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BARIUM IN DRINKING-WATER - Who/sde/wsh/03. 04/76

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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). 





The inhalation of barium carbonate dust adversely affected spermatogenesis in male 

rats exposed to 22.6 mg/m


 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



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). 




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). 


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