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Use of 2-isocyanatoethyl methacrylate and iron (II) perchlorate for bonding tri-n-butylborane-initiated luting agents to dentin.

The present study investigated the effect of 2-isocyanatoethyl methacrylate (IEM) and iron (II) perchlorate on dentin adhesion. Four primers were evaluated, consisting of aqueous 2-hydroxyethyl methacrylate (HEMA) solutions containing 5, 10, 20 or 50 micromol/g iron (II) perchlorate. Five luting agents were prepared with methyl methacrylate (MMA), poly(methyl methacrylate) (PMMA), tri-n-butylborane (TBB) initiator and IEM. The concentrations of IEM in the luting agents were 0.2, 0.4, 0.8, 2.0 and 4.0 wt%. Extracted bovine teeth were ground to expose the dentin, etched with an aqueous solution of 10 wt% phosphoric acid, primed, and then bonded with stainless-steel rods; tensile bond strengths were determined after 1 d immersion in water. The highest bond strength (20.7 MPa) was recorded for the group using 10 micromol/g iron (II) perchlorate and 2.0 wt% IEM. The use of IEM was effective in decreasing the optimal concentration of iron (II) perchlorate, and this may contribute to the color stability of iron-containing pretreatment agents.

Acid Etching, Dental↗

Perchlorate is hypoglycaemic by amplifying glucose-stimulated insulin secretion in mice.

The chaotropic anion perchlorate (ClO4-) is a potent amplifier of stimulated insulin secretion in vitro. Acute effects of perchlorate on serum glucose and insulin levels were investigated in normal mice. Intraperitoneal injection of single doses of NaClO4 at 10-300 mg kg-1 body wt showed only a slight, reducing effect on the basal serum glucose level, reaching statistical significance only at 300 mg kg-1 body wt. However, a single dose of NaClO4 (300 mg kg-1 body wt) given together with a glucose load (0.9 g kg-1 body wt) significantly counteracted the increase in serum glucose and reduced the serum glucose/insulin ratio 20 min after administration. The perchlorate effect was transient and at 60 and 90 min after administration the serum insulin and glucose levels were comparable with those of the glucose-treated control animals. The results suggest that perchlorate enhances glucose-stimulated insulin secretion in mice in vivo and thereby reduces the serum glucose level after a glucose load but does not much affect the basal serum glucose level.

Animals↗

Refining the effects observed in a developmental neurobehavioral study of ammonium perchlorate administered orally in drinking water to rats. II. Behavioral and neurodevelopment effects.

A developmental neurotoxicity study was conducted to generate additional data on the potential functional and morphological hazard to the central nervous system caused by ammonium perchlorate in offspring from in utero and lactation exposure. Female Sprague-Dawley rats (23 to 25/group) were given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 10.0 mg/kg-day perchlorate in the drinking water beginning 2 weeks prior to mating and continuing through day 10 of lactation for the behavioral function assessment or given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 30.0 mg/kg-day beginning on gestation day 0 and continuing through day 10 of lactation for neurodevelopment assessments. Motor activity was conducted on postpartum days 14, 18, and 22 and juvenile brain weights, neurohistopathological examinations, and regional brain morphometry were conducted on postpartum days 10 and 22. This research revealed a sexually dimorphic response, with some brain regions being larger in perchlorate-treated male rats than in comparable controls. Even so, there was no evidence of any obvious exposure-related effects on male rat brain weights or neuropathology. The most consistent exposure-related effect in the male pups was on the thickness of the corpus callosum, with both the right- and left-sided measures of the thickness of this white matter tract being significantly greater for the male pups in the 0.1 and 1.0 mg/kg-day exposure groups. The behavioral testing suggests prenatal exposure to ammonium perchlorate does not affect the development of gross motor movements in the pups.

Administration, Oral↗

An evaluation of neurobehavioral tests used to assess the neurodevelopmental effects of early ammonium perchlorate exposure.

Perchlorate is an anion known to interfere with normal production of thyroid hormones that are integrally involved in the development of the central nervous system and neurobehavioral capacities. Given the identification of drinking water contamination with perchlorate, there are efforts to investigate the effects of exposure in developing fetuses and children in order to guide the establishment of regulatory standards. Systematic neurobehavioral investigations in animal models have been completed to evaluate neurodevelopmental consequences of exposures at different concentrations in drinking water. However, these investigations have not directly addressed the public concern for increased incidences of childhood attention deficit disorders, autism, and lowered IQs of children in areas with known contamination. Although epidemiological data suggest there is not a relationship between drinking-water perchlorate exposure and these childhood disorders, it may be prudent to use animal models to systematically assess the potential for such problems. Given the behavioral complexity of these problems, an appropriate evaluation will require the use of nontraditional neurobehavioral tests such as operant conditioning tasks of varying levels of complexity, and juvenile rat play. Such tests will provide a more direct evaluation of the potential for attention deficits, autism, and lowered IQ scores related to thyroid hormone disruption due to early perchlorate exposure.

Brain↗

Perchlorate and thyroid function: what are the environmental issues?

Ammonium perchlorate, used in the solid-propellant of rocket engines, has contaminated some water supplies and represents a potential public health hazard. Its toxicity is the result of the inhibition of the sodium iodide symporter resulting in reduced iodide uptake, possibly leading to reduced production of thyroid hormone. The fetus is the most vulnerable subject. Studies of newborn screening for thyroid function have yielded conflicting results and have not measured perchlorate or iodine intake. Based on short-term clinical studies in adults, less than 0.5 mg perchlorate per 70-kg adult will not lower thyroid uptake of radioiodine, while 1.6 mg/kg per day will lower thyroid uptake by 20%. To avoid interference with thyroid function, the California Office of Environmental Health Hazard Assessment recommended a public health goal of 6 microg perchlorate per liter of drinking water, but approximately three times that concentration is likely to be safe.

Animals↗

The iodide perchlorate discharge test in women with previous post-partum thyroiditis: relationship to sonographic appearance and thyroid function.

BACKGROUND: Post-partum thyroid disease occurs in 50% of anti-thyroid peroxidase (TPO) antibody positive women (detected at 16 weeks' gestation) and is characterized by a transient episode of hyper, hypo or hyper-hypothyroidism. In approximately 20% of these women the hypothyroidism is permanent. However, the extent of long-term thyroid dysfunction, possibly mediated by immune attack, in those anti-TPO Ab + ve women who have had only transient or no thyroid dysfunction during the postpartum period is not clear. OBJECTIVE: We have therefore studied the frequency of iodide organification defects by iodide perchlorate discharge testing, and of thyroid morphological abnormalities by ultrasound scanning in euthyroid women following their episode of post-partum thyroiditis (PPT). DESIGN: The study group comprised 17 women with previous PPT (PPT + ve) and 12 women who had positive anti-TPO antibodies during pregnancy but who did not develop PPT (PPT - ve). Women were studied 15-47 months following their episode of PPT. RESULTS: Iodide perchlorate discharge tests were positive (more than 10% discharge) in 7 (41%) PPT + ve and 5 (42%) PPT-ve subjects (P = NS). Morphological abnormalities on thyroid ultrasound were detected in 7 of 14 (50%) PPT + ve and 7 of 9 (77%) PPT - ve subjects (P = NS). There was a strong association between abnormalities of iodide organification and morphology: of 11 subjects with positive iodide perchlorate discharge tests, 10 had abnormal (positive) ultrasound scans; of 12 subjects with negative iodide perchlorate discharge tests 8 had negative ultrasound scans (P = 0.013, Fisher's exact test). CONCLUSIONS: Long-term subtle defects of thyroid function and morphology are common in women with anti-TPO antibodies in pregnancy, whether or not they develop post-partum thyroiditis. The clinical significance of these findings is unclear but a continuing thyroid pathological process is suggested.

Adult↗

The effect of sodium perchlorate and ionizing irradiation on the thyroid parenchymal and pituitary thyrotropic cells.

In a 46-week-experiment on 72 female mice the influence of peroral 1.2% sodium perchlorate application, total ionizing irradiation with 8 Gy on 5 consecutive days and their interaction on the pituitary-thyroid axis was studied by histological and stereological methods. It was observed that perchlorate alone caused long-term and strong hypothyroidism with hypertrophic and hyperplastic thyroid epithelial cells as well as pituitary thyrotropic cells. When only irradiation was used, no uniform changes in the structure and function of these cells could be detected. The interaction of perchlorate and irradiation showed similar effects as thyrostatics alone, with some exceptions; paradoxically, minor hyperplasia of thyrotropic as well as of parafollicular cells was observed. A high percentage of the follicular cell carcinoma was found after perchlorate application and after its combination with irradiation. No medullary carcinoma was found.

Animals↗

Kinetics of [123I]iodide uptake and discharge by perchlorate in studies of inhibition of iodide binding by antithyroid drugs.

Thyroidal binding of iodide was studied by kinetic analysis of [123I]iodide uptake and its discharge by perchlorate in 80 hyperthyroid subjects receiving antithyroid drug therapy. Five dosage regimens ranging from 5 mg carbimazole twice daily to 15 mg methimazole twice daily were studied. Binding inhibition was estimated at 5-7 h after drug as an index of the mean effect of the 12 hourly regimen. In all cases, except one in the lowest dose group, binding was found to be markedly reduced with mean binding rates ranging from 0.002 to 0.020 min-1 (normal greater than 0.15 min-1). The net clearance of iodide in the lowest dose group was reduced to a mean value near the upper limit of the euthyroid range, whereas in the highest dose group it lay at the lower limit of the euthyroid range. These results were reflected in the serum thyroid hormone response. There was a reducing incidence of inadequate control of hyperthyroidism and an increasing incidence of hypothyroidism with increasing thiourylene dose. The exit rate constant of free iodide for the various doses showed values from 0.048 to 0.055 min-1. Corresponding mean values for the discharge rate constant after perchlorate were 0.087 to 0.105 min-1. This suggests that perchlorate increases the rate of iodide release from the thyroid gland. Studies at a later interval after drug (12-14 h) showed no change in discharge rate constant. This leads to the conclusion that perchlorate may further inhibit iodide binding in subjects receiving antithyroid drug therapy.

Antithyroid Agents↗

Ammonium perchlorate effects on thyroid function and growth in bobwhite quail chicks.

Bobwhite quail chicks were used to investigate ammonium perchlorate (AP; NH4ClO4) effects on thyroid function and growth. Beginning at 3 to 4 d posthatch, we evaluated organismal thyroid status (circulating hormones), activation of the hypothalamic-pituitary-thyroid axis (thyroid wt) and thyroidal hormone content over a wide range of AP concentrations (50 microg/L - 4,000 mg/L) in drinking water, for relatively short (2-week) and longer (8-week) exposures. Thyroidal thyroxine (T4) content, the most sensitive index of decreased thyroid function, decreased markedly in response to increasing perchlorate exposure. Thyroid weight and plasma T4 were less sensitive indicators and similar in their ability to detect thyroid changes. Growth measurements (body wt and skeletal growth) were very insensitive indices. Because thyroids contain large hormone stores, with low exposures or short time periods, these stores can be used to maintain circulating hormones, at least temporarily. Most depletion of thyroidal T4 occurred during the first two weeks of AP exposure. Subsequent decreases were at a slower rate presumably because thyrotropin stimulation of the thyroids at least partially compensated for some of the perchlorate effect. Additional studies of the interactions between AP concentration and exposure time are needed for understanding the complex nature of thyroid responses to perchlorate.

Animals↗

Metamorphic inhibition of Xenopus laevis by sodium perchlorate: effects on development and thyroid histology.

The perchlorate anion inhibits thyroid hormone (TH) synthesis via inhibition of the sodium-iodide symporter. It is, therefore, a good model chemical to aid in the development of a bioassay to screen chemicals for affects on thyroid function. Xenopus laevis larvae were exposed to sodium perchlorate during metamorphosis, a period of TH-dependent development, in two experiments. In the first experiment, stage 51 and 54 larvae were exposed for 14 d to 16, 63, 250, 1,000, and 4,000 microg perchlorate/ L. In the second experiment, stage 51 larvae were exposed throughout metamorphosis to 8, 16, 32, 63, and 125 microg perchlorate/L. Metamorphic development and thyroid histology were the primary endpoints examined. Metamorphosis was retarded significantly in the first study at concentrations of 250 microg/L and higher, but histological effects were observed at 16 microg/L. In the second study, metamorphosis was delayed by 125 microg/L and thyroid size was increased significantly at 63 microg/L. These studies demonstrate that inhibition of metamorphosis readily can be detected using an abbreviated protocol. However, thyroid gland effects occur at concentrations below those required to elicit developmental delay, demonstrating the sensitivity of this endpoint and suggesting that thyroidal compensation is sufficient to promote normal development until perchlorate reaches critical concentrations.

Animals↗

Evaluation of adult quail and egg production following exposure to perchlorate-treated water.

Twenty-three adult female northern bobwhite (Colinus virginianus) quail were exposed to 0, 0.01, 0.1, and 1 mM ammonium perchlorate (AP) in drinking water for 30 d. Eggs laid in all treatment groups, including control, were collected, dated, given an identification number, and weighed. On day 30 of exposure, 10 birds were euthanized by carbon dioxide asphyxiation. Gross toxicological endpoints and thyroid histology were evaluated in 10 birds. Egg production and accumulation of perchlorate in the eggs (n = 10) and liver (n = 5) were determined. Perchlorate did not affect body or organ weights significantly; however, at 1 mM, AP caused alteration of thyroid gland morphology. Perchlorate did not affect egg production, but significant accumulation was observed in the eggs and livers of exposed birds.

Animals↗

Zero-valent iron treatment of RDX-containing and perchlorate-containing wastewaters from an ammunition-manufacturing plant at elevated temperatures.

The use of zero-valent iron for treating wastewaters containing RDX and perchlorate from an army ammunition plant (AAP) in the USA at elevated temperatures and moderately elevated temperature with chemical addition was evaluated through batch and column experiments. RDX in the wastewater was completely removed in an iron column after 6.4 minutes. Increasing the temperature to 75 degrees C decreased the required retention time to 2.1 minutes for complete RDX removal. Perchlorate in the wastewater was completely removed by iron at an elevated temperature of 150 degrees C in batch reactors in 6 hours without pH control. Significant reduction of perchlorate by zero-valent iron was also achieved at a more moderate temperature (75 degrees C) through use of a 0.2 M acetate buffer. Based on the evaluation results, we propose two innovative processes for treating RDX-containing and perchlorate-containing wastewaters: a temperature and pressure-controlled batch iron reactor and subsequent oxidation by existing industrial wastewater treatment plant; and reduction by consecutive iron columns with heating and acid addition capabilities and subsequent oxidation.

Explosive Agents↗

Environmentally relevant concentrations of ammonium perchlorate inhibit thyroid function and alter sex ratios in developing Xenopus laevis.

Embryos and larvae of the South African frog Xenopus laevis were exposed to ammonium perchlorate (AP) or control medium for 70 d. The dosage levels (59 ppb, 14,140 ppb) bracketed a range of perchlorate concentrations measured in surface waters at the Longhorn Army Ammunition Plant (LHAAP) in Karnack, Texas, USA. The experiment also included a 28-d nontreatment recovery period to assess the reversibility of AP effects. There were no significant effects of AP on mortality or hatching success. There were no effects of AP on developmental abnormalities such as bent/asymmetric tails or edema. Ammonium perchlorate inhibited forelimb emergence, the percentage of animals completing tail resorption, and hindlimb development during the 70-d exposure period. Only the upper AP concentration reduced whole-body thyroxine content, whereas both concentrations caused significant hypertrophy of the thyroid follicular epithelium. Both concentrations of AP caused a skewed sex ratio, significantly reducing the percentage of males at metamorphosis. The effects of AP on metamorphosis and thyroid function were reversed during the 28-d nontreatment recovery period. We conclude that AP inhibits thyroid activity and alters gonadal differentiation in developing X. laevis. These effects were observed at concentrations at or below concentrations reported in surface waters contaminated with ammonium perchlorate, suggesting that this contaminant may pose a threat to normal development and growth in natural amphibian populations.

Animals↗

[Determination of trace level of bromate and perchlorate in drinking water by ion chromatography with microwave preconcentration].

A simple sample preconcentration technique for the determination of trace level of bromate and perchlorate in drinking water with ion chromatography is presented. With the hydrophobic anion-exchange column and a sodium hydroxide eluent in linear gradient, bromate and perchlorate can be determined in a single injection within 35 min. Prior to ion chromatographic analysis, the drinking water sample was treated with the OnGuard Ag cartridge to remove the superfluous chloride and concentrated in 20-fold with poly(tetrafluoroethylene)(PTFE) beaker in a domestic microwave oven in 15 min. The recoveries of the analytes are better than 90%. The detection limits for bromate, perchlorate, iodate and chlorate were 0.10 microgram/L, 0.20 microgram/L, 0.11 microgram/L and 0.21 microgram/L, respectively. The developed method is applicable for the quantitation of bromate and perchlorate in real drinking water samples.

Bromates↗

[Dose-time effects of competitive displacement of radiopertechnetate by sodium perchlorate following oral and intravenous administration].

The effect of various doses of sodium perchlorate in several dose fractions on the extent and the time scale of displacement of radiopertechnetate, in dependence on application mode, was studied. An intravenous dose of 50 mg perchlorate was in respect of competitive suppression of organs actively concentrating pertechnetate as effective as intravenous 1000 mg ClO-4- simultaneously or 1000 mg orally 30 min before the injection of radiopertechnetate. An intravenous injection of perchlorate given later also produces a complete and immediately beginning depletion of pertechnetate already accumulated in the thyroid, within a period of 195 min after 99m-TcO-4-injection with a corresponding increase in blood levels. 20 mg result in incomplete depletion which becomes complete after a second additional dose. The intravenous application of perchlorate offers advantages in clinical use.

Administration, Oral↗

Effect of perchlorate on mitochondrial function.

Administration of sodium perchlorate to rats for 45 days leads to decreased activities of citric acid cycle enzymes. The oxidation of succinate both in state 3 and state 4 conditions and endogenous ATP content of mitochondria decreased during perchlorate toxicity. The significant decrease in cytochrome aa3 in perchlorate-treated rats may be one of the prime factors involved in the decreased rate of respiration. The permeability of mitochondria of perchlorate-treated rats is altered as indicated by increased oxidation of NADH and low respiratory control ratio (RCR).

Animals↗

Lipoprotein profile during perchlorate toxicity.

Perchlorate administration to rats for 45 days alters the lipoprotein profile in plasma. The levels of cholesterol, phospholipids and triglycerides in HDL, LDL and VLDL fractions are significantly increased in perchlorate-treated rats. Post-heparin lipolytic activity of plasma of sodium perchlorate-treated rats is decreased. The risk factor, i.e. the total cholesterol/HDL cholesterol, increases in the experimental animals, indicating that the treatment of rats with perchlorate may develop the susceptibility of the animals to cardiac heart disease.

Animals↗

Suppression by perchlorate of technetium-99m and iodine-123 secretion in milk of lactating goats.

Lactating goats were infused with either technetium-99m (99mTc) or iodine-123 (123I) together with chlorine-36 (36Cl) through an indwelling catheter previously placed in an external pudic mammary artery. The radioisotope infusions were repeated together with 100 mg of sodium perchlorate. There was a rapid transfer of 99mTc and 123I into milk, reaching a peak concentration 30 min after a 15-min infusion. The fractional secretion of 99mTc and 123I in milk was reduced by 70%-80% and 60%-66%, respectively, by perchlorate. The fractional secretion of 36Cl was not affected by perchlorate, and the shape of the 36Cl secretion curve differed from those of 99mTc and 123I, which were similar. It is probable, therefore, that the latter nuclides were secreted by a transport route different from that of chloride. Available data describing the secretion of 99mTc in human milk after pertechnetate administration was reviewed, and it was concluded that perchlorate pretreatment significantly reduced the secretion of 99mTc in human breast milk.

Animals↗