EPA-540/1-86-021
                      Agency
Office of Emergency and
Remedial Response
Washington DC 20460
Off'ce of Research and Development
Office of Health and Environmental
Assessment
Environmental Criteria and
Assessment Office
Cincinnati OH 45268
                      Superfund
xvEPA
                       HEALTH EFFECTS  ASSESSMENT
                       FOR BARIUM

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                                           EPA/540/1-86-021
                                           September 1984
       HEALTH EFFECTS  ASSESSMENT
                FOR  BARIUM
    U.S. Environmental  Protection  Agency
     Office of Research and  Development
Office of Health  and  Environmental Assessment
Environmental Criteria  and Assessment  Office
            Cincinnati,  OH  45268
    U.S. Environmental  Protection  Agency
  Office of  Emergency and Remedial Response
Office of Solid Waste and  Emergency  Response
            Washington, DC  20460

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                                  DISCLAIMER

    This  report  has  been  funded  wholly  or  1n  part by  the  United  States
Environmental  Protection  Agency under  Contract  No.  68-03-3112  to  Syracuse
Research Corporation.  It has been  subject  to  the Agency's peer and adminis-
trative review, and  It has  been  approved  for  publication as an EPA document.
Mention of  trade  names or  commercial  products  does  not  constitute  endorse-
ment or recommendation for use.
                                      11

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                                    PREFACE
    This report  summarizes  and evaluates Information  relevant  to a prelimi-
nary  Interim  assessment  of  adverse health  effects associated  with barium.
All  estimates  of  acceptable  Intakes and  carcinogenic potency  presented  1n
this  document  should  be  considered   as  preliminary  and  reflect  limited
resources  allocated  to  this  project.   Pertinent  toxlcologlc   and  environ-
mental data were located  through  on-Hne  literature searches  of the Chemical
Abstracts,   TOXLINE,  CANCERLINE  and  the  CHEMFATE/DATALOG  data  bases.   The
basic  literature   searched   supporting   this   document   1s   current  up  to
September,   1984.    Secondary  sources of  Information  have  also  been  relied
upon  1n  the  preparation of  this  report  and  represent  large-scale  health
assessment   efforts  that  entail   extensive  peer   and  Agency   review.   The
following  Office of Health  and Environmental Assessment  (OHEA)  sources  have
been extensively utilized:


    U.S.  EPA.   1980b.   Mini-Reviews on  the  Cardnogenidty,  Mutagenlc-
    1ty,  Teratogen1c1ty  and  Chronic  Tox1c1ty   of  Selected  Compounds.
    Environmental   Criteria   and   Assessment  Office,   Cincinnati,  OH.
    Internal draft.

    U.S.  EPA.  1983b.  Reportable  Quantity for  Barium.   Prepared by the
    Environmental  Criteria  and  Assessment Office,  Cincinnati,  OH, OHEA
    for  the  Office of Solid  Waste and Emergency  Response,  Washington,
    DC.

    The Intent 1n  these assessments  Is  to  suggest  acceptable  exposure  levels
whenever  sufficient data  were available.   Values were not derived or  larger
uncertainty factors were employed  when  the  variable data  were  limited  In
scope tending to generate conservative  (I.e., protective)  estimates.  Never-
theless,  the  Interim  values  presented  reflect  the  relative degree of  hazard
associated  with  exposure or  risk to the chemlcal(s) addressed.

    Whenever possible, two categories of  values  have  been  estimated for  sys-
temic toxicants  (toxicants for which cancer  1s  not  the endpolnt of concern).
The  first,  the  AIS or  acceptable  Intake  subchronlc,  1s  an  estimate of  an
exposure level  that  would  not  be  expected  to cause  adverse   effects  when
exposure  occurs  during  a limited  time  Interval  (I.e., for an  Interval  that
does not constitute a  significant  portion of  the Hfespan).    This type  of
exposure estimate  has not  been  extensively  used  or  rigorously  defined,  as
previous   risk  assessment  efforts  have  been   primarily  directed  towards
exposures from toxicants  In  ambient air or water where  lifetime exposure  1s
assumed.    Animal  data  used   for  AIS estimates  generally Include  exposures
with durations of  30-90 days.  Subchronlc human data are rarely available.
Reported  exposures   are usually  from chronic  occupational  exposure situations
or from reports  of  acute accidental exposure.
                                      111

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    The  AIC,  acceptable  Intake  chronic,   1s  similar 1n  concept  to  the  ADI
(acceptable  dally  Intake).   It  1s  an estimate  of an  exposure  level  that
would  not  be expected  to cause  adverse effects  when  exposure occurs  for  a
significant  portion  of  the Hfespan  [see  U.S.  EPA  (1980a)  for a discussion
of  this  concept].   The  AIC  1s  route specific   and  estimates   acceptable
exposure  for a  given  route with  the  Implicit  assumption that  exposure  by
other routes 1s Insignificant.

    Composite  scores  (CSs)  for  noncardnogens  have  also  been  calculated
where data  permitted.   These  values  are used for  ranking  reportable quanti-
ties; the methodology for their development 1s explained  1n U.S. EPA (1983a).

    For  compounds for which there  Is  sufficient  evidence of  carcinogenldty,
AIS  and AIC values  are  not derived.   For a  discussion of risk assessment
methodology  for  carcinogens refer  to U.S. EPA  (1980a).  Since  cancer  Is  a
process  that  1s  not characterized by a threshold,  any  exposure  contributes
an  Increment of  risk.   Consequently,  derivation of  AIS  and  AIC values would
be  Inappropriate.   For  carcinogens,  q-]*s  have been  computed  based  on  oral
and Inhalation data 1f available.
                                      1v

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                                   ABSTRACT
    In  order  to  place  the  risk  assessment  evaluation  1n proper  context,
refer  to  the preface  of  this  document.  The  preface  outlines  limitations
applicable to all documents of  this  series as  well  as the appropriate Inter-
pretation and use of the quantitative estimates presented.

    An oral AIC of  3.6  mg/day  has  been  estimated for barium based on a LOAEL
of  100  mg Ba/a,  1n  drinking water.   This estimate  1s  based primarily  on a
rat study  showing an  Increase  1n systolic blood  pressure following consump-
tion of water  containing  100 mg Ba/a.   The  data used for  this  estimate are
limited and  new  data  should be  evaluated when  available.   Data  were Inade-
quate for development  for estimation of an oral AIS for barium.

    A CS  of  45  was associated  with shortened Hfespan  1n  male  mice treated
with Ba+2 in the drinking water.

    An AIS and AIC  for Inhalation  exposure have  been estimated  as  0.098 and
0.01 mg/day,  respectively.  These  estimates   are  based  on  an  animal  study
showing reproductive  effects  1n rats  following exposure to 3.62  mg Ba/m3.
Appropriate  human   data  addressing  reproductive Issues  are not  available.
Corroborating animal studies are also unavailable.    The  data base  for these
estimates  1s considered   extremely  limited.    The  AIC   1s  well  below  the
recommended TLV for occupational exposures, reflecting concern  for  potential
reproductive effects.

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                               ACKNOWLEDGEMENTS
    The  Initial  draft  of  this  report  was  prepared  by Syracuse  Research
Corporation under  Contract No.  68-03-3112  for  EPA's  Environmental  Criteria
and  Assessment  Office,  Cincinnati,  OH.   Dr.  Christopher  DeRosa and  Karen
Blackburn were the Technical Project Monitors  and  Helen Ball  was the Project
Officer.  The final documents  1n  this  series  were  prepared for the Office of
Emergency and Remedial Response, Washington, DC.

    Scientists from  the  following U.S. EPA offices  provided  review  comments
for this document series:

         Environmental Criteria and Assessment Office, Cincinnati, OH
         Carcinogen Assessment  Group
         Office of Air Quality  Planning and Standards
         Office of Solid Waste
         Office of Toxic Substances
         Office of Drinking Water

Editorial review for the document series was provided by:

    Judith Olsen and Erma Durden
    Environmental Criteria and  Assessment Office
    Cincinnati, OH

Technical support services for  the document series  was provided by:

    Bette Zwayer, Pat Daunt, Karen Mann and Jacky Bohanon
    Environmental Criteria and  Assessment Office •
    Cincinnati, OH
                                      v1

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                         TABLE OF CONTENTS
1. ENVIRONMENTAL CHEMISTRY AND FATE 	
2. ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS .
2.1. ORAL 	
2.2. INHALATION 	
3. TOXICITY IN HUMANS AND EXPERIMENTAL ANIMALS 	
3.1. SUBCHRONIC 	
3.1.1. Oral 	
3.1.2. Inhalation 	 	
3.2. CHRONIC 	
3.2.1. Oral 	
3.2.2. Inhalation 	
Page
	 1
	 3
	 3
	 3
	 4
	 4
	 4
	 4
	 5
	 5
	 8
3.3.   TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS.


-3.4.
3.3.1. Oral 	
3.3.2. Inhalation 	
TOXICANT INTERACTIONS 	
4. CARCINOGENICITY 	
4.1.
4.2.


4.3.
4.4.
5. REGULi
HUMAN DATA 	
BIOASSAYS 	
4.2.1. Oral 	
4.2.2. Inhalation 	
OTHER RELEVANT DATA 	
WEIGHT OF EVIDENCE 	
VTORY STANDARDS AND CRITERIA 	
	 8
, 	 8
	 	 8
	 9
, 	 9
, 	 9
	 9
	 9
	 9
	 10
	 11
                                 V11

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TABLE OF CONTENTS (cont.)
6.
7.
APPE
RISK ASSESSMENT .... 	
6.1. ACCEPTABLE INTAKE SUBCHRONIC (AIS) 	
6.1.1. Oral 	
6.1.2. Inhalation 	
6.2. ACCEPTABLE INTAKE CHRONIC (AIC) 	
6.2.1. Oral 	
6.2.2. Inhalation 	
6.3. CARCINOGENIC POTENCY (q-|*) 	
REFERENCES 	
NDIX: Summary Table for Barium 	
Page
	 12
	 12
	 12
	 12
	 13
	 13
	 14
	 14
	 15
	 19
          V111

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                             LIST  OF  ABBREVIATIONS





ADI                     Acceptable dally Intake



AIC                     Acceptable Intake chronic



AIS                     Acceptable Intake subchronlc



bw                      Body weight



CAS                     Chemical Abstract Service



CNS                     Central nervous system



CS                      Composite score



DNA                     Deoxyr1bonucle1c add



GI                      Gastrointestinal



LOAEL                   Lowest-observed-adverse-effect level



MED                     Minimum effective dose



NOAEL                   No-observed-adverse-effect level



NOEL                    No-observed-effect level



RQ                      Reportable.quantity



RVjj                     Dose-rating  value



RVe                     Effect-rating value



SGOT                    Serum glutamlc oxaloacetlc transamlnase



SGPT                    Serum glutamlc pyruvlc transamlnase



TLV                     Threshold limit value
                                      1x

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                     1.   ENVIRONMENTAL CHEMISTRY AND FATE
    Barium 1s an alkaline-earth metal belonging  to  Group IIA of  the periodic
table.    Elemental  barium  has  a  CAS  Registry number  of  7440-39-2.   The
Inorganic chemistry  of  barium  consists  exclusively of  compounds  1n  the  2
valence  state.    Selected   physical   properties  of  a  few  environmentally
significant barium compounds  are given 1n Table 1-1.
    The following discussion  of  the  fate and  transport  of  barium  1n various
environmental media  Is  speculative and  1s  based on analogy  to  the environ-
mental  behavior of other metals and  the known  chemical  properties  of barium
and Its compounds.
    The  physical   sources  of  atmospheric   barium  are  probably  Industrial
emissions.   Barium  1s  likely  to be  present   In  partlculate  form  In  the
atmosphere.   Although  chemical   reactions  may  cause   spedatlon  of  the
chemical  In  air,  the main  mechanisms for the  removal  of barium  compounds  1n
the atmosphere  are  likely  to be  wet precipitation and  dry  deposition.   The
residence time of barium 1n  the  atmosphere  may be  several  days,  depending on
the partlculate size  and the  chemical nature of the partlculate.
    In aquatic media, barium 1s likely  to  be  present  primarily  as  suspended
partlculate matter or sediments.   The soluble  form  of  barium 1n  most aquatic
systems may  be controlled by  the  solubility product of barium carbonate.   In
the absence  of  any other  possible removal  mechanisms, the  residence time  of
barium 1n aquatic systems could be several hundred  years.
    In soils, barium  Is not  expected  to be  very mobile because of  Us forma-
tion of  water-Insoluble salts  and Us   Inability  to  form  soluble  complexes
with humic and  fulvlc materials.   Under acidic  conditions,  however,  some  of
the water  Insoluble  barium compounds may  become soluble and  move  back into
groundwater.
                                    -1-

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                                                 TABLE 1-1
                          Selected Physical Properties of a Few Barium Compounds3
Element/
Compound
Barium
Barium
carbonate
Barium
chloride
Barium
oxide
Barium
sulflde
Barium
sulfate
Atomic/
Molecular
Formula Weight
Ba 137.34
BaCOs 197.35
BaCl2 208.25
BaO 153.34
BaS 169.40
BaS04 233.40
Specific
Gravity/
Density
3.51 g/cm3
at 20°C
4.43
3.856 g/cm3
at 24°C
5.72
4.25 g/cm3
at 15°C
4.50 g/cm3
at 15°C
Water
Solubility
decomposes
2 mg/100 mab
at 20°C
37.5 g/100 mlb
at 26°C
3.48 g/100 mil
at 20°C
decomposes
0.222 mg/100 ml
at 18°C
Vapor Pressure
(mm Hg)
10 mm at 1049°C
NA
NA
NA
NA
NA
3Source: Weast, 1980
bThese data are for the alpha-lsomer
NA = Not available

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          2.  ABSORPTION FACTORS IN HUMANS AND EXPERIMENTAL ANIMALS
2.1.   ORAL
    Pertinent data regarding the absorption of barium  from  the  GI  tract  were
not located  1n  the available literature.  Systemic  toxic effects have  been
observed following oral  exposure,  Implying that  some  absorption does  occur.
McCauley and Washington  (1983) studied   the  absorption of  various  barium
salts  and  reported relative  absorption rates of  barium chloride >  barium
sulfate > barium carbonate.
2.2.   INHALATION
    Pertinent data regarding  the absorption  of  barium from  the  respiratory
tract  were  not  located 1n  the  available  literature.   Systemic toxldty  has
been observed  following  Inhalation exposure,  Implying that  some  absorption
does occur.   Gore and Patrick  (1982)   found  that,  1n rats,  Intratracheally
administered barium sulfate was concentrated  1n  the area  Immediately  beneath
the basement membrane within 24 hours and  remained  1n  this  area for  at least
7 days.
                                    -3-

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                3.  TOXICITY  IN  HUMANS  AND  EXPERIMENTAL  ANIMALS
3.1.   SUBCHRONIC
3.1.1.   Oral.  Tardlff  et  al.  (1980) administered  drinking water  contain-
ing  0,   10,   50  or  250  mg  Ba**/l  (as  barium  chloride)  to  groups  of  30
Charles  River rats of both sexes  for  4,  8  or 13 weeks.   The authors reported
that  these  concentrations  corresponded  to doses of  0,  1.7, 8.1  or  38.1  mg
Ba/kg bw/day  for  males  and  0, 2.1, 9.7  or  45.7  mg  Ba/kg bw/day for females.
The diet  supplied -0.5  yg  Ba/kg  bw/day.   There were  significant decreases
1n  the  relative  weights  of   the  adrenals   1n  males  1n  the  50  and  250  mg/8.
groups after  8  weeks,  but  not after 13  weeks, and  1n  the  females  In the 250
mg/8.  group  only  after   13  weeks.   Relative adrenal  weights  also  appeared
lower In  the  10 and  50  mg/J. females, but  these decreases  were  not statis-
tically   significant.   Relative  adrenal  weights  were higher  1n the  250 ppm
females   after 8  weeks.   The  significance  of   these  findings   1s  uncertain
since a  clear  dose  effect  or  dose duration  pattern  does  not  emerge..   The
authors   state  that  the differences  1n adrenal weights  did  not  appear  to  be
dose  related.   No adverse effects were observed  with   respect  to  food  con-
sumption, body  weight, clinical  signs, mortality,  hemoglobin levels, hemato-
crlt, red  cell  count, leukocyte  count,  prothrombln  time,  flbrlnogen,  serum
enzyme activities  (SGOT, SGPT),  blood  urea nitrogen,  serum sodium, potassium
or calcium, gross pathology,  or  hlstopathology.
3.1.2.   Inhalation.   Tarasenko  et  al.  (1977)  Investigated the  effects  of
Inhalation  exposure  to  barium   (as  barium  carbonate dust)  on  the  general
health  and  reproductive function 1n  male  and  female  rats.   Unspecified
numbers   of  male rats were exposed to BaCO_  dust  at  levels  of  5.2 and  1.15
                                            O
mg/m3, 4 hours/day  for  6  months.   The  animals In  the high-dose  group had
decreased body  weight,  changes  1n hematologlc  parameters,  decreased  clear-
ance  times  for  bromosulphthaleln  by  the  liver,  and  other "general  toxic

                                    -4-

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effects."  The  low-dose  animals  had no  observed  effects resulting  from  the


exposure.   In  the   reproductive   toxldty  evaluation  an  atmospheric  con-


centration   of   22.6   mg  BaCO_/m3   resulted   In   decreased  numbers   of
                                O

spermatozolds and  a  lower  percentage  of motile  sperm  forms  In  male  rats


exposed  for  one cycle  of  spermatogenesis  (dally duration  of exposure  not


reported).   Exposure of  females   to  13.4 mg  BaC03/m3  for  4 months  (dally


duration  of  exposure  not  reported)  resulted   1n  Increased  mortality  1n


subsequent  Utters  and  a general  underdevelopment  of  the newborn  pups.   No


systemic  effects  were   reported   for  the  female  rats   exposed  to  3.1  mg


BaCO_/m3,  but   this  exposure   level  did   produce   some  ovarian   follicle
    J

atresla.   Exposure  of   males  to  an  atmospheric  concentration  of  5.2  mg


BaCO_/m3,  4  hours/day   for  4  months  resulted  In  Increased  mortality  of
    
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    Animals exposed  to 1  ppm barium  for  1-16 months  showed no  changes  1n
average systolic  blood pressure.   Animals  exposed to  10 ppm barium  showed
small but  significant  (p<0.01)  Increases  1n mean  systolic blood  pressure  of
6, 7 and 4 mm Hg  over  controls  after  8,  12 and 16 months, respectively.  The
100  ppm  barium-exposed animals  had significant  Increases  1n mean  systolic
pressures   (p<0.001) which  averaged 12, 16  and 16 mm  Hg  after 1, 12  and  16
months, respectively.   Heart  physiology  and biochemistry was  evaluated only
1n  the  100 ppm barium-exposed  animals at  16  months.   These  animals  showed
depressed   rates  of   cardiac  contraction   and  depressed  electrical  excit-
ability.    In   addition,  cardiac  ATP,  phosphocreatlne  and  phosphorylatlon
potential  were decreased and AOP was Increased.
    U.S.  EPA (1985) considered  the  Increases 1n  systolic  blood pressure seen
following  exposure to  10 ppm  to  be not large  enough to constitute an adverse
health  effect   and  designated  the associated  dose,  0.51  mg/kg  bw/day,  a
NOAEL.  U.S.  EPA  (1985)   designated  the  dose  associated with  the  100  ppm
barium exposure,  5.1  mg/kg/day, a  LOAEL.   U.S.  EPA (1985) also  pointed  out
that  the  basal  level   of other  trace  metals,  particularly calcium,  supplied
to  animals throughout  the study  may have contributed  to  the  toxldty  of
barium.
    Brennlman  et  al.   (1979a,b,   1981)  Investigated the relationship between
barium concentrations  1n the  drinking  water and  Increased blood  pressure  and
mortality   1n   several  communities  1n  Illinois.   These  communities  were
divided  Into   high-exposure  (>2.0-10  mg  Ba/i)   and   low-exposure  (<0.2  mg
Ba/a,)  populations.   Communities with  populations >2500  1n  the 1970  census
were  chosen  for  comparison.   The  high-exposure  communities   (total  popula-
tion = 25,433)  had an average   of  7   mg  Ba/8.  1n  their  drinking  water,  and
the  low-exposure  communities  (total population =  46,905) had an  average  of
                                    -6-

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0.1  mg Ba/t.   For  comparison  of  blood  pressures,  1000   Individuals  (age
>18)  from  each community  were  tested.   Mortality  data  were  obtained  from
death  certificates.    No  significant   differences   In  blood  pressure  were
observed.   The  significantly  Increased  death  rate  among males  and  females
combined was  due  to  "all cardiovascular diseases,"  "heart  disease"  and  "all
causes."   When  analyzed  separately,   the  only  statistically  significant
differences were an  Increase  1n  deaths  from "all  cardiovascular diseases" In
males and  from  "all  causes"  In females.   The authors pointed out the follow-
ing confounding factors  to be  considered  In the evaluation  of their results:
1)  Inability  to control  for  use of home water  softeners,  2) movement 1n and
out   of   the  community,   3) high   variability   1n   barium   well   water
concentrations.
    Schroeder  and  Mltchener   (1975a) administered barium acetate at  a  level
of  5  mg Ba/a,  1n  the drinking water to Long-Evans  rats  for  their lifetimes.
Both  the   control  and  treated groups  consisted  of  52  male  and  52 female
animals.   The authors  considered   the  slight  changes observed,  growth  rate
(Increased  In older  females), longevity (Insignificant decrease  In  the  mean
of  the last  surviving  10% In both males  and  females),  gross  pathology and
hlstopathology, to have  no biologic significance.
    In  a  comparison  study,   Schroeder  and  Mltchener (1975b)  administered
drinking water  containing barium  acetate   (5 mg  Ba/l)  to groups of  42  male
and  36  female Swiss  mice for  their lifetimes.   Controls consisted of 54 mice
of  each sex.   No effect  was observed  on  body  weight,  gross  pathology or
hlstopathology.   Longevity,  defined as the  mean age  at  death  of  the  last
surviving  10%  of  animals, was  slightly  reduced  (p<0.025)  In  the  treated
males  (815 days vs.  920 days  for controls), but  the average age at death did
not differ between the  treated (548 days) and control (540 days) males.
                                      -7-

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3.2.2.   Inhalation.   Pertinent   data   regarding  the  chronic   Inhalation
toxldty of barium were not located 1n the available literature.
3.3.   TERATOGENICITY AND OTHER REPRODUCTIVE EFFECTS
3.3.1.   Oral.   Pertinent  data   regarding   the   teratogenldty  or  other
reproductive effects of  orally administered  barium  1n  humans  or  experimental
animals were not located 1n the available literature.
3.3.2.   Inhalation.   Pertinent   data    regarding   the  teratogenldty   of
inhaled  barium  In  humans  or  experimental  animals  were not  located 1n  the
available  literature.    Data  relating  to reproductive  function  in  experi-
mental animals have been included in Section 3.1.2.
3.4.   TOXICANT INTERACTIONS
    The  toxic  effects  of  barium  result  largely  from  an increase  In muscle
excitability,  particularly cardiac  muscle;  effects  on  the  hematopoietic
system; and  effects  on  the CNS (ACGIH,  1980).  Welch  et al.  (1983)  reported
that  the  antinodceptlve  and  lethal  effects of  barium chloride  could  be
reversed by  naloxone  or  atroplne.  Naloxone  was  more  effective  in  blocking
the antinociceptive effects and atroplne  was  a more effective antagonist  for
the lethal  effects.
                                    -8-

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                             4.  CARCINOGENICITY
4.1.   HUMAN DATA
    Pertinent  data  regarding  the  potential  carclnogenldty  of  barium  to
humans following either oral or  Inhalation  exposure were not  located  1n  the
available literature.
4.2.   BIOASSAYS
4.2.1.   Oral.  Schroeder and MHchener  (1975a,b)  Investigated the carclno-
genldty of  barium  acetate  administered 1n  the  drinking water to both  rats
and mice.   In both  studies, animals  (52 rats/sex/group and 42-54 mice/sex/
group)  were maintained  on  drinking  water   containing  5 mg  Ba/8.  for  their
lifetimes.   The Incidence of gross total tumors and  malignant  tumors  In  male
rats  were,  respectively, 4/26  (15%)  and  2/26  (8%) 1n  controls,  and  8/30
(26%) and 6/30  (20%) 1n the treated  animals.   In  female rats,  the  respective
Incidences  were 17/24  (70%) and  8/24 (33%)   1n controls, and  15/30 (45%)  and
9/33  (27%)   In the  treated  animals..  The  observed  differences  1n.tumor
Incidence were not  statistically  significant.  In  mice,  the Incidences  of
multiple tumors, lymphoma leukemia,  lung tumors and  total tumors were  nearly
Identical 1n the treated and control  groups.
4.2.2.   Inhalation.   Pertinent   data   regarding   the  carclnogenldty   of
Inhaled barium were  not located 1n the available  literature.
4.3.   OTHER RELEVANT DATA
    N1sh1oka  (1975) reported  that  barium  chloride produced  no Increased
mutation  frequency  1n   repair   deficient   strains   of  Bacillus  subtnis.
Negative results have  were  obtained  In tests  for  the  Induction of errors  In
viral DNA transcription 1n vitro (Loeb et al.,  1978).
                                    -9-

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4.4.   WEIGHT OF EVIDENCE
    IARC has not  evaluated  the risk of humans  associated  with  oral  or inha-
lation  exposure  to barium.   Using  the criteria  for  evaluating  the  overall
weight  of  evidence of carclnogenidty  to  humans  proposed by  the Carcinogen
Assessment Group  of  the  U.S.  EPA  (Federal  Register,  1984), barium  1s  most
appropriately designated  a  Group D chemical  -  not classified.   No  data  are
available  regarding   the  carcinogeniclty   of   barium  to  humans.   Although
barium was not apparently carcinogenic  to  rats  and mice  1n the Schroeder  and
Mltchener (1975a,b) bioassays, only one dosage  level was  used  which  elicited
few toxic effects and was apparently not near the  acceptable intakes.
                                    -10-

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                     5.   REGULATORY  STANDARDS  AND  CRITERIA







    The ACGIH  (1980,  1983)  has  proposed a TLV  of  0.5  mg/m3, based  on  the



results of  Hyatt  (1980),  who  had employed this  limit  for several  years  at



the  Los  Alamos Laboratories  with  satisfactory  results  for  the control  of



exposure to barium  nitrate.   All  jurisdictions that have  adopted  limits  for



barium compounds have accepted the TLV of 0.5  mg/m3 (ACGIH, 1980).
                                    -11-

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                              6.   RISK  ASSESSMENT



6.1.   ACCEPTABLE INTAKE SUBCHRONIC (AIS)



6.1.1.   Oral.   Only  one study  on  the  effects  of subchronic  oral  adminis-



tration  of  barium was  found  1n  the  available  literature.   Tardlff  et  al.



(1980)  reported  decreased  relative  adrenal weights  In male  rats  receiving



doses  as  low as  8.1  mg  Ba/kg bw/day  for  8 weeks;  however,  there were  no



differences after 13  weeks.   Female  relative adrenal weights  appeared to  be



depressed  after   13   weeks  exposure  to  45.7  mg/kg/day.   As  discussed  1n



Section  3.1.1.,  the  significance of these  findings is uncertain.   For  risk



assessment  purposes,  these  data  appear  to  represent a  free-standing NOAEL



and therefore are inadequate  for  estimation  of an AIS.   In Section 6.2.1.  on



chronic toxicity, adequate data are available.



6.1.2.   Inhalation.   The only study pertinent  to  the  subchronic  inhalation



toxicity  of barium is  that  of  Tarasenko et al.  (1977).  Exposure of  male



rats  to  atmospheric  concentrations  of  3.62  mg  Ba/m3  (5.2  mg  BaC03/m3),



4  hours/day,  for  4  months  resulted  in  "general" signs  of   toxicity  that



included decreased body weight and  liver function and increased mortality of



fetuses  following  mating  of  treated  males  with untreated  females.   An



exposure  to  0.80 mg  Ba/m3   (1.15  mg  BaCO-Xm3)  resulted  in  no  observed



toxic  effects in the  adult males; however,  effects on  reproductive perform-



ance  were  not reported for  this  dose  group.  The  exposure level  of 0.80  mg



Ba/m3  is a  NOEL.  Assuming   a  breathing volume  of 0.26  mVday  for rats,



and  multiplying  by  4 hours/24 hours to  represent  continuous  exposure,  this



exposure  corresponds  to a  dose  of  0.035 mg Ba/day or  0.14 mg  Ba/kg  bw/day



(average weight  of 0.246  kg).  Applying an  uncertainty  factor  of 100,  10 for



interspecies  conversion and  10  to  allow for  the  most sensitive  members  of



the  population,  results  in  an  AIS  of  0.0014  mg  Ba/kg  bw/day or  0.098  mg



Ba/day  for a 70  kg human.





                                     -12-

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6.2.   ACCEPTABLE INTAKE CHRONIC (AIC)

6.2.1.   Oral.   Two  studies  contained  data   useful   for   establishing  a

threshold for  toxldty  from chronic  oral  exposure to barium.   Brennlman et

al.  (1979a,b)  reported  a significant  Increase  1n  death from  "total  cardio-

vascular diseases" In communities whose water supply  contained  an average of

7  mg  Ba/a,   compared   with  communities  whose  water  supply  contained  an

average  of  0.1  mg Ba/s,.   However,  as  noted  previously  a  number of  con-

founding factors limit the usefulness of this study.

    U.S. EPA  (1985) utilized  the 16-month LOAEL of 5.1  mg/kg/day defined by

Perry et al.  (1983)  in  a study where  barium was administered  to rats  In the

drinking water  as the  basis  for an  ADI  estimate.   They  applied  an  uncer-

tainty  factor  of 100 (10  for  Interspedes  extrapolation  and  10  for  Inter-

Individual   variability).   An  additional   uncertainty  factor  to estimate  a

NOAEL from a LOAEL was not considered appropriate because


    "...a major  limitation  of  this  study [Perry  et  al.,  1983]  1s the
    minimized  exposure  to trace metals  (e.g.,  Ca)  in  the  food,  water
    and  laboratory  environment,  and  this may  have  contributed  to the
    observed  effects.    To  accomodate  for  this,   the   EPA  feels  that
    selection of an uncertainty factor of  100 1s more  appropriate."


Using the  LOAEL  of 5.1  mg/kg/day,  multiplying  by  70  kg and dividing  by 100

resulted in  an ADI of  3.6  mg/day.   This ADI may  serve as  an  AIC estimate

until additional data  concerning the toxicology  of  barium are available.

    A CS  for  slightly  reduced  longevity  in male mice  exposed  to drinking

water  containing  Ba+   at  5  ppm   in  the  Schroeder  and  MHchener  (1975b)

experiment was calculated.  Assuming  that mice  drink  water equivalent  to 17%

of  their  body  weight/day,   the  animal  dose is  0.85 mg  Ba* /kg/day.   The

corresponding  human MED was derived  by multiplying  the animal dose  by the

cube root of  the  ratio  of the  body  weight of mice  (0.04  kg approximated from
                                     -13-

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data provided)  to  that of  humans  (assumed to  be  70 kg).  The  result,  0.07
mg/kg/day, multiplied by 70 kg yields  a  human  MED  of 4.9 mg/day, correspond-
ing  to  an  RV.  of  4.5.    An  RVg  of  10  Is  appropriately  applied  to  the
effect  of reduced  longevity.    A  CS  of  45,  the  product  of  RVrf and  RVg,
results.
6.2.2.   Inhalation.   Pertinent   data  regarding   the   chronic   Inhalation
toxldty of barium  were  not located 1n  the  available  literature.   A  TLV for
barium  of  0.5 mg/m3 has  been  1n effect for  several years with  no reported
adverse  effects.   Assuming  an  average  workday  breathing  volume  of 10  m3
and multiplying by  5/7 to  convert  from 5-day to 7-day exposures result 1n an
estimated NOEL  of  3.57  mg/day.  As can  be readily seen, however,  this value
is  higher  than the  subchronlc NOEL defined  by animal  studies.   Two strat-
egies  are  feasible.   One  could assume that  the  animal  extrapolation  results
1n  an  overly  conservative  AIS and adjust  the  AIS upward based on  the  TLV.
Alternatively,  the  AIS  could be  adjusted  downward.    Adverse  reproductive
outcomes  have  been  reported   1n   animal   studies  with BaC03  at  3.62  mg
Ba/m3.   These  types  of  effects   are  difficult   to  detect  1n  the  human
population and probably  would not  be apparent  1n exposed workers  even  1f
present,  unless  careful  ep1dem1olog1cal  Investigations  designed to evaluate
these  endpolnts were conducted.  In  view of  this,  1t 1s recommended that the
AIS  for  Inhalation  of  0.098 mg/day be adopted  as  a chronic Interim ADI  with
an  additional  uncertainty  factor of 10.    This  results  1n a suggested AIC of
0.01 mg  barium/day.  This  estimate should  be carefully reevaluated when  more
complete reproduction data are available.
6.3.   CARCINOGENIC POTENCY (q^)
     Pertinent  data  regarding  a  carcinogenic potential  for  barium following
either  oral or  Inhalation  exposure were  not  located 1n  the available litera-
ture.  Therefore, no q * could be derived.

                                    -14-

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                                7.   REFERENCES







ACGIH  (American  Conference  of  Governmental  Industrial Hyg1en1sts).   1980.



Documentation  of  the  Threshold   Limit  Values,  4th  ed.   Cincinnati,  OH.



p. 35.  (Cited 1n U.S. EPA, 1983b)







ACGIH  (American  Conference  of  Governmental  Industrial Hyg1en1sts).   1983.



Threshold  Limit  Values for  Chemical  Substances and  Physical  Agents  1n  the



Workroom with Intended Changes for  1983-1984.  Cincinnati,  OH.







Brennlman,  G.,   W.   Kojola,  P.  Levy, B.  Carnow  and  T.  Namekata.   1979a.



Health  Effects   of  Human  Exposure  to  Barium  1n  Drinking  Water.   NTIS  PB



292268.  (Cited 1n U.S. EPA, 1980b)







Brennlman,  G.R.,  T.   Namekata,  W.H.  Kojola,  B.W.   Carnow  and  P.S.  Levy.



1979b.   Cardiovascular  disease death  rates  1n  communities  with  elevated



levels of  barium In drinking water.   Environ. Res.  20: 318-324.







Brennlman. G.R., W.H.  Kojola,  P.S.  Levy,  B.W. Carnow and T.  Namekata.  1981.



High  barium  levels  1n  public drinking  water  and   Its  association  with



elevated blood pressure.   Arch. Environ. Health.  36: 28-32.







Federal  Register.   1984.   Environmental Protection  Agency.   Proposed guide-



lines for  carcinogenic  risk assessment.  Federal Register.  49: 46204-46299.







Gore,  D.J. and G.  Patrick.   1982.   A quantitative  study  of the penetration



of  Insoluble particles Into  the   tissue  of  the  conducting  airways.   Ann.



Occup. Hyg.   26(1-4):  149-161.  (CA 98:30673n)





                                    -15-

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Hyatt, E.G.  1980.  Communication to TLV Committee member.   (Cited  1n  ACGIH,
1980)

Loeb, L.,  M. Slrover  and  S.  Agarwal.  1978.  Infidelity of  DNA  synthesis  as
related  to  mutagenesls   and  cardnogenesls.   Adv.  Exp.  Med.   B1ol.  91:
103-115.  (Cited 1n U.S.  EPA,  1980b)

McCauley,  P.T.  and I.S.  Washington.  1983.  Barium  bloavaHablHty  as the
chloride,  sulfate  or  carbonate  salt  1n the rat.  Drug  Chem.  Toxlcol.   6(2):
209-217.  (CA 99:17715d)

N1sh1oka,  H.   1975.  Mutagenlc  activities of  metal  compounds  1n  bacteria.
Mutat. Res.  31: 185-189.   (Cited 1n  U.S.  EPA,  1980b)

Perry, H.M., E.F-.  Perry,  M.N. Erlanger and S.J.  Kopp.   1983.   Cardiovascular
effects  of  chronic  barium  1ngest1on.   In.:  Proc.  17th  Ann.  Conf.   Trace
Substances  1n   Environmental  Health,  Vol.  17.  Univ.  of  Missouri  Press,
Columbia, MO.  p. 155-164.

Schroeder, H. and  M.  MHchener.   1975a.    Life-term studies  1n rats:  Effects
of aluminum, barium, beryllium and tungsten.  J. Nutr.   105:  421-427.

Schroeder,  H.   and M.  MHchener.   1975b.   Life-term effects  of  mercury,
methyl mercury and  nine other trace  metals on mice.   J.  Nutr.  105: 452-458.
(Cited 1n U.S.  EPA, 1980b, 1983b)
                                    -16-

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Tarasenko, M., 0.  Promin  and  A.  Sllayev.  1977.   Barium  compounds  as  Indus-



trial poisons  (an  experimental  study).   J. Hyg.  Epidem.  Microbiol.  Immunol.



21: 361.  (Cited 1n U.S. EPA,  1980b)







Tardiff,  R.G., M.  Robinson  and  N.S. Ulmer.  1980.   Subchronic  oral  toxicity



of  barium chloride  in  rats.    J.  Environ.  Pathol.  Toxicol.   4:  267-275.



(Cited  in U.S. EPA, 1983b)







U.S.  EPA.  1980a.   Guidelines  and Methodology  Used  in  the Preparation  of



Health  Effects  Assessment  Chapters  of  the  Consent  Decree  Water  Quality



Criteria.  Federal Register.  45: 79347-79357.







U.S.  EPA.  1980b.   Mini-Reviews on the  Carcinogenicity,  Mutagenicity,  Tera-



togenicity  and   Chronic   Toxidty  of   Selected  Compounds.   Environmental



Criteria  and Assessment Office, Cincinnati, OH.  Internal draft.







U.S.  EPA. 1983a.   Methodology  and Guidelines  for Reportable Quantity Deter-



minations Based  on  Chronic  Toxidty  Data.   Prepared by  the  Environmental



Criteria  and  Assessment  Office,  Cincinnati,  OH,  OHEA for the Office of Solid



Waste and Emergency  Response, Washington, DC.







U.S.  EPA. 1983b.   Reportable  Quantity  for  Barium.  Prepared by the Environ-



mental  Criteria  and Assessment  Office,  Cincinnati,  OH,  OHEA for  the Office



of  Solid  Waste and  Emergency Response, Washington, DC.







U.S.  EPA.  1985.   Drinking Water   Criteria  Document for Barium.   Office  of



Drinking  Water,  Washington, DC.  External Review Draft.
                                     -17-

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Welch, S.P.,  F.J.  Vocd  and W.L.  Oewey.   1983.   Ant1noc1cept1ve and  lethal



effects of  Intraventrlcularly  administered  barium and  strontium: Antagonism



by atroplne sulfate or naloxone hydrochlorlde.   Life  Sd.   33(4):  359-364.







Weast, R.C.,  Ed.   1980.   CRC  Handbook  of  Chemistry and  Physics,  61st ed.



CRC Press, Boca Raton, FL.   p.  880-881;  D-199.
                                    -18-

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                                                  APPENDIX



                                          Summary  Table  for  Barium
Species
Inhalation
AIS rat
AIC human
Oral
AIS
AIC rat
Maximum mice
composite
score
Experimental
Dose/Exposure

0.8 mg Ba/m3
0.5 mg/m3


100 ppm Ba
drinking water
100 ppm Ba*2 In
drinking water
for 16 months
(RVd = 2.8)
Effect Acceptable Intake
(AIS or AIC)

NOEL 0.098 mg/day
NOEL based subchronlc 0.01 mg/day
study

ND
LOAEL for Increased 3.6 mg/day
blood pressure
Increased blood 19.6
pressure (RVe = 7)
Reference

Tarasenko
et al., 1977
Tarasenko
et al., 1977


Perry et al.,
1983
Schroeder and
Mltchener,
1975b; U.S.
EPA, 1983b
ND = Not derived

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