Acute, high dose ethylene glycol administration produces no neuroinflammation, no abnormal brain or liver histology, significant urinary oxalate excretion, and minimal nephrotoxicity in male CD-1 mice.

The hallmarks of ethylene glycol (EG) toxicity are very well characterized in rat and female mouse models, and includes glycolate-mediated metabolic acidosis with calcium oxalate monohydrate (COM) target-organ accumulation. However, high dose, acute EG target organ toxicity has yet to be assessed in male CD-1 mice. Therefore, our studies utilize 9-week-old, male CD-1 mice to assess EG toxicity at 3 concentrations (3, 6, and 12 g/kg) in the mouse for 24, 48, and 72 h. Results indicate that 6 and 12 g/kg EG induce a 2.5-fold increase in serum creatinine 72h-post gavage with minor kidney damage, and no COM crystal tissue deposition with majority of oxalate being excreted in the urine. Oxalate alone (4 and 10 mM) induces a 27% and 31% decrease in ATP, respectively after 6 and 12 h in mouse proximal tubule cells in vitro. Additionally, only the 12 g/kg EG dose induced significant metabolic acidosis at 24 h, but not at 48 or 72 h. Furthermore, at these EG doses there was no gross brain tissue injury or neuroinflammation. These results imply that even at significantly higher EG doses, male CD-1 mice are insensitive to EG-induced target organ damage due to high urinary oxalate excretion.