1. April 4, 2019
A Small Dose of Toxicology - Overview

2. Precautionary Assessment
April 4, 2019
Precautionary Assessment
“Precautionary Assessment"-- a community approach to risk assessment (Critical Analysis of Risk Assessment & Alternative Approaches)
Northwest Toxic Communities Coalition April 5,, 2009
Steven G. Gilbert, PhD, DABT
A Small Dose of Toxicology - Overview

3. April 4, 2019
Doubt Is Their Product
How Industry’s Assault on Science Threatens Your Health”
David Michaels
Oxford
A Small Dose of Toxicology - Overview

4. A Small Dose of Toxicology
April 4, 2019
A Small Dose of Toxicology
See: smdose
A Small Dose of Toxicology - Overview

5. Small Dose of Toxicology
April 4, 2019
Small Dose of Toxicology
A Small Dose of Toxicology - Overview

6. Milestones of Toxicology
April 4, 2019
Milestones of Toxicology
A Small Dose of Toxicology - Overview

7.
A free toxicology encyclopedia and resource center that anyone can edit.
Toxipedia provides comprehensive, accurate, and scientifically based information on the hazards and risks of chemical and physical agents, with the goal of advancing human and environmental health. Toxipedia

9. Coupling art and science to forge a more healthy and peaceful world
Healthy World Theater
Coupling art and science to forge a more healthy and peaceful world
Healthy World Theater reaches to the heart to promote awareness and understanding through the arts to create a more healthy and peaceful world so that all creatures may reach, maintain, and enjoy their potential.

10. World Library of Toxicology – www.wltox.org

11. LDDI Consensus Statement
April 4, 2019
LDDI Consensus Statement
Scientific Consensus Statement on Environmental Agents Associated with Neurodevelopmental Disorders
Developed by the Collaborative on Health and the Environment’s
Learning and Developmental Disabilities Initiative
November 7, 2007
A Small Dose of Toxicology - Overview

12. Child Health

13. So Many Chemicals so Little Data
April 4, 2019
So Many Chemicals so Little Data
2863 above 1 Million pounds
12 or 0.4%
good data
21.4% some
data
78.2% no data
A Small Dose of Toxicology - Overview

14. April 4, 2019
The Consequences
Nearly 12 million children (17%) under age 18 in the US suffer from one or more developmental disabilities
Learning disabilities – 5-10% of kids in public school
ADHD – 3-6% of all school kids, maybe higher
A Small Dose of Toxicology - Overview

15. April 4, 2019
Risk Assessment
"We should remember that risk assessment data can be like the captured spy: If you torture it long enough, it will tell you anything you want to know."
(William Ruckelshaus -1st administrator of U.S. EPA 1984.)
A Small Dose of Toxicology - Overview

16. April 4, 2019
Risk Assessment
Philip Handler said about balancing risks and benefits:
“A sensible guide would surely be to reduce exposure to hazard whenever possible, to accept substantial hazard only for great benefit, minor hazard for modest benefit, and no hazard at all when the benefit seems relatively trivial.” (Handler, 1979).
Handler P Some comments on risk. In: The National Research Council in 1979; Current Issues and Studies. Washington, DC: National Academy of Sciences, 3-24.
A Small Dose of Toxicology - Overview

17. Risk Assessment – Arbitrary and Capricious
April 4, 2019
Outline
Risk Assessment – Arbitrary and Capricious
Vision and Ethics
Principles of Risk Assessment
Risk Assessment - examples
Weaknesses of Risk Assessment
Beyond Risk Assessment to Precautionary Assessment
A Small Dose of Toxicology - Overview

18. Vision for Child Health
April 4, 2019
Vision for Child Health
“Children can develop and mature in an environment that allows them to reach and maintain their full potential.”
A Small Dose of Toxicology - Overview

19. Human & Environmental Health
April 4, 2019
Human & Environmental Health
“Conditions that ensure that all living things have the best opportunity to reach and maintain their full genetic potential.”
S. Gilbert (1999)
A Small Dose of Toxicology - Overview

20. Socially responsible white guys?
April 4, 2019
Socially responsible white guys?
A Small Dose of Toxicology - Overview

21. Aldo Leopold The First Bioethicist
April 4, 2019
The First Bioethicist
Aldo Leopold
"A thing is right when it tends to preserve the integrity, stability, and beauty of the biotic community. It is wrong when it tends otherwise." - Aldo Leopold, 1949, A Sand County Almanac
A Small Dose of Toxicology - Overview

22. April 4, 2019
Limits on Freedom
“An ethic, ecologically, is a limitation on freedom of action in the struggle for existence”
Aldo Leopold
A Small Dose of Toxicology - Overview

23. “The Commons” The Tragedy of the Commons
April 4, 2019
“The Commons”
The Tragedy of the Commons
By Garrett Hardin, Science, 1968
A Small Dose of Toxicology - Overview

24. The Tragedy of the Commons By Garrett Hardin, Science, 1968
April 4, 2019
Technical Solutions
“It is our considered professional judgment that this dilemma has no technical solution.”
The Tragedy of the Commons
By Garrett Hardin, Science, 1968
A Small Dose of Toxicology - Overview

25. Problems – Solutions? Lead and kids Fetal alcohol syndrome
April 4, 2019
Problems – Solutions?
Lead and kids
Fetal alcohol syndrome
Nuclear disarmament
Bioterrorism
Ocean Fisheries
Persistent chemicals
The Commons
Another point that Hardin made was that many problems do not have a technical solution – these can range from Tick-tack-toe to disarmament to managing fish stocks and to many of the issues that our panelist will briefly discuss.
A Small Dose of Toxicology - Overview

26. Sir Austin Bradford Hill
April 4, 2019
Sir Austin Bradford Hill
"All scientific work is incomplete - whether it be observational or experimental. All scientific work is liable to be upset or modified by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have or postpone the action that it appears to demand at a given time. "
Sir Austin Bradford Hill (1965)
A Small Dose of Toxicology - Overview

27. Determining Causation
April 4, 2019
Determining Causation
Strength of association
Consistency of findings
Biological gradient
Temporal sequence
Biologic or theoretical plausibility
Coherence with established knowledge
Specificity of association
Sir Austin Bradford Hill (1965)
A Small Dose of Toxicology - Overview

28. Precautionary Principle
April 4, 2019
Precautionary Principle
“When an activity raises threats of harm to human health or the environment, precautionary measures should be take even if some cause and effect relationships are not fully established scientifically.”
Wingspread Conference, 1998.
A Small Dose of Toxicology - Overview

29. Central components Setting goals (Health indicators)
April 4, 2019
Central components
Setting goals (Health indicators)
Taking preventive action in the face of uncertainty
Shifting the burden of responsibility to the proponents of an activity (Who benefits?)
Exploring a wide range of alternatives to possibly harmful actions (Is it necessary?)
Increasing public participation in decision making (transparency of information & environmental justice)
A Small Dose of Toxicology - Overview

30. Key Words of Toxicology
April 4, 2019
Key Words of Toxicology
Dose / Response
Hazard X Exposure = Risk
Individual Susceptibility
A Small Dose of Toxicology - Overview

31. Modern Risk Assessment
April 4, 2019
Modern Risk Assessment
Developed in s
Concern over increased cancer rates
Expanded to non-cancer effects
A Small Dose of Toxicology - Overview

32. April 4, 2019
Perspective
"If someone had evaluated the risk of fire right after it was invented, they may well have decided to eat their food raw."
Julian Morris of the Institute of Economic Affairs in London
A Small Dose of Toxicology - Overview

33. Quantitative Risk Assessment
April 4, 2019
Quantitative Risk Assessment
Process of estimating association between an exposure to a chemical or physical agent and the incidence of some adverse outcome.
National Research Council, Risk Assessment in the Federal Government: Managing the Process. National Academy Press, Washington, DC, 1983
A Small Dose of Toxicology - Overview

34. Steps in Risk Assessment
April 4, 2019
Steps in Risk Assessment
Hazard Identification
Exposure Assessment
Dose-Response Assessment
Risk Characterization
A Small Dose of Toxicology - Overview

35. What Hazard? Obvious Subtle
April 4, 2019
What Hazard?
Obvious
Death, Cancer, Acid burn, Birth defect, asthma …..
Subtle
Decreases in learning and memory (lead)
Loss of potential
Sensitivity of the individual (child)
A Small Dose of Toxicology - Overview

36. Hazard Identification
April 4, 2019
Hazard Identification
Review human and animal data to determine if a chemical or agent has biological effects.
A Small Dose of Toxicology - Overview

37. Toxicity Endpoints Carcinogenicity Mutations Altered immune function
April 4, 2019
Toxicity Endpoints
Carcinogenicity
Mutations
Altered immune function
Teratogenicity
Altered reproductive function
Neuro-behavioral toxicity
Organ-specific effects
Ecological effects (wildlife, environmental persistence)
A Small Dose of Toxicology - Overview

38. Exposure Assessment Route of exposure (skin, oral, inhalation)
April 4, 2019
Exposure Assessment
Route of exposure (skin, oral, inhalation)
Amount of exposure (dose)
Duration of exposure
To whom (animals, humans, environment)
Children, other sensitive individuals
A Small Dose of Toxicology - Overview

39. Exposure Issues Home environment Workplace (occupational) School Food
April 4, 2019
Exposure Issues
Home environment
Workplace (occupational)
School
Food
Consumer products
Global and local environment
A Small Dose of Toxicology - Overview

40. Dose-Response Assessment
April 4, 2019
Dose-Response Assessment
How much exposure to a chemical or agent will cause what effect?
Dose – Response
A Small Dose of Toxicology - Overview

41. Some Jargon LOAEL – Lowest Observed Adverse Effect Level (mg/kg)
April 4, 2019
Some Jargon
LOAEL – Lowest Observed Adverse Effect Level (mg/kg)
NOAEL – No Observed Adverse Effect Level (mg/kg)
RfD – Reference Dose (mg/kg-day)
A Small Dose of Toxicology - Overview

42. Greater Dose – Greater Response
April 4, 2019
Greater Dose – Greater Response
Response
ED50
Threshold (NOAEL)
LOAEL
Dose
A Small Dose of Toxicology - Overview

43. Risk Characterization
April 4, 2019
Risk Characterization
Risk = Hazard X Exposure
Hazard (including sensitive populations)
Low dose extrapolation
Exposure
Route of exposure, amount, duration
dermal, oral, inhalation, injection
To Whom? Sensitive Individuals?
A Small Dose of Toxicology - Overview

44. Use of Uncertainty Factors
April 4, 2019
Use of Uncertainty Factors
Divide Dose by Power of 10
Human variability
Interspecies extrapolation
Children
Subchronic to chronic extrapolation
Absence of a NOAEL
Database uncertainty
A Small Dose of Toxicology - Overview

45. Human Subject Variability
April 4, 2019
Human Variability
Human Subject Variability
Lifestyle – risk of exposure to ….
Occupation – risk of exposure to ….
Breathing & digestion – uptake of chemicals
Metabolism & kidney function – elimination
Age, gender & disease – susceptibility to toxicity
Socio/economic facts
A Small Dose of Toxicology - Overview

46. April 4, 2019
Doubt / Uncertainty
"Doubt is our product since it is the best means of competing with the 'body of fact' that exists in the mind of the general public.“
1969 an executive at Brown & Williamson owned by R. J. Reynolds Tobacco Company
(Doubt Is Their Product by David Michaels in Scientific American, June 15, 2005)
A Small Dose of Toxicology - Overview

47. Use of Uncertainty Factors
April 4, 2019
Use of Uncertainty Factors
Animal Dose Response Data
NOAEL (No Observed Adverse Effect Level) or LOAEL
Divide by 10
(Account for inadequate animal data)
(Animal to Human Extrapolation)
(Human Variability or Individual Sensitivity)
Reference Dose (RfD) Or Acceptable Daily Intake (ADI)
A Small Dose of Toxicology - Overview

48. What Is This? O CH3 CH3 N N O N N CH3 7 1 3 April 4, 2019
Caffeine – 1,3,7-trimethylxanthine N
CH3
A Small Dose of Toxicology - Overview

49. Mercury & Toxicology

50. April 4, 2019
The Mercury Cycle
A Small Dose of Toxicology - Overview

51. April 4, 2019
Atmospheric Hg
A Small Dose of Toxicology - Overview

52. Neurobehavioral Effects
Blindness - Deafness
Cerebral Palsy - Seizures
Abnormal reflexes & muscle tone
Retarded motor development
Visual and Auditory Deficits
Delayed motor development
Human and animal data

53. Effects On The Brain Decrease in Brain Size Cell loss
Disorganization of cells
Cell migration failures
Behavioral effects – learning and memory

54. Fetal Effects of MeHg

55. Animal - Risk Assessment
MONKEY - 25 µg/kg - LOAEL
RAT - 10 µg/kg - LOAEL
RAT - 50 µg/kg - replicated

56. Animal - Risk Assessment
2.5 µg/kg NOAEL (animals)
0.25 µg/kg - Human
0.025 µg/kg - Sensitive populations
(the rule of dividing by 10)

57. Human - Risk Assessment
• ppm hair - LOAEL •
• ppb blood - LOAEL •
• µg/kg •
• 0.06 µg/kg - RfD •
Gilbert, S.G., and Grant-Webster, K.S. Neurobehavioral effects of developmental methylmercury exposure. Env. Health Persep. 103(Suppl 6), , 1995.

58. MeHg Consumption Limits
US EPA – 0.1 ug/kg-day
US FDA – 1 ppm (mg/kg) in tuna

59. "Lead makes the mind give way."
Ancient Awareness
"Lead makes the mind give way."
Greek
Dioscerides - 2nd BC

60. Agency Blood Lead Levels

61. Recycling Lead

62. Limitations of Risk Assessment
April 4, 2019
Limitations of Risk Assessment
Lack of adequate data
Most sensitive endpoint
Low dose extrapolation
Exposure information
Multiple chemical exposures
Complex – expert driven – undemocratic
Individual sensitivity
Narrow perspective – Ethical??
A Small Dose of Toxicology - Overview

63. Precautionary Assessment
April 4, 2019
Precautionary Assessment
An approach to evaluating the scientific, safety, community, ethical, and social issues related to a compound or procedure.
Community / Social Issues
Exposure Issues
Hazard / Toxicity
A Small Dose of Toxicology - Overview

64. Precautionary Assessment
April 4, 2019
Precautionary Assessment
Community / Social Issues
G = Goal
N = Need
F = Future Generations
D = Democratic, community based process
A = Alternatives
A Small Dose of Toxicology - Overview

65. Precautionary Assessment
April 4, 2019
Precautionary Assessment
Initial
Parameter
Score
Comment
Community / Social Issues
Evaluate effects on the community and related social issues. G
G=Goal
1-3
1-a lot, 2-some, 3-little. Does this move forward the goal of human and environmental health? N
N=Need
1-a lot, 2-some, 3-little or not sure. Ask the question: Is it necessary? Do we really need this? F
F=Future Generations
1-little, 2-some, 3-high impact. Is there a potential impact on future generations of humans and other species? D
D=Democratic, community based process
1-a lot of community involvement and consultation, 2-some, 3-little. Was the community consulted early and often in the process? Was the process democratic and inclusive. A
A=Alternatives
1-alternatives were carefully considered, 2-some consideration, 3-no consideration. Where alternatives considered?
Total
5-15
5-good, supportive of health and community 15-poor, not supportive of health or community
A Small Dose of Toxicology - Overview

66. Precautionary Assessment
April 4, 2019
Precautionary Assessment
Exposure Issues
E = Exposure
M = Multiple exposures
Ch = Children exposed
CP = Consumer products
O = Occupational exposure
F = Food exposure
A Small Dose of Toxicology - Overview

67. Precautionary Assessment
April 4, 2019
Precautionary Assessment
Exposure Issues
Evaluate potential exposure issues. E
E=Exposure
0-3
0-none, 1-little, 2-some, 3-high. Do we have control over the exposure? M
M=Multiple exposures
0-none, 1-little, 2-some, 3-high. Is there exposure to other chemicals with similar hazard? Ch
Ch=Children exposed
0,3,5
0-none, 3-little, 5-some or high or don't know. Children are often more vulnerable. Are children being exposed. CP
CP=Consumer products
0-not in consumer products, 1-little, 2-some, 3- a lot or do not know. Is this compound in consumer products? O
O=Occupational exposure
0-no occupational exposure, 1-little, 2-some, 3- a lot or do not know. Is there occupational exposure? F
F=Food exposure
0-not in food supply, 1-little, 2-some, 3- a lot or do not know. Is the compound present in the food supply.
Total
0-20
0-no exposure, no problems 20-significant exposure, serious concern
A Small Dose of Toxicology - Overview

68. Precautionary Assessment
April 4, 2019
Precautionary Assessment
Hazard / Toxicity
H = Hazard
IS = Individual Sensitivity
EC = Ecological hazard
UC = Uncertainty
V = Volume
P = Persistent
A Small Dose of Toxicology - Overview

69. Precautionary Assessment
April 4, 2019
Precautionary Assessment
Hazard / Toxicity
Evaluate potential hazards. H
H=Hazard
1,5,10
1-low, 5-some, 10-high. Follow classical hazard evaluation, pick endpoint, exam relevant quality studies (cancer, reproductive, neurotoxicity, irreversible) IS
IS=Individual Sensitivity
1-3
1-little 2-some, 3-a lot. Determine if any individuals are more sensitive than health adult such as the very young or old. EC
EC=Ecological hazard
1-little 2-some, 3-a lot. Is it a hazard to other species or the environment? V
V=Volume
1-5
how much is produced (1=research only, 2=<1000 lbs, 3=<10,000, 4=<100,000, 5=>100,000 or do not know) P
P=Persistent
1-little persistence 2-some, 3-a lot of persistence or do not know. Is the compound presistent in the environment? B
B=Bioaccumulate
1-little 2-some, 3-a lot. Does it bioaccumulative in humans or animals or move up the food chain? UC
UC=Uncertainty
1-little 2-some, 3-a lot. How certain is the information?
Total
7-30
7-low hazard 30-significant hazards or unknowns, serious concern
A Small Dose of Toxicology - Overview

70. Precautionary Assessment
April 4, 2019
Precautionary Assessment
Lead
Community / Social Issues - 12/15
Exposure Issues – 16/20
Hazard / Toxicity – 27/30
A Small Dose of Toxicology - Overview

71. April 4, 2019
Rights and Policy
We have a right to an environment in which we can reach and maintain our potential
A matter of POLICY not Risk Assessment
A Small Dose of Toxicology - Overview

72. Precautionary Principle
April 4, 2019
Precautionary Principle
“When an activity raises threats of harm to human health or the environment, precautionary measures should be take even if some cause and effect relationships are not fully established scientifically.”
Wingspread Conference, 1998.
A Small Dose of Toxicology - Overview

73. Central components Setting goals (Health indicators)
April 4, 2019
Central components
Setting goals (Health indicators)
Taking preventive action in the face of uncertainty
Shifting the burden of responsibility to the proponents of an activity (Who benefits?)
Exploring a wide range of alternatives to possibly harmful actions (Is it necessary?)
Increasing public participation in decision making (transparency of information & environmental justice)
A Small Dose of Toxicology - Overview

74. April 4, 2019
WSPHA 2006 Resolutions
The Washington State Public Health Association (WSPHA at unanimously adopted two important resolutions at the 13th Annual Washington State Joint Conference on Health that addressed human health and the environment.
“Endorsing the Precautionary Principle as a Public Health Tool for Preventing Harm from Persistent Bioaccumulative Toxic Chemicals (PBTs)”
Resolved that - “The WSPHA endorses the precautionary principle as a vital component of our preventive approach to public health in Washington State, advancing the goal that all people have an opportunity to reach and maintain their full potential.”
A Small Dose of Toxicology - Overview

75. April 4, 2019
WSPHA 2006 Resolutions
“Supporting Safer Chemicals Policies to Benefit Human and Environmental Health”.
This resolution addressed the need to 1) reduce exposure to PBTs, 2) encourages development and use of safer, cost-effective alternative products, materials, and processes, 3) development of ‘green chemistry’, and 4) provide full information on the health effects of all chemicals placed into the marketplace.
A Small Dose of Toxicology - Overview

76. WSPHA 2008 Resolutions Submittal: October 2008 Annual Meeting
April 4, 2019
WSPHA 2008 Resolutions
Submittal: October 2008 Annual Meeting
Title: Supporting Actions to Reduce Exposures to Lead to Benefit Children’s Health, Learning and Futures
RESOLVED, THAT:
WSPHA supports a reduction of the CDC blood lead level guidelines for action from 10 μg/dL to 2 μg/dL as a crucial step toward achieving a goal that no child in Washington State hasa blood lead level above 2 μg/dL
A Small Dose of Toxicology - Overview

77. Seattle PP working group – CHE-WA
April 4, 2019
Seattle Initiative
City Comprehensive Plans
Every citizen of Seattle has an equal right to a healthy and safe environment.
Seattle sees the Precautionary Principle approach as its policy framework to develop laws for a healthier and more just Seattle.
Seattle Precautionary Principle White Paper (
Seattle PP working group – CHE-WA
A Small Dose of Toxicology - Overview

78. April 4, 2019
Conclusion
The Precautionary Principle is part of the evolution in our thinking and decision making toward ensuring human and environmental health.
A Small Dose of Toxicology - Overview

79. The Potential of Children
April 4, 2019
The Potential of Children
A Small Dose of Toxicology - Overview

80. Additional Information
April 4, 2019
Additional Information
National Research Council, Risk Assessment in the Federal Government: Managing the Process. National Academy Press, Washington, DC, 1983
World Health Organization - The International Programme on Chemical Safety (IPCS) – Risk Assessment –
U.S. Environmental Protection Agencies - National Center for Environmental Assessment (NCEA) –
A Small Dose of Toxicology – Risk Assessment -
A Small Dose of Toxicology - Overview

81. April 4, 2019
Risk Assessment
A Small Dose of Toxicology - Overview

82. Characteristics of Risk
April 4, 2019
Characteristics of Risk
Characteristic Level Examples
Knowledge Little known Food additives
Much known Alcoholic drinks
Newness Old Guns
New Space travel
Voluntariness Not voluntary Crime
Voluntary Rock climbing
Control Not controllable Natural disasters
Controllable Smoking
Dreadedness Little dread Vaccination
Great dread Nerve gas
Catastrophic Not likely Sunbathing
potential Likely War
Equity Distributed Skiing
Undistributed Hazardous dump
Adapted from Kraus and Slovic (1988), Risk Anal., 8: 435.
A Small Dose of Toxicology - Overview

83. Overweight & Obese
April 4, 2019
A Small Dose of Toxicology - Overview

84. Risk Perceptions Unknown w w Knowable w w w w w w w Dread Little Dread
April 4, 2019
Risk Perceptions
Unknown w
Food coloring w
DNA Research
Knowable w w
Saccharin
Nuclear Power
Newness
Lack of scientific knowledge
Exposure is unknown/unknowable
Microwave ovens w w
Asbestos w
Aspirin
Herbicides w
Pesticides w
Dread
Little Dread
Dreaded
Catastrophic potential
Involuntariness
Personal risk
Inequity w
Anesthetics w
Power Tools w
Smoking w w
Dynamite
Alcohol w w
Warfare
Motor vehicles w
Handguns
Known
A Small Dose of Toxicology - Overview

85. Estimated Costs - National
April 4, 2019
Estimated Costs - National
Estimated Costs of Pediatric Disease of Environmental Origin, United States,1997 (billions)
Best Estimate
Low Estimate
High Estimate
Lead Poisoning  
$43.4
Asthma 
$2.0
$0.7
$2.3
Cancer 
$0.3
$0.2
Neurobehavioral Disorders
$9.2
$4.6
$18.4
TOTAL
$54.9
$48.8
$64.8
(From “Environmental Pollutants and Disease in American Children,” Landrigan, Schechter, et.al., 2002)
A Small Dose of Toxicology - Overview

86. Estimated Costs - Washington
April 4, 2019
Estimated Costs - Washington
Diseases and disabilities (asthma, cancer, lead exposure, birth defects, and neurobehavioral effects) attributable to environmental contaminants.
Disease/Disability (2004 $ million)
Best Estimate
Direct Costs
Indirect Costs
Range
Childhood
$1,875
$310.6
$1,565
$1,600-$2,200
Adult & child
$2,734
$782.1
$1,953
$2,800-$3,500
Kate Davies Economic costs of diseases and disabilities attributable to environmental contaminants in Washington State. Antioch University Seattle
A Small Dose of Toxicology - Overview

87. Asthma & Diabetes
April 4, 2019
A Small Dose of Toxicology - Overview