Concise International Chemical Assessment Document 33

Concise International Chemical Assessment Document 33

16

mg/litre (160 mg barium/kg body weight per day for

males and 200 mg barium/kg body weight per day for

females). The next lower exposure level, 1250 mg/litre (75

mg barium/kg body weight per day in males and 90 mg

barium/kg body weight per day in females), is a chronic

NOAEL. The incidences of neoplasms in the barium-

exposed mice were not significantly higher than in

control mice. In the 2500 mg/litre female mice, the

incidences of several neoplasms were significantly lower

than in the controls; the authors attributed this finding

to the marked reduction in survival in the barium-

exposed animals.

Schroeder & Mitchener (1975a) exposed Long-

Evans rats (52 per sex per group) to 0 or 5 mg barium/litre

(as barium acetate) in drinking-water from weaning to

natural death (approximately 2 years). Dosages from

drinking-water were 0.61 mg barium/kg body weight per

day for males and 0.67 mg barium/kg body weight per

day for females based on reference body weights and

water intakes from US EPA (1988). The diet was charac-

terized as a “low metal” diet, and it included 60% rye

flour, 30% dried skim milk, 9% corn oil, 1% iodized

chloride, and assorted vitamins; the barium content was

not reported. Barium had no significant effect on the

growth of males, but increased the growth of older

females. The incidence of proteinuria in males exposed to

barium for approximately 152 days (at 173 days of age)

was significantly higher than in controls. Female rats at

532 and 773 days of age had higher serum cholesterol

concentrations, and males at these ages had serum

glucose levels different from controls; the authors

attached no biological or toxicological significance to

these serum chemistry results. Histopathology of heart,

lung, kidney, liver, and spleen did not reveal alterations.

No significant increases in the number of gross tumours

were observed in the barium-exposed male or female rats.

Kopp et al. (1985) treated weanling female Long-

Evans rats with barium chloride in their drinking-water

(100 mg/litre) for 16 months and compared them with a

control group supplied with water containing no barium.

All animals received a standard rye-based diet, low in

heavy metal content. Random batches of this feed were

assayed for metal content and contained 1.5 µg barium/g

feed. Average final body weights for both groups were

found to be the same (control, 421 g; 100 mg barium/litre,

431 g). Furthermore, the measured haematological

characteristics as well as feed and water consumption

were not affected during the 16-month experiment.

However, a significant increase in the average systemic

blood pressure was detected in the barium-exposed rats

after 1 month exposure and thereafter. 

In similarly exposed Charles River CD white mice

(36–54 per sex) (Schroeder & Mitchener, 1975b), dosages

from drinking-water were 1.18 mg barium/kg body weight

per day for males and 1.20 mg barium/kg body weight per

day for females (US EPA, 1988). Growth and body

weights were not affected by the barium treatment.

Histology of the heart, lung, liver, kidney, and spleen

was normal. In males, longevity (defined as the mean life

span of the last surviving five animals of each sex in

each treatment group) was significantly reduced. The

mean life span, however, was not affected. The

incidences of lymphoma leukaemia and lung tumours in

the male and female mice exposed to barium were not

significantly different from the incidences in the control

mice.

Perry et al. (1983, 1985, 1989) exposed female

weanling Long-Evans rats to 0, 1, 10, or 100 mg barium/

litre (as barium chloride) in drinking-water for 1, 4, and 16

months. Drinking-water was fortified with five essential

metals (1 mg molybdenum/litre, 1 mg cobalt/litre, 5 mg

copper/litre, 10 mg manganese/litre, and 50 mg zinc/litre).

All animals received a rye-based diet with low trace metal

content based on that used by Schroeder & Mitchener

(1975a,b). After 8 months of exposure to 10 mg/litre,

mean systolic blood pressure had increased by 6 mmHg

(800 Pa) and continued to be significantly elevated

through 16 months (+4 mmHg [530 Pa]). Significant

increases in mean systolic blood pressure were evident

at 100 mg/litre starting at 1 month (+12 mmHg [1600 Pa])

and continuing through 16 months (+16 mmHg [2130

Pa]). An additional 12 rats, exposed for 16 months to 100

mg/litre, exhibited a reduction of ATP and

phosphocreatinine content of the myocardium,

depressed rates of cardiac contraction, and depressed

electrical excitability (compared with 18 control rats).

Since this study used a diet low in essential metals,

specifically calcium, the observation of barium chloride-

related effects on hypertension in rats is of questionable

significance to humans.

8.6

Genotoxicity and related end-points

There is a limited amount of information available

on the genotoxicity of barium compounds. No in vivo

studies have been conducted. Most in vitro studies

have found that barium chloride and barium nitrate did

not induce gene mutations in bacterial assays with or

without metabolic activation. Ames assays with

Salmonella typhimurium strains TA1535, TA1537,

TA1538, TA97, TA98, and TA100 with or without

metabolic activation (Monaco et al., 1990, 1991; NTP,

1994), rec assays with Bacillus subtilis strains H17 and

H45 (Nishioka, 1975; Kanematsu et al., 1980), and a

microscreen assay with Escherichia coli with metabolic 

---