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Chemical%20Hormesis

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Environmental Health Sciences Department. University of Massachusetts. Coworker: Linda Baldwin ... be considered as a real concept in the biological sciences ... – PowerPoint PPT presentation

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Title: Chemical%20Hormesis


1
Chemical Hormesis
  • Monty L. Herr, PhD, CIH

2
ParacelsusWhat is it that is not poison? All
things are poison and none without poison. Only
the dose determines that a thing is not poison.
3
Dose-ResponseNoncarcinogenic Effects
  • Threshold Response
  • Can determine a no-effect level

4
Dose-Response Curve
Threshold Response Case
100

o
o
o
Toxic Response Probability
NOAEL
0,0
Dose or Exposure
5
Dose-ResponseCarcinogenic Effects
  • Nonthreshold response
  • No dose is risk free

6
Dose-Response Curve
Zero Threshold Linear Response Case
100

o
o
o
Toxic Response Probability
Zero Threshold
0,0
Dose or Exposure
7
Dose-Response Curve
Non-Linear Response Case - Hormesis
100

o
o
o
Toxic Response Probability
0,0
Dose or Exposure
8
Hormesis Curve
Maximum response (averages 130-160 of control)
Distance to NOAEL (averages 5-fold)
NOAEL
Control
Hormetic Zone (averages 10- to 20-fold)
Increasing Dose
Dose-response curve depicting the quantitative
features of hormesis
9
Ed Calabrese
  • Environmental Health Sciences Department
  • University of Massachusetts
  • Coworker Linda Baldwin

10
Chemical Hormesis
  • BELLE Biological Effects of Low Level Exposures
  • http//www.belleonline.com/
  • Low-dose stimulation/high-dose inhibition -
    Arndt-Schultz Law

11
February 13, 2003
  • Dangerous levels of toxins miscalculated
  • Potential pollutants and poisons may be
    beneficial in low doses.

12

June 9, 2003 A Little Poison Can Be Good For You
The received wisdom about toxins and radiation
may be all wet.

13
  • September 2003
  • HORMESIS
  • Nietzsche's Toxicology
  • Whatever doesn't kill you might make you stronger

14
October 17, 2003
  • HORMESISSipping From a Poisoned Chalice

15
December 12, 2003
A scientist finds benefit in small doses of
toxins

AMHERST -- Edward J. Calabrese, a gray-haired man
who works in a rundown office surrounded by
documents on highly toxic chemicals, has an
explosive idea.
16
  • December 19, 2003
  • Scientists Revisit Idea That a Little Poison
    Could Be Beneficial
  • By Sue Begley

17

18
  • Knight Ridder papers
  • 27 February 2004
  • Hormesis TheoryTiny Bits of Toxins Do Affect
    People
  • By Seth Borenstein

19
  • April 5, 2004
  • LOW-DOSE EFFECTS
  • Debate expands on how to extrapolate data from
    high-dose tests for environmental contaminants.
  • By Cheryl Hogue, pp. 50-54

20

U.S. News and World Report October 18, 2004 Is
There a Tonic in the Toxin?

21
HORMESIS
  • DEFINITION
  • Dose response phenomenon characterized by a low
    dose stimulation and a high dose inhibition.

22
Criteria used to judge data for evidence of
hormesis
  • The magnitude of the low dose stimulatory
    response
  • The number of doses establishing the reliability
    of the beta-curve
  • Statistical power
  • The reproducibility of the findings

23
To evaluate high conformity to the J-curve
  • Establishment of an endpoint-specific lowest
    observed effect level (LOEL) and
    no-observed-effect level (NOEL)
  • expected to have ? 2 doses below the NOEL.

24
Hormesis Curve
Maximum response (averages 130-160 of control)
Distance to NOAEL (averages 5-fold)
NOAEL
Control
Hormetic Zone (averages 10- to 20-fold)
Increasing Dose
Dose-response curve depicting the quantitative
features of hormesis
25


Females





Males

METHANOL
FRUIT FLY LONGEVITY
26




Males

Females

GAMMA RAYS
MOUSE LUNG ADENOMAS
27

Testosterone









Luteinizing hormone

Alcohol and Rat Serum Levels
28







Effects of metals on phagocytosis in the clam,
Mya arenaria, hemocytes
29
(No Transcript)
30
CADMIUM AND RAT TESTICULAR CANCER






Source Waalkes, 1988
31
Results of initial screening organized by agent
  • Agent Percent
  • Alcohol and metabolites 6.2
  • Antibiotics 7.9
  • Auxin related 4.6
  • Hydrocarbons 3.4
  • Metals 29.6
  • Herbicides 7.2
  • Insecticides 6.1
  • Fungicides 1.5
  • Pesticides 2.9
  • Miscellaneous 30.6

32
Results of initial screen organized by endpoint
  • Percent
  • Growth 62.2
  • Metabolic Effects 15.2
  • Longevity 5.2
  • Survival 5.7
  • Reproduction 5.7
  • Miscellaneous 5.8

33
Results of initial screening organized by test
model
  • Percent
  • Bacteria 9.3
  • Protozoa 3.0
  • Fungi 6.4
  • Plants 34.9
  • Animals 46.3

34
Generalizability of Hormesis
  • Numerous species
  • Broad range of chemical classes
  • Broad range of biological endpoints

35
PERSPECTIVE 1
  • HORMESIS a concept with much supportive
    experimental evidence that is reproducible

36
PERSPECTIVE 2
  • HORMESIS Based on Perspective 1 it should be
    considered as a real concept in the biological
    sciences

37
PERSPECTIVE 3
  • HORMESIS IS GENERALIZABLE
  • Across biological models
  • Across endpoints measured
  • Across Chemical Classes/Physical Agents

38
PERSPECTIVE 4
  • Based on Perspective 3, HORMESIS is
    evolutionarily based, with broad potential
    implications

39
PERSPECTIVE 5
  • HORMESIS very common in toxicological/pharmacolo
    gical literature, making it a central concept

40
PERSPECTIVE 6
  • HORMESIS a normal component of the traditional
    dose response, being graphically contiguous with
    the NO(A)EL.

41
PERSPECTIVE 7
  • HORMESIS readily definable quantitative
    features, that are broadly generalizable, making
    it reasonably predictable.

42
PERSPECTIVE 8
  • HORMESIS far more common than the threshold
    dose response in fair, head to head comparisons
  • this would make the hormetic model the most
    dominant in toxicology.

43
PERSPECTIVE 9
  • HORMESIS no single hormetic mechanism there
    appears to be a common underlying biological
    strategy underlying such phenomena.

44
PERSPECTIVE 10
  • HORMESIS important implications for toxicology,
    risk assessment, risk communication, cost-benefit
    assessments, clinical medicine, drug development
    and numerous other areas

45
PERSPECTIVE 11
  • HORMESIS should become the object of formal
    evaluation by leading advisory bodies such as the
    National Academy of Sciences

46
Estimate of articles showing hormesis
  • Total number of toxicology articles published
    since 1900
  • 500,000
  • 2 of the total number employed 6 or more doses
  • 10,000
  • 10 of articles have 3 doses ? NOEL
  • 1000
  • 90 have 3 doses within 2 orders of magnitude of
    NOEL
  • 900

47
Hormesis Curve
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