Concise International Chemical Assessment Document 33

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 

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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 

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