Dr. Khalid Farooq kayfarooq@gmail

1. TOXICOLOGY Dr. Khalid Farooq kayfarooq@gmail.com

2. Toxicology The study of the adverse effects of chemicals in biological systems Phytotoxins Zootoxins Bacteriotoxins Toxicant - the specific poisonous chemical.

3. Definitions Toxicology: Study of poisons Poison: Substance that causes harmful effects when administered, either by accident or by design, to a living organism Descriptive definition Study of detection, occurrence, properties, effects, and regulation of toxic substances

4. Definitions Toxicant:Any chemical that can potentially produce harm is toxicant, (e.g. Lead, Pesticides, Sodium cyanide, Benzene). Toxin: Chemicals that are produce by living organisms, (e.g. Rattlesnake venom or poisonous mushrooms). Poison:Any substance that when ingested, inhaled, or absorbed or when applied to, injected into or developed within the body in relatively small amounts may, by its chemical action, cause death or injury. Toxic substance: Can be a particular chemical or a mixture of chemicals that collectively have toxic properties, (e.g. Asbestos, Lead chloride).

5. Introduction Toxicology is arguably the oldest scientific discipline, as the earliest humans had to recognize which plants were safe to eat. Most exposure of humans to chemicals is via naturally occurring compounds consumed from food plants. Humans are exposed to chemicals both inadvertently and deliberately.

6. Branches/Disciplines • Biochemical and molecular toxicology • Behavioral toxicology • Nutritional toxicology • Carcinogenesis • Teratogenesis • Mutagenesis • Organ toxicity

7. Branches/Disciplines • Analytical toxicology • Clinical toxicology • Veterinary toxicology • Forensic toxicology • Environmental toxicology • Industrial toxicology • Agricultural toxicology -------Interdisciplinary-------

8. Domestic poisoning 92% of all poisonings happen at home. • The household products implicated in most poisonings are: cleaning solutions, fuels, medicines, and other materials such as glue and cosmetics. • Certain animals secrete a poison called venom, usually injected with a bite or a sting, and others animals harbor infectious bacteria. • Some household plantsare poisonous to humans and animals.

9. History 2700 B.C. - Chinese journals: plant and fish poisons 1200-1900 B.C. - Egyptian documents that had directions for collection, preparation, and administration of more than 800 medicinal and poisonous recipes. 800 B.C. - India - Hindu medicine includes notes on poisons and antidotes. 50-100 A.D. - Greek physicians classified over 600 plant, animal, and mineral poisons.

10. History 50- 400 A.D. - Romans used poisons for executions and assassinations. The philosopher, Socrates, was executed using hemlock for teaching radical ideas to youths. Avicenna (A.D. 980-1036) Islamic authority on poisons and antidotes. 1200 A.D. - Spanish rabbi Maimonides writes first-aid book for poisonings, Poisons and Their Antidotes

11. History Swiss physician Paracelsus(1493-1541) credited with being “the father of modern toxicology.” “All substances are poisons: there is none which is not a poison. The right dose differentiates a poison from a remedy.” • Dose Response relationship. • Mercury for the treatment of Syphilis. “On the miners sickness and other diseases of miners”

12. HistoryItalian physicianRamazzini (1713) published“De MorbisArtificumDiatriba” (Diseases of Workers) describing "asthma" in bakers, miners, farmers, gilders, tinsmiths, glass-workers, tanners, millers, grain-sifters, stonecutters, ragmen, runners, riders, porters, and professors. Ramazzini outlined health hazardsof the dusts, fumes, or gasesthat such workers inhaled. The bakers and horse riders described by Ramazzini would today probably be diagnosed as suffering from allergen-induced asthma. The lung diseases suffered by most of the other workers would now be classified as "pneumoconiosis," a group of dust-related chronic diseases.

13. History Spanish physicianOrfila (1815) established Forensic Toxicology as a distinct scientific discipline. Book :Traite de Poisons

14. Catherine de Medici (1519-1589) • Queen of France • Poisoning skills • Treating poor and sick people with poison. • Dose response • Signs and symptoms • Descriptive toxicologist.

15. History Paul Ehrlich: developed staining proceduresto observe cell and tissues and pioneered the understanding of how toxicants influence living organisms(20th century).

16. History 20th Century Rachel Carson- alarmed public about dangers of pesticides in the environment.

17. Madame Giulia Toffana (1635-1719) Agua TOFFANA (Arsenic)

18. Catherine Deshayes "La Voisin“ (1638-1680)

19. The Dose Makes the Poison • An apparently nontoxic chemical can be toxic at high doses. (Too much of a good thing can be bad). • Highly toxic chemicals can be life saving when given in appropriate doses. (Poisons are not harmful at a sufficiently low dose).

20. Approximate Lethal Doses of Common Chemicals(Calculated for a 160 lb. human from data on rats) Chemical Lethal Dose Sugar (sucrose) 3 quarts Alcohol (ethyl alcohol) 3 quarts Salt (sodium chloride) 1 quart Herbicide (2, 4-D) one half cup Arsenic (arsenic acid) 1-2 teaspoons Nicotine one half teaspoon Food poison (botulism) microscopic Lethal Doses

21. Toxin and source

22. Occupational and Environmental Toxicology Environmental toxicants (air and water pollutants) are substances harmful to the environment and to humans. Environmental toxicants are both natural and man made. Public perception that man-made ones are more serious than natural ones - Reality: both are serious. 5,000,000 yearly deathsworldwide due to bacterial toxicants (Salmonella, E. coli)

23. Occupational and Environmental Toxicology Many examples of diseases associated with specific occupations were recorded in antiquity, but they were not considered serious because the health of the workers was not a societal concern. - Paracelsus - Miner’s Disease (1533) - Hill & Pott (1761 &1775) - Radium dial painters, “aniline dye” workers (1900) - Shoe salesmen (1950s) - Industrial chemical workers (1940-present)

24. Occupational and Environmental Toxicology Paracelsus - Miner’s Disease (1533) came from inhaling metal vapors, foundation for the field of chemotherapy. Hill (1761) linked tobacco (snuff) to cancer. Pott (1775) linked scrotal cancer in chimneysweeps.

25. Occupational and Environmental Toxicology Radium dial painters: “aniline dye” workers (1900) painters licked their brushes to pull it to a point. Shoe salesmen(1950s) shoe-fitting fluoroscopes: radiation of feet in shoes of children and repeated exposure for salesmen.

26. Occupational and Environmental Toxicology Industrial chemical workers Workers typically are exposed to a greater number of carcinogens for longer periods of time. Occupations with high risk of cancer : Health care workers, pharmaceutical and laboratory workers, refinery workers, rubber workers, furniture makers, and pesticide workers.

27. Bhopal Gas Tragedy

28. Amongst the worst Industrial Disasters of its time. Occurrence: 3rd December 1984. Place of occurrence: Bhopal, Madhya Pradesh, India. Company: Union Carbide Corporation. Chemical: Methyl Isocyanate (27 tons)

29. Among the 500,000 people exposed to the gas, 20,000 have died till date and 120,000 continue to suffer devastating health effects as a result of their exposure.

30. Bhopal Scenario Union Carbide Corporation

31. Union Carbide Corporation • Started in 1969 in bhopal • Phosgene, Monomethlyamine, Methyl Isocyanate (MIC) and the pesticide Carbaryl, also known as Sevin. • Taken over by DOW Chemicals in 2001. • DOW refused Union Carbide’s Liabilities in Bhopal, India.

32. Toxic Materials in Soil and Water

33. Gas Vent Scrubber Gas Vent Scrubber Stack

34. Effects on Human Health • Respiratory Disorders – Irritation to the lungs, causing coughing and/or shortness of breathing. Higher exposure caused build up of fluids (pulmonary edema). Caused Asthama. • Cancer Hazard – Caused mutation (genetic changes). It caused cancer. • Reproductive Hazard – Association between exposure to Methyl Isocyanate and miscarriages. It may damage the growing fetus.May also affect fertility in men and women. • Traces of many toxins were found in the Brest Milk of mothers and were inturn transmitted to the recepient babies.

35. Animal Slaughter

36. Toxicology Terms Toxicity - The adverse effects that a chemical may produce. Dose- The amount of a chemical that gains access to the body.

37. Lead

38. Lead In Homes, vehicles, fuel, etc…

39. Lead Poisoning • Lead has no known biological function. • There is no proven safe lower limit for lead. • Lead Pb++, competes with Ca++, Fe++ • It is cheap, useful,easy to mine, therefore • Lead is ubiquitous- in air, food, water, soil, ceilings etc. • Leaded petrol means that all environmental dusts are high in lead-contaminating ceiling dust, topsoil, window wells etc.

40. Uses and Sources of Lead •   Paint (until 1970) •   Petrol (tetraethyl lead) • Household dust (via settlement of air pollution) • Ceiling dust • Occupational • Solder • Ceramic glazes •   Pesticides (lead arsenate) • Cigarettes •   Mines, smelters

41. More Uses and Sources of Lead • TV's, Computer monitors •   Batteries, Bullets Sinkers • Aviation • X-ray shields • Crystal-ware (high levels in decanters) • Explosives • Non-stick linings of pots (in the past) • Plastic colouring (wire, blinds) • Pewter

42. Occupational Lead smelters Painter/decorators Battery manufacturers Stain-glass workers Jewellery makers Bronze workers etc... Environmental paint (walls, furniture, toys) water food air (petrol, industry), dust/soil Other traditional remedies (Ayruvedic) surma & kohl cosmetics lead shot lead glazed ceramics foreign body ingestion e.g. curtain/fishing weight, snooker chalk Lead poisoningSources

43. Absorption of Lead • Lead goes down iron or calcium absorption pathway in GIT. • Children absorb lead well orally (~50%) cf adults poorly (~10%). Children also have more hand to mouth activity. • Lead absorption is enhanced if diet is poor in iron or calcium. • Pica is one of the worst risk factors. • Lead can be inhaled. • Tetraethyl lead can be absorbed via skin.

44. Absorption of Lead

45. Environmental lead exposureWater • Lead in water: • Largely from lead pipes/solderings/fittings • Water lead contamination from ground lead has occurred in Nepal • WHO max water lead content: 10µg/l • ~ 20-30% UK homes exceed this limit

46. Environmental lead exposurePaint • Pre 1960’s up to 40% lead in paint • rapid drying, weather resistance, colouring • Domestic paint now <0.06% lead (600ppm) • BUT leaded paint remains in many homes • walls, furniture, toys • Lead exposure from paint: • sanding, heat stripping, flaking, pica • contamination of carpets/curtains, dust

47. Ayurvedic Traditional Remedies • Numerous reports of lead, mercury, thallium, arsenic poisoning from Ayurvedic (& Chinese) remedies • 40% of the >6000 medicines in Ayurveda contain at least one heavy metal • Thought by practitioners to have therapeutic properties and/or to increase the efficacy of other herbal contents • Used most commonly for chronic disorders and so there is a greater risk of heavy metal accumulation

48. Ayurvedic Traditional Remedies • Case 1: 68 mg/g lead i.e. 6.8 % • 76 mg/g mercury i.e. 7.6 % • 12 mg/g arsenic i.e. 1.2 % • i.e. 15.5 % heavy metals • Case 2: 50 mg/g lead i.e. 5.0 % • 39 mg/g mercury i.e. 3.9 % • i.e. 8.9 % heavy metals

49. Contribution ofSources

50. Reduction of Lead hazards in the home