The document discusses toxicology, focusing on the chemical basis of toxic agents, systemic responses, and specific toxic substances including metals and pesticides. It provides statistical insights on poison exposure incidents, emphasizes the importance of antidotes, and covers historical perspectives on poisoning. The various fields of toxicology, such as occupational and forensic toxicology, are also explored along with clinical implications and treatments for poisoning cases.

1. Course: CHEMICAL PATHOLOGY II (MLT223)
Lecture 6; Toxicology
(General Toxicology)
Dr. Martin Awe Akilla
Department of Medical Laboratory Technology
School of Applied Sciences and Arts
BTU-Sumbrungu Campus
akillamgh78@gmail.com

2. Learning Objectives
Students should understand and appreciate:
 the Chemical basis of toxicology
 Systemic responses to toxic agents
 the toxicology of ionizing radiation
 the general toxicology of pesticides
 The toxicity of some metals
 Clinical toxicology

3. RECOMMENDED BOOKS
 Rang HP, Dale MM, Ritter JM. Pharmacology. 7th ed. Edinburgh:
Churchill Livingstone; 2007.
 Medical Pharmacology at a Glance. 8th ed. - Michael J Neal
 Goodman & Gilman's The Pharmacological Basis of Therapeutics. 12th
ed. ed. New York: McGraw-Hill, 2011.
 Champe P.C. (2005): Lippincott’s Illustrated reviews: biochemistry.
Philadelphia: Lippincott Williams and Wilkins.
 Crook M. A. (2006): Clinical chemistry and metabolic medicine (7th
ed). Edward Arnold Publishers, UK.
 Jameson J.L. (2006): Harrison’s endocrinology. New York: McGraw
Hill

4. Introduction
 2.1 million cases of human exposures reported in 2000
 92% of the exposures occurred at home
 14% occurred in a health care facility
 2% occurred at work
 Children > 3 years were involved in 40% of the cases
 52.7% occurred in children > 6 years
 Male predominance is found among poison exposures younger than
13 years
 Children > 6 comprised 2.2% of the fatalities
 59% of fatalities occur in the 20-49 year age group

5. Introduction, cont.
 85.9% of poison exposure were unintentional
 suicide intent was present in 7.5% of the cases
 therapeutic errors comprised 7% of exposures
 920 fatalities reported
 94% of adolescent and 79% of adults were intentional
 Automatic capital offense to poison someone
 Most poisonings occur at home just before meal time
 Most poisonings enter the body orally - 76.2%
 More people die in the US from suicides than from homicides

6. Definition of terms
 Toxicology - the study of poisons
 Toxicologist - one who studies poisons
 Hazard - likelihood an event will occur based on how the product is
packaged, formulated, or its accessibility
 Risk - the probability that an event will occur based on patient
vulnerability
 Toxic substance - poisons
 Poison - any chemical substance which can cause harm
 Drug overdose - taking a harmful amount of a drug

7. Definition of terms
 Antidotes: from the Greek anti - against and didonai - to give
 the remedy for counteracting a poison
 3 types:
 chemical - reacts chemically with the poison to form a harmless compound, ie. chelators
and heavy metals
 mechanical - prevents absorption, ie. activated charcoal
 physiologic - counteracts the effects of the poison by producing opposite physiologic
effects, ie. atropine and organophosphate poisoning
 Universal antidote - 2 parts activated charcoal, 1 part magnesium oxide and 1
part tannic acid

8. Historical perspective
 Poisonings date to antiquity
 Deuteronomy 14:9-10, Moses said do not eat fish which do not have fins or
scales cause it is unclean
 Job 6:4 mentions poisoned arrows
 1500 BC the Ebers papyrus
 King of Pontus first to develop antidotes in the first century before Christ

9.  Toxicon pharmacon
→Latin for
“Arrow poison”

10. Historical perspective, cont.
 Plato reported the death of Socrates by hemlock (Conium maculatum)
 13th century Peter of Abanos reviewed the literature and divided poisons
into those of plant, animal and mineral origin
 Paracelsus, 1493-1541 said that “all substances are poisons, there is none
which is not poisonous. Solely the dose determines that which is poisonous
or not.”

11. Historical perspective, cont.
 Middle ages poisoning was considered a hazard of living much like dying in an
auto crash is today
 Orfila, 1787-1853, attending physician for Louis 18th of France, wrote the first
book on General Toxicology and is considered the father of modern toxicology

12. Diversity of Toxicology
 Occupational Toxicology - OSHA - The Occupational Safety and Health Act of
1970 grew out of the need to protect workers in the work place
 Environmental Toxicology - EPA - study of chemicals that contaminate food, water,
soil and the atmosphere.
 Forensic Toxicology - medico-legal aspects of poisons
 Clinical Toxicology - deals with the pathophysiologic aspects of clinical presentation
of intoxication

13. GENERAL TOXICOLOGY
 CHEMICAL BASIS OF TOXICOLOGY
 SYSTEMIC RESPONSES TO TOXIC AGENTS
 TOXICOLOGY OF IONIZING RADIATION
 GENERAL TOXICOLOGY OF PESTICIDES
 METAL TOXICITY
 CLINICAL TOXICOLOGY

14. CHEMICAL BASIS OF TOXICOLOGY
 ABSORPTION & DISTRIBUTION
 BIOCHEMISTRY OF TOXICITY

15. CHEMICAL BASIS OF TOXICOLOGY
 ADSORPTION
 DIFFUSION
 LIPID/WATER PARTITION COEFFICIENT
 CONCENTRATION INSIDE & OUTSIDE THE CELL

16. CHEMICAL BASIS OF TOXICOLOGY
 ADSORPTION
 SPECIALIZED TRANSPORT
 ACTIVE TRANSPORT
 FACILITATED DIFFUSION
 MEMBRANE PROCESSES
 PHAGOCYTOSIS
 PINOCYTOSIS

17. CHEMICAL BASIS OF TOXICOLOGY
 ADSORPTION
 SKIN
 DMSO
 CCL4
 PARATHION/MALATHION
 SARIN (POTENT NERVE GAS)

18. CHEMICAL BASIS OF TOXICOLOGY
 ADSORPTION
 LUNGS
 PARTICULATES
 VOLATILE GASES
 VOLATILE ORGANICS

19. CHEMICAL BASIS OF TOXICOLOGY
 DISTRIBUTION
 CELL TO CELL
 ORGAN TO ORGAN
 MOVEMENT INTO TOTAL BODY WATER
 PLASMA WATER
 INTERSTITIAL WATER
 INTRACELLULAR WATER

20. CHEMICAL BASIS OF TOXICOLOGY
 BIOCHEMISTRY OF TOXICITY
 REACTION TYPES
 OXIDATION
 REDUCTION
 HYDROLYSIS
 CONJUGATION

21. CHEMICAL BASIS OF TOXICOLOGY
 OXIDATION
 OXYGEN IS INCORPORATED INTO THE SUBSTRATE

22. CHEMICAL BASIS OF TOXICOLOGY
 REDUCTION
 THE ADDITION OF ELECTRONS TO THE COMPOUND UNDERGOING REDUCTION

23. CHEMICAL BASIS OF TOXICOLOGY
 HYDROLYSIS
 THE ENZYMATIC CLEAVAGE OF BONDS BY WATER
 ADDITION OF HYDROGEN

24. CHEMICAL BASIS OF TOXICOLOGY
 CONJUGATION
 USUALLY LAST STEP IN METABOLIC TRANSFORMATION
 USUALLY GENERATE NON-TOXIC PRODUCTS OF HIGH POLARITY
 RAPID EXCRETION

25. CHEMICAL BASIS OF TOXICOLOGY
 CONJUGATION
 GLUCURONYL TRANSFER
 ACETYLATION
 SULFATION
 GLUTATHIONE CONJUGATION

26. SYSTEMIC RESPONSES TO TOXIC AGENTS
 FACTORS CONTROLLING TARGET ORGAN TOXICITY
 DERMATOTOXICOLOGY
 NEPHROTOXIC AGENTS (KIDNEYS)
 HEPATOTOXIC AGENTS (LIVER)

27. SYSTEMIC RESPONSES TO TOXIC AGENTS
 FACTORS CONTROLLING TARGET ORGAN TOXICITY
 ROUTE OF EXPOSURE
 DISTRIBUTION IN THE BODY
 METABOLISM
 EXCRETION
 SENSITIZATION

28. SYSTEMIC RESPONSES TO TOXIC AGENTS
 DERMATOTOXICOLOGY
 TOXIC DAMAGE (SKIN)
 PRIMARY IRRITATION
 ABSOLUTE IRRITANTS
 RELATIVE IRRITANTS

29. SYSTEMIC RESPONSES TO TOXIC AGENTS
 DERMATOTOXICOLOGY
 TOXIC DAMAGE (SKIN)
 SUNLIGHT-ASSOCIATED TOXICITIES
 PHOTO ALLERGY
 PHOTOTOXICITY

30. SYSTEMIC RESPONSES TO TOXIC AGENTS
 DERMATOTOXICOLOGY
 TOXIC DAMAGE (EYE)
 CORNEA
 LENS - CATARACT (DINITROPHENOL)
 RETINA
 OPTIC NERVE - BLINDNESS (CS2 , METHANOL)

31. SYSTEMIC RESPONSES TO TOXIC AGENTS
 NEPHROTOXIC AGENTS (KIDNEYS)
 HEAVY METALS
MERCURY LEAD
CADMIUM BISMUTH
URANIUM ARSENIC

32. SYSTEMIC RESPONSES TO TOXIC AGENTS
 NEPHROTOXIC AGENTS (KIDNEYS)
 MISCELLANEOUS CHEMICALS
ETHYLENE GLYCOL
CARBON TETRACHLORIDE
KEROSENE

33. SYSTEMIC RESPONSES TO TOXIC AGENTS
 HEPATOTOXIC AGENTS (LIVER)
 TOXICITY ASSOCIATED WITH LIPID SOLUBLE AGENTS
 DIRECT LIVER INJURY
 ALCOHOLIC TYPE
 TOXIC METABOLITE
 CHRONIC HEPATOTOXICITY

34. SYSTEMIC RESPONSES TO TOXIC AGENTS
 HEPATOTOXIC AGENTS (LIVER)
 HEPATIC CHEMICAL CARCINOGENS
VINYL CHLORIDE ARSENIC
PHENOBARBITAL BUTTER YELLOW
TRICHLOROETHYLENE DIOXANE
AFLATOXIN NITROSAMINES
POLYHALOGENATED POLYCYCLIC HYDROCARBONS

35. TOXICOLOGY OF IONIZING RADIATION
 INTERACTIONS OF IONIZING RADIATION WITH MATTER
 EFFECTS ON BIOLOGICAL SYSTEMS

36. TOXICOLOGY OF IONIZING RADIATION
 INTERACTIONS OF IONIZING RADIATION WITH MATTER
 INDIRECTLY IONIZING (PHOTONS)
 X-RAYS
 GAMMA RAYS
 NEUTRONS
 NEUTRAL MESONS

37. TOXICOLOGY OF IONIZING RADIATION
 INTERACTIONS OF IONIZING RADIATION WITH MATTER
 DIRECTLY IONIZING (CORPUSCULAR)
 POSITRONS
 ALPHA PARTICLES
 BETA PARTICLES
 CHARGED MESONS
 ACCELERATOR PARTICLES
 FISSION FRAGMENTS

38. TOXICOLOGY OF IONIZING RADIATION
 EFFECTS ON BIOLOGICAL SYSTEMS
 ACUTE RESPONSE
 SKIN
 GASTROINTESTINAL SYSTEM
 HEMATOPOIETIC SYSTEM
 CENTRAL NERVOUS SYSTEM SYNDROME

39. TOXICOLOGY OF IONIZING RADIATION
 EFFECTS ON BIOLOGICAL SYSTEMS
 LOW LEVEL RESPONSE
 RADIATION CARCINOGENESIS
 5 REM (ROENTGEN EQUIVALENT MAN)

40. GENERAL TOXICOLOGY OF PESTICIDES
 CHLORINATED HYDROCARBON PESTICIDES
 ORGANOPHOSPHATE & CARBAMATE INSECTICIDES
 HERBICIDES
 PYRETHROID INSECTICIDES

41. GENERAL TOXICOLOGY OF PESTICIDES
 CHLORINATED HYDROCARBON PESTICIDES
 LIPID SOLUBLE
 BIO-ACCUMULATION
 MANY ARE CARCINOGENIC
 ALDRIN
 DIELDRIN

42. GENERAL TOXICOLOGY OF PESTICIDES
 ORGANOPHOSPHATE & CARBAMATE INSECTICIDES
 CHOLINESTERASE INHIBITORS
 ATROPINE
 PRALIDOXIME (2-PAM)
 DELAYED NEUROPATHY
 TRI-ORTHO-CRESYL PHOSPHATE (TOCP)

43. GENERAL TOXICOLOGY OF PESTICIDES
 HERBICIDES
 GREATEST TOTAL VOLUME OF PRODUCTION
 KILL PLANTS OR INHIBIT PLANT GROWTH
 AMINOTRIAZOLE
 2,4-DICHLOROPHENOXYACETIC ACID (2,4-D)

44. GENERAL TOXICOLOGY OF PESTICIDES
 PYRETHROID INSECTICIDES
 NATURAL & SYNTHETIC ANALOGUES
 POTENTIAL NEUROTOXICANTS
 FAIRLY LARGE DOSES REQUIRED
 RELATIVELY SAFE INSECTICIDES

45. METAL TOXICITY
 GENERAL FACTORS INFLUENCING TOXICITY
 TOXIC ACTION OF SPECIFIC METALS

46. METAL TOXICITY
 ALKALINE EARTH METALS
 Na, K, Ca, Fe
 ESSENTIAL TRACE ELEMENTS
 Zn, Mg, Cu, Ni, Mn, Co, Cr, I, Me, Se

47. METAL TOXICITY
 GENERAL FACTORS INFLUENCING TOXICITY
 MOLECULAR SITE OF ACTION
 ABSORPTION
 ORGAN SELECTIVITY

48. METAL TOXICITY
 GENERAL FACTORS INFLUENCING TOXICITY
 SOLUBILITY
 ELECTROCHEMICAL NATURE
 ABILITY TO FORM STABLE LIGANDS OR CHELATES

49. METAL TOXICITY
 TOXIC ACTION OF SPECIFIC METALS
 GROUP IA (Li, Na, K, Rb, Cs)
 ESSENTIAL ELEMENTS
 EXCESSIVE INTAKE CAN INDUCE TOXICITY

50. METAL TOXICITY
 TOXIC ACTION OF SPECIFIC METALS
 GROUP IB (Cu, Ag, Au)
 BASICALLY NON-TOXIC

51. METAL TOXICITY
 TOXIC ACTION OF SPECIFIC METALS
 GROUP IIA (Be, Mg, Ca, Sr, Ba)
 BASICALLY NON-TOXIC
 BERYLLIUM CAUSES LUNG FIBROSIS

52. METAL TOXICITY
 TOXIC ACTION OF SPECIFIC METALS
 GROUP IIB (Zn, Cd, Hg)
 FORM STRONG COVALENT BONDS - AFFINITY FOR THIOL BONDS
 MERCURY & CADMIUM HAVE CUMULATIVE EFFECT

53. METAL TOXICITY
 TOXIC ACTION OF SPECIFIC METALS
 GROUP IIIA (Al, In, Tl)
 RARELY CAUSE INTOXICATION DUE TO LIMITED USAGE
 DAMAGE INVOLVES KIDNEY & LIVER NECROSIS AND SEVERE BRAIN DAMAGE

54. METAL TOXICITY
 TOXIC ACTION OF SPECIFIC METALS
 GROUP IIIB (Sc, Y, and LANTHANIDES)
 LOW SOLUBILITY AND RARITY OF EXPOSURE
 THORIUM IS AN EXCEPTION DUE TO RADIOACTIVITY

55. METAL TOXICITY
 TOXIC ACTION OF SPECIFIC METALS
 GROUP IVA (Ge, Sn, Pb)
 GERMANIUM & TIN ARE OF LOW SOLUBILITY AND TOXICITY
 ORGANIC FORMS CAUSE NEUROTOXICITY
 LEAD - INORGANIC & ORGANIC FORMS HIGHLY TOXIC

56. METAL TOXICITY
 TOXIC ACTION OF SPECIFIC METALS
 GROUP IVB (Ti, Zr, Hf)
 LOW SOLUBILITY AND TOXICITY
 ZIRCONIUM PRODUCES HYPER-SENSITIVITY IN SKIN & LUNG
 DEODORANTS
 HAIR SPRAYS

57. METAL TOXICITY
 TOXIC ACTION OF SPECIFIC METALS
 GROUP V (ARSENIC [As])
 EXPOSURE MAINLY IN MANUFACTURING
 WEED KILLERS
 WOOD PERSERVATIVES
 INSECTICIDES

58. METAL TOXICITY
 TOXIC ACTION OF SPECIFIC METALS
 GROUP V (ARSENIC [As])
 As2O5 BROKEN DOWN TO As2O3 (MORE TOXIC FORM)
 PROGRESSIVE NEUROPATHY, ANEMIA AND ULCERATION OF NASAL SEPTUM
 CANCER OF SKIN, LUNG AND UPPER RESPIRATORY TRACT

59. CLINICAL TOXICOLOGY

60. CLINICAL TOXICOLOGY
Drugs That Increase Sexual Gratification
 Sildenafil (Viagra)
 For hypotension, administer normal saline.
 For cardiac arrest, follow local protocols.
 Marijuana
 Supportive care is indicated.

61. CLINICAL TOXICOLOGY
Drugs That Increase Sexual Gratification
 Cocaine and other stimulant drugs
 Administer serial boluses of normal saline.
 Amyl nitrite
 Hypotension may result.
 Ecstasy

62. CLINICAL TOXICOLOGY
Drugs That Increase Sexual Gratification
 Dextromethorphan
 Large doses can lead to:
 Hallucinations
 Loss of motor control
 Dream like euphoria

63. CLINICAL TOXICOLOGY
Drugs Used to Facilitate Sexual Assault
 GHB (Gamma-hydroxybutyrate)
 Odorless and colorless liquid, with a salty taste
 Exerts its effects within 30 to 60 minutes
 Can produce a hypnotic effect

64. CLINICAL TOXICOLOGY
Drugs Used to Facilitate Sexual Assault
 GHB (cont’d)
 Establish and maintain the airway.
 Monitor LOC.
 Assist breathing and administer oxygen.
 Establish vascular access.
 Provide rapid transport.

65. CLINICAL TOXICOLOGY
Drugs Used to Facilitate Sexual Assault
 Rohypnol (roofies)
 Potent benzodiazepine
 Illegal to make or distribute

66. CLINICAL TOXICOLOGY
TEMPERATURE
INCREASED DECREASED
AMPHETAMINES ALCOHOLS
COCAINE BARBITURATES
BELLADONNA ALKALOIDS CLONIDINE
FLUOROACETATE GLUTETHIMIDE
HEXACHLOROBENZENE HALOPERIDOL
SALICYLATES PHENOTHIAZINES
TRICYCLIC ANTIDEPRESSANTS

67. CLINICAL TOXICOLOGY
PULSE
BRADYCARDIA ARRHYTHMIAS
ALCOHOLS ARSENIC
CARBAMATES CAFFEINE
ORGANOPHOSPHATES SOLVENTS

68. CLINICAL TOXICOLOGY
RESPIRATORY RATE
INCREASED DECREASED
CARBON MONOXIDE ALCOHOLS
CYANIDE CO
FLUOROACETATE CYANIDE
HEXACHLOROBENZENE PHENOTHIAZINES
METHANOL
NITRITES

69. CLINICAL TOXICOLOGY
BLOOD PRESSURE
INCREASED DECREASED
AMPHETAMINES BARBITURATES
BELLADONNA ALKALOIDS CYANIDE
COCAINE IRON
PHENCYCLIDINE NITRITES

70. CLINICAL TOXICOLOGY
SKIN
DRY MOIST
ANTIHISTAMINES ALCOHOLS
BELLADONNA ALKALOIDS ARSENIC
GLUTETHIMIDE CARBAMATES
MERCURY
ORGANOPHOSPHATES
THALLIUM

71. CLINICAL TOXICOLOGY
SKIN COLOR
FLUSHED CYANOTIC
ALCOHOLS ANILINE DYES
BORIC ACID CO
CARBON MONOXIDE CYANIDE
MSG NITRITES
NITRITES

72. CLINICAL TOXICOLOGY
SKIN COLOR
JAUNDICED
ANILINE DYES
ARSENIC
ARSINE GAS
CARBON TETRACHLORIDE
IRON
PHOSPHORUS

73. CLINICAL TOXICOLOGY
ODORS
ACETONE: ACETONE, ALCOHOLS, PHENOLS
AROMATIC: HYDROCARBONS
BITTER ALMONDS: CYANIDE
GARLIC:ARSENIC, DMSO, ORGANOPHOSPHATES, PHOSPHATES, TELLURIUM,
THALLIUM
PEARS: CHLORAL HYDRATE
ROTTEN EGGS: HYDROGEN SULFIDE
SHOE POLISH: NITROBENZENE
VIOLETS: TURPENTINE
WINTERGREEN: METHYLSALICYLATE

74. CLINICAL TOXICOLOGY
GASTROINTESTINAL TRACT
VOMITING PAIN
ACIDS ARSENIC
ALKALI IRON
ARSENIC BLACK WIDOW
CAMPHOR
IRON
FLUORIDE

75. CLINICAL TOXICOLOGY
CENTRAL NERVOUS SYSTEM
CONVULSIONS COMA
CAMPHOR ALCOHOL
CHLORINATED HYDROCARBONS CARBAMATES
LEAD CO
NICOTINE CYANIDE
ORGANOPHOSPHATES HYDROCARBONS
PHENOTHIAZINES H2S
LEAD
ORGANOPHOSPHATES

76. CLINICAL TOXICOLOGY
CENTRAL NERVOUS SYSTEM
ATAXIA PARALYSIS
ALCOHOLS CARBAMATES
HYDROCARBONS THALLIUM
PHENYTOIN ORGANOPHOSPHATES

77. CLINICAL TOXICOLOGY
ANTIDOTES
 COMPETITIVE ANTAGONIST
 OXYGEN FOR CARBON MONOXIDE POISONING
 NONCOMPETITIVE ANTAGONIST
 ATROPINE FOR ORGANOPHOSPHATE POISONING

78. CLINICAL TOXICOLOGY
ANTIDOTES
 CHEMICAL NEUTRALIZATION
 SODIUM THIOSULFATE FOR CYANIDE POISONING
 METABOLIC INHIBITION
 ETHANOL FOR METHANOL POISONING

79. CLINICAL TOXICOLOGY
ANTIDOTES
 OXIDATION-REDUCTION REACTIONS
 METHYLENE BLUE FOR METHEMOHEMOGLOBINEMIA
(CYANIDE)
 CHELATING AGENTS
 CALCIUM EDTA FOR LEAD OR ZINC POISONING
 DIMERCAPROL (BAL) FOR ARSENIC POISONING

80. THANK YOU