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59 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

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.

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

Air pollutant exposure field modeling using air quality model-data fusion methods and comparison with satellite AOD-derived fields: application over North Carolina, USA

Authors: Huang, Ran; Zhai, X; Ivey, CE; Friberg, MD; Hu, X; Liu, Y; Di, Q; Schwartz, J; Mulholland, JA; Russell, AG (2018) HERO ID: 4439732

[Less] In order to generate air-pollutant exposure fields for health studies, a data fusion (DF) approach is . . . [More] In order to generate air-pollutant exposure fields for health studies, a data fusion (DF) approach is developed that combines observations from ambient monitors and simulated data from the Community Multiscale Air Quality (CMAQ) model. These resulting fields capture the spatiotemporal information provided by the air quality model, as well as the finer temporal scale variations from the pollutant observations and decrease model biases. Here, the approach is applied to develop daily concentration fields for PM2.5 total mass, five major particulate species (OC, EC, SO42-, NO3-, and NH4 (+)), and three gaseous pollutants (CO, NOx , and NO2) from 2006 to 2008 over North Carolina (USA). Several data withholding methods are then conducted to evaluate the data fusion method, and the results suggest that typical approaches may overestimate the ability of spatiotemporal estimation methods to capture pollutant concentrations in areas with limited or no monitors. The results show improvements in capturing spatial and temporal variability compared with CMAQ results. Evaluation tests for PM2.5 led to an R-2 of 0.95 (no withholding) and 0.82 when using 10% random data withholding. If spatially based data withholding is used, the R-2 is 0.73. Comparisons of DF-developed PM2.5 total mass concentration with the spatiotemporal fields derived from two other methods (both use satellite aerosol optical depth (AOD) data) find that, in this case, the data fusion fields have slightly less overall error, with an RMSE of 1.28 compared with 3.06 mu g/m(3) (two-stage statistical model) and 2.74 (neural network-based hybrid model). Applying the Integrated Mobile Source Indicator (IMSI) method shows that the data fusion fields can be used to estimate mobile source impacts. Overall, the growing availability of chemically detailed air quality model fields and the accuracy of the DF field, suggest that this approach is better able to provide spatiotemporal pollutant fields for gaseous and speciated particulate pollutants for health and planning 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

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.

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

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

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

Prenatal exposure estimation of BPA and DEHP using integrated external and internal dosimetry: A case study

Authors: Martínez, MA; Rovira, J; Sharma, RP; Nadal, M; Schuhmacher, M; Kumar, V (2017) Environmental Research 158:566-575. HERO ID: 3972271

[Less] Prenatal exposure to Endocrine disruptors (EDs), such as Bisphenol A (BPA) and di (2-ethylhexyl) phthalate . . . [More] Prenatal exposure to Endocrine disruptors (EDs), such as Bisphenol A (BPA) and di (2-ethylhexyl) phthalate (DEHP), has been associated with obesity and diabetes diseases in childhood, as well as reproductive, behavioral and neurodevelopment problems. The aim of this study was to estimate the prenatal exposure to BPA and DEHP through food consumption for pregnant women living in Tarragona County (Spain). Probabilistic calculations of prenatal exposure were estimated by integrated external and internal dosimetry modelling, physiologically based pharmacokinetic (PBPK) model, using a Monte-Carlo simulation. Physical characteristic data from the cohort, along with food intake information from the questionnaires (concentrations of BPA and DEHP in different food categories and the range of the different food ratios), were used to estimate the value of the total dietary intake for the Tarragona pregnancy cohort. The major contributors to the total dietary intake of BPA were canned fruits and vegetables, followed by canned meat and meat products. In turn, milk and dairy products, followed by ready to eat food (including canned dinners), were the most important contributors to the total dietary intake of DEHP. Despite the dietary variations among the participants, the intakes of both chemicals were considerably lower than their respective current tolerable daily intake (TDI) values established by the European Food Safety Authority (EFSA). Internal dosimetry estimates suggest that the plasma concentrations of free BPA and the most important DEHP metabolite, mono (2-ethylhexyl) phthalate (MEHP), in pregnant women were characterized by transient peaks (associated with meals) and short half-lives (< 2h). In contrast, fetal exposure was characterized by a low and sustained basal BPA and MEHP concentration due to a lack of metabolic activity in the fetus. Therefore, EDs may have a greater effect on developing organs in young children or in the unborn child.

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

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

Authors: Shin, MY; Kim, S; Lee, S; Kim, HJ; Lee, JJ; Choi, G; Choi, S; Kim, S; Kim, SY; Park, J; Moon, HB; Choi, K; Kim, S (2017) Science of the Total Environment 616-617:510-516. HERO ID: 4168000

[Less] Many scientists made estimates of the body burden of PBDEs from breastmilk and house dust. Interestingly, . . . [More] 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.

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

Gestation-Specific Changes in the Anatomy and Physiology of Healthy Pregnant Women: An Extended Repository of Model Parameters for Physiologically Based Pharmacokinetic Modeling in Pregnancy

Authors: Dallmann, A; Ince, I; Meyer, M; Willmann, S; Eissing, T; Hempel, G (2017) HERO ID: 4470985

[Less] BACKGROUND: In the past years, several repositories for anatomical and physiological . . . [More] BACKGROUND: In the past years, several repositories for anatomical and physiological parameters required for physiologically based pharmacokinetic modeling in pregnant women have been published. While providing a good basis, some important aspects can be further detailed. For example, they did not account for the variability associated with parameters or were lacking key parameters necessary for developing more detailed mechanistic pregnancy physiologically based pharmacokinetic models, such as the composition of pregnancy-specific tissues.

OBJECTIVES: The aim of this meta-analysis was to provide an updated and extended database of anatomical and physiological parameters in healthy pregnant women that also accounts for changes in the variability of a parameter throughout gestation and for the composition of pregnancy-specific tissues.

METHODS: A systematic literature search was carried out to collect study data on pregnancy-related changes of anatomical and physiological parameters. For each parameter, a set of mathematical functions was fitted to the data and to the standard deviation observed among the data. The best performing functions were selected based on numerical and visual diagnostics as well as based on physiological plausibility.

RESULTS: The literature search yielded 473 studies, 302 of which met the criteria to be further analyzed and compiled in a database. In total, the database encompassed 7729 data. Although the availability of quantitative data for some parameters remained limited, mathematical functions could be generated for many important parameters. Gaps were filled based on qualitative knowledge and based on physiologically plausible assumptions.

CONCLUSION: The presented results facilitate the integration of pregnancy-dependent changes in anatomy and physiology into mechanistic population physiologically based pharmacokinetic models. Such models can ultimately provide a valuable tool to investigate the pharmacokinetics during pregnancy in silico and support informed decision making regarding optimal dosing regimens in this vulnerable special population.