Toxicity of sodium bromide in rats: effects on endocrine system and reproduction.

Bromide has a low acute oral toxicity, with LD50 values in rodents ranging from 3500 to 7000 mg/kg body weight. It is rapidly absorbed and steady-state serum levels have been reached in rats within 4 weeks. The biological half-life of bromide, and consequently the serum levels, are strongly dependent on chloride intake. Feeding of sodium bromide to rats for 90 days in concentrations of 0, 75, 300, 1200, 4800 and 19,200 mg/kg diet led to a complex of changes in the endocrine system, thyroid activation being the most prominent. Furthermore, in the highest dose groups a decrease in spermatogenesis in the testes and decreased secretory activity of the prostate or a reduction in the number of corpora lutea in the ovaries were found. A three-generation reproduction study of the same dietary concentrations showed in the two highest dose groups a decrease in fertility which appeared to be reversible upon bromide withdrawal. Macroscopically, no changes in the offspring were observed. From these studies a no-effect level for bromide ion of 240 mg/kg diet was determined, corresponding to a tentative Acceptable Daily Intake (ADI) of 0.12 mg/kg body weight. This is in good agreement with a preliminary ADI of 0.1 mg/kg established in an experiment with human volunteers, but is considerably lower than the ADI of 1 mg/kg estimated by FAO/WHO. It is suggested that bromide exerts an inhibitory effect on the thyroid, resulting in an increased hormonal stimulation of this organ by the pituitary gland.