Effects of mercury exposure on fetal body burden and its association with infant growth.

Several studies have been conducted among South Korean to investigate effects of high blood mercury (Hg) levels. In this study fetal body burden of Hg in 344 pregnant women were estimated using a physiologically-based pharmacokinetic model (PBPK) and its associative effects on the growth of infants were analyzed. The association between cord blood Hg and growth variables at birth was analyzed based on parameters such as the sex of the newborn, living area, maternal age group, gestation day, maternal body mass index . We investigated the effects of Hg on infant growth through follow-ups, using a non-linear mixed model. The mean Hg levels in maternal and cord blood were 4.47 µg/L and 7.35 µg/L, respectively. Among the subjects, the corresponding fetal body burden for Methylmercury ranged between 26.3-86.9 mg. Cord blood Hg levels positively correlated with length at birth. Furthermore, the high cord blood group showed greater growth rates compared to the low cord blood group. Therefore, we suggest that pregnant women should make efforts to mitigate exposures to Hg, specifically from diet. Further research is suggested to investigate the relationship between the follow-up growth of the infants and Hg levels, considering fish consumption, diet information, and other environmental pollutants.

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.

Within- and between-person variability of urinary phthalate metabolites and bisphenol analogues over seven days: Considerations of biomonitoring study design.

Urine was used as a part of a human biomonitoring study based on the excretion kinetics of less-persistent contaminants, such as phthalates and bisphenol A (BPA). Despite the advantages of being non-invasive and easy to collect, urine can show a large variability of concentrations of phthalate metabolites and BPA within a person depending on sampling time. Therefore, it is essential to assess the variability of urinary concentrations for comprehensive sampling design in the context of exposure and risk assessments. In this study, 18 phthalate metabolites and eight BPs were measured in all spot urine (n = 401) collected from 12 participants for seven consecutive days to evaluate within- and between-person variabilities. The intraclass correlation coefficients (ICCs) for all spot urines were poor for monomethyl phthalate (ICC: 0.002) and BPA (0.121) but were moderate for monoethyl phthalate (0.514) and monobenzyl phthalate (0.462). Based on the results of di (2-ethylhexyl) phthalate (DEHP) metabolites, the half-life and differences in metabolic capability seem to affect the ICCs. Urinary mono (2-ethylhexyl) phthalate (MEHP), a primary metabolite of DEHP, was suggested as a short-term exposure marker of DEHP in our study. Creatinine- and specific gravity-adjusted concentrations of phthalate metabolites and BPs resulted in increased ICCs, implying requirements for randomly collected spot urine. Most analytes in the first morning voids (FMVs) were correlated significantly with those in the daily composites, suggesting the feasibility of FMVs to estimate the daily exposure dose. This study facilitates a more comprehensive sampling design and data interpretation strategy for human biomonitoring studies.

Simultaneous assessment of organophosphate flame retardants, plasticizers, trace metals, and house dust mite allergens in settled house dust.

Settled house dust (SHD) is a reservoir for various contaminants, including endocrine-disrupting chemicals (EDCs), trace metals, and house dust mite allergens. This study aimed to characterize various chemical and biological contaminants in SHD and identify determinants governing the indoor contaminants. In total, 106 SHD samples were collected from 106 houses in Seoul and Gyeonggi Province, Korea, in 2021. Bedding dust samples were collected from 30 of these 106 houses. All participants completed a questionnaire comprised of housing and lifestyle-related factors. The samples were analyzed for 18 organophosphate flame retardants (OPFRs), 16 phthalates, five alternative plasticizers (APs), seven trace metals, and two house dust mite allergens (Dermatophagoides farinae type 1 [Der f1] and Dermatophagoides pteronyssinus type 1 [Der p1]). A multiple regression analysis was conducted to identify the determinants governing the concentrations and profiles of various contaminants. OPFRs, phthalates, APs, and trace metals were detected in all SHD samples, indicating ubiquitous contamination in indoor environments. Among the three EDC groups, APs were detected at the highest concentrations (geometric mean [GM] (geometric standard deviation, [GSD]): 1452 (1.6) µg/g in total), followed by phthalates (GM (GSD): 676 (1.4) µg/g in total) and OPFRs (GM (GSD): 10 (1.4) µg/g in total). Der f1 was detected in all bedding dust samples with significantly higher levels than Der p1 (GM (GSD): 0.1 (1.8) µg/g vs. 1.4 × 10-3 (2.3) µg/g). The concentrations of OPFRs, plasticizers, and trace metals in SHD were significantly associated with the type and number of electronic appliances and combustion activities. Der f1 was significantly associated with the number of occupants and water penetration. Ventilation, vacuum cleaning, and wet cleaning or dry mopping significantly reduced the levels of most contaminants in SHD. As residents are persistently exposed to a wide array of pollutants, comprehensive and adequate measures are required to prevent potential exposures.

Lead and mercury levels in repeatedly collected urine samples of young children: A longitudinal biomonitoring study.

Early life exposures to lead (Pb) and mercury (Hg) were reported to be associated with various adverse health outcomes. However, limited data was available for urinary Pb and Hg levels in young children and the proportion of children at risk by age, as well as inter- and intra-subject variations of urinary Pb and Hg levels. Therefore, we collected total 491 urine samples from 241 children by urine collection at birth and at intervals of 3 months until 27 months of age for each child (at 10 monitoring time points), measured urinary Pb and Hg levels, and then evaluated the proportion of children at risk by age and the intra-class correlation (ICC) of the urinary Pb and Hg levels. Both the urinary Pb and Hg levels were significantly different according to the monitoring time points (p < 0.0001 for both Pb and Hg). The number of children with Hg level over the Human BioMonitoring (HBM) I (7 µg/L) and II (25 µg/L) in the first urine at birth were 3 (2.2%) and 1 (0.7%), respectively, while the urinary samples at the other time points did not show Hg level over HBM I or HBM II. However, the exceedance rate for urinary Pb based on HBM values was not calculated due to unavailable HBM values. On the other hands, the proportion of the children with Pb and Hg levels over the reference value derived on the 95th percentile of representative samples (RV95) (1.7 µg/L for Canadian Pb and 0.4 µg/L for German Hg) was relatively high, ranging from 20.0% to 100.0% for Pb and from 13.6% to 100.0% for Hg. The ICC of the repeated measurements from birth to 27 months was 0 for Pb and 0.89 for Hg, while the ICC after the exclusion of the first urine at birth was 0.13 for Pb and 0.47 for Hg. Furthermore, the Pb and Hg exposures were consistent among the high-exposure group for Pb and among all population for Hg. Our data showed Korean children were exposed to relatively high levels of Pb and Hg. However, our Pb and Hg levels in children were based on only urine samples without urinary correction and without consideration of the levels in any other bio-samples such as bloods. Therefore, to explore the Pb and Hg exposures using urine samples warrant further investigation with large sample size considering urinary correction and other bio-samples in the future.

Physicochemical characteristics of colloidal nanomaterial suspensions and aerosolized particulates from nano-enabled consumer spray products.

Physicochemical properties between colloidal engineered nanomaterials (ENMs) and aerosols released from consumer spray products were characterized. A dynamic light scattering (DLS), transmission electron microscopy (TEM), and inductively coupled plasma mass spectrometer (ICP-MS) were used to evaluate the suspended ENMs in the products. Direct-reading instruments, TEM, and ICP-MS were used to characterize the properties of aerosolized ENMs. The aerosolized organic compounds with ENMs were assumed to be vaporized for a short time after spraying. The median diameter of ENMs in product solutions measured by DLS was about 200-350 nm, while individual particle was confirmed from 3 to 50 nm by TEM. The size of aerosolized ENMs was ranged from 7 to 44 nm, and their aggregates were about 100-1000 nm in near distance. Some inorganic substances including raw nanomaterials were also found in the aerosol. The particles released from the propellant sprays were identified in far distance, while they were not found in far distance when pump sprays were used. The number concentration from the propellant sprays increased up to 6000 particles/cm3 /g at near distance and dispersed to far distance, while the most of droplets emitted from pump sprays were settled down near sprayer's location. We found other metals besides labeled ENMs are included in each product and the characteristics of the particles are different when they are sprayed.

Characteristics of Exposure to Chloromethylisothiazolinone (CMIT) and Methylisothiazolinone (MIT) among Humidifier Disinfectant-Associated Lung Injury (HDLI) Patients in South Korea.

This study aimed to quantify both chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) dissolved in different product brands and to characterize the exposure to these chemicals among humidifier disinfectant-associated lung injury (HDLI) patients. Both CMIT and MIT dissolved in different humidifier disinfectant (HD) products were quantified using gas chromatography-mass spectrometry. The inhalation level of CMIT and MIT was estimated based on HD-associated factors as reported by HDLI patients. A total of eleven HD products marketed until the end of 2011 were found to contain CMIT and/or MIT. The level of combined CMIT and/or MIT dissolved in these HD products ranged from 12 to 353 ppm. The level varied among HD products and the year of manufacture. The average inhalation levels were estimated to be 7.5, 4.1, and 3.2 µg/m3 for the definite, probable, and possible groups, respectively. If probable and possible groups were collapsed together, the inhalation level of the collapsed group was significantly different from that of the definite group (p < 0.001). All HDLI patients responded as having used HD not only while sleeping, but also as having a humidifier treated with HD within close proximity every day in insufficiently ventilated spaces. These HD use characteristics of patients may be directly/indirectly linked to the HDLI development.

Birth Cohort Consortium of Asia: Current and Future Perspectives.

BACKGROUND: The environmental health of children is one of the great global health concerns. Exposures in utero and throughout development can have major consequences on later health. However, environmental risks or disease burdens vary from region to region. Birth cohort studies are ideal for investigating different environmental risks. METHODS: The principal investigators of three birth cohorts in Asia including the Taiwan Birth Panel Study (TBPS), the Mothers and Children's Environmental Health Study (MOCEH), and the Hokkaido Study on Environment and Children' Health (Hokkaido Study) coestablished the Birth Cohort Consortium of Asia (BiCCA) in 2011. Through a series of five PI meetings, the enrolment criteria, aim of the consortium, and a first-phase inventory were confirmed. RESULTS: To date, 23 birth cohorts have been established in 10 Asian countries, consisting of approximately 70,000 study subjects in the BiCCA. This article provides the study framework, environmental exposure and health outcome assessments, as well as maternal and infant characteristics of the participating cohorts. CONCLUSIONS: The BiCCA provides a unique and reliable source of birth cohort information in Asian countries. Further scientific cooperation is ongoing to identify specific regional environmental threats and improve the health of children in Asia.

Spatial-Temporal Dispersion of Aerosolized Nanoparticles During the Use of Consumer Spray Products and Estimates of Inhalation Exposure.

We evaluated the spatial-temporal dispersion of airborne nanomaterials during the use of spray consumer products and estimated the level of consumer inhalation exposure. A total of eight spray products including five propellant and three pump types were selected to evaluate the dispersion of airborne nanoparticles across time and space in a cleanroom which could control the background particles. Four products were advertised to contain silver and one contained titanium nanoparticles, while three products were specified no ENM but as being manufactured through the use of nanotechnology. We used direct-reading instruments with a thermodesorber unit to measure the particles (number, mass, surface area), as well as filter sampling to examine physicochemical characteristics. Sampling was conducted simultaneously at each location (1 m, near-field; 2, 3 m, far-field) by distance from the source. We estimated the inhaled doses at the breathing zone, and the doses deposited in each part of the respiratory tract using the experimental data and mathematical models. Nanoparticles released from the propellant sprays persisted in the air and dispersed over a large distance due to their small size (1466-5565 particles/cm3). Conversely, the pump sprays produced larger droplets that settled out of the air relatively close to the source, so the concentration was similar to background level (<200 particles/cm3). The estimates of inhalation exposure also suggested that exposure to nanoparticles was greater with propellant sprays (1.2 × 108 ± 4.0 × 107 particles/kgbw/day) than pump sprays (2.7 × 107 ± 6.5 × 106 particles/kgbw/day). We concluded that the propellant sprays create a higher risk of exposure than the pump sprays.

Occurrence and prenatal exposure to persistent organic pollutants using meconium in Korea: Feasibility of meconium as a non-invasive human matrix.

Prenatal exposure to persistent organic pollutants (POPs) is of great concern due to the vulnerability of fetus. Nineteen Polychlorinated biphenyls (PCBs), 18 organochlorine pesticides (OCPs) including DDTs, HCHs, chlordanes, and hexachlorobenzene, and 22 polybrominated diphenyl ethers (PBDEs) were measured in meconium samples from 72 newborn infants using high resolution gas chromatography/mass spectrometry. The median concentrations (on wet weight basis) of PCBs, OCPs, and PBDEs were 26.8pg/g, 66.7pg/g, and 2.32pg/g, respectively. Highly significant correlations were observed among the compounds of PCBs and OCPs, suggesting their similar sources and kinetic behaviors. BDE 47 had significant correlations with PCBs and OCPs, whereas BDE 209 was not correlated with any of the contaminants due to different exposure sources. The concentrations of p,p'-DDE, ß-HCH, and trans-nonaCHL between paired maternal blood-meconium and cord blood-meconium showed significant correlations, while PCBs and PBDEs were not significantly correlated in the paired samples. Maternal age and gestational age were demographic parameters affecting POP levels in meconium. Multiple regression analysis showed that the levels of several OCPs in cord and maternal serum were contributing factors governing the levels of these contaminants in meconium. Our results indicate that meconium can be utilized as a human matrix for prenatal exposure to several OCPs.

Association between Several Persistent Organic Pollutants in Serum and Adipokine Levels in Breast Milk among Lactating Women of Korea.

Exposure to several persistent organic pollutants (POPs) has been linked to alteration of lipid metabolism. Adipokines, such as leptin and adiponectin, are hormones that play roles in lipid metabolism, and have been suggested as markers of health effects that may lead to obesity. To date, only serum adipokines have been associated with POPs exposure. In the present study, for the first time, the associations between leptin and adiponectin in breast milk, and several POPs in serum were investigated among 82 lactating Korean women between 25 and 46 years of age. Breast milk adipokines are important because adipokine intake of infant through breastfeeding may influence the growth of infants. The median concentrations of leptin and adiponectin in skimmed milk of the Korean lactating women were 17.9 ng/L and 16.5 µg/L, respectively. Leptin concentrations in breast milk were negatively associated with ∑hexachlorohexane (HCH), oxychlordane, ∑chlordane, or 2,2',4,4',5,5'-hexachlorobiphenyl (CB 153) levels in maternal serum. Linear relationships between adiponectin and POPs concentrations were not observed, however, nonmonotonic relationship which showed generally positive associations was suggested for p,p'-dichlorodiphenyltrichloroethane (DDT) and ∑chlordane in quartile analysis. Our observations show that POPs at the current level of exposure may be associated with the alteration of lipid metabolism among lactating women. Implication of adipokine transfer to breastfed infants is of concern and deserves further investigation.

Synthetic musk compounds and benzotriazole ultraviolet stabilizers in breast milk: Occurrence, time-course variation and infant health risk.

Synthetic musk compounds (SMCs) and benzotriazole ultraviolet stabilizers (BUVSs) are used as additives in many consumer products. Limited data are available on the accumulation of SMCs in human fluids, and no data are available on BUVSs. In this study, 208 human breast milk samples were collected from 87 participants during the lactation period at <7, 15, 30, and 90 days after delivery in Korea. The total concentrations of SMCs and BUVSs ranged from

Infant exposure to polybrominated diphenyl ethers (PBDEs) via consumption of homemade baby food in Korea.

Limited data are available on the residue levels of polybrominated diphenyl ethers (PBDEs) in baby food. In this study, 24 PBDE congeners were determined in 147 homemade baby food samples collected from 97 households for 6-, 9-, 12-, 15-, and from 24 to 27-month-old infant groups during the period of 2012-2013. The concentrations of total PBDEs (ΣPBDE) ranged from 24.5 to 6000 (mean: 263) pg/g fresh weight, higher than those found in commercial formulae from the United States. The predominant congeners were BDEs 209 and 47, accounting for 92% of the ΣPBDE concentrations, reflected by high deca-BDE consumption in Korea. The residue levels and detection rates of BDE 47 in the baby food samples showed a gradual increasing trend with an increase in infant ages, due to changes in the food ingredients from hypoallergenic to greasy. The daily intakes of BDEs 47 and 209 via baby food consumption ranged from 0.04 to 0.58, 0.80 to 20.3, and 1.06 to 22.3 ng/kg body weight/day for 6-, 9-, 12-, 15-, and 24-27-month-old infant groups, respectively; these intakes were lower than the oral reference doses proposed by the US EPA. Together with three exposure sources, baby food, breast milk and dust ingestion for 6-month-old infants, the daily intake of ΣPBDE was 25.5 ng/kg body weight/day, which was similar to the intake via baby food consumption only for over 24-month-old infants in our study. This indicates that baby food is an important exposure pathway of PBDEs for over 24-month-old infants. This is the first study regarding the occurrence and exposure assessment of PBDEs via homemade baby food.

Identification and quantification of acetyl tributyl citrate (ATBC) metabolites using human liver microsomes and human urine.

Plasticizers are chemicals that make plastics flexible, and phthalates are commonly used. Due to the toxic effects of phthalates, there is increasing use of non-phthalate plasticizers like acetyl tributyl citrate (ATBC). ATBC has emerged as a safer alternative, yet concerns about its long-term safety persist due to its high leachability and potential endocrine-disrupting effects. This study aims to identify ATBC metabolites using human liver microsomes and suspect screening methods, and to explore potential urinary biomarkers for ATBC exposure. Using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry, we identified ATBC metabolites, including acetyl dibutyl citrate (ADBC), tributyl citrate (TBC), and dibutyl citrate (DBC). Urine samples from 15 participants revealed the presence of ADBC in 5, TBC in 11, and DBC in all samples, with DBC concentrations pointedly higher than the other metabolites. These metabolites show promise as biomarkers for ATBC exposure, though further validation with human data is required. Our results underscore the need for comprehensive studies on ATBC metabolism, exposure pathways, and urinary excretion to accurately assess human exposure levels.

Homemade weaning foods as a source of lead and mercury exposure in Korean infants - A dietary risk assessment study.

Lead (Pb) and mercury (Hg) are neurodevelopmental toxicants that pose risks to cognitive and behavioral health. Given early childhood's vulnerability to these metals, understanding their sources and pathways of exposure during infancy is crucial for public health. During the weaning process, infants may be exposed to metals through the baby food they consume. We aimed to assess metal exposure through homemade weaning foods by analyzing 288 samples consumed by 157 Korean infants aged 6-, 9-, 12-, 15-, and 24-27 months. Pb was detected in 65 % of samples, with levels reaching up to 169 ng/g. Notably, 58 % exceeded the Maximum Level (ML) of 10 ng/g, with a median concentration of 14.7 ng/g fresh weight. Total Hg was found in 88 % of samples, with a median concentration of 4.56 ng/g fresh weight. Estimated median daily intakes of Pb and Hg were 0.29 and 0.09 µg/kg/d, respectively. Considering a benchmark dose for Pb (0.5 µg/kg/d by EFSA), 94 % (the margin of exposure <10) of all age groups was estimated to have a potential health concern associated with homemade baby food consumption. For Hg, only 6 % exceeded a hazard quotients of 1 compared to a provisional tolerable weekly intake for Hg (4 µg/kg/week by WHO). This study marks the first direct assessment of daily Pb and Hg intake through homemade baby food among Korean infants. Our findings underscore the urgent need for heightened awareness regarding metal exposure through homemade baby food.

Low-dose metabolism of benzene in humans: science and obfuscation.

Benzene is a ubiquitous air pollutant that causes human leukemia and hematotoxic effects. Although the mechanism by which benzene causes toxicity is unclear, metabolism is required. A series of articles by Kim et al. used air and biomonitoring data from workers in Tianjin, China, to investigate the dose-specific metabolism (DSM) of benzene over a wide range of air concentrations (0.03-88.9 p.p.m.). Kim et al. concluded that DSM of benzene is greatest at air concentrations <1 p.p.m. This provocative finding motivated the American Petroleum Institute to fund a study by Price et al. to reanalyze the original data. Although their formal 'reanalysis' reproduced Kim's finding of enhanced DSM at sub-p.p.m. benzene concentrations, Price et al. argued that Kim's methods were inappropriate for assigning benzene exposures to low exposed subjects (based on measurements of urinary benzene) and for adjusting background levels of metabolites (based on median values from the 60 lowest exposed subjects). Price et al. then performed uncertainty analyses under alternative approaches, which led them to conclude that '… the Tianjin data appear to be too uncertain to support any conclusions …' regarding the DSM of benzene. They also argued that the apparent low-dose metabolism of benzene could be explained by 'lung clearance.' In addressing these criticisms, we show that the methods and arguments presented by Price et al. are scientifically unsound and that their results are unreliable.

Polybrominated diphenyl ethers (PBDEs) in breast milk of Korea in 2011: current contamination, time course variation, influencing factors and health risks.

Breast milk is a valuable biological specimen to assess maternal and infant exposure to polybrominated diphenyl ethers (PBDEs). In this study, 208 breast milk samples were collected from 89 participants during lactation period, at <7, 15, 30, and 90 days postpartum, in four cities in Korea, and were determined for 19 PBDE congeners. The total PBDE concentrations (ΣPBDE) ranged from 0.23 to 68.4 (mean: 2.73) ng/g lipid weight, and were within the ranges reported for European and Asian countries. Within a month of lactation after delivery, no significant changes were found in the PBDE concentrations. The predominance of BDE 153 rather than BDE 47 was found in the most samples that BDE 153 was detected, and was likely to be associated with stepwise debromination of BDE 209. No associations were found between PBDE concentrations in breast milk and demographic parameters, except for ΣPBDE with maternal age and delivery mode. Certain types of diet such as corn, seafood and nut correlated significantly with PBDE levels in breast milk. The estimated daily intakes of ΣPBDE for breast-feeding infants were lower than the guidelines proposed by the US EPA, indicating limited health risk from PBDEs through breast feeding.

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.

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.

Free Cortisol Mediates Associations of Maternal Urinary Heavy Metals with Neonatal Anthropometric Measures: A Cross-Sectional Study.

Prenatal exposure to heavy metals is known to be associated with adverse birth outcomes and oxidative stress biomarkers. In this study, we examined whether maternal free cortisol or 8-Hydroxy-2-Deoxyguanosine (8-OHdG) could mediate associations between maternal heavy metal exposure and birth outcomes. A total of 182 healthy pregnant women were recruited. Heavy metals (including Pb, Hg, and Cd), free-cortisol, and 8-OHdG were analyzed in urine at delivery. Birth outcomes including birth weight, length, Ponderal index, and head circumference were measured. To examine associations of maternal urinary heavy metals with biomarkers and birth outcomes, generalized linear models were employed. Birth length was positively associated with Pb (ß = 0.78, 95% CI: 0.09−1.46) and Hg (ß = 0.84, 95% CI: 0.23−1.45) (both p < 0.05). The Ponderal index, a measure of a newborn's leanness, was negatively associated with maternal urinary Pb (ß = −0.23, 95% CI: −0.46−−0.07) and Hg (ß = −0.26, 95% CI: −0.44−−0.08) (both p < 0.05). No association between maternal Cd and birth outcomes was observed. Most heavy metals showed positive associations with free cortisol and 8-OHdG. Free cortisol was identified as a mediator underlying the observed relationship between Hg and birth length or Ponderal index. This study observed adverse birth outcomes from maternal exposures to Pb and Hg. Increased free cortisol related to Hg exposure was suggested as a possible causal pathway from Hg exposure to birth outcomes such as the Ponderal index.