1. A Small Dose of Toxicology Intro Principles of Toxicology A Small Dose of Toxicology Introduction to the Health Effects of Chemicals Steven G. Gilbert, PhD, DABT www.asmalldoseof.org www.toxipedia.org

2. A Small Dose of Toxicology Intro Principles of Toxicology Child Health

3. A Small Dose of Toxicology Intro Principles of Toxicology The study of poisons or the adverse effects of chemical and physical agents on living organisms. Toxicology Definitions

4. A Small Dose of Toxicology Intro Principles of Toxicology 399 BC Death of Socrates by Hemlock Socrates was charged with religious heresy and corrupting the morals of local youth. The active chemical used was the alkaloid coniine which, when ingested causes paralysis, convulsions and potentially death. Ancient Awareness

5. A Small Dose of Toxicology Intro Principles of Toxicology From Romeo and Juliet - act 5 Come bitter pilot, now at once run on The dashing rocks thy seasick weary bark! Here’s to my love! O true apothecary! Thy drugs are quick. Thus with a kiss I die. Shakespeare (1564-1616) Historical Awareness

6. A Small Dose of Toxicology Intro Principles of Toxicology “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

7. A Small Dose of Toxicology Intro Principles of Toxicology Hong Kong Princess Diana Ambassador to Mexico Coeur d’Alene, Silver Valley, ID Tacoma $100 Billion, $65 Billion Food, noise, dust 11,000 to 689,000 Children What do these have in common?

8. A Small Dose of Toxicology Intro Principles of Toxicology Who are these white guys?

9. A Small Dose of Toxicology Intro Principles of Toxicology “It is not the truth that makes you free. It is your possession of the power to discover the truth. Our dilemma is that we do not know how to provide that power.” Richard Lewontin (New York Review of Books, Jan 7, 1997) Power To Discover The Truth

10. A Small Dose of Toxicology Intro Principles of Toxicology What Is This? N N N N CH 3 O O 1 3 7

11. A Small Dose of Toxicology Intro Principles of Toxicology Key Words Risk = Hazard X Exposure Dose / Response Individual Sensitivity

12. A Small Dose of Toxicology Intro Principles of Toxicology “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy.” Paracelsus (1493-1541) Paracelsus

13. A Small Dose of Toxicology Intro Principles of Toxicology “The sensitivity of the individual differentiates a poison from a remedy. The fundamental principle of toxicology is the individual’s response to a dose.” S. G. Gilbert (1997) An Individual View

14. A Small Dose of Toxicology Intro Principles of Toxicology Superman

15. A Small Dose of Toxicology Intro Principles of Toxicology Neuron

16. A Small Dose of Toxicology Intro Principles of Toxicology 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 Toxicology Intro Principles of Toxicology What Is This? C H H HOHC H H (CH 3 -CH 2 - OH)

18. A Small Dose of Toxicology Intro Principles of Toxicology Effects of Prenatal Alcohol

19. A Small Dose of Toxicology Intro Principles of Toxicology FAS Child

20. A Small Dose of Toxicology Intro Principles of Toxicology Mouse – Scanning EM

21. A Small Dose of Toxicology Intro Principles of Toxicology FAS & FAE Most common preventable cause of adverse CNS development Fetal Alcohol Syndrome (FAS) 4,000-12,000 infants per year in US Fetal Alcohol Effect (FAE) 7,000-36,000 infants per year in US 1 to 3 infants per 1,000 world wide??

22. A Small Dose of Toxicology Intro Principles of Toxicology 1981 - U.S. Surgeon General first advised that women should not drink alcoholic beverages during pregnancy. 1988 - U.S. requires warning labels on all alcoholic beverages sold in the United States. 1990 - U.S. Dietary Guidelines state that women who are pregnant or planning to become pregnant should not drink alcohol. 1998 - 19 states require the posting of alcohol health warning signs where alcoholic beverages are sold Policy Approaches

23. A Small Dose of Toxicology Intro Principles of Toxicology A Small Dose of Lead

24. A Small Dose of Toxicology Intro Principles of Toxicology Lead In Homes

25. A Small Dose of Toxicology Intro Principles of Toxicology Lead History Greek 2 nd BC Lead Makes the Mind Give Way

26. A Small Dose of Toxicology Intro Principles of Toxicology Lead - Absorption Orally Consumed Lead Absorbed In Place of Calcium CHILDREN – 30-50% OF LEAD ADULTS – 5-10% OF LEAD Increased During Pregnancy

27. A Small Dose of Toxicology Intro Principles of Toxicology Children Vulnerability CHILDREN are more vulnerable exposure than ADULTS Size Consume More Food Inhale More Air Developing Nervous System Increased need for Calcium

28. A Small Dose of Toxicology Intro Principles of Toxicology Agency Blood Lead Levels

29. A Small Dose of Toxicology Intro Principles of Toxicology A Small Dose of Mercury

30. A Small Dose of Toxicology Intro Principles of Toxicology The Mercury Cycle

31. A Small Dose of Toxicology Intro Principles of Toxicology Limit the amount of canned tuna you eat, based on your bodyweight. Guidelines are: Women of childbearing age should limit the amount of canned tuna they eat to about one can per week (six ounces.) A woman who weighs less than 135 pounds should eat less than one can of tuna per week. Children under six should eat less than one half a can of tuna (three ounces) per week. Specific weekly limits for children under six range from one ounce for a twenty pound child, to three ounces for a child weighing about sixty pounds. WA State Advisory http://www.doh.wa.gov/fish/FishAdvMercury.htm

32. A Small Dose of Toxicology Intro Principles of Toxicology Structure of PBDEs X & Y are number of Bromine atoms Common Penta, Octa, and Deca PolyBrominated Diphenyl Ether O Br x Br y

33. A Small Dose of Toxicology Intro Principles of Toxicology PBDEs in House Dust (ppb) From EWG - Toxic Fire Retardants Contaminate American Homes - http://www.ewg.org/reports/inthedust/summary.php

34. A Small Dose of Toxicology Intro Principles of Toxicology PBDEs in Breast Milk (ppb) From EWG - Toxic Fire Retardants in Breast Milk from American Mothers - http://www.ewg.org/reports/mothersmilk/es.php

35. A Small Dose of Toxicology Intro Principles of Toxicology PBDEs In Milk Fat (adapted from Northwest Environmental Watch, 2004)

36. A Small Dose of Toxicology Intro Principles of Toxicology Pollution in People http://www.pollutioninpeople.org/

37. A Small Dose of Toxicology Intro Principles of Toxicology Key Words Risk = Hazard X Exposure Dose / Response Individual Sensitivity

38. A Small Dose of Toxicology Intro Principles of Toxicology Effects of Amount on Response

39. A Small Dose of Toxicology Intro Principles of Toxicology Effects of Size on Response

40. A Small Dose of Toxicology Intro Principles of Toxicology Glasses of Wine - Dose Response 0 25 50 75 100 012345678 Glasses of Wine % Difficulty Walking All Effected NO Effect Amount half are effected

41. A Small Dose of Toxicology Intro Principles of Toxicology Dose (mg/kg body weight) Increasing dose Dose Response Function 0 25 50 75 100 0102030405060708090100 % Response NO Effect All Effected Half Effected

42. A Small Dose of Toxicology Intro Principles of Toxicology Ethyl alcohol10,000 Salt (sodium chloride)4,000 Iron (Ferrous sulfate)1,500 Morphine 900 Mothballs 500 (paradichlorobenzene) Aspirin250 DDT250 Cyanide10 Nicotine1 Tetrodotoxin (from fish)0.01 Dioxin (TCDD)0.001 Botulinum Toxin0.00001 Bee Venom?? Agent LD-50 (mg/kg)

43. A Small Dose of Toxicology Intro Principles of Toxicology 1) Skin (dermal) 2) Lung (inhalation) 3) Oral (gut) Route of exposure Exposure & Absorption

44. A Small Dose of Toxicology Intro Principles of Toxicology Number of Times Time Between 4 Beers in an hour or 4 Beers in 4 Days Frequency Of Exposure

45. A Small Dose of Toxicology Intro Principles of Toxicology Acute Exposure Sub-chronic Exposure Chronic Exposure Duration Of Exposure

46. A Small Dose of Toxicology Intro Principles of Toxicology Where It Goes (body water, fat, bone) Where It Accumulates Distribution

47. A Small Dose of Toxicology Intro Principles of Toxicology How The Body Breaks It Down What It Turns Into How Fast It Does It Metabolism

48. A Small Dose of Toxicology Intro Principles of Toxicology N N N N CH 3 O O 1 3 7 Caffeine - 1,3,7 Trimethylxanthine

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

50. A Small Dose of Toxicology Intro Principles of Toxicology Young or Old Male or Female Individual Variability Genetics Differences Species Differences Susceptibility & Variability

51. A Small Dose of Toxicology Intro Principles of Toxicology N CH 3 N What Is This?

52. A Small Dose of Toxicology Intro Principles of Toxicology The Potential of Children

53. A Small Dose of Toxicology Intro Principles of Toxicology Principles of Toxicology

54. A Small Dose of Toxicology Intro Principles of Toxicology Additional Information A Small Dose of Toxicology www.asmalldoseof.org

55. A Small Dose of Toxicology Intro Principles of Toxicology Authorship Information For Additional Information Contact Steven G. Gilbert, PhD, DABT E-mail: smdose@asmalldoseof.org Web: www.asmalldoseof.org This presentation is supplement to “A Small Dose of Toxicology”

56. A Small Dose of Toxicology Intro Principles of Toxicology Pesticide Application

57. A Small Dose of Toxicology Intro Principles of Toxicology Classes Of Pesticides  Insecticides (kill insects) Organochlorines Organophosphates Carbamates Synthetic Pyrethroids  Herbicides (kill plants)  Rodenticides (kill rodents)  Fungicides (kill fungus)  Fumigants (kill whatever)

58. A Small Dose of Toxicology Intro Principles of Toxicology Other Exposure  Dietary exposure Pesticide residues on crops, dust – hand to mouth  Community exposure Airborne drift from commercial app  Contaminated drinking water Leaching from soils to ground water

59. A Small Dose of Toxicology Intro Principles of Toxicology Focus – long-term prevention of pest problems Reduce or eliminate chemical pest control methods Monitor for the presence of pests before treating Nonchemical strategies (make habitat less attractive, physical controls) Learn about your pests Integrated Pest Management (IPM)