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 sodium selenate was evaluated using a short-term reproductive and developmental toxicity screen. This study design was selected to use a known toxic compound in a truncated test. This design extended previous studies by addressing both reproduction and development.
Sodium Selenate at dose levels of 0, 7.5, 15.0, and 30.0 ppm was administered in the drinking water over a 30-Day period. One group of male (10 per group) and three groups of female rats designated as Group A (peri-conception exposure, 10 per group), Group B (gestational exposure, 13 per group), and Group C (vaginal cytology, 10 per group) were used for each dose level. Control animals received deionized water, the vehicle.
Weekly absolute body weights and feed and water consumption values decreased with increasing dose. Water consumption decreased in all groups and was dramatically reduced in the 30 ppm group by approximately 70-80% compared to the controls. The majority of the 30 ppm females appeared thin during cageside observations on SD 7-30. Mortality was observed only in the 30 ppm group, especially just prior to or during parturition of the Group B females. The average calculated consumption of sodium selenate for Groups 2-4, was 0.5, 0.8, and 1.1 mg/kg/day, respectively.
Final body weights at necropsy for the 15 and 30 ppm males were 12% and 20%, respectively, lower than controls. Changes in relative organ weights (absolute organ weight/ body weight) were noted in the 15 and 30 ppm groups but they were attributed to the decrease in body weight, since animal size effects organ size (Stevens et. al. 1989). Sperm endpoints were generally unchanged. No treatment-related microscopic lesions were noted in the right kidney, liver, spleen, left testis, or left epididymis.
Group A females (treated before, during, and after mating) in the 30 ppm group had significantly fewer implants per litter and corpora lutea when compared to controls. The number live fetuses per litter were also slightly decreased. Because of the large reductions in fluid intake, it is believed that changes in reproductive parameters were the result of dehydration.
For the 30 ppm Group B gestationally-exposed females, there was a decrease in the number of live pups per litter (68% of control value), adjusted live pup weight (44% of control value), and the proportion of pups born alive (58% of control value). The average gestation length increased by 5% when compared to controls. The adjusted live pup weight was decreased during lactation for the 15 and 30 ppm females. Pup survival was reduced by 21% for the 15 ppm females, but was not statistically significant (due to high standard error, low sample size, and lack of dose response) when compared to the control group. Pup survival at 30 ppm was decreased by 73% when compared to the control group. These effects cannot be separated from dehydration, as indicated by the decreased water consumption and weekly mean absolute body weights in these groups. Treatment-related gross lesions were observed in 15 and 30 ppm Group B females. These included pale and small adrenals, thickened stomach walls, stomach adhesions involving abdominal organs, enlarged and small kidneys, enlarged spleen, and implantation sites with nodular material.
Evaluation of the Group C female vaginal cytology data revealed that the estrous cycle in the 7.5 and 15.0 ppm Group C females was comparable to the controls. The 30 ppm Group C females spent less time in estrus than the controls, and there was a 22% increase in cycle length.
Results of this study indicated that sodium selenate produced toxicity at 15 and 30 ppm, which had more restricted water consumption but also greater sodium selenate intake, than at 7.5 ppm. Reproductive toxicity was noted in both Group A and B females at 30 ppm based on increased gestation length and decreased number of live pups, live pup weight, proportion of pups born alive, number of implants and corpora lutea per litter, and pup survival. However, the toxicity of sodium selenate could not be separated from the effects due to reduced water consumption. Sodium selenate produced only minor effects on male reproductive function. Based on decreased weekly mean absolute body weights, and feed and water consumption values, a maximum tolerated dose was reached at 15 ppm. The no-observable-adverse-effect-level was not determined in females because there were decreased absolute body weights at 7.5 ppm. In this study, sodium selenate was not a selective reproductive toxicant, as it caused body weight decreases at doses below those that affected reproduction.