Although selenium is an essential element for humans, acute toxicity has been reported after high oral exposure.
The published literature on the acute toxicity of oral selenium was gathered and ...reviewed.
Reported symptoms and signs include abdominal symptoms, such as vomiting, diarrhea, pain, and nausea, as well as garlic-like odor on the breath. In cases of severe toxicity, cardiac and pulmonary symptoms may develop and ultimately lead to mortality. Mortality has been described after the ingestion of gun bluing solutions, which often contain selenous acid among other potentially toxic substances. Mortality has also been reported after the ingestion of other forms of selenium. Ingested doses associated with mortality are in the range of 1–100 mg Se/kg body weight. Blood levels associated with mortality are above 300 μg Se/L (normal level: 100 μg/L), whereas urinary levels associated with the same endpoint are above170 μg Se/L (normal level: 20–90 μg/L).
The acute toxicity associated with oral selenium ingestion and the blood and urinary levels of selenium in different cases of poisonings were reviewed. Mortality is a risk of acute selenium poisoning. Concentrations of selenium in blood and urine samples in non-fatal cases are close to those observed in fatal cases.
Selenium is a trace element traditionally ingested either in its organic form via food or in its inorganic form through nutritional supplements, while selenium formulated as nanoparticles is a ...putative long-acting alternative. To understand the physiology and toxicology of the different selenium formulations, it is important to determine how their selenium content is absorbed, distributed, metabolised and excreted; therefore, we reviewed their biokinetics following oral exposure.
We retrieved and reviewed the literature on the absorption, distribution, metabolism, and excretion of oral exposure to different forms of selenium.
Selenium in both the organic form (containing carbon to selenium chemical bonds) and the inorganic form is absorbed into the blood in humans. The mean normal blood level of many studies was 139 μg/L. There are indications that selenium from organic sources is more bioavailable than selenium from inorganic sources. Selenium is distributed throughout the body, including in breast milk. The elimination of selenium mainly involves the faecal and urinary pathways, whereas breath, saliva and hair are minor contributors. Urinary metabolites include trimethylselenium ions, selenosugars and Se-methylselenoneine.
Selenium is absorbed to a high extent, and selenium from organic sources is more bioavailable than from inorganic sources. Selenium, as expected as an essential trace element, is distributed throughout the body. Selenium is extensively metabolised, and various excretion metabolites have been identified in both urine and breath, while some selenium is also excreted via faeces.
To protect from toxicity at supra-essential doses of selenium, it is important to determine dose levels at which adverse effects occur.
We identified relevant literature on the repeated dosage of ...selenium and extracted dose descriptors on reported endpoints, except on genotoxicity/carcinogenicity.
Selenium forms with toxicological data were organic ones: selenomethionine, selenocystine/selenocysteine; and inorganic ones, including selenite (SeO32-), selenate (SeO42-), selenium sulphide (SeS2), selenide (Se2-) and selenium nanoparticles. Clinical signs of selenium toxicity in humans include a garlicky-smelling breath, hair loss, and nail changes. One human study showed increased mortality following daily ingestion of 300 µg Se per day for 5 years, equal to a lowest-observed-adverse-effect level (LOAEL) of ∼4.3 µg/kg bw/days. The corresponding no-observed-adverse-effect level (NOAEL) was ∼2.9 µg Se/kg bw/day. One study reported an increased risk of type 2 diabetes after ∼2.9 µg Se/kg bw/day, but other studies with similar doses found no increases in mortality or incidence of type 2 diabetes. NOAELs on affected body weight in animal studies were 0.24–1.2 mg Se/kg bw/day. Other endpoints of selenium toxicity in animals include hepatotoxicity with a NOAEL as low as 2 µg/kg bw/day in rats, as well as gastrointestinal, cardiovascular, and reproductive toxicities with NOAELs of 0.6 (gastrointestinal), 0.08, and 0.4 (cardiovascular) and ≥ 0.04 mg Se/kg bw/day (reproductive), respectively.
Dose descriptors describing selenium toxicity were as low as 2–3 µg Se/kg bw/day.
Objective
Iodine fortification (IF) induces an initial increase followed by a decrease in the incidence of hyperthyroidism in the general population. Within the population of hyperthyroid patients, ...the sex‐, age‐ and subtype distribution changes after IF. The risk of atrial fibrillation (AF) in hyperthyroid patients may be influenced by these factors. Therefore, we aimed to examine how the association between incident hyperthyroidism and AF was affected by IF increasing the population iodine intake from moderate‐mild iodine deficiency to low adequacy.
Design, Patients and Measurements
Incident hyperthyroid patients were included at the date of first inpatient or outpatient diagnosis, and AF diagnoses within 3 months before to 6 months after the index date were identified in Danish nationwide registers, 1997–2018. The relative risk (RR) of AF each calendar year (reference: 1997; IF introduced: 2000) was analyzed in Poisson regression models adjusted for age, sex, educational level, geographic region, and comorbidities.
Results
Overall, in 62,201 patients with incident hyperthyroidism 7.9% were diagnosed with AF. There was a minor nonsignificantly increased risk of AF during the first years after IF followed by a gradual decrease to RR 0.76 (0.62–0.94) in 2017. There were no statistically significant differences in the development in the risk of AF by sex, age group, or geographic region.
Conclusions
Results indicate that IF may reduce the risk of concomitant AF in hyperthyroid patients. If these results are confirmed, IF may not only reduce the population incidence of hyperthyroidism but also reduce the burden of morbidity in the remaining hyperthyroid patients.
Accurately segmenting foods from optical images is a challenging task, yet becoming possible with the help of recent advances in Deep Learning based solutions. Automated identification of food items ...opens up possibilities of useful applications like nutrition intake monitoring. Given large variations in food choices, Deep Learning based solutions still struggle to generate human level accuracy. In this work, we propose a novel Sequential Transfer Learning method using Hierarchical Clustering. This novel approach simulates a step by step problem solving framework based on clustering of similar types of foods. The proposed approach provides up to 6% gain in accuracy compared to traditional network training and generated a robust model performing better in challenging unseen cases. This approach is also tested for segmenting foods in Danish school children meals for dietary intake monitoring as an application.
Objective
The incidence of hypothyroidism is not expected to differ by socioeconomic factors. However, the decision to test and initiate treatment may differ. We aimed to examine whether educational ...level influences the probability of thyroid stimulation hormone (TSH)‐measurement and initiation of levothyroxine treatment.
Design
Citizens in the greater Copenhagen Area during 2001‐2015 were included. Individual‐level data on educational level, diagnoses, GP‐contact, TSH‐measurement and medication were derived from administrative and healthcare registers. The relative risks (RR) between educational levels of annual TSH‐measurement and treatment initiation following a TSH‐measurement were analysed in Poisson regression models with generalized estimation equations.
Results
A TSH‐measurement was performed in 19% of 9,390,052 person years. The probability of TSH‐measurement was higher with short (RR 1.16 95% CI 1.15–1.16) and medium (RR 1.11 95% CI 1.06–1.12) compared with long education.
Treatment was initiated after 0.8% of 2,049,888 TSH‐measurements. For TSH < 5 mIU/L, RR for treatment initiation ranged between 0.47 (95%CI 0.39–0.57) and 0.78 (95%CI 0.67–0.91) for short and medium compared with long education. For TSH 5–10 mIU/L, there was no statistically significant difference. For TSH > 10 mIU/L, RR was 1.07 (95% CI 1.02–1.12) for short and 1.08 (95% CI 1.03–1.13) for medium compared with long education.
Conclusion
The probability of TSH‐measurement was higher with shorter education, and the probability of treatment initiation with TSH > 10 mIU/L was marginally higher with short‐medium education compared with long education. However, the probability of treatment initiation with TSH < 5 mIU/L, that is treatment incongruous with guidelines, was substantially higher in persons with long education.
Recent findings show that cerium oxide (CeO2) nanoparticles may undergo in vivo-induced size transformation with the formation of smaller particles that could result in a higher translocation ...following pulmonary exposure compared to virtually insoluble particles, like titanium dioxide (TiO2). Therefore, we compared liver deposition of CeO2 and TiO2 nanoparticles of similar primary sizes 1, 28 or 180 days after intratracheal instillation of 162 μg of NPs in female C57BL/6 mice. Mice exposed to 162 μg CeO2 or TiO2 nanoparticles by intravenous injection or oral gavage were included as reference groups to assess the amount of NPs that reach the liver bypassing the lungs and the translocation of NPs from the gastrointestinal tract to the liver, respectively. Pulmonary deposited CeO2 nanoparticles were detected in the liver 28 and 180 days post-exposure and TiO2 nanoparticles 180 days post-exposure as determined by darkfield imaging and by the quantification of Ce and Ti mass concentration by inductively coupled plasma-mass spectrometry (ICP-MS). Ce and Ti concentrations increased over time and 180 days post-exposure the translocation to the liver was 2.87 ± 3.37% and 1.24 ± 1.98% of the initial pulmonary dose, respectively. Single particle ICP-MS showed that the size of CeO2 nanoparticles in both lung and liver tissue decreased over time. No nanoparticles were detected in the liver following oral gavage. Our results suggest that pulmonary deposited CeO2 and TiO2 nanoparticles translocate to the liver with similar calculated translocation rates despite their different chemical composition and shape. The observed particle size distributions of CeO2 nanoparticles indicate in vivo processing over time both in lung and liver. The fact that no particles were detected in the liver following oral exposure showed that direct translocation of nanoparticles from lung to the systemic circulation was the most important route of translocation for pulmonary deposited particles.
Environmental factors such as diet, intake of vitamin D supplements and exposure to sunlight are known to influence serum vitamin D concentrations. Genetic epidemiology of vitamin D is in its infancy ...and a better understanding on how genetic variation influences vitamin D concentration is needed. We aimed to analyse previously reported vitamin D-related polymorphisms in relation to serum 25(OH)D concentrations in 201 healthy Danish families with dependent children in late summer in Denmark. Serum 25(OH)D concentrations and a total of 25 SNPs in GC, VDR, CYP2R1, CYP24A1, CYP27B1, C10or88 and DHCR7/NADSYN1 genes were analysed in 758 participants. Genotype distributions were in Hardy-Weinberg equilibrium for the adult population for all the studied polymorphisms. Four SNPs in CYP2R1 (rs1562902, rs7116978, rs10741657 and rs10766197) and six SNPs in GC (rs4588, rs842999, rs2282679, rs12512631, rs16846876 and rs17467825) were statistically significantly associated with serum 25(OH)D concentrations in children, adults and all combined. Several of the SNPs were in strong linkage disequilibrium, and the associations were driven by CYP2R1-rs10741657 and rs10766197, and by GC-rs4588 and rs842999. Genetic risk score analysis showed that carriers with no risk alleles of CYP2R1-rs10741657 and rs10766197, and/or GC rs4588 and rs842999 had significantly higher serum 25(OH)D concentrations compared to carriers of all risk alleles. To conclude, our results provide supporting evidence that common polymorphisms in GC and CYP2R1 are associated with serum 25(OH)D concentrations in the Caucasian population and that certain haplotypes may predispose to lower 25(OH)D concentrations in late summer in Denmark.
Little is known about the mechanism underlying the genotoxicity observed in the liver following pulmonary exposure to carbon black (CB) nanoparticles (NPs). The genotoxicity could be caused by the ...presence of translocated particles or by circulating inflammatory mediators released during pulmonary inflammation and acute-phase response. To address this, we evaluated induction of pulmonary inflammation, pulmonary and hepatic acute-phase response and genotoxicity following exposure to titanium dioxide (TiO
), cerium oxide (CeO
) or CB NPs. Female C57BL/6 mice were exposed by intratracheal instillation, intravenous injection or oral gavage to a single dose of 162 μg NPs/mouse and terminated 1, 28 or 180 days post-exposure alongside vehicle control.
Liver DNA damage assessed by the Comet Assay was observed after intravenous injection and intratracheal instillation of CB NPs but not after exposure to TiO
or CeO
. Intratracheal exposure to NPs resulted in pulmonary inflammation in terms of increased neutrophils influx for all NPs 1 and 28 days post-exposure. Persistent pulmonary acute phase response was detected for all NPs at all three time points while only a transient induction of hepatic acute phase response was observed. All 3 materials were detected in the liver by enhanced darkfield microscopy up to 180 days post-exposure. In contrast to TiO
and CeO
NPs, CB NPs generated ROS in an acellular assay.
Our results suggest that the observed hepatic DNA damage following intravenous and intratracheal dosing with CB NPs was caused by the presence of translocated, ROS-generating, particles detected in the liver rather than by the secondary effects of pulmonary inflammation or hepatic acute phase response.
Breast cancer (BC) is one of the most common cancers in women. Evidence suggests that genetic variation in antioxidant enzymes could influence BC risk, but to date the relationship between ...selenoproteins and BC risk remains unclear. In this report, a study population including 975 Danish cases and 975 controls matched for age and hormone replacement therapy (HRT) use was genotyped for five functional single nucleotide polymorphisms (SNPs) in SEPP1, GPX1, GPX4 and the antioxidant enzyme SOD2 genes. The influence of genetic polymorphisms on breast cancer risk was assessed using conditional logistic regression. Additionally pre-diagnosis erythrocyte GPx (eGPx) activity was measured in a sub-group of the population. A 60% reduction in risk of developing overall BC and ductal BC was observed in women who were homozygous Thr carriers for SEPP1 rs3877899. Additionally, Leu carriers for GPX1 Pro198Leu polymorphism (rs1050450) were at ∼2 fold increased risk of developing a non-ductal BC. Pre-diagnosis eGPx activity was found to depend on genotype for rs713041 (GPX4), rs3877899 (SEPP1), and rs1050450 (GPX1) and on HRT use. Moreover, depending on genotype and HRT use, eGPx activity was significantly lower in women who developed BC later in life compared with controls. Furthermore, GPx1 protein levels increased in human breast adenocarcinoma MCF7 cells exposed to β-estradiol and sodium selenite.In conclusion, our data provide evidence that SNPs in SEPP1 and GPX1 modulate risk of BC and that eGPx activity is modified by SNPs in SEPP1, GPX4 and GPX1 and by estrogens. Our data thus suggest a role of selenoproteins in BC development.
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