Mode of Action: Oxalate Crystal-Induced Renal Tubule Degeneration and Glycolic Acid-Induced Dysmorphogenesis—Renal and Developmental Effects of Ethylene Glycol

Journal Article · Sat Oct 01 00:00:00 EDT 2005 · Critical Reviews in Toxicology

DOI:https://doi.org/10.1080/10408440591007322· OSTI ID:876954

Corley, Rick A; Meek, M E; Carney, E W

Ethylene glycol can cause both renal and developmental toxicity, with metabolism playing a key role in the mode of action (MOA) for each form of toxicity. Renal toxicity is ascribed to the terminal metabolite oxalic acid, which precipitates in the kidney in the form of calcium oxalate crystals and is believed to cause physical damage to the renal tubules. The human relevance of the renal toxicity of ethylene glycol is indicated by the similarity between animals and humans of metabolic pathways, the observation of renal oxalate crystals in toxicity studies in experimental animals and human poisonings, and cases of human kidney and bladder stones related to dietary oxalates and oxalate precursors. High-dose gavage exposures to ethylene glycol also cause axial skeletal defects in rodents (but not rabbits), with the intermediary metabolite, glycolic acid, identified as the causative agent. However, the mechanism by which glycolic acid perturbs development has not been investigated sufficiently to develop a plausible hypothesis of mode of action, nor have any cases of ethylene glycol-induced developmental effects been reported in humans. Given this, and the variations in sensitivity between animal species in response, the relevance to humans of ethylene glycol-induced developmental toxicity in animals is unknown at this time.

• Research Organization: Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 876954
• Report Number(s): PNNL-SA-46251; CRTXB2; TRN: US200608%%31
• Journal Information: Critical Reviews in Toxicology, Vol. 35, Issue 8-9; ISSN 1040-8444
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BLADDER
GLYCOLIC ACID
GLYCOLS
KIDNEYS
METABOLISM
METABOLITES
OXALATES
OXALIC ACID
TOXICITY
TUBULES
POISONING
RABBITS
RODENTS
SENSITIVITY
BIOLOGICAL EFFECTS
developmental toxicity
Glycolate
Human Relevance
Oxalate
Renal toxicity