Etidronic acid

Definition and Structure The ingredients in this report share the same structural Etidronic Acid core (Figure 1). Etidronic Acid, a crystalline diphosphonate with both detergent and chelating utilities, is a tetraprotic acid with the acidity of the first proton being rather strong, to the last being rather weak (pK a ’s: pK a1 1.35 ±0.08; pK a2 2.87 ±0.01; pK a3 7.03 ±0.01; and pK a4 11.3).4 The other three ingredients in this report are salts of Etidronic Acid (Table 1). Regardless of which of these four ingredients is added to a formulation, the pH of the formulation will dictate the degree of protonation in situ. Figure 1. Etidronic Acid Physical and Chemical Properties In addition to the acid disassociation characteristics above, other noteworthy physical and chemical properties are provided in Table 2. The particle size of a sample of Tetrasodium Etidronate ranged from <63 to 15,000 µm when measured using mesh sieves (Table 3).3  Distributed for comment only -- do not cite or quote Method of Manufacture One method of manufacture of Etidronic Acid and Disodium Etidronate starts with mixing phosphorus trichloride and acetic acid.5 The resulting phosphorous acid anhydride mixture is heated, resulting in a condensation reaction. The product is then hydrolyzed to yield Etidronic Acid. The acid is neutralized with sodium hydroxide to create Disodium Etidronate. Etidronic Acid can also be prepared by reaction of an acetic acid/acetic anhydride mixture with phosphorus acid.6 Impurities Typical Etidronic Acid prepared for market is reported to be 95% ± 2% pure (excluding water present in commercial … [kırpıldı — bölüm toplam 8631 karakter]

Animal Ocular irritation studies are summarized in Table 11. Etidronic Acid was corrosive to the eyes of rabbits at 100%, irritating at 10% and not irritating at 1%.2,7 Disodium Etidronate was not irritating to the eyes of rabbits at up to 20%. A dentifrice containing 10% Disodium Etidronate and a mouthwash containing 1% Disodium Etidronate were moderately irritating to the eyes of rabbits.26,28 Tetrasodium Etidronate was a mild-to-moderate irritant to the eyes of rabbits at 23% to 30%.26 MUCOUS MEMBRANE IRRITATION Dental cotton rolls with approximately 1 mL of a dentifrice or a mouthwash with and without Disodium Etidronate (3% and 1%, respectively) were placed on gingiva of Beagle dogs (n=3); the dog’s mouths were held closed for 20 to 30 sec to ensure good contact.28 Two treatment schedules were used: (1) the products were applied 5 times daily for 4 days, or (2) the same treatment was used but the treated areas were rinsed with 25-30 mL of tap water within 5 sec after cessation of treatment after each exposure. The treatments were continued for up to 20 days. The gingiva of each dog was examined before each treatment for signs of irritation or epithelial sloughing. Once damage to the gingiva was observed, treatment was stopped. The results for all of the treatment groups were similar to controls. The dentifrice, with and without Disodium Etidronate, caused visible irritation on day 4 without rinsing and not at all by day 20 with rinsing. Without rinsing, the mouthwash, with and without Disodium Etidronate, caused visible irritation on day 20. With rinsing, the mouthwash, with and without Disodium Etidronate, caused no damage by day 20. CLINICAL AND RETROSPECTIVE STUDIES Adverse Effects In human subjects, adverse effects reported for oral medicinal exposure to etidronate (400-500 mg/day) included … [kırpıldı — bölüm toplam 7699 karakter]

Acute Toxicity Studies Dermal Dermal toxicity studies are summarized in Table 6. In two studies, the dermal LD 50 of Etidronic Acid in rabbits was reported to be >7940 and >10,000 mg/kg in rabbits; clinical signs at very high doses included moderate weakness, reduced appetite, and activity.2,7,26 In two studies, the dermal LD 50 for Tetrasodium Etidronate was >5000 mg/kg in rabbits; clinical signs at very high doses included oral and nasal discharge.3,26 Oral Acute oral toxicity studies are summarized in Table 6. In several studies, the oral LD 50 of Etidronic Acid was reported to range from 1008 to >5000 mg/kg in rats; clinical signs included reduced appetite and activity, increasing weakness, diarrhea, tremors and collapse followed by death.2,7 In one study, the LD 50 in mice was reported to be 1100 mg/kg Etidronic Acid.2,7 In one study, the oral LD 50 in rats of Disodium Etidronate was 1340 mg/kg; the LD 50 for a dentifrice and a mouthwash formulation containing Disodium Etidronate was >25,000 mg/kg (equivalent to >750 mg active Etidronic Acid/kg) and 25 mg/kg (equivalent to 250 mg active Etidronic Acid/kg), respectively.28 Over four studies, the reported oral LD 50 of Disodium Etidronate ranged from >1000 to >5000 mg/kg in mice.26 The oral LD 50 of Disodium Etidronate ranged from 581 to 1140 mg/kg in rabbits at various life stages.28 The oral median effective dose (ED 50 ) for adverse effects was 84.8 mg/kg Disodium Etidronate in dogs; varying degrees of stomach and intestinal irritation were observed at higher dosages (250 to 10,000 mg/kg), and the severity was dose-dependent.28 Orally administered Disodium Etidronate (1% and 3%) in a dentifrice increased the emetic properties, and the ED 50 for adverse effects of a mouthwash containing Disodium Etidronate (1%) was 5.10 mL/kg in dogs.28 In several additional studies, the oral LD 50 of Tetrasodium Etidronate in rats ranged from 2850 to 5300 mg/kg … [kırpıldı — bölüm toplam 19772 karakter]

Animal Ten ocular irritation studies are summarized in Table 11. Etidronic Acid was corrosive to the eyes of rabbits at 100%, irritating at 10% and not irritating at 1%.2,7 Disodium Etidronate was not irritating to the eyes of rabbits at up to 20%. A dentifrice containing 10% Disodium Etidronate and a mouthwash containing 1% Disodium Etidronate were moderately irritating to the eyes of rabbits.26,28 Tetrasodium Etidronate was a mild-to-moderate irritant to the eyes of rabbits at 23% to 30%.26  Distributed for Comment Only -- Do Not Cite or Quote MUCOUS MEMBRANE TOXICITY Irritation Dental cotton rolls with approximately 1 mL of a dentifrice or a mouthwash with and without Disodium Etidronate (3% and 1%, respectively) were placed on gingiva of Beagle dogs (n=3); the dog’s mouths were held closed for 20-30 sec to ensure good contact.28 Two treatment schedules were used: (1) the products were applied 5 times daily for 4 days, or (2) the same treatment was used but the treated areas were rinsed with 25-30 mL of tap water within 5 sec after cessation of treatment after each exposure. The treatments were continued for up to 20 days. The gingiva of each dog was examined before each treatment for signs of irritation or epithelial sloughing. Once damage to the gingiva was observed, treatment was stopped. The results for all of the treatment groups were similar to controls. The dentifrice, with and without Disodium Etidronate, caused visible irritation on day 4 without rinsing and not at all by day 20 with rinsing. Without rinsing, the mouthwash, with and without Disodium Etidronate, caused visible irritation on day 20. With rinsing, the mouthwash, with and without Disodium Etidronate, caused no damage by day 20.

Definition and Structure The ingredients in this report share the same structural Etidronic Acid core (Figure 1). Etidronic Acid, a crystalline diphosphonate with both detergent and chelating utilities, is a tetraprotic acid with the acidity of the first proton being rather strong, to the last being rather alkaline (pKa’s: pK a1 1.35 ±0.08; pK a2 2.87 ±0.01; pK a3 7.03 ±0.01; and pK a4 11.3).4 The other three ingredients in this report are simple salts of Etidronic Acid (Table 1). Regardless of which of these four ingredients is added to a formulation, the pH of the formulation will dictate the degree of protonation in situ. Figure 1. Etidronic Acid Physical and Chemical Properties Physical and chemical properties are provided in Table 2. The particle size of a sample of Tetrasodium Etidronate ranged from <63 to ≤15,000 µm when measured using mesh sieves (Table 3).3 Method of Manufacture One method of manufacture of Etidronic Acid and Disodium Etidronate starts with mixing phosphorous trichloride and acetic acid.5 The resulting phosphorous acid is treated with heat, resulting in a condensation reaction. The product is then hydrolyzed to yield Etidronic Acid. The acid is neutralized with sodium hydroxide to create Disodium Etidronate. Etidronic Acid can also be prepared by reaction of an acetic acid/acetic anhydride mixture with phosphoric acid.6 Impurities Etidronic Acid is reported to be 95%±2% pure (excluding water present in commercial preparations).7 The impurities include other organophosphates and inorganic phosphorus-containing acids (including acetic acid, hydrogen  Distributed for Comment Only -- Do Not Cite or Quote … [kırpıldı — bölüm toplam 8484 karakter]

Cited by 7. Background Growth factors embedded in the extracellular matrix of the dentin play an important role in the migration, proliferation, and differentiation of dental pulp stem cells in regenerative endodontics. In regenerative endodontic treatments, the type of irrigation solution used is crucial for the release of growth factors (GFs) from the dentin matrix. This study evaluated the effectiveness of

EPA ToxValDB skin/eye data — endpoint: Skin Irritation, classification: Category 1. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data — endpoint: Eye Irritation, classification: Category 1. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data — endpoint: Skin Sensitization, classification: Classification not possible. Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.

EPA ToxValDB skin/eye data — endpoint: Eye Irritation, classification: Category 8.3A (Category 1). Caveat: this is an aggregated record; dose, species and route of exposure must be considered together.