Safety of PVAP and PVAP-T including a 90-day dietary toxicity study in rats and genotoxicity tests with polyvinyl acetate phthalate (PVAP).

Abstract The safety of PVAP was evaluated in a 90-day subchronic toxicity study in rats. Sprague Dawley Crl:CD(SD) rats were administered a dietary concentration of 0.75%, 1.5% and 5.0% PVAP for a minimum of 90 days. There were no adverse effects reported. The no-observed-adverse-effect level (NOAEL) in the 90-day sub chronic study was the 5% dietary concentration, which corresponds to a dose of 3120 mg/kg/day for males and 3640 mg/kg/day for females, the highest level tested. PVAP is co-processed with titanium dioxide to produce polyvinyl acetate phthalate and titanium dioxide (PVAP-T). The chemical composition, physiochemical properties and specifications of PVAP-T are unchanged during manufacturing process based on various analytical studies. Therefore, the toxicological data that support the safety of PVAP can be used to support the use of PVAP-T as a pharmaceutical excipient. An independent expert panel evaluated the safety of PVAP and PVAP-T. Based on the toxicology study results, safety assessment and the estimated exposure assessment for PVAP and PVAP-T, the expert panel concluded that PVAP and PVAP-T could safely be used in drug products up to 829 mg per day which was the estimated exposure provided to the expert panel for current applications of PVAP and PVAP-T.