Toxicity of litholytic ethylenediaminetetraacetic acid solutions to the urothelium of the rat and dog

Oosterlinck, Willem; Verbeeck, Ronald; Cuvelier, Claude; Verplaetse, H.; Verbaeys, Antony

doi:10.1007/bf00305309

Cited by 8 publications

(6 citation statements)

References 5 publications

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“…11 It is also approved for oral use in treating heavy metal intoxication. 12 Some groups 13,14 reported urothelial toxicity when using EDTA intravesically. However, these studies differed from our own as they used EDTA at higher concentrations and higher pH values, and the EDTA was administered for prolonged periods of time.…”

Section: Discussionmentioning

confidence: 99%

EDTA‐induced urothelial cell shedding for the treatment of superficial bladder cancer in the mouse

Nativ¹,

Dalal²,

Hidas³

et al. 2006

Int J of Urology

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Aim:The aim of this study was to determine the effect of intravesical EDTA instillation on the development of intravesically implanted tumor cells in normal mice. Methods: The mouse bladder tumor (MBT-2) model was used in female C3H/eb mice to evaluate the amount of normal urothelial cell shedding, and the degree of tumor growth inhibition following intravesical EDTA instillation in comparison with phosphatebuffered saline (PBS) instillation. Results: At 1 h after instillation, the number of urothelial cells aspirated was 500-1000 per PBS-treated mouse and 10 000-20 000 per EDTA-treated mouse (P < 0.00001). The bladder weight, which reflected the effect of the agent on the tumor, was similar in the untreated and PBS-treated mice (105.46 ± 46 mg and 106.2 ± 50 mg, respectively). It was significantly lower in the EDTAtreated mice (80.4 ± 42 mg) (P = 0.0045). Conclusions: Intravesical administration of EDTA results in significant normal and neoplastic urothelial cell shedding. Intravesical irrigation with EDTA may prevent adherence of the malignant cells to the bladder wall following tumor resection.

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Section: Discussionmentioning

confidence: 99%

EDTA‐induced urothelial cell shedding for the treatment of superficial bladder cancer in the mouse

Nativ¹,

Dalal²,

Hidas³

et al. 2006

Int J of Urology

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“…Calcium chelating agents such as EDTA were toxic to the urothelium (Oosterlinck et al 1992) due to the calcium-binding mechanism itself. Dipotassium EDTA buffered with triethanolamine (TEA; pH 8 to 8.5) induced severe lesions to the urothelium of the rat and dog, such that erosion of <20% to >80% of the urothelium was observed (Oosterlinck et al 1991). At a concentration of 3.125 mM, Dipotassium EDTA caused severe lesions of the urinary bladder mucosa; slow perfusion rates and alternating treatment with physiological solution did not decrease the toxicity (Verplaetse et al 1985(Verplaetse et al , 1986.…”

Section: Effects On Mucosamentioning

confidence: 99%

Final Report on the Safety Assessment of EDTA, Calcium Disodium EDTA, Diammonium EDTA, Dipotassium EDTA, Disodium EDTA, TEA-EDTA, Tetrasodium EDTA, Tripotassium EDTA, Trisodium EDTA, HEDTA, and Trisodium HEDTA

2002

Int J Toxicol

106

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EDTA (ethylenediamine tetraacetic acid) and its salts are substituted diamines. HEDTA (hydroxyethyl ethylenediamine triacetic acid) and its trisodium salt are substituted amines. These ingredients function as chelating agents in cosmetic formulations. The typical concentration of use of EDTA is less than 2%, with the other salts in current use at even lower concentrations. The lowest dose reported to cause a toxic effect in animals was 750 mg/kg/day. These chelating agents are cytotoxic and weakly genotoxic, but not carcinogenic. Oral exposures to EDTA produced adverse reproductive and developmental effects in animals. Clinical tests reported no absorption of an EDTA salt through the skin. These ingredients are likely, however, to affect the passage of other chemicals into the skin because they will chelate calcium. Exposure to EDTA in most cosmetic formulations, therefore, would produce systemic exposure levels well below those seen to be toxic in oral dosing studies. Exposure to EDTA in cosmetic formulations that may be inhaled, however, was a concern. An exposure assessment done using conservative assumptions predicted that the maximum EDTA dose via inhalation of an aerosolized cosmetic formulation is below that shown to produce reproductive or developmental toxicity. Because of the potential to increase the penetration of other chemicals, formulators should continue to be aware of this when combining these ingredients with ingredients that previously have been determined to be safe, primarily because they were not significantly absorbed. Based on the available data, the Cosmetic Ingredient Review Expert Panel found that these ingredients are safe as used in cosmetic formulations.

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“…Our study also addresses the safety of the infusion of this formulation of 2% tEDTA. Other studies have found that various other forms of EDTA potentially caused urothelial damage in a variety of animal models . In these studies, the urinary tract was intermittently infused with various EDTA formulations for 6 to >20 hours.…”

Section: Discussionmentioning

confidence: 99%

“…In over 260 patients evaluated, over 50% had complete dissolution of their stones (146/260 patients) . Other studies using various solutions containing EDTA suggested potential topical urothelial toxicity . As a result, EDTA irrigation techniques for chemolysis of calcium stones were never adopted.…”

Section: Introductionmentioning

confidence: 99%

“…18 Other studies using various solutions containing EDTA suggested potential topical urothelial toxicity. [18][19][20] As a result, EDTA irrigation techniques for chemolysis of calcium stones were never adopted. However, more recent studies utilizing lower concentrations of EDTA solutions for irrigation have found no adverse effects on the urothelium.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic use of tetrasodium ethylenediaminetetraacetic acid solution for treatment of subcutaneous ureteral bypass device mineralization in cats

Chik

Berent

Weisse

et al. 2019

Veterinary Internal Medicne

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Background Subcutaneous ureteral bypass (SUB) device placement is an increasingly popular treatment option for decompression of ureteral obstruction in cats. Mineralization occlusion of the device occurs in a minority of cases but is the most common complication. Objective To evaluate a 2% tetrasodium ethylenediaminetetraacetic acid (tEDTA) solution for treatment of mineralization occlusion in cats with SUBs. Animals Six client‐owned cats (8 obstructed devices). Methods Case series. Each cat was found to have device occlusion based on a combination of ultrasound examination, SUB irrigation, and failure to identify another cause of device obstruction. Each SUB was drained, irrigated using sterile saline, and infused with 1‐2 mL of 2% tEDTA solution. Success was defined as normalization of flow during subsequent ultrasound visualization while irrigating. The volume and frequency of tEDTA instillations, time to achieve device patency, follow‐up biochemical and ultrasound findings, and future reobstruction events were recorded. Results Resolution of mineralization was documented in all 8 SUBs. Reobstruction events occurred in 2 cats, all of which resolved after additional tEDTA infusions, but 1 cat ultimately required device exchange at 356 days from the first tEDTA infusion. In 1 cat, a single infusion was prematurely discontinued because of persistent pelvic dilatation after 1.25 mL of tEDTA had been instilled. No complications were observed. Conclusions and Clinical Importance Tetrasodium EDTA infusions can be safely considered as a treatment option for mineralized SUB devices in cats. This solution was easily infused, well tolerated, and avoided the need for SUB device exchange in the majority of cats in which it was used.

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Toxicity of litholytic ethylenediaminetetraacetic acid solutions to the urothelium of the rat and dog

Cited by 8 publications

References 5 publications

EDTA‐induced urothelial cell shedding for the treatment of superficial bladder cancer in the mouse

EDTA‐induced urothelial cell shedding for the treatment of superficial bladder cancer in the mouse

Final Report on the Safety Assessment of EDTA, Calcium Disodium EDTA, Diammonium EDTA, Dipotassium EDTA, Disodium EDTA, TEA-EDTA, Tetrasodium EDTA, Tripotassium EDTA, Trisodium EDTA, HEDTA, and Trisodium HEDTA

Therapeutic use of tetrasodium ethylenediaminetetraacetic acid solution for treatment of subcutaneous ureteral bypass device mineralization in cats

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