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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 59 (1987), S. 382-383 
    ISSN: 1432-0738
    Keywords: Gallium nitrate ; Deferoxamine mesylate ; Citric acid ; Succinic acid ; Malic acid ; Oxalic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twelve chelating agents were administered to mice by IP injection to compare their relative effectiveness in preventing death after a single IP injection of gallium nitrate. Na2Ca-ethylenediaminetetraacetate (EDTA), Na3Ca-diethylenetriaminepentaacetate (DTPA), dimercaptosuccinic acid (DMSA), 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron), sodium diethyldithiocarbamate (DDC), L-cysteine and sodium salicylate were not effective for acute gallium nitrate intoxication. The therapeutic indices of the effective chelators were: 25.4 (deferoxamine mesylate), 35.7 (citric acid), 42.3 (succinic acid), 52.2 (malic acid) and 111.1 (oxalic acid).
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0738
    Keywords: Cobalt ; Intraperitoneal administration ; Mice ; EDTA ; DTPA ; DMSA ; N-Acetylcysteine ; Glutathione ; L-Cysteine ; D,L-penicillamine ; BAL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of the chelating agents Na2Ca-ethylendiaminetetraacetate (EDTA), Na3Ca-diethylentriaminepentaacetate (DTPA), L-cysteine, 2,3-dimercaptosuccinic acid (DMSA), N-acetyl-L-cysteine (NAC), glutathione, D,L-penicillamine (D,L-PEN) and 2,3-dimercaptopropanol (BAL) on the toxicity, distribution and excretion of intraperitoneally injected cobalt were studied in male Swiss mice. To determine the effect of the various chelators on the toxicity of cobalt, various doses of CoCl2 (0.60–1.80 mmol/kg) were given, followed immediately by the IP administration of the chelator (at a dose equal to one-fourth of their respective LD50). EDTA and DTPA were the most effective. EDTA, DTPA and L-cysteine, NAC and glutathione were also the most effective in increasing the urinary excretion of cobalt and reducing the concentration of the metal in various tissues. EDTA appears to be the most effective agent of those tested in the prevention of acute cobalt intoxication.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 66 (1992), S. 188-192 
    ISSN: 1432-0738
    Keywords: Developmental toxicity ; Gallium nitrate ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gallium nitrate, a drug with antitumor activity, is presently undergoing clinical trials as a chemotherapeutic agent for the treatment of certain malignancies. Since there are very limited published animal toxicity data available, this study was conducted to investigate the potential adverse developmental effects of this drug. Pregnant Swiss mice were administered intraperitoneally gallium nitrate at 12.5, 25, 50, and 100 mg/kg/day on days 6, 8, 10, 12, and 14 of gestation. Monitors for maternal toxicity were body weight, food consumption and clinical signs. At sacrifice (day 18) maternal weight, liver and kidney weights, and gravid uterine weights were measured. Gestational parameters monitored were numbers of total implants, resorptions, postimplantation losses, and dead fetuses. Live fetuses were sexed, weighed, and examined for external, internal and skeletal malformations and variations. Maternal toxicity was noted in all the gallium nitrate-treated groups. Embryo/fetal toxicity was evidenced by a decrease in the number of viable implants, a reduction in fetal weight, and an increase in the number of skeletal variations (12.5, 25, 50 and 100 mg/kg). No significant increase in the incidence of malformations was observed at 12.5, 25, or 50 mg/kg. The no-observable-adverse-effect level (NOAEL) for both maternal and developmental toxicity of gallium nitrate was 〈12.5 mg/kg.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 61 (1988), S. 321-323 
    ISSN: 1432-0738
    Keywords: Zinc ; Mice ; Intraperitoneal administration ; Zinc antidotes ; EDTA ; DTPA ; CDTA ; d-penicilamine ; DMPS ; DMSA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Sixteen chelating agents were examined to determine their relative efficacy as antidotes in acute zinc acetate intoxication in mice after i.p. administration. For a i. p. dose of 0.49 mmol/kg (LD50) of zinc acetate, the i. p. administration of chelating agents at a 2∶1 and 5∶1 mole ratio resulted in a significant antidotal action for EDTA, DTPA, CDTA, d-penicillamine (d-PA), DMPS and DMSA. EGTA, l-cysteine, triethylentetraamine (TTHA), N-acetylcysteine (NAC), 4,5-dihydroxi-1,3-benzenedisulfonic acid (Tiron), sodium salicylate, glutathione, sodium diethyldithiocarbamate (DDC), 6-mercaptopurine and N-acetyl-d, l-penicillamine (NAPA) were not effective for acute zinc acetate poisoning. The therapeutic indices and therapeutic effectiveness of the most effective chelators were, respectively: EDTA (5.0, 7.0), DTPA (7.3, 13.7), CDTA (8.6, 6.3), d-PA (4.6, 1.9), DMPS (1.3, 1.0), DMSA (3.2, 5.4). DTPA, CDTA, and EDTA appear to be the most effective agents of those tested in offsetting acute zinc intoxication in mice.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 69 (1995), S. 467-471 
    ISSN: 1432-0738
    Keywords: Key words: Maternal toxicity ; Developmental toxicity ; Deferoxamine ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Deferoxamine (DFO), an efficient chelating agent available for the treatment of iron and aluminium overload, was evaluated for developmental toxicity in Swiss mice. Intraperitoneal injections of DFO were given to pregnant animals at 0, 44, 88, 176, and 352  mg/kg per day on gestational days 6 through 15. Maternal clinical status was monitored daily during and after treatment. Fetal parameters, including external, visceral, and skeletal malformations and variations, were assessed. Mice were killed on day 18. No maternal mortality was observed, but dams exhibited reduced body weight gain during treatment at 88, 176, and 352 mg/kg per day. Body weight at termination, corrected body weight, and food consumption were reduced in all groups. In contrast, the only significant treatment-related embryo/fetal effect was a decrease in the number of live fetuses per litter at 352 mg/kg per day. The no-observable-adverse-effect level (NOAEL) for maternal toxicity of DFO was 〈44 mg/kg per day, whereas the NOAEL for developmental toxicity was 176 mg/kg per day. In summary, intraperitoneal administration of DFO to mice during organogenesis produced developmental toxicity in the presence of maternal toxicity. Because of the remarkable maternal toxicity of DFO, extreme caution in the use of this drug is recommended during pregnancy.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Archives of environmental contamination and toxicology 19 (1990), S. 185-189 
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract The efficacy of several chelating agents in alleviating acute lead intoxication has been investigated in male Swiss mice. The relative effectiveness of diethyl-enetriaminepentaacetic acid (DTPA), ethyleneglycolbis-(β-amino-ethylether)-N,N′-tetraacetic acid (EGTA), cyclohexanediaminetetraacetic acid (CDTA), L-cysteine, N-acetyl-L-cysteine (NAC), ascorbic acid, sodium diethyldithiocarbamate (DDC), 2,3-dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercapto-1-propanesulfonate (DMPS) in reducing lethality of lead was examined. Significant increases in survival were noted with CDTA, ascorbic acid, DMSA, and DMPS. Therapeutic effectiveness (TEF) was determined for these compounds; TEF for ethylenediamine-tetraacetic acid (EDTA) and for 2,3-dimercaptopropanol (BAL) was also determined; CDTA (2.33) and EDTA (1.73) showed the highest values. In subsequent experiments, the effect of the chelating agents on the distribution and excretion of lead was investigated. Lead acetate trihydrate was administered subcutaneously at doses of 37.8 mmol/kg (LD50), and fifteen minutes later, chelators were given intraperitoneally at doses approximately equal to one-fourth of their respective LD50 values. EDTA, DTPA and CDTA were the most effective agents in increasing the urinary excretion of lead, whereas DTPA, CDTA, and DDC increased significantly the fecal excretion of lead. EDTA, DDC, and CDTA were the most effective chelators in reducing the concentration of lead found in various tissues. On the basis of these results, CDTA may be considered as an alternative in the treatment of acute lead poisoning.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Archives of environmental contamination and toxicology 18 (1989), S. 612-616 
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract The effects of the chelating agents monosodium glutamate, Tiron, tartaric acid, ascorbic acid, 1,4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6), 2,3-dimercaptosuccinic acid (DMSA), succinic acid, malic acid, ethylendiaminetetraacetic acid (EDTA), ethylenglycol-bis-(β-amino-ethylether)-N,N′ tetraacetic acid (EGTA), cyclohexanediaminetetraacetic acid (CDTA) and diethylentriaminepentaacetic acid (DTPA) on the distribution and excretion of intraperitoneally injected strontium were investigated in male Swiss mice. Strontium nitrate was given at a dose equal to 3.78 mmol/kg and ten minutes after, chelators were administered intraperitoneally at doses approximately equal to one-fourth of their respective LD50 values. DTPA, followed by CDTA, EDTA and tartaric acid, was consistently the most effective in increasing the urinary excretion of strontium. Only ascorbic acid increased significantly the fecal excretion of strontium. CDTA, DTPA and ascorbic acid were also the most effective chelators in reducing the concentration of strontium found in various tissues. CDTA, DTPA and tartaric acid are the most effective agents of those tested in the removal of strontium after a single administration.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Archives of environmental contamination and toxicology 21 (1991), S. 612-620 
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract The effect of increasing the time interval between strontium exposure and chelation therapy was studied in male Swiss mice. Diethylenetriaminepentaacetic acid (DTPA), ethyleneglycol-bis(β-amino-ethylether)-N,N′-tetraacetic acid (EGTA), 4,7,13,16,21,24-hexaoxa-1,10-diazabycyclo[8.8.8]-hexacosane (Kryptofix® 222), tartaric acid, and 1,13-bis(8-chinolyl)-1,4,7,10,13-pentaoxatridecan (Kryptofix® 5) were administered intraperitoneally at 0, 6, 12, and 24 h after subcutaneous injection of 1,139 mg/kg of strontium nitrate. Chelating agents were given at doses equal to one-fourth of their respective LD50 values. Daily elimination of strontium into urine and feces was determined for five days after which time the animals were killed, and the concentration of strontium was determined in various tissues. Only Kryptofix 222 was capable of increasing the total urinary elimination of strontium when given immediately after strontium exposure, whereas the amount of total strontium excreted into the feces was significantly enhanced by treatment with EGTA at 0 or 24 h after strontium injection, or with Kryptofix 222 at 6 h after strontium exposure. However, Kryptofix 222, tartaric acid, and Kryptofix 5 reduced the concentration of strontium in bone at 0, 6, or 12 h after strontium injection, whereas at 24 h only Kryptofix 5 significantly lowered the concentration of the metal in bone. The results of this study indicate that the length of time before initiating chelation therapy for strontium removal may influence remarkably the effectiveness of this therapy.
    Type of Medium: Electronic Resource
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