Peroral Subchronic, Chronic Toxicity, and Pharmacokinetic Studies of a 100-KiIodaIton Polymer of Ethylene Oxide (Polyox N-10) in the Fischer 344 Rat

Abstract

Polyox Water Soluble Resins (CAS No. 25322–68–3) are high-molecular-weight polymers of ethylene oxide in a variety of viscosity grades. They are widely used in cosmetic formulations, as pharmaceutical excipients, and food contact applications. The potential for absorption and long-term toxicity (including oncogenicity) from peroral dosing was investigated using an N-10 grade with an average molecular weight of about 100,000 daltons. A subchronic (13-week) toxicity study with up to 3% Polyox N-10 in the diet of Fischer 344 rats showed slight increases in food consumption, body weight, and body weight gain. A dose-related increase in liver weight was observed, but this was not associated with any histopathology, and morphometric analysis showed no alteration in the number or size of the hepatocytes. Because of the lack of correlative pathology findings, the liver weight increase was considered not to be deleterious, but a secondary response to increased food consumption. A chronic (2-year) toxicity/oncogenicity study with up to 2% Polyox N-10 in the diet of Fischer 344 rats showed no effect with respect to clinical signs, body and organ weights, clinical pathology, urinalysis, and neoplastic and non-neoplastic pathology. Pharmacokinetic and material balance studies showed essentially complete recoveries (99% in males, 104% in females) from the excreta, with nearly all the radiolabel being eliminated in the feces (98% in males, 101% in females) in Fischer 344 rats given an oral dose of 14C-labelled Polyox N-10. Recoveries from the urine, expired air, blood, and other tissues were negligible (<1%). In conclusion, Polyox N-10 given orally is not absorbed from the gastrointestinal tract, and does not produce long-term and chronic toxicity, including oncogenicity.