Rationale for local toxicity of calcium chelators

Oosterlinck, Willem; Verbeeck, Ronald; Cuvelier, Claude; Vergauwe, Donald

doi:10.1007/bf00294329

Cited by 6 publications

(3 citation statements)

References 9 publications

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“…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. Oosterlinck et al (1992) perfused rat urinary bladder with various chelating solutions for 6 hours at 1.4 ml/h. Magnesium HEDTA (25 to 200 mM, buffered with TEA), Disodium EDTA (12.5 mM, buffered and unbuffered ), and Potassium EDTA (12.5 mM, buffered), compared to 0.9% saline, signi cantly increased the number of lesions.…”

Section: Effects On Mucosamentioning

confidence: 96%

“…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).…”

Section: Effects On Mucosamentioning

confidence: 99%

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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

110

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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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Section: Effects On Mucosamentioning

confidence: 96%

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

110

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“…In fact, although dissolution of CaOx in vitro has been described [7][8][9][10], a che-molytic agent for the treatment of CaOx stones is not available yet. However, since research in the field of metal chelators is very active [11], new calcium binding compounds, less toxic than the ones now available [12,13], may eventually be developed. Some of these substances could be of potential usefulness in the treatment of CaOx stones, on condition that their capability of dissolving CaOx, an extremely insoluble salt (Ksp = 2.32 !…”

Section: Introductionmentioning

confidence: 99%

Development of an in vitro Assay for the Screening of Substances Capable of Dissolving Calcium Oxalate Crystals

Saso

Valentini²,

Leone³

et al. 1998

Urol Int

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Despite the risk of kidney damage, lithotripsy is the usual way of treating calcium oxalate (CaOx) stones, the most common type of nephrolithiasis, because no effective chemolytic agents are available. However, the search of new calcium chelators, less toxic than the current ones, continues, and some of them could be tested in experimental models of nephrolithiasis, after their ability of dissolving CaOx crystals is verified. In this connection, we developed a simple assay that requires only inexpensive equipment available in most laboratories for the screening of substances potentially capable of dissolving CaOx crystals. In particular, we decided to investigate whether substances previously shown to inhibit CaOx precipitation were also capable of dissolving this salt. Briefly, CaOx tablets of highly reproducible weight (4.55 ± 0.07 mg) were prepared by spinning, at high speed (16,000 g), microcentrifuge tubes in which 500 µl aliquots of 0.1 M sodium oxalate and 0.1 M calcium chloride at pH 6 were added. When these tablets were incubated overnight with solutions at different concentrations of EDTA, sodium citrate, manganese chloride, sodium sulfate, sodium chloride, malic acid, succinic acid and gluconic acid, a significant dissolving activity was observed for EDTA (∼25% at 0.25 M), sodium citrate (∼30% at 1 M) and manganese chloride (∼20% at 0.5 M). A good linear correlation (r² = 0.84, p < 0.05) was found between the affinity for calcium and the activity of EDTA, sodium citrate, sodium sulfate, malic acid, succinic acid and gluconic acid, indicating that these compounds act mainly by chelating the calcium ion. Instead, manganese was supposed to act by interacting with the oxalate ion.

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Chemolytic Treatment of Patients with Urinary Tract Stones

Tiselius

2010

Urinary Tract Stone Disease

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Rationale for local toxicity of calcium chelators

Cited by 6 publications

References 9 publications

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

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

Development of an in vitro Assay for the Screening of Substances Capable of Dissolving Calcium Oxalate Crystals

Chemolytic Treatment of Patients with Urinary Tract Stones

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