Short-Term Reproductive and Developmental Toxicity of Tribromoacetic Acid (CAS No. 75-96-7) Administered in Drinking Water to Sprague Dawley Rats
Report Date: July 28, 1998
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 tribromoacetic acid 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 tribromoacetic acid exposure.
The dose range-finding study was conducted at concentrations of 0, 30, 100, 300, and 500 ppm of TBA in the drinking water for two weeks. Based on decreased water consumption in the 500 ppm males and females, the dose levels of 0, 10, 70, and 400 ppm (Groups 1, 2, 3, and 4, respectively) were selected for the main study, which utilized two groups of male rats designated as Group A (non-BrdU treated animals, 10 rats in Groups 1, 2, 3, and 4) and Group B (BrdU-treated, 5 rats in Groups 1, 2, and 3, and 8 rats in Group 4), and three groups of female rats designated as Group A (peri-conception exposure, 10 rats in Groups 1, 2, 3, and 4), Group B (gestational exposure), and Group C (peri-conception exposure, BrdU-treated, 5 rats in Groups 1, 2, and 3, and 8 animals in Group 4). Control animals received deionized water, the vehicle.
During the treatment period, all animals survived to the scheduled necropsy and there were no clinical signs of general toxicity noted at any dose level. There were no treatment-related findings in body weights or feed consumption, but there was a slight and inconsistent decrease in water consumption in the 400 ppm animals. The overall calculated consumption of TBA for Groups 2-4 was 1, 7, and 39 mg/kg/day, respectively. Male and female gross necropsy findings were comparable across dose groups with the exception of a 40% incidence of mottled kidneys in the 400 ppm A males. Female and male reproductive findings were unremarkable. The visceral evaluation of the newborn heart and brain using Wilson's soft tissue free hand slicing technique did not reveal any treatment-related effects. Adult male organ weights, organ-to-body weight ratios, and clinical chemistry and hematology endpoints were unaffected by TBA treatment with the following exceptions: a 14 % increase in liver-to-body weight ratio in the 400 ppm A males, and an increase of 12% and 10%, respectively, in blood urea nitrogen and serum albumin in the 400 ppm A males. The increases in BUN and albumin represent a small, but possible biologically significant indicator of dehydration, probably attributable to decreased fluid consumption. The increase in BUN accompanied by the increase in mottled kidneys may also suggest mild kidney toxicity which could result in morphological changes with a longer term exposure. No treatment-related histopathology was noted in the organs of the A males or in cellular proliferation as measured by BrdU Labeling Index from the liver, kidney, or urinary bladder from the B males or C females.
The results of this study indicate that TBA at up to 400 ppm marginally reduced water consumption and did not affect reproductive function or produce general toxicity. From these data, TBA is not a reproductive toxicant in males or females at doses up to 400 ppm. This conclusion rests heavily on the shortness of the current exposure, and should be replicated using a longer study before the data are relied on.