The safety of polyethylene glycol-g-polyvinyl alcohol (PEG-PVA) grafted copolymer was evaluated in a 13-week oral toxicity study in rats and in a 9-month oral toxicity study in dogs. Wistar rats were administered 600, 3000, or 15,000 ppm PEG-PVA grafted copolymer in their drinking water whereas beagle dogs were fed 3000, 10,000, or 30,000 ppm PEG-PVA grafted copolymer in the diet. There were no mortalities, no adverse clinical signs, no toxicologically adverse effects on body weight or body weight gain, feed consumption, hematological, clinical chemistry or urinary parameters, or histopathology in either species. In rats, no treatment-related effects were observed in the functional observational battery (FOB) or related measurements of motor activity. Increased water consumption observed in rats at the highest dose was the only test substance-induced effect noted. The no-observed-adverse-effect level (NOAEL) was the highest concentration tested in both species: 15,000 ppm in rats (corresponding to a daily intake of 1611 mg/kg bw for males and 2191 mg/kg bw for females) and 30,000 ppm in dogs (corresponding to a mean daily intake of 783 mg/kg bw for males and 811 mg/kg bw for females).
Keywords: Excipient; FOB; Film coating polymer; Kollicoat® IR; Oral; PEG; PEG–PVA; PVA; Polyethylene glycol-g-polyvinyl alcohol grafted copolymer; Subchronic; functional observational battery; polyethylene glycol; polyethylene glycol-g-polyvinyl alcohol; polyvinyl alcohol.
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