Diethylene glycol-induced toxicities show marked threshold dose response in rats

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 10 g/kg DEG and blood, kidney and liver tissues were collected at 48 h. Both rat strains treated with 10 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 5 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 10 g/kg DEG, but no DGA was present at 2 or 5 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.

Protective effects of vitamin C against oxidative stress induced by diethylene glycol in liver and kidney

“…In accordance with previous studies. The beneficial vitamin C outcome is due to it's a very effectiveness as antioxidant, and an efficient hunter for oxygen free radicals and its being active in maintaining the physiological integrity of different tissues [10,11,12].…”

Comparison of diglycolic acid exposure to human proximal tubule cells in vitro and rat kidneys in vivo

“…However, the question of how these concentrations translate to in vivo dosing remains unanswered. Quantitative analyses of DGA levels in the kidneys of rats treated with DGA or even DEG like those performed in Robinson et al [31] and Landry et al [26] , respectively, would assist in helping to establish how in vivo dosing translates to renal exposure and hence give a better understanding of the in vivo state. Additional studies would be also be needed to better understand how ingested DGA can translate to in vivo blood levels and how these components enter the blood and get filtered through the glomerulus for further exposure to the proximal tubules.…”

Acidentes Ofídicos No Município De Mulungu, Serra De Baturité, Estado Do Ceará

“…O dietilenoglicol é um composto utilizado como solvente industrial ou anticongelante industrial, possuindo sabor adocicado e, ocasionalmente, pode ser ingerido de modo acidental por indivíduos de todas as idades, mas também perigosamente consumido em bebidas alcoólicas em uma tentativa de substituição do etanol (LANDRY et al, 2015).…”