Pharmacokinetic bias analysis of the epidemiological associations between serum polybrominated diphenyl ether (BDE-47) and timing of menarche

Song, Gina; Peeples, Cody R.; Yoon, Miyoung; Wu, Huali; Verner, Marc-André; Andersen, Melvin E.; Clewell, Harvey J.; Longnecker, Matthew P.

doi:10.1016/j.envres.2016.07.004

Cited by 16 publications

(6 citation statements)

References 23 publications

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“…Tissue blood flows are from our ScitoVation database for an adult male (internal database not shown), except for the blood flow to the upper respiratory tract (URT) that was set according to Campbell et al (2015) and the blood flow to the alveolar region that was set according to Butler (1992) . The ScitoVation database includes age-specific physiological parameters for body weight (BW), cardiac output, tissue weights (volumes), and tissue blood flows, and are adapted from published life-stage models ( Wu et al, 2015 ; Song et al, 2016 ; Ruark et al, 2017 ).…”

Section: Methodsmentioning

confidence: 99%

Use of quantitative in vitro to in vivo extrapolation (QIVIVE) for the assessment of non-combustible next-generation product aerosols

Moreau,

Simms,

Andersen

et al. 2024

Front. Toxicol.

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With the use of in vitro new approach methodologies (NAMs) for the assessment of non-combustible next-generation nicotine delivery products, new extrapolation methods will also be required to interpret and contextualize the physiological relevance of these results. Quantitative in vitro to in vivo extrapolation (QIVIVE) can translate in vitro concentrations into in-life exposures with physiologically-based pharmacokinetic (PBPK) modelling and provide estimates of the likelihood of harmful effects from expected exposures. A major challenge for evaluating inhalation toxicology is an accurate assessment of the delivered dose to the surface of the cells and the internalized dose. To estimate this, we ran the multiple-path particle dosimetry (MPPD) model to characterize particle deposition in the respiratory tract and developed a PBPK model for nicotine that was validated with human clinical trial data for cigarettes. Finally, we estimated a Human Equivalent Concentration (HEC) and predicted plasma concentrations based on the minimum effective concentration (MEC) derived after acute exposure of BEAS-2B cells to cigarette smoke (1R6F), or heated tobacco product (HTP) aerosol at the air liquid interface (ALI). The MPPD-PBPK model predicted the in vivo data from clinical studies within a factor of two, indicating good agreement as noted by WHO International Programme on Chemical Safety (2010) guidance. We then used QIVIVE to derive the exposure concentration (HEC) that matched the estimated in vitro deposition point of departure (POD) (MEC cigarette = 0.38 puffs or 11.6 µg nicotine, HTP = 22.9 puffs or 125.6 µg nicotine) and subsequently derived the equivalent human plasma concentrations. Results indicate that for the 1R6F cigarette, inhaling 1/6th of a stick would be required to induce the same effects observed in vitro, in vivo. Whereas, for HTP it would be necessary to consume 3 sticks simultaneously to induce in vivo the effects observed in vitro. This data further demonstrates the reduced physiological potency potential of HTP aerosol compared to cigarette smoke. The QIVIVE approach demonstrates great promise in assisting human health risk assessments, however, further optimization and standardization are required for the substantiation of a meaningful contribution to tobacco harm reduction by alternative nicotine delivery products.

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Section: Methodsmentioning

confidence: 99%

Use of quantitative in vitro to in vivo extrapolation (QIVIVE) for the assessment of non-combustible next-generation product aerosols

Moreau,

Simms,

Andersen

et al. 2024

Front. Toxicol.

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“…Age-specific human physiological parameters, including body weight (BW), cardiac output, tissue weights (or volumes), and tissue plasma flows, were adapted from published life-stage models (Clewell et al , 2004; Ruark et al , 2017; Song et al , 2016; Wu et al , 2015). These published life-stage models use the age-specific physiological parameters of women, which were adapted to represent men based on the most recent National Health and Nutrition Examination Survey (2005–2006) data.…”

Section: Methodsmentioning

confidence: 99%

“…It is critical to obtain enzyme ontogeny data to apply in vitro metabolism data collected using expressed enzymes to predict age-specific metabolic clearance of pyrethroids in vivo (Hines, 2013; Yoon and Clewell, 2016). We collected the enzyme ontogeny information for the CYP and CES enzymes contributing to metabolism of 8 pyrethroids: (1) DLM, (2) CPM, (3) TPM, (4) esfenvalerate, (5) bifenthrin, (6) cyphenothrin, (7) cyhalothrin, and (8) cyfluthrin and conducted nonlinear regression analyses of those age-specific protein expression data from birth to young adulthood reported in the literature (Hines, 2008; Hines et al , 2016; McCarver et al , 2014; Song et al , 2016). Lognormal, hyperbolic, allosteric-sigmoidal, dose-response and, Gompertz growth curves were used, among which the best fit curve based on the Akaike Information Criterion and visual inspection was chosen to describe the maturation profiles of each enzyme expression as a fraction of the adult expression.…”

Section: Methodsmentioning

confidence: 99%

Development and Application of a Life-Stage Physiologically Based Pharmacokinetic (PBPK) Model to the Assessment of Internal Dose of Pyrethroids in Humans

Mallick

Moreau

Song

et al. 2019

Toxicological Sciences

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Abstract To address concerns around age-related sensitivity to pyrethroids, a life-stage physiologically based pharmacokinetic (PBPK) model, supported by in vitro to in vivo extrapolation (IVIVE) was developed. The model was used to predict age-dependent changes in target tissue exposure of 8 pyrethroids; deltamethrin (DLM), cis-permethrin (CPM), trans-permethrin, esfenvalerate, cyphenothrin, cyhalothrin, cyfluthrin, and bifenthrin. A single model structure was used based on previous work in the rat. Intrinsic clearance (CLint) of each individual cytochrome P450 or carboxylesterase (CES) enzyme that are active for a given pyrethroid were measured in vitro, then biologically scaled to obtain in vivo age-specific total hepatic CLint. These IVIVE results indicate that, except for bifenthrin, CES enzymes are largely responsible for human hepatic metabolism (>50% contribution). Given the high efficiency and rapid maturation of CESs, clearance of the pyrethroids is very efficient across ages, leading to a blood flow-limited metabolism. Together with age-specific physiological parameters, in particular liver blood flow, the efficient metabolic clearance of pyrethroids across ages results in comparable to or even lower internal exposure in the target tissue (brain) in children than that in adults in response to the same level of exposure to a given pyrethroid (Cmax ratio in brain between 1- and 25-year old = 0.69, 0.93, and 0.94 for DLM, bifenthrin, and CPM, respectively). Our study demonstrated that a life-stage PBPK modeling approach, coupled with IVIVE, provides a robust framework for evaluating age-related differences in pharmacokinetics and internal target tissue exposure in humans for the pyrethroid class of chemicals.

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“…Song et al. ( 2016 ) developed a PBK model for BDE‐47 in humans, based on the Emond et al. ( 2010 , 2013 ) model, by changing the rat into human parameters.…”

Section: Assessmentmentioning

confidence: 99%

“…These models have been evaluated according to the WHO recommendation (WHO/IPCS, 2010). The structure (compartments) of the models was built according to the PBPK model of BDE-47 previously described by Song et al (2016). For model calibration, the authors used data (estimated oral intakes of BDE-209 and measured serum concentrations of BDE-209) from 26 participants (Chinese subjects).…”

Section: Pbk Models In Humansmentioning

confidence: 99%

Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food

Schrenk,

Bignami,

Bodin

et al. 2024

EFS2

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The European Commission asked EFSA to update its 2011 risk assessment on polybrominated diphenyl ethers (PBDEs) in food, focusing on 10 congeners: BDE‐28, ‐47, ‐49, ‐99, ‐100, ‐138, ‐153, ‐154, ‐183 and ‑209. The CONTAM Panel concluded that the neurodevelopmental effects on behaviour and reproductive/developmental effects are the critical effects in rodent studies. For four congeners (BDE‐47, ‐99, ‐153, ‐209) the Panel derived Reference Points, i.e. benchmark doses and corresponding lower 95% confidence limits (BMDLs), for endpoint‐specific benchmark responses. Since repeated exposure to PBDEs results in accumulation of these chemicals in the body, the Panel estimated the body burden at the BMDL in rodents, and the chronic intake that would lead to the same body burden in humans. For the remaining six congeners no studies were available to identify Reference Points. The Panel concluded that there is scientific basis for inclusion of all 10 congeners in a common assessment group and performed a combined risk assessment. The Panel concluded that the combined margin of exposure (MOET) approach was the most appropriate risk metric and applied a tiered approach to the risk characterisation. Over 84,000 analytical results for the 10 congeners in food were used to estimate the exposure across dietary surveys and age groups of the European population. The most important contributors to the chronic dietary Lower Bound exposure to PBDEs were meat and meat products and fish and seafood. Taking into account the uncertainties affecting the assessment, the Panel concluded that it is likely that current dietary exposure to PBDEs in the European population raises a health concern.

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Pharmacokinetic bias analysis of the epidemiological associations between serum polybrominated diphenyl ether (BDE-47) and timing of menarche

Cited by 16 publications

References 23 publications

Use of quantitative in vitro to in vivo extrapolation (QIVIVE) for the assessment of non-combustible next-generation product aerosols

Use of quantitative in vitro to in vivo extrapolation (QIVIVE) for the assessment of non-combustible next-generation product aerosols

Development and Application of a Life-Stage Physiologically Based Pharmacokinetic (PBPK) Model to the Assessment of Internal Dose of Pyrethroids in Humans

Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food

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