Abstract
Purpose: Phosphoric acid has been widely used as an acid for crystallization of pharmaceuticals. It has been reported that bolus intravenous administration of phosphoric acid to rats causes glomerulopathy as a nephrotoxicity phenotype due to calcium phosphate crystallization during filtration through glomerular capillaries (Tsuchiya et al., 2004). In this study, we conducted an intravenous toxicity study of phosphoric acid in rats to investigate whether this nephrotoxicity can be avoided by decreasing the transient high phosphoric acid concentration in plasma by reducing the rate of administration.
Methods: Phosphate buffer was administered to female rats for 11 days by intravenous bolus administration or 30-minute infusion. Parameters evaluated in this study included mortality, clinical observations, body weights, clinical pathology (hematology, clinical chemistry and urinalysis), gross pathology, organ weights and histopathology.
Results: In the bolus administration group, increase of cystatin-C and albumin (nephrotoxicity biomarkers) in the urinalysis and glomerulopathy in the kidney histopathological examination were observed. On the other hand, 30-minute infusion group showed only transient increase of inorganic phosphorus and decrease of calcium in the clinical chemistry. These transient abnormal findings were milder than in the bolus administration group.
Conclusion: Infusion administration may have lower risk for phosphoric acid induced glomerulopathy or abnormal findings for nephrotoxicity biomarkers than bolus administration in rats.
