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

The adipose tissue:blood partition coefficient (PCat: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 (PCo: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 PCat: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 PCat: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 PCat: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 PCat: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 PCo:w of HLOCs, their PCat:b is equal to the ratio of lipid in adipose tissues and blood.

[1]  J. Robinson,et al.  The organochlorine insecticide content of human tissues. , 1968, Archives of environmental health.

[2]  M E Andersen,et al.  Modeling receptor-mediated processes with dioxin: implications for pharmacokinetics and risk assessment. , 1993, Risk analysis : an official publication of the Society for Risk Analysis.

[3]  Kannan Krishnan,et al.  Molecular Structure-Based Prediction of the Partition Coefficients of Organic Chemicals for Physiological Pharmacokinetic Models , 1996 .

[4]  G. Lucier,et al.  A mechanistic model of effects of dioxin on thyroid hormones in the rat. , 1996, Toxicology and applied pharmacology.

[5]  R. Kimbrough,et al.  Partitioning of polybrominated biphenyls (PBBs) in serum, adipose tissue, breast milk, placenta, cord blood, biliary fluid, and feces. , 1983, Archives of environmental health.

[6]  J. Brown,et al.  Comparative study of DDT and its derivatives in human blood samples in norfolk county and Holland Marsh, Ontario , 1975, Bulletin of environmental contamination and toxicology.

[7]  R. Lilis,et al.  Disposition of polychlorinated biphenyl congeners in occupationally exposed persons. , 1982, Toxicology and applied pharmacology.

[8]  D. Morgan,et al.  Loss of DDT from Storage in Human Body Fat , 1972, Nature.

[9]  M E Andersen,et al.  A physiologically based pharmacokinetic model for 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) in the rat: tissue distribution and CYP1A induction. , 1993, Toxicology and applied pharmacology.

[10]  S. Daum,et al.  Analysis of adipose tissue and serum from PBB (polybrominated biphenyl)-exposed workers. , 1979, Journal of Environmental Pathology And Toxicology.

[11]  J. Pirkle,et al.  Correlation between serum and adipose tissue levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in 50 persons from Missouri , 1988, Archives of environmental contamination and toxicology.

[12]  M. Wolff,et al.  Equilibrium of polybrominatd biphenyl (PBB) residues in serum and fat of Michigan residents , 1979, Bulletin of environmental contamination and toxicology.

[13]  J. Robinson,et al.  Organochlorine insecticides: concentrations in human blood and adipose tissue. , 1966, Archives of environmental health.

[14]  Morgan Dp,et al.  Chlorinated hydrocarbon pesticide residue in human tissues. , 1970 .

[15]  H. Matthews,et al.  Pharmacokinetics of 3,3',5,5'-tetrachlorobiphenyl in the male rat. , 1977, Drug metabolism and disposition: the biological fate of chemicals.

[16]  P. Landrigan,et al.  COHORT STUDY OF MICHIGAN RESIDENTS EXPOSED TO POLYBROMINATED BIPHENYLS: EPIDEMIOLOGIC AND IMMUNOLOGIC FINDINGS , 1979, Annals of the New York Academy of Sciences.

[17]  O. Hutzinger,et al.  Bioaccumulation of super‐lipophilic chemicals in fish , 1984 .

[18]  J F Brown,et al.  Polychlorinated biphenyl (PCB) partitioning between adipose tissue and serum , 1984, Bulletin of environmental contamination and toxicology.

[19]  K. Krishnan,et al.  Mechanistic Animal-Replacement Approaches for Predicting Pharmacokinetics of Organic Chemicals , 1999 .

[20]  H. Matthews,et al.  PHARMACOKINETICS OF HALOGENATED HYDROCARBONS , 1979, Annals of the New York Academy of Sciences.

[21]  H. Mussalo-Rauhamaa.  Partitioning and levels of neutral organochlorine compounds in human serum, blood cells, and adipose and liver tissue. , 1991, The Science of the total environment.

[22]  K. Krishnan,et al.  A mechanistic algorithm for predicting blood:air partition coefficients of organic chemicals with the consideration of reversible binding in hemoglobin. , 1996, Toxicology and applied pharmacology.

[23]  R. Lilis,et al.  Body burden of polychlorinated biphenyls among persons employed in capacitor manufacturing , 1982, International archives of occupational and environmental health.

[24]  E. Laws,et al.  Men with intensive occupational exposure to DDT. A clinical and chemical study. , 1967, Archives of environmental health.

[25]  K Krishnan,et al.  An algorithm for predicting tissue: blood partition coefficients of organic chemicals from n-octanol: water partition coefficient data. , 1995, Journal of toxicology and environmental health.

[26]  H. Matthews,et al.  Use of a physiological compartmental model for the rat to describe the pharmacokinetics of several chlorinated biphenyls in the mouse. , 1980, Drug metabolism and disposition: the biological fate of chemicals.