Toxicological Review of Barium and Compounds

calcium levels in the urine, impaired liver function, and histologic alterations in the heart, liver, 

kidneys, and lungs.  No alterations in the EKG readings were reported.  However, when the rats 

were administered proserine, the EKG readings suggested disturbances in heart conductivity. 

The authors noted that the heart, liver, and kidneys “had a character of mild protein (‘granular’) 

dystrophy.”  In the lungs, the histologic alterations consisted of moderate perivascular and 

peribronchial sclerosis with focal thickening of the intraalveolar septa and collagenation.  No 

incidence data were provided. 

4.3.  REPRODUCTIVE/DEVELOPMENTAL STUDIES—ORAL AND INHALATION 

4.3.1.  Oral Exposure 

Data on the reproductive and developmental toxicity of barium compounds are limited. 

The data base consists of single-generation reproductive toxicity studies in rats and mice (Dietz 

et al., 1992) and a developmental toxicity study conducted by Tarasenko et al. (1977).  The lack 

of information on the animal species, barium dosages, and mode of administration and the poor 

reporting of results preclude using the Tarasenko et al. (1977) study to assess developmental 

toxicity following oral exposure to barium. 

In the Dietz et al. (1992) study, groups of male and female F-344/N rats and B6C3F1 

mice (20/sex/species/group) were exposed to barium chloride dihydrate in the drinking water for 

60 days (males) or 30 days (females).  The barium chloride dihydrate concentrations were 0, 

1000, 2000, or 4000 ppm for the rats and 0, 500, 1000, or 2000 ppm for the mice.  Estimated 

doses were not reported for this study.  The dosages from a subchronic study conducted by the 

same authors (NTP, 1994; Dietz et al., 1992) were therefore used to represent approximate 

dosages for this study.  For the rats, estimated barium doses were 0, 65, 110, and 200 mg/kg-day 

for males and 0, 65, 115, and 180 mg/kg-day for females.  For mice the estimates were 0, 55, 

100, and 205 mg/kg-day for males and 0, 60, 110, and 200 mg/kg-day for females.  After the 

exposure period, males and females from the same exposure groups were housed together until 

there was evidence of mating or until the end of the mating period (8 days).  The following 

endpoints were used to assess potential reproductive toxicity: length of pregnancy, number of 

implantation sites, number of live and dead offspring, pup weights at birth and on the fifth day 

after parturition, external abnormalities of pups, gross examination of the vagina, cervix, 

oviduct, and uterus of the F

0

 dams, and evaluation of sperm density, morphology, and motility, 

and reproductive organ weights of the F

0

 males. 

28

---

Pregnancy rates in the rat study were below historically normal values for the laboratory, 

ranging from 40% in the controls to 65% in the high dose group, but barium treatment did not 

appear to be a factor.  The problem of low fecundity was not investigated by remating because of 

schedule restrictions.  No significant alterations in gestation length, pup survival, or occurrence 

of external abnormalities were observed.  A marginal but statistically not significant reduction in 

live litter sizes was observed in the 4000 ppm treatment group compared to controls at birth and 

day 5 (day 0, 9 ± 1.37 pups in controls compared to 7.2 ± 0.52 pups in the 4000 ppm treatment 

group; day 5, 9.3 ± 1.16 pups in controls compared to 7.1 ± 0.56 in 4000 ppm treatment group; 

mean ± SEM).  The number of implants per pregnant dam were also marginally reduced from 9.6 

± 1.10 in controls to 7.7 ± 5.2 in pups in the 4000 ppm treatment group, but the effect was not 

statistically  significant.  A statistically significant (p<0.01) decrease in live pup weight at birth 

was observed in the 4000 ppm group (5.2 g vs. 5.7 g in controls); however, no significant 

alterations in pup body weight were observed at 5 days of age. 

Pregnancy rates in mice ranged from 55% in controls to 55%-70% in the barium-exposed 

groups.  No alterations in maternal weight gain, average length of gestation, pup survival, or pup 

weights were observed in mice.  A statistically significant (p<0.05) decrease in average litter size 

occurred on days 0 and 5 in the 1000 ppm treatment group but not in the 2000 ppm treatment 

group (day 0, 10.7 ± 0.40 pups in controls compared to 7.9 ± 1.02 pups for 1000 ppm treatment 

group; day 5, 10.8 ± 0.38 pups compared to 7.7 ± 0.97 pups in the 1000 ppm treatment group). 

No external abnormalities were observed in the mouse offspring.  No alterations in epididymal 

sperm counts, sperm motility, sperm morphology, testicular or epididymal weights, or vaginal 

cytology were observed in rats or mice. 

4.3.2.  Inhalation Exposure 

Information on the reproductive/developmental toxicity of inhaled barium compounds is 

limited to a series of studies conducted by Tarasenko et al. (1977).  The results of these studies 

were described in general terms and no data were provided.  The poor reporting of the study 

design and results and the lack of statistical analysis of the data limit the usefulness of the data 

for assessing the reproductive/developmental toxicity of barium. 

Exposure of male rats to 22.6 mg/m

3

 barium carbonate (15.7 mg Ba/m

3

) for one cycle of 

spermatogenesis (daily exposure duration and frequency of exposure were not reported) resulted 

in decreases in the number of spermatozoids, decreased percentage of motile forms and time of 

motility, decreases in osmotic resistance of spermatozoids, increases in the number of ducts with 

desquamated epithelium, and a reduced number of ducts with 12th stage meiosis (Tarasenko et 

29

---