1. A Small Dose of ToxicologyPrinciples of Toxicology - 09/11/10 An Very Brief Introduction to the Principles of Toxicology A Nano-Dose of Toxicology Steven G. Gilbert, PhD, DABT www.asmalldoseof.org www.toxipedia.org

2. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 A Small Dose of Toxicology See: www.asmalldoseof.org -- smdosesmdose

3. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Small Dose of Toxicology

4. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Milestones of Toxicology

5. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 www.toxipedia.org 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. ToxipediaToxipedia

6. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Toxipedia suite of sites www.ipmopedia.org www.healthyworldtheater.org www.wanmec.org www.toxipedia.org www.wltox.org

7. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 The World Library of Toxicology

8. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 www.wltox.org

9. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Connecting Gardeners and Experts for Green Gardening Solutions  Identify Your Pest  Find the Right Plant  Ask the Experts  Garden Design Guide  Indoor Pest Control www.ipmopedia.org Supported by Local Hazardous Waste Management Program in King County, WA.

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11. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Healthy World Theater http://healthyworldtheater.org promote awareness and understanding through the arts to create a more healthy and peaceful world plays, poems, jokes, fiction, music, cartoons, haiku, and even limericks

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13. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Washington Nuclear Museum and Educational Center (WANMEC) http://wanmec.org learning from the past for a safer tomorrow a project of Washington Physicians for Social Responsibility - funded in part by WA DOE

14. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Healthy World Press (www.healthyworldpress.org) publishes interdisciplinary books connecting science, history, and art. Healthy World Press Particles on the Wall Particles on the Wall: An interdisciplinary exhibit connecting science and art in exploring the history of Hanford and major themes of today's nuclear age

15. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Toxipedia www.toxipedia.org Connecting Science and People Washington Nuclear Museum and Education Center - www.wanmec.org Integrate Pest Management www.IPMopedia.org World Library of Toxicology www.wltox.org Healthy World Theater www.healthyworldtheater.org A product of the Institute of Neurotoxicology and Neurological Disorders (INND) For more information contact Steven G. Gilbert at sgilbert@innd.org Connecting Gardeners and Experts for Green Gardening Solutions Learning from the past for a safer tomorrow Uniting art and science for a healthy, peaceful world Connecting Scientists and Experts to Improve Global Health Toxicology History Room www.toxhistoyroom.org Particles On The Wall (POTW) www.particlesonthewall.org

16. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 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 http://www.iceh.org/LDDI.html

17. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 LDDI Consensus Statement http://www.iceh.org/LDDI.html Given the established knowledge, protecting children from neurotoxic environmental exposures from the earliest stages of fetal development clearly is an essential public health measure if we are to help prevent learning and developmental disorders and create an environment in which children can reach and maintain their full potential.

18. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 NW Public Health See: http://healthlinks.washington.edu/nwcphp/nph/ nwph Public Health and the Precautionary Principle By Steven G. Gilbert

19. A Small Dose of ToxicologyPrinciples of Toxicology - 09/11/10 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.

20. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 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) Central components

21. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Child Health

22. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 So Many Chemicals so Little Data 2863 above 1 Million pounds 78.2% no data 21.4% some data 12 or 0.4% good data www.preventingharm.org

23. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10  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 The Consequences

24. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 The study of poisons or the adverse effects of chemical and physical agents on living organisms. Toxicology Definitions

25. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 “Conditions that ensure that all living things have the best opportunity to reach and maintain their full genetic potential.” Steven G. Gilbert, 1999 Human & Environmental Health

26. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 What Is This? N N N N CH 3 O O 1 3 7

27. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Key Words Risk = Hazard X Exposure Dose / Response Individual Sensitivity

28. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Thalidomide  Introduced in 1956 as sedative (sleeping pill) and to reduce nausea and vomiting during pregnancy  Withdrawn in 1961  Discovered to be a human teratogen causing absence of limbs or limb malformations in newborns  5000 to 7000 infants effected  Resulted in new drug testing rules

29. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 What Is This? C H H HOHC H H (CH 3 -CH 2 -OH)

30. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Effects of Prenatal Alcohol

31. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 FAS Child

32. A Small Dose of ToxicologyPrinciples of Toxicology - 09/11/10 A Small Dose of Lead

33. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Lead In Homes

34. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Lead History Greek 2 nd BC Lead Makes the Mind Give Way

35. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Recycling Lead

36. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Agency Blood Lead Levels

37. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Glasses of Wine - Dose Response 0 25 50 75 100 012345678 Glasses of Wine % Difficulty Walking All Effected NO Effect Amount half are effected

38. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Dose (mg/kg body weight) Increasing dose Dose Response Function 0 25 50 75 100 0102030405060708090100 % Response NO Effect All Effected Half Effected

39. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 1) Skin (dermal) 2) Lung (inhalation) 3) Oral (gut) Route of exposure Exposure & Absorption

40. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Number of Times Time Between 4 Beers in an hour or 4 Beers in 4 Days Frequency Of Exposure

41. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Acute Exposure Sub-chronic Exposure Chronic Exposure Duration Of Exposure

42. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Where It Goes (body water, fat, bone) Where It Accumulates Distribution

43. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 In utero Infant Pregnancy elderly Timing

44. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 How The Body Breaks It Down What It Turns Into How Fast It Does It Metabolism

45. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 N N N N CH 3 O O 1 3 7 Caffeine - 1,3,7 Trimethylxanthine

46. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Concentration (µg/ml) Time (hrs) How Long It Takes To Go Half-life 0 2 4 6 8 10 12 14 01234567891011

47. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Young or Old Male or Female Individual Variability Genetics Differences Species Differences Susceptibility & Variability

48. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 “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. Precautionary Principle

49. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Taking preventive action in the face of uncertainty Shifting the burden of proof/responsibility to the proponents of an activity Exploring a wide range of alternatives to possibly harmful actions Increasing public participation in decision making Wingspread Conference, 1998. Central components

50. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Children have a right to a safe, fair and healthy environment Ethical Responsibility to share and use of knowledge Duty to promote health and well being of children Thoughtful public health advocate Knowledge - Responsibility

51. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 The Potential of Children

52. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Principles of Toxicology

53. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Authorship Information Steven G. Gilbert, PhD, DABT E-mail: sgilbert@innd.org Web: www.toxipedia.org

54. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 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 http://toxipedia.org/x/H6xb

55. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 LDDI Consensus Statement Given the established knowledge, protecting children from neurotoxic environmental exposures from the earliest stages of fetal development clearly is an essential public health measure if we are to help prevent learning and developmental disorders and create an environment in which children can reach and maintain their full potential. http://toxipedia.org/x/H6xb

56. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 NW Public Health See: http://healthlinks.washington.edu/nwcphp/nph/ nwph Public Health and the Precautionary Principle By Steven G. Gilbert

57. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 N CH 3 N What Is This?

58. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 Structure of PBDEs X & Y are number of Bromine atoms Common Penta, Octa, and Deca PolyBrominated Diphenyl Ether O Br x Br y

59. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 PBDEs in House Dust (ppb) From EWG - Toxic Fire Retardants Contaminate American Homes - http://www.ewg.org/reports/inthedust/summary.php

60. A Small Dose of ToxicologyPrinciples of Toxicology – 09/11/10 PBDEs in Breast Milk (ppb) From EWG - Toxic Fire Retardants in Breast Milk from American Mothers - http://www.ewg.org/reports/mothersmilk/es.php