1. A Small Dose of Lead – 4/28/05 Converging Issues: Lead, Ethics, and Our Children’s Potential or Should the CDC Lower the Blood lead action lever from 10 to 2 mcg/dl? A Small Dose of ™ Lead Wilson Memorial Hospital April 28, 2005 Steven G. Gilbert, PhD, DABT www.asmalldoseof.org

2. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology See: www.asmalldoseof.org -- smdosesmdose

3. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Child Health

4. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology "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 Lead – 4/28/05 A Small Dose of Toxicology “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 Lead – 4/28/05 A Small Dose of Toxicology “The Commons” The Tragedy of the Commons By Garrett Hardin, Science, 1968

7. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology 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 Lead – 4/28/05 A Small Dose of Toxicology Problems – Solutions?  Lead and kids  Fetal alcohol syndrome  Nuclear disarmament  Bioterrorism  Ocean Fisheries  Persistent chemicals  The Commons

9. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology The study of poisons or the adverse effects of chemical and physical agents on living organisms. Toxicology Definitions

10. A Small Dose of Lead – 4/28/05 A Small Dose 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

11. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology 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?

12. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Who are these white guys?

13. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology What Is This? N N N N CH 3 O O 1 3 7

14. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Key Words of Toxicology Hazard + Exposure = Risk Individual Susceptibility Dose / Response

15. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Effects of Amount on Response

16. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Effects of Size on Response

17. A Small Dose of Lead – 4/28/05 A Small Dose 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

18. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology What Is This? C H H HOHC H H (CH 3 -CH 2 - OH)

19. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology FAS Child

20. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology The Mercury Cycle

21. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology “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

22. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology What Is Plumbun? Plumbing is derived from plumbun, Latin for lead

23. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Lead In Homes

24. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Lead in Families

25. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology  6500 BC. - Lead discovered in Turkey, first mine.  500 BC-300 AD.- Roman lead smelting produces dangerous emissions.  100 BC. - Greek physicians give clinical description of lead poisoning. Ancient Awareness

26. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology "Lead makes the mind give way." Ancient Awareness Greek Dioscerides - 2nd BC

27. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology “If we were to judge of the interest excited by any medical subject by the number of writings to which it has given birth, we could not but regard the poisoning by lead as the most important to be known of all those that have been treated of, up to the present time.” Historical Awareness Orfila, 1817

28. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Public Health Service - L. Sullivan, 1991 “Lead Poisoning remains the most common and societal devastating environmental disease of young children. ” L. Sullivan, 1991

29. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Lead Based Paint Products

30. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology 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

31. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology 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

32. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Lead In Gasoline 1854 - Tetraethyl lead discovered by German chemist 1921 - Midgley discovers that tetraethyl lead curbs engine knock 1922 - Public Health Service warns of dangers of lead production, leaded fuel 1923 - Leaded gasoline goes on sale in selected markets 1936 - 90 percent of gasoline sold in US contains Ethyl 1972 - EPA gives notice of proposed phase out of lead in gasoline. 1986 - Primary phase out of leaded gas in US completed 1994 - Study shows that US blood-lead levels declined by 78 percent from 1978 to 1991 2000 - European Union bans leaded gasoline

33. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Agency Blood Lead Levels

34. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Health Effects Encephalopathy Colic Frank Anemia Hemoglobin Synthesis Peripheral Neuropathies Infertility (MEN) Systolic Blood Pressure (MEN) Nerve Conduction Velocity Erythrocyte Protoporphyrin DEVELOPMENTAL TOXICITY IQ, Memory, Learning Growth

35. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology WOMEN lead crosses the placenta low infant birth weight retarded mental development miscarriages premature birth stillbirth MEN decreased sex drive impotence sterility altered sperm-birth defects Reproductive Effects Of Lead

36. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology 150 10 20 30 40 50 100 Death Encephalopathy Nephropathy Frank Anemia Colic Hemoglobin Synthesis Vitamin D Metabolism Encephalopathy Frank Anemia Decreased Longevity Hemoglobin Synthesis Nephropathy Peripheral Neuropathies Infertility (MEN) Systolic Blood Pressure (MEN) Hearing Acuity Erythrocyte Protoporphyrin (Women) Hypertension (?) Nerve Conduction Velocity Erythrocyte Protoporphyrin Vitamin D Metabolism(?) DEVELOPMENTAL TOXICITY IQ HEARING GROWTH Transplacental Transfer Blood Lead (ug Pb/dl) - Low birth weight - Miscarriages, Stillbirth - Premature birth CHILDREN ADULTS

37. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Sources Of Lead Lead Paint Dust, Soil Water Industry Hobbies Traditional Ethnic Remedies

38. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Herculaneum, Missouri Doe Run – Lead smelter 160,000 tons of lead per year One of the largest lead smelters in US Past over 800 tons of lead released into the environment as part of the smelting process. Reduced to 81 tons in 2001 Target is 34 tons in 2002. Lead Contaminated Town NY Times, Jan 19, 2002

39. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology 1990 – lead removed from Gasoline Between 1976 and 1994, the mean blood lead concentration in children dropped from 13.7 mcg/dL to 3.2 mcg/dL One of the major public health triumphs of the 20th century Lead Out of Gasoline

40. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology California, 1998 Lead poisoning in furniture workers and their families Father 46 µg/dL 18-month-old child BLL 26 µg/dL 4-month-old daughter BLL 24 µg/dL two refinishers BLLs of 29 and 54 µg/dL, the four carpenters BLLs of 46, 46, 47, and 56 µg/dL. Take Home Lead Exposure MMWR - April 06, 2001 / 50(13);246-8

41. A Small Dose of Lead – 4/28/05 A Small Dose 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

42. A Small Dose of Lead – 4/28/05 A Small Dose 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

43. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Lead - Nutrition NUTRITIONAL DEFICIENCIES INCREASE ABSORPTION (high fat diets, iron, calcium) VITAMIN D (from sun) INCREASES

44. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology 25 DAYS -- BLOOD 40 DAYS -- SOFT TISSUE 20 YEARS -- BONE Half-life Of Lead

45. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Needleman, NEJM, 1979

46. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology 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)

47. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology 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 = 0.74 IQ drop

48. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Canfield R, et al. NEJM 2003;348:1517-1526. (slide from BL) IQ and Blood Lead

49. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Consequences

50. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology -- LONG TERM PROBLEMS -- LOW GRADES ABSENTEEISM READING DISABILITY HIGH SCHOOL DROP OUT Childhood Lead Exposure

51. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Increased risk of not graduating from high school (rr 4.8) Poorer reading scores Increased evidence of depression Higher rate of hard drug use Increased risk for attention deficit disorder Increased risk for antisocial behavior Academic & Social Costs Of Lead Exposure

52. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Lead In Ethnic Remedies RemedyUseLead Content Azarcon (Mexico) Digestive problems 76-86% Greta (Mexico) Digestive problems 4-90% Surma (India) Cosmetic to improve eye sight 23-26% Tibet Improve slow development 1-3%

53. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology 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

54. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Agency Blood Lead Levels

55. A Small Dose of Lead – 4/28/05 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

56. A Small Dose of Lead – 4/28/05 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

57. A Small Dose of Lead – 4/28/05 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

58. A Small Dose of Lead – 4/28/05 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.

59. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology 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

60. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Recycling Lead

61. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Lead - References EPA – Lead site – the best http://www.epa.gov/opptintr/lead/index.html CDC Childhood Lead Poisoning Prevention Program http://www.cdc.gov/nceh/lead/lead.htm A Small Dose of Toxicology www.asmalldoseof.org

62. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology A Small Dose of ™ Lead

63. A Small Dose of Lead – 4/28/05 A Small Dose 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”

64. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology  FDA regulations of Drugs  FDA regulations of Dietary Supplements (Dietary Supplement Health and Education Act of 1994 (DSHEA))  Ephedra present an unreasonable risk of illness or injury (Dec, 2003) Safety & Efficacy vs Harm

65. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Taking preventive action in the face of uncertainty Shifting the burden of proof 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

66. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Truth and Lead “How long a useful truth may be known and exist, befort it is generally receiv’d and practis’d on” Benjamin Franklin

67. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology 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

68. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology InvestigatorDateBlood Findings Dioscerides2nd BC100"Lead makes the mind give way." B. Franklin1763100"Dry gripes" A.J. Tuner189480Childhood plumbism R. Byers194380Long-term sequelae CDC197340Undue lead exposure CDC197530Undue lead exposure CDC198525Undue lead exposure WHO198620Undue lead exposure EPA198615Undue lead exposure Fulton et al.198715IQ Deficits Hansen et al.198715IQ Deficits CDC199010Undue lead exposure History Of Lead Toxicology

69. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology What is this? N N N N CH 3 O O 1 3 7

70. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Common Lead Uses  Lead acetate (Pb (C2H3 O2)2· 3H2O) White, crystalline substance Sugar of lead has a sweet taste Paint  Lead tetraethyl (Pb(C2H 5)4) antiknock compound added to gasoline significant contributor to air pollution

71. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Canfield R, et al. NEJM 2003;348:1517-1526 Strengths of study Lead values mean of 6 samples (SD 0.03 mcg/dl) Examiners blind Covariates

72. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology 16% of all American children Children with blood leads above 15 UG/DL 7% of economically favored white children 55% of African American children in poverty source: The nature and extent of lead poisoning in children in the US: a report to Congress - ATSDR Children Affected

73. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Test siblings Find the source Reduce risky behaviors Education about the hazards Education about nutrition Why Screen For Lead Exposure

74. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Children in WA State Blood Lead No.% (mcg/dL) 0-19,56955.3 2-46,43137.2 5-91,103 6.4 10-19 167 1.0 20+ 26 0.15 Children 0-6 tested in 2002-2004 WA State DOH

75. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Policy Implications Drinking water in Seattle Schools

76. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology Mechanisms Of Lead Toxicity Lead-Calcium Interactions Lead-Protein Interactions Lead-Dopamine Systems Interactions Lead-Opioid Systems Interactions

77. A Small Dose of Lead – 4/28/05 A Small Dose of Toxicology EDTA, Bal, Succimer EDTA In Use For 48 Years Little Knowledge Of Benefits Or Hazards Of These Drugs The Treatment Is Removing The Source Of Lead Lead Chelating