A comparison of the binding and distribution of benzo[a]pyrene in human and rat serum

Aarstad, Kjell; Toftgárd, Rune; Nilsen, Odd G.

doi:10.1016/0300-483x(87)90054-0

Cited by 10 publications

(5 citation statements)

References 11 publications

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“…A simplified approach was considered more appropriate based on the limited data available to support description of binding. While binding of B[a]P to various constituents of serum has been explored, only information about fractional binding is currently available (Aarstad et al , 1987). Standard approaches to measurement of binding kinetics, such as equilibrium dialysis or ultrafiltration, are complicated by the high lipophilicity of B[a]P (log KOW ~ 6.1), which causes profound adsorption to or absorption by plastic materials commonly used in experimentation.…”

Section: Discussionmentioning

confidence: 99%

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Preliminary physiologically based pharmacokinetic models for benzo[a]pyrene and dibenzo[def,p]chrysene in rodents

Crowell

Amin

Anderson

et al. 2011

Toxicology and Applied Pharmacology

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Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated as byproducts of natural and anthropogenic combustion processes. Despite significant public health concern, physiologically based pharmacokinetic (PBPK) modeling efforts for PAHs have so far been limited to naphthalene, plus simpler PK models for pyrene, nitropyrene, and benzo[a]pyrene (B[a]P). The dearth of published models is due in part to the high lipophilicity, low volatility, and myriad metabolic pathways for PAHs, all of which present analytical and experimental challenges. Our research efforts have focused upon experimental approaches and initial development of PBPK models for the prototypic PAH, B[a]P, and the more potent, albeit less studied transplacental carcinogen, dibenzo[def, p]chrysene (DBC). For both compounds, model compartments included arterial and venous blood, flow limited lung, liver, richly perfused and poorly perfused tissues, diffusion limited fat, and a two compartment theoretical gut (for oral exposures). Hepatic and pulmonary metabolism was described for both compounds, as were fractional binding in blood and fecal clearance. Partition coefficients for parent PAH along with their diol and tetraol metabolites were estimated using published algorithms and verified experimentally for the hydroxylated metabolites. The preliminary PBPK models were able to describe many, but not all, of the available data sets, comprising multiple routes of exposure (oral, intravenous) and nominal doses spanning several orders of magnitude. Supported by Award Number P42 ES016465 from the National Institute of Environmental Health Sciences.

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Section: Discussionmentioning

confidence: 99%

“…vehicle). Based on reports that B[a]P is readily bound and sequestered in rat plasma proteins and lipoproteins (Aarstad et al , 1987), fractional binding of B[a]P and DBC in blood was described. Saturable metabolism (oxidation) described by the kinetic parameters V MAX and K M occurred in liver and lung compartments.…”

Section: Methodsmentioning

confidence: 99%

Preliminary physiologically based pharmacokinetic models for benzo[a]pyrene and dibenzo[def,p]chrysene in rodents

Crowell

Amin

Anderson

et al. 2011

Toxicology and Applied Pharmacology

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“…For the lipid adjusted concentrations, all of the PAHs were higher in cord blood than in maternal serum except for ANT. Other studies have also found higher concentrations of PAHs in cord blood, which could be because PAHs are generally bound extensively to lipoproteins [25] [26] and, as levels of these have been reported to be higher in newborns than in maternal blood [27], PAHs may accumulate more easily in infants. Another potential reason for this observation could be that PAHs are metabolized slower in the fetus due to age related differences in enzyme function [28].…”

Section: Discussionmentioning

confidence: 93%

Prenatal Exposure to Polycyclic Aromatic Hydrocarbons and Birth Weight in China

Chen¹,

Zheng²,

Bassig³

et al. 2014

OJAP

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Adverse birth outcomes are a leading cause of mortality in children in China, but the environmental influences of these conditions remain largely unexplained in this population. We aimed to evaluate the levels of polycyclic aromatic hydrocarbons (PAHs) in Chinese pregnant women and their newborns, and to examine the association between levels of PAHs and infant birth weight. We conducted a cross-sectional study including 81 pairs of mothers and newborns from four hospitals in four different cities in China. High Performance Liquid Chromatography was used to measure the concentration of nine PAHs in maternal and cord blood and multiple linear regression analyses were used to evaluate the associations of these PAHs with infant birth weight. An-* Corresponding authors. Q. Chen et al. 101 thracene (ANT) had the highest average concentration and detection rate (geometric mean = 69.54 ng/g and 76.5%, respectively) in maternal serum samples, while fluoranthene (FLT) had the highest concentration and detection rate (geometric mean = 68.4 ng/g and 50.6%, respectively) in the cord blood. Most of the measured PAHs in maternal serum and three PAHs in cord blood were inversely but non-significantly associated with birth weight. The strongest associations were observed for higher concentrations of benzo (a) pyrene (BaP) in maternal serum (230.7 g decrease for levels > median vs. < LOD; p = 0.151) and for ANT in cord blood (153.1 g decrease for levels < median vs. < LOD; p = 0.208). Ant and FLT were the predominant PAHs in the maternal and cord blood serum. Serum concentrations of several measured PAHs were associated with a decreased birth weight, although not significantly, suggesting that further studies with larger sample sizes are needed to validate our findings.

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“…This concentrated solution contained not only 200 mg/ml HSA, but also stabilizers: 16 mM sodium acetyltryptophanate, 16 mM sodium caprylate and 140 mM sodium chloride. In human serum, more BaP binds to lipoproteins (containing fatty acid chains) than to albumin [17]. It is therefore presumed that in the experiments containing HSA, BaP was preferentially bound to the caprylic acid (a fatty acid) present in this formulation, which may promote its transplacental transfer in both directions.…”

Section: Discussionmentioning

confidence: 99%

“…BaP has been shown to bind to albumin in a saturable manner [16]; the reported value of 230 lg BaP/ml in human serum includes binding not only to albumin but also to serum lipoproteins, which account for a greater percentage of the total protein-bound BaP [17]. The amino acid sequences of human serum albumin (HSA) and bovine serum albumin (BSA) are 76.5% identical.…”

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confidence: 99%

Transport of Benzo[α]pyrene in the Dually Perfused Human Placenta Perfusion Model: Effect of Albumin in the Perfusion Medium

Mathiesen

Rytting

Mose

et al. 2009

Basic Clin Pharma Tox

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Transport of benzo [a]pyrene (BaP) across the placenta was examined because it is a ubiquitous and highly carcinogenic substance found in tobacco smoke, polluted air and certain foods. Foetal exposure to this substance is highly relevant but is difficult to estimate. The human placenta is unique compared to other species; since it is available without major ethical obstacles, we have used the human placenta perfusion model to study transport from mother to foetus. Placentas were donated after births at Rigshospitalet in Copenhagen from pregnant mothers who signed an informed consent. BaP is lipophilic and studies using cell culture medium in 6-hr placenta perfusions showed minimal transport through the placenta. To increase the solubility of BaP in perfusion medium and to increase physiological relevance, perfusions were also performed with albumin added to the perfusion medium [2 and 30 mg/ml bovine serum albumin (BSA) and 30 mg/ml human serum albumin (HSA)]. The addition of albumin resulted in increased transfer of BaP from maternal to foetal reservoirs. The transfer was even higher in the presence of an HSA formulation containing acetyltryptophanate and caprylate, resulting in a foetal-maternal concentration (FM) ratio of 0.71 € 0.10 after 3 hr and 0.78 € 0.11 after 6 hr, whereas the FM ratio in perfusions without albumin was only 0.05 € 0.03 after 6 hr of perfusion. Less BaP accumulated in placental tissue in perfusions with added albumin. This shows that transplacental transport of the pro-carcinogenic substance BaP occurs, and emphasizes the importance of adding physiological concentrations of albumin when studying the transport of lipophilic substances.

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A comparison of the binding and distribution of benzo[a]pyrene in human and rat serum

Cited by 10 publications

References 11 publications

Preliminary physiologically based pharmacokinetic models for benzo[a]pyrene and dibenzo[def,p]chrysene in rodents

Preliminary physiologically based pharmacokinetic models for benzo[a]pyrene and dibenzo[def,p]chrysene in rodents

Prenatal Exposure to Polycyclic Aromatic Hydrocarbons and Birth Weight in China

Transport of Benzo[α]pyrene in the Dually Perfused Human Placenta Perfusion Model: Effect of Albumin in the Perfusion Medium

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