Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2568449 | Toxicology and Applied Pharmacology | 2015 | 8 Pages |
Abstract
Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10Â g/kg DEG and blood, kidney and liver tissues were collected at 48Â h. Both rat strains treated with 10Â g/kg DEG had equivalent degrees of metabolic acidosis, renal toxicity (increased BUN and creatinine and cortical necrosis) and liver toxicity (increased serum enzyme levels, centrilobular necrosis and severe glycogen depletion). There was no liver or kidney toxicity at the lower DEG doses (2 and 5Â g/kg) regardless of strain, demonstrating a steep threshold dose response. Kidney diglycolic acid (DGA), the presumed nephrotoxic metabolite of DEG, was markedly elevated in both rat strains administered 10Â g/kg DEG, but no DGA was present at 2 or 5Â g/kg, asserting its necessary role in DEG-induced toxicity. These results indicate that mechanistically in order to produce toxicity, metabolism to and significant target organ accumulation of DGA are required and that both strains would be useful for DEG risk assessments.
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Authors
Greg M. Landry, Cody L. Dunning, Fleurette Abreo, Brian Latimer, Elysse Orchard, Kenneth E. McMartin,