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Human Interindividual Variability in Parameters Related to Health Risks

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  • Dale Hattis
  • J Prerna Banati
  • Rob Goble
  • David E. Burmaster

Abstract

This paper reviews existing data on the variability in parameters relevant for health risk analyses. We cover both exposure‐related parameters andparameters related to individual susceptibility to toxicity. The toxicity/susceptibility data base under construction is part of a longer term research effort to lay the groundwork for quantitative distributional analyses of non‐cancer toxic risks. These data are broken down into a variety of parameter types that encompass different portions of the pathway from external exposure to the production of biological responses. The discrete steps in this pathway, as we now conceive them, are: • Contact Rate (Breathing rates per body weight; fish consumption per bodyweight) • Uptake or Absorption as a Fraction of Intake or Contact Rate • General Systemic Availability Net of First Pass Elimination and Dilutionvia Distribution Volume (e.g., intial blood concentration per mg/kg of uptake) • Systemic Elimination (half life or clearance) • Active Site Concentration per Systemic Blood or Plasma Concentration • Physiological Parameter Change per Active Site Concentration (expressed as the dose required to make a given percentage change in different people, or the dose required to achieve some proportion of an individual's maximum response to the drug or toxicant) • Functional Reserve Capacity‐Change in Baseline Physiological Parameter Needed to Produce a Biological Response or Pass a Criterion of Abnormal Function Comparison of the amounts of variability observed for the different parameter types suggests that appreciable variability is associated with the final step in the process‐differences among people in “functional reserve capacity.” This has the implication that relevant information for estimatingeffective toxic susceptibility distributions may be gleaned by direct studies of the population distributions of key physiological parameters in people that are not exposed to the environmental and occupational toxicants thatare thought to perturb those parameters. This is illustrated with some recent observations of the population distributions of Low Density Lipoprotein Cholesterol from the second and third National Health and Nutrition Examination Surveys.

Suggested Citation

  • Dale Hattis & J Prerna Banati & Rob Goble & David E. Burmaster, 1999. "Human Interindividual Variability in Parameters Related to Health Risks," Risk Analysis, John Wiley & Sons, vol. 19(4), pages 711-726, August.
    • Handle: RePEc:wly:riskan:v:19:y:1999:i:4:p:711-726
    DOI: 10.1111/j.1539-6924.1999.tb00441.x
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    References listed on IDEAS

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    1. Dale Hattis & Linda Erdreich & Mary Ballew, 1987. "Human Variability in Susceptibility to Toxic Chemicals— A Preliminary Analysis of Pharmacokinetic Data from Normal Volunteers," Risk Analysis, John Wiley & Sons, vol. 7(4), pages 415-426, December.
    2. Paul S. Price & Russell E. Keenan & Jeffrey C. Swartout & Carol A. Gillis & Heather Carlson‐Lynch & Michael L. Dourson, 1997. "An Approach for Modeling Noncancer Dose Responses with an Emphasis on Uncertainty," Risk Analysis, John Wiley & Sons, vol. 17(4), pages 427-437, August.
    3. Dale Hattis & Ken Silver, 1994. "Human Interindividual Variability–A Major Source of Uncertainty in Assessing Risks for Noncancer Health Effects," Risk Analysis, John Wiley & Sons, vol. 14(4), pages 421-431, August.
    4. David E. Burmaster & Edmund A. C. Crouch, 1997. "Lognormal Distributions for Body Weight as a Function of Age for Males and Females in the United States, 1976–1980," Risk Analysis, John Wiley & Sons, vol. 17(4), pages 499-505, August.
    5. David E. Burmaster, 1998. "A Lognormal Distribution for Time Spent Showering," Risk Analysis, John Wiley & Sons, vol. 18(1), pages 33-35, February.
    6. David E. Burmaster, 1998. "Lognormal Distributions for Total Water Intake and Tap Water Intake by Pregnant and Lactating Women in the United States," Risk Analysis, John Wiley & Sons, vol. 18(2), pages 215-219, April.
    7. Brent Finley & Deborah Proctor & Paul Scott & Natalie Harrington & Dennis Paustenbach & Paul Price, 1994. "Recommended Distributions for Exposure Factors Frequently Used in Health Risk Assessment," Risk Analysis, John Wiley & Sons, vol. 14(4), pages 533-553, August.
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    1. Hilko Van Der Voet & Wout Slob, 2007. "Integration of Probabilistic Exposure Assessment and Probabilistic Hazard Characterization," Risk Analysis, John Wiley & Sons, vol. 27(2), pages 351-371, April.
    2. Ramya Chari & Thomas A. Burke & Ronald H. White & Mary A. Fox, 2012. "Integrating Susceptibility into Environmental Policy: An Analysis of the National Ambient Air Quality Standard for Lead," IJERPH, MDPI, vol. 9(4), pages 1-20, March.
    3. Dale Hattis & Gary Ginsberg & Bob Sonawane & Susan Smolenski & Abel Russ & Mary Kozlak & Rob Goble, 2003. "Differences in Pharmacokinetics Between Children and Adults—II. Children's Variability in Drug Elimination Half‐Lives and in Some Parameters Needed for Physiologically‐Based Pharmacokinetic Modeling," Risk Analysis, John Wiley & Sons, vol. 23(1), pages 117-142, February.
    4. Leona H. Clark & R. Woodrow Setzer & Hugh A. Barton, 2004. "Framework for Evaluation of Physiologically‐Based Pharmacokinetic Models for Use in Safety or Risk Assessment," Risk Analysis, John Wiley & Sons, vol. 24(6), pages 1697-1717, December.
    5. Lorenz R. Rhomberg, 2010. "Uncertainty Factor Conundrums: What Lessons Should We Draw?," Risk Analysis, John Wiley & Sons, vol. 30(3), pages 349-352, March.

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