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

8. 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

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

10. 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

11. 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

12. 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

13. 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

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

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

16. 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

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

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

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

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

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

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

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

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

25. 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

26. 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

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

28. 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

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

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

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

32. 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

33. 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

34. 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

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

36. 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

37. 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

38. 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

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

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

41. 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

42. 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

43. 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

44. 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

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

46. 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

47. 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

48. 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