Mechanism of transport and distribution of organic solvents in blood

Lam, C.C.; Galen, Theodore J.; Boyd, J. F.; Pierson, Duane L.

doi:10.1016/0041-008x(90)90287-5

Cited by 68 publications

(18 citation statements)

References 14 publications

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“…Hydrophobic solvents seem to be carried in blood mainly by haemoglobin. It may be that the hydrophobic sites of haemoglobin are somewhat rigid and different molecules may not fit equally well in these pockets (54). The determination of the blood/air partition coefficient (43 ± 2.2) of 1,3,5-TMB in the present study, however, agrees excellently with the value of 44 previously reported (39).…”

Section: Uptakesupporting

confidence: 40%

Toxicokinetics of Inhaled Trimethylbenzenes in Man

Järnberg

Johanson

Löf

1996

Toxicology and Applied Pharmacology

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Section: Uptakesupporting

confidence: 40%

Toxicokinetics of Inhaled Trimethylbenzenes in Man

Järnberg

Johanson

Löf

1996

Toxicology and Applied Pharmacology

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“…Earlier studies have shown that the blood/air partitioning for many VOCs is much higher in rat blood than in human (HbA) blood (2,3) and that the more hydrophobic solvents partition disproportionately into RBCs (2). The difference in Hb affinity for VOCs between human and rat blood has been attributed to the observation that the rat Hb exists in a quasi-crystalline form inside the RBC, implying that it is more hydrophobic than human Hb, which is water soluble (2).…”

Section: Discussionmentioning

confidence: 99%

“…By incorporating metabolic pathways and rates of metabolism, PBPK models have received considerable interest in predictive toxicology and risk assessment (1). A study of partitioning profiles for five organic solvents (n-hexane, toluene, chloroform, methyl isobutyl ketone, and diethyl ether) in normal human and rat blood indicated that the red blood cell (RBC) is an important carrier for hydrophobic VOCs and that the affinity for the three most hydrophobic VOCs (n-hexane, toluene, and chloroform) is substantially greater for rat RBCs than for human RBCs (2). Gargas et al (3) measured PCs for 36 VOCs in human and in rat blood and showed that they were greater in rat blood than in human blood for 32 of the compounds.…”

mentioning

confidence: 99%

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Partitioning of benzene in blood: influence of hemoglobin type in humans and animals.

Wiester

Winsett

Richards

et al. 2002

Environ Health Perspect

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Earlier studies have shown that air/blood partition coefficients (PCs) for many volatile organic chemicals (VOCs) are much higher in rat blood than in human blood. It has been suggested that the discrepancy could be attributed to the fact that hemoglobin (Hb) in rat blood exists in a quasi-crystalline form of hydrophobicity greater than that of normal human Hb (HbA) and thus has a higher carrying capacity for VOCs. In the present study, we used benzene as a prototypic VOC to examine its relative partitioning into human and animal blood. Additionally, we sought to ascertain whether the water-insoluble form of hemoglobin (HbS) found in subjects with homozygous sickle cell (SC) disease has a greater VOC-carrying capacity than does HbA blood. At a low-O(2) tension, HbS switches to water-insoluble polymers, which physically deforms the red blood cells (RBCs) to the sickle shape. We equilibrated HbA, HbS, Hartley guinea pig, CD1 mouse, and rat (F-344, Wistar, and Sprague-Dawley) blood and their respective fractions with benzene vapor (80 or 400 ppm) for 3 hr at 37 degrees C in air-tight vials. We introduced benzene vapor into the vial head space that contained air or respiratory mixtures of venous-type (low-O(2)) or arterial-type (high-O(2)) gases. The blood measurements included the PC, Hb, partial pressures of O(2)(pO(2)) and CO(2)(pCO(2), pH, and percentage of SCs. The benzene concentration had no effect on these parameters, and the high- and low-O(2) gas mixtures produced the expected changes in pO(2), pCO(2), and pH. At equilibrium, the low-O(2) HbS blood had approximately 85% SCs compared with roughly 15% with air or high-O(2) gas. PCs for rat and mouse blood were about 100% higher than those for human and guinea pig blood, but the PC for deoxygenated HbS blood was only slightly higher than that for HbA or oxygenated HbS blood. Benzene showed higher affinities for RBCs in the deoxygenated HbS, rat, and mouse blood and higher affinity for plasma in the guinea pig blood. There was no evidence of disproportionate partitioning of benzene into oxygenated HbS or into HbA blood forms. These data suggest that the water solubility of Hb alone appears to have little effect on the VOC-carrying capacity of blood and that the influence of species is large in comparison. These latter differences in partitioning may depend on the number of hydrophobic sites on the surface of the plasma/heme proteins and thus be unique to the species.

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“…It has been reported before that partition coefficients for rat blood are higher than those for human blood (Gargas et al, 1989;Lam et al, 1990;Kaneko et al, 1994). When the bilinear model (Eq.…”

Section: Discussionmentioning

confidence: 99%

Empirical Relations Predicting Human and Rat Tissue:Air Partition Coefficients of Volatile Organic Compounds

Meulenberg

Vijverberg

2000

Toxicology and Applied Pharmacology

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Based on the hypothesis that tissue partitioning of volatile organic compounds (VOCs) is due to lipophilic and hydrophilic interactions with tissue components, empirical relations are established between olive oil (P oil:air ), saline (P saline:air ), and tissue partition coefficients (P tissue:air ) for human and rat tissues. Reported values of partition coefficients of a wide range of VOCs with distinct chemical structures (n ‫؍‬ 137) have been compiled from the literature. Bilinear regression analysis shows that partition coefficients of VOCs in human blood, brain, fat, liver, kidney, and muscle tissues are well described by a linear combination of P oil:air and P saline:air with tissue-specific regression coefficients. The regression coefficient associated with the hydrophilic component of VOC partitioning in rat tissues is systematically higher than that of human tissues. For the human model, tissue concentrations calculated from predicted partition coefficients are generally within a factor 4 of tissue concentrations calculated from experimentally observed partition coefficients. These results demonstrate that, without prior knowledge of tissue composition, it is possible to obtain estimates of human tissue partition coefficients of VOCs with an accuracy that is in the same range as that commonly used in risk assessment.

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Mechanism of transport and distribution of organic solvents in blood

Cited by 68 publications

References 14 publications

Toxicokinetics of Inhaled Trimethylbenzenes in Man

Toxicokinetics of Inhaled Trimethylbenzenes in Man

Partitioning of benzene in blood: influence of hemoglobin type in humans and animals.

Empirical Relations Predicting Human and Rat Tissue:Air Partition Coefficients of Volatile Organic Compounds

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