The sorptive capacity of animal protein

deBruyn, Adrian M.H.; Gobas, Frank A.P.C.

doi:10.1897/07-016r.1

Cited by 122 publications

(128 citation statements)

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“…Inclusion of proteins and other tissue components could shift the fish BCF upwards by about one order of magnitude [40]. In addition, DeBruyn and Gobas [41] noticed that for chemicals characterized by low log K OW values (below 2), octanol is a rather poor predictor of the sorptive capacity of proteins. Furthermore, the inaccuracy of K OW and lipid based partitioning models might be greater for H-bond donor compounds [40] and based on chemical structures, all of our compounds with log K OW values below 2 (i.e.…”

Section: Resultsmentioning

confidence: 99%

Measured and Modeled Toxicokinetics in Cultured Fish Cells and Application to In Vitro - In Vivo Toxicity Extrapolation

et al. 2014

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Effect concentrations in the toxicity assessment of chemicals with fish and fish cells are generally based on external exposure concentrations. External concentrations as dose metrics, may, however, hamper interpretation and extrapolation of toxicological effects because it is the internal concentration that gives rise to the biological effective dose. Thus, we need to understand the relationship between the external and internal concentrations of chemicals. The objectives of this study were to: (i) elucidate the time-course of the concentration of chemicals with a wide range of physicochemical properties in the compartments of an in vitro test system, (ii) derive a predictive model for toxicokinetics in the in vitro test system, (iii) test the hypothesis that internal effect concentrations in fish (in vivo) and fish cell lines (in vitro) correlate, and (iv) develop a quantitative in vitro to in vivo toxicity extrapolation method for fish acute toxicity. To achieve these goals, time-dependent amounts of organic chemicals were measured in medium, cells (RTgill-W1) and the plastic of exposure wells. Then, the relation between uptake, elimination rate constants, and log KOW was investigated for cells in order to develop a toxicokinetic model. This model was used to predict internal effect concentrations in cells, which were compared with internal effect concentrations in fish gills predicted by a Physiologically Based Toxicokinetic model. Our model could predict concentrations of non-volatile organic chemicals with log KOW between 0.5 and 7 in cells. The correlation of the log ratio of internal effect concentrations in fish gills and the fish gill cell line with the log KOW was significant (r>0.85, p = 0.0008, F-test). This ratio can be predicted from the log KOW of the chemical (77% of variance explained), comprising a promising model to predict lethal effects on fish based on in vitro data.

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Section: Resultsmentioning

confidence: 99%

Measured and Modeled Toxicokinetics in Cultured Fish Cells and Application to In Vitro - In Vivo Toxicity Extrapolation

et al. 2014

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“…In humans, this ratio is about 0.005 for a large series of polychlorinated biphenyls [14]. In addition, in a recent large compilation of K tis-bld by deBruyn and Gobas [15] the value of 1/K ad-bld is in the range of 0.005 for most of the very highly fat soluble solutes. This value of 0.005 is close to the directly measured values of blood lipid fraction in humans [9] and rats [10] and a value of f L = 0.005 will be assumed here.…”

Section: Methodsmentioning

confidence: 99%

Quantitative relationship between the octanol/water partition coefficient and the diffusion limitation of the exchange between adipose and blood

Levitt

2010

BMC Clin Pharmacol

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BackgroundThe goal of physiologically based pharmacokinetics (PBPK) is to predict drug kinetics from an understanding of the organ/blood exchange. The standard approach is to assume that the organ is "flow limited" which means that the venous blood leaving the organ equilibrates with the well-stirred tissue compartment. Although this assumption is valid for most solutes, it has been shown to be incorrect for several very highly fat soluble compounds which appear to be "diffusion limited". This paper describes the physical basis of this adipose diffusion limitation and its quantitative dependence on the blood/water (Kbld-wat) and octanol/water (Kow) partition coefficient.MethodsExperimental measurements of the time dependent rat blood and adipose concentration following either intravenous or oral input were used to estimate the "apparent" adipose perfusion rate (FA) assuming that the tissue is flow limited. It is shown that the ratio of FA to the anatomic perfusion rate (F) provides a measure of the diffusion limitation. A quantitative relationship between this diffusion limitation and Kbld-wat and Kow is derived. This analysis was applied to previously published data, including the Oberg et. al. measurements of the rat plasma and adipose tissue concentration following an oral dose of a mixture of 13 different polychlorinated biphenyls.ResultsSolutes become diffusion limited at values of log Kow greater than about 5.6, with the adipose-blood exchange rate reduced by a factor of about 30 for a solute with a log Kow of 7.36. Quantitatively, a plot of FA/F versus Kow is well described assuming an adipose permeability-surface area product (PS) of 750/min. This PS corresponds to a 0.14 micron aqueous layer separating the well-stirred blood from the adipose lipid. This is approximately equal to the thickness of the rat adipose capillary endothelium.ConclusionsThese results can be used to quantitate the adipose-blood diffusion limitation as a function of Kow. This is especially important for the highly fat soluble persistent organic chemicals (e.g. polychlorinated biphenyls, dioxins) whose pharmacokinetics are primarily determined by the adipose-blood exchange kinetics.

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“…where F W,S9, F L,S9 , and F P,S9 are the fractions of water, lipid, and protein (v/v; unitless), respectively. The proportionality constant (b) reflects the sorptive capacity of protein relative to that of octanol and was assumed to be 0.05 (deBruyn and Gobas 2007). Measured values of F L,S9 and F P,S9 determined in the present study are provided in the Supplemental Data, Table S2.…”

Section: Ivive and Bioconcentration Factorsmentioning

confidence: 99%

Concentration dependence of in vitro biotransformation rates of hydrophobic organic sunscreen agents in rainbow trout S9 fractions: Implications for bioaccumulation assessment

Saunders¹,

Fontanay²,

Nichols

et al. 2019

Enviro Toxic and Chemistry

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In vitro biotransformation studies were performed to support the bioaccumulation assessment of 3 hydrophobic organic ultraviolet filters (UVFs), 4‐methylbenzylidene camphor (4‐MBC), 2‐ethylhexyl‐4‐methoxycinnamate (EHMC), and octocrylene. In vitro depletion rate constants (kdep) were determined for each UVF using rainbow trout liver S9 fractions. Incubations performed with and without added cofactors showed complete (4‐MBC) or partial (EHMC and octocrylene) dependence of kdep on addition of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), suggesting that hydrolysis of EHMC and octocrylene by NADPH‐independent enzymes (e.g., carboxylesterases) is an important metabolic route. The concentration dependence of kdep was then evaluated to estimate Michaelis–Menten parameters (KM and Vmax) for each UVF. Measured kdep values were then extrapolated to apparent whole‐body biotransformation rate constants using an in vitro–in vivo extrapolation (IVIVE) model. Bioconcentration factors (BCFs) calculated from kdep values measured at concentrations well below KM were closer to empirical BCFs than those calculated from kdep measured at higher test concentrations. Modeled BCFs were sensitive to in vitro binding assumptions employed in the IVIVE model, highlighting the need for further characterization of chemical binding effects on hepatic clearance. The results suggest that the tested UVFs are unlikely to accumulate to levels exceeding the European Union Registration, Evaluation, Authorisation, and Restriction regulation criterion for bioaccumulative substances (BCF > 2000 L kg−1). However, consideration of appropriate in vitro test concentrations and binding correction factors are important when IVIVE methods are used to refine modeled BCFs. Environ Toxicol Chem 2019;38:548–560. © 2018 SETAC

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The sorptive capacity of animal protein

Cited by 122 publications

References 27 publications

Measured and Modeled Toxicokinetics in Cultured Fish Cells and Application to In Vitro - In Vivo Toxicity Extrapolation

Measured and Modeled Toxicokinetics in Cultured Fish Cells and Application to In Vitro - In Vivo Toxicity Extrapolation

Quantitative relationship between the octanol/water partition coefficient and the diffusion limitation of the exchange between adipose and blood

Concentration dependence of in vitro biotransformation rates of hydrophobic organic sunscreen agents in rainbow trout S9 fractions: Implications for bioaccumulation assessment

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