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PubMed2002

A 90-day toxicological evaluation of Compound 1080 (sodium monofluoroacetate) in Sprague-Dawley rats.

Groups of Sprague-Dawley rats received sodium monofluoroacetate (Compound 1080) at 0.025, 0.075, and 0.25 mg/kg by oral gavage once daily for 90 days and were then euthanized. The control and 0.25 mg/kg/day groups included additional rats of each sex that were treated for 90 days, then maintained without treatment for a further 56-day recovery period. Microscopic changes were restricted to the testes and the heart, and were seen only in males dosed with 1080 at 0.25 mg/kg/day and included severe hypospermia in the epididymides, severe degeneration of the seminiferous tubules of the testes, and cardiomyopathy. Sperm evaluation indicated severe decreases in all three sperm parameters evaluated (concentration, % motile, and % abnormal) at 0.25 mg/kg/day. There were no microscopic changes or 1080-related effects on sperm parameters at 0.025 and 0.075 mg/kg/day. The no observable effects level (NOEL) for rats administered 1080 via oral gavage for 90 days was 0.075 mg/kg/day. The lowest observable effects level (LOEL) dose was 0.25 mg/kg/day. After dosing with the LOEL dose of 0.25 mg/kg/day, mean concentrations of 1080 in rat plasma were 0.26 micro g/ml at 1 h and 0.076 microg/ml at 12 h. Rat urine collected from the same animals contained 0.059 microg/ml.

Animals↗
PubMed2005

Sodium monofluoroacetate (Compound 1080) poisoning in dogs.

Sodium monofluoroacetate (Compound 1080) is a widely used pesticide for control of feral animals such as the fox. Accidental poisoning of domestic animals occurs despite strict regulations on 1080 usage. Dogs are particularly susceptible to the toxin. The mechanism of 1080 toxicity, susceptibility of target and non-target species, persistence of 1080 in the environment and risk of accidental poisoning are discussed. Particular emphasis is placed on 1080 toxicity in the dog. Early recognition of intoxication is most important for prognosis and relies upon characteristic clinical signs and diagnostic findings. The treatment of 1080 intoxication remains a challenge with no proven antidotes. However, there are possible benefits from monoacetin, acetamide, calcium salts, colestipol, activated charcoal, peritoneal dialysis, sodium bicarbonate, neurotransmitter modulators and four-methylpyrazole. A recommended treatment protocol for 1080 toxicosis in dogs is included. Safety measures such as the use of wire dog muzzles and investigating alternatives to 1080 in pest control programs may be the key to reducing the incidence of future accidental poisonings.

Animals↗
PubMed2005

Ecotoxicity of sodium fluoroacetate (compound 1080) to soil organisms.

Sodium fluoroacetate (compound 1080) is applied as a vertebrate pesticide in New Zealand for control of introduced mammalian pests. Despite its widespread use, little is known about the soil ecotoxicity of 1080. Therefore, the hazard of 1080 to soil invertebrates, plants, and soil microorganisms was evaluated in a series of controlled laboratory tests. No earthworm (Eisenia fetida) mortality was reported with 1080 exposures up to 865 mg/kg soil. The lowest-observable-effect concentration and the median effect level for earthworm reproduction were 100 and 90 mg/kg soil, respectively, for cocoon production and 100 and 160 mg/kg soil, respectively, for juvenile production. Lettuce (Lactuca sativa) was more sensitive than oats (Avena sativa) to 1080. Lettuce seedling emergence and seedling shoot growth were adversely affected at a soil concentration of 7 mg/kg. The presence of 1080 in soil at concentrations up to 1 g/kg soil did not affect the ability of soil microorganisms to mineralize nitrogen. Furthermore, nitrate mineralization was not inhibited in soil treated with the urine of 1080-poisoned possums (Trichosurus vulpecula). The data collectively indicate that 1080-related effects on soil organisms occur at levels well above those that have been measured in soil (<0.1 mg/kg) following application of 1080 in baits for vertebrate pest control in New Zealand.

Animals↗
PubMed2005

Intercalation compound of diclofenac sodium with layered inorganic compounds as a new drug material.

The intercalation reaction of diclofenac sodium (DFS) with layered inorganic compounds, gamma-titanium phosphate (gamma-TiP), proton type titanium oxide (H-TiO2) and sodium type synthetic mica (Na-TSM), was examined on. The direct reaction of DFS in ethanol-water mixed solvent resulted in the large amount accommodation of DFS. The amount of intercalated DFS was the order of gamma-TiP>H-TiO2>Na-TSM corresponding to the order of acidity. The intercalation using phospholiopids was also examined to assist the intercalation reaction. However, the amount of intercalated DFS was rather small in comparison with those in the direct reaction. DFS accommodated in gamma-TiP dissolved into neutral and basic buffer solution stoichiometry while scarcely dissolved in the acidic solution. The mechanism of the intercalation and reverse dissolution was successfully accounted according to the ion-exchange mechanism between Na+ in DFS and H+ in gamma-TiP. The dissolution from tablet of DFS/gamma-TiP intercalation compound was examined by using a disintegrator. It was found that the dissolution rate appropriately controlled by mixing the disintegrator. The present results suggested the different possibilities in the clinical field to use layered inorganic compounds such as drug delivery system (DDS).

Aluminum Silicates↗
PubMed2002

Intoxication with sodium monofluoroacetate (compound 1080).

The highly toxic sodium monofluoroacetate (SMFA) was banned as a rodenticide in the U.S. in 1972. We report the first case of intentional ingestion in this country in over 15y. A 47-y-old male was brought to the emergency room status post tonic clonic seizure. At 34 h post ingestion, he responded ony to noxious stimuli and at 48 h, he was unresponsive to painful stimuli, was intubated and placed on a ventilator. Over the following 3 d, he was became minimally responsive to external stimuli with bouts of agitation and hypertension. Two days later he was discharged with no evidence of neurologic sequelae. We report this patient to increase awareness of SMFA toxicity, and its ability to cause anion gap metabolic acidosis.

Drug Overdose↗
PubMed2005

Studies on the acute biochemical effects of La(NO3)3 using 1H NMR spectroscopy of urine combined with pattern recognition.

(1)H NMR spectroscopic and pattern recognition-based methods were applied to the studies on the acute biochemical effects of La(NO(3))(3). Male Wistar rats were separated into groups (n=10) and each was treated with one of following compounds, sodium chromate (NaCrO(4)), mercury II chloride (HgCl(2)), 2-bromoethanamine hydrobromide (BEA), carbon tetrachloride (CCl(4)), hydrazine (HYD), alpha-naphthylisothiocyanate (ANIT), and three doses of La(NO(3))(3). Urine samples were collected over a 48-h time course and measured by 600 MHz NMR spectroscopy. Each spectrum was data-processed to provide 205 intensity-related descriptors used as input coordinates in a multidimensional space and analyzed by pattern recognition method. By NMR and principal components analysis (PCA) methods, the biochemical effects classification and time-course trajectories of various doses of La(NO(3))(3) were achieved. The toxicity of La(NO(3))(3) was similar to that of carbon tetrachloride according to the (1)H NMR spectral profiles and toxicity classification. This work illustrates the high reliability of NMR-PR method using (1)H NMR spectroscopy for the exploration and prediction of biochemical effects of rare earths in rats.

1-Naphthylisothiocyanate↗
PubMed1996

Stability of an extemporaneously compounded levothyroxine sodium oral liquid.

The stability of levothyroxine sodium in oral liquid dosage forms compounded from commercially available tablets was studied. Levothyroxine sodium oral liquids (25 micrograms/mL) were prepared from tablets and from powder with and without methylparaben preservative and transferred to amber, high-density polyethylene bottles. Five bottles of each tablet-based formulation were stored at 2-8 degrees C, 23-27 degrees C, and 38-42 degrees C, and five bottles of each powder-based formulation were stored at 38-42 degrees C. On days 3, 8, 14, 22, 31, 61, and 90, samples were taken from each bottle and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. There was significant degradation of levothyroxine sodium in all the formulations. However, the tablet-based formulation without preservative stored at 4 degrees C retained at least 90% of its initial concentration for eight days after compounding. Degradation occurred faster in the tablet-based formulation with preservative. None of the formulations retained > or = 90% initial potency by day 14. An extemporaneous oral liquid formulation of levothyroxine sodium 25 micrograms/mL compounded from crushed tablets was stable for eight days when stored in amber bottles at 4 degrees C.

Drug Compounding↗
PubMed1981

High pressure liquid chromatographic determination of sodium fluoroacetate (compound 1080) in canine gastric content.

A sensitive high pressure liquid chromatographic method was developed for the determination of sodium fluoroacetate (compound 1080) in canine gastric content. The procedure involves extraction of 1080 with water, methyl ethyl ketone, and dilute base, followed by sample cleanup using octadecylsilane bonded phase cartridges and derivatization in ethyl acetate sodium with O-p-nitrobenzyl-N-N'-diisopropylisourea (PNBDI). The compound was chromatographed on a 10 micrometer silica column, and ultraviolet absorbance at 254 and 280 nm was measured. Recovery was greater than 95% for standard 1080 and in the 70-90% range for spiked samples (1-50 ppm).

Animals↗
PubMedDate not supplied

Determination of sodium fluoroacetate (Compound 1080) in biological tissues.

A sensitive gas chromatographic method was developed for the determination of sodium fluoroacetate (Compound 1080 and 1080 poison) in baits and avian tissues. The procedure involves extraction of 1080 with acetone/water (8:1) followed by derivatization with pentafluorobenzyl bromide. Cleanup of the esterified extracts was carried out using minicolumns containing Florisil and the eluates were subsequently analyzed by electron capture gas chromatography. Bait samples were initially screened by thin-layer chromatography and identity of derivatized extracts was confirmed by gas chromatography/mass spectrometry.

Animals↗
PubMed1985

Interaction of alkylmercuric compounds with sodium selenite. III. Biotransformation, levels of metallothioneinlike proteins and endogenous copper in some tissues of rats exposed to methyl or ethylmercuric chloride with and without sodium selenite.

The biotransformation efficiency of alkylmercurial compounds was studied in rat liver, kidneys, blood, and brain after 2-week administration of methylmercuric chloride (MeHg) and ethylmercuric chloride (EtHg) at doses of 0.25 or 2.5 mg Hg/kg, alone or in combination with sodium selenite (Se) at a level of 0.5 mg Se/kg. Simultaneously, the level of metallothioneinlike proteins (MTP) and endogenous copper (Cu) was monitored in tissues of control rats and intoxicated rats. Regardless of the dose, the highest concentrations of inorganic mercury from both the alkylmercurials was found in the rat kidneys. Sodium selenite had a variable effect on the amount of inorganic mercury liberated, depending on the organ and the molar ratio of Hg:Se administered. A statistically significant increase in the levels of MTP and endogenous Cu, compared with control group, was found only in the kidneys of intoxicated rats. This increase was dependent on the concentration of inorganic mercury liberated by biotransformation of alkylmercurials. The observed changes appeared when the level of inorganic mercury exceeded 10 micrograms Hg/g tissue and reached a plateau at about 40 micrograms Hg/g tissue. In the presence of selenium the plateau of MTP and Cu levels were no observed in the kidneys, regardless of the amount of inorganic mercury liberated.

Animals↗
PubMed1992

Immunomodulatory effects of therapeutic gold compounds. Gold sodium thiomalate inhibits the activity of T cell protein kinase C.

Previous studies have shown that the gold compounds, gold sodium thiomalate (GST) and auranofin (AUR), which are effective in the treatment of rheumatoid arthritis, inhibit functional activities of a variety of cells, but the biochemical basis of their effect is unknown. In the current studies, human T cell proliferation and interleukin 2 production by Jurkat cells were inhibited by GST or AUR at pharmacologically relevant concentrations. Because it has been documented that protein kinase C (PKC) is involved in T cell activation, the capacity of gold compounds to inhibit PKC partially purified from Jurkat cells was assayed in vitro. GST was found to inhibit PKC in a dose-dependent manner, but AUR caused no significant inhibition of PKC at pharmacologically relevant concentrations. The inhibitory effect of GST on PKC was abolished by 2-mercaptoethanol. To investigate the effect of GST on the regulation of PKC in vivo, the levels of PKC activity in Jurkat cells were examined. Cytosolic PKC activity decreased slowly in a concentration- and time-dependent manner as a result of incubation of Jurkat cells with GST. To ascertain whether GST inhibited PKC translocation and down-regulation, PKC activities associated with the membrane and cystosolic fractions were evaluated after phorbol myristate acetate (PMA) stimulation of GST incubated Jurkat cells. Translocation of PKC was markedly inhibited by pretreatment of Jurkat cells with GST for 3 d, but the capacity of PMA to down-regulate PKC activity in Jurkat cells was not altered by GST preincubation. The functional impact of GST-mediated downregulation of PKC in Jurkat cells was examined by analyzing PMA-stimulated phosphorylation of CD3. Although GST preincubated Jurkat cells exhibited an increased density of CD3, PMA-stimulated phosphorylation of the gamma chain of CD3 was markedly inhibited. Specificity for the inhibitory effect of GST on PKC was suggested by the finding that GST did not alter the mitogen-induced increases in inositol trisphosphate levels in Jurkat cells. Finally, the mechanism of the GST-induced inhibition of PKC was examined in detail, using purified PKC subspecies from rat brain. GST inhibited type II PKC more effectively than type III PKC, and also inhibited the enzymatic activity of the isolated catalytic fragment of PKC. The inhibitory effect of GST on PKC activity could not be explained by competition with phospholipid or nonspecific interference with the substrate. These data suggest that the immunomodulatory effects of GST may result from its capacity to inhibit PKC activity.

Auranofin↗
PubMed1987

Inhibition of RNA and DNA polymerases by the product of the reaction of selenite with sulfhydryl compounds.

Sodium selenite has previously been shown to inhibit DNA and RNA synthesis in both intact cells and isolated nuclei. Nevertheless, DNA and RNA polymerases, the enzymes responsible for this synthesis, are insensitive to inhibition by selenite. Several DNA and RNA polymerases have now been shown to be inhibited by selenite in the presence of sulfhydryl compounds. This inhibition is due to the reaction of selenite with the sulfhydryl compounds to form selenotrisulfide derivatives which inhibit the enzymes. The selenotrisulfides decrease the Vmax of the polymerase reaction and increase the apparent Km for the triphosphates, but do not alter the apparent Km of the enzyme for the DNA template. There are differences in potency between selenotrisulfides formed from similar sulfhydryl compounds such as mercaptoethanol and mercaptoethylamine. There are also differences in the sensitivity of different polymerases to inhibition by the selenotrisulfides.

Chemical Phenomena↗
PubMed2002

The identification of sodium fluoroacetate (compound 1080) employing NMR spectroscopy.

Nuclear magnetic resonance (NMR) spectroscopy was employed for the purpose of identifying samples of materials suspected of containing sodium fluoroacetate (Compound 1080). Acquisition of routine proton (1H) and carbon (13C) NMR spectra provided a straight-forward means for determining the presence of Compound 1080 in the samples and thus afforded a simple method for analysis and identification of this compound.

Journal Article↗
PubMed1983

Induction of retrovirus gene expression by selenium compounds.

Sodium selenite, sodium selenate, selenium oxide, selenophypoxanthine, selenopurine, selenocysteine, selenoethionine and selenomethionine were tested for their ability to induce endogenous retrovirus expression in cultured AKR mouse embryo fibroblasts. All except selenoethionine were highly toxic to the cells. Only selenomethionine however, had the ability to induce virus expression under the conditions used. The level of virus induction (plaque-forming-units/10(5) cells) was roughly proportional to dose over the range of concentrations from 0.25 mM to 5.0 mM. Induction was best observed when a treatment duration of 48 h was used and required the treatment of actively dividing cells. The induction and the cytotoxic effects of selenomethionine could be abrogated by simultaneous treatment with methionine. A ratio of methionine to selenomethionine of 1:10 inhibited induction by approx. 60% while equivalent amounts of methionine inhibited selenomethionine-mediated induction by greater than 96%, indicating that methionine was more efficiently recognized by the cells than was selenomethionine. A possible mechanism for selenomethionine induction involving the production of undermethylated DNA is presented.

Animals↗
PubMed2003

NaCa4Nb5O17: a layered perovskite AnBnO3n+2 compound.

Sodium tetracalcium pentaniobium heptadecaoxide, NaCa(4)Nb(5)O(17), corresponds to the n = 5 term of the homologous A(n)B(n)O(3n+2) family of structures composed of ABX(3) perovskite layers. The structure consists of perovskite-type blocks of n = 5 layers of NbO(6) octahedra, separated by an interblock region. Successive blocks along the b axis are displaced by 1/2c with respect to each other. The deformation of the NbO(6) octahedra is a minimum at the middle of each block, and increases along the direction of the b axis to a maximum at each end of the block. Ca and Na share the same intrablock sites, coordinated by 12 O atoms, whereas only Ca atoms are found in the interblock cavities, at sites with different coordination geometries.

Journal Article↗