Barium and barium compounds
17
activation (Rossman et al., 1991) have produced negative
results with barium chloride. Negative results have also
been observed for barium nitrate in the rec assay using
B. subtilis strains H17 and H45 (Kanematsu et al., 1980).
Barium chloride induced gene mutations in L5178Y
mouse lymphoma cells with, but not without, metabolic
activation (NTP, 1994). Neither barium acetate nor barium
chloride decreased the fidelity of DNA synthesis in
avian myeloblastosis virus DNA polymerase (Sirover &
Loeb, 1976). In mammalian cells, barium chloride did not
induce sister chromatid exchanges or chromosomal
aberrations in cultured Chinese hamster ovary cells, with
or without activation (NTP, 1994). In summary, except for
the mouse lymphoma assay, results of in vitro tests
have been generally negative.
8.7
Reproductive toxicity
Data on the reproductive and developmental
toxicity of barium compounds are limited. Decreased
ovary weight and ovary/brain weight ratio were seen in
female rats administered oral gavage doses of 198 mg
barium/kg body weight per day, once a day for 10 days
(Borzelleca et al., 1988). In single-generation reproduc-
tive toxicity studies in rats and mice (Dietz et al., 1992),
groups of 20 male and 20 female F344/N rats and B6C3F
1
mice were exposed to barium chloride dihydrate in
drinking-water for up to 60 days. The barium chloride
dihydrate concentrations were 0, 1000, 2000, or
4000 mg/litre (estimated by the authors to be 0, 50, 100,
and 200 mg/kg body weight per day) for the rats and 0,
500, 1000, or 2000 mg/litre (estimated by the authors to
be 0, 50, 100, and 200 mg/kg body weight per day) for the
mice. The authors measured weekly body weight
changes and water consumption, which were used to
estimate daily barium exposure in both mice and rats.
After the completion of the exposure period (60 days),
males and females from the same dosage groups were
housed together until there was evidence of mating or
until the end of the mating period (8 days). This rodent
study reported fertility index, fetal and maternal toxicity,
and developmental toxicity end-points in fetus and
neonates. There were no indications of reproductive or
developmental toxicity in any of the exposure groups.
However, the results should be interpreted cautiously
because of below-normal pregnancy rates in all groups
of exposed, as well as control, rats and mice.
Ridgeway & Kanofsky (1952) examined the
developmental toxicity of barium by injecting 20 mg
barium chloride into the yolk sac of developing chick
embryos. When injection was made on day 8 of devel-
opment, developmental defects were observed in toes. In
contrast, no effects were seen when injection was made
on day 4 of development.
Tarasenko et al. (1977) also reported that a shorten-
ing of the mean duration of the estrous cycle and an
alteration in the proportion of mature and dying ovarian
follicles were observed in rats exposed to 13.4 mg barium
carbonate/m
3
(9.3 mg barium/m
3
) for 4 months, compared
with a control group. These effects were not observed in
rats exposed to 3.1 mg/m
3
(2.2 mg barium/m
3
). The
authors also reported that rats in the 13.4 mg/m
3
group
gave birth to underdeveloped offspring that showed
considerable mortality and slow body weight gain during
the first 2 postnatal months.
8.8
Immunological and neurological effects
Only limited information is available on the immu-
notoxicity and neurotoxicity of barium compounds
(IPCS, 1990). Intravenous infusion of barium chloride
into anaesthetized dogs resulted in muscle flaccidity and
paralysis, which appeared to result from severe hypo-
potassaemia (Roza & Berman, 1971).
9. EFFECTS ON HUMANS
9.1
Case reports
Intentional or accidental ingestion of barium com-
pounds (i.e., barium carbonate, barium chloride) causes
gastroenteritis (vomiting, diarrhoea, abdominal pain),
hypopotassaemia, hypertension, cardiac arrhythmias,
and skeletal muscle paralysis. Potassium infusion is used
clinically to reverse the toxic effects of barium (Diengott
et al., 1964; Gould et al., 1973; IPCS, 1990; US EPA, 1990,
1998).
According to RTECS (1985), the lowest lethal acute
oral doses for barium chloride and barium carbonate are
11.4 and 57 mg/kg body weight, respectively; for barium
carbonate, a dose as low as 29 mg/kg body weight
causes flaccid paralysis, paraesthesia, and muscle
weakness.
Opacities were detected on lung X-rays of three
patients for up to 2 years following accidental aspiration
of barium sulfate orally administered for observation of
the gastrointestinal tract (Buschman, 1991).
In a case report involving the grinding of barite
ore, a worker was exposed over a period of 10 years to
extremely high total dust concentrations (approximately
212 000 particles/cm
3
for 1.5 h and 60 000 particles/cm
3
for
1 h), although it was not stated how these measurements
were made (Pendergrass & Greening, 1953). Analysis
Concise International Chemical Assessment Document 33
18
indicated that 49% of the workplace airborne dust was
barium sulfate,
although particle size was not stated.
After 2 years of exposure to the barite ore dust, fine
nodulation was observed on lung X-rays, apparently
due to the presence of barium sulfate. The presence of
barium sulfate in the lung tissue was confirmed by chem-
ical analysis and light microscopy at autopsy 11 years
after cessation of exposure. Several histopathological
findings were observed, including fibrosis (although
mostly characteristic of silicosis). The histopathological
findings were considered to be due to the silica and
anthracite exposure; the X-ray opacities seen were
attributed to the presence of the barium sulfate.
In an extensive study, temperature and pulse rate
measurements were taken as an indication of an acute
inflammatory response for 291 humans administered a
single unstated dose of a 50% w/v barium sulfate sus-
pension for bronchographic purposes (Nelson et al.,
1964). The method of administration was unstated, but
the suspension was presumed to have been instilled
into the trachea and then blown into the lungs. In
154 patients, there was radiological evidence of the
presence of barium sulfate in the bronchial tree at the
time of the last available X-ray (various time points
ranging from <1 week to >1 year after administration); in
135 patients, on the other hand, there was no radio-
logical evidence of residual barium sulfate in the lungs
1 year after bronchography. Forty-one of these patients
exhibited complete elimination of the barium sulfate from
the lungs within 1 week; it was stated that in some of
these patients, this clearance occurred within 24 h.
Wones et al. (1990) administered 1.5 litres/day of
distilled drinking-water containing various levels of
barium chloride to 11 healthy male volunteers aged
27–61 years (mean 39.5 years, median 41 years). None of
the subjects was taking any medications, and none had
hypertension, diabetes, or cardiovascular disease.
Barium concentrations in the drinking-water consumed
by the subjects prior to the study were known to be very
low. No barium was added for the first 2 weeks, which
served as a control period; drinking-water containing
5 mg barium/litre (0.14 mg barium/kg body weight per
day using reference values of 2 litres/day for water
consumption and 70 kg for body weight) was adminis-
tered for the next 4 weeks, and drinking-water containing
10 mg barium/litre (0.21 mg barium/kg body weight per
day) was administered for the last 4 weeks of the study.
Diets were controlled to mimic US dietary practices
(barium content of the diet was not determined, but the
authors mentioned that a typical hospital diet provides
0.75 mg barium/day, or 0.011 mg barium/kg body weight
per day using a 70-kg reference weight). All beverages
and food were provided, and subjects were instructed to
consume only what was provided. The subjects were
also instructed to keep their level of exercise constant
and to abstain from alcohol, and smokers were told to
smoke consistently throughout the study. Systolic and
diastolic blood pressures were measured in the morning
and evening. Blood was collected at the beginning and
periodically, particularly as four consecutive daily
samples at the end of each of the three study periods.
Twenty-four-hour urine collections were performed at
the end of each study period. Twenty-four-hour
continuous electrocardiographic monitoring was
performed on 2 consecutive days at the end of each
study period.
Blood pressures were not significantly affected by
barium exposure (Wones et al., 1990). A trend towards
increased total serum calcium with barium exposure was
noted but was not considered to be clinically significant.
No significant changes were observed in plasma total
cholesterol, triglycerides, low-density lipoprotein (LDL)
or high-density lipoprotein (HDL) cholesterol, LDL:HDL
ratio, and apolipoproteins A1, A2, and B. Serum glucose,
albumin, and potassium levels and urinary levels of
sodium, potassium, or metanephrines (catecholamine
breakdown products) were unchanged.
Electrocardiograms revealed no changes in cardiac cycle
intervals, including the QT interval; the study authors
noted that the lack of shortening of the QT interval
provided evidence that the slight increase in serum
calcium was not clinically significant. In addition, no
significant arrhythmias, no increase in ventricular
irritability, and no apparent conduction problems were
seen with barium exposure. This study did not identify a
LOAEL; the NOAEL is 0.21 mg barium/kg body weight
per day.
Transient cell transformations resembling severe
premalignant dysplasia were noted following single
topical applications (four times at intervals of 4–6 weeks)
of 1.25 mmol barium chloride/litre to the cervix of a
woman with no known history of abnormal cervical
cytology (Ayre, 1966). In another case (Ayre
& LeGuerrier, 1967), cell transformations similar to
extreme dysplasia and resembling cell findings of cancer
in situ were observed following a single topical appli-
cation of 1.25 mmol barium chloride/litre (mixed with
equal amounts of 70% dimethylsulfoxide) to the cervix.
9.2
Epidemiological studies
Brenniman & Levy (1984) reported an ecological
epidemiological study of mortality and morbidity in
populations living in communities in Illinois, USA, with
elevated levels of barium in municipal drinking-water