The reason for the discrepancy between the findings of Perry et al. (1989, 1985), NTP
(1994) and McCauley et al. (1985) is not known. However, it is possible that mineral
concentrations of diet used by Perry et al. (1989, 1985) may have been a contributing factor.
The calcium content of the rye-based diet, 3.8 mg/kg, was below the 5 mg/kg that is
recommended for maintenance, growth, and reproduction of rats (NRC, 1995). The influence of
dietary calcium on the potentially hypertensive effect of barium is unknown, but there is some
evidence the reduced dietary calcium is a risk factor for hypertension in humans (McCarron et
al., 1984). In view of a possible association between the barium-induced cardiovascular effects
and calcium and potassium intake, the relevance of the data from Perry et al. (1989, 1985) to
animals maintained on standard diets or to humans is uncertain. Moreover, hypertensive effects
were not observed in other animal studies (NTP, 1994; McCauley et al., 1985) or in studies of
repeated exposure in humans (Wones et al., 1990; Brenniman et al., 1981).
Renal toxicity appears to be the most sensitive effect of chronic barium exposure.
Chronic and subchronic rodent studies conducted by McCauley et al. (1985), Schroeder and
Mitchener (1975a), and NTP (1994) provide evidence for an association between barium
exposure and renal toxicity. Unfortunately, no human studies have investigated the effects of
barium exposure on the kidneys. Acute renal failure has been reported in a case of intentional
barium poisoning (Wetherill et al., 1981) in which the patient was treated with intravenous
sulfate and precipitated barium sulfate apparently obstructed the tubules resulting in renal
necrosis.
McCauley et al. (1985) detected glomerular damage in unilaterally nephrectomized rats
and Dahl salt-sensitive and salt-resistant rats that received 1000 ppm barium in drinking water
(150 mg/kg-day). Schroeder and Mitchener (1975a) found evidence of glomerular damage (i.e.,
proteinuria) in mice exposed to a much lower concentration of barium (5 ppm or 0.61 mg/kg-
day). The proteinuria was not accompanied by an increased incidence of renal lesions and,
unfortunately, this study only employed one exposure concentration. As with other studies that
used the low-metal rye-based diet, there is some uncertainty about the potential association with
the reduced calcium and potassium concentrations in the diet.
NTP (1994) identified renal toxicity as the primary treatment-related effect in chronic
and subchronic studies of F-344/N rats and B6C3F1 mice. Chemical-related nephropathy was
observed in male and female mice following chronic or subchronic drinking water exposure to
barium chloride. These lesions were characterized by tubule dilatation, renal tubule atrophy,
tubule cell regeneration, hyaline cast formation, multifocal interstitial fibrosis, and the presence
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of crystals, primarily in the lumen of the renal tubules. NTP pathologists concluded that these
lesions were morphologically distinct from the spontaneous degenerative renal lesions
commonly observed in aging mice. Survival rates were significantly reduced in the high dose
group by 65% for males and 26% for females when compared to controls. Mortalities were
attributed to the chemical-related renal lesions (NTP, 1994). Chemical-related nephropathy was
also observed in rats following subchronic exposure. In the chronic rat study, spontaneous
nephropathy was observed in the majority of animals in both control and treatment groups,
precluding the detection of any treatment-related effect. Increased kidney weights were
observed in male and female rats and female mice following 13 weeks of exposure. Female rats
were the only animals with increased kidney weights following 15 months of exposure.
Mammals exposed to elevated concentrations of barium tend to accumulate significant
concentrations of the metal in their bones (WHO, 1990; Bauer et al., 1956). The uptake of
barium in bone tissue was evaluated in F-344/N rats sacrificed at the 15-month interim of the
NTP (1994) 2-year drinking water study. Barium concentrations in upper, middle, and lower
sections of the femur were increased by approximately three orders of magnitude in the high
dose groups when compared to controls. Minimal reductions in calcium concentrations were
observed in the same femur sections and no effect on bone density was observed. The biological
implications of increased barium deposition in bone tissue remains unclear. Additional research
is needed to fully investigate the potential for adverse effects of elevated barium concentrations
in bone tissue.
Dietz et al. (1992) evaluated the reproductive toxicity of barium in rats and mice. No
alterations in epididymal sperm counts, sperm motility, sperm morphology, testicular or
epididymal weights, or vaginal cytology were observed in rats or mice. No significant
alterations in gestation length, pup survival, or the occurrence of external abnormalities were
observed. A statistically significant (p<0.01) decrease in the birth weight of live rat pups was
observed in the 4000 ppm group when compared to control (approximately 9%), but no effect
was observed at 5 days of age. A statistically significant (p<0.05) decrease in average litter size
was observed in mice in the 1000 ppm treatment group but not in the 2000 ppm treatment group.
The observed effects, decreased birth weight and decreased litter size, were either transient or
not dose-dependent.
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