Effects of polyethylene glycol 400 (PEG 400) following 13 weeks of gavage treatment in Fischer-344 rats

Fischer-344 rats (10/group/sex) were administered polyethylene glycol 400 (PEG 400) by gavage at 1.0, 2.5 or 5.0 ml/kg (1.1, 2.8 and 5.6 g/kg, respectively) body weight/day 5 days/wk for 13 wk. Animals in the control group received water by gavage (5.0 ml/kg body weight/treatment day). An additional 10 rats/sex/group were assigned to the control and high-dose groups for a 6-wk recovery period. Evaluation of potential renal toxicity was identified as a primary objective. There was no mortality or changes in haematology or clinical chemistry measurements attributed to PEG 400 toxicity. Loose faeces in the mid- and/or high-dose group of both sexes were attributed to bulk cathartic effects of PEG 400. Slight decreases in food consumption and body weights in the mid- and/or high-dose group of male rats and female rats were attributed to the physical presence of PEG 400 in the intestinal tract. However, a direct effect of PEG 400 on the intestinal tract was not ruled out. Increased water consumption was attributed to a possible increase in serum osmolality due to the absorption of the PEG 400 or a reflection of the water dosing received by the control Animals. Increased urinary concentration and decreased urinary pH were at least partially attributed to absorption, possible metabolism, and urinary excretion of PEG 400. Small increases in absolute and/or relative kidney weights observed in many dose groups, were attributed to the osmotic effect of the test substance and/or metabolites in the urine. The significance of a slight increase in relative kidney weights in female rats following the recovery period was unknown. Although no microscopic changes were observed in the kidneys or urinary bladder, a slight, reversible renal toxicity may have resulted in male rats treated by gavage with 2.5 ml/kg/day and rats of both sexes treated by gavage with 5.0 ml PEG 400 kg/day. This was based on the increased concentration of protein and bilirubin, urinary vascular cell findings and N-acetyl-beta-D-glucosaminidase activity.