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I'm interested in finding a 'compartment/kinetic' model or models for =
heavy metal toxicity that is in the vein of pharmacokinetic models for drugs.
Might you be able to point me to one/some?
Mike Mickley, P.E., Ph.D.
Mickley & Associates
752 Gapter Road
Boulder, CO 80303
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Ellen O'Flaherty at the University of Cincinnati has published a number of
papers on physiological kinetics models of metals including lead and
Please find below a selection of references.
1: Beck BD, Mattuck RL, Bowers TS, Cohen JT, O'Flaherty E.
The development of a stochastic physiologically-based pharmacokinetic model for
Sci Total Environ. 2001 Jul 2;274(1-3):15-9.
PMID: 11453291 [PubMed - indexed for MEDLINE]
2: O'Flaherty EJ, Kerger BD, Hays SM, Paustenbach DJ.
A physiologically based model for the ingestion of chromium(III) and
chromium(VI) by humans.
Toxicol Sci. 2001 Apr;60(2):196-213.
PMID: 11248132 [PubMed - indexed for MEDLINE]
3: Fleming DE, Chettle DR, Webber CE, O'Flaherty EJ.
The O'Flaherty model of lead kinetics: an evaluation using data from a lead
Toxicol Appl Pharmacol. 1999 Nov 15;161(1):100-9.
PMID: 10558927 [PubMed - indexed for MEDLINE]
4: O'Flaherty EJ.
A physiologically based kinetic model for lead in children and adults.
Environ Health Perspect. 1998 Dec;106 Suppl 6:1495-503. Review.
PMID: 9860908 [PubMed - indexed for MEDLINE]
5: O'Flaherty EJ.
Physiologically based models of metal kinetics.
Crit Rev Toxicol. 1998 May;28(3):271-317. Review.
PMID: 9631283 [PubMed - indexed for MEDLINE]
A.J. MacDonald Ph.D
Senior Scientist, Modelling and Simulation
ICPP, Pre-Clinical Safety
Novartis Pharma AG
(T) +41 61 696 77 98
(F) +41 61 696 69 92
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Lead appers to be the most studied metal ion, and several models have been
suggested to describe its pharmacokinetics. Pharmacokinetic models have been
suggested also for aluminum, polonium, etc. Several relevant references are
listed below (the references on O'Flaherty model for lead and other metals
have been already sent to the PharmPK, and are not listed here):
Pounds JG, Leggett RW. The ICRP age-specific biokinetic model for lead:
validations, empirical comparisons, and explorations. Environ Health
Perspect 1998; 106, Suppl: 61505-11
Leggett RW. An age-specific kinetic model of lead metabolism in humans.
Environ Health Perspect 1993; 101 (7): 598-616
Mason HJ. A biokinetic model for lead metabolism with a view to its
extension to pregnancy and lactation; (1). Further validation of the
original model for non-pregnant adults. Sci Total Environ 2000; 246 (1):
Leggett RW, Eckerman KF. A systemic biokinetic model for polonium. Sci Total
Environ 2001; 275 (1-3): 109-25
Yokel RA, McNamara PJ. Aluminium toxicokinetics: an updated minireview.
Pharmacol Toxicol 2001; 88 (4): 159-67
David Stepensky, PhD student
Department of Pharmaceutics, School of Pharmacy,
The Hebrew University of Jerusalem, P.O.B. 12065,
Jerusalem, 91120, Israel.
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I just wrote a basic chapter on Pharmacokinetic Approach and
Mathematical Modeling of Metals for a section "Modeling of trace
element species in health and disease" which soon will be published
in the "Handbook of Elemental Speciation" (edit. Rita Cornelis) by
John Wiley & Sons. Since it is copyrighted and in press, I cannot
send you the manuscript, but here are the synopsis and references
with some Internet sites that you may find useful before the book
hits the shelves.
Janusz Z. Byczkowski, Ph.D.,D.Sc.,D.A.B.T.
212 N. Central Ave.
Fairborn, OH 45324
JZB Consulting web site: http://members.aol.com/JanuszB/consult.htm
5.3. "Modeling of trace element species in health and disease"
5.3.1. Pharmacokinetic Approach and Mathematical Modeling
18.104.22.168. PK Modeling Methods
(1) Descriptive PK Models
(2) Predictive PBPK Models
22.214.171.124. Descriptive PK Models of Nickel and Cadmium
a. Noncompartmental Approach
b. Compartmental Model
126.96.36.199. Predictive PBPK model of chromium
188.8.131.52. Other successful PBPK models of metals
(1) PBPK model of methylmercury in human gestation and development
(2) Biokinetic model of lead (IEUBK).
5.3.1. 5. Conclusions
(1) A.P. Kulkarni and J.Z. Byczkowski, 'Effects of transition metals
on biological oxidations' in "Environmental Oxidants", Advances in
Environmental Sciences and Technology, J.O. Nriagu (Ed.), J. Wiley &
Sons, New York, NY, Chapter 16, pp. 475 - 496 (1994).
(2) J.Z. Byczkowski and J.R.J. Sorenson, Sci. Total. Environ., 37, 133 (1984).
(3) C.A. Menzie, 'Hormesis in Ecological Risk Assessment: a Useful
Concept, a Confusing Term, and/or a Distraction?' in "The Role of
Hormesis in Ecotoxicology and Ecological Risk Assessment", Belle
Newsletter, 10 (1), 7 (2001). Also available on the World Wide Web:
(4) J.Z. Byczkowski, 'Pharmacokinetic/Dynamic Modeling', in
"Standard Handbook of Environmental Science, Health and Technology",
J. Lehr (Ed.), McGraw-Hill, New York, NY, Chapter 8.6 (2000).
(5) M. Gibaldi and D. Perrier, 'Pharmacokinetics', Marcel Dekker,
New York, NY, 2nd ed. (1982).
(6) F.W. Sunderman, Jr, 'Toxicokinetics of Nickel in Humans', in
"Nickel and Human Health, Current Perspectives", Advances in
Environmental Sciences and Technology, E. Nieboer and J.O. Nriagu
(Eds), J. Wiley & Sons, New York, NY, Chapter 5, pp. 69 - 76 (1992).
(7) T. Kjellstr–m and G.F. Nordberg, Environ. Res., 16, 248 (1978).
(8) S.H. Yang and M.E. Andersen, 'Pharmacokinetics' in "Introduction
to Biochemical Toxicology", E. Hodgson and P.E. Levi (Eds), Appleton
& Lange, Norwalk, CT, 2nd ed., Chapter 3, pp. 49-73 (1994).
(9) E.J. O'Flaherty, B.D. Kerger, S.M. Hays, and D.J. Paustenbach,
Toxicol. Sci., 60, 196 (2001).
(10) H.J. Clewell, J.M. Gearhart, P.R. Gentry, T.R. Covington, C.B.
VanLandingham, K.S. Crump, and A.M. Shipp, Risk Analysis, 19, 547
(11) J.Z. Byczkowski and J.C. Lipscomb, Risk Analysis, 21, 869 (2001).
(12) R. Rozanska, B. Baranowska-Dutkiewicz, and T. Dutkiewicz, Int.
J. Occupat. Med. Environ. Health, 9, 37 (1996).
(13) C.P. Yu, T.H. Hsieh, A.R. Oller, and G. Oberd–rster, Regulatory
Toxicol. Pharmacol., 33, 165 (2001).
(14) D.B. Menzel, Toxicology Lett., 43, 67 (1988).
(15) T. Kjellstr–m and G. Nordberg, 'Kinetic model of cadmium
metabolism' in "Cadmium and Health: A Toxicologic and Epidemiological
Appraisal. Vol. I. Exposure, Dose and Metabolism", CRC Press, Boca
Raton, FL, pp. 179-197 (1985).
(16) L. Friberg, M. Piscator, G.F. Nordberg, and T. Kjellstr–m,
"Cadmium in the Environment", CRC Press, Cleveland, OH. pp. 79-89
(17) G. Oberd–rster, 'Deposition and retention modeling of inhaled
cadmium in rat and human lung: An example for extrapolation of
effects and risk estimation' in "Extrapolation of Dosimetric
Relationships for Inhaled Particles and Gases", Academic Press, NY,
pp. 345-370 (1989).
(18) J.Z. Byczkowski, "Linear PK Model for Cadmium Inhalation - KNOB,
codes and parameters" available on the World Wide Web:
(19) ATSDR (Agency for Toxic Substances and Disease Registry),
"Toxicological Profile for Cadmium" U.S. Department of Health and
Human Services, Public Health Service, Atlanta, GA (1999). Also
available on the World Wide Web:
(20) J.M. Frazier, 'Need for physiologically based toxicokinetic
models estimating target organ dosage following oral ingestion of
cadmium', in "Water Contamination and Health", R.G.M. Wang (Ed.),
Marcel Dekker, Inc., New York, NY, pp. 281 - 304 (1994).
(21) E.J. O'Flaherty, Toxicol. Appl. Pharmacol., 138, 54 (1996).
(22) ATSDR (Agency for Toxic Substances and Disease Registry),
"Toxicological Profile for Chromium" U.S. Department of Health and
Human Services, Public Health Service, Atlanta, GA (2000). Also
available on the World Wide Web:
(23) E.J. O'Flaherty, Critical Rev. Toxicol., 28, 271 (1998).
(24) J.M. Gearhart, H.J. Clewell III, K.S. Crump, A.M. Shipp, and A.
Silvers, Water, Air, and Soil Pollution., 80, 49 (1995).
(25) J.Z. Byczkowski, Drug Inf. J. 30, 401 (1996).
(26) J.Z. Byczkowski, E.R. Kinkead, H.F. Leahy, G.M. Randall and J.W.
Fisher, Toxicol. Appl. Pharmacol. 125, 228 (1994).
(27) J.Z. Byczkowski, " Codes of a PBPK Model for Lactational
Transfer of Methylmercury" available on the World Wide Web:
(28) U.S. EPA - TRW (U.S. Environmental Protection Agency - Technical
Review Workgroup for Lead), "The Integrated Exposure Uptake
Biokinetic (IEUBK) Model for Lead in Children" Build 244 posted on
October 15, 2001, available on the World Wide Web:
(29) P. White, P. Van Leeuwen, B. Davis, M. Maddaloni, K. Hogan, A.
Marcus, and R. Elias, Environmental Health Perspectives 106 (Suppl.
6), 1513 (1998).
(30) L. Zaragoza and K. Hogan, Environmental Health Perspectives 106
(Suppl. 6), 1555 (1998).
(31) E.J. O'Flaherty, Toxicology Lett. 82/83, 367 (1995).
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