pmc logo image
Logo of envhperEHP WebsiteAbout EHPPublicationsNews By TopicAuthorsSubscribePressEmail AlertsSearch EHP

Formats:

Environ Health Perspect. 1998 December; 106(Suppl 6): 1495–1503.
PMCID: PMC1533452
Research Article
A physiologically based kinetic model for lead in children and adults.
E J O'Flaherty
Department of Environmental Health, University of Cincinnati College of Medicine, Ohio, USA.
Abstract
A physiologically based model of lead kinetics in children and adults has been developed and tested. The premises on which the physiologically based model is founded are reviewed in this paper. Because 95% or more of the body burden of lead in adults is found in the bone, bone metabolism is central to the model. Bone volumes are expressed as functions of body weight. Bone formation and resorption rates are estimated from human studies of stable labeled calcium kinetics. Cortical and trabecular bone are modeled separately, with their surface-to-volume ratios taken into account. Standardized growth curves are used to relate body weight to age. Other model features such as organ volumes and physiologic functions are related to body weight based on measurements made in human subjects over a range of ages. Calibrations of the model to two human data sets are shown, and two applications to specific research questions are illustrated. A brief comparison of the structure of this model with that of the Leggett model, and a comparison of the output of this model with that of the integrated exposure uptake biokinetic model of the U.S. Environmental Protection Agency, are also included.
Full text
Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
  • O'Flaherty EJ. Physiologically based models for bone-seeking elements. III. Human skeletal and bone growth. Toxicol Appl Pharmacol. 1991 Nov;111(2):332–341. [PubMed]
  • O'Flaherty EJ. Physiologically based models for bone-seeking elements. IV. Kinetics of lead disposition in humans. Toxicol Appl Pharmacol. 1993 Jan;118(1):16–29. [PubMed]
  • O'Flaherty EJ. Physiologically based models for bone-seeking elements. V. Lead absorption and disposition in childhood. Toxicol Appl Pharmacol. 1995 Apr;131(2):297–308. [PubMed]
  • Leggett RW. An age-specific kinetic model of lead metabolism in humans. Environ Health Perspect. 1993 Dec;101(7):598–616. [PubMed]
  • GONG JK, ARNOLD JS, COHN SH. COMPOSITION OF TRABECULAR AND CORTICAL BONE. Anat Rec. 1964 Jul;149:325–331. [PubMed]
  • LEE WR, MARSHALL JH, SISSONS HA. CALCIUM ACCRETION AND BONE FORMATION IN DOGS: AN EXPERIMENTAL COMPARISON BETWEEN THE RESULTS OF CA-45 KINETIC ANALYSIS AND TETRACYCLINE LABELLING. J Bone Joint Surg Br. 1965 Feb;47:157–180. [PubMed]
  • Jerome CP, Carlson CS, Register TC, Bain FT, Jayo MJ, Weaver DS, Adams MR. Bone functional changes in intact, ovariectomized, and ovariectomized, hormone-supplemented adult cynomolgus monkeys (Macaca fascicularis) evaluated by serum markers and dynamic histomorphometry. J Bone Miner Res. 1994 Apr;9(4):527–540. [PubMed]
  • Stevens W, Bruenger FW, Atherton DR, Smith JM, Taylor GN. The distribution and retention of hexavalent 233U in the beagle. Radiat Res. 1980 Jul;83(1):109–126. [PubMed]
  • Rubin MI, Bruck E, Rapoport M, Snively M, McKay H, Baumler A. MATURATION OF RENAL FUNCTION IN CHILDHOOD: CLEARANCE STUDIES. J Clin Invest. 1949 Sep;28(5 Pt 2):1144–1162. [PubMed]
  • Dietrich KN, Berger OG, Succop PA. Lead exposure and the motor developmental status of urban six-year-old children in the Cincinnati Prospective Study. Pediatrics. 1993 Feb;91(2):301–307. [PubMed]
  • Van de Vyver FL, D'Haese PC, Visser WJ, Elseviers MM, Knippenberg LJ, Lamberts LV, Wedeen RP, De Broe ME. Bone lead in dialysis patients. Kidney Int. 1988 Feb;33(2):601–607. [PubMed]
  • O'Flaherty EJ. Physiologically based models for bone-seeking elements. I. Rat skeletal and bone growth. Toxicol Appl Pharmacol. 1991 Nov;111(2):299–312. [PubMed]
  • O'Flaherty EJ. Physiologically based models for bone-seeking elements. II. Kinetics of lead disposition in rats. Toxicol Appl Pharmacol. 1991 Nov;111(2):313–331. [PubMed]
  • Rabinowitz MB, Kopple JD, Wetherill GW. Effect of food intake and fasting on gastrointestinal lead absorption in humans. Am J Clin Nutr. 1980 Aug;33(8):1784–1788. [PubMed]
  • Polák J, O'Flaherty EJ, Freeman GB, Johnson JD, Liao SC, Bergstrom PD. Evaluating lead bioavailability data by means of a physiologically based lead kinetic model. Fundam Appl Toxicol. 1996 Jan;29(1):63–70. [PubMed]
  • Freeman GB, Johnson JD, Killinger JM, Liao SC, Feder PI, Davis AO, Ruby MV, Chaney RL, Lovre SC, Bergstrom PD. Relative bioavailability of lead from mining waste soil in rats. Fundam Appl Toxicol. 1992 Oct;19(3):388–398. [PubMed]
  • Freeman GB, Johnson JD, Liao SC, Feder PI, Davis AO, Ruby MV, Schoof RA, Chaney RL, Bergstrom PD. Absolute bioavailability of lead acetate and mining waste lead in rats. Toxicology. 1994 Jul 1;91(2):151–163. [PubMed]
  • Inskip MJ, Franklin CA, Baccanale CL, Manton WI, O'Flaherty EJ, Edwards CM, Blenkinsop JB, Edwards EB. Measurement of the flux of lead from bone to blood in a nonhuman primate (Macaca fascicularis) by sequential administration of stable lead isotopes. Fundam Appl Toxicol. 1996 Oct;33(2):235–245. [PubMed]
  • Pounds JG, Leggett RW. The ICRP age-specific biokinetic model for lead: validations, empirical comparisons, and explorations. Environ Health Perspect. 1998 Dec;106 Suppl 6:1505–1511. [PubMed]
  • Bromley RG, Dockum NL, Arnold JS, Jee WS. Quantitative histological study of human lumbar vertebrae. J Gerontol. 1966 Oct;21(4):537–543. [PubMed]
  • Dunnill MS, Anderson JA, Whitehead R. Quantitative histological studies on age changes in bone. J Pathol Bacteriol. 1967 Oct;94(2):275–291. [PubMed]
  • Lloyd E, Rowland RE, Hodges D, Marshall JH. Surface to volume ratios of bone determined by computer analysis of microradiographs. Nature. 1968 Apr 27;218(5139):365–366. [PubMed]
  • Amstutz HC, Sissons HA. The structure of the vertebral spongiosa. J Bone Joint Surg Br. 1969 Aug;51(3):540–550. [PubMed]
  • Dyson ED, Jackson CK, Whitehouse WJ. Scanning electron microscope studies of human trabecular bone. Nature. 1970 Mar 7;225(5236):957–959. [PubMed]
  • Merz WA, Schenk RK. Quantitative structural analysis of human cancellous bone. Acta Anat (Basel). 1970;75(1):54–66. [PubMed]
  • Lloyd E, Hodges D. Quantitative characterization of bone: a computer analysis of microradiography. Clin Orthop Relat Res. 1971;78:230–250. [PubMed]
  • Beddoe AH, Darley PJ, Spiers FW. Measurements of trabecular bone structure in man. Phys Med Biol. 1976 Jul;21(4):589–607. [PubMed]
  • Beddoe AH. Measurements of the microscopic structure of cortical bone. Phys Med Biol. 1977 Mar;22(2):298–308. [PubMed]
  • Vedi S, Compston JE, Webb A, Tighe JR. Histomorphometric analysis of dynamic parameters of trabecular bone formation in the iliac crest of normal British subjects. Metab Bone Dis Relat Res. 1983 1984;5(2):69–74. [PubMed]
  • Sontag W. Quantitative measurement of periosteal and cortical-endosteal bone formation and resorption in the midshaft of female rat femur. Bone. 1986;7(1):55–62. [PubMed]
  • Sontag W. Quantitative measurements of periosteal and cortical-endosteal bone formation and resorption in the midshaft of male rat femur. Bone. 1986;7(1):63–70. [PubMed]
  • Sim FH, Kelly PJ. Relationship of bone remodeling, oxygen consumption, and blood flow in bone. J Bone Joint Surg Am. 1970 Oct;52(7):1377–1389. [PubMed]
  • Whiteside LA, Simmons DJ, Lesker PA. Comparison of regional bone blood flow in areas with differing osteoblastic activity in the rabbit tibia. Clin Orthop Relat Res. 1977 May;(124):267–270. [PubMed]
  • BAUER GC, CARLSSON A, LINDQUIST B. Bone salt metabolism in humans studied by means of radiocalcium. Acta Med Scand. 1957 Aug 13;158(2):143–150. [PubMed]
  • HEANEY RP, WHEDON GD. Radiocalcium studies of bone formation rate in human metabolic bone disease. J Clin Endocrinol Metab. 1958 Nov;18(11):1246–1267. [PubMed]
  • BRONNER F, RICHELLE LJ, SAVILLE PD, NICHOLAS JA, COBB JR. Quantitation of calcium metabolism in postmenopausal osteoporosis and in scoliosis. J Clin Invest. 1963 Jun;42:898–905. [PubMed]
  • Neer R, Berman M, Fisher L, Rosenberg LE. Multicompartmental Analysis of Calcium Kinetics in Normal Adult Males. J Clin Invest. 1967 Aug;46(8):1364–1379. [PubMed]
  • Abrams SA, Esteban NV, Vieira NE, Sidbury JB, Specker BL, Yergey AL. Developmental changes in calcium kinetics in children assessed using stable isotopes. J Bone Miner Res. 1992 Mar;7(3):287–293. [PubMed]
  • Leggett RW, Eckerman KF, Williams LR. Strontium-90 in bone: a case study in age-dependent dosimetric modeling. Health Phys. 1982 Sep;43(3):307–322. [PubMed]