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

Abstract

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.

Bioaccumulation potential of air contaminants: Combining biological allometry, chemical equilibrium and mass-balances to predict accumulation of air pollutants in various mammals

“…This observation is consistent with results from several studies (Lin 1998;Gargas et al 1989;Lam et al 1990) and has been attributed to a weaker binding to plasma-proteins such as albumin and/or hemoglobin in humans compared to rats (Lin 1998;Gargas et al 1989;Wiester et al 2002;Lam et al 1990). This suggests that the sorptive capacity of human blood proteins is overestimated by our model.…”

“…Differences in experimental techniques, for example differences in equilibration time may also contribute to the observed variability in empirical blood-air partition coefficients (Wiester et al 2002).…”

Use of Physiologically Based Biokinetic (PBBK) Modeling to Study Estragole Bioactivation and Detoxification in Humans as Compared with Male Rats

“…This is the result of a threefold higher value of the estimated partition coefficient of estragole in human liver. This phenomenon has previously been attributed to a higher solubility of lipophilic compounds in rat blood over human blood, which is assumed to be a result of species differences in the hemoglobin structure ( Lam et al , 1990 ; Wiester et al , 2002 ). In case of 1′-hydroxyestragole, the AUC 0–24h of this metabolite in the liver is predicted to be 144-fold higher in human than in male rat, which can be explained by a higher level of formation of this metabolite as well as a lower metabolic clearance of this metabolite in human liver.…”

ATSDR evaluation of health effects of benzene and relevance to public health

“…According to Wiester, et al (2002), benzene blood:gas partition coefficients for mice and humans are 17.44 and 8.12, respectively. Therefore the default value of 1 is applied, in which case, the LOAEL HEC is equivalent to the LOAEL ADJ = 2.55 ppm.…”

“…LOAEL If the animal blood:gas partition coefficient is greater than the human blood:gas partition coefficient, a default value of 1 is used for the ratio. According to Wiester, et al (2002), benzene blood:gas partition coefficients for mice and humans are 17.44 and 8.12, respectively. Therefore the default value of 1 is applied, in which case, the LOAEL HEC is equivalent to the LOAEL ADJ = 2.55 ppm.…”