Relative lipid content as the sole mechanistic determinant of the adipose tissue:blood partition coefficients of highly lipophilic organic chemicals

Abstract

The adipose tissue:blood partition coefficient (PC_at:b) refers to the ratio of chemical concentration or solubility in adipose tissue and blood. The solubility of a chemical in adipose tissue or whole blood is equal to the sum total of its solubility in lipid and water fractions of these matrices. For highly lipophilic organic chemicals (HLOCs, i.e., chemicals with log n-octanol:water partition coefficients (PC_o:w) greater than four), their solubility in the water fractions of both tissue and blood is negligible, and therefore their solubility in lipid fractions of tissue and blood alone determines PC_at:b. Since the numerical value representing chemical solubility in lipids is likely to be the same for both blood lipids and adipose tissue lipids, the PC_at:b values should be hypothetically, equal to the ratio of lipid content of adipose tissue and blood. The objective of the present study was therefore to verify whether the PC_at:bs of HLOCs (volatile organics, dioxins, PCBs, PBBs, DDT) are equal to the ratio of adipose tissue and blood lipid levels. The data on lipid content of rat and human blood and adipose tissues were obtained from the literature. The calculated tissue:blood lipid ratios were comparable to the human and rat PC_at:b of volatile organic chemicals, dioxins, PCBs, PBBs and/or DDT obtained from the literature. These results then suggest that, regardless of the identity and PC_o:w of HLOCs, their PC_at:b is equal to the ratio of lipid in adipose tissues and blood.

Introduction

The biopersistence of chemicals is determined by the rates of elimination and accumulation. In mammals, for example, the greater the storage of chemicals in adipose tissues, the greater is the possibility for continued internal exposure even after the cessation of external exposure. The degree of accumulation in adipose tissues is determined by the adipose tissue:blood partition coefficient (PC_at:b). By definition, adipose tissue:blood partition coefficient is the numerical value representing the ratio of concentration in adipose tissues and blood at equilibrium.

Even though the general perception is a proportional increase in adipose tissue:blood partition coefficient as a function of lipophilicity or n-octanol:water partition coefficient (PC_o:w) of chemicals, this may not be entirely true above a certain PC_o:w value. This has actually been demonstrated in aquatic toxicology studies with respect to the bioconcentration of lipophilic organics. Here, the bioconcentration factor (BCF) of organic chemicals has been shown to be dependent on PC_o:w, for upto log PC_o:w value of four. However for chemicals with log PC_o:w > 6 the BCF in fish appears to be fairly constant, suggestive of a plausible upper limit of bioconcentration (Bruggeman et al., 1984). In the case of aquatic biota it is not so much the adipose tissue per se that accounts for chemical storage, but it is the neutral lipid portion of the various tissues. These observations suggest that there may as well be an apparent upper limit of chemical partitioning into tissues other than the adipose tissue. The occurrence of such a phenomenon would imply that there is a theoretical upper limit of tissue:blood partition coefficients (PC_t:b). There has not been any attempt (i) to identify the theoretical upper limit of PC_t:b in mammals, or the PC_o:w value after which there would no longer exist a demonstrable linear relationship between PC_o:w and PC_t:b, and (ii) to elucidate the mechanistic basis for such a lack of linear relationship between PC_o:w and PC_t:b. The present study focussed to evaluate these characteristics for the adipose tissue:blood partition coefficients (PC_at:b) of organic chemicals.