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 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 chlorodibromomethane 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 chlorodibromomethane exposure.
A dose-range finding study was conducted at concentrations of 0, 5, 50, 150, and 450 ppm in drinking water in order to select concentrations for the 35-day study. Based on dose-related body weight gain reductions and decreased water consumption, the concentrations for the 35-day study were selected to be 0, 50, 150, and 450 ppm. 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 clinical signs of general toxicity noted at any dose level. The male and female mean absolute body weights, feed consumption, clinical observations, and gross findings were comparable across dose groups. Water consumption was decreased by 13-44% at most of the intervals in all treated groups. The overall average calculated consumption of CDBM for Groups 2-4 was 5.7, 16.3, and 40.3 mg/kg/day, respectively. The male organ weights and organ-to-body weight ratios were also comparable across dose groups. There were no treatment-related reproductive findings in the males or females. There were biologically significant changes noted in male clinical chemistry endpoints: all treated males showed increases (although not always significant) in alkaline phosphatase (22-41%) and 5 nucleotidase (11-24%) and a decrease in total serum protein (5%) which may indicate mild liver damage.
Results of this study indicate that CDBM treatment did produce possible mild liver dysfunction in the 50, 150, and 450 ppm dose levels in males. A maximum tolerated dose in both males and females was achieved at 450 ppm based on a greater than 40% reduction in water consumption at that concentration of CDBM. Male and female reproductive function was not adversely affected in this study. From these data, CDBM may be a general toxicant at 50, 150, or 450 ppm in male rats and 450 ppm in female rats, but is not a reproductive toxicant in males or females at dose levels up to 450 ppm.