1. A Small Dose of Toxicology Children & Environment – 6/25/05 Children: The Health Effects of A Small Dose of Chemicals A Small Dose of Toxicology Steven G. Gilbert, PhD, DABT www.asmalldoseof.org Children and Their Environment June 25, 2005

2. A Small Dose of ToxicologyChildren & Environment – 6/25/05 A Small Dose of Toxicology See: www.asmalldoseof.org -- smdosesmdose

3. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Child Health

4. A Small Dose of ToxicologyChildren & Environment – 6/25/05 "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 The First Bioethicist ---------- 1887 - 1948 ---------- Aldo Leopold

5. A Small Dose of ToxicologyChildren & Environment – 6/25/05 “An ethic, ecologically, is a limitation on freedom of action in the struggle for existence” Aldo Leopold Limits on Freedom

6. A Small Dose of ToxicologyChildren & Environment – 6/25/05 “The Commons” The Tragedy of the Commons By Garrett Hardin, Science, 1968

7. A Small Dose of ToxicologyChildren & Environment – 6/25/05 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

8. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Problems – Solutions?  Lead and kids  Fetal alcohol syndrome  Nuclear disarmament  Bioterrorism  Ocean Fisheries  Persistent chemicals  The Commons

9. A Small Dose of ToxicologyChildren & Environment – 6/25/05 The study of poisons or the adverse effects of chemical and physical agents on living organisms. Toxicology Definitions

10. A Small Dose of ToxicologyChildren & Environment – 6/25/05 399 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

11. A Small Dose of ToxicologyChildren & Environment – 6/25/05 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 Historical Awareness

12. A Small Dose of ToxicologyChildren & Environment – 6/25/05 “Conditions that ensure that all living things have the best opportunity to reach and maintain their full genetic potential.” Steven G. Gilbert, 1999 Environmental & Human Health

13. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Hong Kong Princess Diana Ambassador to Mexico Coeur d’Alene, Silver Valley, ID Tacoma Seattle Schools $100 Billion, $65 Billion Food, noise, dust 11,000 to 689,000 Children What do these have in common?

14. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Who are these white guys?

15. A Small Dose of ToxicologyChildren & Environment – 6/25/05 What Is This? N N N N CH 3 O O 1 3 7

16. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Key Words Risk = Hazard X Exposure Dose / Response Individual Sensitivity

17. A Small Dose of ToxicologyChildren & Environment – 6/25/05 “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

18. A Small Dose of ToxicologyChildren & Environment – 6/25/05 “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

19. A Small Dose of ToxicologyChildren & Environment – 6/25/05 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

20. A Small Dose of ToxicologyChildren & Environment – 6/25/05 What Is This? C H H HOHC H H (CH 3 -CH 2 - OH)

21. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Effects of Prenatal Alcohol

22. A Small Dose of ToxicologyChildren & Environment – 6/25/05 FAS Child

23. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Fetal Effects of MeHg

24. A Small Dose of ToxicologyChildren & Environment – 6/25/05 The Mercury Cycle

25. A Small Dose of Toxicology Children & Environment – 6/25/05 A Small Dose of Lead

26. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Lead In Homes

27. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Lead History Greek 2 nd BC Lead Makes the Mind Give Way

28. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Lead in Families

29. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Agency Blood Lead Levels

30. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Structure of PBDEs X & Y are number of Bromine atoms Common Penta, Octa, and Deca PolyBrominated Diphenyl Ether O Br x Br y

31. A Small Dose of ToxicologyChildren & Environment – 6/25/05 PBDEs in House Dust (ppb) From EWG - Toxic Fire Retardants Contaminate American Homes - http://www.ewg.org/reports/inthedust/summary.php

32. A Small Dose of ToxicologyChildren & Environment – 6/25/05 PBDEs in Breast Milk (ppb) From EWG - Toxic Fire Retardants in Breast Milk from American Mothers - http://www.ewg.org/reports/mothersmilk/es.php

33. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Key Words Risk = Hazard X Exposure Dose / Response Individual Sensitivity

34. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Effects of Amount on Response

35. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Effects of Size on Response

36. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Glasses of Wine - Dose Response 0 25 50 75 100 012345678 Glasses of Wine % Difficulty Walking All Effected NO Effect Amount half are effected

37. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Dose (mg/kg body weight) Increasing dose Dose Response Function 0 25 50 75 100 0102030405060708090100 % Response NO Effect All Effected Half Effected

38. A Small Dose of ToxicologyChildren & Environment – 6/25/05 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)

39. A Small Dose of ToxicologyChildren & Environment – 6/25/05 1) Skin (dermal) 2) Lung (inhalation) 3) Oral (gut) Route of exposure Exposure & Absorption

40. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Number of Times Time Between 4 Beers in an hour or 4 Beers in 4 Days Frequency Of Exposure

41. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Acute Exposure Sub-chronic Exposure Chronic Exposure Duration Of Exposure

42. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Where It Goes (body water, fat, bone) Where It Accumulates Distribution

43. A Small Dose of ToxicologyChildren & Environment – 6/25/05 How The Body Breaks It Down What It Turns Into How Fast It Does It Metabolism

44. A Small Dose of ToxicologyChildren & Environment – 6/25/05 N N N N CH 3 O O 1 3 7 Caffeine - 1,3,7 Trimethylxanthine

45. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Concentration (µg/ml) Time (hrs) How Long It Takes To Go Half-life 0 2 4 6 8 10 12 14 01234567891011

46. A Small Dose of ToxicologyChildren & Environment – 6/25/05 “Conclusions: Blood lead concentrations, even those below 10 mgc/dL, are inversely associated with children’s IQ scores at three and five years of age, and associated declines in IQ are greater at these concentrations than at higher concentrations. These findings suggest that more U.S. children may be adversely affected by environmental lead than previously estimated.” Canfield et al. 2003, NEJM, 384 Canfield et al…, 2003

47. A Small Dose of ToxicologyChildren & Environment – 6/25/05 25 DAYS -- BLOOD 40 DAYS -- SOFT TISSUE 20 YEARS -- BONE Half-life Of Lead

48. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Lead Based Paint 1887 - US medical authorities diagnose childhood lead poisoning 1904 - Child lead poisoning linked to lead-based paints 1909 - France, Belgium and Austria ban white-lead interior paint 1914- Pediatric lead-paint poisoning death from eating crib paint is described 1921 - National Lead Company admits lead is a poison 1922 - League of Nations bans white-lead interior paint; US declines to adopt 1943- Report concludes eating lead paint chips causes physical and neurological disorders, behavior, learning and intelligence problems in children 1971- Lead-Based Paint Poisoning Prevention Act passed

49. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Lead Industry Advertisements http://www.cincinnatichildrens.org/research/project/enviro/hazard/lead/lead-advertising/default.htmhttp://www.cincinnatichildrens.org/research/project/enviro/hazard/lead/lead-advertising/default.htm History of Lead Industry Advertisements (LINK)LINK http://www.cincinnatichildrens.org/research/project/enviro/hazard/lead/lead-advertising/default.htm

50. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Lead-associated Reading Deficits in U.S. Children Blood lead levels (  g/dl) Reading Score Lanphear BP, et al. Public Health Reports 2000;115:521-529. (BL’s slide)

51. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Canfield R, et al. NEJM 2003;348:1517-1526 IQ and Blood Lead Life time overall Increase in 1 mcg/dl = 0.87 IQ drop Covariates - 1 mcg/dl = 0.46 IQ drop 1 to 10 mcg/dl (bigger drop) Increase in 1 mcg/dl = 1.37 IQ drop Non-linear - 1 mcg/dl = 7.4 IQ drop

52. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Environmental Pollutants and Disease in American Children: Estimates of Morbidity, and Costs for Lead Poisoning, Asthma, Cancer, and Developmental Disabilities, by Landrigan, P. et al. EHP, 110, July 2002, 721-728. Cost of Childhood Lead Assumptions in calculating costs All lead is harmful and from environment Blood lead of children age 5 – 2.7 ug/dl (CDC) 5-year old boys (1,960,200) and girls (1,869,800) 1 ug/dl of lead = 0.25 IQ point reduction Cost – boys $27.8 and girls $15.6 Billion Total Costs $43.4 Billion

53. A Small Dose of Toxicology Children & Environment – 6/25/05 Current CDC Policy Blood lead level µg/dL) b Actions Time frame for beginning intervention 10-14Provide caregiver lead education. Provide follow-up testing. Refer the child for social services if necessary. Within 30 days 15-19Above actions, plus: If BLLs persist (i.e., 2 venous BLLs in this range at least 3 months apart) or increase, proceed according to actions for BLLs 20-44. Within 2 weeks 20-44Above actions, plus: Provide coordination of care (case management). Provide clinical evaluation and care. c Provide environmental investigation and control current lead hazards. Within 1 week 45-70Above actions.Within 48 hours 70 or higherAbove actions, plus hospitalize child for chelation therapy immediately. Within 24 hours

54. A Small Dose of Toxicology Children & Environment – 6/25/05 Proposed CDC Policy Blood lead level (µg/dL) ActionsTime frame for beginning intervention <2No action 2-5Provide caregiver lead education. Provide follow-up testing. Refer the child for social services to investigate possible sources of lead exposure. Within 30 days 5-10Above actions, plus:If BLLs persist (i.e., 2 venous BLLs in this range at least 3 months apart) or increase, proceed according to actions for BLLs 10-20. Within 2 weeks 10-20Above actions, plus: Provide coordination of care (case management). Provide clinical evaluation and care. Provide environmental investigation and control current lead hazards. Within 1 week 20-70Above actions.Within 24 hours 70 or higherAbove actions, plus hospitalize child for chelation therapy immediately. Within 24 hours

55. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Recycling Lead

56. A Small Dose of Toxicology Children & Environment – 6/25/05 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.

57. A Small Dose of ToxicologyChildren & Environment – 6/25/05 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

58. A Small Dose of ToxicologyChildren & Environment – 6/25/05 The Potential of Children

59. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Principles of Toxicology www.asmalldoseof.org

60. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Additional Information A Small Dose of Toxicology www.asmalldoseof.org Inst. Children’s Env Health (ICEH) –www.iceh.org

61. A Small Dose of ToxicologyChildren & Environment – 6/25/05 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”

62. A Small Dose of Toxicology Children & Environment – 6/25/05 An Introduction To The Health Effects of Arsenic (As) A Small Dose of ™ Arsenic

63. A Small Dose of ToxicologyChildren & Environment – 6/25/05 A Therapeutic Agent and A Poison 2400 Years Ago In Greece and Rome Ancient Awareness

64. A Small Dose of ToxicologyChildren & Environment – 6/25/05 For many years used to treat syphilis and amebic dysentery But caused skin cancer in patients treated with arsenicals Historical Awareness

65. A Small Dose of ToxicologyChildren & Environment – 6/25/05 By product of smelting for cooper, lead, zinc Last smelter in Tacoma Washington closed in 1985 – still dealing with pollution issues Annual use 20,000 tons imported Production

66. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Chronic exposure (drinking water) Skin cancer (recognized 100 years ago) Garlic odor on breath Excessive perspiration Muscle tenderness and weakness Changes in skin pigmentation Paresthesia in hands and feet Peripheral vascular disease Gangrene of feet – Blackfoot disease Chronic - Toxicity

67. A Small Dose of ToxicologyChildren & Environment – 6/25/05 Exposure  Drinking water  Burning arsenic treated wood  Handling treated wood

68. A Small Dose of ToxicologyChildren & Environment – 6/25/05 US Arsenic Map

69. A Small Dose of ToxicologyChildren & Environment – 6/25/05  Arsenic in drinking water is a worldwide human health hazard  Avoid the use of arsenic treated wood  Reduce or avoid arsenic exposure Summary

70. A Small Dose of Toxicology Children & Environment – 6/25/05 Children with >10 mcg/dL In 1999 and 2000, 2.2% of children 1-5 year age had lead levels that were above 10 mcg/dL. Approximately 20 million children under age 5, thus about 440,000 children in the US have blood lead levels above 10 mcg/dL. From CDC