Toxicity Of Diethylene Glycol Research Articles

THE TERATOGENIC EFFECT OF DIETHYLENE GLYCOL (DEG) ON FETUS MORPHOLOGY IN WHITE MICE (MUS MUSCULUS L.)

Objective: Diethylene glycol is listed in the Inventory of Cosmetic Ingredients as a solvent, viscosity controller, and fragrance. Most of diethylene glycol's toxicity is caused by ingesting the contaminated product. This study aims to determine the effect of a teratogen caused by diethylene glycol on mice fetuses.
 Methods: In this study, 20 mice were used, which were divided into four groups. Diethylene glycol was given with three variations of doses 1662.5, 3325, and 6650 mg/kgBW during the organogenesis period, day 6-15. The effects of teratogens observed were maternal body weight, fetal body weight, and number of fetuses, which were analyzed using one-way ANOVA, as well as morphological and skeletal abnormalities, which were analyzed descriptively.
 Results: Based on the results of the study, there was a significant difference in the body weight of the mice given diethylene glycol and the control group (p<0.05). There was no significant difference in body weight and the number of fetuses in the control and treatment groups (p>0.05). On the results of fixation of Bouins' solution, defects in the form of hemorrhage, resorption sites, and slow growth were found. At the same time, the results of the fixation of alizarin red solution found defects in the sternal, nasal, caudal, metacarpal, metatarsal, and phalanges bones.
 Conclusion: The conclusion based on the research is that diethylene glycol has the potential to provide teratogenic effects on mouse fetuses.

Variable sensitivity to diethylene glycol poisoning is related to differences in the uptake transporter for the toxic metabolite diglycolic acid

Introduction/Context Poisonings with diethylene glycol are characterized by acute kidney injury and peripheral neuropathy. In animal studies on the toxicities of diethylene glycol and its metabolite diglycolic acid, remarkable differences in susceptibility to acute kidney injury were observed in identically-dosed rats. In those studies, only about 60% showed acute kidney injury, yet all rats with acute kidney injury showed marked diglycolic acid accumulation in tissues, while no diglycolic acid accumulated in rats without injury. Diglycolic acid is taken into renal cells via sodium-dependent dicarboxylate transporters. When sodium-dependent dicarboxylate transporter-1 is inhibited or knocked down in human kidney cells, diglycolic acid uptake and toxicity are reduced. We hypothesize that the variation in sensitivity to tissue diglycolic acid retention and to diethylene glycol/diglycolic acid toxicity is explained by differential expression of sodium-dependent dicarboxylate transporter-1 in rat kidneys. Methods Using kidney tissue from previous studies, we performed rt-PCR analysis of sodium-dependent dicarboxylate transporter-1 mRNA. In those studies, Wistar-Han rats were either gavage with diethylene glycol 6 g/kg every 12 h for 7 days or with single doses of diglycolic acid 300 mg/kg. Kidney tissue was harvested after euthanasia and preserved in formalin. Tissue slices were homogenized and RNA was isolated using an RNAstorm FFPE RNA Isolation Kit. The expression of sodium-dependent dicarboxylate transporter-1 mRNA was compared between groups that showed diglycolic acid accumulation and acute renal injury with those that showed no diglycolic acid accumulation or toxicity. Results Significantly higher expression of sodium-dependent dicarboxylate transporter-1 mRNA was present in the kidneys of rats with acute kidney injury and diglycolic acid accumulation compared to those in rats that had no diglycolic acid in their kidneys and no acute kidney injury. Discussion The likelihood of acute kidney injury after dosing of rats with diethylene glycol or diglycolic acid is linked with an enhanced ability to take up diglycolic acid into renal cells via the sodium-dependent dicarboxylate transporter-1. The variability in diethylene glycol toxicity in humans, as reported in epidemiological studies, may also be linked with differences in tissue uptake of diglycolic acid. Conclusions Animals with acute kidney injury after exposure to diethylene glycol or diglycolic acid had higher sodium-dependent dicarboxylate transporter-1 expression and greater diglycolic acid accumulation in renal tissues than animals without acute kidney injury.

High-Anion-Gap Metabolic Acidosis During a Prolonged Hospitalization Following Perforated Diverticulitis: An Educational Case Report.

The metabolic acidoses are generally separated into 2 categories on the basis of an anion gap calculation: high-anion-gap and normal anion-gap metabolic acidosis. When a high-anion-gap metabolic acidosis (HAGMA) is not clearly explained by common etiologies and routine confirmatory testing, specialized testing can definitively establish rare diagnoses such as 5-oxoproline, d-lactate accumulation, or diethylene glycol toxicity. A 56-year-old woman had a prolonged hospital admission following perforated diverticulitis requiring sigmoid resection. Her hospitalization was complicated by feculent peritonitis and surgical wound dehiscence needing prolonged broad-spectrum antibiotics and wound debridements. She developed acute kidney injury and HAGMA in the hospital. Chart review showed that she received a large cumulative dose of acetaminophen during her hospital stay. Laboratory studies showed markedly increased serum 5-oxoproline causing HAGMA. Patient was admitted to the intensive care unit and treated with N-acetylcysteine and renal replacement therapy. After admission to the intensive care unit, the patient continued to require vasopressor and ventilatory support for septic shock and a ventilator-associated pneumonia. After an initial recovery and resolution of her HAGMA, she subsequently suffered recurrent aspirations which were fatal. 1. The acronym GOLD MARK is useful when assessing patients with HAGMA and most causes of HAGMA can be established with routine testing.2. When the etiology of HAGMA remains unclear, additional testing can be required to diagnose rare causes of HAGMA.3. Rare causes of HAGMA are diethylene glycol, 5-oxoproline, and d-lactate accumulation.4. Acidosis secondary to 5-oxoproline accumulation can occur even with "therapeutic" doses of acetaminophen in patients receiving it regularly for a prolonged period and who have depleted glutathione stores.5. Risk factors for glutathione depletion include malnutrition, older age, sepsis, pregnancy, multiple chronic illnesses, and chronic kidney disease.

Human health assessment for long-term oral ingestion of diethylene glycol

Diethylene glycol (DEG) is an organic chemical that is used mostly as a chemical intermediate and has minor uses as a solvent or antifreeze in consumer products; these minor uses could result in potential human exposure. Potential short and long-term human exposures also occur from misuses. The considerable reporting of DEG misuses as a substitute for other solvents in drug manufacturing and summaries of important events in the history of DEG poisonings are reviewed. Given the potential for human exposure, the disposition and toxicity of DEG were examined, and a health assessment was performed. Toxicokinetics and metabolism studies are evaluated, along with a discussion on the renal toxicity mode of action in the rat. Additionally, in-depth assessments of the key animal research studies on the toxic effects of DEG from oral ingestion for various exposure time periods are presented with determination of NOAELs and LOAELs from the long-term exposure animal studies. These are applied in the derivation of a reference dose for a non-cancer endpoint from chronic exposure, resulting in a value of 0.3 mg DEG/kg bw.

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

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

Comparative acute toxicity of diethyleneglycol dinitrate to freshwater aquatic organisms

AbstractThe acute toxicity of diethyleneglycol dinitrate (DEGDN) to nine freshwater aquatic organisms was determined. Juvenile fathead minnow, bluegill, channel catfish and rainbow trout were exposed to the compound for 96 h. The invertebrates tested for 48 h included the neonate water flea, early‐young amphipod, midge larva and the mayfly larva. The effect of DEGDN on the growth of the green alga Selenastrum capricornutum was also studied.The toxicity of DEGDN was relatively low to the nine freshwater species tested. Toxicity values ranged from a 5‐d EC50 (standing crop) of less than 58.4 mg/L for the alga to a 96‐h LC50 of 491.4 mg/L for the fathead minnow. The most sensitive invertebrate, the daphnid, was more sensitive than the most sensitive fish, the bluegill.

Studies on the Toxicity of Diethylene Glycol, Elixir of Sulfanilamide-Massengill and a Synthetic Elixir

Studies on the Toxicity of Diethylene Glycol, Elixir of Sulfanilamide-Massengill and a Synthetic Elixir