Topical Application of Perchlorate: A Toxicity Study in Rats.

PURPOSE: To investigate the ocular safety profile of topical perchlorate as a potential preventive treatment for nasolacrimal obstruction associated with excessive use of radioactive iodine therapy. METHODS: Nine Wistar male rats (18 eyes) were randomly assigned to receive an ocular application (topical eye drop on the OD, 3 times a day for 5 days) consisting of either: 1) sterile saline solution, 2) 30 mg/ml NaClO4 or 3) 30 mg/ml KClO4. The rat eyes were examined daily for corneal cloudiness/clarity, discharge, mucous secretions, conjunctival injection, eyelid erythema, and/or changes in behavior. Seven days after the first dose, the rats were euthanized and OU were harvested, fixed, embedded in paraffin, and stained with H&E and Masson's trichrome using standard techniques. RESULTS: The data collected over the 7 days revealed no behavior changes or ocular complications in any of the 3 study groups. Pathologic analysis of the corneas revealed normal findings on all groups without signs of inflammation, fibrosis, or any other abnormality, and no difference between the treated and control eyes. CONCLUSIONS: The findings of this study suggest that the use of topical perchlorate is safe to use on eyes in high concentrations. The efficacy of this compound in minimizing fibrosis of the nasolacrimal sac and duct warrants further study.

Thyroid-gonadal hormonal interplay in zebrafish exposed to sodium perchlorate: Implications for reproductive health.

Perchlorate, a widespread environmental contaminant originating from various industrial applications, agricultural practices, and natural sources, poses potential risks to ecosystems and human health. While previous studies have highlighted its influence on the thyroid endocrine system and its impact on gonadal maturation, reproduction, and sex hormone synthesis, the specific interplay between thyroid and steroid hormones, in this context, remains largely unexplored. Therefore, this study was undertaken to investigate the adverse effects and underlying mechanisms triggered by exposure to sodium perchlorate (SP) on reproductive endocrine activity in zebrafish. For 21 d, the fish were exposed to test SP concentrations (0, 3, 30, 300 mg/L), which were determined based on the exposure concentrations that induced various toxic effects in the fish, considering naturally occurring concentrations. Exposure to SP, except at 3 mg/L in males, significantly decreased the production of thyroid hormone (TH) in both female and male zebrafish. Moreover, gonadal steroid levels were markedly reduced in both sexes. The expression of hepatic vitellogenin (VTG) mRNA in female zebrafish was significantly decreased, whereas aromatase activity in male zebrafish was significantly elevated in the SP exposure groups. The reduced levels of THs and gonadal steroid hormones were strongly correlated. Abnormal responses to SP exposure led to reduced reproductive success in the 300 mg/L SP exposure group. These findings indicate that prolonged and continuous exposure to a specific concentration of SP may lead to long-term reproductive problems in zebrafish, primarily through hormonal imbalances and suppression of hepatic VTG mRNA expression.

Ammonium perchlorate: serum dosimetry, neurotoxicity, and resilience of the neonatal rat thyroid system.

The environmental contaminant perchlorate impairs the synthesis of thyroid hormones by reducing iodine uptake into the thyroid gland. Despite this known action, moderate doses of perchlorate do not significantly alter serum thyroid hormone in rat pups born to exposed dams. We examined perchlorate dosimetry and responsivity of the thyroid gland and brain in offspring following maternal exposure to perchlorate. Pregnant rat dams were delivered perchlorate in drinking water (0, 30, 100, 300, 1000 ppm) from gestational day 6 to postnatal day (PN) 21. Perchlorate was present in the placenta, milk, and serum, the latter declining in pups over the course of lactation. Serum and brain thyroid hormone were reduced in pups at birth but recovered to control levels by PN2. Dramatic upregulation of Nis was observed in the thyroid gland of the exposed pup. Despite the return of serum thyroid hormone to control levels by PN2, expression of several TH-responsive genes was altered in the PN14 pup brain. Contextual fear learning was unimpaired in the adults, supporting previous reports. Declining levels of serum perchlorate and a profound upregulation of Nis gene expression in the thyroid gland are consistent with the rapid return to the euthyroid state in the neonate. However, despite this recovery, thyroid hormone insufficiencies in serum and brain beginning in utero and present at birth appear sufficient to alter TH action in the fetus and subsequent trajectory of brain development. Biomarkers of that altered trajectory remain in the brain of the neonate, demonstrating that perchlorate is not devoid of effects on the developing brain.

Effects of perchlorate and exogenous T4 exposures on body condition and endochondral ossification of Rana chensinensis tadpoles.

Perchlorate, as an endocrine-disrupting chemical (EDC), is largely produced and used in the military, fireworks, fertilizers, and other industries and widely exists in water. Although perchlorate is known to destroy the normal function of thyroid hormones (THs) in amphibians and interfere with their growth and development, the impact of TH levels caused by sodium perchlorate (NaClO4) on endochondral ossification and skeletal development is poorly investigated, and the underlying molecular mechanism has not been clarified. The present study aimed to explore the potential effects of NaClO4 and exogenous thyroxine (T4) on the skeletal development of Rana chensinensis tadpoles and elucidate the related molecular mechanisms. Our results showed that histological changes occurred to the femur and tibia-fibula of tadpoles raised in 250 µg/L NaClO4 and 5 µg/L exogenous T4, and the length of their hindlimbs was significantly reduced. In addition, exogenous T4 exposure significantly interfered with the expression of Dio3, TRß, MMP9, MMP13, and Runx2, inhibiting the endochondral ossification process. Therefore, we provide robust evidence that the changes in TH levels caused by NaClO4 and exogenous T4 will adversely affect the endochondral ossification and skeletal development of R. chensinensis tadpoles.

Towards translating in vitro measures of thyroid hormone system disruption to in vivo responses in the pregnant rat via a biologically based dose response (BBDR) model.

Despite the number of in vitro assays that have been recently developed to identify chemicals that interfere with the hypothalamic-pituitary-thyroid axis (HPT), the translation of those in vitro results into in vivo responses (in vitro to in vivo extrapolation, IVIVE) has received limited attention from the modeling community. To help advance this field a steady state biologically based dose response (BBDR) model for the HPT axis was constructed for the pregnant rat on gestation day (GD) 20. The BBDR HPT axis model predicts plasma levels of thyroid stimulating hormone (TSH) and the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Thyroid hormones are important for normal growth and development of the fetus. Perchlorate, a potent inhibitor of thyroidal uptake of iodide by the sodium iodide symporter (NIS) protein, was used as a case study for the BBDR HPT axis model. The inhibitory blocking of the NIS by perchlorate was associated with dose-dependent steady state decreases in thyroid hormone production in the thyroid gland. The BBDR HPT axis model predictions for TSH, T3, and T4 plasma concentrations in pregnant Sprague Dawley (SD) rats were within 2-fold of observations for drinking water perchlorate exposures ranging from 10 to 30,000 µg/kg/d. In Long Evans (LE) pregnant rats, for both control and perchlorate drinking water exposures, ranging from 85 to 82,000 µg/kg/d, plasma thyroid hormone and TSH concentrations were predicted within 2 to 3.4- fold of observations. This BBDR HPT axis model provides a successful IVIVE template for thyroid hormone disruption in pregnant rats.

Exploring cell aggregation as a defense strategy against perchlorate stress in Chlamydomonas reinhardtii through multi-omics analysis.

Perchlorate (ClO4-) is a type of novel, widely distributed, and persistent inorganic pollutant. However, the impacts of perchlorate on freshwater algae remain unclear. In this study, the response and defense mechanisms of microalgae (Chlamydomonas reinhardtii) under perchlorate stress were investigated by integrating physiological and biochemical monitoring, transcriptomics, and metabolomics. Weighted gene co-expression network analysis (WGCNA) of transcriptome data was used to analyze the relationship between genes and phenotype and screen the key pathways. C. reinhardtii exhibited aggregate behavior when exposed to 100- and 200-mM perchlorate but was restored to its unicellular lifestyle when transferred to fresh medium. WGCNA results found that the "carbohydrate metabolism" and "lipid metabolism" pathways were closely related to cell aggregation phenotype. The differential expression genes (DEGs) and differentially accumulated metabolites (DAMs) of these pathways were upregulated, indicating that the lipid and carbohydrate metabolisms were enhanced in aggregated cells. Additionally, most genes and metabolites related to phytohormone abscisic acid (ABA) biosynthesis and the mitogen-activated protein kinase (MAPK) signaling pathway were significantly upregulated, indicating their crucial roles in the signal transmission of aggregated cells. Meanwhile, in aggregated cells, extracellular polymeric substances (EPS) and lipid contents increased, photosynthesis activity decreased, and the antioxidant system was activated. These characteristics contributed to C. reinhardtii's improved resistance to perchlorate stress. Above results demonstrated that cell aggregation behavior was the principal defense strategy of C. reinhardtii against perchlorate. Overall, this study sheds new light on the impact mechanisms of perchlorate to aquatic microalgae and provides multi-omics insights into the research of multicellular-like aggregation as an adaptation strategy to abiotic stress. These results are beneficial for assessing the risk of perchlorate in aquatic environments.

Physiologically-based toxicokinetic model for the prediction of perchlorate distribution and its application.

Perchlorate is a stable and readily transportable thyroid hormone disruptor, and prevalent exposure to perchlorate through food and drinking water has raised public concern about its health effects. The physiologically based toxicokinetic (PBTK) model as a dose prediction method is effective to predict the toxicant exposure dose of an organism and helps quantitatively assess the dose-dependent relationship with toxic effects. The current study aimed to establish a multi-compartment PBTK model based on updated time-course datasets of single oral exposure to perchlorate in rats. With adjustment of the kinetic parameters, the model fitted well the toxicokinetic characteristics of perchlorate in urine, blood, and thyroid from our experiments and the literature, and the coefficient of determination (R2) between the fitting values and the experimental data in regression analysis was greater than 0.91, indicating the robustness of the current model. The results of sensitivity analysis and daily repeated exposure simulations together confirmed its effective renal clearance. According to the distribution characteristic of perchlorate, a correlation study of internal and external exposure was conducted using urinary perchlorate as a bioassay indicator. The developed multi-compartment model for perchlorate updates important toxicokinetic data and kinetic parameters, providing analytical and modeling tools for deriving total exposure levels in the short term.

Perchlorate, nitrate, and thiocyanate: Environmental relevant NIS-inhibitors pollutants and their impact on thyroid function and human health.

Thyroid disruptors are found in food, atmosphere, soil, and water. These contaminants interfere with the thyroid function through the impairment of thyroid hormone synthesis, plasma transport, peripheral metabolism, transport into the target cells, and thyroid hormone action. It is well known that iodide uptake mediated by the sodium-iodide symporter (NIS) is the first limiting step involved in thyroid hormones production. Therefore, it has been described that several thyroid disruptors interfere with the thyroid function through the regulation of NIS expression and/or activity. Perchlorate, nitrate, and thiocyanate competitively inhibit the NIS-mediated iodide uptake. These contaminants are mainly found in food, water and in the smoke of cigarettes. Although the impact of the human exposure to these anions is highly controversial, some studies indicated their deleterious effects in the thyroid function, especially in individuals living in iodine deficient areas. Considering the critical role of thyroid function and the production of thyroid hormones for growth, metabolism, and development, this review summarizes the impact of the exposure to these NIS-inhibitors on thyroid function and their consequences for human health.

Potassium perchlorate effects on primordial germ cells of developing medaka larvae.

Perchlorate is a chemical compound commonly used in military artillery and equipment. It has been detected in drinking water, air, soil, and breast milk. Exposure of humans to perchlorate can occur in the theater of war and areas adjacent to military training grounds. A high concentration of perchlorate has been found to affect reproduction in vertebrates, including fish. However, whether environmental concentrations of perchlorate can affect primordial germ cells (PGCs), the founders of sperm and eggs, is not clearly understood. In the present study, we examined the effects of 0, 10, 100, and 1000 µg/L potassium perchlorate exposure on the embryonic development of medaka and their PGCs. Perchlorate exposure delayed hatching time, reduced heartbeat, inhibited migration of PGCs, and increased developmental deformities in the larvae. The 10 and 20 mg/L concentrations of perchlorate were lethal to embryos, whereas vitamin C co-treatment (1 mg/L) completely blocked perchlorate-induced mortality. RNA-seq analysis of isolated PGCs showed a non-linear pattern in expression profiles of differentially altered genes. Significantly upregulated genes were found in PGCs from the 10 and 1000 µg/L groups, whereas the 100 µg/L groups showed the highest number of significantly downregulated genes. Gene ontology analysis predicted differentially expressed genes to be involved in proteolysis, metabolic processes, peptides activity, hydrolase activity, and hormone activity. Among the cellular components, extracellular, intracellular, sarcoplasmic, and 6-phosphofructokinase and membrane-bounded processes were affected. Ingenuity Pathway Analysis of PGC transcriptomes revealed thyroid hormone signaling to be affected by all concentrations of perchlorate. The present results suggested that perchlorate affected the development of medaka larvae and vitamin C was able to ameliorate perchlorate-induced embryo mortality. Additionally, perchlorate altered the global transcriptional network in PGCs in a non-linear fashion suggesting its potential effects on developing germ cells and fertility.

Integration of probabilistic exposure assessment and risk characterization for perchlorate in infant formula and supplementary food.

Infants are the primary susceptible population to perchlorate exposure-related adverse health effects, while information on their dietary intake of perchlorate via infant food remains limited. This study determined perchlorate in six categories of baby food commodities commonly consumed by 0-36 months infants. A probabilistic approach with Monte Carlo simulation was used to estimate perchlorate's daily intake (EDI) considering uncertainty and variability. Results showed that the average perchlorate concentration in infant food ranged from 3.42 to 22.26 µg/kg. The mean (SD) EDIs of perchlorate were 0.42(0.20), 0.62(0.20), and 0.46(0.14) µg/kg-bw/day for 0-6, 7-12, and 13-36-months infants, respectively. Infant formula was the major contributor (34%-74%) to EDIs of perchlorate in all age groups. Probabilistic risk characterization showed the cumulative probability of EDIs exceeding the RfD (0.70 µg/kg-bw/day) were 6.5%, 37.9%, and 4.5% for 0-6, 7-12, and 13-36-months infants, respectively. The cumulative risk of perchlorate exposure from different infant food intake should be noted.

Health risk assessment of perchlorate and chlorate in red swamp crayfish (Procambarus clarkii) in China.

Perchlorate and chlorate are both strong oxidants and thyroid toxicants that are widely distributed in soil, water and human foods. The red swamp crayfish (Procambarus clarkii) is a common aquatic organism that is popular in Chinese culinary dishes. Dietary intake is the main route of human exposure to perchlorate and chlorate, though the health risks of crayfish consumption are unknown. Thus, this study investigated the quantities of perchlorate and chlorate in red swap crayfish from sampling sites in five provinces located near the Yangtze River in China, along with the associated health risks of consuming this species. Perchlorate was detected in 55.6-100 % of crayfish samples in each sampling location, and chlorate was found in 100 % of samples cross all sites. Concentrations of perchlorate in crayfish from upstream provinces (Hubei, Hunan and Jiangxi) were higher than those from downstream provinces (Anhui and Jiangsu). Perchlorate and chlorate concentrations were positively correlated in crayfish, suggesting that chlorate may be a degradation byproduct of perchlorate. The quantities of both pollutants in hepatopancreas tissue were higher than in muscle tissues (p < 0.05), such that we do not recommend ingesting crayfish hepatopancreas. Hazard quotient (HQ) values for chlorate in crayfish were <1 across all provinces, suggesting no potential health risk of chlorate exposure through crayfish consumption. However, perchlorate concentrations in crayfish from the Jiangxi province had an associated HQ value >1, suggesting potential risks for human health. These results will be useful in informing mitigation measures aimed at reducing perchlorate exposure associated with crayfish consumption.

Gestational Exposure to Perchlorate in the Rat: Thyroid Hormones in Fetal Thyroid Gland, Serum, and Brain.

Iodine is essential for the production of thyroid hormones. Perchlorate is an environmental contaminant that interferes with iodine uptake into the thyroid gland to reduce thyroid hormone synthesis. As thyroid hormones are critical for brain development, exposure to perchlorate during pregnancy is of concern for the developing fetal brain. In this study, we (1) define profiles of thyroid hormone in the maternal and fetal compartments of pregnant rats in response to inhibition of the sodium-iodide symporter (NIS) by perchlorate and (2) expand inquiry previously limited to serum to include fetal thyroid gland and brain. Perchlorate was added to the drinking water (0, 1, 30, 300, and 1000 ppm) of pregnant rat dams from gestational days (GD) 6-20. On GD20, blood, thyroid gland, and brain were collected from the fetus and dam for thyroid hormone and molecular analyses. Thyroid gland and serum thyroid hormones were dose-dependently reduced, with steeper declines evident in the fetus than in the dam. The thyroid gland revealed perturbations of thyroid hormone-action with greater sensitivity in the fetus than the dam. Thyroid hormones and thyroid hormone-responsive gene expression were reduced in the fetal cortex portending effects on brain development. These findings are the first quantitative assessments of perchlorate-induced deficits in the fetal thyroid gland and fetal brain. We provide a conceptual framework to develop a quantitative NIS adverse outcome pathway for serum thyroid hormone deficits and the potential to impact the fetal brain. Such a framework may also serve to facilitate the translation of in vitro bioactivity to the downstream in vivo consequences of NIS inhibition in the developing fetus.

Aggregating exposures and toxicity equivalence approach into an integrated probabilistic dietary risk assessment for perchlorate, nitrate, and thiocyanate: Results from the National food monitoring study and National Food Consumption Database.

Perchlorate, nitrate, and thiocyanate, namely thyroid disrupting chemicals (TDCs), are found ubiquitously in the environment, leading to broad human exposure and primary uptake through the food web and drinking water. TDCs are all competitive inhibitors of thyroid iodide uptake activity, but limited studies have assessed the cumulative risk of dietary exposure to multiple TDCs. Thus, in this study, we analyzed the individual exposure risk from 310 food samples in 11 categories, and also assessed the cumulative health risks from TDCs for the Taiwanese population using a perchlorate equivalent concentration (PEC) approach. Consequently, this study not only demonstrated the non-carcinogenic health risks from individual exposure but also highlighted that the cumulative exposure to these TDCs may adversely affect human thyroid functioning. Vegetables, livestock, fruits, and dairy products are the most susceptible to PEC exposure. We highlighted nitrate as the main contributor to PEC exposure. Finally, controlling the overall TDC concentrations from vegetables, livestock, fruits, and dairy products is emphasized in this study. This is the first study to conduct a cumulative risk assessment of dietary exposure to TDCs using the PEC approach for the Taiwanese population through probabilistic and sensitivity analyses.

Effects of sodium perchlorate and 6-propylthiouracil on metamorphosis and thyroid gland histopathology in the European common frog (Rana temporaria).

Several chemicals have been identified as thyroid hormone axis disrupting chemicals (THADCs) able to interfere with the thyroid hormone system during fetal life and early life stages, thereby impairing neurodevelopment in mammals and inducing development and growth disorders in fish and amphibians. However, identification of THADCs is particularly challenging, and thyroid modalities are currently only assessed in vivo by mammalian and amphibian tests. The aquatic African clawed frog (Xenopus laevis/tropicalis) is the model species of the amphibian test guidelines developed by the OECD and the United States Environmental Protection Agency, but as most European amphibians are semi-aquatic, concern has been raised whether the sensitivity of native European species is comparable to Xenopus. A shortened version of the OEDC test guideline 241 (Larval Amphibian Growth and Development Assay, LAGDA) was used to investigate the effects of two model THADCs on the metamorphosis and thyroid histopathology in the European common frog (Rana temporaria). R. temporaria eggs were collected on the field and exposed till metamorphic climax to sodium perchlorate (11.9-426.5 µg/L perchlorate concentrations) and 6-propylthiouracil (PTU: 1.23-47.7 mg/L). PTU severely delayed metamorphosis and affected several thyroid gland histopathological endpoints at slightly lower concentrations compared to Xenopus. As opposed to what was described in similar Xenopus studies, we observed no effect of perchlorate on the investigated endpoints. Interspecies differences may be linked to mechanisms of action.

Effects of perchlorate and exogenous T4 exposures on development, metamorphosis and endochondral ossification in Bufo gargarizans larvae.

Several endocrine-disrupting chemicals (EDCs) have been proven to interfere with the physiological function of thyroid hormone (TH), which affected growth and development. However, few studies have investigated the effects of EDCs on TH axis with consequence for skeletal development in amphibians. This study thus examined the potential role of perchlorate and T4 in growth, development and endochondral ossification during metamorphosis of Bufo gargarizans. Our studies showed that NaClO4 treatment caused weight gain and delayed the developmental stage in B. gargarizans tadpoles, while T4 decreased body size and survival rate, accelerated metamorphic duration and increased the risk of early death. Histological sections suggested that NaClO4 and T4 treatments caused damages to thyroid tissue, such as decreased thyroid gland size, follicle size, colloid area, the height of follicular epithelial cells and the number of follicles. In addition, the double skeletal staining and RT-qPCR showed that NaClO4 and T4 treatments inhibited the endochondral ossification by regulating TH synthesis (TRs, Dios) and endochondral ossification-related genes (MMPs, Runxs, VEGFs and VEGFRs) expression levels, which might affect terrestrial locomotion and terrestrial life. Altogether, these thyroid injury and gene expression changes as caused by NaClO4 and T4 may have an influence on development and endochondral ossification during the metamorphosis of amphibians.

Perchlorate Contamination: Sources, Effects, and Technologies for Remediation.

Perchlorate is a persistent pollutant, generated via natural and anthropogenic processes, that possesses a high potential for endocrine disruption in humans and biota. It inhibits iodine fixation, a major reason for eliminating this pollutant from ecosystems. Remediation of perchlorate can be achieved with various physicochemical treatments, especially at low concentrations. However, microbiological approaches using microorganisms, such as those from the genera Dechloromonas, Serratia, Propionivibrio, Wolinella, and Azospirillum, are promising when perchlorate pollution is extensive. Perchlorate-reducing bacteria, isolated from harsh environments, for example saline soils, mine sediments, thermal waters, wastewater treatment plants, underground gas storage facilities, and remote areas, including the Antarctica, can provide removal yields from 20 to 100%. Perchlorate reduction, carried out by a series of enzymes, such as perchlorate reductase and superoxide chlorite, depends on pH, temperature, salt concentration, metabolic inhibitors, nutritional conditions, time of contact, and cellular concentration. Microbial degradation is cost-effective, simple to implement, and environmentally friendly, rendering it a viable method for alleviating perchlorate pollution in the environment.

Perchlorate exposure does not induce obesity or non-alcoholic fatty liver disease in zebrafish.

Perchlorate is a water-soluble contaminant found throughout the United States and many other countries. Perchlorate competitively inhibits iodide uptake at the sodium/iodide symporter, reducing thyroid hormone synthesis, which can lead to hypothyroidism and metabolic syndromes. Chronic perchlorate exposure induces hepatic steatosis and non-alcoholic fatty liver disease (NAFLD) in developing threespine stickleback (Gasterosteus aculeatus). We hypothesized that perchlorate would also induce zebrafish (Danio rerio) to develop phenotypes consistent with NAFLD and to accumulate lipids throughout the body. We exposed zebrafish embryos to four concentrations of perchlorate treated water (10µg/L, 10mg/L, 30mg/L, and 100mg/L) and a control (0mg/L) over the course of 133 days. Adult zebrafish were euthanized, sectioned, H&E and Oil Red-O stained, and analyzed for liver morphology and whole body lipid accumulation. In a representative section of the liver, we counted the number of lipid droplets and measured the area of each droplet and the total lipid area. For whole body analysis, we calculated the ratio of lipid area to body area within a section. We found that zebrafish exposed to perchlorate did not differ in any measured liver variables or whole body lipid area when compared to controls. In comparison to stickleback, we see a trend that control stickleback accumulate more lipids in their liver than do control zebrafish. Differences between the species indicate that obesogenic effects due to perchlorate exposure are not uniform across fish species, and likely are mediated by evolutionary differences related to geographic location. For example, high latitude fishes such as stickleback evolved to deposit lipid stores for over-winter survival, which may lead to more pronounced obesogenic effects than seen in tropical fish such as zebrafish.

A comparison of thyroidal protection by iodine and perchlorate against radioiodine exposure in Caucasians and Japanese.

Radioactive iodine released in nuclear accidents may accumulate in the thyroid and by irradiation enhances the risk of cancer. Radioiodine uptake into the gland can be inhibited by large doses of stable iodine or perchlorate. Nutritional iodine daily intake may impact thyroid physiology, so that radiological doses absorbed by the thyroid as well as thyroid blocking efficacy may differ in Japanese with a very rich iodine diet compared to Caucasians. Based on established biokinetic-dosimetric models for the thyroid, we derived the parameters for Caucasians and Japanese to quantitatively compare the effects of radioiodine exposure and the protective efficacy of thyroid blocking by stable iodine at the officially recommended dosages (100 mg in Germany, 76 mg in Japan) or perchlorate. The maximum transport capacity for iodine uptake into the thyroid is lower in Japanese compared to Caucasians. For the same radioiodine exposure pattern, the radiological equivalent thyroid dose is substantially lower in Japanese in the absence of thyroid blocking treatments. In the case of acute radioiodine exposure, stable iodine is less potent in Japanese (ED50 = 41.6 mg) than in Caucasians (ED50 = 2.7 mg) and confers less thyroid protection at the recommended dosages because of a delayed responsiveness to iodine saturation of the gland (Wolff-Chaikoff effect). Perchlorate (ED50 = 10 mg in Caucasians) at a dose of 1000 mg has roughly the same thyroid blocking effect as 100 mg iodine in Caucasians, whereas it confers a much better protection than 76 mg iodine in Japanese. For prolonged exposures, a single dose of iodine offer substantially lower protection than after acute radioiodine exposure in both groups. Repetitive daily iodine administrations improve efficacy without reaching levels after acute radioiodine exposure and achieve only slightly better protection in Japanese than in Caucasians. However, in the case of continuous radioiodine exposure, daily doses of 1000 mg perchlorate achieve a high protective efficacy in Caucasians as well as Japanese (> 0.98). In Caucasians, iodine (100 mg) and perchlorate (1000 mg) at the recommended dosages seem alternatives in case of acute radioiodine exposure, whereas perchlorate has a higher protective efficacy in the case of longer lasting radioiodine exposures. In Japanese, considering protective efficacy, preference should be given to perchlorate in acute as well as prolonged radioiodine exposure scenarios.

Bioavailability Evaluation of Perchlorate in Different Foods In Vivo: Comparison with In Vitro Assays and Implications for Human Health Risk Assessment.

Perchlorate in various foods continuously arouses public health concern. Bioavailability is a critical parameter to better estimate perchlorate exposure from diets. In this study, perchlorate bioavailability in five foods was determined in an in vivo mouse model and compared with in vitro bioaccessibility/bioavailability. The estimated in vivo perchlorate bioavailability for different foods ranged from 18.01 ± 4.53% to 45.60 ± 7.11%, with the order lettuce > pork > rice > milk powder > soybean. Moisture, fiber, and fat in foods were identified as critical factors affecting perchlorate bioavailability (correlation r = 0.71, 0.52, and -0.67, respectively). Linear regression analysis revealed that the in vitro perchlorate bioavailability determined using the Caco-2 cell model has the potential to estimate the in vivo perchlorate bioavailability in foods (R2 = 0.67, slope = 1.33, and y intercept = 4.99). These findings provide insights into the effects of the food matrices on perchlorate bioavailability and could contribute to decrease the uncertainty regarding perchlorate dietary exposure risk assessment.

Combined effects of perchlorate and hexavalent chromium on the survival, growth and reproduction of Daphnia carinata.

Perchlorate and hexavalent chromium (Cr(VI)) are common cocontaminants in aquatic environments due to their high water solubility, stability, mobility, and some coapplications. However, few studies have investigated their combined toxicity to organisms. In this work, we studied the acute and chronic toxicities of perchlorate and Cr(VI), alone and in combination, with survival, growth, and reproduction as endpoints using Daphnia carinata as a model organism. For a single contaminant, Cr(VI) was found to be more toxic than perchlorate to D. carinata not only in terms of survival but also in terms of growth and reproduction. In regard to the combined pattern, the interactive effects on survival, growth, and reproduction were mainly additivity, antagonism, and synergism, respectively, suggesting that the interactive response of perchlorate and Cr(VI) is endpoint-specific. Due to significant synergism, over 21 days of observation, the inhibition of 0.1 mg/L perchlorate and 0.2 mg/L Cr(VI) on cumulative offspring per female in the first seven broods reached 63.9 ± 3.6%, suggesting that long-term exposure to perchlorate and Cr(VI) at environmentally relevant concentrations may affect D. carinata reproduction in the natural environment. Our results will be significant for understanding the complicated combined toxicity of perchlorate and Cr to aquatic organisms.