Subacute oral toxicity of tetraethylene glycol and ethylene glycoladministered to Wistar rats

Schladt, Ludwig; Ivens, Inge A.; Karbe, E.; Rühl-Fehlert, Christine; Bomhard, E.

doi:10.1016/s0940-2993(98)80096-1

Cited by 31 publications

(19 citation statements)

References 21 publications

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“…Schladt et al . () showed that tetraethylene glycol dosed up to 2 g kg –1 day –1 to Wistar rats for a period of 4 weeks did not cause any kidney effects compared with the known kidney toxicant ethylene glycol dosed in the same study. Ethylene glycol (2 g kg –1 day –1 ) caused slight decreases in urinary potassium, calcium and phosphate (males only) and a lower urinary pH.…”

Section: Discussionmentioning

confidence: 91%

Safety data on 19 vehicles for use in 1 month oral rodent pre‐clinical studies: administration of hydroxypropyl‐ß‐cyclodextrin causes renal toxicity

Healing

Sulemann

Cotton

et al. 2015

J of Applied Toxicology

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Potential new drugs are assessed in pre-clinical in vivo studies to determine their safety profiles. The drugs are formulated in vehicles suitable for the route of administration and the physicochemical properties of the drug, aiming to achieve optimal exposure in the test species. The availability of safety data on vehicles is often limited (incomplete data, access restricted/private databases). Nineteen potentially useful vehicles that contained new and/or increased concentrations of excipients and for which little safety data have been published were tested. Vehicles were dosed orally once daily to HanWistar rats for a minimum of 28 days and a wide range of toxicological parameters were assessed. Only 30% (w/v) hydroxypropyl-ß-cyclodextrin was found unsuitable owing to effects on liver enzymes (AST, ALT and GLDH), urinary volume and the kidneys (tubular vacuolation and tubular pigment). 20% (v/v) oleic acid caused increased salivation and hence this vehicle should be used with caution. As 40% (v/v) tetraethylene glycol affected urinary parameters, its use should be carefully considered, particularly for compounds suspected to impact the renal system and studies longer than 1 month. There were no toxicologically significant findings with 10% (v/v) dimethyl sulphoxide, 20% (v/v) propylene glycol, 33% (v/v) Miglyol®812, 20% (w/v) Kolliphor®RH40, 10% (w/v) Poloxamer 407, 5% (w/v) polyvinylpyrrolidone K30 or 10% (v/v) Labrafil®M1944. All other vehicles tested caused isolated or low magnitude effects which would not prevent their use. The aim of sharing these data, including adverse findings, is to provide meaningful information for vehicle selection, thereby avoiding repetition of animal experimentation.

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Section: Discussionmentioning

confidence: 91%

Safety data on 19 vehicles for use in 1 month oral rodent pre‐clinical studies: administration of hydroxypropyl‐ß‐cyclodextrin causes renal toxicity

Healing

Sulemann

Cotton

et al. 2015

J of Applied Toxicology

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“…TTEG's production and used as a solvent, plasticizer, lubricant, softening agent for paper tissue, a ceramic paste [3] printing ink binder and a liquid desiccant for natural gas. Moreover, tetraethylene glycol to the eye and the upper respiratory tract has slightly stimulation [4].…”

Section: Introductionmentioning

confidence: 99%

Oxidation of triethylene glycol and tetraethylene glycol by ditelluratocuprate(III) in alkaline medium - A kinetic and mechanistic study

2013

Eur. J. Chem.

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KEYWORDSThe kinetics of oxidation of triethylene glycol (TEG) and tetraethylene glycol (TTEG) by ditelluratocuprate(III) (DTC) in alkaline liquids were investigated spectrophotometrically in the temperature range of 20 o C to 40 o C. It was found that the reaction followed pseudo-first order in DTC and less than unit order in reductants. The rate constant kobs of pseudo-first order reaction decreased with an increase of [TeO4 2-], whereas adding [OH -] enhanced the constant. In addition, there was a negative salt effect. A suitable assumption involving preequilibriums before the rate controlling step and a free radical mechanism was proposed from the kinetics study. The rate equations derived from mechanism can explain all experimental phenomena. Moreover, the activation parameters at 298.2K and rate constants of the ratedetermining step were evaluated.

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“…However, EG, NH 4 Cl, and vitamin D 3 each has nephrotoxic effects and the administration of these compounds at high doses greatly aggravates the general condition of the rats 6,8 , 9 . In addition, if calcium oxalate deposits are rapidly observed in wide areas of the kidneys, this would indicate an abnormal physiological condition.…”

Section: Introductionmentioning

confidence: 99%

Study of a rat model for calcium oxalate crystal formation without severe renal damage in selected conditions

et al. 2005

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Background : Although nephrotoxic in high doses, ethylene glycol (EG) has been used with ammonium chloride (NH 4 Cl) or vitamin D 3 to study calcium oxalate stone formation in rat models. In the present study we used EG alone or with NH 4 Cl to study hyperoxaluria, crystaluria, and crystal attachment to renal epithelial cells in rats with minimal renal damage . Methods : Six-week-old male Sprague-Dawley (SD) rats were given food and special drinking water.In experiment 1 the drinking water contained 1.0% NH 4 Cl plus four different concentrations of EG (0.8%, 0.4%, 0.2%, 0.1%). In experiment 2 the drinking water contained EG alone (0.8%, 0.4%, 0.2%, 0.1%). Urine was collected for 24 h before the rats were sacrificed. In experiment 1 the rats were sacrificed 5-13 days after starting the special water. In experiment 2 the rats were sacrificed 7-21 days after starting the special water. Bladder urine was also obtained. Blood and urine were tested for calcium, phosphorus, and creatinine. In addition, urine was tested for pH, oxalate and Nacetyl-b -D glucosaminidase (NAG). Kidney sections were stained with hematoxylin-eosin, von Kossa and Pizzolato stain. Crystal morphology was determined using polarizing microscopy, and composition was determined using high-resolution X-ray powder diffraction . Results : Experiment 1: Aggravation of renal function, an increase in urinary oxalate and NAG excretion, and crystals observed in the kidneys all correlated with EG concentration and length of drinking time. In bladder urine, calcium oxalate monohydrate (COM) crystals exceeded calcium oxalate dihydrate (COD) crystals. Experiment 2: Renal function remained unchanged. Oxalate excretion increased and NAG increased slightly. Crystals occurred only in the papillary tip region. Crystals in bladder urine were mostly COD . Conclusion : In the current rat model, calcium oxalate crystaluria could be induced without severe renal damage in selected cases. Either and/or both COM and COD might form and interact with kidney epithelium. We propose different experimental conditions to study the various phases of calcium oxalate stone formation in young male SD rats.

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Subacute oral toxicity of tetraethylene glycol and ethylene glycoladministered to Wistar rats

Cited by 31 publications

References 21 publications

Safety data on 19 vehicles for use in 1 month oral rodent pre‐clinical studies: administration of hydroxypropyl‐ß‐cyclodextrin causes renal toxicity

Safety data on 19 vehicles for use in 1 month oral rodent pre‐clinical studies: administration of hydroxypropyl‐ß‐cyclodextrin causes renal toxicity

Oxidation of triethylene glycol and tetraethylene glycol by ditelluratocuprate(III) in alkaline medium - A kinetic and mechanistic study

Study of a rat model for calcium oxalate crystal formation without severe renal damage in selected conditions

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