Disposition of glycolic acid into the embryo following oral administration of ethylene glycol during placentation in the rat and rabbit.

This article investigates the role of the placenta in the developmental toxicity of ethylene glycol (EG) by examining the distribution of EG and its metabolites glycolic acid (GA) and oxalic acid (OX) in pregnant rats and rabbits at early and late stages of placentation. The study found that while EG and OX did not preferentially accumulate in embryonic tissues, GA selectively accumulated in rat embryos during early placentation (gestation day 11) but not later or in rabbits at any stage. This selective GA accumulation in rats correlates with the expression and polarity of monocarboxylate transporter isoforms (MCT1 and MCT4) in the placenta, which differ between species; notably, the human placental MCT polarity resembles that of rabbits. The findings suggest that GA-induced embryonic acidosis via MCT-mediated transport may underlie EG developmental toxicity in rodents, whereas rabbits—and by extension humans—are less susceptible due to placental transporter differences, supporting the rabbit as a more relevant model for human risk assessment.