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“Physical and Chemical Agents of Disease” and “Toxicity of Chemicals”

“Physical and Chemical Agents of Disease” and “Toxicity of Chemicals”. Dr. George Van Orden. Acknowledgement. Some of the slides used in this presentation were prepared by Dr. Peter Strom and Dr. Craig Phelps Environmental Science Department Rutgers University.

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“Physical and Chemical Agents of Disease” and “Toxicity of Chemicals”

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  1. “Physical and Chemical Agents of Disease”and “Toxicity of Chemicals” Dr. George Van Orden

  2. Acknowledgement Some of the slides used in this presentation were prepared by Dr. Peter Strom and Dr. Craig Phelps Environmental Science Department Rutgers University

  3. Human Exposures to Environmental Hazards • Chemical agents • Electromagnetic radiation • Ionizing radiation • Heavy metals • Air pollution • Temperature increases from global warming

  4. Physical Agents of Disease • Heat/Temperature • Denature Proteins • Hyperthermia/Hypothermia • Noise • Acute and Chronic Damage • Stress • Radiation • Ionizing • Alpha particle • Beta Particle • Gamma • X-ray • Non-ionizing • Low energy UV light • Microwave

  5. Electromagnetic Spectrum

  6. Chemical Agents • Acute Exposure • Chronic Exposure • Metabolism/Excretion/Storage • Mixed Function Oxidase (MFO’s) • Metallothionins • Cytochrome P450 • Kidneys • Lungs (gas or vapor from blood) • Skin (water or oils) • Bile Duct (from liver, fat soluble) • Storage in lipids, tissue and bone

  7. Routes of Exposure • Penetration through the skin • Absorption through the lungs • Absorption through the gastrointestinal tract • Injection • Particulates • >0.01 and <2 microns in size are retained by lung

  8. Occupational Lung Diseases • Silicosis • Pneumoconiosis (coal workers, black lung) • Asbestosis • Occupational Asthma • Byssinosis (cotton, flax, hemp) • Chronic Obstructive Pulmonary Disease • Permanent Condition • Chronic Bronchitis • Emphysema • Asthma may lead to a permanent airway restriction condition

  9. Toxicology • The science that examines the effects of poisonous chemicals and other agents on humans and wildlife. • Toxicity – the degree of harm that a substance can inflict • Toxicant – an substance with toxic properties • Toxin – a naturally produced toxic substance

  10. Ecotoxicology • Effects of chemicals on the ecosystem • Survival of humanity depends on the survival of other species. • Ecosystem – network of interactions between physical, chemical and biological components within an area.

  11. Environmental Toxicology • The study of how toxic substances affect public health and the environment as well as the behavior of toxicants in the environment.

  12. History • Late 1930’s – Muller’s discovery of the insecticidal properties of dichlorodiphenyltrichloroethane (DDT) and several organohalides resulting in a wider use of insecticides. DDT was first synthesized in 1874.

  13. 1930’s – discovery of sulfanilamide (antibiotic). • Needed an effective delivery system • Highly insoluble in an aqueous medium • Prepared originally with ethanol (elixir) • Later found that sulfanilamide was more soluble in diethylene glycol. • Drug sold in the glycol solution but was still labeled “elixir” • Several patients died of acute kidney failure • Body metabolizes glycol into oxalic acid and glycolic acid which crystallize in the kidney tubules • Resulted in Senator Copland’s Bill – titled Food, Drug and Cosmetic Act of 1938 (drug labeling, proof of drug safety, advertising and seizures of products by FDA) • Sulfanilamide disaster lead to toxicological studies

  14. Dr. Geiling • Geiling and his group of scientists (late 1930’s) in Chicago • Leaders in toxicology • Focused on toxicology of organophosphates, antimalarial drugs and radionuclides

  15. More on the History • After World War II a growing concern for the environment and the effects from industrial development. • Chemical industry developed rapidly • “Good life through chemistry” • Chemical and Industrial waste disposal • Chemical fertilizers, pesticides • Better crop productions and control of insects • Mosquito control and the use of DDT (NJ example) • malaria

  16. History • All of these events between 1940and 1946 led to the explosion in toxicology. • Organophosphate cholinesterase inhibitors discovered by Willy Lang and Gerhard Schrader (scientists from Geiling’s group) later replaced DDT in the 1960’s • Over time saw a deterioration of air and water quality • Urban smog caused widespread fatalities • Donora, PA (1948) • London, England (1952)

  17. Donora, Pennsylvania (1948) • 5 day inversion • 20 people died • Damp blanket of smoggy air with sulfur

  18. Donora, PA - 1948 20 deaths, 6000 illnesses 14,000 total population highest per capita death rate Particles

  19. Great London Smog - 1952 • 5 day period • 3000 excess deaths • Caused by atmospheric inversion • Cool surface air trapped by overlaying warm air • Use of coal burning equipment

  20. London Killer Fog

  21. 1957 • Roger Revelle and Hans Suess published a paper calling attention to atmospheric carbon dioxide increasing due to fossil fuels. • July 1986 (29 years later) “Nature” magazine forecasted climate change from increase in CO2 and the “Greenhouse Effect.”

  22. DDT (Dichlorodiphenyltrichloroethane) Widespread use of DDT began during the early 1940s and reached a maximum during the 1960s. Due to concerns about the possible adverse effects upon the health of humans and wildlife, application of DDT was prohibited in 1972 in the U.S. Most developed nations banned the use of DDT; however, some countries still continue to use DDT.

  23. Facts about DDT Not regarded as a highly toxic pesticide Formerly employed worldwide to control insects and harmful mosquitoes that carry malaria Was credited at one time with saving millions of people from death due to malaria

  24. Facts about DDT (continued) Concentrates in the adipose (fatty) tissues of the body Estimated half-life of approximately 10 years All living organisms on earth contain some levels of this pesticide.

  25. Human Health Effects of DDT Linked to: Cancer (pancreatic, non-Hodgkin’s lymphoma, and breast) Reproductive effects Impaired lactation Falling sperm counts Impaired neurologic function (irritability, dizziness, and numbness)

  26. Biomagnification of DDT

  27. 1960’s • Tragic “Thalidomide” Incident • Publication of “Silent Spring” by Rachel Carson • Overuse of pesticides will eventually kill off the songbirds • Toxicology started to look at teratogenic effects • “Dilution is the solution to pollution” • Runoff from fields containing fertilizers – eutrophication • Irrigation of poorly drained fields lead to salinization of land.

  28. Rachel Carson • 1907-1964 • Marine Biologist from Pennsylvania • MA from Johns Hopkins U. • Author of ‘Silent Spring’ • Received much attention, because she wrote • and presented scientific facts well • She was disturbed by the widespread and indiscriminate use of pesticides • Many of these pesticides were known to affect wildlife e.g. kill birds • She lobbied very hard to control and ban certain highly toxic chemicals • Testified before congress in 1963 and called for new policies with respect to human health and the environment

  29. 1970’s • Love Canal • Toxic Substance Control Act (TSCA) • What to do with chemical waste? • Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) • Started to identify contaminated sites throughout the country • Exposure to humans (air, water, soil, food) • Contaminated sites originated mainly due to the improper disposal of hazardous chemicals (waste) • Started to see effects on humans • Chronic illnesses (organ diseases, cancers) • Birth defects

  30. Love Canal • Love Canal • Hooker Chemical - 265,000 tons waste, 1942-1975 • Donates site; town builds school and housing there • Cancer cluster - 4 x miscarriages, other diseases • 700 families relocated

  31. Love Canal

  32. Bhopal, India • 1984 accident discharged methyl isocyanate into the air from a Union Carbide pesticide manufacturing facility • One of the largest industrial accidents of the 20th century • Overnight death of approximately 4,000 individuals and over 100,000 injuries (many thousand of the injured died later) • Primary cause of death was pulmonary edema • Many survivors showed signs of compromised respiration (e.g. bronchoalveolar lesions and decreased lung funtions) and impaired vision.

  33. 1980’s • May 1985 – British research team reported levels of atmospheric ozone over the Antarctica had declined sharply. • Ozone hole • UV Radiation and skin cancer • July 1986 (Nature magazine) – CO2 and Greenhouse effect.

  34. 1989 Environmental Defense Fund (Mission Statement) is a leading national nonprofit organization representing more than 700,000 members. Since 1967, we have linked science, economics and law to create innovative, equitable and cost-effective solutions to society's most urgent environmental problems. • “Environmental Defense Fund” lists 8 most critical issues: • Greenhouse effect • Ocean pollution • Protecting wildlife and habitat • Recycling • Saving the rain forests • Acid rain • Antarctica (Ozone hole) • Toxins (toxic substances)

  35. International Regulation • The Stockholm Convention on Persistent Organic Pollutants (2001) • Calls for an end to the use and release of 12 POPs

  36. Environmental toxicology is driven by legislation • National Environmental Policy Act • Clean Air Act • Federal Environmental Pesticide Control Act • Federal Water Pollution Control Act • Safe Drinking Water Act • Toxic Substances Control Act • Resource Conservation and Recovery Act • Comprehensive Environmental Response, Compensation and Liabilities Act • Clean Water Act

  37. First piece of environmental legislation was the National Environmental Policy Act • 1970 • Created the EPA • Initially 5000 employees (1970) • Budget of 1.3 B • In 1995 there were >18,000 employees, budget of 7.2 B • USA is divided into 10 management regions • Clean Air Act • Also in 1970 • Required the EPA to set standards • EPA in charge of controlling mobile and stationary emissions sources • EPA controls hazardous pollutants • Amended in 1977 to set compliance standards • Amended again in 1990 to regulate acid rain and CFC emissions

  38. Federal Environmental Pesticide Control Act • 1972 • amended by FIFRA – Federal Insecticide, Fungicide, and Rodenticide Act • Required manufactures to provide PMNs (Pre Manufacture Notice) with toxicological information to register a pesticide • Federal Water Pollution and Control Act • 1972 • Provided sewage treatment plant grants for many municipalities • Set effluent limits based on technology standards • Toxicity testing is used to set maximum allowable concentrations of toxicants in discharges and receiving waters • Goal was to have all water fishable and swimmable by 1983 • Established goal to eliminate pollution discharges by 1985

  39. Safe Drinking Water Act • 1974 • Set mandatory drinking water standards • Controlled underground injection of wastes (aquifer protection) • Amended in 1984 to set a schedule for establishing drinking water standards for 80 chemicals (provides notice to consumers) • Toxic Substances Control Act • 1976 • Regulated the use of chemicals in manufacturing and production • Goal was to characterize the human health and environmental impact of EVERY chemical manufactured in the USA • EPA has only 90 days to review and evaluate data

  40. Resource Conservation and Recovery Act • 1976 • Controlled the disposal of solid waste • Set new hazardous waste regulations • Comprehensive Environmental Response, Compensation and Liabilities Act • Also known as SUPERFUND • 1980 • Provided funding mechanisms to clean up abandoned waste sites • Amended in 1984 to ban ‘land disposal of hazardous waste • Amended in 1986 to include requirements for community emergency plans and publication of corporate Toxic Release Inventories • Established program to develop innovative approaches for cleanup and assessment of hazards

  41. Clean Water Act • 1987 • sets national water quality standards • Toxicological (animal) testing of ‘xenobiotics’ is federally mandated by • Federal Insecticide, Fungicide, and Rodendicide Act (FIFRA) • Federal Environmental Pesticide Control Act • Federal Water Pollution Control Act • Safe Drinking water act • Toxic Substances control Act

  42. What is the extent of the problem? • Thousands of chemicals are manufactured and released into the environment. • Accidental release (e.g.. Oil spills) • Released on purpose (e.g.. Pesticides and household products) • Permitted discharges to air, water and soil • historic disposal practices (to land and water) • “Dilution is the solution to pollution” and “out of sight, out of mind” • Jackson Twp. Aquifer (1972) contaminated (volatile organics) from disposal of toxic waste in the Municipal landfill. • Van Dyk Research • Rowe International • Colloid Chemical • Leaking underground storage tanks • The toxicity of most of these compounds is unknown.

  43. Concerns • Occupational exposure • Contaminated drinking water • Hazmat spills – effect on responders and ecosystem • Contaminated air, water, soil, food and biota • Overuse of pesticides • Terrorism – chemical agents

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