Barium - Toxicology of Metals - page 403

variability of these values from species to species was
perhaps due to different degrees of sulfate precipitation
in the alimentary canal before absorption, depending
on dietary and gastrointestinal physiology factors. The
approximate LD 50 of BaCl 2 after intraperitoneal admin-
istration to rats was 24 mg/kg (Maretic' et al ., 1957) and
after intracerebroventricular administration to mice,
2.4 mg/kg (Segreti et al ., 1979).
Toxicology and carcinogenicity studies were per-
formed in rats and mice administered barium chlo-
ride dihydrate in drinking water in concentrations up
to 4000 mg/L for 15 days, 13 weeks, and 2 years (NTP,
1994). No evidence of carcinogenic activity was found
in rats or mice. There were no clear barium-related neu-
robehavioral effects or reproductive toxicity. Results
from the general toxicity studies are briefl y presented
in the following. After 13 weeks at the highest dose,
200 mg/kg body weight to males and 180 mg/kg body
weight to females, the body weights were signifi cantly
lower (13% in males and 8% in females) compared
with controls. Increased kidney weight was observed
in female rats at doses >65 mg/kg body weight, and in
males at the highest dose. At the highest dose level, kid-
ney lesions, characterized by renal tubule dilatation in
the outer stripe of the outer medulla and cortex occurred
in 3 of 10 males and 3 of 10 females. In the 2-year study,
the highest doses, 60 mg/kg for males and 75 mg/kg
for females, resulted in decreased body weights com-
pared with controls (5% in males and 11% in females),
a signifi cant increase in kidney weight in females, but
no kidney lesions. At 2 years, females in all dose groups
had lower liver weights than controls. Cardiovascular
studies in the rats did not reveal any effects on heart
rate, systolic blood pressure, or electrocardiogram.
The NTP study in mice demonstrated greater liver
weights after 15 days at the highest dose, correspond-
ing to 70 and 85 mg/kg body weight in males and
females, respectively. At 13 weeks with the highest
dose, 450 mg/kg for males and 495 mg/kg for females,
6 of 10 male and 7 of 10 females died. Multifocal and
diffuse nephropathy characterized by tubule dilatation,
regeneration, and atrophy occurred in 10 of 10 males
and 9 of 10 females at the highest dose. In the 2-year
study, survival was signifi cantly lower in the highest
dose groups, 160 mg/kg and 200 mg/kg in males and
females, respectively, because of renal toxicity. The
incidences of nephropathy were increased in male and
female mice. Body weights were 8% lower in males
and 12% lower in females, compared with controls.
Long-term feeding studies in rats, with the drink-
ing water containing 10-250 mg Ba 2+ /mL (as chloride),
resulted in no measurable toxic effects (Tardiff et al .,
1980). Perry et al (1989) reported increased systolic blood
pressure by 6 mmHg in rats after 8 months of exposure to

0.82 mg Ba/kg body weight (as barium chloride) and by
12 mmHg after 1 month of exposure to 7.4 mg/kg body
weight. It should be noted that the animals received a diet
with a low content of trace elements, including calcium
and potassium, which may have caused a higher sensi-
tivity to cardiovascular effects of barium. An increased
incidence of proteinuria in male rats was reported after
5 months of exposure to 5 mg/L of barium acetate in
drinking water, corresponding to approximately 0.6 mg
Ba/kg body weight and a diet characterized as “low
metal” (Schroeder and Mitchener, 1975).
Chickens were found to tolerate 1 g Ba 2+ /kg in
their diet; 2 g/kg caused slight depression of growth;
4 g/kg caused substantial depression of growth but
no increase in mortality; 8 g/kg was the approximate
LD 50 in 4 weeks; 16 g/kg killed chickens in 7 days and
32 g/kg in 5 days. The results were similar with bar-
ium hydroxide and acetate (Johnson et al ., 1960).
The human symptoms and signs of acute barium
intoxication were well reproduced in animal experi-
ments. The cardiomyopathies in dogs and guinea pigs
included ectopic ventricular contractions, ventricular
tachycardia, and, fi nally, ventricular fi brillation. The
noncardiac effects were salivation, diarrhea, hyperten-
sion, skeletal muscle paralysis, and respiratory paral-
ysis (Schott and McArdle, 1974). Infusion of barium
chloride into anesthetized dogs produced all of the
preceding, plus a prompt and substantial hypokalemia.
Potassium administration prevented or reversed all of
these effects except the hypertension, which seemed to
have a different etiology not connected to the Ba 2+ -K +
antagonism (Roza and Berman, 1971). The involve-
ment of the renin-angiotensin system in mediating the
hypertensive effects after long-term, low-level barium
exposure has been discussed, but there is a lack of
direct information (EPA, 1999). Intracerebroventricular
injection of BaCl 2 in mice produced severe convulsions,
preventable by pretreatment with atropine sulfate
or naloxone hydrochloride (Segreti et al ., 1979). This
effect seems related to the blockage by barium of the
potassium conductance of axons, a phenomenon well
studied in squids (Armstrong and Taylor, 1980; Eaton
and Brodwick, 1980). However, barium could exert a
stimulant action of the adrenal medulla even in dener-
vated cats, attributable to increase in the permeability
of chromaffi n cell membranes and resulting in release
of catecholamines (Douglas and Rubin, 1964).

8 TREATMENT

Treatment of poisoning by soluble barium salts may
be preventive or curative. Preventive treatment entails
inhibition of absorption by administration of sodium