Renal tumors in male rats following long-term administration of bazedoxifene, a tissue-selective estrogen receptor modulator.

Bazedoxifene acetate (BZA) is a selective estrogen receptor modulator that is approved in a number of countries for the prevention and/or treatment of osteoporosis in postmenopausal women. To assess carcinogenic potential, BZA was administered ad libitum in the diet to male and female rats for 2 years. The achieved mean dosages of BZA were approximately 1.31 to 56.9 mg/kg/day at dietary concentrations of 0.003% to 0.1%. BZA treatment resulted in a reduction and a delayed onset in total tumor burden in both male and female rats. Survival rates were enhanced due to decreased pituitary and mammary tumors and decreased body weight gain in BZA-treated animals compared with controls. In male rats only, an increase in renal tubular tumors was observed. The greater increase in tumor incidence in male rats given BZA was associated with the increased survival and increased time for development of late onset tumors. These findings are consistent with a non-genotoxic mechanism, unique to male rats, that involves test article-induced corticomedullary mineralization, renal tubular injury, and exacerbation of naturally occurring chronic progressive nephropathy in aged male rats that led to a sequela of proliferative changes and tumor formation.

Effects of surface and groundwater interactions on phosphorus transport within streambank sediments.

Understanding internal stream P transfers is important in controlling eutrophication. To determine the direction of groundwater and surface water interactions and evaluate P retention within streambank sediments, groundwater well pairs, about 5-m deep, were installed at three locations along a second-order, eutrophic stream in north-central Texas. Well cores were analyzed for P, and groundwater levels were monitored for about 2 yr. Water levels in wells furthest upstream always indicated a losing stream, while wells further downstream showed a gaining stream except during flow reversals with storm events and periods with reservoir backwater. Total-P from well cores ranged from 54 to 254 mg kg(-1) and was typically high near surface, decreased downward until redoximorphic features were encountered and then increased notably with depth to near or above surface concentrations. Very little extractable P occurred in sediments from the two upstream well sets; however, the set furthest downstream showed extractable P throughout with a high of 21 mg kg(-1) near the bottom. Repeated wetting-drying at sites A and B as noted by redoximorphic features may have shifted P into more stable sediment-bound forms. The decrease in extractable P at sites A and B compared to site C may be explained by conditions at C that were wetter and potentially anaerobic. Because the overall stream reach was more often losing than gaining, there appears to be a mass flow of P into streambank sediments. Streambank erosion may then transport this P downstream if not controlled.