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GENERAL TOXICOLOGY.  CHEMICAL BASIS OF TOXICOLOGY  SYSTEMIC RESPONSES TO TOXIC AGENTS  TOXICOLOGY OF IONIZING RADIATION  GENERAL TOXICOLOGY OF PESTICIDES.

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Presentation on theme: "GENERAL TOXICOLOGY.  CHEMICAL BASIS OF TOXICOLOGY  SYSTEMIC RESPONSES TO TOXIC AGENTS  TOXICOLOGY OF IONIZING RADIATION  GENERAL TOXICOLOGY OF PESTICIDES."— Presentation transcript:

1 GENERAL TOXICOLOGY

2  CHEMICAL BASIS OF TOXICOLOGY  SYSTEMIC RESPONSES TO TOXIC AGENTS  TOXICOLOGY OF IONIZING RADIATION  GENERAL TOXICOLOGY OF PESTICIDES  METAL TOXICITY  CLINICAL TOXICOLOGY

3 CHEMICAL BASIS OF TOXICOLOGY  ABSORPTION & DISTRIBUTION  BIOCHEMISTRY OF TOXICITY

4 CHEMICAL BASIS OF TOXICOLOGY  ADSORPTION DIFFUSION DIFFUSION »LIPID/WATER PARTITION COEFFICIENT »CONCENTRATION INSIDE & OUTSIDE THE CELL

5 CHEMICAL BASIS OF TOXICOLOGY  ADSORPTION SPECIALIZED TRANSPORT SPECIALIZED TRANSPORT »ACTIVE TRANSPORT »FACILITATED DIFFUSION »MEMBRANE PROCESSES n PHAGOCYTOSIS n PINOCYTOSIS

6 CHEMICAL BASIS OF TOXICOLOGY  ADSORPTION SKIN SKIN »DMSO »CCL 4 »PARATHION/MALATHION »SARIN (POTENT NERVE GAS)

7 CHEMICAL BASIS OF TOXICOLOGY  ADSORPTION LUNGS LUNGS »PARTICULATES »VOLATILE GASES »VOLATILE ORGANICS

8 CHEMICAL BASIS OF TOXICOLOGY  DISTRIBUTION CELL TO CELL CELL TO CELL ORGAN TO ORGAN ORGAN TO ORGAN MOVEMENT INTO TOTAL BODY WATER MOVEMENT INTO TOTAL BODY WATER »PLASMA WATER »INTERSTITIAL WATER »INTRACELLULAR WATER

9 CHEMICAL BASIS OF TOXICOLOGY  BIOCHEMISTRY OF TOXICITY REACTION TYPES REACTION TYPES »OXIDATION »REDUCTION »HYDROLYSIS »CONJUGATION

10 CHEMICAL BASIS OF TOXICOLOGY  OXIDATION OXYGEN IS INCORPORATED INTO THE SUBSTRATE OXYGEN IS INCORPORATED INTO THE SUBSTRATE

11 CHEMICAL BASIS OF TOXICOLOGY  REDUCTION THE ADDITION OF ELECTRONS TO THE COMPOUND UNDERGOING REDUCTION THE ADDITION OF ELECTRONS TO THE COMPOUND UNDERGOING REDUCTION

12 CHEMICAL BASIS OF TOXICOLOGY  HYDROLYSIS THE ENZYMATIC CLEAVAGE OF BONDS BY WATER THE ENZYMATIC CLEAVAGE OF BONDS BY WATER »ADDITION OF HYDROGEN

13 CHEMICAL BASIS OF TOXICOLOGY  CONJUGATION USUALLY LAST STEP IN METABOLIC TRANSFORMATION USUALLY LAST STEP IN METABOLIC TRANSFORMATION USUALLY GENERATE NON-TOXIC PRODUCTS OF HIGH POLARITY USUALLY GENERATE NON-TOXIC PRODUCTS OF HIGH POLARITY »RAPID EXCRETION

14 CHEMICAL BASIS OF TOXICOLOGY  CONJUGATION GLUCURONYL TRANSFER GLUCURONYL TRANSFER ACETYLATION ACETYLATION SULFATION SULFATION GLUTATHIONE CONJUGATION GLUTATHIONE CONJUGATION

15 SYSTEMIC RESPONSES TO TOXIC AGENTS  FACTORS CONTROLLING TARGET ORGAN TOXICITY  DERMATOTOXICOLOGY  NEPHROTOXIC AGENTS (KIDNEYS)  HEPATOTOXIC AGENTS (LIVER)

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

17 SYSTEMIC RESPONSES TO TOXIC AGENTS  DERMATOTOXICOLOGY TOXIC DAMAGE (SKIN) TOXIC DAMAGE (SKIN) »PRIMARY IRRITATION n ABSOLUTE IRRITANTS n RELATIVE IRRITANTS

18 SYSTEMIC RESPONSES TO TOXIC AGENTS  DERMATOTOXICOLOGY TOXIC DAMAGE (SKIN) TOXIC DAMAGE (SKIN) »SUNLIGHT-ASSOCIATED TOXICITIES n PHOTO ALLERGY n PHOTOTOXICITY

19 SYSTEMIC RESPONSES TO TOXIC AGENTS  DERMATOTOXICOLOGY TOXIC DAMAGE (EYE) TOXIC DAMAGE (EYE) »CORNEA »LENS - CATARACT (DINITROPHENOL) »RETINA »OPTIC NERVE - BLINDNESS (CS 2, METHANOL)

20 SYSTEMIC RESPONSES TO TOXIC AGENTS  NEPHROTOXIC AGENTS (KIDNEYS) HEAVY METALS HEAVY METALS MERCURYLEAD CADMIUMBISMUTH URANIUMARSENIC

21 SYSTEMIC RESPONSES TO TOXIC AGENTS  NEPHROTOXIC AGENTS (KIDNEYS) MISCELLANEOUS CHEMICALS MISCELLANEOUS CHEMICALS ETHYLENE GLYCOL CARBON TETRACHLORIDE KEROSENE

22 SYSTEMIC RESPONSES TO TOXIC AGENTS  HEPATOTOXIC AGENTS (LIVER) TOXICITY ASSOCIATED WITH LIPID SOLUBLE AGENTS TOXICITY ASSOCIATED WITH LIPID SOLUBLE AGENTS DIRECT LIVER INJURY DIRECT LIVER INJURY »ALCOHOLIC TYPE »TOXIC METABOLITE CHRONIC HEPATOTOXICITY CHRONIC HEPATOTOXICITY

23 SYSTEMIC RESPONSES TO TOXIC AGENTS  HEPATOTOXIC AGENTS (LIVER) HEPATIC CHEMICAL CARCINOGENS HEPATIC CHEMICAL CARCINOGENS VINYL CHLORIDEARSENIC PHENOBARBITALBUTTER YELLOW TRICHLOROETHYLENEDIOXANE AFLATOXINNITROSAMINES POLYHALOGENATED POLYCYCLIC HYDROCARBONS

24 TOXICOLOGY OF IONIZING RADIATION  INTERACTIONS OF IONIZING RADIATION WITH MATTER  EFFECTS ON BIOLOGICAL SYSTEMS

25 TOXICOLOGY OF IONIZING RADIATION  INTERACTIONS OF IONIZING RADIATION WITH MATTER INDIRECTLY IONIZING (PHOTONS) INDIRECTLY IONIZING (PHOTONS) »X-RAYS »GAMMA RAYS »NEUTRONS »NEUTRAL MESONS

26 TOXICOLOGY OF IONIZING RADIATION  INTERACTIONS OF IONIZING RADIATION WITH MATTER DIRECTLY IONIZING (CORPUSCULAR) DIRECTLY IONIZING (CORPUSCULAR) »POSITRONS »ALPHA PARTICLES »BETA PARTICLES »CHARGED MESONS »ACCELERATOR PARTICLES »FISSION FRAGMENTS

27 TOXICOLOGY OF IONIZING RADIATION  EFFECTS ON BIOLOGICAL SYSTEMS ACUTE RESPONSE ACUTE RESPONSE »SKIN »GASTROINTESTINAL SYSTEM »HEMATOPOIETIC SYSTEM »CENTRAL NERVOUS SYSTEM SYNDROME

28 TOXICOLOGY OF IONIZING RADIATION  EFFECTS ON BIOLOGICAL SYSTEMS LOW LEVEL RESPONSE LOW LEVEL RESPONSE »RADIATION CARCINOGENESIS n 5 REM (ROENTGEN EQUIVALENT MAN)

29 GENERAL TOXICOLOGY OF PESTICIDES  CHLORINATED HYDROCARBON PESTICIDES  ORGANOPHOSPHATE & CARBAMATE INSECTICIDES  HERBICIDES  PYRETHROID INSECTICIDES

30 GENERAL TOXICOLOGY OF PESTICIDES  CHLORINATED HYDROCARBON PESTICIDES LIPID SOLUBLE LIPID SOLUBLE BIO-ACCUMULATION BIO-ACCUMULATION MANY ARE CARCINOGENIC MANY ARE CARCINOGENIC »ALDRIN »DIELDRIN

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

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

33 GENERAL TOXICOLOGY OF PESTICIDES  PYRETHROID INSECTICIDES NATURAL & SYNTHETIC ANALOGUES NATURAL & SYNTHETIC ANALOGUES POTENTIAL NEUROTOXICANTS POTENTIAL NEUROTOXICANTS »FAIRLY LARGE DOSES REQUIRED RELATIVELY SAFE INSECTICIDES RELATIVELY SAFE INSECTICIDES

34 METAL TOXICITY  GENERAL FACTORS INFLUENCING TOXICITY  TOXIC ACTION OF SPECIFIC METALS

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

36 METAL TOXICITY  GENERAL FACTORS INFLUENCING TOXICITY MOLECULAR SITE OF ACTION MOLECULAR SITE OF ACTION ABSORPTION ABSORPTION ORGAN SELECTIVITY ORGAN SELECTIVITY

37 METAL TOXICITY  GENERAL FACTORS INFLUENCING TOXICITY SOLUBILITY SOLUBILITY ELECTROCHEMICAL NATURE ELECTROCHEMICAL NATURE ABILITY TO FORM STABLE LIGANDS OR CHELATES ABILITY TO FORM STABLE LIGANDS OR CHELATES

38 METAL TOXICITY  TOXIC ACTION OF SPECIFIC METALS GROUP IA (Li, Na, K, Rb, Cs) GROUP IA (Li, Na, K, Rb, Cs) »ESSENTIAL ELEMENTS »EXCESSIVE INTAKE CAN INDUCE TOXICITY

39 METAL TOXICITY  TOXIC ACTION OF SPECIFIC METALS GROUP IB (Cu, Ag, Au) GROUP IB (Cu, Ag, Au) »BASICALLY NON-TOXIC

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

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

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

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

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

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

46 METAL TOXICITY  TOXIC ACTION OF SPECIFIC METALS GROUP V (ARSENIC [As]) GROUP V (ARSENIC [As]) »EXPOSURE MAINLY IN MANUFACTURING n WEED KILLERS n WOOD PERSERVATIVES n INSECTICIDES

47 METAL TOXICITY  TOXIC ACTION OF SPECIFIC METALS GROUP V (ARSENIC [As]) GROUP V (ARSENIC [As]) »As 2 O 5 BROKEN DOWN TO As 2 O 3 (MORE TOXIC FORM) »PROGRESSIVE NEUROPATHY, ANEMIA AND ULCERATION OF NASAL SEPTUM »CANCER OF SKIN, LUNG AND UPPER RESPIRATORY TRACT

48 CLINICAL TOXICOLOGY

49 TEMPERATURE INCREASEDDECREASED AMPHETAMINESALCOHOLS COCAINEBARBITURATES BELLADONNA ALKALOIDSCLONIDINE FLUOROACETATEGLUTETHIMIDE HEXACHLOROBENZENEHALOPERIDOL SALICYLATESPHENOTHIAZINES TRICYCLIC ANTIDEPRESSANTS

50 CLINICAL TOXICOLOGY PULSE BRADYCARDIAARRHYTHMIAS ALCOHOLSARSENIC CARBAMATESCAFFEINE ORGANOPHOSPHATESSOLVENTS

51 CLINICAL TOXICOLOGY RESPIRATORY RATE INCREASEDDECREASED CARBON MONOXIDEALCOHOLS CYANIDECO FLUOROACETATECYANIDE HEXACHLOROBENZENEPHENOTHIAZINES METHANOLNITRITES

52 CLINICAL TOXICOLOGY BLOOD PRESSURE INCREASEDDECREASED AMPHETAMINESBARBITURATES BELLADONNA ALKALOIDSCYANIDE COCAINEIRON PHENCYCLIDINENITRITES

53 CLINICAL TOXICOLOGY SKIN DRYMOIST ANTIHISTAMINESALCOHOLS BELLADONNA ALKALOIDSARSENIC GLUTETHIMIDECARBAMATES MERCURY ORGANOPHOSPHATES ORGANOPHOSPHATES THALLIUM THALLIUM

54 CLINICAL TOXICOLOGY SKIN COLOR FLUSHEDCYANOTIC ALCOHOLSANILINE DYES BORIC ACIDCO CARBON MONOXIDECYANIDE MSGNITRITES NITRITES

55 CLINICAL TOXICOLOGY SKIN COLOR JAUNDICED ANILINE DYES ARSENIC ARSINE GAS CARBON TETRACHLORIDE IRONPHOSPHORUS

56 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

57 CLINICAL TOXICOLOGY GASTROINTESTINAL TRACT VOMITINGPAIN ACIDSARSENIC ALKALIIRON ARSENICBLACK WIDOW CAMPHORIRONFLUORIDE

58 CLINICAL TOXICOLOGY CENTRAL NERVOUS SYSTEM CONVULSIONSCOMA CAMPHORALCOHOL CHLORINATED HYDROCARBONSCARBAMATES LEADCO NICOTINECYANIDE ORGANOPHOSPHATESHYDROCARBONS PHENOTHIAZINESH 2 S LEAD LEAD ORGANOPHOSPHATES ORGANOPHOSPHATES

59 CLINICAL TOXICOLOGY CENTRAL NERVOUS SYSTEM ATAXIAPARALYSIS ALCOHOLSCARBAMATES HYDROCARBONSTHALLIUM PHENYTOIN ORGANOPHOSPHATES

60 CLINICAL TOXICOLOGY ANTIDOTES  COMPETITIVE ANTAGONIST OXYGEN FOR CARBON MONOXIDE POISONING OXYGEN FOR CARBON MONOXIDE POISONING  NONCOMPETITIVE ANTAGONIST ATROPINE FOR ORGANOPHOSPHATE POISONING ATROPINE FOR ORGANOPHOSPHATE POISONING

61 CLINICAL TOXICOLOGY ANTIDOTES  CHEMICAL NEUTRALIZATION SODIUM THIOSULFATE FOR CYANIDE POISONING SODIUM THIOSULFATE FOR CYANIDE POISONING  METABOLIC INHIBITION ETHANOL FOR METHANOL POISONING ETHANOL FOR METHANOL POISONING

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


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