The subchronic rat studies included neurobehavioral and cardiovascular assessments.
Behavioral assessments were conducted prior to exposure and at treatment days 45 and 90.
Behavioral endpoints included spontaneous motor activity, forelimb and hindlimb grip strength,
thermal sensitivity, and startle response to acoustic and air-puff stimulus. The cardiovascular
assessments were also conducted prior to exposure and at days 45 and 91. Cardiac endpoints
included EKG readings and blood pressure measurements.
Three males and one female in the 4000 ppm treatment group died during the last week
of the study. These mortalities were considered by the authors to be chemical-related but the
cause of death was not evident by histopathologic examination. No other mortalities were
observed. Water consumption in the 4000 ppm treatment group was decreased by 30% relative
to that of controls. Body weights of animals in this treatment group were significantly reduced
by approximately 13% for males and 8% for females when compared to controls.
Increased absolute and relative kidney weights were observed in female rats from the
2000 and 4000 ppm treatment groups when compared to controls; mean relative kidney weights
were increased by 13% and 19%, respectively. Mean relative kidney weight for male rats in the
4000 ppm treatment group was increased by 12%. Mean absolute liver weight was decreased
16% in males from the 4000 ppm treatment group. Mean absolute and relative liver weights in
the females from the 4000 ppm treatment group were decreased 16% and 7%, respectively.
Mean absolute thymus weight for females in the 4000 ppm treatment group was depressed 22%.
The investigators attributed the changes in tissue weights of organs other than the kidney to be
associated with the decrease in mean body weights.
Chemical-related nephropathy were observed in 3/10 male and 3/10 female rats in the
4000 ppm treatment group. These lesions were described as minimal to mild, focal to multifocal
areas of dilatation of the proximal convoluted tubules. These changes were characterized as
unlike the spontaneous renal lesions that occur in rats. Tubule dilation was not observed in
controls or in other treatment groups. Early lesions of spontaneous nephropathy were observed
in all males and a small number of females in all of the exposure groups as well as the controls
(these changes were not characterized in the report). Lymphoid depletion in the spleen and
thymus was observed in animals from the 4000 ppm treatment group that died during the study.
No other histologic changes were reported.
Serum phosphorus levels were significantly elevated in female rats with drinking water
concentrations
$
500 ppm and in male rats receiving concentrations
$
2000 ppm. Dietz et al.
(1992) did not consider the elevated serum phosphorus levels in female rats to be biologically
20
significant. The investigators felt that the statistical significance of this observation was a result
of a mean value for the control group that was lower than historical controls. No other
chemical-related or biologically significant changes in serum or hematology parameters were
observed.
A significant decrease in the magnitude of undifferentiated motor activity was observed
at day 90 in the 4000 ppm treatment group. Marginal decreases were seen in all other barium-
exposed groups except the females in the 1000 ppm treatment group. No significant or dose-
related changes were observed in other neurobehavioral endpoints. The preliminary report of
this study (Dietz et al., 1992) stated that there were no consistent effects on behavior produced
by barium chloride and that the observed neurobehavioral changes could be attributed to the
general condition of the rats and mice in the high dose groups. The final NTP (1994) report did
not discuss the toxicological significance of the neurobehavioral test results in rats.
Cardiovascular assessments revealed no barium-associated differences in heart rate, EKG
readings, or blood pressures. A LOAEL of 180 mg/kg-day can be identified for a statistically
significant decrease in body weights. A NOAEL of 110 mg/kg-day can be identified for the
absence of this effect.
4.2.1.4. NTP (1994) Chronic Rat Study
In the chronic rat study, male and female F-344/N rats (60 animals/group/sex) received
drinking water containing 0, 500, 1250, or 2500 ppm BaCl
2
×2H
2
O for 104 weeks (males) or 105
weeks (females). Using weekly water consumption and body weight data, the authors estimated
the doses of barium were 15, 30, and 60 mg/kg-day for males and 15, 45, and 75 mg/kg-day for
females, respectively. The animals were fed an NIH-07 mash diet. Barium concentration of the
diet was not reported. In a 15-month interim evaluation, venous blood was collected from all
rats for hematology and clinical chemistry, which included analysis of plasma barium
concentrations. In addition, a limited number of rats (10 from each group) were sacrificed at
month 15. The remaining animals stayed on the study until they were moribund, died naturally,
or were terminally sacrificed. Necropsy and complete histopathologic examinations were
performed on all animals. Bone density and femur concentrations of barium, calcium, and
phosphorus levels were measured at the 15-month interim. Body weights were monitored
throughout the study, and organ weights were determined in the animals sacrificed at the 15
month interim.
The survival of the exposed males was increased (62%, 58%, and 67% for the 500, 1250,
and 2500 ppm treatment groups, respectively) compared to the control group (44%). The
increased survival of the treated animals was attributed to a high incidence of leukemia in the
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