 15 077 15- 5 16 II 01
Illinois
dead, renal 00 0 000000 0000110 111101- 300 5
Illinois.
dyin^wlill 00 0 000000 0000 50 30 2 100 10 01- 57 00- 83
turiloi i
mol'lllii'ty? 0 82 18 00 95 18 5 1 100 18 15 9 100 21 37.5 11 100 65 55 71 100 91 95 IOO IOO IOO IOO
no tumors
nlortaul'y? 00 0 000000 0000130 21 35 0 1 - 15 01 - 58
luinorb
' Soiuxo: Uoe, et ul. 1965
(" - i ontrolb
A VIM age dose ol lead pliosphate, ing/kg/day
-------
%
DEAD
100
90
80
70
60
50
40
30
20
10
0
i>
100
0
'2.6
Control
_L
101
b
200
201
-i,
300
301
-4-
400
401
4,
500
501
.1, .
600
601
J/
700
TIME INTERVALS, DAYS
FIGURE 5
Cumulative Mortality Among Rats
not having Renal Tumors
Source: Roe, et al. 1965
C-60
-------
1970) involved more than one level of lead administration. The
results obtained by Mao and Molnar (1967) serve to confirm the
results of Van Esch, et al. (1962) in that both groups used the same
regimen of lead in the diet (1 percent lead acetate) and got simi-
lar incidences of renal tumors [50 percent by Van Esch (1962) vs.
77.5 percent by Mao and Molnar (1967)]. Both also noted that the
first appearance of tumors was at about 300 days following initia-
tion of lead administration. Mao and Molnar (1967) are the only
authors who conducted any lead analyses. They reported 19.3 to
54.2 yg Pb/g kidney cortex as compared to 3.1 yg Pb/g in a single
normal specimen. By way of comparison to man, Barry (1975) report-
ed a mean of 0.66 yg/g in kidney cortex of 10 occupationally-
exposed adult males, with a standard deviation of + 0.56 uq/g.
Oyasu, et al. (1970) used a dietary regimen of lead subacetate
for 326 to 432 days, either alone or combined with indole in one
case and acetylaminofluorene (AAF) in the other. Neither of these
substances alone caused renal tumors. Therefore, the data for lead
with and without these additional substances could be combined.
Fifty-nine percent of 130 animals receiving 1 percent lead sub-ace-
tate in the diet eventually developed renal tumors. This report,
incidentally, is the only one in which oral feeding of lead was to
cause tumors other than renal. Eight percent of the 130 lead-fed
rats developed gliomas. All but one of these were cerebral. One
was cerebellar. The incidence of gliomas in animals receiving AAF
alone was 2.5 percent, compared to 0.3 percent in controls. There
did not seem to be any synergistic effect between AAF and lead.
Lead did not cause any other types of tumors. The toxic effects of
lead in this study, apart from carcinogenesis, were not reported.
C-61
-------
Van Esch and Kroes (1969) have reported that basic lead ace-
tate causes renal tumors in mice, but not in hamsters. These were
lifetime studies with lead being incorporated into the diet begin-
ning at five weeks of age for the mice and three to four weeks of
age for the hamsters. Two levels of lead were used, 0.1 percent and
1 percent, cut back to 0.5 percent early in the study owing to tox-
icity. Only one renal tumor was found at the high level of lead
intake in the mice, but this was probably because most of the mice
died within the first 100 days of lead administration. Fourteen
percent of the mice receiving 0.1 percent basic lead acetate devel-
oped renal tumors. There were no renal tumors in hamsters at
either dosage level of lead. Mortality was somewhat increased at
both levels of lead administration.
Another report of experimental carcinogenesis is a report of
induction of lung tumors in Syrian hamsters using intratracheal
injection of lead oxide (Kobayachi and Okamoto, 1974) . Actually,
tumors were produced only when benzo(a)pyrene (BP) was injected
simultaneously with lead oxide. Neither compound alone caused
tumor formation under the conditions described. This cooperative
effect was obtained using 10 weekly injections. The tumors were
predominantly adenomas of bronchio-alveolar origin. In addition to
this effect, both lead alone and in combination with BP caused a
very high incidence of alveolar metaplasia, which the authors spec-
ulate may be a preneoplastic change. BP alone caused a very low
incidence of alveolar metaplasia. All treatments, including the
methylcellulose injection vehicle alone caused some deaths.
C-62
-------
The final study concerning the carcinogenic effects of lead is
the most significant of all (Azar, et al. 1973). It confirms other
studies showing that lead causes renal tumors in rats and that male
animals are more susceptible than females. A dose-related effect
is clearly evident (Table 11) (Figure 6) . The dose of lead re-
quired to produce tumors did not clearly result in increased mor-
tality among the animals; however, at dietary lead intake above
1,000 ppm, weight gains were reduced.
In summary, there is little doubt that certain compound of
lead are carcinogenic or at least co-carcinogenic in some species
of experimental animals.
Teratogenicity
There is little information in the literature to suggest that
lead has a teratogenic effect in man. Although there were numerous
reports of a high incidence of stillbirths and miscarriages among
women working in the lead trades, fetal anomalies were not de-
scribed. It must also be pointed out that these women were Droba-
bly exposed to much higher concentrations of lead than for occupa-
tionally exposed men today. Recent literature is devoid of any
references to teratogenic effects of lead in man.
In experimental animals, on the other hand, lead has been
shown repeatedly to have teratogenic effects. Early studies demon-
strated this in chick embryos by injection of lead into the yolk
sac (Catzione and Gray, 1941; Karnofsky and Ridgway, 1952). Tera-
togenesis has also been observed in rodents. These studies were
done using high doses of lead given intravenously or intraperitone-
ally. For example, McClain and Becker (1975) used single intra-
C-63
-------
TABLE 11
Mortality and Kidney Tumors in Rats Fed
Lead Acetate for Two Years*
o
i
Dietary Pba
(ppm)
5
18
62
141
548
3
1,130
2,102
No. of Rats
of Each Sex
100
50
50
50
50
20
20
20
% Mortality
Male
37
36
36
36
52
50
50
80
Female
34
30
28
28
36
35
50
35
% Kidney Tumors
Male
0
0
0
0
10
0
50
80
Female
0
0
0
0
0
0
0
35
*Source: Azar, et al. 1973
aMeasured concentration of Pb in diet
Includes rats that died or were sacrificed in extremis
-------
99
90
80
Percent
animals
with renal 50
tumors
10
99
90
80
50
10
10.1
0.2
0.5
10
ppm Dietary Pb x IT
FIGURE 6
Probit Plot of Incidence of Renal Tumors
in Male Rats
Source: Azar, et al. 1973
C-65
-------
peritoneal doses of 25 to 70 mq/kg in rats. They found that terato-
logic effects occurred when administration was on day 9. Adminis-
tration later in pregnancy resulted in embryotoxicity (fetal re-
sorption) but not in teratogenic effects. Carpenter and Perm
(1977) observed teratologic effects in hamsters following the
administration of 50 mg/kg Pb(N03)2 intravenously on day 8. Chron-
ic administration of lead in the drinking water of pregnant rats at
very high concentrations (up to 250 mg/1) resulted in delayed fetal
development and fetal resorption without teratologic effects (Kim-
mel, et al. 1976).
In summary, it seems that, in man, embryotoxicity precedes
teratogenicity in the lead sensitivity scale. This is supported by
historical experience in occupationally exposed women and by animal
studies.
Mutagenicity
Pertinent data could not be located in the available litera-
ture concerning the mutagenicity of lead.
Reproductive Effects
As was indicated in the previous section, lead has been known
to cause miscarriages and stillbirths in women working in the lead
trades during the latter half of the 19th century and probably on
into the early part of the 20th century. It is very difficult to
estimate minimally toxic exposure for stillbirth and miscarriages
because exposure data, e.g., PbB are lacking for women who experi-
enced this problem. The minimally toxic level of exposure may
actually be quite low. Lane (1949) reported on the outcome of 15
pregnancies incurred among 150 women working in an unspecified lead
C-66
-------
trade during World War II. Three of these women had miscarriages -
an incidence seven times normal. Unfortunately the numbers were
too small to be assigned statistical significance. Lead exposure
was modest, air lead being 75 ug/m and urinary lead excretion in
men working with these women being 75 to 125 yg/1. A more recent
Japanese study also is suggestive of miscarriages occurring among
women with only modest exposure (Nogaki, 1958). These women were
the wives of lead workers. Unfortunately, the actual level of lead
exposure was not reported.
It has recently been reported that the incidence of premature
fetal membrane rupture in term and preterm infants is much higher
30 to 50 miles west of a lead mining area of Missouri (17 percent)
than in a Missouri urban area remote from lead mining activities
(0.41 percent) (Fahim, et al. 1976). Maternal and fetal PbBs at
birth also differed significantly for normal births vs. births with
premature membrane rupture. Maternal and fetal PbBs for the normal
deliveries were about 14 and 4 yg/dl, respectively, whereas they
were about 26 and 13 respectively for mothers and infants with mem-
brane rupture. This provocative study needs confirmation. It is
difficult to understand, for example, why fetal PbB should be so
much lower than maternal PbB in all groups.
There is a possibility that lead affects fertility as well as
the conception. Lancranjan, et al. (1975) reported that signifi-
cant levels of teratospermia occurred among men working in a lead
storage battery factory. Their PbBs were 30 to 80 yg/dl. Although
many studies have attempted to correlate semen quality with fertil-
ity, the extent to which abnormally-shaped sperms participate' in
C-67
-------
fertilization is unclear. Experimental animal studies have shown
reduced fertility of both maternal and paternal origin (Stowe and
Goyer, 1971).
There have been numerous conflicting reports concerning the
occurrence of chromosomal aberrations in lymphocytes of lead-
exposed workers (O'Riordan and Evans, 1974; Forni, et al. 1976).
The reason for these conflicting findings is not clear. DeKnudt,
et al. (1977a) suggest that ancillary factors may be critical; for
example, the level of calcium intake. They base this conclusion on
the lack of correspondence between lead effects in two widely sepa-
rated lead-using plants, one being a secondary lead smelter and the
other being a plant manufacturing "tin" dishes. Lead exposures
were roughly comparable: PbBs were on the order of 45-100 yg/dl.
Severe chromosomal aberrations were found in one plant whereas no
such effects were seen in the other. They further point out that no
severe aberrations have been seen in at least some animal studies
in which lead exposure was heavy and nutrition apparently adequate
(Jacquet, et al. 1977; De Knudt, et al. 1977b). The implications
of chromosomal aberrations which have been reported are not known.
A recent report by Wibberley, et al. (1977), which demonstrates a
striking increased incidence of high placental lead associated with
stillbirths or congenital malformations, further suggests that a
relationship exists between intrauterine exposure to lead and re-
productive casualty.
Renal Effects
There is considerable information in man concerning the renal
effects of lead. Two distinctive effects occur in both adults and
C-68
-------
children. One. is reversible oroximal tubular damage, which is seen
mainly with short-term exposure. The other effect is reduced glo-
merular function which has generally been considered to be of a
slow, progressive nature.
Tubular damage is manifested as the Fanconi triad of glyco-
suria, hypophosphatemia with phosphaturia, and generalized amino-
aciduria. The last-named manifestation appears to occur more con-
sistently than either glycosuria or phosphaturia. It was first
described more than 20 years ago in lead smelter workers (Clarkson
and Kench, 1956). In adults, the condition probably is uncommon at
PbBs below 70 ug/dl. Thus, in a recent series of seven workers, all
of whom had PbBs 70 ug/dl, with a range of 71-109, none had amino-
aciduria or glycosuria. Significantly, five had hemoglobins below
12 g/dl (Cramer, et al. 1974). Similarly, in a series of 15 infants
hospitalized for lead poisoning, all having PbBs _^_100 ug/dl at
entry, only three had aminoaciduria, with PbBs of 246, 299, and 798
ug/dl (Chisolm, 1968).
Reduced glomerular filtration with attendant rise in serus
urea concentration is generally considered to be a progressive dis-
ease, implying prolonged lead exposure. It is accompanied by
interstitial fibrosis, obliteration of glomeruli and vascular
lesions (Morgan, et al. 1966) . It occurs at relatively low levels
of lead exposure, at least relative to the levels associated with
aminoaciduria. For example, in Cramer's series of seven workers,
none of whom had aminoaciduria, three had low renal clearance of
2
inulin (^90 ml/min/1.73m ). In another study of eight men with
occupational lead exposure (PbBs = 29-98) , four had reduced glomer-
C-69
-------
ular filtration rates (Wedeen, et al. 1975). Of these four cases,
one had a PbB of 48 yg/dl at entry. The maximal PAH secretion rate
(Tm ) was also reduced, indicating coexistent tubular damage.
Among the other three cases, two had only a marginal depression of
TnlPAH-
From these and other studies, it appears that the kidney is
sensitive to glomerular-vascular damage, with an imprecisely known
threshold for effect which may be below PbB = 50 ug/dl.
Cardiovascular Effects
Dingwall-Fordyce and Lane (1963) reported an excess mortality
rate due to cerebrovascular disease among lead workers. These
workers were employed during the first quarter of the 20th century
when lead exposure was considerably higher than it has been more
recently. There was no similar elevated mortality among men em-
ployed more recently however. Similarly, in Cooper's more recent
epidemiological study there was no excess mortality attributable to
stroke or other diseases associated with hypertension or vasculo-
pathy (Cooper and Gaffey, 1975; Cooper, 1978). It would appear
from these studies that the vascular effects of lead only occur
with heavy industrial lead exposure - probably in excess of what is
encountered today.
There have been reports of heart failure (Kline, 1960) and of
electrocardiographic abnormalities (Kosmider and Pentelenz, 1962)
attributable to lead exposure. However, these cases have always
involved clinical lead intoxication. It does not seem likely,
therefore, that the heart is a critical target for lead effects.
C-70
-------
Miscellaneous Effects
Sporadic reports of other biological effects of lead in man
exist, but these are difficult to evaluate as to associated lead
exposure. They have frequently been reported only at high exposure
levels and only by one or two investigators. For example, Dodic,
et al. (1971) reported signs of impaired liver function in 11 of 91
patients hospitalized for lead poisoning. No information was pro-
vided as to indices of lead exposure. Impairment of thyroid func-
tion has been reported in moonshine whiskey drinkers hospitalized
for lead poisoning (Sandstead, et al. 1969) . The degree of lead
exposure was not clearly indicated, but it can be assumed to have
been high. Intestinal colic has long been recognized as a sign of
lead in industrially exposed people. It probably also occurs in
children with lead poisoning. Beritic (1971) reported that it
occurs with PbBs as low as about 40 ug/dl. This seems unlikely
since the cases he reported also were anemic, a condition associat-
ed with the considerably higher PbBs. A number of studies have
suggested that a relationship exists between lead exposure and
amyotrophic lateral sclerosis (ALS). The most recent report on
this examined plasma lead levels in 16 cases of ALS and in 18 con-
trols and found significant differences at the 0.05 level (Conradi,
et al. 1978) .
Finally, animal studies indicate that relatively high levels
of lead exposure interfere with resistance to infectious disease
(Hemphill, et al. 1971; Gainer, 1974). There are no reports of an
abnormal infectious disease incidence among people with high lead
exposure, however.
C-71
-------
CRITERION FORMULATION
Existing Guidelines and Standards
Since lead is ubiquitous in the environment, several govern-
ment agencies have become involved in regulating its use. The most
recent action was taken by the Consumer Product Safety Commission
(CPSC). In 1977 the CPSC lowered the maximum allowable concentra-
tion of lead in house paint to 0.06 percent. At present the Occupa-
tional Safety and Health Administration (OSHA) is preparing a set
of regulations regarding occupational lead exposure. Similarly,
the U.S. EPA has set an ambient air lead standard. The U.S. FDA has
provided new guidelines for the regulation of sources of lead in
foods and cosmetics. Given the multi-media nature of lead exposure
to man, it is essential that any action taken in regard to one
source, such as water, be coordinated with similar actions being
taken for other media such as air and diet.
Current Levels of Exposure
Approximately 1 percent of taowater samples have been found to
exceed the current standard of 50 yg/1. This is generally a prob-
lem in softwater areas, particularly where lead pipes convey the
water supply to the tap from the surface connection. The contri-
bution of the diet is approximately 200 lag/day for adults. For
children (ages three months to nine years) the diet contributes 40
to 200 ug of lead per day. On the basis of current information, it
is impossible to judge how much dietary lead is attributable to the
water used in food preparation. The concentration of lead in ambi-
ent air ranges from approximately 0.1 ug/m3 in rural areas to as
much as 10 yg/m3 in areas of heavy automotive traffic.
C-72
-------
Special Groups at Risk
In addition to these usual levels of exposure from environ-
mental media, there exist miscellaneous sources which are hazard-
ous. The level of exposure resulting from contact is highly vari-
able. Children with pica for paint chips or for soil may experi-
ence elevation in blood lead ranging from marginal to sufficiently
great to cause clinical illness. Certain adults may also be ex-
posed to hazardous concentrations of lead in the workplace, notably
in lead smelters and storage battery manufacturing plants. Again,
the range of exposure is highly variable. Women in the workplace
are more likely to experience adverse effects from lead exposure
than men due to the fact that their hematopoietic system is more
lead-sensitive.
Basis and Derivation of Criterion
The approach that will be taken here in assessing the impact
of lead in water on human health is basically the same as has been
taken by the U.S. EPA (1977) for lead in air. The critical target
organ or system must first be identified. Then, the highest inter-
nal dose of lead that can be tolerated without injury to the target
organ must be specified. Finally, the impact of lead in water on
the maximum tolerated internal dose must be estimated, as well as
the likely consequences of specific reductions in the maximum
allowable concentrations of lead in water.
In identifying the critical organ or system, great reliance is
placed on the concentration of lead in the blood (PbB) as an index
of internal dose. Such an indirect measurement is necessary be-
cause of the multi-media character of lead intake. Tt is virtually
C-73
-------
impossible to measure total lead intake in people in any meaningful
way. Because intake and output fluctuate greatly from day to day,
measurement of total lead intake would require long-term balance
studies. Variables have a substantial influence on the rate and
degree of lead uptake from the external environment. Some groups
have proposed alternatives to PbB as a measure of internal dose,
e.g., FEP and tooth lead. FEP is not suitable because it is a bio-
logical response to lead. As such, it is subject to influences
other than lead, notably iron deficiency. Tooth lead is a poten-
tially useful index of lead exposure, but with the present state of
the art being what it is, tooth lead is difficult to interpret. It
only provides an integrated profile of past lead exposure. One is
not able to say when the exposure occurred. It has the additional
limitation of not being available on demand. Teeth are shed spon-
taneously only in childhood. Moreover, only a very small data base
is available for dose-effect and dose-response using any measure of
dose other than PbB. The use of PbB as a measure of internal dose
is widely accepted, simply because nothing better is available.
Having specified that PbB is the best measure of internal dose
currently available, the next question concerns the lowest PbB lev-
els at which adverse health effects occur. Two recent documents
(U.S. EPA, 1977; WHO, 1977) have been published in which "judgments
were rendered in this regard (Table 12). It will be noted that the
estimates are strikingly similar. The estimated no-effect levels
are based on limited populations and probably are lower to some
undefinable degree in the total population at risk. Slightly more
information was available to the U.S. EPA panel than to the WHO
C-74
-------
TABLE 12
Summary of Lowest PbBs Associated with Observed
Biological Effects in Various Population Groups3
Lowest Observed
Effect Level
(yg Pb/100 ml
Blood)
Effect
Population Group
10
15-20
25-30
40
40
40
50
50-60
50-60
80-100
100-120
ALAD inhibition
Erythrocyte protoporphyrin
elevation
Erythrocyte protoporphyrin
elevation
Increased urinary ALA
excretion
Anemia
Coproporphyrin elevation
Anemia
Cognitive (CNS) deficits
Peripheral neuropathies
Encephalopathic symptoms
Encephalopathic symptoms
Children and adults
Women and children
Adult males
Children and adults
Children
Adults and children
Adults
Children
Adults and children
Children
Adults
No Observed Effect Levels in Terms of PbBb
No Observed
Effect Level
(yg Pb/100 ml
Blood)
Effect
Population Group
10
20-25
20-30
25-35
30-40
40
40
40
40-50
50
50-60
60-70
60-70
80
Erythrocyte ALAD inhibition
FEP
FEP
FEP
Erythrocyte ATPase inhibition
ALA excretion in urine
CP excretion in urine
Anaemia
Peripheral neuropathy
Anaemia
Minimal brain dysfunction
Minimal brain dysfunction
Encephalopathy
Encephalopathv
Adults and children
Children
Adult females
Adult males
General
Adults and children
Adults
Children
Adults
Adults
Children
Adults
Children
Adults
Source: U.S. EPA, 1977
Source: World Health Organization, 1977
C-75
-------
panel since it reviewed literature through mid-1977, whereas the
WHO expert groups reviewed literature only through 1976. In addi-
tion, the U.S. EPA performed statistical calculations based on the
known distribution of blood lead levels in the United States.
Both sets of data in Table 12 are in error in one regard. They
use the term "anemia" inappropriately under the "Effect" column.
What they really mean is "decrement in hemoglobin." Anemia is a
clinical term used to denote a degree of hemoglobin decrement which
is below the normal range for that class of individuals, e.g., men
or children.
The question that arises in considering Table 12 is which is
the critical effect? Precisely the same issue confronted the U.S.
EPA in its deliberations concerning establishment of a national
ambient air quality standard for lead (42 FR 630979). It focused
on the lead effects in children since they are more sensitive than
adults.
It ruled that the maximum safe blood lead level for any given
child should be somewhat lower than the threshold for a decline in
hemoglobin level (40 yg Pb/dl). In considering how much lower this
limit should be, the U.S. EPA cited the opinion of the Center for
Disease Control, as endorsed by the American Academy of Pediatrics,
that the maximum safe blood lead level for any given child should
be 30 yg/dl. Based upon epidemiological and statistical considera-
tions, the U.S. EPA estimated that if the geometric mean PbB were
kept at 15 yg/dl, 99.5 percent of children would have PbB < 30
yg/dl. This position provides a substantial margin of safety which
accomodates minor excursions in lead exposure due to adventitious
C-76
-------
sources. Controls on lead in obligatory media (e.g., air and
water) do not protect children from the hazards of pica for lead-
base paint chips or soil and dust contaminated with lead from such
sources as fallout from the smoke zone of lead smelters.
In its deliberations concerning an ambient air lead standard,
the U.S. EPA estimated that the contribution of sources other than
air to PbB is 10 to 12 ug/dl. This is presumably composed over-
whelmingly of dietary sources which, in turn, is composed of both
food and water.
The next question concerns the contribution of water to lead
exposure. Only three useful studies of the interrelationship be-
tween PbB and lead in drinking water are available. Overall, the
Moore, et al. (1977a) study, the one by Hubermont, et al. (1978),
and the calculations made from U.S. EPA data collected in the
Boston area (Greathouse and Craun, 1976) are credible because they
are consistent with other information concerning the curvilinear
relationship between PbB and air Pb. The implication of the equa-
tion describing the relationship between PbB and water lead is that
with increasing lead in water, the incremental rise in PbB becomes
progressively smaller, as with air lead vs. PbB and dietary lead
vs. PbB (see "Contributions of Lead from Diet vs. Air to PbB" in the
Pharmacokinetics section). The water lead vs. PbB relationship
differs in one significant respect, however, from the air lead vs.
PbB relationship in that the baseline PbB (0 water PbB) is indepen-
dent of the contribution of water lead to PbB. Thus, regardless of
whether one starts with a baseline PbB of 11 pg/dl, as was indicat-
ed in the Moore, et al. (1977a) study or whether one starts at some
:-77
-------
other PbB level, e.g., 20 ug/dl, the add-on PbB from any given
level in water will be the same. Such is not the case in the Azar
analysis of air Pb vs. PbB (see "Contributions of Lead from Diet
vs. Air to PbB" in the Pharmacokinetics section). Here, the higher
the baseline, the less is the contribution of air Pb. This is be-
cause log PbB is proportional to baseline PbB + log air concentra-
tion. Future research may provide better insight into whether this
discrepancy is real and, if so, why. The question is of some prac-
tical importance. For instance, if you have a baseline PbB (no
lead in water) of 30 yg/dl, such as in a child acquiring lead from
paint, it would be of some importance to know whether an additional
increment of lead in water would have the same .impact on PbB as it
would in a child having a baseline of PbB of 10 yg/dl. An Azar-type
model would suggest a lesser impact starting from the higher base-
line PbB.
So far as a specific recommendation regarding a water quality
for Pb is concerned, a stand must be taken using the available
data. Beginning with the assumption that a PbB of 12 yg/dl is
essentially attributable to food and water and that the average
lead content of water consumed is 10 yg/1, approximately 5 ug Pb/dl
blood (from Table 6) is attributable to the water that is used in
food and beverage preparation and in direct consumption. If the
water Pb were consistently consumed at the present Pb standard of
50 yg/1 instead of at 10 yg/1/ an additional contribution of ap-
proximately 3.4 yg/dl to PbB would result (8.57 - 5.13 from Table
6). This would yield a. total PbB of 12 + 3.5 or 15.4 yg/dl, the
approximate maximum geometric mean PbB compatible with keeping 99.5
C-78
-------
percent of the population under PbB = 30 ug/dl. Thus, based on most
recent data, the present water standard of 50 yg Pb/1 may be viewed
as representing the upper limit of acceptability. This criteria is
based on empirical observation of blood lead in human population
groups consuming their normal amount of water and food daily. Spe-
cific amounts of foods or drinking water consumed were not quanti-
fied, but it can be assumed that they reflect an average consump-
tion of water, fish, shellfish, and other foods.
All the assumptions that have been made in arriving at an
estimate of the impact of lead in water on PbB have been on the
conservative side. For instance, unpublished data from the Com-
mission of the European Communities suggest that the impact of lead
in water on PbB is appreciably less than has been estimated from
published data used in this document [personal communication from
Alexander Berlin, et al. (1978), Commission of the European Com-
munities, Luxembourg]1. Furthermore, data from a study (Morse, et
al. 1978) of the effect of lead in water on the PbB of a population
of children in a relatively small town are reassuring. They indi-
cate that among children whose water supply contained 50 to 180 yg
Pb/1, PbBs averaged 17.2 yg/dl2.
Subsequent to the writing of this report, these data were submit-
ted to the EPA by Dr. Berlin. They were studied and judged not to
alter the conclusions arrived at in this document concerning PbB
vs. lead in water (see Appendix).
2
It should be pointed out, however, that the contribution from
other sources is not indicated, thus, the relative water lead con-
tribution is unknown.
C-79
-------
Finally, there remains the issue of the carcinogenic effects
of lead. Using data from one species of laboratory animal (the
rat) it was possible to construct a seemingly valid dose-response
curve and to calculate a dietary level of lead which would predict
an incidence of cancer in 1:100,000 people. This calculated diet-
ary level of lead is 29 yg/kg. Since this estimate includes lead
from all sources, its implications are beyond the scope of this
document. It should be noted, however that the International
Agency for Research on Cancer, Lyon, France considers the experi-
mental animal evidence to be of dubious significance with regard to
man (IARC, 1972) .
The Agency has not yet resolve all of the issues concerning
the potential carcinogenicity of lead, but will complete its review
in the near future. All of the data will be subjected to an exten-
sive peer review by outside experts and in-house scientists. De-
pending upon the final conclusions of the review, the water quality
criteria for lead may be re-evaluated.
C-80
-------
REFERENCES
Albert, R.E., et al. 1974. Follow-up of children overexposed to
lead. Environ. Health Perspect. Exp. Issue No. 7: 33.
Alexander, F.W., et al. 1973. The Uptake and Excretion by Chil-
dren of Lead and other Contaminants. In; Proc. Int. Symp. Environ.
Health. Aspects of Lead. Amsterdam, 2-6 Oct., 1972. Comm. Eur.
Commun., Luxembourg. p. 319.
Alvares, A.P., et al. 1975. Drug metabolism in normal children,
lead poisoned children and normal adults. Clin. Pharmacol. Ther.
17: 179.
Angle, C.R., et al. 1975. Lead and Iron Deficiency. In: D.D.
Hemphill (ed.), Trace Substances in Environmental Health. IX. Uni-
versity of Missouri Press.
Azar, A., et al. 1973. Review of Lead Studies in Animals Carried
out at Haskell Laboratory - Two-year Feeding Study and Response to
Hemorrhage Study. In; Proc. Int. Symp. Environ. Health. Aspects
of Lead. Amsterdam, 2-6 Oct., 1972. Comm. Eur. Commun., Luxem-
bourg, p. 199.
Azar, A., et al. 1975. An epidemiologic approach to community air
lead exposure using personal air samplers. Environ. Dual. Safe.
Suppl. II: Lead. 254.
C-81
-------
Barltrop, D. 1966. The prevalence of pica. Am. Jour. Dis. Child.
112: 116.
Barltrop, D. and H.E. Khoo. 1975. The influence of nutritional
factors on lead absorption. Postgrad. Med. Jour. 51: 795.
Barltrop, D. and F. Meek. 1975. Absorotion of different lead com-
pounds. Postgrad. Med. Jour. 51: 805.
Barltrop, D. , et al. 1974. Significance of high soil lead con-
centrations for childhood lead problems. Environ. Health Perspect.
Exp. Iss. 7: 75.
Barry, P.S.I. 1975. A comparison of concentrations of lead in
human tissues. Br. Jour. Ind. Med. 32: 119.
Beattie, A.D., et al. 1972. Environmental lead pollution in an
urban soft-water area. Br. Med. Jour. 2: 491.
Beattie, A.D., et al. 1975. Role of chronic, low level lead expo-
sure in the aetiology of mental retardation. Lancet. 1: 7907.
Beritic, T. 1971. Lead concentration found in human blood in
association with lead colic. Arch. Environ. Health. 23: 289.
Berk, P.D., et al. 1970. Hemotologic and biochemical studies in a
case of lead poisoning. Am. Jour. Med. 48: 137.
C-82
-------
Berlin, A., et al. 1978. Research on lead in drinking water in
Europe. Comra. Eur. Commun.
Betts, P.R., et al. 1973. Lead intoxication in children in Birm-
ingham. Br. Med. Jour. 1: 402.
Bicknell, J. , et al. 1968. Lead in mentally retarded children.
Jour. Mental Def. Res. 12: 282.
Boggess, W.R. (ed.) 1978. Lead in the Environment, NSF/RA-770214.
Bolanowska, W.J., et al. 1967. Triethyllead in the biological
material in cases of acute terathyllead poisoning. Arch. Toxicol.
22: 278.
Boyland, E., et al. 1962. The induction of renal tumors by feeding
lead acetate to rats. Br. Jour. Cancer. 16: 283.
Bull, R.J., et al. 1978. Delays in the postnatal increase of cere-
bral cytochrome concentrations in lead-exposed rats. Neurooharma-
cology. (in press)
Byers, R.K. and E.E. Lord. 1943. Late effects of lead poisoning on
mental development. Am. Jour. Dis. Child. 66: 471.
Carpenter, S.J. and V.H. Perm. 1977. Embryopathic effects of lead
in the hamster. Lab. Invest. 37: 369.
C-83
-------
Carson, T. , et al. 1974. Slowed learning in lambs prenatally
exposed to lead. Arch. Environ. Health. 29: 154.
Catzione, 0. and P. Gray. 1941. Experiments on chemical inter-
ference with the early morphogenesis of the chick. II. The effects
of lead on the central nervous system. Jour. Exp. Zool. 87: 71.
Center for Disease Control. 1977. Surveillance of childhood and
lead poisoning - United States. Morbid. Mortal Week. Rep. 26: 49.
Chisolm, J.J. 1968. The use of chelating agents in the treatment
of acute and chronic lead intoxication in childhood. Jour.
Pediatr. 73: 1.
Clark, A.R.L. 1977. Placental transfer of lead and its effects on
the newborn. Postgrad. Med. Jour. 53: 674.
Clarkson, T.W. and J.E. Kench. 1956. Urinary excretion of amino
acids by men absorbing heavy metals. Biochem. Jour. 62: 361.
Cohen, N. 1970. The retention and distribution of lead-210 in the
adult baboon. Ph.D. thesis. University Microfilms International,
Ann Arbor, Michigan.
Conradi, S., et al. 1978. Jour. Neurol. Neurosurg. Psych.
41: 389.
C-84
-------
Cooper, W.C. 1976. Cancer mortality patterns in the lead indus-
try. Ann. N.Y. Acad. Sci. 271: 250.
Cooper, W.C. 1978. Mortality in workers in lead production faci-
lities and lead battery plants during the period 1971-1975. A re-
port to Internat. Lead Zinc Res. Organ., Inc.
Cooper, W.C. 1980. Occupational lead exposure: What are the
risks? Letter to the editor. Science. 208: 129.
Cooper, W.C. and W.R. Gaffey. 1975. Mortality of lead workers.
Jour. Occup. Med. 17: 100.
Cramer, K., et al. 1974. Renal ultrastructure, renal function and
parameters of lead toxicity in workers with different periods of
lead exposure. Br. Jour. Ind. Med. 31: 113.
Crofton, K.M., et al. 1978. Developmental delays in exploration
and locomotor activity in male rats exposed to low level Pb. Sub-
mitted to Science. .
DeKnudt, Gh., et al. 1977a. Chromosomal aberrations in workers
professionally exposed to lead. Jour. Toxicol. Environ. Health.
3: 885.
DeKnudt, Gh., et al. 1977b. Chromosomal abnormalities in lympho-
cytes from monkeys poisoned with lead. Mutat. Res. 45: 77.
C-85
-------
de la Burde, B. and M.S. Choate. 1972. Does asymptomatic lead
exposure in children have late sequelae? Jour. Pediatr. 81: 108.
de la Burde, B. and M.S. Choate. 1975. Early asymptomatic lead
exposure and development at school age. Jour. Pediatr. 87: 638.
Dingwall-Fordyce, J. and R.E. Lane. 1963. A follow-up study of
lead workers. Br. Jour. Ind. Mech. 30: 313.
Dodic, S. , et al. 1971. Stanjc jetre w pojedinih profesionalnih
intosksikaiija. In; III Jugoslavanski Kongres Medicine Dela,
Ljubljana, 1971.
Elwood, P.C., et al. 1976. Dependence of blood-lead on domestic
water lead. Lancet. 1: 1295.
Fahim, M.S., et al. 1976. Effects of subtoxic lead levels on preg-
nant women in the state of Missouri. Res. Commun. Chem. Pathol.
Pharmacol. 13: 309.
Forbes, G.B. and J.C. Rei'na. 1974. Effect of age on gastrointes-
tinal absorption (Fe, Sr, Pb) in the rat. Jour. Nutr. 102: 647.
Forni, A., et al. 1976. Initial occupational exposure to lead.
Arch. Environ. Health. 31: 73.
Gaffy, W.R. 1980. Letter to the editor. Science. 208: 130.
C-86
-------
Gage, J.C. and M.H. Litchfield. 1969. The migration of lead from
paint films in the rat gastrointestinal tract. Jour. Oil. Col.
Chem. Assoc. 52: 236.
Gainer, J.H. 1974. Lead aggravates viral disease and represses
the antiviral activity of interferon inducers. Environ. Health
Perspect. Exp. 7: 113.
Gant, V.A. 1938. Lead poisoning. Ind. Med. 7: 679.
Garber, B.T. and E. Wei. 1974. Influence of dietary factors on the
gastrointestinal absorption of lead. Toxicol. Appl. Pharmacol.
27: 685.
Granick, J.L., et al. 1973. Studies in lead poisoning. II. Corre-
lation between the ratio of activiated to inactivated aminolevulin-
ic acid dehydratase of whole blood and the blood lead level. Bio-
chem. Med. 8: 149.
Greathouse, D.G. and G.F. Craun. 1976. Epidemiologic Study of the
Relationship between Lead in Drinking Water and Blood Lead Levels.
^n: D.D. Hemphill (ed.), Trace Substances in Environmental Health.
X. University of Missouri Press, p. 9.
Griffin, T.B., et al. 1975. Clinical Studies on Men Continuously
Exposed to Airborne Particulate Lead. In: F. Coulston and F. Korte
(eds.), Environ. Qual. and Safety. Suppl. Vol. II: 221. Georg.
Thieme. Stuttgart.
C-87
-------
Haeger-Aronsen, B. , et al. 1974. Effect of lead on Q -aminole-
vulinic acid dehydratase activity in red blood cells. Arch. Envi-
ron. Health. 29: 150.
Hammond, P.B. 1977. Exposure of humans to lead. Ann. Rev. Pharma-
col. Toxicol. 17: 197.
Hammond, P.B. and A.L. Aronson. 1964. Lead poisoning in cattle
and horses in the vicinity of a smelter. Ann. N.Y. Acad. Sci.
Ill: 595.
Hammond, P.B., et al. 1977. Sources of lead in children. Prog.
Rep. NSF/RANN Grant No. AEN-7414760.
Harris, R.W. and W.R. Elsea. 1967. Ceramic glaze as a source of
lead poisoning. Jour. Am. Med. Assoc. 303: 344.
Hemphill, F.E., et al. 1971. Lead suppression of mouse resistance
of Salmonella typhimurium. Science. 172: 1031.
Hernberg, S., et al. 1967. Nonrandom shortening of red cell sur-
vival times in men exposed to lead. Environ. Res. 1: 247.
Heusgem, C. and J. DeGraeve. 1973. Importance de 1'apport ailmen-
taire en plomb dand 1'est de la Belgique. In; Proc. Int. Symp.
Environ. Health Aspects of Lead, Amsterdam, 2-6 October, 1972.
Comm. Eur. Commun. Luxembourg. p. 85.
C-88
-------
Hopkins, D.R. and W.N. Houk. 1976. Federally-assisted screening
projects for childhood lead poisoning control. Am. Jour. Pub.
Health. 66: 485.
Horiuchi, K. and I. Takada. 1954. Studies on the industrial lead
poisoning. I. Absorption, transportation, deposition and excretion
of lead. 1. Normal limits of lead in the blood, urine and feces
among healthy Japanese urban habitants. Osaka City Med. Jour.
1: 117.
Horiuchi. K. , et al. 1956. Studies on the industrial lead poi-
soning. I. Absorption, transportation, deposition and excretion of
lead. 2. A study on the lead content in daily food in Japan. Osaka
City Med. Jour. 3: 95.
Hubermont, G. , et al. 1978. Placental transfer of lead, mercury
and cadmium in women living in a rural area. Int. Arch. Occup.
Environ. Health. 41: 117.
Hunt, W.F., Jr., et al. 1971. A Study in Trace Element Pollution
of Air in Seventy-seven Midwestern Cities. In; D.D. Hemphill
(ed.), Trace Substances in Environmental Health. IV. University of
Missouri Press, p. 56.
International-Agency for Research on Cancer. 1972. Evaluation of
carcinogenic risk of chemicals to man. World Health Organ., Lyon,
France.
C-89
-------
Jacquet, P., et al. 1977. Cytogenetic investigations on mice
treated with lead. Jour. Toxicol. Environ. Health. 2: 619.
Jandl, J.H., et al. 1959. Transfer of iron from serum iron —
binding protein to human reticulobytes. Jour. Clin. Invest.
38: 161.
Jennett, J.C., et al. 1977. Transport and Distribution of Lead
from Mining, Milling, and Smelting Operations in a Forest Ecosys-
tem. In; W.R. Boggess and B.C. Wixson (eds.), Lead in the Environ-
ment. NSF/RA-880215.
Joselow, M.M. and J.D. Bogden. 1974. Lead content of printed
media. (Warning: spitballs may be hazardous to your health.) Am.
Jour. Pub. Health. 64: 238.
Jugo, S. 1977. Metabolism of toxic heavy metals in growing organ-
isms: A review. Environ. Res. 13: 36.
Kang, H.K., et al. 1980. Occupational lead exposure and cancer.
Letter to the editor. Science. 207: 935.
Karnofsky, D.A. and L.P. Ridgway. 1952. Production of injury to
the central nervous system of the chick embryo by lead salts.
Jour. Pharmacol. Exp. Therap. 104: 176.
C-90
-------
Kehoe, R.A. 1961. The metabolism of lead in man in health and
disease. The Harben Lectures, 1960. Jour. Res. Inst. Pub. Health
Hyg. 34: 1.
Kimmel, C.A., et al. 1976. Chronic lead exposure: Assessment of
developmental toxicity. Teratology. 13: 27 A (Abst.)
Klein, M. , et al. 1'970. Earthenware containers as a source of
fatal lead poisoning. Case study and public-health considerations.
New England Jour. Med. 385: 669.
Kline, T.S. 1960. Myocardial changes in lead poisoning. AMA
Jour. Dis. Child. 99: 48.
Kneip, T.J., et al. 1974. New York University Inst. Environ. Med.
Contract No. CPSC-74-153.
Kobayashi, N. and T. Okamoto. 1974. Effects of lead oxi^e on the
induction of lung tumors in Syrian hamsters. Jour. Natl. Cancer
Inst. 52: 1605.
Kolbye, A.C., et al. 1974. Food exposures to lead. Environ.
Health Perspect. 7: 53.
Kosmider, S. and T. Pentelenz. 1962. Zmiany elektro kardiogray-
ficzne u. starszychosol, 2. prezwleklym zauo-dowym zatruciem olo-
wiem. Pol. Arch. Med. Wein. 32: 437.
C-91
-------
Kostial, K., et al. 1971. Lead absorption from the intestine in
newborn rats. Nature. 233: 564.
Kotok, D. 1972. Development of children with elevated blood lead
levels: A controlled study. Jour. Pediatr. 80: 57.
Lagerwerff, J.V. and A.W. Specht. 1970. Contamination of roadside
soil and vegetation with cadmium, nickle, lead and zinc. Environ.
Sci. Technol. 4: 583.
Lamm, S.H. and J.F. Rosen. 1974. Lead contamination in milk fed to
infants: 1972-1973. Pediatrics. 53: 137.
Lancranjan, I., et al. 1975. Reproductive ability of workmen
occupationally exposed to lead. Arch. Environ. Health. 30: 396.
Landrigan, P.J. and E.L. Baker. 1976. Increased lead absorption
with aremia and slowed nerve conduction in children near a lead
smelter. Pediatrics. 89: 904.
Landrigan, P.J., et al. 1975. Epidemic lead absorption near an
ore smelter. The role of particulate lead. New England Jour. Med.
292: 123.
Lane, R.E. 1949. The care of the lead worker. Br. Jour. Ind. Med.
6: 1243.
C-92
-------
Lansdown, R.G., et al. 1974. Blood-lead levels, behavior and
intelligence. A population study. Lancet. 1: 1166.
Laug, E.P. and P.M. Kunze. 1948. Penetration of lead through
skin. Jour. Ind. Hyg. Toxicol. 30: 256.
Lilis, R., et al. 1977. Lead effects among secondary lead smelter
workers with blood levels below 80 yg/100 ml. Arch. Environ.
Health. Nov. 1977. p. 256.
Mao, P. and J.J. Molnar. 1967. The fine structure and histochem-
istry of lead-induced renal tumors in rats. Am. Jour. Pathol.
50: 571.
Maxfield, M.E., et al. 1972. Effect of lead on blood regeneration
following acute hemorrhage in dogs. Am. Ind. Hyg. Assoc. Jour.
33: 326.
McCabe, L.J. 1970. Metal levels found in distribution samples.
Am. Water Works Assoc. Seminar on Corrosion by Soft Water. Wash-
ington, D.C.
McCauley, P.T., et al. 1979. Association of alterations in energy
metabolism with lead-induced delays in rat cerebral cortical devel-
opment. Neuropharmacology. 18: 93.
C-93
-------
McClain, R.M. and B.A. Becker. 1975. Teratogenicity, fetal tox-
icity and placental transfer of lead nitrate in rats. Toxicol.
Appl. Pharmacol. 31: 72.
McNeil, J.L., et al. 1975. Evaluation of long-term effects of
elevated blood lead concentrations in asymptomatic children.
Arhiv. Rig. Rada. Toksikol. 14: 97.
Meredith, P.A., et al. 1977. Delta-aminolaevulinic acid metabo-
lism in normal and lead-exposed humans. Toxicol. 9: 1.
Milburn, H. , et al. 1976. An investigation of lead workers for
subclinical effects using three performance tests. Ann. Occup.
Hyp. 19: 239.
Millar, J.A., et al. 1970. Lead and ALAD (a-aminolevulinic acid
dehydratase) levels in mentally retarded children and in lead poi-
soned suckling rats. Lancet. 2: 695.
Mitchell, D.G. and K.M. Aldous. 1974. Lead content of foodstuffs.
Environ. Health Perspect. Exp. Issue. 7: 59.
Moore, M.R., et al. 1977a. Contribution of lead in water to blood-
lead. Lancet. 2: 661.
Moore, M.R., et al. 1977b. A retrospective analysis of blood-lead
in mentally-retarded children. Lancet. 1: 717.
C-94
-------
Mooty, E.M., et al. 1975. Relationship of diet to lead poisoning
in children. Pediatrics. 55: 636.
Morgan, B.B. and J.D. Repko. 1974. In; C. Xintaras, et al. (eds.),
Behavioral Toxicology. Early Detection of Occupational Hazards.
U.S. Dept. Health Edu. Welfare, Washington, D.C.
Morgan, J.M., et al. 1966. Neohropathy in chronic lead poisoning.
Arch. Int. Med. 118: 17.
Morse, D.L., et al. 1978. Accepted for publication, Am. Jour.
Pub. Health.
Murthy, G.M. and U.S. Rhea. 1971. Cadmium, copper, iron, lead,
manganese and zinc in evaporated milk, infant products and human
milk. Jour. Dairy Sci. 54: 1001.
National Academy of Sciences. 1972. Airborne lead in perspective.
Washington, D.C.
National Academy of Sciences. 1977. Drinking water and health.
Washington, D.C.
Nelson, W.C., et al. 1973. Mortality among orchard workers ex-
posed to lead arsenate spray: A cohort study. Jour. Chron. Dis.
26: 105.
C-95
-------
Nogaki, K. 1958. On action of lead on body of lead refinery work-
ers: Particularly conception, pregnancy and parturition in case of
females and their newborn. Excerp. Med. XVII. 4: 2176.,
Nordman, C.N. 1975. Environment lead exposure in Finland. A
study on selected population groups. Ph.D. thesis. University of
Helsinki.
O'Riordan, M.L. and H.J. Evans. 1974. Absence of significant
chromosome damage in males occupationally exposed to lead. Nature.
247: 50.
Oyasu, R. , et al. 1970. Induction of cerebral gliomas in rats with
dietary lead subacetate and 2-acetylaminofluorene. Cancer Res.
30: 1248.
Perino, J. and C.B. Ernhart. 1974. The relation of subclinical
lead level to cognitive and sensorimotor impairment in black pre-
schoolers. Jour. Learn. Dis. 7: 26.
Perlstein, M.A. and R. Attala. 1966. Neurologic sequelae of
plumbism in children. Clin. Pediat. 6: 266.
Piddington, S.K. and J.M. White. 1974. The effect of lead on total
globin and a and B chain synthesis; in vitro and in vivo. Br. Jour.
Haematol. 27: 415.
C-96
-------
Prerovska, I. and J. Teisinger. 1970. Excretion of lead and its
biological activity several years after termination of exposure.
Br. Jour. Ind. Med. 27: 352.
Pringle, B.H., et al. 1968. Trace metal accumulation by estuarine
mollusks. Proc. Am. Soc. Civil. Eng., Jour. San. Eng. Div. SA3,
455-475.
Prpic-Majic, D., et al. 1973. Delta-aminolevulinic acid dehydra-
tase activity, lead blood levels, and the reticulocyte count.
Environmental health aspects of lead. Proc. Symp. held in Amster-
dam, Holland, Oct. 2-6, 1972. Comm. Eur. Commun. Luxembourg.
Pueschel, S.M., et al. 1972. A screening and follow up study of
children with an increased lead burden. Jour. Am. Med. Assoc.
222: 462.
Rabinowitz, M.B., et al. 1973. Lead metabolism in the normal
human: Stable isotope studies. Science. 182: 725.
Rabinowitz, M.B., et al. 1974. Studies of human lead metabolism
by use of stable isotope tracers. Environ. Health Perspect. Exp.
Issue. 7: 145.
Rastogi, S.C. and J. Clausen. 1976. Absorption of lead through
the skin. Toxicol. 6: 371.
C-97
-------
Rhyne, B.C. and R.A. Goyer. 1971. Cytochrome content of kidney
mitochondria in experimental lead poisoning. Exp. Mol. Pathol.
14: 386.
Roe, F.J.C., et al. 1965. Failure of testosterone or xanthopterin
to influence the induction of renal neoplasms by. lead in rats. Br.
Jour. Cancer. 19: 860.
Roels, H.A., et al. 1975. Response of free erythrocyte porphyrin
and urinary a-aminolevulinic acid in men and women moderately ex-
posed to lead. Int. Arch. Arbeitsmed. 34: 97.
Roels, H.A., et al. 1978. Lead and cadmium absorption among chil-
dren near a nonferrous metal plant. A follow-up study of a test
case. Environ. Res. 15: 290.
Sachs, H.K. 1974. Effects of a screening program on changing pat-
terns of lead poisoning. Environ. Health Perspect. Exp. Issue.
7: 41.
Sandstead, H.H., et al. 1969. Lead intoxication and the thyroid.
Arch. Int. Med. 123: 632.
Sassa, S., et al. 1973. Studies in lead poisoning. I. Micro-
analysis of erythrocyte protoporphyrin levels by spectrophotometry
in the detection of lead poisoning in the subclinical range. Bio-
chem. Med. 8: 135.
C-98
-------
Schaller, K.H., et al. 1976. The blood lead level of mothers and
their newborris and the amount of lead in the tissue of human pla-
centa in relation to the environment. Arch. Occup. Environ.
Health. 37: 265.
Schroeder, H.A., et al. 1961. Abnormal trace metals in man: Lead.
Jour. Chronic Dis. 14: 408.
Schulz-Baldes, M. 1972. Toxizitat und anreicherung von Blei bei
der Miesmuschel Mytilis edulis im Laborexperiment. Mar. Biol.
16: 266. (Ger.)
Schulz-Baldes, M. 1974. Lead uptake from seawater and food, and
lead loss in the common mussel My t i Us edulis. Mar. Biol.
25: 177.
Secchi, G.C., et al. 1971. Ricerche sull'attivita ALA-deidrasica
eritrocitaria di soggetti non eposti a contatto Professionale con
plombo ed abitanti in zone ruralied urbane. Med. Lav. 62: 435.
Secchi, G.C., et al. 1974. Delta-aminolevulinic acid dehydratase
activity in erythrocytes and liver tissue in man. Arch. Environ.
Health. 28: 130.
Selander, S. and K. Cramer. 1970. Interrelationships between lead
in blood, lead in urine, and ALA in urine during lead work. Br.
Jour. Ind. Med. 27: 28.
C-99
-------
Shuster, C.N. and B.H. Pringle. 1969. Trace metal accumulation by
the American Eastern oyster, Crassostrea virginica. Proc. Natl.
Shellfish Assoc. 59: 91.
Six, K.M. and R.A. Goyer. 1970. Experimental enhancement of lead
toxicity by low dietary calcium. Jour. Lab. Clin. Med. 76: 933.
Six, K.M. and R.A. Goyer. 1972. The influence of iron deficiency
on tissue content and toxicity of ingested lead in the rat. Jour.
Lab. Clin. Med. 79: 128.
Smith, F.L., et al. 1938. The early diagnosis of acute and latent
plubmism. Am. Jour. Clin. Pathol. 8: 471.
Sobel, A.E., et al. 1938. Influence of dietary calcium and Dhos-
phorous upon action of vitamin D in experimental lead poisoning.
Proc. Soc. Exp. Biol. Med. 38: 435.
Stephan, C.E. 1980. Memorandum to J. Stara. U.S. EPA. July 3.
Stowe, H.D. and R.A. Goyer. 1971. The reoroductive ability and
progeny of F-j^ lead-toxic rats. Fertil. Steril. 22: 755.
Strand, L.J., et al. 1972. The induction of d-aminolevulinic acid
synthetase in cultured liver cells. Jour. Biol. Chem. 247: 2820.
C-100
-------
Suketa, Y. , et al. 1975. Changes in heoatic ^-aminolevulinic
acid in lead-intoxicated rats. Jour. Toxicol. Environ. Health.
1: 127.
Talbot, V., et al. 1976. Lead in Port Phillip Bay mussels. Mar.
Pollut. Bull. 7: 234.
Tepper, L.B. and L.S. Levin. 1972. A survey of air and population
lead levels in selected American communities. Final report to U.S.
Environ. Prot. Agency.
Ter Haar, G.L. and R. Aronow. 1974. New information on lead in
dirt and dust as related to the childhood lead problem. Environ.
Health Perspect. Exp. Issue. 7: 83.
Thompson, J.A. 1971. Balance between intake and output of lead in
normal individuals. Br. Jour. Ind. Med. 28: 189.
Tola, S. 1973. Effect of blood lead concentration, age, sex, and
exposure time on the erythrocyte d-aminolevulinic acid dehydratase
activity. Work Environ. Health. 10: 26.
Tola, S., et al. 1973. Parameters indicative of absorption and
biological effect in new lead exposure: A prospective study. Br.
Jour. Ind. Med. 30: 134.
C-101
-------
U.S. EPA. 1977. Air quality criteria for lead. Pub. No. EPA
600/8-77-017. U.S. Environ. Prot. Agency.
U.S. EPA. 1980. Seafood consumption data analysis. Stanford Re-
search Institute International, Menlo Park, California. Final re-
port, Task 11. Contract No. 68-01-3887.
U.S. Food and Drug Administration. 1975. Compliance program eval-
uation. FY-1947. Heavy metals in foods survey. Bur. Foods, Wash-
ington, D.C.
Van Esch, G.J. and R. Kroes. 1969. The induction of renal tumors
by feeding basic lead acetate to mice and hamsters. Br. Jour. Can-
cer. 23: 765.
Van Esch, G.J., et al. 1962. The induction of renal tumors by
feeding basic lead acetate to rats. Br. Jour. Cancer. 16: 289.
Wedeen, R.P., et al. 1975. Occupational lead nephropathy. Am.
Jour. Med. 59: 630.
Wetherill, G.W., et al. 1974. Proc. Int. Symp. Paris, France,
June, 1974. Comm. Eur. Commun., U.S. Environ. Prot. Agency, World
Health Organ.
Wibberley, D.J., et al. 1977. Lead levels in human placentas from
normal and malformed births. Jour. Med-Genetics. 14: 339.
C-102
-------
Wong, C.S. and P. Berrang. 1976. Contamination of tap water by
lead pipe and solder. Bull. Environ. Contam. Toxicol. 15: 530.
World Health Organization. 1977. Environmental Health Criteria 3
Lead. Geneva.
Zardogian, G.E., et al. 1979. Crassostrea virginica as an indica-
tor of lead pollution. Mar. Biol. 52: 189.
Ziegler, E.E., et al. 1978. Absorption and retension of lead by
infants. Pediatr. Res. 12: 29.
Zielhuis, R.L. 1975. Dose response relationships for inorganic
lead. I. Biochemical and haematological responses. II. Subiective
and functional responses. Chronic sequelea. No-response levels.
Int. Arch. Occup. Health. 35: 1,19.
Zollinger, H.U. 1953. Durch Chronische Bleivergiftung Erzeugte
Nierenadenome und Carcinoma bei Ratten und Ihre Beziehunqen zu Den
Entsprechenden Neubildung des Menschen. (Kidney adenomas and car-
cinomas in rats caused by chronic lead poisoning and their rela-
tionship to corresponding human neoplasma). virchow Arch. Pathol.
Anat. 323: 694.
Zurlo, N. and A.M. Griffini." 1973. Le plomb dans les aliments et
les boissons consommes a Milan. In; Proc. Int. Symp. Environ.
Health. Aspects of Lead. Amsterdam, 2-6 Oct., 1972. Comra. Eur.
Commun. Luxembourg.
C-103
-------
APPENDIX*
Results of the research examined in the Commission of the
European Communities (CEC) paper are summarized in Tables 1 and 2.
The data presented in Table 1 are equations developed by the auth-
ors concerning the relationship of blood lead (PbB) to water lead
(PbW). Table 2 consists of calculations of the contribution of 100
yg Pb/1 of water to PbB (as yg/dl) . Some of these calculations were
made by Berlin, et al. (1978) , interpolating from data points in
the articles cited. Others were made using the equations provided
by the authors of the articles cited.
Three types of equations are presented:
(1) PbB = a + b PbW
(2) PbB = a + log PbW
In all cases "a" is the baseline expressing PbB at PbW = 0. Of
these three mathematical relationships, the third appears to be the
most valid for two reasons: (1) the largest number of subjects are
involved in studies using this equation, and (2) it corresponds to
the analysis of U.S. EPA data (Greathouse and Craun, 1976) as cited
in the lead criterion document, which also involved a very large
number of subjects. Moreover calculations made of PbB vs. PbW
using the U.S. EPA data were for females aged 20 to 50, a sub-popu-
lation which probably gets a larger proportion of its water from
*Summary of "Research of PbB vs. Lead in Drinking Water in Europe"
as presented by A. Berlin, et al. (1978) , Commission of the European
Communities.
C-104
-------
TABLE 1
Relationships between PbW and PbB*
Relationship
Remarks
Reference
PbB = 0.018 PbW +22.9
r = 0.417
PbW = ng/1
PbB = vig/100 ml
First morning flush
Addis and Moore, 1974
PbB = 0.76 + 0.15 PbW
PbB = 0.80 + 0.20 PbW
PbW and PbB in ymol/1
r = 0.58, first morning flush
r = 0.52, running sample
Moore, 1977a
o
i
M
O
Ln
PbB = 0.533 -f 0.675 PbW
PbB = 0.304 + 1.036 3 PbW
PbW and PbB in ymol/1
first morning flush
running sample
Moore, et al. 1977
PbB = 9.62 + 1.74 log PbW
PbW in pq/1 PbB in ug/lOOml
first morning flush
Lauwerys, et al. 1977
PbB = 0.8 + 0.19 PbW
PbB = 0.8 -I- 0.53 PbW
PbW and PbB in ymol/1
first morning flush
full flush (paired samples)
Moore, 1977b
PbB = 19.6 + 7.2 PbW
PbW in ppm, PbB in ug/lOOml
first morning flush
Elwood, et al. 1976
PbB = 20.7 -I- 12.6 PbW
As above.
Re-evaluated data
Beattie, et al. 1976
*Source: Berlin, et al. 1978
-------
TABLE 2
Increment in PbB for an Increase of 100 yq/1 in Pbw
(for Concentrations around 100 yg/1) *
Increment in PbB
Remarks
Reference
o
i
i—•
o
cr>
1.3 yg/100ml
1.2 nq/100ml
3.4 yg/lOOml
3.3 pg/lOOml
1.8 ug/100ml
2.0 vig/100ml
6.0 yg/lOOml
3.9 yg/100m]
0.83 pq/lOOml
For running sample (linear
interpolation) 20-1040 yg/1 PbW
First flush (linear inter-
polation) 10-250 yg/1 PbW
For running sample (linear
interpolation) 10-250 yg/1 PbW
For first flush (linear inter-
polation) 35-350 yg/1 PbW
Using the linear equation derived
by the authors
Using the linear equation derived
by the author for running water
samples.
Using the non-linear equation
derived by the authors for
running water samples.
Using the non-linear equation de-
rived by the authors for first
morning flush.
Using the log equation derived
by the authors
In view of the low PbW value,
the extrapolation is uncertain.
De Graeve, et al. 1975
Beattie, et al. 1972
Covell, 1975
Addis, et al. 1974
Addis, et al. 1974
Moore, 1977a
Moore, et al. 1977
Moore, et al. 1977
Lauwerys, et al. 1977
Vos, et al. 1977
-------
TABLE 2 (Continued)
o
i
Increment in PbB
1.9 ug/100ml
5.3 yg/lOOml
0.72
1.3 yg/lOOml
Remarks
Using the linear equation derived
by the authors for morning flush
Using the linear equation derived
by the authors for full flush
Using the linear equation derived
by the authors for morning flush.
Using the re-evaluated linear
equation derived by the authors
for morning flush.
Reference
Moore, et al. 1977
Moore, et al. 1977
Elwood, et al. 1976
Beattie, et al. 1976
*Source: Berlin, et al. 1978
-------
the domestic supply than the population at large. In that regard,
the only comparable population was 70 pregnant female subjects in
the study of Hubermont, et al. (1978) cited in the CEC document as
Lauwreys, et al. (1977).
In summary, of the studies cited in the CEC document, most
weight should probably be given to the Moore, et al. (1977a) cita-
tion, on the basis of large numbers of samples of water and study
subjects, and to the Hubermont, et al. (1978) study on the basis of
a substantial number of subjects which were probably partaking of
more of the domestic water supply than other sub-classes by virtue
of pregnancy and sex.
So far as the actual calculations in Table 2 are concerned,
there is one error. The CEC document calculates that the equation
of Hubermont, et al. (1978) (cited as Lauwreys, et al. 1977) would
predict that PbW at 100 yg/1 would result in a PbB contribution of
0.83 yg/dl. The error is obvious. In the equation, the PbB contri-
bution of water is given by PbB = 1.74 log PbW. In fact, 0.83 =
1.74 log 3, not 1.74 log 100. The correct calculation is PbB =
1.74 X 2 = 3.48, since log 100 = 2.
Of the 13 estimates of PbB vs. PbW in Table 2, only 5 could be
verified. These were Addis, et al. (1974) (interpolation), Addis,
et al. (1974) using authors' equation, Moore (1977a) using author's
equation, Beattie, et al. (1976) using author's equation, and
Moore, et al. (1977) , non-linear morning flush. Of the remaining
nine, one was miscalculated by CEC and the remaining eight could
not be verified by this author because the caper was unavailable
(Covell, 1975; Elwood, 1976), or because the necessary data were
C-108
-------
not in the paper (De Graeve, et al. 1975; Moore, et al. 1977 using
non-linear equation for running water; Moore, et al. 1977 using
linear equation for morning flush and running water calculations),
or because it was not possible to see how CEC made an interpolation
from the data cited (Beattie, et al. 1972).
In summary, the two most credible studies among the nine actu-
ally scrutinized in this addendum were the very ones utilized in
the criterion document for lead. Of the two reviewed by the CEC but
not examined at the time of this writing (Covell, 1975; Elwood,
1976) , one was reviewed prior to development of the criterion docu-
ment and rejected on the basis of the seemingly inappropriate use
of a linear regression model (see "Contributions of Lead from Diet
vs. Air to PbB" in the Pharmacokinetics section). It is therefore
concluded that information provided by CEC does not alter the eval-
uations made in the criterion document.
0109
-------
REFERENCES
Addis, C. and M. R. Moore. 1974. Lead levels in the water of sub-
urban Glasgow. Nature. 252: 120.
Beattie, A.D., et al. 1972. Environmental lead pollution in an
urban soft-water area. Br. Med. Jour. 32: 491.
Beattie, A.D., et al. 1976. Blood lead and domestic water lead.
Lancet. 2: 200.
Berlin, A., et al. 1978. Research on lead in drinking water in
Europe. Comm. Eur. Commun.
Covell, B. 1975. Lead content in household water in Edinburgh.
Health Bull. 33: 114.
De Graeve, J., et al. 1975. Plombemie d'une copulation adulte de
1'Est de la Belgique. Rev. Epidem. Med. Soc. et Sante Publ.
23: 131.
Elwood, P.C., et al. 1976. Dependence of blood lead on domestic
water lead. Lancet. 1: 1295.
Hubermont, G., et al. 1978. Placental transfer of lead, mercury,
and cadmium in women living in a rural area. Importance of drink-
ing water in lead exposure. Int. Arch. Occup. Environ. Health.
41(2): 117.
C-110
-------
Lauwerys, R., et al. 1977. Influence of contamination of water by
lead on exposure of pregnant mothers and their newborns. (Manu-
script)
Moore, M.R. 1977a. Lead in Drinking water in soft water areas —
health hazards. Sci. Total Environ. 7: 109.
Moore, M.R. 1977b. Materno-foetal lead studies. Personal com-
munication.
Moore, M.R., et al. 1977. The contribution of lead in drinking
water to blood lead. Lancet. 2: 661.
Vos, M. , et al. 1977. Een orienterend onderzoek naar de corre-
latie tussen watermetalen in bloedmetalen in de gemeenten Hoens-
broek en Brunssum. (In press)
•D.S. GOVERNMENT PRINTING OFFICE: 1980-0-720-016/5960
C-lll
------- |