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A Small Dose of Toxicology

A Small Dose of Toxicology. An Introduction to the Health Effects of Common Chemicals and A Bit of Ethics. College of Veterinary Medicine Texas A&M, College Station February 21, 2005. Steven G. Gilbert, PhD, DABT “A Small Dose of Toxicology” www.asmalldoseof.org.

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A Small Dose of Toxicology

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  1. A Small Dose of Toxicology An Introduction to the Health Effects of Common Chemicals and A Bit of Ethics College of Veterinary Medicine Texas A&M, College Station February 21, 2005 Steven G. Gilbert, PhD, DABT “A Small Dose of Toxicology” www.asmalldoseof.org

  2. A Small Dose of Toxicology See: www.asmalldoseof.org -- smdose

  3. Child Health

  4. Current Bioethical Issues • Check the local news paper • Stem cells (state, national, international) • Genetically Engineered Organisms • Knowing your genes • In vetro fertilization – choosing your child's genes and characteristics • Global warming • Nanotechnology • Chemicals exposures – human health • Environmental health

  5. Convergence of Issues • Expanding Knowledge of Biological sciences – genomics, stem cells • Ability to engineer life • Vulnerability of Children • Global issues – warming, famine, war • Policy Approach within an ethical framework • Social responsibilities • No technical solutions • Restriction of freedoms

  6. Socially Responsibility What is social responsibility? What are our responsibilities to society?

  7. The First Bioethicist Aldo Leopold "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 ---------- 1887 - 1948 ----------

  8. Limits on Freedom “An ethic, ecologically, is a limitation on freedom of action in the struggle for existence” Aldo Leopold

  9. “The Commons” The Tragedy of the Commons By Garrett Hardin, Science, 1968

  10. 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

  11. Problems – Solutions? • Lead and kids • Fetal alcohol syndrome • Nuclear disarmament • Bioterrorism • Ocean Fisheries • Persistent chemicals • The Commons

  12. Toxicology Definitions The study of poisons or the adverse effects of chemical and physical agents on living organisms.

  13. Ancient Awareness 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.

  14. Historical Awareness 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)

  15. Environmental Health “Conditions that ensure that all living things have the best opportunity to reach and maintain their full genetic potential.” Steven G. Gilbert, 1999

  16. What do these have in common? • 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

  17. Who are these white guys?

  18. What Is This? O CH3 CH3 N N 7 1 3 O N N CH3

  19. Risk = Hazard X Exposure Key Words Dose / Response Individual Sensitivity

  20. Paracelsus “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy.” Paracelsus (1493-1541)

  21. An Individual View “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)

  22. Case Studies • Thalidomide • Ethanol (Alcohol) • Methylmercury • Lead • PBDEs

  23. Effects of Amount on Response

  24. Effects of Size on Response

  25. 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

  26. H H C C OH H H H What Is This? (CH3-CH2-OH)

  27. Effects of Prenatal Alcohol

  28. FAS Child

  29. Mouse – Scanning EM

  30. 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??

  31. Policy Approaches • 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

  32. Are we doing enough? Given what we know about the fetal effects of alcohol are we doing enough?

  33. A Small Dose of Lead

  34. Lead In Homes

  35. Greek 2nd BC Lead History Lead Makes the Mind Give Way

  36. Lead History • 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. “Lead makes the mind give way.” • 1904 - Child lead poisoning linked to lead-based paints. • 1922 - League of Nations bans white-lead interior paint; U.S. declines to adopt • 1923 - Leaded gasoline goes on sale in selected markets • 1971- U.S. Lead-Based Paint Poisoning Prevention Act passed • 1923 - Leaded gasoline goes on sale in selected markets • 1986 - Primary phase out of leaded gas in US completed

  37. Lead Out of Gasoline 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

  38. Lead - Absorption Orally Consumed Lead Absorbed In Place of Calcium CHILDREN – 30-50% OF LEAD ADULTS – 5-10% OF LEAD Increased During Pregnancy

  39. Half-life Of Lead • 25 DAYS -- BLOOD • 40 DAYS -- SOFT TISSUE • 20 YEARS -- BONE

  40. Lead in Families

  41. CDC Blood Lead Levels

  42. Are we doing enough? CDC Lead level 10 to 2 Mcg/dL? Lead in the drinking water of Seattle schools! SB 5189 Reducing childhood lead exposure

  43. A Small Dose of Mercury

  44. Polluting with HG Discharge in Minamata Bay

  45. Fetal Effects of MeHg

  46. Life-Long Effects of MeHg

  47. The Mercury Cycle

  48. WA State Advisory 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. http://www.doh.wa.gov/fish/FishAdvMercury.htm

  49. Are we doing enough? Mercury in our fish Restrictions on eating fish

  50. Structure of PBDEs O Bry Brx PolyBrominated Diphenyl Ether X & Y are number of Bromine atoms Common Penta, Octa, and Deca

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