BARIUM IN DRINKING-WATER
7
monitored throughout the study, and organ weights were determined in the animals
killed at 15 months. Neurobehavioural and cardiovascular studies were not performed.
A marginally increased survival of males in the exposed groups (percent probability
of survival: 62%, 58% and 67% for the 500, 1250 and 2500 mg/litre groups,
respectively) compared with that of the male controls (44%) was attributed to a
decreased incidence of leukaemia. Survival of the females was not significantly
affected. For male rats receiving 2500 mg/litre, the final mean body weights were 5%
lower than for controls. The final mean body weights of females receiving 1250 and
2500 mg/litre were 6% and 11% lower, respectively, than those of controls.
Water consumption was decreased in a dose-related manner; at the highest exposure
level, the
decrease, relative to controls, was 22% in males and 25% in females.
Absolute and relative organ weights, determined only at the 15-month interim
evaluation, were not affected in the males. In the females, a statistically significant
increase in relative kidney weights occurred at 2500 mg/litre. Determination of
haematology and clinical chemistry values at the 15-month interim evaluation showed
no significant differences between control and exposed rats. Chemical-related kidney
lesions were not observed in rats in these 2-year studies; the only potential indication
of renal toxicity was the increased relative kidney weight seen in the females at 2500
mg/litre. In addition, there were no chemical-related histological changes in any other
organs or tissues.
The IPCS working group (IPCS, 2001) considered that the highest exposure level
tested in this study, 2500 mg of barium per litre in drinking-water (60 mg of barium
per kg of body weight per day for males and 75 mg of barium per kg of body weight
per day for females), could be a chronic NOAEL or LOAEL for rats, depending on
interpretation of the increased relative kidney weight in females.
However, when taking into account the results in the 13-week US NTP (1994) study
in rats, in which increased relative and absolute kidney weights were seen in female
rats receiving 2000 mg of barium per litre in drinking-water (115 mg of barium per kg
of body weight per day) and kidney lesions and greater increases in relative and
absolute kidney weights were seen in female rats at 4000 mg/litre (180 mg of barium
per kg of body weight per day), the increased relative kidney weights in females of
the 2-year study were considered to be suggestive of potential renal effects. Therefore,
75 mg of barium per kg of body weight per day was designated a chronic LOAEL and
45 mg of barium per kg of body weight per day a chronic NOAEL for female rats for
renal effects in the US NTP (1994) study (IPCS, 2001).
5.4 Reproductive and developmental toxicity
There are only limited data on the reproductive and developmental toxicity of barium
compounds; however, in a one-generation reproductive study in mice and rats, there
was no indication of reproductive or developmental toxicity at dose levels up to 200
mg/kg of body weight per day (Dietz et al., 1992).
BARIUM IN DRINKING-WATER
8
The inhalation of barium carbonate dust adversely affected spermatogenesis in male
rats exposed to 22.6 mg/m
3
and shortened the estrous cycle and disturbed the
morphological structure of the ovaries in female rats exposed to 13.4 or 3.1 mg/m
3
for
4 months (Tarasenko et al., 1977). There appear to be no suitable studies with which
to make a meaningful assessment of developmental toxicity.
5.5 Mutagenicity and related end-points
The information available on the genotoxicity of barium compounds is relatively
limited, with no in vivo studies available. The data available have been reviewed by
IPCS (2001). The majority of the in vitro studies conducted indicate that barium
chloride and barium nitrate do not induce gene mutations in bacterial assays, with or
without metabolic activation (IPCS, 2001). In particular, barium
has consistently
given negative results in several Ames
Salmonella strains, and it did not induce
chromosome aberrations or sister chromatid exchanges in Chinese hamster ovary cells
in vitro. Barium chloride did not increase the frequency of mutation in repair-deficient
strains of Bacillus subtilis (Nishioka, 1975) or induce errors in viral DNA
transcription in vitro (Loeb et al., 1978). Barium chloride did induce gene mutations
in L5178Y mouse lymphoma cells with, but not without, metabolic activation (US
NTP, 1994). The weight of evidence supports the conclusion that barium does not
possess any significant genotoxic potential.
5.6 Carcinogenicity
In extremely limited lifetime bioassays of rats and mice exposed to 5 mg/litre of
barium (as barium acetate)
in drinking-water, no evidence was found on gross
examination at autopsy to show that barium is carcinogenic (Schroeder & Mitchener,
1975a,b). In well conducted studies on both mice and rats, described above, there was
no indication of an increase in neoplasms (US NTP, 1994).
6. EFFECTS ON HUMANS
Barium is not considered to be an essential element for human nutrition (Schroeder et
al., 1972).
At high concentrations, barium causes vasoconstriction by its direct stimulation of
arterial muscle, peristalsis as a result of the violent stimulation of smooth muscles and
convulsions and paralysis following stimulation of the central nervous system
(Stockinger, 1981). Depending on the dose and solubility of the barium salt, death
may occur in a few hours or a few days. The acute toxic oral dose is between 3 and 4
g (Reeves, 1986). Repeated exposures to barium chloride in table salt are believed to
have caused recurrent outbreaks of “pa-ping” disease (a transient paralysis resembling
familial periodic paralysis) in China (Shankle & Keane, 1988), but recovery was
usually rapid (IPCS, 1990).