Systemic toxicity and toxicokinetics of a high dose of polyethylene glycol 400 in dogs following intravenous injection

Abstract

Polyethylene glycol 400 (PEG-400) has been used in injections. However, limited data are available concerning the toxicity of a high dose of PEG-400 following intravenous (i.v.) injection. The aim of the present study was to estimate the systemic toxicity and toxicokinetics of a high dose of PEG-400 in dogs following i.v. injection. Twenty-four dogs were divided into four groups: a control group receiving normal saline and three test groups receiving 4.23, 6.34, and 8.45 g/kg of PEG-400, respectively, by i.v. injection once a day for 30 days. The repeated-dose toxicity of PEG-400 was assessed. Toxicokinetic parameters of PEG-400 in dogs were estimated on days 1 and 30. Dry mouth and dry nasal mucus membrane were observed in dogs treated with 6.34 and 8.45 g/kg of PEG-400. Cloudy swelling of kidney cell and increased glomerular volume were observed in dogs treated with 8.45 g/kg of PEG-400 when the animals were sacrificed 24 hours after the last injection. No significant histological changes were found 21 days later. Repeated dosing did not affect the toxicokinetic profile of PEG-400 in dogs. This study has shown that the toxicity of a high dose of PEG-400 following repeated intravenous injections is low, and alterations produced are reversible.

Biodegradable and Biocompatible Poly(Ethylene Glycol)‐based Hydrogel Films for the Regeneration of Corneal Endothelium

“…For both glucose and albumin measurements, the chambers were maintained at 35 °C with magnetic stirring in each cell. At set times (30,45,60,80, and 100 min), aliquots (2 mL) were removed from the target cell and replaced with fresh PBS (2 mL). For glucose measurements, samples were prepared for spectrophotometric analysis using a glucose assay kit and analysed using a Shimadzu UV-1800 spectrophotometer at 540 nm.…”

“…These results are unsurprising since degradation of the fi lm via hydrolysis of the ester bonds would yield low toxicity compounds such as PEG, sebacic acid, and 6-hydroxyhexanoic acid (from degradation of the PCL). Whereas PEG is approved by the FDA for certain human applications and is considered to be non-toxic, [ 45,46 ] sebacic acid is a dicarboxylic acid naturally present in cells as an intermediate in fatty acid oxidation. [ 47 ] Sebacic acid also has a very high LD50 (oral, rat) of 14.4 g kg −1 , which supports its low toxicity.…”

Intraperitoneal administration of high doses of polyethylene glycol (PEG) causes hepatic subcapsular necrosis and low-grade peritonitis with a rise in hepatic biomarkers

“…A maximum dilution of 30% is recommended when PEG is administered intravenously to humans and dogs, as higher concentrations may cause haemolysis (Rowe et al, 2009;Li et al, 2011). It remains to be clarified whether this is also a consequence of the hydrophilic properties of PEG-400 which are in our study the apparent cause for the local recruitment of fluid into the peritoneal cavity early (1 and 3 h) after its ip administration.…”

Thrombotic Microangiopathy Associated with Intravenous Injection of Opana ER®: University Medical Center Case Series

“…However, PEG has been used in certain IV medications with very few studies on toxicity. It does appear the major target organ for toxicity was the kidney when high doses of PEG were given to laboratory animals [8]. The disparity in molecular weights between the PEG used in this study of toxicokinetics and the PEO used in Opana ER could possibly contribute to systemic manifestations [7,8].…”