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.
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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.
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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.
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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
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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
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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.
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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.
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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).
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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.
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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).
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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.
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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
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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.
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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)
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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)
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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.
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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.
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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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