Fatty acids, C14-18 and C16-18-unsatd., barium salts

Neurotoxicity

Additional information

Oral exposure of rats and mice to barium chloride was not associated with changes in brain weight or gross or microscopic lesions of the brain as documented by the following studies.

The administration of barium chloride in doses of 100, 145, 209, and 300 mg/kg bw/d for 10 days produced no significant adverse health effects up to doses of 209 mg/kg bw/d (NOAEL) (Borzelleca et al., 1988). In a 15-day study rats were exposed to 125, 250, 500, 1000, or 2000 ppm barium chloride in drinking water. No significant differences in neurobehavioral and behavioural parameters and brain weight were observed (NTP, 1994). Thus, the highest dose of 2000 ppm corresponding to an average daily dose of 110 mg Ba/kg bw can be considered as NOAEL for these parameters.

 

In a 13-week study by NTP (1994) rats and mice were exposed to 125, 500, 1000, 2000, or 4000 ppm barium chloride in drinking water. The no-observable-effect concentration was estimated to be 2000 ppm as based on changes of the final mean body weights, mean body weight gains, mortality, and renal toxicity at 4000 ppm. Thus, the dose of 2000 ppm represents the NOAEL value of this study corresponding to 110 and 115 mg Ba/kg bw/d to male and female rats, respectively, and 205 and 200 mg Ba/kg bw/d to male and female mice, respectively. The study design of the 13-week barium chloride drinking water study on rats and mice by Dietz et al. (1992; cf. above) also included a behavioural test battery. Rats and mice exposed to 2000 ppm or lower did not show any consistent changes in behavioural indices (motor activity, fore- and hind limb grip strength, and thermal sensitivity). No significant or dose-related effects were seen in the startle response to acoustic and air-puff stimuli or the hind limb foot splay. The NOAEL of 2000 ppm barium chloride corresponded to final barium doses of 61 and 81 mg Ba/kg bw/d to male and female rats, respectively, and of 165 and 166 mg Ba/kg bw/d to male and female mice, respectively.

Histological examination of 34 tissues of rats which were exposed to 1, 10, 100 or 250 ppm barium chloride in drinking water for up to 68 weeks demonstrated no significant changes (McCauley et al., 1985).

Taking all studies together, it is proposed to derive as NOAEL for effects on the brain a dose of 61 mg Ba/kg bw/d (male rats) from the 13-week study on rats (Dietz et al., 1992).

No data were available regarding neurological effects in animals following inhalation or dermal exposure.

In an epidemiological study by Morton et al. (1976), a statistically significant negative correlation was found between barium concentrations in tap water and neural tube malformation rates of the central nervous system in South Wales. Thus, this statistical study is of limited value in identifying adverse effects of barium in humans.

Some sporadic evidence for neurological activity of barium ions has been obtained from a number of in vitro investigations in specific tissue preparations (cervical ganglia, adrenal glands, guinea pig ileum longitudinal muscle) and cell types (glomus cells of carotid bodies).