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Reduction of perchlorate and nitrate by microbial communities in vadose soil.

Perchlorate contamination is a concern because of the increasing frequency of its detection in soils and groundwater and its presumed inhibitory effect on human thyroid hormone production. Although significant perchlorate contamination occurs in the vadose (unsaturated) zone, little is known about perchlorate biodegradation potential by indigenous microorganisms in these soils. We measured the effects of electron donor (acetate and hydrogen) and nitrate addition on perchlorate reduction rates and microbial community composition in microcosm incubations of vadose soil. Acetate and hydrogen addition enhanced perchlorate reduction, and a longer lag period was observed for hydrogen (41 days) than for acetate (14 days). Initially, nitrate suppressed perchlorate reduction, but once perchlorate started to be degraded, the process was stimulated by nitrate. Changes in the bacterial community composition were observed in microcosms enriched with perchlorate and either acetate or hydrogen. Denaturing gradient gel electrophoresis analysis and partial sequencing of 16S rRNA genes recovered from these microcosms indicated that formerly reported perchlorate-reducing bacteria were present in the soil and that microbial community compositions were different between acetate- and hydrogen-amended microcosms. These results indicate that there is potential for perchlorate bioremediation by native microbial communities in vadose soil.

Acetates↗

Urinary perchlorate and thyroid hormone levels in adolescent and adult men and women living in the United States.

BACKGROUND: Perchlorate is commonly found in the environment and known to inhibit thyroid function at high doses. Assessing the potential effect of low-level exposure to perchlorate on thyroid function is an area of ongoing research. OBJECTIVES: We evaluated the potential relationship between urinary levels of perchlorate and serum levels of thyroid stimulating hormone (TSH) and total thyroxine (T4) in 2,299 men and women, > or = 12 years of age, participating in the National Health and Nutrition Examination Survey (NHANES) during 2001-2002. METHODS: We used multiple regression models of T4 and TSH that included perchlorate and covariates known to be or likely to be associated with T4 or TSH levels: age, race/ethnicity, body mass index, estrogen use, menopausal status, pregnancy status, premenarche status, serum C-reactive protein, serum albumin, serum cotinine, hours of fasting, urinary thiocyanate, urinary nitrate, and selected medication groups. RESULTS: Perchlorate was not a significant predictor of T4 or TSH levels in men. For women overall, perchlorate was a significant predictor of both T4 and TSH. For women with urinary iodine < 100 microg/L, perchlorate was a significant negative predictor of T4 (p < 0.0001) and a positive predictor of TSH (p = 0.001). For women with urinary iodine > or = 100 microg/L, perchlorate was a significant positive predictor of TSH (p = 0.025) but not T4 (p = 0.550). CONCLUSIONS: These associations of perchlorate with T4 and TSH are coherent in direction and independent of other variables known to affect thyroid function, but are present at perchlorate exposure levels that were unanticipated based on previous studies.

Adolescent↗

Novel biomarkers of perchlorate exposure in zebrafish.

Perchlorate inhibits iodide uptake by thyroid follicles and lowers thyroid hormone production. Although several effects of perchlorate on the thyroid system have been reported, the utility of these pathologies as markers of environmental perchlorate exposures has not been adequately assessed. The present study examined time-course and concentration-dependent effects of perchlorate on thyroid follicle hypertrophy, colloid depletion, and angiogenesis; alterations in whole-body thyroxine (T4) levels; and somatic growth and condition factor of subadult and adult zebrafish. Changes in the intensity of the colloidal T4 ring previously observed in zebrafish also were examined immunohistochemically. Three-month-old zebrafish were exposed to ammonium perchlorate at measured perchlorate concentrations of 0, 11, 90, 1,131, and 11,480 ppb for 12 weeks and allowed to recover in clean water for 12 weeks. At two weeks of exposure, the lowest-observed-effective concentrations (LOECs) of perchlorate that induced angiogenesis and depressed the intensity of colloidal T4 ring were 90 and 1,131 ppb, respectively; other parameters were not affected (whole-body T4 was not determined at this time). At 12 weeks of exposure, LOECs for colloid depletion, hypertrophy, angiogenesis, and colloidal T4 ring were 11,480, 1,131, 90, and 11 ppb, respectively. All changes were reversible, but residual effects on angiogenesis and colloidal T4 ring intensity were still present after 12 weeks of recovery (LOEC, 11,480 ppb). Whole-body T4 concentration, body growth (length and weight), and condition factor were not affected by perchlorate. The sensitivity and longevity of changes in colloidal T4 ring intensity and angiogenesis suggest their usefulness as novel markers of perchlorate exposure. The 12-week LOEC for colloidal T4 ring is the lowest reported for any perchlorate biomarker in aquatic vertebrates.

Angiogenesis Inducing Agents↗

Thyroid function and reproductive success in rodents exposed to perchlorate via food and water.

The purpose of the present study was to determine if exposure to perchlorate via food items would have effects on mammals similar to those caused by exposure through drinking water at approximately equivalent doses. Prairie voles (Microtus ochrogaster) and deer mice (Peromyscus maniculatus) were used to assess the potential toxicity of perchlorate-contaminated food items. Voles and mice were divided randomly into three treatment groups--perchlorate-contaminated food (PCF), perchlorate-contaminated water (PCW), and control groups--such that each treatment group contained equal numbers of males and females. Rodents in PCF treatment groups were fed chow formulated with soybean plant matter that had been grown with perchlorate-contaminated irrigation water. Individuals in the control and PCF groups were provided distilled/deionized drinking water, whereas the PCW group received drinking water containing sodium perchlorate. Only slight differences among treatment groups were observed in a variety of endpoints, including reproductive success, tissue perchlorate concentrations, thyroid hormone concentrations, and thyroid histology. However, trends observed in the present study suggest that perchlorate exposure via water may result in slightly greater effects than exposure to perchlorate via food. These data and recent reports of perchlorate in a wide variety of food items indicate that exposure via food intake is an important consideration when examining cumulative risk among humans, livestock, and wildlife.

Animal Feed↗

The pharmacokinetics of perchlorate and its effect on the hypothalamus-pituitary-thyroid axis in the male rat.

Perchlorate, an environmental contaminant, is known to disturb the hypothalamus-pituitary-thyroid (HPT) axis by blocking iodide accumulation in the thyroid. Iodide deficiency can lead to hypothyroidism and goiter in rats. The objective of the study was to characterize the pharmacokinetics of perchlorate in male Sprague-Dawley rats relative to inhibition of thyroidal radiolabeled iodide uptake and onset of up-regulation of the HPT axis. Radiolabeled perchlorate (3.3 mg/kg (36)ClO(-)(4)) was excreted in urine (99.5% over a 48-h period). (36)ClO(-)(4) is rapidly distributed into tissues with preferential sequestration into skin, gastrointestinal tract (GT), and thyroid. Calculated half-lives of (36)ClO(-)(4) from the skin, thyroid, plasma, GT, and GT contents were 32.0, 7.6, 7.3, 10.0, and 8.6 h, respectively. Perchlorate was very effective at inhibiting thyroidal uptake of radiolabeled iodide ((125)I(-)). In animals iv dosed with perchlorate followed by an iv challenge of (125)I(-), thyroidal (125)I(-) uptake was diminished by 11, 29, 55, and 82% at 11 h postdosing in the 0.01, 0.1, 1.0, and 3.0 mg/kg perchlorate dose groups, respectively. In perchlorate drinking water studies, dose-dependent inhibition in thyroidal uptake of (125)I(-) initially occurred with corresponding increases in serum thyroid-stimulating hormone (TSH) levels and decreases in thyroid hormone levels. TSH stimulated recovery from the initial perchlorate blocking effects was evident during 14 days of treatment in the 1.0 and 3.0 mg/kg per day treatment groups. However, recovery of serum thyroid hormones at these doses was much slower despite evidence for iodide sufficiency in the thyroid. These results suggest that the typical homeostatic mechanisms of the thyroid may respond differently at high doses of perchlorate used in this rat study (above 1 mg/kg per day) or perchlorate may be acting on the HPT axis by mechanisms other than thyroidal (125)I(-) uptake inhibition.

Animals↗

Molecular assessment of inoculated and indigenous bacteria in biofilms from a pilot-scale perchlorate-reducing bioreactor.

Bioremediation of perchlorate-contaminated groundwater can occur via bacterial reduction of perchlorate to chloride. Although perchlorate reduction has been demonstrated in bacterial pure cultures, little is known about the efficacy of using perchlorate-reducing bacteria as inoculants for bioremediation in the field. A pilot-scale, fixed-bed bioreactor containing plastic support medium was used to treat perchlorate-contaminated groundwater at a site in Southern California. The bioreactor was inoculated with a field-grown suspension of the perchlorate-respiring bacterium Dechlorosoma sp. strain KJ and fed groundwater containing indigenous bacteria and a carbon source amendment. Because the reactor was flushed weekly to remove accumulated biomass, only bacteria capable of growing in biofilms in the reactor were expected to survive. After 26 days of operation, perchlorate was not detected in bioreactor effluent. Perchlorate remained undetected by ion chromatography (detection limit 4 mug L(-1)) during 6 months of operation, after which the reactor was drained. Plastic medium was subsampled from top, middle, and bottom locations of the reactor for shipment on blue ice and storage at -80 degrees C prior to analysis. Microbial community DNA was extracted from successive washes of thawed biofilm material for PCR-based community profiling by 16S-23S ribosomal intergenic spacer analysis (RISA). No DNA sequences characteristic of strain KJ were recovered from any RISA bands. The most intense bands yielded DNA sequences with high similarities to Dechloromonas spp., a closely related but different genus of perchlorate-respiring bacteria. Additional sequences from RISA profiles indicated presence of representatives of the low G+C gram-positive bacteria and the Cytophaga-Flavobacterium-Bacteroides group. Confocal scanning laser microscopy and fluorescence in situ hybridization (FISH) were also used to examine biofilms using genus-specific 16S ribosomal RNA probes. FISH was more sensitive than RISA profiling in detecting possible survivors from the initial inoculum. FISH revealed that bacteria hybridizing to Dechlorosoma probes constituted <1% of all cells in the biofilms examined, except in the deepest portions where they represented 3-5%. Numbers of bacteria hybridizing to Dechloromonas probes decreased as biofilm depth increased, and they were most abundant at the biofilm surface (23% of all cells). These spatial distribution differences suggested persistence of low numbers of the inoculated strain Dechlorosoma sp. KJ in parts of the biofilm nearest to the plastic medium, concomitant with active colonization or growth by indigenous Dechloromonas spp. in the biofilm exterior. This study demonstrated the feasibility of post hoc analysis of frozen biofilms following completion of field remediation studies.

Bacteria↗

Thyroid endocrine disruption in stonerollers and cricket frogs from perchlorate-contaminated streams in east-central Texas.

In October 2001 and March 2002, a field survey of central stonerollers (Campostoma anomalum) from perchlorate-contaminated streams in central Texas was conducted to assess thyroid endocrine disruption. A survey of adult male and female cricket frogs (Acris crepitans) was performed at the same site between 2001 and 2003. Perchlorate is an oxidizer primarily used in solid-fuel rockets, and many sites that processed or used perchlorate are now contaminated. Histological analysis revealed that the fish from contaminated sites had increased thyroid follicular hyperplasia, hypertrophy, and colloid depletion. Multivariate analysis was generally found to be more powerful than univariate analysis. Seasonal differences existed in the degree of thyroidal perturbation were discovered, and fish were generally less sensitive to thyroidal perturbations in March compared to October. Thyroidal histological indicators were also correlated to levels of perchlorate in the fish, water, and periphyton. Periphyton was frequently most strongly correlated to thyroidal indices, suggesting that exposure through the food chain may be of import. In addition, one of the presumed reference sites turned out to be contaminated with perchlorate, and this was reflected by thyroidal biomarkers before perchlorate was detected in the stream water or biota. There was no evidence of colloid depletion or hyperplasia in frogs from any of the sites, although frogs from two sites with greatest mean water perchlorate concentrations exhibited significantly greater follicle cell hypertrophy. Furthermore, there was a significant positive correlation between follicle cell height and mean water perchlorate concentrations for frogs collected from all sites. This is the first known published account of perchlorate-induced thyroid disruption in fish under field situations, only the second known published account for amphibians, and also points out the value of biomarkers for contaminant biomonitoring.

Animals↗

Effects of perchlorate on earthworm (Eisenia fetida) survival and reproductive success.

The effects of perchlorate on earthworm, Eisenia fetida, survival and reproductive success were evaluated using three types of tests: dermal contact (filter paper), sand, and artificial soil. All studies utilized a range of perchlorate concentrations in order to simulate levels that are likely to occur in the environment under different scenarios (typical soil levels vs. spill levels). The OECD filter paper contact test involved exposing earthworms to the test compound on moist filter paper for 14 days to evaluate earthworm survival under a worst-case dermal exposure scenario. A similar test involved exposing the earthworms to perchlorate-contaminated sand, where earthworm survival decreased as concentration of perchlorate increased, with no worms surviving 14 days at the highest treatment concentrations (>2000 microg/g). However, the perchlorate concentrations that affected the survival of E. fetida are likely to occur only under extreme conditions (e.g. spills). The effect of perchlorate on the reproductive success (cocoon production) of E. fetida over a 4-week test period in artificial soil and a 3-week test period in sand was also examined. Production of cocoons was observed in soil containing up to 100 microg/g perchlorate, with no production in the uppermost treatment groups (1000 microg/g). Cocoon production was highest in the control group, although overall cocoon production appeared to be low. In contrast to the acute toxicity tests, perchlorate did affect earthworm reproduction at environmentally relevant soil concentrations. In addition, preliminary data suggest that cocoons produced under perchlorate contamination did not hatch as well as cocoons produced in control soil despite incubation of both sets of cocoons in clean soil or sand.

Animals↗

Perchlorate removal in sand and plastic media bioreactors.

The treatment of perchlorate-contaminated groundwater was examined using two side-by-side pilot-scale fixed-bed bioreactors packed with sand or plastic media, and bioaugmented with the perchlorate-degrading bacterium Dechlorosoma sp. KJ. Groundwater containing perchlorate (77microg/L), nitrate (4mg-NO(3)/L), and dissolved oxygen (7.5mg/L) was amended with a carbon source (acetic acid) and nutrients (ammonium phosphate). Perchlorate was completely removed (<4microg/L) in the sand medium bioreactor at flow rates of 0.063-0.126L/s (1-2gpm or hydraulic loading rate of 0.34-0.68L/m(2)s) and in the plastic medium reactor at flow rates of <0.063L/s. Acetate in the sand reactor was removed from 43+/-8 to 13+/-8mg/L (after day 100), and nitrate was completely removed in the reactor (except day 159). A regular (weekly) backwashing cycle was necessary to achieve consistent reactor performance and avoid short-circuiting in the reactors. For example, the sand reactor detention time was 18min (hydraulic loading rate of 0.68L/m(2)s) immediately after backwashing, but it decreased to only 10min 1 week later. In the plastic medium bioreactor, the relative changes in detention time due to backwashing were smaller, typically changing from 60min before backwashing to 70min after backwashing. We found that detention times necessary for complete perchlorate removal were more typical of those expected for mixed cultures (10-18min) than those for the pure culture (<1min) reported in our previous laboratory studies. Analysis of intra-column perchlorate profiles revealed that there was simultaneous removal of dissolved oxygen, nitrate, and perchlorate, and that oxygen and nitrate removal was always complete prior to complete perchlorate removal. This study demonstrated for the first time in a pilot-scale system, that with regular backwashing cycles, fixed-bed bioreactors could be used to remove perchlorate in groundwater to a suitable level for drinking water.

Bacteria↗

Trace perchlorates in a radiological liquid-waste treatment facility.

Waste management programs at the Radioactive Liquid Waste Treatment Facility (RLWTF) at the Los Alamos National Laboratory (LANL) are concerned with the levels of perchlorates due to the effects it can have on the environment and resultant regulations. The RLWTF treats industrial and radioactive wastes generated at multiple research and production facilities across the LANL. Perchloric acid is the major source of the perchlorate ion in the RLWTF used in the analytical chemistry laboratories and for metal dissolution. Perchlorate is present in the influent to the RLWTF at concentrations up to several thousands microg/l level. Ion chromatography is the method of choice to analyze the concentrations of perchlorate in the wastewater generated at the RLWTF. Perchlorate was separated by elution through a CS16/CG16 with an EG40 eluent generator. To minimize background conductivity and enhance analyte conductance, an anion self-regenerating suppressor was used. The method achieved a perchlorate method detection limit of 1 microg/l. The method is successfully being used to monitor the perchlorate levels at the RLWTF and provide data for the pilot tests to remove perchlorate from the RLWTF effluent.

Chromatography, Ion Exchange↗

Effects of perchlorate on depolarization-induced conformational changes in the junctional foot protein and Ca2+ release from sarcoplasmic reticulum.

Perchlorate is one of the most potent activators of skeletal muscle excitation-contraction (E-C) coupling reported in the literature, but the detailed mechanism of its action remains to be elucidated. In an attempt to further resolve the mode of perchlorate action, the effects of increasing concentrations of perchlorate on the voltage-dependent (T-tubule-mediated) and voltage-independent portions of Ca2+ release were investigated using the isolated triad model. Low concentrations of perchlorate (< or = 10 mM) activated SR Ca2+ release only when the T-tubule moiety was chemically depolarized. Higher concentrations of perchlorate (30-100 mM), on the other hand, produced significant activation of SR Ca2+ release, regardless of whether or not the T-tubule was depolarized. In order to gain further insights, we monitored the conformational change in the junctional foot protein (JFP), which presumably is an important intermediate step in E-C coupling [Yano, M., El-Hayek, R., & Ikemoto, N. (1995) J. Biol. Chem. 270, 3017-3021], using the fluorescently labeled triad preparation. Again, low concentrations of perchlorate (< or = 10 mM) produced a preferential activation of voltage-dependent protein conformational change, while higher concentrations of perchlorate produced significant activation of voltage-independent protein conformational change. An increase in the ryanodine binding by perchlorate occurred only in the higher concentration range where the voltage-independent protein conformational change was activated. These results suggest that perchlorate activates E-C coupling by acting on at least two different steps: at lower concentrations, on the T-tubule-to-JFP signal transmission step; at higher concentrations, on the JFP directly.

Animals↗

Perchlorate and iodide in dairy and breast milk.

Perchlorate inhibits iodide uptake and may impair thyroid and neurodevelopment in infants. Recently, we unambiguously identified the presence of perchlorate in all seven brands of dairy milk randomly purchased from grocery stores in Lubbock, TX. How widespread is perchlorate in milk? Perchlorate in 47 dairy milk samples from 11 states and in 36 human milk samples from 18 states were measured. Iodide was also measured in a number of the samples. Perchlorate was detectable in 81 of 82 samples. The dairy and breast milk means were, respectively, 2.0 and 10.5 microg/L with the corresponding maximum values of 11 and 92 microg/L. Perchlorate is present in virtually all milk samples, the average concentration in breast milk is five times higher than in dairy milk. Although the number of available measurements are few at this point, for breast milk samples with a perchlorate content greater than 10 microg/L, the iodide content is linearly correlated with the inverse of the perchlorate concentration with a r2 of >0.9 (n = 6). The presence of perchlorate in the milk lowers the iodide content and may impair thyroid development in infants. On the basis of limited available data, iodide levels in breast milk may be significantly lower than it was two decades ago. Recommended iodine intake by pregnant and lactating women may need to be revised upward.

Animals↗

Perchlorate and nitrate in leafy vegetables of North America.

In previous studies trace levels of perchlorate were found in lettuce (Lactuca sativa L.) irrigated with Colorado River water, which is contaminated with low levels of perchlorate from aerospace and defense related industries. In this paper, we report the results of a survey conducted across North America to evaluate the occurrence of perchlorate in leafy vegetables produced outside the lower Colorado River region, and evaluate the relative iodide uptake inhibition potential to perchlorate and nitrate in these leafy vegetables. Conventionally and organically produced lettuce and other leafy vegetable samples were collected from production fields and farmers' markets in the central and coastal valleys of California, New Mexico, Colorado, Michigan, Ohio, New York, Quebec, and New Jersey. Results show that 16% of the conventionally produced samples and 32% of the organically produced samples had quantifiable levels of perchlorate using ion chromatography. Estimated perchlorate exposure from organically produced leafy vegetables was approximately 2 times that of conventional produce, but generally less than 10% of the reference dose recommended by the National Academy of Sciences. Furthermore, the iodide uptake inhibition potential of perchlorate was less than 1% of that of the nitrate present. These data are consistent with those of other reported perchlorate survey work with lettuce, bottled water, breast milk, dairy milk, and human urine, and suggest a wide national presence of perchlorate.

Environmental Monitoring↗

Biological reduction of perchlorate in ion exchange regenerant solutions containing high salinity and ammonium levels.

The most promising technologies to remove perchlorate from water are ion exchange and biological reduction. Although successful, ion exchange only separates perchlorate from water; it does not eliminate it from the environment. The waste streams from these systems contain the caustic or saline regenerant solutions used in the process as well as high levels of perchlorate. Biological reduction could be used to treat the regenerant waste solutions from the ion exchange process. A treatment scheme, combining ion exchange and biodegradation, is proposed to completely remove perchlorate from the environment. Perchlorate-laden resins generate brines containing salt concentrations up to 6% or caustic solutions containing up to 0.5% ammonium. Both, high salt and ammonium hydroxide concentrations are potentially toxic to microorganisms. Therefore, the challenge of the proposed system is to find perchlorate reducing microorganisms that are effective under such stressful conditions. Preliminary results have shown that salt concentrations as low as 0.5% reduced the perchlorate biodegradation rate by 30%; salt concentrations greater than 1% decreased this rate to 40%. Although biodegradation was seen in ammonium levels of 0.4%, 0.6% and 1%, the perchlorate biodegradation rate was 90% of that at 0% ammonium hydroxide. Further research will focus on the isolation and/or acclimation of microorganisms that are able to biodegrade perchlorate under these stressful conditions.

Ammonium Hydroxide↗

The effect of oral consumption of perchlorate, alone and in combination with ethanol, on plasma thyroid hormone and brain catecholamine concentrations in the rat.

Literature has reported a controversy concerning the effects of the environmental pollutant perchlorate on pertinent physiological systems. However, no research to date has evaluated the effect of concomitant consumption of perchlorate and an additional environmental contaminant on physiological systems. The present preliminary investigation served to assess the effects of oral consumption of perchlorate, alone and in combination with ethanol, on thyroid hormone and brain catecholamine concentrations in female rats of gestational age. Forty, female Myers' high ethanol-preferring rats were randomly assigned to 1 of 7 groups that received: (1) deionized water, both bottles (2) deionized water and 10% ethanol (v/v), two separate bottles (3) 300 microg/l perchlorate solution in deionized water, both bottles (4) 300 microg/l perchlorate in deionized water and in 10% ethanol (v/v), two separate bottles (5) 3000 microg/l perchlorate solution in deionized water, both bottles (6) 3000 microg/l perchlorate in deionized water and in 10% ethanol (v/v), two separate bottles (7) 0.01% propylthiouracil solution in deionized water, both bottles. At cessation of the treatment period, plasma triiodothyronine (T3) and thyroxine (T4) levels were measured by radioimmunoassay and brain area concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and norepinephrine were measured by high performance liquid chromatography. Perchlorate consumption, alone and/or in combination with ethanol consumption, failed to produce significant alterations from control values for triiodothyronine, thyroxine, dopamine, DOPAC, or norepinephrine. The data suggest that the no-observed effect level of perchlorate consumption on thyroid hormone and brain catecholamine concentrations is above the 3000 microg/l concentration in the adult female rat.

Alcohol-Induced Disorders, Nervous System↗

Identification, characterization, and classification of genes encoding perchlorate reductase.

The reduction of perchlorate to chlorite, the first enzymatic step in the bacterial reduction of perchlorate, is catalyzed by perchlorate reductase. The genes encoding perchlorate reductase (pcrABCD) in two Dechloromonas species were characterized. Sequence analysis of the pcrAB gene products revealed similarity to alpha- and beta-subunits of microbial nitrate reductase, selenate reductase, dimethyl sulfide dehydrogenase, ethylbenzene dehydrogenase, and chlorate reductase, all of which are type II members of the microbial dimethyl sulfoxide (DMSO) reductase family. The pcrC gene product was similar to a c-type cytochrome, while the pcrD gene product exhibited similarity to molybdenum chaperone proteins of the DMSO reductase family members mentioned above. Expression analysis of the pcrA gene from Dechloromonas agitata indicated that transcription occurred only under anaerobic (per)chlorate-reducing conditions. The presence of oxygen completely inhibited pcrA expression regardless of the presence of perchlorate, chlorate, or nitrate. Deletion of the pcrA gene in Dechloromonas aromatica abolished growth in both perchlorate and chlorate but not growth in nitrate, indicating that the pcrABCD genes play a functional role in perchlorate reduction separate from nitrate reduction. Phylogenetic analysis of PcrA and other alpha-subunits of the DMSO reductase family indicated that perchlorate reductase forms a monophyletic group separate from chlorate reductase of Ideonella dechloratans. The separation of perchlorate reductase as an activity distinct from chlorate reductase was further supported by DNA hybridization analysis of (per)chlorate- and chlorate-reducing strains using the pcrA gene as a probe.

Amino Acid Sequence↗

Perchlorate ion enhances mouse thyroid responsiveness to thyrotropin, human chorionic gonadotropin and long acting thyroid stimulator.

Perchlorate treatment of mice increased by 1.5-2-fold the thyroid secretory response to TSH, hCG and LATS, in the McKenzie bioassay. Perchlorate alone did not increase basal plasma radioactivity. Perchlorate augmentation of the secretory response index was roughly proportional to the level of stimulation; it was similar for all three stimulators despite their different time courses of action which were unaltered by perchlorate; it was the same whether perchlorate administration preceded, coincided with or shortly followed injection of the stimulator, a finding in keeping with the slow clearance of this ion. The perchlorate effect was dose-related, although within a narrow range (6.25-12.5 microng/mouse). Near-maximal per chlorate effect was obtained with a dose (12.5 microng) which, when tested in different experimental conditions (MMI-blocked thyroid), discharged 80% of intrathyroidal radioiodide. Perchlorate exerted its augmenting effect by enhancing thyroid secretion: it increased plasma radioiodothyronines and radioiodide concentrations without decreaseing the blood disappearance rates of iodide and iodothyronines. The potentiating effect of perchlorate probably takes place at a step prior to cyclic AMP action since it did not affect dbcAMP-stimulated secretion. The perchlorate effect may be indirect, through mobilization of minute amounts of intrathyroidal iodide.

Animals↗

Genetic factors that might lead to different responses in individuals exposed to perchlorate.

Perchlorate has been detected in groundwater in many parts of the United States, and recent detection in vegetable and dairy food products indicates that contamination by perchlorate is more widespread than previously thought. Perchlorate is a competitive inhibitor of the sodium iodide symporter, the thyroid cell-surface protein responsible for transporting iodide from the plasma into the thyroid. An estimated 4.3% of the U.S. population is subclinically hypothyroid, and 6.9% of pregnant women may have low iodine intake. Congenital hypothyroidism affects 1 in 3,000 to 1 in 4,000 infants, and 15% of these cases have been attributed to genetic defects. Our objective in this review is to identify genetic biomarkers that would help define subpopulations sensitive to environmental perchlorate exposure. We review the literature to identify genetic defects involved in the iodination process of the thyroid hormone synthesis, particularly defects in iodide transport from circulation into the thyroid cell, defects in iodide transport from the thyroid cell to the follicular lumen (Pendred syndrome), and defects of iodide organification. Furthermore, we summarize relevant studies of perchlorate in humans. Because of perchlorate inhibition of iodide uptake, it is biologically plausible that chronic ingestion of perchlorate through contaminated sources may cause some degree of iodine discharge in populations that are genetically susceptible to defects in the iodination process of the thyroid hormone synthesis, thus deteriorating their conditions. We conclude that future studies linking human disease and environmental perchlorate exposure should consider the genetic makeup of the participants, actual perchlorate exposure levels, and individual iodine intake/excretion levels.

Autoantigens↗