Basics of Toxicology

1. Basics of Toxicology Ústav lékařské chemie a klinické biochemie 2. LF UK a FN Motol

2. Content • Poison • Subject of toxicology? • Scale of acute toxicity • Correlation of effect and dose • Poisoning and poison effect • Poison effect: administration, dose, characteristics, death • Administration, distribution, biotransformation and elimination • The effects of poisons • Molecular, subcellular and cellular effect • Fate of foreign compounds • Poisonous effect • Direct effect, biochemical effect, immunotoxicity and genotoxicity • Special Part

3. 1. Subject of toxicology? Poison compound, capable, after infiltrating the organism, to cause its damage or death

4. 1. Subject of toxicology? Poison compound, capable, after infiltrating the organism, to cause its damage or death Toxin of natural origin

5. 1.2 Scale of acute toxicity IGOR LINHART. Toxikologie: Interakce škodlivých látek s živými organismy, jejich projevy a důsledky. 1. vyd. Praha: Vysoká škola chemicko-technologická v Praze, 2012. ISBN 978-80-7080-806-1.

6. 1.3 Correlation betweentheeffect and dose

7. 2. Poisoning • Disruption of dynamic and homeostatic physiological balance • Effect acute or chronic

8. 2.1 2. Poisoning: Administration • Oral • Injection • Skin • Rectum, vagina, bladder • Inhalation • Saccus conjunctivae, meatusacusticusexternus

9. 2.2 Poison effect: Dose • Race • Sex • Age • Body weight and nutrition • Habit • Species • Diseases

10. 2.3 Poison effect: Characteristics of the compound • Dose

11. 2.3 Poison effect: Characteristics of the compound • Dose 33 years old maningested 4g of Nicotinum, but survived, due to the intense vomiting. Lethal dose is about 0.01g, therefore man ingested dose 400 times higher than lethal dose

12. 2.3 Poison effect: Characteristics of the compound • Dose • Combination • Physical properties of th poison • Origin of the poison • Environment • Storage and excretion of the poison 33 years old maningested 4g of Nicotinum, but survived, due to the intense vomiting. Lethal dose is about 0.01g, therefore man ingested dose 400 times higher than lethal dose.

13. 2.4 Poison effect : Death • Homicide • Suicide • Self-harm

14. 2.4 Poison effect : Death Sokrates • Homicide • Suicide • Self-harm

15. 2.4 Poison effect : Death Sokrates • Homicide • Suicide • Self-harm High ranked Nazi German leaders had poison deposits in teeth, known are deposits in jewellery…

16. 2.5 Poison effect : Death Accident

17. 2.5 Poison effect : Death • Medicinal: • Home cure • Baryumsluphuricum-baryumcarbonicum • Overdose Accident

18. 2.5 Poison effect : Death Mass poisoning in Japan - 11891 babies poisoned by infant formula, which contained sodium phosphate, with arsenic Infant formula had been sold for over 1-3 month with the death toll of 113 babies. • Medicinal: • Home cure • Baryumsluphuricum-baryumcarbonicum • Overdose Accident

19. 2.5 Poison effect : Death Mass poisoning in Japan - 11891 babies poisoned by infant formula, which contained sodium phosphate, with arsenic Infant formula had been sold for over 1-3 month with the death toll of 113 babies. • Medicinal: • Home cure • Baryumsluphuricum-baryumcarbonicum • Overdose Accident • Abortion • Aphrodisiacs • Industry poisoning (Bhopal) • Drug addiction

20. 2.5 Poison effect : Death Mass poisoning in Japan - 11891 babies poisoned by infant formula, which contained sodium phosphate, with arsenic Infant formula had been sold for over 1-3 month with the death toll of 113 babies. • Medicinal: • Home cure • Baryumsluphuricum-baryumcarbonicum • Overdose Accident • Abortion • Aphrodisiacs • Industry poisoning (Bhopal) • Drug addiction • Rotten food • CO poisoning • Aconite honey • Milk and cheese from veratrum fed animals • Rabbit meat after feeding on Atropa belladonna

21. 3.1 The effects of poisons • Molecular level • Subcellular level • Cellular level • Death of the cell

22. 3.1 The effects of poisons • Molecular level • Subcellular level • Cellular level • Deathofthe cell Necrosis Apoptosis Enzymatic decomposition and release of the cell content Apoptotic bodies Phagocytosis

23. 3.2 Molecularlevel ALA-dehydratase δ-aminolevulinic acid porphobilinogen

24. 3.2 Molecularlevel ALA-dehydratase δ-aminolevulinic acid Pb2+ porphobilinogen

25. 3.2 Molecular level ALA-dehydratase δ-aminolevulinic acid Pb2+ porphobilinogen

26. 3.3 Molecular level

27. 3.3 Molecular level CO

28. 3.3 Molecular level CO

29. 3.3 Molecular level CO CN-

30. 4. Fate of foreign compounds • Ingestion • Distribution • Biotransformation • Elimination

31. 4.1 Ingestion • GIT • Respiratory system • Skin • Covering epithelium; lipids and phospholipids; surface – high resorbtion ability • Physical and chemical properties of the compounds

32. 4.2 Distribution • Membrane transport • Compound deposits in organism

33. 4.3 Biotransformation • Enzymatic conversion (common) • Localization: liver, kidneys, lungs, GIT, brain … • Endoplasmic reticulum and cytosol

34. 4.4 Elimination • Urine • Stool • Breathing out • Skin

35. 5. Poisonous effect • Direct effect 2. Biochemical effect 3. Immunotoxic effect 4.Genotoxicity

36. 5.1 Direct effect • Acids and alkalies, irritant gases, solvents

37. 5.2 Biochemical effects • Inhibition of oxygen transfer (CO, MetHb) • Inhibition of respiratory chain (KCN) • Inhibition of the enzymes (Pb)

38. 5.3 Immunotoxic effect • Immunosupression • Hypersensibilasation and allergy • Autoimmune reactions

39. 5.4 Genotoxicity • Ability to damage DNA • Ability to induce or support malignant process • Ability to induce development abnormalities

40. 6. Special Part: the effect of some toxic compounds

41. 6.1 Acids and alkalis • Inorganic acids: H2SO4, HCl, HF and its salts, HNO3, H3BO3

42. 6.1 Acids and alkalis • Inorganic acids: H2SO4, HCl, HF and its salts, HNO3, H3BO3 23 year old man died 13 hours after accidentally inhaling vapours emerging from the acid bath (sulphur and nitric acids) used for treating brass plates.

43. 6.1 Acids and alkalis • Inorganic acids: H2SO4, HCl, HF and its salts, HNO3, H3BO3 4% solution of boric acid had been mistaken form physiological solution, 1000 ml had been administrated, patient died 7 days later. Children in hospital received infant formula diluted with 2.5% solution of boric acid. 23 year old man died 13 hours after accidentally inhaling vapours emerging from the acid bath (sulphur and nitric acids) used for treating brass plates.

44. 6.1 Acids and alkalis • Inorganic acids: H2SO4, HCl, HF and its salts, HNO3, H3BO3 • Inorganic alkalies: NaOH, KOH, Sodium silicate, soap, washing soda, ammonium

45. 6.1 Acids and alkalis • Inorganic acids: H2SO4, HCl, HF and its salts, HNO3, H3BO3 • Inorganic alkalies: NaOH, KOH, Sodium silicate, soap, washing soda, ammonium GP poured some ammonia solution into the flask marked „Solutio physiologica natrii chlorati“ for his personal use and left the flask on the table, in his short absence, nurse took this flask and used it for dilution streptomycin , which then injected to 8 year boy, death came immediately.

46. 6.2 Nonmetals and their compounds • Chlorine, iodine, water, hydrogen peroxide, white phosphorus and phosphides, arsenic

47. 6.2 Nonmetals and their compounds • Chlorine, iodine, water, hydrogen peroxide, white phosphorus and phosphides, arsenic Man had been attacked and injured with knife coated by vaseline containing zinc phosphide. Despite of immediate medical help man died after 60 h by uraemia..

48. 6.3 Nonmetals and their compound • Chlorine, iodine, water, hydrogen peroxide, white phosphorus and phosphides, arsenic 16 old man: drank 8 l of water in one hour (stake), died hours later. Man had been attacked and injured with knife coated by vaseline containing zinc phosphide. Despite of immediate medical help man died after 60 h by uraemia..

49. 6.4 Metals and their compounds • Barium and its salts, cadmium, mercury, plumb Uterus irrigation with sublimate or potassium permanganate as an abortion method.

50. 6.5Plant poisons