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1,766 References Were Found:

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Applied concepts in PBPK modeling: How to extend an open systems pharmacology model to the special population of pregnant women

Authors: Dallmann, A; Solodenko, J; Ince, I; Eissing, T (2018) CPT: Pharmacometrics & Systems Pharmacology 7:419-431. HERO ID: 4470799

[Less] This tutorial presents the workflow of adapting an adult physiologically based pharmacokinetic (PBPK) . . . [More] This tutorial presents the workflow of adapting an adult physiologically based pharmacokinetic (PBPK) model to the pregnant populations using the Open Systems Pharmacology (OSP) software suite (www.open-systems-pharmacology.org). This workflow is illustrated using a previously published PBPK model for metronidazole that is extrapolated to pregnancy by parameterizing and extending the model structure in terms of pregnancy-induced physiological changes. Importantly, this workflow can be applied to other scenarios where PBPK models need to be re-parameterized or structurally modified.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Fetal physiologically-based pharmacokinetic models: systems information on fetal biometry and gross composition

Authors: Abduljalil, K; Johnson, TN; Rostami-Hodjegan, A (2018) Clinical Pharmacokinetics 57:1149-1171. HERO ID: 4470812

[Less] BACKGROUND: Postulating fetal exposure to xenobiotics has been based on animal studies; . . . [More] BACKGROUND: Postulating fetal exposure to xenobiotics has been based on animal studies; however, inter-species differences can make this problematic. Physiologically-based pharmacokinetic models may capture the rapid changes in anatomical, biochemical, and physiological parameters during fetal growth over the duration of pregnancy and help with interpreting laboratory animal data. However, these models require robust information on the longitudinal variations of system parameter values and their covariates.

OBJECTIVE: The objective of this study was to present an extensive analysis and integration of the available biometric data required for creating a virtual human fetal population by means of equations that define the changes of each parameter with gestational age.

METHODS: A comprehensive literature search was carried out on the parameters defining the growth of a fetus during in-utero life including weight, height, and body surface area in addition to other indices of fetal size, body fat, and water. Collated data were assessed and integrated through a meta-analysis to develop mathematical algorithms to describe growth with fetal age.

RESULTS: Data for the meta-analysis were obtained from 97 publications, of these, 15 were related to fetal height or length, 32 to fetal weight, 4 to fetal body surface area, 8 to crown length, 5 to abdominal circumference, 12 to head circumference, 14 to body fat, and 12 to body water. Various mathematical algorithms were needed to describe parameter values from the time of conception to birth.

CONCLUSION: The collated data presented in this article enabled the development of mathematical functions to describe fetal biometry and provide a potentially useful resource for building anthropometric features of fetal physiologically-based pharmacokinetic models.

Journal Article
Journal Article

Development of growth equations from longitudinal studies of body weight and height in the full term and preterm neonate: From birth to four years postnatal age

Authors: Troutman, JA; Sullivan, MC; Carr, GJ; Fisher, J (2018) HERO ID: 4471076

[Less] Physiologically based pharmacokinetic (PBPK) models are developed from compound-independent information . . . [More] Physiologically based pharmacokinetic (PBPK) models are developed from compound-independent information to describe important anatomical and physiological characteristics of an individual or population of interest. Modeling pediatric populations is challenging because of the rapid changes that occur during growth, particularly in the first few weeks and months after birth. Neonates who are born premature pose several unique challenges in PBPK model development. To provide appropriate descriptions for body weight (BW) and height (Ht) for age and appropriate incremental gains in PBPK models of the developing preterm and full term neonate, anthropometric measurements collected longitudinally from 1,063 preterm and 158 full term neonates were combined with 2,872 cross-sectional measurements obtained from the NHANES 2007-2010 survey. Age-specific polynomial growth equations for BW and Ht were created for male and female neonates with corresponding gestational birth ages of 25, 28, 31, 34, and 40 weeks. Model-predicted weights at birth were within 20% of published fetal/neonatal reference standards. In comparison to full term neonates, postnatal gains in BW and Ht were slower in preterm subgroups, particularly in those born at earlier gestational ages. Catch up growth for BW in neonates born at 25, 28, 31, and 34 weeks gestational age was complete by 13, 8, 6, and 2 months of life (males) and by 10, 6, 5, and 2 months of life (females), respectively. The polynomial growth equations reported in this paper represent extrauterine growth in full term and preterm neonates and differ from the intrauterine growth standards that were developed for the healthy unborn fetus.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

The development of a pregnancy PBPK Model for Bisphenol A and its evaluation with the available biomonitoring data

Authors: Sharma, RP; Schuhmacher, M; Kumar, V (2018) Science of the Total Environment 624:55-68. HERO ID: 4471201

[Less] Recent studies suggest universal fetal exposure to Bisphenol A (BPA) and its association with the adverse . . . [More] Recent studies suggest universal fetal exposure to Bisphenol A (BPA) and its association with the adverse birth outcomes. Estimation of the fetal plasma BPA concentration from the maternal plasma BPA would be highly useful to predict its associated risk to this specific population. The objective of current work is to develop a pregnancy-physiologically based pharmacokinetic (P-PBPK) model to predict the toxicokinetic profile of BPA in the fetus during gestational growth, and to evaluate the developed model using biomonitoring data obtained from different pregnancy cohort studies. To achieve this objective, first, the adult PBPK model was developed and validated with the human BPA toxicokinetic data. This validated human PBPK model was extended to develop a P-PBPK model, which included the physiological changes during pregnancy and the fetus sub-model. The developed model would be able to predict the BPA pharmacokinetics (PKs) in both mother and fetus. Transplacental BPA kinetics parameters for this study were taken from the previous pregnant mice study. Both oral and dermal exposure routes were included into the model to simulate total BPA internal exposure. The impact of conjugation and deconjugation of the BPA and its metabolites on fetal PKs was investigated. The developed P-PBPK model was evaluated against the observed BPA concentrations in cord blood, fetus liver and amniotic fluid considering maternal blood concentration as an exposure source. A range of maternal exposure dose for the oral and dermal routes was estimated, so that simulation concentration matched the observed highest and lowest mother plasma concentration in different cohorts' studies. The developed model could be used to address the concerns regarding possible adverse health effects in the fetus being exposed to BPA and might be useful in identifying critical windows of exposure during pregnancy.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Physiologically based pharmacokinetic (PBPK) modeling of human lactational transfer of methylmercury in China

Authors: Ou, L; Wang, H; Chen, C; Chen, L; Zhang, W; Wang, X (2018) Environment International 115:180-187. HERO ID: 4471224

[Less] Methylmercury can readily cross the human placental barrier and the blood-brain barrier and cause damage . . . [More] Methylmercury can readily cross the human placental barrier and the blood-brain barrier and cause damage to the vulnerable developing brains of the fetus and infants. Most of the previous studies on the maternal transfer of methylmercury to the next generation have focused on the prenatal period. In this study, human physiologically based pharmacokinetic (PBPK) models of methylmercury were established for breastfeeding mothers and suckling infants based on the existing model prototypes of previous studies. Relevant parameters of the models were modified, and the validation was conducted based on measured data in North China. The models could effectively describe the human lactational transfer of methylmercury, including the time-dependent methylmercury levels in different tissues and organs of the breastfeeding mothers and suckling infants. The results indicated that 77.2% and 14.9% of methylmercury were excreted via hair and breast milk, respectively, from breastfeeding mothers during the first year after delivery. Meanwhile, 79.2% was excreted from the suckling infants during the first year after delivery via hair. Lactational transfer of methylmercury was considered an important pathway of methylmercury exposure for the breastfeeding infants, which accounted for approximately 80% of the accumulated adverse impacts at the early stages of human development.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Quantifying population exposure to air pollution using individual mobility patterns inferred from mobile phone data

Authors: Nyhan, MM; Kloog, I; Britter, R; Ratti, C; Koutrakis, P (2018) HERO ID: 4543561

[Less] A critical question in environmental epidemiology is whether air pollution exposures of large populations . . . [More] A critical question in environmental epidemiology is whether air pollution exposures of large populations can be refined using individual mobile-device-based mobility patterns. Cellular network data has become an essential tool for understanding the movements of human populations. As such, through inferring the daily home and work locations of 407,435 mobile phone users whose positions are determined, we assess exposure to PM2.5. Spatiotemporal PM2.5 concentrations are predicted using an Aerosol Optical Depth- and Land Use Regression-combined model. Air pollution exposures of subjects are assigned considering modeled PM2.5 levels at both their home and work locations. These exposures are then compared to residence-only exposure metric, which does not consider daily mobility. In our study, we demonstrate that individual air pollution exposures can be quantified using mobile device data, for populations of unprecedented size. In examining mean annual PM2.5 exposures determined, bias for the residence-based exposures was 0.91, relative to the exposure metric considering the work location. Thus, we find that ignoring daily mobility potentially contributes to misclassification in health effect estimates. Our framework for understanding population exposure to environmental pollution could play a key role in prospective environmental epidemiological studies.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Detection of titanium particles in human liver and spleen and possible health implications

Authors: Heringa, MB; Peters, RJB; Bleys, RLAW; van der Lee, MK; Tromp, PC; van Kesteren, PCE; van Eijkeren, JCH; Undas, AK; Oomen, AG; Bouwmeester, H (2018) HERO ID: 4585525

[Less] BACKGROUND: Titanium dioxide (TiO2) is produced at high volumes and applied in many . . . [More] BACKGROUND: Titanium dioxide (TiO2) is produced at high volumes and applied in many consumer and food products. Recent toxicokinetic modelling indicated the potential of TiO2 to accumulate in human liver and spleen upon daily oral exposure, which is not routinely investigated in chronic animal studies. A health risk from nanosized TiO2 particle consumption could not be excluded then.

RESULTS: Here we show the first quantification of both total titanium (Ti) and TiO2 particles in 15 post-mortem human livers and spleens. These low-level analyses were enabled by the use of fully validated (single particle) inductively coupled plasma high resolution mass spectrometry ((sp)ICP-HRMS) detection methods for total Ti and TiO2 particles. The presence of TiO2 in the particles in tissues was confirmed by Scanning Electron Microscopy with energy dispersive X-ray spectrometry.

CONCLUSIONS: These results prove that TiO2 particles are present in human liver and spleen, with ≥24% of nanosize (< 100 nm). The levels are below the doses regarded as safe in animals, but half are above the dose that is deemed safe for liver damage in humans when taking into account several commonly applied uncertainty factors. With these new and unique human data, we remain with the conclusion that health risks due to oral exposure to TiO2 cannot be excluded.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

In vivo effects: Methodologies and biokinetics of inhaled nanomaterials

Authors: Oberdörster, G; Kuhlbusch, TAJ (2018) NanoImpact 10:38-60. [Review] HERO ID: 4680992

[Less] Inhalation is the prevailing route of inadvertent exposure for manufactured nanomaterials (MNs). For . . . [More] Inhalation is the prevailing route of inadvertent exposure for manufactured nanomaterials (MNs). For assessing potential adverse effects, indepth knowledge about Exposure-Dose-Response relationships is required to define a risk as a function of hazard and relevant exposure. Intrinsic (physico-chemical) and extrinsic (functional) MN properties determine the biological/toxicological properties (effects) of MNs. Predictive testing strategies are useful for comparative hazard and risk characterization against toxicologically well-defined positive and negative benchmark materials involving studies in rodents, cells, and cell-free (abiotic) assays.

Inhalation studies can be used for hazard identification as well as for hazard and risk characterization of inhaled MNs. A design to provide dose-response data is ideal, but less so if only exposure-response data are available. Information should also be provided for biokinetics and for identifying secondary targets. Bolus-type dosing (intratracheal instillation; oropharyngeal aspiration) can be useful for hazard identification and characterization, but not for risk characterization. Combining results from bolus dosing or in vitro tests with results of a subchronic inhalation study of the same group of MNs can be a suitable predictive bridging approach.

In vitro cellular assays designed to determine in vivo effects and underlying mechanisms present additional challenges. Cellular dose equivalency to in vivo is difficult to achieve because of static, mostly acute in vitro systems with no MN clearance. The dose dependency of mechanisms has to be considered as well. Still, in vitro tests are suitable for toxicity ranking against well-characterized benchmarks (Hazard ID). Regarding abiotic assays, predictive toxicity ranking using the metric of specific MN surface reactivity (ROS assays) is a promising screening tool, but requires further validation and standardization. Dynamic abiotic dissolution assays are also a promising tool for predicting in vivo dissolution rates but require standardization.

Information about MN dissolution using static (equilibrium solubility, μg/L) and dynamic (dissolution rate, ng/cm2/day) abiotic in vitro assays provide different information about the solubilization of MNs reflecting either static in vitro or dynamic in vivo conditions. Results of both assays may be useful for categorization if performed in physiologically relevant fluids. Because the in vivo dissolution rates of MNs can differ widely, it is too simplistic to group MNs just into soluble and poorly soluble materials. Static (equilibrium solubility) and dynamic (dissolution rate) abiotic assays are based on different concepts. Results from dynamic dissolution in relevant physiological fluids - rather than just water - add valuable information about the extrinsic functional characteristics of MNs, which may be considered as a grouping tool into high, moderate, low and insoluble MNs.

Systemic biodistribution of MNs depends on the point-of-entry. For example, MNs deposited by inhalation or instillation in the respiratory tract distribute differently than intravenously administered MNs; thus, biokinetic models based on data from intravenous MN administration should not be used to model biodistribution following inhalation. The significance of biodissolution for biokinetics, effects and underlying mechanisms has to be assessed in separate in vivo studies, involving biopersistence/biodurability and ultra-high resolution imaging for analysing bioprocessing and biotransformations at a sub-cellular level.

With respect to grouping, several strategies are necessary to cover all classes of MNs of different compositions and for different exposure routes, all of which are to be considered in regulatory decision-making. The suggested grouping and extrapolation framework presented in this paper could be pivotal in leveraging subchronic inhalation data with data from alternative test methods, thus leading to more efficient, cost-effective, and – in the long run – animal and cost saving methods to obtain needed input data for regulatory use.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Estimating causal effects of local air pollution on daily deaths: Effect of low levels

Authors: Schwartz, J; Bind, MA; Koutrakis, P (2017) Environmental Health Perspectives 125:23-29. HERO ID: 3227881

[Less] BACKGROUND: While many time series studies have established associations of daily pollution . . . [More] BACKGROUND: While many time series studies have established associations of daily pollution variations with daily deaths, there are fewer at low concentrations, or focused on locally generated pollution, which is becoming more important as regulations reduce regional transport. Causal modeling approaches are also lacking.

OBJECTIVE: To use causal modeling to estimate the impact of local air pollution on mortality at low concentrations.

METHODS: Using an instrumental variable approach, we developed an instrument for variations in local pollution concentrations that is unlikely to be correlated with other causes of death, and examined its association with daily deaths in the Boston area. We combined height of the planetary boundary layer and wind speed, which impact concentrations of local emissions, to develop the instrument for PM2.5, BC, or NO2 variations that were independent of year, month, and temperature. We also used Granger causality to assess whether omitted variable confounding existed.

RESULTS: We estimated that an interquartile range increase in the instrument for local PM2.5 was associated with a 0.90% increase in daily deaths (95% CI 0.25, 1.56). A similar result was found for BC, and a weaker association with NO2. The Granger test found no evidence of omitted variable confounding for the instrument. A separate test confirmed the instrument was not associated with mortality independent of pollution. Furthermore, the association remained when all days with PM2.5 concentrations above 30 μg/m(3) were excluded from the analysis (0.84% increase in daily (95% CI 0.19, 1.50).

CONCLUSIONS: We conclude that there is a causal association of local air pollution with daily deaths at concentrations below EPA standards. The estimated attributable risk in Boston exceeded 1,800 deaths during the study period, indicating important public health benefits can follow from further control efforts.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Hydroxylated polycyclic aromatic hydrocarbons as biomarkers of exposure to wood smoke in wildland firefighters

Authors: Adetona, O; Simpson, CD; Li, Z; Sjodin, A; Calafat, AM; Naeher, LP (2017) Journal of Exposure Science and Environmental Epidemiology 27:78-83. HERO ID: 3363586

[Less] Wildland firefighter's exposure to wildland fire or vegetative biomass smoke has mostly been assessed . . . [More] Wildland firefighter's exposure to wildland fire or vegetative biomass smoke has mostly been assessed by personal monitoring to airborne pollutants. However, the use of biomarkers may accurately reflect the internal (systemic) dose received by the firefighter. In this study, we assessed occupational exposure to wildland fire smoke in 14 wildland firefighters working at prescribed burns at the Savannah River Site, South Carolina by measuring the urinary concentrations of nine hydroxylated metabolites of polycyclic aromatic hydrocarbons (OH-PAHs). Except for 1-hydroxynaphthalene, preshift median concentrations of the OH-PAHs were higher compared with the median concentrations reported among the US general population, indicating elevated exposures to PAHs among the wildland firefighters during the prescribed burn season. The postshift concentrations of OH-PAHs were 83-323% (P<0.0001) higher compared with the preshift concentrations. Higher postshift concentrations of individual OH-PAHs were observed in 49 (87.5%) to 53 (94.6%) of all the 56 pre-post sample pairs. Additionally, the cross-shift (pre- to postshift) increase in 4-hydroxy-phenanthrene urinary concentration was marginally associated (P<0.1) with work shift exposure to PM2.5 and significantly associated (P<0.05) with levoglucosan, which is a marker of wildland fire or vegetative biomass smoke. These results suggest that OH-PAHs, especially 4PHE, may be useful biomarkers of wildland fire smoke exposure.Journal of Exposure Science and Environmental Epidemiology advance online publication, 11 November 2015; doi:10.1038/jes.2015.75.