Ecological Research Series

THE  SHORT-TERM EFFECTS  OF  LEAD  ON
            DOMESTIC  AND  WILD  ANIMALS
                            Environmental Research Laboratory
                           Office of Research and Development
                           U.S. Environmental Protection Agency
                                  Corvallis, Oregon 97330

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                 RESEARCH  REPORTING SERIES

Research reports of the Office of Research and Development, U.S. Environmental
Protection Agency,  have been grouped  into five series. These five broad
categories were established to facilitate further development and application of
environmental technology. Elimination of traditional grouping was consciously
planned to foster technology transfer and a maximum interface in related fields.
The five series are:

     1.    Environmental Health Effects Research
     2.    Environmental Protection Technology
     3.    Ecological Research
     4.    Environmental Monitoring
     5.    Socioeconomic Environmental Studies
This report has been assigned to the ECOLOGICAL RESEARCH series. This series
describes research  on the effects  of pollution on  humans, plant and  animal
species, and materials. Problems are assessed for their long- and short-term
influences. Investigations include formation, transport, and pathway studies to
determine the fate of pollutants and their effects. This work provides the technical
basis for setting standards to minimize undesirable changes in living organisms
in the aquatic, terrestrial, and atmospheric environments.
This document is available to the public through the National Technical Informa-
tion Service, Springfield, Virginia 22161.

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                                      EPA-600/3-77-009
                                      January  1977
      THE  SHORT-TERM  EFFECTS  OF  LEAD  ON
        DOMESTIC  AND WILD ANIMALS
                    by
               R. P. Botts
Corvallis Environmental Research Laboratory
          Corvallis, Oregon 97330
CORVALLIS ENVIRONMENTAL RESEARCH LABORATORY
    OFFICE OF RESEARCH AND DEVELOPMENT
   U.S. ENVIRONMENTAL PROTECTION AGENCY
         CORVALLIS, OREGON  97330

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                                 DISCLAIMER
     This report has been reviewed by the Con/all is Environmental  Research
Laboratory, U.S. Environmental  Protection Agency,  and approved for publication
Mention of trade names or commercial  products does not constitute  endorsement
or recommendation for use.
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                                 FOREWORD
     Effective regulatory and enforcement actions by the Environmental
Protection Agency would be virtually impossible without sound scientific
data on pollutants and their impact on environmental stability and human
health.  Responsibility for building this data base has been assigned to
EPA's Office of Research and Development and its 15 major field installa-
tions, one of which is the Corvallis Environmental  Research Laboratory
(CERL).

     The primary mission of the Corvallis Laboratory is research on the
effects of environmental pollutants on terrestrial, freshwater, and marine
ecosystems; the behavior, effects and control of pollutants in lake systems;
and the development of predictive models on the movement of pollutants in
the biosphere.

     This report presents a discussion on the extent of lead found in wild
and domestic animals and some of the short term effects of this toxic sub-
stance.
                                            A.F. Bartsch
                                            Director, CERL
                                    m

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                                  ABSTRACT
     Small  quantities of lead,  a ubiquitous and toxic element,  may be found
in practically all  species of plants and animals.   The list of  animals,  both
domestic and wild,  reportedly intoxicated by lead  is impressive.

     The sources of lead poisoning vary with species of animals.   Lead base
paints, used motor  oils, spent  lead shot and pastures contaminated by lead
smelters seemingly  have been most often incriminated.

     The lesions associated with lead intoxication may vary widely both
within and between  species of animals.   Lesions and symptoms of the central
nervous system are  the most prominent.

     Toxic levels for various species as reported  in the literature vary
widely and seemingly a single toxic dose for each  species,  as yet, has not
been definitely established.

     The diagnosis  and treatment of lead intoxication may become  laborious
and time consuming.  Most symptoms  reported involve central nervous system
dearrangement.  Treatment of most clinical  cases is disappointing generally
because of the acute nature of  lead poisoning.

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                                  CONTENTS
Section                                                     Page

   I.  Conclusions	1
  II.  Introduction 	  2
 III.  Sources of Lead and the Epizootiology of
       Lead Toxicosis	4
  IV.  Metabolism of Lead	7
   V.  Lesions Associated with Lead Intoxication	11
  VI.  Other Functional Effects Associated with Lead
       Poisoning	14
 VII.  Toxic Levels of Lead for Various Species of
       Animals	16
VIII.  Signs, Symptoms and Diagnosis 	  19
  IX.  Clinical Pathology and Chemical  Analysis	21
   X.  Treatment	22
  XI.  References	23

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                                 Section I

                                CONCLUSIONS


     From data reported in the literature crude estimates of the occurrence
of lead poisoning may be derived.  Approximately 150,000 cattle are annually
exposed to toxic levels of lead and 20,000 acute cases occur per year.   Of
these, 15,000 animals succumb to lead poisoning.  In addition,  it is estimat-
ed that 1,000,000 migratory waterfowl succumb to lead poisoning due to
consuming spent lead shot.

     The metabolism of lead compounds is very complicated and variable  both
within and between species.  For most mammals including man 1-5% of the lead
taken orally will be absorbed.  One may estimate for ruminants  that 83.6% is
excreted through the feces; 14.8% through the urine, and 1.6% through the
milk.  Lead, once taken internally is retained by the body; particularly,
the bones tenaciously retain lead and may account for as much as 80% of the
total body burden.

     The exact mechanisms giving rise to the pathological lesions associated
with lead poisoning have not been clarified.  This is particularly true for
chronic encephalopathy and nephropathy.  Several enzymes are known to be
inhibited by lead and among this group are several enzymes shown or suspected
of being involved in renal tubular transport.

     Even with the voluminous literature concerning lead, toxic levels  for
various species of animals have not been precisely determined,  nor is there
general agreement on what constitutes a safe level of intake for extended
periods of time.

     Generally, the treatment of lead poisoning is disappointing because of
the acute nature of most clinical cases.  Thus more emphasis should be
placed on preventive rather than therapeutic programs to avoid the losses
due to lead poisoning.

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                                  Section II

                                 INTRODUCTION
     Lead is one of the oldest metals used by mankind; Romans and medieval
Britons constructed lead water pipes (1).   Usage has expanded until today
the total annual U.S. consumption in 1968 was 1,328,970 tons (2).  Approxi-
mately 184,316 tons annually are emitted to the atmosphere from sources such
as combustion of gasoline, fuel oil, and coal in addition to several  other
industrial sources.  The most abundant lead ore is Galena (PbS) (1).   Approxi-
mately 32 percent of the U.S. consumption is obtained from primary smelters,
38 percent from secondary recovery, and 30 percent from imports (2).

     Lead is an ubiquitous and toxic element.  Small quantities can be found
in practically all  living tissues of plants and animals.   Soils, limestone,
sandstone, shale and igneous rocks contain quantities varying from 7  to 20
ppm (3).  Much has  been written about lead, and thousands of cases of lead
poisoning have been reported in both the human and veterinary medical litera-
ture.   The species  of animals that have either died or been obviously ill
from increased lead intake include:

     A.   Farm livestock and pets

          1 .   Horses
          2.   Cattle
          3.   Swine
          4.   Dogs
          5.   Sheep (this review failed to find any reports involving
               naturally occuring lead poisoning).

     B.   Wild animals

          1 .   Ducks
          2.   Geese
          3.   Andean Condor
          4.   Doves
          5.   Quail
          6.   Pheasants
          7.   Falcon

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     C.    Zoo animals

          1.    Non-human primates
          2.    Leopards
          3.    Australian fruit bats
          4.    Parrots
          5.    Polar bear
          6.    Lorikeets
          7.    Ferrets

     Most of the reported incidents of poisoning involved  small  numbers of
animals.  However, contamination of vegetation by industrial  operations(4-
13) often results in death to several  animals at one  time.   Because  lead  is
the most common accidental poison of farm animals (14),  it is of considerable
economic importance to agriculture.

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                                 Section  III

           SOURCE OF LEAD AND THE EPIZOOTIOLOGY  AND  LEAD  TOXICOSIS


     The diagnosis of lead poisoning  is not  precise  in  all  cases.   For  this
reason, knowledge of the epizootiology of lead poisoning  can  help in  arriv-
ing at a definitive diagnosis, in addition to determining the occurrence  of
the disease and defining the circumstances of exposure.

EPIZOOTIOLOGY

     Although definite estimates  of the incidence, morbidity  and mortality
in domestic and wild animals is lacking,  the literature contains some
information concerning the epizootiology  of  lead poisoning.   Reports  often
state that the morbidity is low and the mortality or case fatality  rate is
high (14, 15).  Lead poisoning is diagnosed  more frequently in cattle and
dogs than other species (14).

     For cattle, the incidence of lead poisoning has been estimated as
approximately 167 cases per year  per  1,000,000 animals  (2).   However, several
tenuous assumptions were made in  order to derive this estimate.  The  propor-
tional mortality for lead poisoning (e.g., no. of animals dying of  lead
poisoning per all animal deaths)  in cattle is estimated to be 1.7 percent
for calves and 4.5 percent for older  cattle  (16).  The  morbidity of animals
exposured to toxic levels of lead is  estimated to be 11-15 percent  and  the
case fatality rate is 55-85 percent (17). Two possible explanations  are
offered to explain the above estimates.   Either, few animals--only  the  most
serious cases—are presented to diagnostic laboratories or few exposed
animals receive doses of sufficient magnitude to cause  illness.  If one can
accept the incidence of lead poisoning to be approximately 0.016 percent  (2)
per year and the morbidity of animals exposed to toxic  lead levels  to be  11-
15 percent (17), then one may conclude that  the  ratio of  exposed to unexposed
cattle is 1:600 to 1:900.  With a total 1969 cattle  population of 123,748,000
in the U.S., one can estimate that between 137,000 and  190,000 cattl* are
annually exposed to toxic levels  of lead  and that 20,000  cases of lead
poisoning occur per year.

     Lead intoxication has a definite seasonal trend for  cattle (17), dogs(19)
and human beings (2).  During a five  year period (1965-1970), 41 percent  of
the bovine cases of a large diagnostic center occurred  during April,  May  and
June (17).  In contrast, lead poisoning in dogs  more often is diagnosed in
summer and fall (19).  The seasonal trend for cattle, at  least in  Iowa,
coincides with the time when cattle are released to  spring pastures (17).

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      Very  little  information  is  available on  the age distribution of lead
 poisoning.   For dogs,  poisoning  apparently occurs more frequently in younger
 animals, possibly because  of  their  indiscriminate chewing habits (2, 19).

      The incidence of  lead poisoning  is  unknown for practically all species
 of wild animals.   However, an estimated  one million ducks, geese and swans
 die  annually in the U.S. of lead poisoning (20).

      The sources  of lead poisoning  are varied and often depend on such
 factors as  the characteristics of the animal  and its peculiar husbandry
 considerations.   Consumption  of  spent lead shot for wildlife species such as
 ducks, geese, swans, mourning doves,  pheasants, condor and falcons most
 often has  been incriminated (21-25) as the source of lead poisoning.  The
 consumption of flaking-paint  containing  lead  is a common source for zoo
 animals  (26-28).   For  domestic and  pet animals, the sources of lead poisoning
 are  more variable.  In one study (17) the sources of lead incriminated for
 cattle were paint (29  percent),  oil  (25  percent), unknown (24 percent)
 junkpiles  (11 percent) grease (6 percent) and batteries (5 percent).  Table
 1 lists the most  often quoted sources of lead by species (4,5,6,7,8,9,10,17,
 29-33).

        Table 1.   Sources  of  Lead Poisoning for Various Species

                              of  Livestock
      Species                                 Sources


      Cattle                    Lead  base  paint, used motor oil, grease,
                               used  batteries, junkpiles containing
                               lead,  putty,  roofing material, linoleum
                               contaminated  water, contaminated feed
                               contaminated  pastures from lead smelters

      Horses                    Contaminated  pastures from lead smelters

      Swine                     Lead  base  paint

      Dog                       Paint,  linoleum, shot gun slugs, curtain
                               weights, plaster


      Some of  these  diverse  sources  are more potent in terms of their lead
 content.  Grease  may  contain  as much  as  450,000 ppm (17) and oil as much as
500 ppm (34).   Horses  and cattle have died grazing on  contaminated  pastures
that contained as  much as 2,000 ppm (35)  of lead.

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     The epizootiology of lead poisoning may be  briefly summarized:

     1 .    For Farm Animals

          a.    The disease occurs  more  often in  spring.
          b.    The morbidity is low and mortality high.
          c.    The sources most often  incriminated include paint,  used
               oil, grease, and discarded batteries.

     2.    For Dogs

          a.    The disease occurs  more  often in  summer  and fall.
          b.    Most often it is a  disease of young dogs.
          c.    Several sources have been suggested.

     3.    For Wildlife

          a.    Consumption of spent lead shot is  the  primary  source.
          b.    Approximately 1,000,000  migratory  birds  are lost annually.

     4.    For Zoo Animals

          a.    Lead base  paint consumed after it  has  flaked from
               cages and  enclosures is  the  primary source.

     Obviously,  the salient features of a program to  reduce the occurrence
of lead  poisoning would involve:

     1.    On  the farm, implement clean  husbandry  practices.   In particular

          a.    Don't drain the oil  from motor vehicles  in  pastures.
          b.    Don't discard batteries,  paint buckets,  or  used grease
               cans in pastures.
          c.    Erect fences to keep animals  out of old  junk piles

     2.    With non-lead paint,  thoroughly clean and repaint all cages
          for animals.

     3.    For wildlife, a preventive program (being implemented)(2)
          involves  developing  a  substitute  for lead shot.

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                                 Section IV

                             METABOLISM OF LEAD
ABSORPTION
     The absorption of lead compounds is quite complex and  involves  three
different routes:  inhalation, ingestion, and absorption  through  the skin.
Of these inhalation is most efficient, and skin absorption  is  the least
efficient.  For man, 14-45 percent of inhaled lead is retained, whereas  only
5-15 percent of that ingested is retained (36).  Factors  that  may modify
retention of lead particulates in the lungs are the particle  size, mucous
flow, ciliary action, and the alveolar clearance rate (36).

     The percent retained by ingestion or the digestive coefficient  is
computed by determining the ratio—the portion retained/portion consumed.  The
digestive coefficient of lead varies widely between species from  5-15 percent
in man (36) to as little as 1-3 percent in cattle and one percent in rabbits
(37).  For many toxic metals, the rate of absorption depends  on  such factors
as the chemical form of the lead, the age of the animal,  the  pH  of the
gastro-intestinal tract, the gut transient time, the gut  microflora, and the
presence or absence of other metals.  For example reducing the calcium level
in the diet may increase the lead absorption in rats (38).   In contrast
vitamin D has a reverse effect (39).  Furthermore lead absorption by the
gastro-intestinal tract is greater in young than in old rats  (40,41).

TRANSPORT, DISTRIBUTION AND EXCRETION

     Once lead is absorbed, it enters into a state of exchange between
tissues and the blood.  The various organs retain different amounts of  lead.
Transport, distribution and excretion of lead may be best conceptualized as
a series of compartments interconnected with one another  via  the  blood
(Figure 1).

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Fig. 1:   Hypothetical  Transport of Lead
     G.I.
     Tract
     Lungs
                                                                      Bone
     Each compartment receives and will  retain lead from the blood.   The
retention time of the lead depends on its biological  half-time t]/2,  which
in turn depends upon the strength of the bond between lead and the binding
tissue.

     If the transfer from a tissue can be assumed to be a first-order
decay, the^]/2 is the time required for 1/2 of the present burden of lead
to be transferred from the tissue to the blood.  In many biological  systems,
the transfer of material between compartments can be simulated by assuming a
first order decay (42,43).  Then the transfer rate depends only on the concen-
tration in the originating compartment and the transfer coefficient for that
compartment.  The transfer coefficient,  k, is related to t]/2 by the  equa-
tion:
     One can appreciate that the concentrations in the various organs will
change with time after a single dose of lead is absorbed and that these
concentrations will  depend partly upon the t-|/2-

     Since blood is  the medium that transports lead, it assumes an important
role in the metabolism of lead.  Based on tracer studies (44) in the dog and
wet chemical analysis of tissues and blood from sheep (45), one may conclude
that blood contains  more than one compartment.  Results reported in dogs (44)
indicate at least three compartments.   Some suggest (36) four compartments:
red blood cells (RBCs),  specific metalloproteins, plasma proteins and low
molecular weight plasma proteins.  The transfer rate is much slower (that is
the ti/2 is longer)  for RBCs than for plasma or sera; thus, for the most
part, the concentration would be greater in the RBCs than in the plasma.
Forty and one-half hours after receiving an oral  dose of lead, the RBC to
plasma ratio was 122 in a calf (46).  In contrast, this ratio was estimated
to be 11 in sheep, 40 hours after an intravenous dose (45).  This latter

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data (45) show that the ti/2 is longer for RBCs than for serum, and conse-
quently, the fraction bound to serum would be transferred more readily to
other tissues.  Several factors that combine to maintain the level of lead
in the blood include the initial dose of lead, the tl/2 of the compartments
in the blood, and the ti/2 of the various compartments perfused by the
blood.  From the results reported in dogs (44) after 20 days the level in the
blood fell to an estimated 5.8 percent of the level at the time of injection
and, after an additional 260 days, further fell to approximately 2.5 percent.
This fact demonstrates the persistence of lead once it is taken internally.

     The distribution of lead in the various tissues at any one time after a
dose of lead depends on the perfusion of the tissue, the fraction in the
blood that is diffusable, and the t-j/2 of the perfused tissues.  Concentra-
tion of lead in -different tissues demonstrate remarkable variations.  Gen-
erally, lead is concentrated in bone, liver and kidney tissues—concentra-
tions as much as 100 times greater than in plasma or muscle.  In a calf
analyzed 42.5 hours after injection with lead, 34 percent of the total body
burden was found in the liver, 33 percent in the bone, and 21 percent in the
blood (46).  In rabbits 96 hours after injection, 21 percent of the lead was
found in the liver, 70 percent in the bone, and one percent in the blood (45).
The kidney concentrates lead but, because of the relative weight, contains
appreciably less of the total body burden.  A publication reported data for
a calf that consumed a daily average of 0.1 mg of lead for 169 days (47).  If
one assumes total body ratios of .04 for blood, .04 for bone, and .03 for
liver, one can estimate that approximately 80% of the total body burden is
located in bone and 5 percent in the liver.  At low intake levels and after
a sufficient length of time, an equilibrium is reached where excretion equals
intake.  Then the concentrations in the various compartments do not change,
and that compartments (bone for lead) with the longest t-j/2 will contain an
appreciable amount of the total body burden.  The t-|/? for bone in dogs was
estimated to be 7500 days (48).  In contrast a t-j/2 of blood was estimated to
be 3.5 days(42).

     Lead absorbed by the gastrointestinal tract can be excreted via four
routes:  (1) glandular excretion and epithelial shedding of the gastro-
intestinal tract, (2) biliar excretion, (3) urinary excretion, and (4)
mammary glandular excretion (36).

     The relative importance of these routes is unknown for many animals.
After intravenous injection of lead, the ratio of the fecal (i.e., the sum
of the glandular excretion and epithelial shedding) to total excretion can
be computed.  In the dog this ratio is approximately 0.65  (44); in sheep over
a 10 day collection period the ratio was 0.84 (36).  The discrepancies between
this ratio for dogs and sheep may be due to the fact that the dose of lead
received by the dog (44) was much less on a per weight basis than that re-
ceiyed by the sheep (37) or due to differences in the metabolism of lead.
Toxic doses of lead may change excretory functions and result in changes of
excretory pathways.  For example, when cadmium causes renal damage, cadmium
excretion increases (36).

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     Mammary gland excretion is much less than urinary excretion.   From data
collected 6 days in one cow (46),  the mammary gland excretion  was  10 percent
of the value for urinary excretion.

     Combining the data from sheep (37)  and cow (46),  one can  compute a crude
excretion ratio:  fecal excretion--83.6  percent;  urinary excretion--14.8
percent; and mammary excretion--!.6  percent.
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                                  Section V

                  LESIONS ASSOCIATED WITH LEAD INTOXICATION


     The functional and pathological effects quoted in the literature are
quite irregular and variable for man and various species of animals.

ANEMIA

     When the synthesis of RBCs and their components is decreased anemia
occurs.  In most cases of lead intoxication, anemia is not a predominating
clinical sign; however, the toxic effects of lead have motivated research to
understand porphyrin metabolism which is controlled by several  enzymes (49).
The list of enzymes that lead inhibits or enhances is impressive.  Many of
these effects are demonstrable in vitro only, and in some instances,  at
concentrations that never have been observed in clinically ill  individuals
(49).

     Heme synthesis may be briefly outlined as (2):

                            ALA synthetase (ALAS)
     Succinyl CoA + Glycine 	y 6_amino Ievu1inic    (1)

     acid (ALA)

         ALA dehydrase
     ALA 	> porphobilinogen (PBG)

     PBG 	»• uroporphybinogen III (URO III)                 (3)

             urogenase
     URO III 	> coproporphybilinogen III (coproIII)          (4)

               coprogenase
     Copro III 	-*• protoporphyrin IX (proto IX)             (5)

              Heme synthetase
     Proto IX 	> Heme                                    (6)

     Steps (1), (2), (3 or 4), (5) and (6) have been demonstrated to be
inhibited by lead (2, 49).  Overt clinical lead poisoning is accompanied
by increased ALA and coproporphyrin in the urine and blood (50).  _In_
vitro studies suggest that steps (2) and (5) are most sensitive to lead
inhibition (47).  Depressed ALA dehydrase activity in erythrocytes and


                                     11

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elevated urine and serum ALA have been observed in cattle chronically
poisoned (51).  In addition to inhibiting heme synthesis lead apparently
suppresses globulin synthesis (49).

     Other anemia-related abnormalities that have been observed in man and
animals include:

     1.   Shortened survival of RBCs (52)
     2.   Reticulocytosis (2,33,53)
     3.   Decreased hemoglobin (53,  54, 55)
     4.   Basophilic stippling of RBCs (2)
     5.   Siderocytosis (54)
     6.   Increased osmotic and mechanical fragility (2,49)
     7.   Loss of intracellular K+ ions (49)
     8.   Immature forms of RBCs in  general circulation (33)
     9.   Erythroid hyperplasia of the bone marrow (54)
     10.  Mitosis of erythrocytes in the peripheral  blood in fowl  (22,56).

     Basophilic stippling, often mentioned as a symptom of lead poisoning,
is due to accumulations of cytoplasm and nuclear fragments along with non-
heme iron in developing erythrocytes (2).  In general, the anemia associated
with lead poisoning is not severe and is difficult to distinguish from
anemia due to other causes.

NEPHROPATHY

     In man, renal insufficiency is  a late sequela of lead poisoning (1,2,54).
The pathogenesis of renal insufficiency is not clearly defined (2) and
apparently occurs in those individuals who are exposed to lead over long
periods of time (1,2,54).  Lead-induced renal  insufficiency is characterized
by glycosuia and hyper-amino aciduria (2, 54).In addition to amino aciduria
and glycosuria extreme exposure can  cause hypophosphatemia and hyperphospha-
turia (Fanconi syndrome) (2).  Uric  acid excretion sometimes is reduced
causing saturine gout (2).

     Most clinical findings point to renal tubular dysfunction.  Electron
microscopic and biochemical studies  demonstrate alterations in mitochondrial
structures and cellular oxidation processes (58,59).   The enzymes, alkaline
phosphatase, carbonic anhydrase, ATPases, and cytochrome oxidase all inhib-
ited by lead (49)--are known or suspected of being involved in renal tubular
transport mechanisms (60).  The most consistent lesion associated with lead
poisoning is intranuclear inclusion  bodies of the proximal tubules. *These
inclusions, believed to be lead protein complex (61), are reported in various
species of mammals and birds dying of lead poisoning (22,56,62,63,64).
Although cloudy swelling and degenerative changes of the tubules can be
observed, those conditions are usually mild and inconspicuous  (15,65).
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In summary, the significance of renal insufficiency in lead poisoning of
domestic animals is unknown and has not been described, probably because
domestic animals are not exposed to lead long enough for renal  insufficiency
to be observed.

NERVOUS SYSTEM

     Symptoms of central nervous system dearrangement predominate in most
diagnosed cases of lead poisoning.  In man acute encephalopathy due to lead
intoxication is characterized by rapid onset of seizures, often followed by
coma.  In acute encephalopathy (2) vascular injury is the lesion most often
associated with edema of the brain.  In contrast, patients with chronic
encephalopathy develop progressive mental deterioration with loss of motor
control (2).  The etiology of chronic encephalopathy is not clear and may be
due to several other factors.

     Encephalopathy dominates in most diagnosed cases of lead poisoning in
domestic animals.  Apparently, as in man, vascular injury is the initiating
lesion (55).  In cattle, brain lesions progress from a prominence of endo-
thelial cells of the capillaries to the development of edema foci and neuro-
nal degenerative changes.  These focal lesions develop a laminar pattern
accompanied by enlargement of astrocytes.  Chronically ill animals develop
lesions in the tips of the gyri, accompanied by capillary endothelial prolif-
eration, astrocytic proliferation, spongy degeneration, neuronal necrosis,
cavitation due to loss of cells, and capillary proliferation in these areas.

     In dogs, the reported lesions are similar to those in cattle (66).
Damage to the small vessels include necrotic endothelium, usually associated
with laminar necrosis in the cerebral cortex.  Gliosis and capillary prolif-
eration are observed in the chronically ill.  In per acute cases, significant
lesions may not be observed (67).

Lesions of the central nervous system are not severe in birds.   Chickens
tolerate relatively high doses of lead (68), and CNS lesions are not well
defined in the literature.  Geese  experience cerebral edema with serious
fluid accumulation in the spaces of Virchow-Rubin (69).  However, routine
staining procedures failed to demonstrate any significant lesions in poisoned
ducks (22).

PERIPHERAL NEUROPATHY

In man, peripheral neuropathy is observed and characterized by motor involve-
ment with no sensory nerve aberrations.  Chronically poisoned experimental
animals develop segmental demyelination of some nerve fibers (2).  Electro-
physiological studies of poisoned baboons revealed no abnormalities of nerve
conduction (70).  Horses with lead poisoning exhibit signs of severe inspira-
tory dyspnea (4), possibly having the same histological basis as peripheral
neuropathy observed in man (15).
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                                 Section VI

          OTHER FUNCTIONAL EFFECTS ASSOCIATED WITH LEAD POISIONING


     Numerous organ-systems reportedly (2)  impaired by lead intoxication
include:

     1 .    Decreased iodine uptake
     2.    Decreased gonadotrophic hormones
     3.    Abnormal  function of the pituitary-adrenal  axis
     4.    Myopathy of skeletal muscles
     5.    Cardiac arrhythmias
     6.    Decreased fertility
     7.    Abnormal  serum albumins and serum  globulin  levels (54)
     8.    Elevated serum cholesterol  levels  (54)

     As in man, a variety of abnormalities  have been  reported in  domestic
and experimental animals.  Apparently lead  is immuno-suppressive  evidenced
by reduced lysozyme in dogs poisoned  with lead (54).   Lead decreases the
resistance of mice to Salmonella typhimurium (71), in addition to decreasing
the number of splenic cells producing both  Igm and IgG antibodies (72).   Lead
poisoning in the dog produces acidophilic intranuclear inclusion  bodies  in
the liver.  Liver function tests reported in dogs (73) and cattle (55) occa-
sionally indicate elevated levels of  some enzymes (e.g., serum glutamic
oxalacetic transaminase, serum pyruvic transaminase,  and ornithine and
carbamyl transferase).

     The gastroenteritis associated with lead intoxication varies from no
lesions in cattle (15) to severe lesions in  sheep (29).  One dog  experienced a
perforated gastric ulcer with lead poisoning (74).  In another report, 24
percent of poisoned cattle had some form of  gastroenteritis (17).

     Abnormal changes in bony tissue  have been reported in horses suffering
from lead poisoning (63).  Their lesions included edematous synovia!, mem-
branes,  erosion of joint surfaces, and exostosis.  Radiographs of experi-
mental  poisoned dogs demonstrated radio-opaque lines  of the distal radii and
thoracic spines (73).    One study of  the interactions of lead, zinc, cadmium
in pigs(75) reported radio-opaque lines in  the metaphysis.  Other changes
associated with lead poisoning include chromosome damage (76), abortion
(76,77), reduced fertility (76), and  endocardia!  and  epicardial hemorrhages
(16).

     The relative frequency of the lesions  and reported functional effects
are unknown and probably vary widely  even within species.  One report (17)


                                     14

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lists the frequency of gross lesions in cattle as:   gastroenteritis  (24
percent), petechiation of the epicardium and myocardium (21  percent),  pulmo-
nary congestion (16 percent), and degenerative changes of the kidneys  (16
percent).  Other lesions with reported frequencies  of less than  10 percent
are:  fatty liver, pale muscles; petechiation of subcutaneous tissue,  thymus,
and trachea; cystitis; opaque cornea; ocular hemorrhage;  edema and hyperemia
of the brain; and swollen mesenteric lymph nodes.

     The lesions reported in ducks and geese poisoned with lead  contrast
sharply with that reported in mammals.  In ducks the most notable  lesions
are atrophic pectoral muscles and emaciation with  loss of fat deposits (22).
Other lesions include impaction of the proventriculus, small  spleen, and
vacuolization of hepatic cord cells.  In addition  to the  lesions reported in
ducks, geese, experience marked cephalic edema involving  eyelids,  submandibu-
lar region, and the brain (69).
                                     15

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                                Section VII

             TOXIC LEVELS  OF  LEAD  FOR VARIOUS SPECIES OF ANIMALS
     The toxic and/or lethal  levels of  lead, listed in Table 2 by species of
animals, reported in the literature vary widely.

                                Table 2

                   TOXIC LEVELS  OF LEAD  (ORAL DOSE)
Species
Cattle




Reference
29
29
29
29
4
Comments
Single lethal dose for calves
200-400 mg/kg B.W.
Single lethal does for adult cattle
600-800 mg/kg B.W.
Adult cattle will tolerate 6 mg/kg
B.W. /day for 2-3 years
Adult cattle will tolerate 250 ppm
of lead in ration for 2-3 years
6mg/kg/day (equivalent to 275 ppm
Horses
                   35
81


35
in the ration) is minimal  chronic
fatal dose.

5 out of 8 animals died grazing
pasture containing a median of 516 ppm
of lead

5 out of 15 animals died and an
additional 5 were symptomatic grazing
pasture containing 350 ppm.

1 out of 6 cows died after consuming 5
mg/kg B.W./day for 69 days.

2 out of 2 horses died grazing pastures
with median concentration of 516 ppm.
                                     16

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                    4              2.4 mg/kg/day equivalent to 150 ppm in
                                   ration is the minimum chronic fatal
                                   dose (for 6 months)

                   78              4 out of 9 animals died and an additional
                                   2 were symptomatic when grazing pastures
                                   for 4 months containing 200-840 ppm.

                   56              5 out of 6 young horses and 1  out  of  22
                                   older animals were symptomatic when
                                   grazing pastures containing 38, 90
                                   and 246 ppm.

Sheep              79              2 out of 2 sheep apparently normal  for'
                                   45 days consuming 5  mg/kg/day.

                   79              2 out of 2 pregnant  animals aborted
                                   and died on 59th and 106th  day
                                   consuming 9 mg/kg/B.W./day

                   29              1 out of 1 pregnant  sheep aborted  when
                                   consuming 1 mg/kg B.W./day  for 50  days.

                   29              1 out of 1 died when consuming 8 mg/kg
                                   B.W./day for 220 days.

                   76              10 out of 10 were asymptomatic for 26
                                   weeks consuming 4.5  mg/kg B.W./day

                   82              4 out of 4 were symptomatic when
                                   consuming 100 mg/kg  B.W./day for 30
                                   days.

Dog                67              3 mg/kg B.W./day for 180 days produces
                                   symptoms

                   67              10-30 mg/kg B.W./day produces symptoms
                                   from 13th day

                   67              600 mg/kg/day for 2  days is lethal

                   73              Consuming 100 ppm in the ration produces
                                   symptoms

Poultry            80              100 ppm of PbAC in ration for 4 weeks
                                   asymptomatic

                   80              1000 ppm in the ration for  4 weeks
                                   depressed weight gains

                   56              2000 ppm in the ration for  3 weeks
                                   asymptomatic

                                     17

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                   56              5000 ppm in  ration  for 3  weeks  produced
                                   necrosis of  renal tubules

                   68              Feeding 160  mg/kg/day for 35  days
                                   asymptomatic

Ducks              22              10 out of 10 developed symptoms after
                                   consuming eight #6  lead shot.

                   83              Consuming 6  mg/kg B.W./day for  137
                                   days was asymptomatic

                   83              Consuming 8-12  mg/kg  B.W./day had
                                   average survival times of 28  and 25
                                   days.

Fish               19              Toxic  or lethal  levels vary widely
                                   depending on the kind of  water  and
                                   length of exposure.   Vary from  0.01
                                   to 63  ppm.

Other aquatic
life               19              Toxic  levels for daphnia  and  cyclops
                                   varied from  0.01 to 128 ppm.


     The fatal or minimal  toxic doses reported  in  the  literature are
difficult to interpret.  From Table 2, assuming a  safety factor  of 2-3,
older cattle should tolerate 2 mg/kg B.W./day or 80-100  ppm  in the
ration for 2 to 3 years.   Sheep should tolerate 10 mg/kg B.W./day  or,
assuming that sheep consume approximately 3 percent of their body  weight
per day, they should tolerate 50 ppm of their ration for approximately
one-half year.  However,  pregnant sheep have aborted at  these levels  (29).
Assuming a horse consumes  2.1 percent of  its body  weight per day,  1.0 to
1.2 mg/kg B.W./day or 40-50 ppm in the ration for  time periods of  less
than one-half year should  be tolerated.  These  implied safe  levels were
computed by making several  assumptions; consequently,  less subtle  effects
could be observed at levels of lead intake lower than  these.
                                    18

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                                Section VIII

                        SIGNS, SYMPTOMS AND DIAGNOSIS


     The diagnosis of lead poisoning depends on identifying these factors
(14):

     1.   Opportunity for exposure and the sources.
     2.   Symptoms compatible with lead poisoning.
     3.   Concentrations of lead in fluids, tissues, and organs of intoxi-
          cated animals and concentrations of lead  in the source.
     4.   Gross and microscopic lesions compatible  with lead poisoning.

     In some extreme instances, test animals may have to be exposed to  the
source to determine effects of that particular lead  concentration.

SIGNS AND SYMPTOMS

     The gross symptoms observed in lead poisoning  of domestic animals
result from disturbances of the gastrointestinal tract and central  nervous
system.  Most cases of intoxication are acute or subacute; consequently,  the
course of the disease will be short, about 2-3 days  (14).

Cattle

     Experimental evidence collected in young calves indicates that 2-3 days
after exposure symptoms will be observed; however,  this time interval  is
modified by initial dose (24).  In fatal cases, the  first symptoms observed
may be impressive; uncontrolled vocalization, extreme ataxia,  nystagmus,
excessive salivation, sudden collapse, and death (29).  Generally lack  of
appetite with diarrhea and constipation will be observed.  In  some instances
marked anemia is observed.

     The frequency of some symptoms for cattle have  been reported as (17):

     1.   Blindness                51%
     2.   Excessive salivation     45%
     3.   Muscular twitching       33%
     4.   Hyperirritability        33%
     5.   Convulsion               32%
     6.   Depression               32%
     7.   Grinding teeth           24%
     8.   Ataxia                   18%
                                     19

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     9.   Circling                 16%
     10.  Bellowing                13%
     11.  Diarrhea                 10%
     12.  Pushing against objects  10%

SHEEP

     Generally, the symptoms of sheep contrast with those seen in cattle;
rather than excitement, depression often is reported (30).  Progressive
anorexia, in addition to constipation and diarrhea (29), lethargy and ataxia
are typical symptoms.

HORSES

     Inspiratory dyspnea, "roaring" after exercise, is the most often
reported symptom of horses (4,84).  Pharyngeal paralysis with regurgitation
also occurs, and severe cases evidence ataxia, paralysis, and clonic convul-
sions  (84).

DOGS

     Symptoms for dogs are similar to those reported for cattle including
excessive salivation, uncontrolled jaw movements, hyperesthesia of the skin
and recumbency with pedal movements (67).  Onset may be very rapid with
apparent recovery from an acute episode following by vomiting (67).  Pharyn-
geal paralysis also is reported (30).

DUCKS AND GEESE

     Severe weight loss, marked weakness, and atrophy of pectoral muscles
are usually reported in ducks and geese (22,69).  Cephalic edema and charac-
teristic high pitched vocalizations in geese, contrast with that reported in
ducks  (69).

FISH

     Fish residing in fresh water containing lead ions develop a coagulated
film of mucous over the entire body, particularly noticeable over the
gills (2).   This condition frequently occurs in fish exposed to other heavy
metals.
                                     20

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                                 Section IX

                  CLINICAL PATHOLOGY AND CHEMICAL ANALYSIS


     Many of the clinical pathologic observations noted with lead poisoning
are associated with the development of anemia.  Cattle experience  hemoglobin
levels of 5 gm/100 ml and packed cell volumes of 20 percent(55)  as well  as
elevated reticulocyte counts (19,55).  Serum glutamic oxalacetic transaminase
and serum glutamic pyruvic transaminase are elevated (73); however, in some
instances these enzymes are not elevated (55).  Increased prophyrins in  the
urine seemingly is an inconsistent finding (53).  Delta-amino levulinic  acid
(D.A.L.A.) in the serum and urine of man becomes elevated before the appear-
ance of symptoms (2).  In cattle(49) and sheep(85) elevated D.A.L.A. has been
reported.  Stippling of red blood cells often is reported; however, condi-
tions other than lead intoxication cause stippling of dog RBCs (86).  A  count
of 15 or more stippled cells per 10,000 may suggest lead poisoning.  Other
findings reported in intoxicated animals include: lead lines in  the meta-
physes and epiphyses of the radii (33,63,73) and epithelial  casts in urine
sediment (19).

     Chemical analysis of fluids, tissues, and sources is the most frequently
used method to support the clinical diagnosis of lead poisoning.   Kidney,
liver, and blood tissues often are analyzed for lead content. Ten, 20,  and
0.35 ppm in the liver, kidney, and blood respectively are levels indicative
of lead poisoning (4,30).  Others suggest 50 ppm in the kidney cortex and 10
ppm in the liver as significant (29).  Levels considered significant in  the
dog are:  blood (35 yg/100 ml); urine (75 yg/liter); hair (88 yg/gram);  and
liver (3.6 yg/gram)(87).

     The antemortem diagnosis of lead poisoning in domestic animals probably
is not as crucial as for human beings.  Primarily because the course of  the
disease is more acute and a few animals will have succumbed before the
problem becomes evident.  The differential diagnosis should include any
disease of the central nervous and gastrointestinal system (17).
                                     21

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                                 Section X

                                 TREATMENT
     Because of the acute nature in most domestic animals, the treatment
generally is disappointing.   The treatment regimen may include (85):

     1     Sedation for convulsive seizures.
     2.   Small oral  doses of magnesium sulphate.
     3.   Parenteral  or forced feeding
     4.   Ethylenediaminetetracetate (EDTA).

     The recommended  dosage of EDTA varies.   Some recommend a 12.5 percent
solution given at the rate of 1.0 g/30 Ib (13.6 kg/day)  (84).  The dose
should be divided in  two doses given intravenously and very slowly.   The
dose can be repeated  until symptoms improve.   Others  suggest a 10 percent
solution given intravenous at 1.0 gm/30 Ib (13.6 kg)/day limiting the total
dose to 5 gm/30 Ib (13.6kg)  per week suspended for one week after 7.5 gm/30
lb(13.6kg) has been given.  Toxic signs include accelerated heart and respir-
atory rates with muscular tremors (84).
                                    22

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     Feedlot Cattle.  Jour. Am.  Vet.  Med. Ass.   155(12):1892-1903.
     1969.

66.  Zook, B. C.  The Pathologic  Anatomy  of Lead  Poisoning in  Dogs.
     Vet. Path. 9(5):310-327.  1972.

67.  Robertson, C. M.  A Case of  Acute Lead Poisoning in  a Dog.  Vet.
     Rec. 86:195-196.  1970.
                                     27

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68.  Vengris, V. E. and C. J.  Mare.   Lead Poisoning in  Chickens  and  the
     Effect of Lead on Interferon and Antibody Production.   Can.  J.
     Comp. Med. 38:328-335.  1974.

69.  Bagley, L. N. and L.  N.  Locke.   Lead Poisoning in  Canada  Geese  in
     Delaware Avian Dis. 11:601-608.   1967.

70.  Hopkins, A.  Experimental  Lead  Poisoning in  the Baboon.   Br.  J.
     Ind. Med. 27:130-140.  1970.

71.  Hemphill, F. E., M. L. Kaeberle  and W.  B.  Buck.   Lead  Suppression
     of Mouse Resistance to Salmonella typhimurium.   Science.   172:1031-
     1032.

72.  Keller, L. D. and S.  Kovacic.   Decreased Antibody  Formation  in  Mice
     Exposed to Lead.  Nature 250:149.  1974.

73.  Stowe, H. D., R. A. Groyer, M.  M. Krigman, M.  Wilson and  M.  Gates.
     Experimental Oral Lead Toxicity  in Young Dogs.   Arch.  Path.  95(2):
     106-116.  1973.

74.  Sass, B.  Perforating Gastric Ulcer Associated with Lead  Poisoning
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75.  Hsu, Frank Shin-Yun.   Lead, Zinc, and Calcium  Interation  in  Growing
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76.  Carson, T. L., G. A.  Van Gelder, W. B.  Buck, and L. J.  Hoffman.
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78.  Egan, D. A. and T. O'Cuill.  Cumulative  Lead Poisoning  in Horses in
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     1970.

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     198-203.  1967.
                                     28

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82.  Van Gelder, G. A., T. Carson, R. M. Smith, and W.  B.  Buck.   Behavioral
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                                    29

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                                   TECHNICAL REPORT DATA
                            (Please read Instructions on the reverse before completing)
 1. REPO
      M-600/3-77-009
                              2.
                                                           3. RECIPIENT'S ACCESSION>NO.
 4. TITLE AND SUBTITLE
     THE SHORT-TERM   EFFECTS  OF LEAD ON DOMESTIC
     AND WILD ANIMALS
                              5. REPORT DATE
                                 January 1977
                              6. PERFORMING ORGANIZATION CODE
 7. AUTHOR(S)

     R.P. Botts
                                                           8. PERFORMING ORGANIZATION REPORT NO
 9. PERFORMING ORGANIZATION NAME AND ADDRESS
     Corvallis Environmental  Research Laboratory
     Corvallis, Oregon 97330
                               10. PROGRAM ELEMENT NO.

                                  1AA602	
                               11. CONTRACT/GRANT NO.
 12. SPONSORING AGENCY NAME AND ADDRESS
     Corvallis Environmental  Research Laboratory
     200 S.W. 35th St.
     Corvallis, Oregon 97330
                               13. TYPE OF REPORT AND PERIOD COVERED
                                in-house,  literature review
                               14. SPONSORING AGENCY CODE
                                                              EPA-ORD
 15. SUPPLEMENTARY NOTES
 16. ABSTRACT
  Small quantities  of  lead,
  all species of  plants  and
  reportedly intoxicated by
a ubiquitous and  toxic  element, may be found
animals.  The  list  of animals, both domestic
lead is impressive.
   in  practically
   and wild,
  The sources of  lead  poisoning vary with species of  animals.  Lead base paints,  used
  motor oils, spend  lead  shot and pastures contaminated  by lead smelters seemingly have
  been most often  incriminated.  The lesions associeated with  lead intoxication  may vary
  widely both within and  between species of animals.   Lesions  and symptoms of  the centra
  nervous system  are the  most prominent.  Toxic levels for various species as  reported
  in the literature  vary  widely and seemingly a single toxic dose for each species, as
  yet, has not been  definitely established.

  The diagnosis and  treatment of lead intoxication may become  laborious and  time consum-
  ing.  Most sysmptoms, reported involve central nervous system dearrangement.   Treat-
  ment of most clinical cases is disappointing generally because of the acute  nature of
  lead poisoning.
 7.
                                KEY WORDS AND DOCUMENT ANALYSIS
                  DESCRIPTORS
                                              b.lDENTIFIERS/OPEN ENDED TERMS
                                                                         c. cos AT I Field/Group
  animal  diseases
  lead poisoning
  animal  nutrition
  veterinary medicine
                   lead  poisoning in wild
                      and  domestic animals

                      sources and effects
                      of lead poisoning in
                      animals
   02/E
   06/F,T
 B. DISTRIBUTION STATEMENT


  RELEASE TO PUBLIC
                 19.
                                This Report)'
21. NO. OF PAGES
                                                 35
                                              20. SECURITY CLASS (This page)
                                                UNCLASSIFIED
                                            22. PRICE
EPA Form 2220-1 (9-73)
                                            30

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