Dietary effects of ortho-phenylphenol and sodium ortho-phenylphenate on rat urothelium

Ortho-phenylphenol (OPP) and sodium ortho-phenylphenate (NaOPP) are pestici des used commercially in the food industry that have been shown to be carci nogenic to rat urothelium. Dietary administration of 1.25% OPP or 2.0% NaOP P caused increased incidences of urothelial hyperplasia and eventually caus ed tumors in male F344 rats, with NaOPP apparently having a more potent eff ect. In other studies, various sodium salts such as saccharin and ascorbate enhanced bladder carcinogenesis, although the acid forms of these salts di d not. In studies with high dietary doses of these sodium salts, an amorpho us precipitate was produced in the urine; precipitate formation was pH depe ndent. In previous experiments in which high doses of OPP were fed for up t o 17 weeks, severe hyperplasia of the urothelium was produced, but without the formation of an urinary amorphous precipitate, calculi, or abnormal mic rocrystalluria. In addition, we found no evidence of OPP-DNA adduct formati on in the urothelium. The present study was conducted to determine if feedi ng NaOPP . 4 H2O to male F344 rats as 2.0% of the diet resulted in the form ation of an amorphous precipitate in the urine, and if NaOPP caused an incr eased mineral concentration in the urine and/or kidneys. NaOPP administrati on produced a higher urinary pH than did OPP fed as 1.25% of the diet. Neit her amorphous precipitate nor other solids were observed in the urine of th e OPP or NaOPP-treated rats, and urinary calcium concentrations in the trea ted groups were similar to control OPP and NaOPP had similar proliferative effects on rat urothelium after 10 weeks of treatment by light microscopy, scanning electron microscopy (SEM), and bromodeoxyuridine (BrdU) labeling i ndices. The results of this study indicate that formation of abnormal urina ry solids is not part of the mechanism by which OPP or NaOPP exert their ef fects on the rat bladder epithelium.