Commercial Activity - Lead Targets: Blood cells (anemia), kidney (gout), sperm (infertility)

1. Commercial Activity - Lead Targets: Blood cells (anemia), kidney (gout), sperm (infertility) Nervous system most sensitive target Adults: Occupational exposures Lead smelters, battery factories, lead additives Painters got peripheral neuropathy (wrist drop) Children: Colic (acute) and mental retardation (chronic) Legacy of leaded paint and gasoline • Eating peeling paint (many inner cities) • Playing in contaminated yards (e.g., Oakland) Occupational Safety and Health

2. Commercial activity – Acrylamide Sweden 1997: Hallandsas tunnel construction halted. Acrylamide used in grouting to prevent water seepage. 20 workers experienced neurological symptoms (reversible). Several cows grazing nearby showed severe neural effects. Dead fish found in hatchery supplied by water from tunnel. Acrylamide found in ground water near tunnel. Sensitive methods developed to detect acrylamide showed high background levels in humans. Surprisingly high levels found in fried foods (potato chips). Potential exposures in typical labs using acrylamide gels (including DNA identification labs). Occupational Safety and Health

3. Asbestos • Used in plaster, fire retardants, taxidermy • Can can pulmonary fibrosis • Can result in lung cancer • OSHA Asbestos Standard: • Annual exam and termination exam • History, physical • Pulmonary function study • Periodic chest x-ray Occupational Safety and Health

4. Solvents • Used to clean and thin paints • Can affect skin, liver, blood (benzene), peripheral and central nervous systems • History and physical exam • Urine for metabolites • Carbon monoxide in exhaled air, or carboxyhemoglobin in blood for methylene chloride Occupational Safety and Health

5. Intracellular Targets of Neurotoxins Ion channels – Signal conduction Sodium Potassium Calcium Chloride Synaptic region – Neurotransmitter processing Release Reuptake of excess Receptor response (stimulate, block) Channels and receptors - multigene families Located in different parts of the nervous system Responsible for differential effects Occupational Safety and Health

6. Psychoactive/Psychedelic Marijuana Short term use – relaxation; Long term – loss of motivation Loss of coordination, slow reaction time, disordered thought Legalized for medical use in some states (controversial) Sometimes contaminated with herbicide paraquat LSD Strong hallucinogen, vivid colors Flashbacks common PCP/Ketamine At first, feelings of strength, invulnerability, detachment Then confusion, agitation, depression Long term – depression, suicide, schizophrenia Natural sources Cacti (peyote) – mescaline Mushrooms – psilocybin, ibotenic acid Occupational Safety and Health

7. Depressants Alcohol Responsible for about half of traffic deaths Poor job performance and disrupted family life Health problems: Cirrhosis, Fetal alcohol syndrome Barbiturates (sedatives) Sleep inducing, can induce dependence Especially dangerous when used with alcohol Tranquilizers (anxiolytics) Benzodiazepines (Valium, Librium) among most used Variants not approved include Rohypnol Causes loss of short term memory Used for personal attacks Occupational Safety and Health

8. Drugs of Abuse Opioids, Amphetamines, Cocaine Scope of problem in USA Half a million heroin addicts Six million cocaine users Personal tragedies common among users Families adversely affected (vicious circle of poverty, crime) 75% of crime lab evidence is drug related Impurities always suspect Features Stimulation of reward center: Euphoria (like endorphins) Increase dopamine in nucleus accumbens Tolerance: Require increasing doses (100x, previously fatal) Continued use can lead to psychoses (paranoid schizophrenia) Withdrawal: Dysphoria, depression, craving Occupational Safety and Health

9. Opioid Action as Analgesic Codeine not attractive as street drug (low potency) Maintenance: Methadone prevents withdrawal, no euphoria Said to obviate need for marijuana as painkiller Research to find derivatives with only analgesic action Only partially successful: Oxycontin used by 1 million patients with chronic pain, 25% abuse use Illicit syntheses often attempted, often consequences tragic. Poor technique → dangerous derivatives (Parkinson’s) Cocaine derivatives in clinical use Lidocaine, procaine successful as local anesthetics Result from blocking neuronal sodium channels Occupational Safety and Health

10. Uses of Amphetamines and Derivatives Treatment for narcolepsy - 1930’s Maintaining military alertness - 1940’s Occupational alertness (students, truckers) – 1950’s Appetite suppressant Suppress childhood attention deficit disorder Dietary supplement (ephedrine) as “natural energizer” Occupational Safety and Health

11. US Department of Transportation Regulation Toxic Materials PROTECTION : (1) Recirculating oxygen (2) Demand compressed air/O2 (3) Recirculating self generating oxygen (4) Suits wear that made of material impervious to the toxic material Occupational Safety and Health

12. O2 Requirement Oxygen content (suffocation) Occupational Safety and Health

13. CHEMICAL THREATS • Chemical warfare agents(CWAs) • Mustard (HD) • Nerve agents (G, V) • Have seen previous terrorist use (Aum Shinrikyo) • Toxic industrial chemicals (TICs) • Large array of materials • Reasonably accessible • Accidents have caused numerous casualties (Bhopal) • Non-traditional agents (NTAs) • Not TICs Occupational Safety and Health

14. BIOLOGIC TOXINS WITH BIOTERRORISM POTENTIAL Occupational Safety and Health

15. Occupational Safety and Health

16. BIOHAZARD • DEFINITION • A biological agent, such as an infectious microorganism, or a condition that constitutes a threat to humans, especially in biological research or experimentation. • The potential danger, risk, or harm from exposure to such an agent or condition. • MEANING • any bacterium or virus or toxin that could be used in biological warfare • hazard to humans or the environment resulting from biological agents or conditions Occupational Safety and Health

17. BIOLOGICAL HAZARD SIGNS. The biological hazard warning shall be used to signify the actual or potential presence of a biohazard and to identify equipment, containers, rooms, materials, experimental animals, or combinations thereof, which contain, or are contaminated with, viable hazardous agents. Occupational Safety and Health

18. Bacillus anthracis Smallpox day 1 day 2 Chickenpox Gram strain of Yersinia pestis Occupational Safety and Health

19. “THE COWPOCK” BY JAMES GILRAY, 1802 Occupational Safety and Health

20. Biohazard Risk Level 1: Unlikely pathogenicity to humans No community risk ASSIGNMENT OF PATHOGENS TO BIOHAZARD RISK LEVELS 1-4 E. coli Biohazard Risk Level 2: Possible pathogenicity to humans Unlikely community risk Hep. A Biohazard Risk Level 3: Serious pathogenicity to humans Moderate community risk Usually prophylaxis / treatment YF, Hep. C* Ebola, smallpox Biohazard Risk Level 4: Serious pathogenicity to humans High risk of spreading to community No available treatment or prevention Occupational Safety and Health

21. BIOTERRORISM THREATS • Anthrax • Plague • Tularemia • Smallpox • Brucellosis • Q fever • Cholera • Venezuelan equine encephalitis • Ebola, Lassa, Marburg • Botulinum toxin • Staphylococcus enterotoxin B Occupational Safety and Health

22. HIGH CONSEQUENCE THREATS Engineered organisms Smallpox Anthrax Bulk Food Contam Agro Terror CutaneousAnthrax Salmonella Food poisoning Occupational Safety and Health

23. ANTHRAX Occupational Safety and Health

24. ANTHRAX • The anthrax bacteria live in two forms • The growing bacterium -- the weapon • causes disease because it produces very potent toxins (poisons) • The dormant spore -- the vehicle • spreads by air • extremely resistant to many challenges • can survive in the environment for decades • Ingested by animals (herbivores) while grazing • Humans are infected • through contact with infected animals and their products • because of human intervention • Spores are not made inside the living body Occupational Safety and Health

25. Bacteria make the poison • Name:Bacillus anthracis • Bacteria multiply inside the body • Bacteria produce toxins (poisons) that cause disease Occupational Safety and Health

26. IMPORTANT POINTS • Spores are infectious -- but they are not made in a living body • Anthrax is not transmitted from person to person • Spores can sustain lots of stresses, withstand vigorous manipulation, last for very long time • Spores are extremely sturdy • Bacteria are made in the body and they produce the killing poisons • Antibiotics block bacteria, but not the poison. Therefore, antibiotics must be given soon after suspected exposure • Spores must have a certain, small size to reach the lower part of the respiratory tree -- they tend to clump • Very challenging to produce large stocks of spores of small size to “optimize” infection (so-called weapon-grade) • Spores, once deposited, tend to stay on the ground • Risk of air-borne infection from deposited spores is low • It takes ~ 10,000 spores to initiate an infection • Anthrax tends to be rare, even where soil is contaminated Occupational Safety and Health

27. HOW CAN A PERSON GET INFECTED WITH ANTHRAX • Spores are inhaled • Inhalation anthrax • Spores enter skin through small lesions • Skin (cutaneous) anthrax • Spores are ingested • Gastro-intestinal (GI) anthrax Occupational Safety and Health

28. INHALATION ANTHRAX -- BY AIR Occupational Safety and Health

29. INHALATION ANTHRAX -- SYMPTOMS • Initial symptoms usually appear a week from exposure • Illness begins with non-specific, flu-like symptoms • malaise, fatigue, fever, chest discomfort, dry cough • Abrupt appearance of respiratory distress • severe breathing problems and shock • Chest radiograph may show swelling of the soft tissues in the middle of the chest, and fluid in the chest cavity Occupational Safety and Health

30. INHALATION ANTHRAX -- A CHEST X-RAY Occupational Safety and Health

31. Inhalation anthrax -- the outcome • As of 11/21/2001, six of 11 patients with inhalation anthrax have survived • Prompt recognition of the early features of inhalation anthrax is important • If untreated, the disease is generally fatal within 24 to 36 hours after the onset of severe symptoms Source: Centers for Disease Control Occupational Safety and Health

32. SKIN ANTHRAX most common • Anthrax by contact • Usually affects exposed skin areas,such as arms, hands, face, neck • About 20% of untreated cases of skin anthrax result in death • Deaths are rare following appropriate antibiotic therapy least common Occupational Safety and Health

33. Skin Anthrax • Lesions usually appear within a week from exposure • Starts as a raised itchy bump that develops into a vesicle and then a painless ulcer • The main characteristic is the black area at the center of the ulcer • The skin lesion is surrounded by very extensive swelling • Ulcer usually leaves no permanent scar Occupational Safety and Health

34. Gastrointestinal Anthrax • Anthrax by consumption of contaminated food • Initial symptoms are nausea, loss of appetite, vomiting, and fever • Later symptoms are abdominal pain, vomiting of blood, and severe diarrhea • In some cases, symptoms are swelling and gland enlargement in the neck, accompanied by difficulty to swallow and to breath • About 25%-60% of untreated cases result in death Occupational Safety and Health

35. How can we tell ….. • that it is anthrax? • By recognizing clinical signs and symptoms • By recovering spores from nasal swabs • By identifying anthrax bacteria from nasal swabs, infected tissues or body fluids • that person A and person B have been infected by the same/different strain of anthrax? • By using the genetic material of bacteria as their “fingerprint” Occupational Safety and Health

36. WHAT CAN DOCTORS DO TO CONTROL ANTHRAX? • Use antibiotics (after suspected exposure) • Use a vaccine (usually before exposure) Occupational Safety and Health

37. Antibiotics and anthrax • There are three types of antibiotics approved for anthrax • Ciprofloxacin (fluoroquinolone) • Doxycyclin (tetracycline) • Amoxicillin (penicillin) Source: Food and Drug Administration Occupational Safety and Health

38. POST-EXPOSURE PROPHYLAXIS • Indicated to prevent inhalation anthrax after a confirmed or suspected aerosol exposure • Initial therapy with ciprofloxacin or doxycycline is recommended for all adults and children • Use of tetracyclines and fluoroquinolones in children has adverse effects • As soon as penicillin susceptibility of the organism has been confirmed, prophylactic therapy for children should be changed to amoxicillin • No evidence that one drug is more or less effective than the other for prevention of anthrax infection Source: Centers for Disease Control Occupational Safety and Health

39. THE ANTHRAX VACCINE • The current US vaccine for human use is a cell-free filtrate vaccine, i.e., it contains no dead or live bacteria • Multiple immunizations are required • Six doses: 0-2-4 weeks and 6-12-18 months • Yearly boosters are given to maintain immunity • Limited information on efficacy (how protective) • Limited information on safety (side effects) • Problems with production and quality control reported • In the US, anthrax vaccination is recommended for • People who work directly with the organism in the laboratory • Veterinarians who handle potentially infected animal products • All U.S. military personnel (since 1998) • Pregnant women should be vaccinated only if absolutely necessary Occupational Safety and Health

40. SMALLPOX, Variola major Occupational Safety and Health

41. SMALLPOX, Variola major • Clinical symptoms • Acute • Fever • Headache • Vomiting • Backache • Orthopox virus • DNA virus • Brick-shaped structure 200 nm in diameter • Incubation 8-16 days • Mortality 30% Smallpox - Rash • Rash • Begins on face, hands, forearms & spreads to lower extremities within 7 days • Lesions on palms & soles of feet • Synchronous progression: maculesvesicles pustules scabs Occupational Safety and Health

42. Smallpox, disease Occupational Safety and Health

43. Smallpox, disease Occupational Safety and Health

44. Smallpox, disease Occupational Safety and Health

45. PLAGUEYersinia pestis • Distribution • Highest in 4 corners area – Western states • Prairie dog population Occupational Safety and Health

46. PLAGUEYersinia pestis • Transmission – • Inhalation • Direct contact • Fleas Occupational Safety and Health

47. PLAGUE, Clinical presentations • Bubonic • Flu-like with painful buboes (lymph nodes) • Septicemic • Similar to bubonic • No swelling of lymph nodes Occupational Safety and Health

48. PLAGUE • Pneumonic • Highest mortality • Rapid transmission • Fever • Hemoptosis • Lymphadenopathy • Cough Occupational Safety and Health

49. BIOLOGIC TOXINS WITH BIOTERRORISM POTENTIAL Biological Agents of Highest ConcernCategory A Agents Botulinum toxin (Botulism, BOTOX) Biological Toxins of 2nd Highest ConcernCategory B Agents Ricin toxin from Ricinus communis (castor bean) Epsilon toxin from Clostridium perfringens Staphlococcus enterotoxin B Occupational Safety and Health

50. Clostridium Botulinum • C. botulinum spores found in soil worldwide • Toxin causative agent of botulism • Types A-G; A,B&E most commonly associated with human disease • Most potent toxin known (lethal dose 1ng/kg) • Inactivated by chlorine (~20min) and sunlight (1-3hrs); destroyed by heat (5min at 85C) • Absorbed into circulation via mucosal surface or wound, not intact skin • Interferes with nerve transmission  paralysis Occupational Safety and Health