Comprehensive Physiology Wiley Online Library

Accumulation and Release of Chemicals by Adipose Tissue

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 General Pharmacodynamics of Environmental Chemicals
2 Rates of Accumulation and Release for Different Chemicals
2.1 Short‐Lived Chemicals
2.2 Long‐Lived Chemicals
3 Physiological Factors in Accumulation and Release of Chemicals by Adipose Tissue
3.1 Adipose Tissue Perfusion Rates
3.2 Altered Adipose Tissue Mass
3.3 Status of Drug‐Metabolizing Enzymes
4 Effects of Stored Chemicals on Adipose Tissue Physiology
Figure 1. Figure 1.

Conceptual distribution into lipids of tissues and animal products of a lipophilic pesticide, and its elimination. Tissue storage depots are chiefly the adipose tissues.

Figure 2. Figure 2.

A, storage relationships between dieldrin (HEOD) in the diet and representative tissues. The log‐log relationship may be expressed as a storage ratio in comparing different tissues, species, or chemicals, where the storage ratio is equivalent to the antilog of the y intercept (or antilog a when log y = a + b log x). B, relationships between dieldrin (HEOD) levels in blood and representative tissues. The concentrations in tissues are log‐linear with respect to the blood values, and thereby also to the HEOD content of the diet (A).

From Walker et al. 45
Figure 3. Figure 3.

A lipid‐phase model of dieldrin distribution, U, based on regional lipid compartments, M, and associated regional blood flows, Q. S, rate of delivery of dieldrin to the intestinal lumen; θ, its absorption coefficient; Γ, its rate of biotransformation. Specific compartments: B, general blood pool; L, liver; K, kidneys; BR, brain; GI, gastrointestinal tract; F, adipose tissue; M, muscle; OT, other organs, including skin and bone.

From Lindstrom et al. 22
Figure 4. Figure 4.

Estimated dieldrin concentration in lipid phase of adipose tissue and blood during its accumulation and depletion for a 300‐g male rat fed 25 ppm dieldrin in the diet and consuming 20 g food daily. Dieldrin administration was terminated on day 40.

Adapted from Lindstrom et al. 22
Figure 5. Figure 5.

Computed model curves for dieldrin accumulation in depot fat and arterial blood in man, using feeding rates, flows, and compartment sizes for a 68‐kg man. For comparison to the curves, data are plotted for observations made by Hunter & Robinson 18 on human subjects.

Adapted from Lindstrom et al. 22
Figure 6. Figure 6.

Depletion curves for polychlorinated biphenyl isomers from swine adipose tissue. Numbers indicate gas‐liquid chromatography retention values relative to DDE = 100; higher numbers represent more lipophilic isomers

From Borchard et al. 3, reproduced with permission of the copyright owner


Figure 1.

Conceptual distribution into lipids of tissues and animal products of a lipophilic pesticide, and its elimination. Tissue storage depots are chiefly the adipose tissues.



Figure 2.

A, storage relationships between dieldrin (HEOD) in the diet and representative tissues. The log‐log relationship may be expressed as a storage ratio in comparing different tissues, species, or chemicals, where the storage ratio is equivalent to the antilog of the y intercept (or antilog a when log y = a + b log x). B, relationships between dieldrin (HEOD) levels in blood and representative tissues. The concentrations in tissues are log‐linear with respect to the blood values, and thereby also to the HEOD content of the diet (A).

From Walker et al. 45


Figure 3.

A lipid‐phase model of dieldrin distribution, U, based on regional lipid compartments, M, and associated regional blood flows, Q. S, rate of delivery of dieldrin to the intestinal lumen; θ, its absorption coefficient; Γ, its rate of biotransformation. Specific compartments: B, general blood pool; L, liver; K, kidneys; BR, brain; GI, gastrointestinal tract; F, adipose tissue; M, muscle; OT, other organs, including skin and bone.

From Lindstrom et al. 22


Figure 4.

Estimated dieldrin concentration in lipid phase of adipose tissue and blood during its accumulation and depletion for a 300‐g male rat fed 25 ppm dieldrin in the diet and consuming 20 g food daily. Dieldrin administration was terminated on day 40.

Adapted from Lindstrom et al. 22


Figure 5.

Computed model curves for dieldrin accumulation in depot fat and arterial blood in man, using feeding rates, flows, and compartment sizes for a 68‐kg man. For comparison to the curves, data are plotted for observations made by Hunter & Robinson 18 on human subjects.

Adapted from Lindstrom et al. 22


Figure 6.

Depletion curves for polychlorinated biphenyl isomers from swine adipose tissue. Numbers indicate gas‐liquid chromatography retention values relative to DDE = 100; higher numbers represent more lipophilic isomers

From Borchard et al. 3, reproduced with permission of the copyright owner
References
 1. Ballard, K., and S. Rosell. Adrenergic neurohumoral influences on circulation and lipolysis in canine omental adipose tissue. Circulation Res. 28: 389–396, 1971.
 2. Baron, R. L., and M. S. Walton. Dynamics of HEOD (dieldrin) in adipose tissue of the rat. Toxicol. Appl. Pharmacol. 18: 958–963, 1971.
 3. Borchard, R. E., M. E. Welborn, W. B. Wiekhorst, D. W. Wilson, and L. G. Hansen. Pharmacokinetics of polychlorinated biphenyl components in swine and sheep after a single oral dose. J. Pharm. Sci. 64: 1294–1299, 1975.
 4. Brodie, B. B., E. Bernstein, and L. C. Mark. The role of body fat in limiting the duration of action of thiopental. J. Pharmacol. Exptl. Therap. 105: 421–426, 1952.
 5. Campbell, T. C., and J. R. Hayes. Role of nutrition in the drug‐metabolizing enzyme system. Pharmacol. Rev. 26: 171–197, 1974.
 6. Chadwick, R., A. Peoples, and M. Cranmer. The effect of protein quality and ascorbic acid deficiency on stimulation of hepatic microsomal enzymes in guinea pigs. Toxicol. Appl. Pharmacol. 24: 603–611, 1975.
 7. Cook, R. M., and K. A. Wilson. Removal of pesticide residues from dairy cattle. J. Dairy Sci. 54: 712–717, 1971.
 8. Dale, W. E., T. B. Gaines, and W. J. Hayes. Storage and excretion of DDT in starved rats. Toxicol. Appl. Pharmacol. 4: 89–106, 1962.
 9. Davies, J. E., W. F. Edmundson, A. Maceo, G. L. Irvin, J. Cassady, and A. Barquet. Reduction of pesticide residues in human adipose tissue with diphenylhydantoin. Food Cosmet. Toxicol. 9: 413–423, 1971.
 10. Findlay, G. M., and A. S. W. deFreitas. DDT movement from adipocyte to muscle cell during lipid utilization. Nature 229: 63–65, 1971.
 11. Fitzhugh, O. G., and A. A. Nelson. The chronic oral toxicity of DDT (2,2‐bis‐[p‐chlorophenyl]‐1,1,1‐trichloroethane). J. Pharmacol. Exptl. Therap. 89: 18–30, 1947.
 12. Gannon, N., R. P. Link, and G. C. Decker. Storage of dieldrin in tissues of steers, hogs, lambs, and poultry fed dieldrin in their diets. J. Agr. Food Chem. 7: 826–828, 1959.
 13. Garrettson, L. K., and A. Curley. Dieldrin, Studies on a poisoned child. Arch. Environ. Health 19: 814–822, 1969.
 14. Goldstein, A., L. Aronow, and S. M. Kalman. Principles of Drug Action: The Basis of Pharmacology (2nd ed.). New York: Wiley, 1974, p. 339.
 15. Hermann, G., and H. C. Wood. Influence of body fat on duration of thiopental anesthesia. Proc. Soc. Exptl. Biol. Med. 80: 318–319, 1952.
 16. Hukuhara, T., D. Heye, D. J. Hildebrandt, and U. Schwabe. Funktionelle Bedeutung der Speicherung des Insecticids DDT im Fettgewebe bei Futterung an Ratten. Naunyn‐Schmiedebergs Arch. Exptl. Pathol. Pharmakol. 242: 540–550, 1960.
 17. Hunter, C. G., and J. Robinson. Pharmacodynamics of dieldrin (HEOD) I. Ingestion by human subjects for 18 months. Arch. Environ. Health 15: 614–626, 1967.
 18. Hunter, C. G., and J. Robinson. Aldrin, dieldrin and man. Food Cosmet. Toxicol. 6: 253–260, 1968.
 19. Hunter, C. G., J. Robinson, and M. Roberts. Pharmacodynamics of dieldrin (HEOD). Ingestion by human subjects for 18 to 24 months, and postexposure for eight months. Arch. Environ. Health 18: 12–21, 1968.
 20. Kato, R., P. Vossanelli, G. Frontino, and E. Chiesara. Variation in the activity of liver microsomal drug‐metabolizing enzymes in rats in relation to the age. Biochem. Pharmacol. 13: 1037–1051, 1964.
 21. Lehman, A. J. The minute residue problem. Assoc. Food Drug Officials US Quart. Bull. 20: 95–99, 1956.
 22. Lindstrom, F. T., J. W. Gillett, and S. E. Rodecap. Distribution of HEOD (dieldrin) in mammals: I. Preliminary model. Arch. Environ. Contamination Toxicol. 2: 9–42, 1974.
 23. Matthews, H. B., and M. W. Anderson. The distribution and excretion of 2,4,5,2',5'‐pentachlorobiphenyl in the rat. Drug Metab. Disposition 3: 211–219, 1975.
 24. Miller, D. D. Effect of thyroprotein and a low‐energy ration on removal of DDT from lactating dairy cows. J. Dairy Sci. 50: 1444–1447, 1967.
 25. Moss, J. A., and E. E. Hathway. Transport of organic compounds in the mammal. Biochem J. 91: 384–393, 1964.
 26. Oberg, B., and S. Rosell. Sympathetic control of consecutive vascular sections in canine subcutaneous adipose tissue. Acta Physiol. Scand. 71: 47–56, 1967.
 27. Papper, E. M., R. C. Peterson, J. J. Burns, E. Bernstein, P. Lief, and B. B. Brodie. Physiological disposition of certain N‐alkylthiobarbiturates. Anesthesiology 16: 544–550, 1955.
 28. Patterson, W. I., and A. J. Lehman. Pesticides: Some Chemical Considerations and Toxicological Interpretations. Assoc. Food Drug Officials US Quart. Bull. 17: 3–12, 1953.
 29. Paulson, G. L., R. J. Dubos, and J. L. Knittle. Effect of long term dietary exposure to dieldrin and DDT on adipose tissue. Federation Proc. 30: 577a, 1971.
 30. Perl, W., G. T. Lesser, and J. M. Steele. The kinetics of distribution of the fat‐soluble inert gas cyclopropane in the body. Biophys. J. 1: 111–135, 1960.
 31. Price, H. L. A dynamic concept of the distribution of thiopental in the human body. Anesthesiology 21: 40–45, 1960.
 32. Price, H. L., P. J. Konvat, J. N. Safer, E. H. Conner, and M. L. Price. The uptake of thiopental by body tissues and its relation to the duration of narcosis. Clin. Pharmacol. Therap. 1: 16–22, 1960.
 33. Quaife, M. L., J. S. Winbush, and O. G. Fitzhugh. Survey of quantitative relationships between ingestion and storage of aldrin and dieldrin in animals and man. Food Cosmet. Toxicol. 5: 39–50, 1967.
 34. Robinson, J. Dynamics of organic insecticides in vertebrates and ecosystems. Nature 215: 33–35, 1967.
 35. Robinson, J., M. Roberts, M. Baldwin, and A. I. T. Walker. The pharmacokinetics of HEOD (dieldrin) in the rat. Food Cosmet. Toxicol. 7: 317–332, 1969.
 36. Sedlak, V. A. Solubility of benzene hexachloride isomers in rat fat. Toxicol. Appl. Pharmacol. 7: 79–83, 1965.
 37. Shah, A. H., and F. E. Guthrie. Penetration of insecticides through the isolated midgut of insects and mammals. Comp. Gen. Pharmacol. 1: 391–399, 1970.
 38. Sharma, R. P., C. M. Stowe, and A. L. Good. Studies on the distribution and metabolism of thiopental in cattle, sheep, goats and swine. J. Pharmacol. Exptl. Therap. 172: 128–137, 1970.
 39. Stoewsand, G. S., Dietary protein and dieldrin toxicity. In: Pesticides Symposia, edited by W. B. Deichmann. Miami: Halos, 1970, p. 139–145.
 40. Street, J. C. DDT antagonism to dieldrin storage in adipose tissue of rats. Science 146: 1580–1581, 1964.
 41. Street, J. C. Organochlorine insecticides and stimulation of liver microsomal enzymes. Ann. NY Acad. Sci. 160: 274–290, 1969.
 42. Street, J. C., R. C. Baker, D. J. Wagstaff, and F. M. Urry. Pesticide interactions in vertebrates: Effects of nutritional and physiological variables. Proc. Intern. Congr. Pesticide Chem., IUPAC, 2nd, Tel Aviv, 1971, vol. 2, p. 281–302.
 43. Street, J. C., and R. W. Chadwick. Stimulation of dieldrin metabolism by DDT. Toxicol. Appl. Pharmacol. 11: 68–71, 1967.
 44. Street, J. C., and R. W. Chadwick. Ascorbic acid requirements in relation to organochlorine insecticides. Ann. NY Acad. Sci. 238: 132–143, 1975.
 45. Walker, A. I. T., D. E. Stevenson, J. Robinson, E. Thorpe, and M. Roberts. The toxicology and pharmacodynamics of dieldrin (HEOD): Two‐year oral exposure of rats and dogs. Toxicol. Appl. Pharmacol. 15: 345–373, 1969.
 46. Wesley, R. L., A. R. Stemp, R. B. Harrington, B. J. Liska, R. L. Adams, and W. J. Stadelman. Further studies on depletion of DDT residues from laying hens. Poultry Sci. 48: 1269–1275, 1969.
 47. Wesley, R. L., A. R. Stemp, B. J. Liska, and W. J. Stadelman. Depletion of DDT from commercial layers. Poultry Sci. 40: 321–324, 1966.
 48. Wollman, H., and T. C. Smith. Uptake, distribution, elimination, and administration of inhalational anesthetics. In: The Pharmacological Basis of Therapeutics (5th ed.), edited by L. S. Goodman and A. Gilman. New York: Macmillan, 1975, p. 73.
 49. Zabik, M. E., and R. Schemmel. Dieldrin storage of obese and semi‐starved rats. Arch. Environ. Health 27: 25–30, 1973.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

J. C. Street, R. P. Sharma. Accumulation and Release of Chemicals by Adipose Tissue. Compr Physiol 2011, Supplement 26: Handbook of Physiology, Reactions to Environmental Agents: 483-493. First published in print 1977. doi: 10.1002/cphy.cp090130