Report Date: June 11, 1996
The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental toxicity criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
The potential toxicity of sodium bromate was evaluated using a short-term reproductive and developmental toxicity screen. This study design was selected to identify the process (development; female reproduction; male reproduction; various somatic organs/processes) that is the most sensitive to sodium bromate exposure.
A dose range-finding study was conducted at concentrations of 0, 250, 500, 1000, and 2000 ppm in order to select concentrations for the 35-day study. Based on dose-related body weight reductions and decreased feed and water consumption, the concentrations for the 35-day study were selected to be 0, 25, 80, and 250 ppm. For the main study, Sprague-Dawley rats were administered sodium bromate at these concentrations in the drinking water over a 35-day period. One group of male rats (10 per group) and two groups of female rats designated as Group A (peri-conception, 10 per group) and Group B (gestational exposure, 13 per group) were used at each dose level. Control animals received deionized water, the vehicle.
During the treatment period, all animals survived to the scheduled necropsy and there were no general toxic effects noted at any level. The overall average calculated consumption of sodium bromate for Groups 2-4 was approximately 2.6, 9.0, and 25.6 mg/kg body weight/day, respectively. There were no changes observed in the reproductive data for the Group A and Group B females. The male and female weekly absolute body weights, feed consumption, water consumption, clinical observations, and gross findings were comparable among dose groups. The male organ weights and organ-to-body weight ratios were also comparable across dose groups. Although there was no effect on male fertility, there was a slight decrease in epididymal sperm density, which decreased with increasing concentration and reached significance in the 250 ppm males (reduced by 18%). Sodium bromate resulted in no treatment-related gross or microscopic changes in the kidney, liver, spleen, testis, or epididymis. Serum ALT was decreased by 14% in the 80 and 250 ppm groups. Because this change was small, and in the absence of changes in other liver enzymes, this was deemed to be biologically insignificant.
Results of this study indicate that sodium bromate treatment did not produce any adverse signs of general toxicity in any of the dose levels tested, and based on these findings, a maximum tolerated dose was not reached. Female reproductive function was not adversely affected in this study. Sodium bromate appeared to slightly reduce male epididymal sperm density at 250 ppm. Based on the lack of general toxicity findings at any dose, and the epididymal sperm density decrease at 250 ppm , the no observable adverse effect level was determined to be 80 ppm. From these data, sodium bromate may be a selective male reproductive toxicant at 250 ppm since male reproductive toxicity was noted in the absence of general toxicity.