Identification of candidate exposure biomarkers for acetyl tributyl citrate and acetyl triethyl citrate using suspect screening in human liver microsomes.

Acetyl tributyl citrate (ATBC) and acetyl triethyl citrate (ATEC) are increasingly used as alternatives to phthalates in various products, including food packaging, medical devices, and personal care items, raising concerns about their potential health impacts. This study aimed to investigate the in vitro human metabolism of ATBC and ATEC and identify potential exposure biomarkers applicable in human biomonitoring. Pooled human liver microsomes were utilized to conduct in vitro metabolism assays of deuterium labeled ATBC (ATBC-d3) and ATEC, and ultra performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-qToF/MS) was employed for analysis. Suspect screening workflow and confidence level assignment were applied for metabolite identification. Time-course analysis revealed rapid metabolism of both compounds, with estimated apparent half-lives of approximately 5 min for ATBC-d3 and less than 15 min for ATEC. Eleven metabolites were identified for ATBC-d3 and six for ATEC. The predominant chemical reactions observed were carboxylic ester hydrolysis, deacetylation, and hydroxylation. Based on their abundance and specificity, MB1 (hydroxylated) and MB11 (hydrolyzed and hydroxylated) were proposed as candidate exposure biomarkers for ATBC, and ME1 (hydrolyzed and deacetylated) for ATEC. The identified metabolites and proposed sequences of kinetic process enhance our understanding of the fate of these compounds in the human body, potentially informing future toxicological assessments and guiding the development of more comprehensive human biomonitoring strategies.

A structural analysis of the rail unit of an indoor assistive mobility system.

BACKGROUND: Individuals with gait disturbances, such as that post-stroke, are discharged home to undergo outpatient rehabilitation. Rehabilitation in the community is not as effective as that in hospital, due to long travel times and short program duration. OBJECTIVE: This study analyzed rail unit structure, with the aim of assisting home indoor assistive mobility system (HIAMS) development, allowing patients to undergo gait-related rehabilitation training at home. METHODS: The HIAMS consists of a mobile rail running around the whole room, a turn-table for movement between rails, and a weight-supporting component. Structural analysis was performed using the Abaqus/CAE solution (Version 6.14, Dassault systems, Inc.) to verify device safety, according to the load applied to the rail and turn-table units. The load was applied vertically at 150 kg to reflect the weight of potential users. RESULTS: Structural analysis was performed on the weight-supporting components, which was consist of turn-table case, bearing components (center, left), connective bracket and rail rollers. The safety factors of each components were estimated as 1.31, 5.39 (bearing, center), 8.45 (bearing, left), 1.43 and 3.61 in sequence. CONCLUSION: We demonstrated a safety factor of ⩾ 1.3 for the key system units, suggesting this technology is safe for use in the home rehabilitation training of individuals with gait impairment post-ICU stay.

Toxicokinetic analyses of naphthalene, fluorene, phenanthrene, and pyrene in humans after single oral administration.

Polycyclic aromatic hydrocarbons (PAHs) are generated by incomplete combustion of organic matter. They have health effects in multiple organs and can cause lung, skin, and bladder cancers in humans. Although data regarding their toxicity is available, information on the absorption, distribution, metabolism, and excretion of PAHs in humans is very limited. In the present study, deuterium-labeled naphthalene (Nap), fluorene (Flu), phenanthrene (Phe), and pyrene (Pyr) were orally administered as a single dose (0.02-0.04 mg/kg) to eight healthy adults. Both serum and urine samples were monitored for 72 h after the exposure. Parent compounds and PAH metabolites (monohydroxy-PAHs; OH-PAHs) were measured by headspace-solid phase microextraction coupled with gas chromatography-mass spectrometry and high-performance liquid chromatography-tandem mass spectrometry, respectively. Based on the time-concentration profiles in serum and urine, non-compartmental analysis was performed, and two-compartment models were constructed and validated for each PAH. Subsequently, all of the parent compounds were rapidly absorbed (Tmax: 0.25 to 1.50 h) after oral administration and excreted in urine with a biological half-life (T1/2) of 1.01 to 2.99 h. The fractional urinary excretion (Fue) of OH-PAHs ranged from 0.07 % to 11.3 %; their T1/2 values ranged from 3.4 to 11.0 h. The two-compartment models successfully described the toxicokinetic characteristics of each PAH and its metabolites. Fue and the two-compartment models could be useful tools for exposure simulation or dose-reconstruction of PAHs. The results of this study will provide useful information for interpreting biomonitoring data of PAHs.

Pharmacokinetics of transdermal methyl-, ethyl-, and propylparaben in humans following single dermal administration.

Parabens are common chemicals used as preservatives in foods, cosmetics, and personal care products. Although transdermal exposure to parabens occurs, studies on human pharmacokinetics (PK) following dermal exposure to parabens are scarce. In this study, the PK following dermal exposure to parabens was determined and compared with our previous findings on oral exposure. A paraben mixture cream containing 0.8% deuterated methyl-, ethyl-, and propylparaben (MeP-d4 0.26%; EtP-d4 0.26%, and PrP-d4 0.28%) was dermally applied to the whole arm of five male volunteers at a dose of 24 g/person over 30 min. Blood and urine samples were collected at several intervals over the course of 48 h to measure the levels of MeP-d4, EtP-d4, and PrP-d4 and their conjugated metabolites using HPLC-MS/MS. As a result of non-compartmental analysis, the average peak values of total (sum of conjugated and unconjugated metabolites) MeP-d4, EtP-d4, and PrP-d4 were reached at 7.8 h, 10.5 h, and 5.3 h, indicating a slower absorption rate compared to that of oral exposure (<2 h). The terminal elimination half-lives of MeP-d4, EtP-d4, and PrP-d4 were 12.2 h, 12.0 h, and 9.3 h, respectively. Fractional urinary excretion (Fue) of total MeP-d4, EtP-d4, and PrP-d4 was 1.7%, 2.3%, and 1.9%, respectively. The Fue of total and unconjugated PrP-d4 following dermal exposure was five times lower and three times higher, respectively, compared with those after oral exposure, suggesting that PrP is relatively less metabolized to the conjugated form after dermal exposure. Taken together, dermal exposure to paraben leads to a longer apparent half-life and results in higher proportions of biologically active unconjugated parabens in the systemic circulation as compared to oral exposure. This study provides insights into the kinetic properties of parabens and their metabolites in humans.

Concentrations of blood and urinary arsenic species and their characteristics in general Korean population.

Arsenic (As) exposure has been extensively studied by investigating As species (e.g., inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)) in urine, yet recent research suggests that blood could be a possible biomarker of As exposure. These investigations, however, were conducted on iAs-contaminated areas, and evidence on populations exposed to low levels of iAs is limited. This study aimed to describe the levels and distributions of As species in urine and blood, as well as to estimate methylation efficiency and related factors in the Korean population. Biological samples were obtained by the Korean Ministry of Food and Drug Safety. A total of 2025 urine samples and 598 blood samples were utilized in this study. Six As species were measured using ultra-high-performance liquid chromatography with inductively coupled plasma mass spectrometry (UPLC-ICP-MS): As(V), As(III), MMA, DMA, arsenobetaine (AsB), and arsenocholine (AsC). Multiple linear regression models were used to examine the relationship between As species (concentrations and proportions) and covariates. AsB was the most prevalent species in urine and blood. The relative composition of iAs, MMA, DMA, and AsC in urine and blood differed significantly. Consumption of blue-backed fish was linked to higher levels of AsB in urine and blood. Type of drinking water and multigrain rice consumption were associated with increased iAs concentration in urine. Except for iAs, every species had correlations in urine and blood in both univariate and multivariate analyses. Adolescents and smokers presented a lower methylation efficiency (higher %MMA and lower %DMA in urine) and females presented a higher methylation efficiency (lower %iAs, %MMA, and higher %DMA in urine). In conclusion, blood iAs concentration cannot represent urinary iAs; nonetheless, different compositions of urine and blood might reflect distinct information about iAs exposure. Further investigations on exposure factors and health are needed using low-exposure groups.

Development of an actuation system to apply hydrogen storage alloy for the rehabilitative system.

BACKGROUND: Hydrogen has advantages that can be used as energy, but research on safe use is needed. OBJECTIVE: In this study, an actuation system for rehabilitation is developed to drive the actuator using hydrogen storage alloy and to analyze the hydrogen release characteristics of the alloy. METHODS: The system is automatically control and report the pressure, temperature and hydrogen flow using LabVIEW-based modules and LabVIEW software. Zr0.9Ti0.1Cr0.6Fe1.4 alloy was selected as hydrogen storage alloy. 5 MPa of hydrogen pressure was applied at 8.56 g of alloy powder for activation process and the temperature outside was maintained at 19∘C to 21∘C. The amount of hydrogen absorption was measured about 1.47 wt%. The actuation test was conducted at the temperature from 25∘C to 80∘C, increased by every 5∘C. The actuation height was measured at each load of 5, 10, 15, and 20 kg. The voltage and current which is applied to peltier elements were set to 5.0 V and 2.5 A. The pressure changing in the system was checked for 5 min for each temperature, however, if the temperature at which the pressure inside the system changed, the time to heat the module was increased to 20 min. Hydrogen was first released at 70∘C. RESULTS: The loads of 5 and 10 kg were raised by 87 and 19 mm at 70∘C, respectively. At 75∘C, loads of 5, 10 and 15 kg were raised by 131, 70, and 15 mm, respectively. At 80∘C, 5, 10, 15, and 20 kg were raised by 150, the end of the actuator, 83, 55, and 28 mm, respectively. CONCLUSIONS: The actuation system in this paper can be applied to assistive device and rehabilitation system for assisting the movement of daily life of the elderly or people with disability.

Mercury Exposure and Associations with Hyperlipidemia and Elevated Liver Enzymes: A Nationwide Cross-Sectional Survey.

Mercury (Hg) has obesogenic properties. However, the associated health outcomes of population-level mercury exposure were unclear. This study investigated the relationships between blood mercury levels and obesity-related outcomes such as hyperlipidemia and elevated liver enzymes. Using the second cycle of the Korean National Environmental Health Survey (n = 6454), we performed logistic regression to examine the effects of Hg on hyperlipidemia and elevated liver enzymes. The blood mercury levels were significantly higher in the hyperlipidemia group (n = 3699, male: 4.03 µg/L, female: 2.83 µg/L) compared to the non-hyperlipidemia group (n = 2755, male: 3.48 µg/L, female: 2.69 µg/L), and high blood mercury levels were associated with an 11% higher risk of hyperlipidemia. The elevated liver enzymes group had higher mean blood mercury levels (n = 1189, male: 4.38 µg/L, female: 3.25 µg/L) than the normal group (n = 5265, male: 3.64 µg/L, female: 2.70 µg/L), and elevated blood mercury was associated with a 35% higher risk of elevated liver enzymes. Moreover, the effect was constant after adjusting for personal medications. These results indicate that mercury exposure is significantly associated with hyperlipidemia and elevated liver enzymes.

Study on injection molding analysis of glasses-type wearable device for facial skin care.

BACKGROUND: With the improvement in the standard of living, there has been increasing interest in facial skin care. In particular, it has been observed that people pay extra attention to eye-skin when they visit skin care parlors for special treatment and care. OBJECTIVE: There is a need for skin care devices that would enable convenient skin care anywhere, including at home and on the move. In this research, we developed a prototype of a glasses-type skin care device with a LED (Light-Emitting Diode) irradiation function and performed injection molding analysis of the skin care device model for mass production. METHODS: First, the product was designed using a universal design to improve the wearability of the glasses-type skin care device. The first prototype of the skin care device was produced using an integrated LED optical module capable of irradiating at three LED wavelengths to investigate the structural function of the product. The prototype was classified into three mechanisms and injection molding analysis was performed. The fill time, temperature at flow front, injection pressure, clamp force, and deflection values were analyzed according to the appropriate number and location of gates into which the PC + PBT (Polycarbonate + Polybutylene terephthalate) resin was introduced. RESULTS: We found that all the other parts except the temple section of the device were inferior in moldability. CONCLUSION: In further studies, the 3D prototype will be modified to enhance moldability, and injection molding analysis with other materials as well as with PC + PBT resin will be performed.

Study on an actuation system development using temperature control of metal hydrides.

BACKGROUND: Hydrogen storage using metal hydride (MH) offers various advantages so the global research and development using MH alloys keeps growing. OBJECTIVE: In this paper, we developed a new actuation system using temperature control of the MH module. METHODS: The actuation system consisted of an MH module, fan, mass flow controller (MFC), solenoid valve, actuator, and a temperature and pressure sensor. The MH module, two fans and temperature sensors were set for heating and cooling the MH power by electricity. Two MFCs and four pneumatic solenoid valves were used for controlling the direction and measuring hydrogen flow. Two actuators were used to evaluate performance of the MH alloy, and all the results were measured by LabVIEW software. Hydrogen was absorbed by the MH alloy by pressurizing at 1 MPa, and the absorbed hydrogen was desorbed using a vacuum pump. RESULTS: The temperature condition of the driving test was 20-50∘C. As the module was heated, it was confirmed that the actuator connected to the system was driven by the pressure of desorbed hydrogen. CONCLUSION: It is confirmed that the actuation system is suitable for the evaluation of characteristics of MH alloy. Future studies are planned to develop MH alloys and test the actual driving performance using this system.

Pharmacokinetic profile of propyl paraben in humans after oral administration.

Parabens are commonly used as antimicrobial preservatives in consumer products. Because of their possible endocrine-disrupting activities, their safety has become a public concern. Although pharmacokinetic studies on parabens have been conducted in animals, limited information exists on their pharmacokinetic profiles in humans. In the present study, we determined the pharmacokinetic characteristics of propyl paraben (PP) in humans following a single oral administration of 0.6 mg/kg bw of deuterium labeled-PP. We also conducted experiment with similar design but different exposure amount (2.5 mg/kg bw) to verify the validity of the model to be developed. Blood and urine were collected at several intervals over the course of 48 h to measure levels of PP and its metabolites (conjugates and hydrolysates) in 12 male volunteers. The unconjugated parent compound (free PP), glucuronide and sulfate conjugates, p-hydroxybenzoic acid, and p-hydroxyhippuric acid were measured using HPLC-MS/MS. It was found that PP was rapidly absorbed via ingestion within 2 h and quickly eliminated (terminal half-life, 2.9 h). The fraction of administered dose excreted in the urine was 0.05% for free PP, 8.6% for total PP (free + conjugates), 23.2% for p-hydroxyhippuric acid, and 7.0% for p-hydroxybenzoic acid. Utilizing this pharmacokinetic profile, we successfully constructed a multi-compartment model where the disposition of PP was well described with two compartments and that of its metabolites was explained with first-order reactions. The present pharmacokinetic model provides insights into the kinetic properties of the disposition of PP and its metabolites in humans, and it can be used for risk assessment with biomonitoring of PP.

Prenatal contribution of 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) to total body burden in young children.

Many scientists made estimates of the body burden of PBDEs from breastmilk and house dust. Interestingly, they have not included the prenatal contribution to the body burden in young children after birth. In order to address how the prenatal contribution is important in the risk assessment of PBDEs in infants up to five years old, we used the median measurements of BDE-47 as a model chemical in 108 neonates in Korea, and made simulations of its disposition out of body from birth to five years. During the simulation periods, the environmental exposure was considered for house dust, babyfood, breastmilk consumption, etc., with assumption of typical exposure scenario applicable to general infants in Korea. About 22% of the total amounts of BDE-47 in newborn remained up to 5years after birth. The relative amounts of BDE-47 from the prenatal source were 20%, 14%, 10%, 8%, 6%, and 4% of the total body burden for 1-, 2-, 3-, 4- and 5-year after birth, respectively. The contribution from breastfeeding was 95.2% and 92.2% of the total postnatal exposure amounts at 6-month and 1-year after birth, respectively. After cease of breastfeeding at 1-yr, house dust and food were the important sources of exposure up to 5-yr; however, their contributions to the bodyburden were negligible with consideration of the remaining amounts of the analytes from the breastmilk and prenatal exposure. Suggestively, the innate amounts and pharmacokinetics should be counted in estimating bodyburden of BDE-47.

Risk assessment for phthalate exposures in the elderly: A repeated biomonitoring study.

Recent studies indicated that exposure to phthalates affects the development of a variety of diseases in the elderly population. However, limited information was available about the variability of phthalate daily intakes (DIs) and the proportion of the population that is highly exposed to phthalates. Therefore, we measured the levels of three phthalate metabolites, mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl phthalate (MnBP) in 4014 urine samples repeatedly collected from 1646 elderly people. The DIs of di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DnBP) were calculated using urinary MEHHP, MEOHP, and MnBP levels, and then the proportion of the population that was highly exposed to DEHP and DnBP was calculated. The intra-class correlation (ICC) for MEHHP, MEOHP, and MnBP levels was 0.07, 0.02, and 0.03, respectively, and exposures to DEHP and DnBP were strongly correlated with each other (correlation coefficient=0.89 and p-value<0.0001). The geometric mean of estimated DI was 8.8µg/kgbody-weight/day (range 0.005-3382.0) for DEHP and 1.5µg/kgbody-weight/day (range 0.0002-1076.8) for DnBP. The percentages of urine samples with DEHP > reference dose (RfD, 20µg/kgbody-weight/day) and DnBP > tolerable daily intake (TDI, 10µg/kgbody-weight/day) were 20.2% and 3.6%, respectively. The Korean elderly were co-exposed to DEHP and DnBP, and the variation of DEHP and DnBP metabolite levels was mainly attributed to intra-individual variation, rather than inter-individual variation. Furthermore, Korean elderly were exposed to the hazards of DEHP and DnBP based on the high level of the exceedance rate over TDI or RfD for DEHP and DnBP. Since the elderly are very susceptible to environmental pollutants, the harmful effects of DEHP and DnBP in the elderly population should be further studied in the future.

Placental and lactational transfer of decabromodiphenyl ether and 2,2',4,4'-tetrabromodiphenyl ether in dam-offspring pairs of Sprague-Dawley rats.

Although several studies have conducted maternal transfer of individual PBDE congener in experimental animals, there is a paucity of research on differences in maternal transfer of PBDE congeners. The purpose of the study was to investigate and compare placental and lactational transfer of BDE 47, -209 and its metabolites in rat dam-offspring pairs following repeated administration of BDE 47 and -209. 13C-BDE 47, BDE 209 and its debrominated congeners were detected both in dam serum and offspring body, which indicates that PBDEs can be maternally transferred. In addition, BDE 196 and -197 appeared in offspring body earlier than in maternal serum, which suggests that debromination can be occur in offspring body. BDE 209 increased in both dam and offspring while levels of 13C-BDE 47 was not increased in dam serum. 13C-BDE 47 seems to be stored in breast milk rather than in maternal serum, which can be assumed through the drastic increase of the congener in suckling pups. The magnitude of lactational transfer of the administered congeners was greater than that of placental transfer. And 13C-BDE 47 was relatively more transferred to suckling pups than BDE 209 through breastfeeding.

Polybrominated Diphenyl Ethers in Maternal Serum, Breast Milk, Umbilical Cord Serum, and House Dust in a South Korean Birth Panel of Mother-Neonate Pairs.

Polybrominated diphenyl ethers (PBDEs) have been used as flame retardants. Although many reports have indicated an association between exposure to PBDEs and developmental neurotoxicity, the relative contributions of different sources of dust PBDE congeners to the levels in various tissues of mother-baby pairs is not well understood. The aims of this study were thus to measure the quantitative relationship between the level of PBDEs in house dust and tissues of mother-neonate pairs, and to investigate the chemical sources of the PBDEs. Forty-one mother-neonate pairs were recruited and provided samples of maternal serum (n = 29), umbilical cord serum (n = 25), breast milk (n = 50), and house dust (n = 41), where PBDEs were determined with high-resolution gas chromatography coupled with high-resolution mass spectrometry. While deca- (e.g., BDE 209, detected 100%), nona- (BDE 206/207, 95.1%), octa- (BDE 183, 100%), penta- (BDE 99/153, 100%, 98%) and tetra-BDEs (BDE 47, 100%) were detected abundantly in dust, penta- (BDE 99, 76%, 92%) and tetra-BDEs (BDE 47, 84%, 98%) were detected abundantly in umbilical cord serum and breast milk, respectively; tetra-BDEs (BDE 47, 86%) were detected more often relative to other congeners in maternal serum. Spearman's pairwise comparison showed that the levels of BDE 47 (ρ = 0.52, p < 0.001) and -99 (ρ = 0.64, p < 0.01) in umbilical cord serum were associated with BDE 209 levels in dust; BDE 47 in maternal serum also showed correlation with BDE 99 in cord serum (ρ = 0.48, p < 0.01) but there was no significant correlation between maternal BDE 47 and dust BDE 209. On the other hand, a comparison of the distribution among congeners suggested probable associations of BDE 47 in maternal serum, breast milk, and umbilical cord serum with BDE 209 in dust; and of BDE 99 in maternal and umbilical cord serum, breast milk, and dust with BDE 209 in dust. Although further studies are needed, a radar chart-based distributional comparison among congeners supported associations between BDE 47 or -99 in human tissues and BDE 209 in dust.

Validation of the Korean version of the Eating Disorder Inventory-2: psychometric properties and cross-cultural comparison.

PURPOSE: The purpose of the present study was to examine the validity and reliability of the Korean version of the Eating Disorder Inventory-2 (EDI-2) in Korean patients with eating disorders and healthy controls, and to investigate cultural differences of EDI-2 between a Korean group and a North American standardization sample. MATERIALS AND METHODS: The Korean version of the EDI-2 was prepared after comprehensive clinical assessment of Korean patients with eating disorders (n=327) as well as female undergraduates (n=176). Results were compared between eating disorder subgroups (anorexia nervosa, bulimia nervosa and eating disorders not otherwise specified) and those of a North American standardization sample and healthy controls. RESULTS: The results showed that the Korean EDI-2 had adequate internal consistency (0.77-0.93) and discriminated well between patients with eating disorders and healthy controls on all subscales. Significant differences in EDI-2 subscale scores between the eating disorder groups and the healthy control group were observed; however, there was no discernible difference among the eating disorder subgroups. When compared with a North American standardization sample, the Korean control group showed significantly higher scores for drive for thinness and asceticism. When patient groups were compared, the Korean group showed significantly lower scores for perfectionism. CONCLUSION: As expected, the results accurately reflected psychometric properties of the Korean version of EDI-2 for eating disorder patients in Korea. These findings also suggest that common characteristics for the eating disorder exist as a whole rather than with significant difference between each subgroup. In addition, significant differences between the Korean and the North American groups for both patients and controls also demonstrated specific cultural differences.

Sleep disturbance in women with eating disorder: prevalence and clinical characteristics.

The prevalence of sleep disturbance among 400 patients, diagnosed with anorexia nervosa (AN) or bulimia nervosa (BN), was assessed via structured interviews. Sleep disturbance was reported in 50.3% of patients, especially among those with the binge-eating/purging subtype. Patients with sleep disturbance had more disturbing symptoms; including higher binge frequency and vomiting frequency. Additional differences were also identified.

Seasonal variation in dissolved gaseous mercury and total mercury concentrations in Juam Reservoir, Korea.

Dissolved gaseous mercury (DGM) and total mercury (TM) concentrations were measured in Juam Reservoir, Korea. DGM concentrations were higher in spring (64+/-13pgL(-1)) and summer (109+/-15pgL(-1)), and lower in fall (20+/-2pgL(-1)) and winter (23+/-6pgL(-1)). In contrast, TM concentrations were higher in fall (3.2+/-0.1ngL(-1)) and winter (3.3+/-0.1ngL(-1)) than in spring (2.3+/-0.1ngL(-1)) and summer (2.2+/-0.4ngL(-1)). DGM concentrations were correlated with water temperature (p<0.0001), ORP (p<0.0001), UV intensity (UV-A: p=0.008; UV-B: p=0.003), and DOC concentration (p=0.0107). DGM concentrations varied diurnally with UV intensity. The average summer DGM (109+/-15pgL(-1)) and TM (2.2+/-0.4ngL(-1)) concentrations in Juam Reservoir were higher than the averages for North American lakes (DGM=38+/-16pgL(-1); TM=1.0+/-1.2ngL(-1)), but lower than levels reported for Baihua Reservoir in China.