the barium-exposed workers (24
:
g/dL) and the comparison group (32
:
g/dL). Although the
results of this study suggest an association between exposure to barium and hypertension, the
results should be interpreted cautiously because (1) a small number of workers were examined,
(2) it appears that blood pressure was measured only once, and (3) the workers were exposed to a
number of other chemicals, including lead, which is associated with an increase in blood
pressure.
The health effects associated with occupational exposure to barium during arc welding
with barium-containing stick electrodes and flux-cored wires were investigated by Zschiesche et
al. (1992). A group of 18 healthy welders not using barium-containing consumables in the past
10 days were divided into three groups: group A (n = 8, mean age of 30.4 years) performed arc
welding with barium-containing stick electrodes, group B (n = 5, mean age of 43.6 years)
performed arc welding with barium-containing self-shielded flux-cored wires, and group C (n =
5, mean age of 32.0 years) performed arc welding with barium-containing self-shielded flux-
cored wires using welding guns with built-in ventilation systems. All welders performed
welding with barium-free consumables on Thursday and Friday of the first week of the study.
Barium-containing consumables were used during week 2 of the study and on Monday of week
3. The subjects welded for an average of 4 hours per day. The average barium concentrations in
the breathing zones were 4.4 (range of 0.1-22.7), 2.0 (0.3-6.0), and 0.3 (0.1-1.5) mg/m
3
for
groups A, B, and C, respectively. No exposure-related subjective symptoms of health or
neurological signs were found. No significant differences between pre- and post-shift EKG,
pulse rate, whole blood pH, base excess and standard bicarbonate, and plasma concentrations of
sodium, magnesium, and total and ionized calcium were observed. During week 2, decreases in
plasma potassium concentrations were observed in groups A and C; the levels returned to the
normal range under continuation of barium exposure and were not statistically different from
levels during week 1 (no barium exposure). This drop in serum potassium levels was not
observed in group B, which had a similar barium exposure level as group A.
4.2. PRECHRONIC/CHRONIC STUDIES AND CANCER BIOASSAYS IN
ANIMALS—ORAL AND INHALATION
4.2.1. Oral Studies
The National Toxicology Program (NTP) conducted a series of toxicity and
carcinogenicity studies with barium chloride dihydrate (BaCl
2
×2H
2
O). The chemical was
15
administered in drinking water to mice and rats for 13 weeks or 2 years (NTP, 1994). A
preliminary report of the 13-week subchronic studies was published by Dietz et al. (1992).
4.2.1.1. NTP (1994) Subchronic Mouse Study
In subchronic mouse studies, male and female B6C3F1 mice (10 animals/group/sex)
received BaCl
2
×2H
2
O in their drinking water at concentrations of 0, 125, 500, 1000, 2000, and
4000 ppm for 13 weeks. Using weekly water consumption and body weight data, the authors
estimated the doses of barium were 15, 55, 100, 205, and 450 mg/kg-day for the males and 15,
60, 110, 200, and 495 mg/kg-day for the females, respectively. The animals were fed NIH-07
pellets. Barium concentration of the diet was not reported. Complete histopathologic
examinations were performed on all mice in the control, 2000 ppm, and 4000 ppm treatment
groups, and histopathologic examinations of the kidneys were performed on the male mice in the
1000 ppm treatment group. Organ and body weights were measured and neurobehavioral
assessments (at 0, 45, and 90 days) were performed on animals of all groups. Hematology and
clinical chemistry analyses were not performed.
In the 4000 ppm treatment group, 6/10 male and 7/10 female mice died; survivors were
debilitated. In the 125 ppm treatment group, one of the ten male mice died. No mortalities were
observed in any of the other treatment groups. Water consumption for the male mice in the 4000
ppm treatment group was 18% lower than that of controls. In all other treatment groups water
consumption was similar to that of controls. In the 4000 ppm treatment group, body weights of
both sexes were significantly reduced, with final body weights 30%-50% lower than those for
controls. Absolute kidney weights were decreased 23%, relative kidney weights increased 12%
in the males, while in the females absolute kidney weights were decreased 21%, but relative
kidney weights were increased 40%. Absolute and relative thymus weights were decreased in
both sexes. Decreased absolute and relative liver weights were seen in animals receiving
drinking water concentrations of 1000 ppm BaCl
2
×2H
2
O or greater. Relative liver weights were
decreased by 25% in males receiving 4000 ppm, but only 10% in females, when compared to
controls.
Chemical-related nephropathy occurred in 10/10 male and 9/10 female mice in the 4000
ppm treatment group. The lesions were characterized by tubule dilatation, renal tubule atrophy,
tubule cell regeneration, and the presence of crystals primarily in the lumen of the renal tubules.
Atrophy of the thymus and spleen was observed in a significant number of males and females
that received 4000 ppm. NTP (1994) described the thymic lesions as necrotic or moderate to
marked depletion of thymic lymphocytes. In some cases, only remnants of stromal cells were
16