Transcript Toxicology_2.ppt

GENERAL TOXICOLOGY
GENERAL TOXICOLOGY

CHEMICAL BASIS OF TOXICOLOGY

SYSTEMIC RESPONSES TO TOXIC AGENTS

TOXICOLOGY OF IONIZING RADIATION

GENERAL TOXICOLOGY OF PESTICIDES

METAL TOXICITY

CLINICAL TOXICOLOGY
CHEMICAL BASIS OF
TOXICOLOGY

ABSORPTION & DISTRIBUTION

BIOCHEMISTRY OF TOXICITY
CHEMICAL BASIS OF TOXICOLOGY

ADSORPTION
DIFFUSION
» LIPID/WATER PARTITION COEFFICIENT
» CONCENTRATION INSIDE & OUTSIDE THE
CELL
CHEMICAL BASIS OF TOXICOLOGY

ADSORPTION
SPECIALIZED TRANSPORT
» ACTIVE TRANSPORT
» FACILITATED DIFFUSION
» MEMBRANE PROCESSES
 PHAGOCYTOSIS
 PINOCYTOSIS
CHEMICAL BASIS OF TOXICOLOGY

ADSORPTION
SKIN
» DMSO
» CCL4
» PARATHION/MALATHION
» SARIN (POTENT NERVE GAS)
CHEMICAL BASIS OF TOXICOLOGY

ADSORPTION
LUNGS
» PARTICULATES
» VOLATILE GASES
» VOLATILE ORGANICS
CHEMICAL BASIS OF TOXICOLOGY

DISTRIBUTION
CELL TO CELL
ORGAN TO ORGAN
MOVEMENT INTO TOTAL BODY WATER
» PLASMA WATER
» INTERSTITIAL WATER
» INTRACELLULAR WATER
CHEMICAL BASIS OF TOXICOLOGY

BIOCHEMISTRY OF TOXICITY
REACTION TYPES
» OXIDATION
» REDUCTION
» HYDROLYSIS
» CONJUGATION
CHEMICAL BASIS OF TOXICOLOGY

OXIDATION
OXYGEN IS INCORPORATED INTO THE
SUBSTRATE
CHEMICAL BASIS OF TOXICOLOGY

REDUCTION
THE ADDITION OF ELECTRONS TO THE
COMPOUND UNDERGOING REDUCTION
CHEMICAL BASIS OF TOXICOLOGY

HYDROLYSIS
THE ENZYMATIC CLEAVAGE OF BONDS
BY WATER
» ADDITION OF HYDROGEN
CHEMICAL BASIS OF TOXICOLOGY

CONJUGATION
USUALLY LAST STEP IN METABOLIC
TRANSFORMATION
USUALLY GENERATE NON-TOXIC
PRODUCTS OF HIGH POLARITY
» RAPID EXCRETION
CHEMICAL BASIS OF TOXICOLOGY

CONJUGATION
GLUCURONYL TRANSFER
ACETYLATION
SULFATION
GLUTATHIONE CONJUGATION
SYSTEMIC RESPONSES TO TOXIC
AGENTS

FACTORS CONTROLLING TARGET ORGAN
TOXICITY

DERMATOTOXICOLOGY

NEPHROTOXIC AGENTS (KIDNEYS)

HEPATOTOXIC AGENTS (LIVER)
SYSTEMIC RESPONSES TO TOXIC AGENTS

FACTORS CONTROLLING TARGET ORGAN
TOXICITY
ROUTE OF EXPOSURE
DISTRIBUTION IN THE BODY
METABOLISM
EXCRETION
SENSITIZATION
SYSTEMIC RESPONSES TO TOXIC AGENTS

DERMATOTOXICOLOGY
TOXIC DAMAGE (SKIN)
» PRIMARY IRRITATION
 ABSOLUTE
 RELATIVE
IRRITANTS
IRRITANTS
SYSTEMIC RESPONSES TO TOXIC AGENTS

DERMATOTOXICOLOGY
TOXIC DAMAGE (SKIN)
» SUNLIGHT-ASSOCIATED TOXICITIES
 PHOTO ALLERGY
 PHOTOTOXICITY
SYSTEMIC RESPONSES TO TOXIC AGENTS

DERMATOTOXICOLOGY
TOXIC DAMAGE (EYE)
» CORNEA
» LENS - CATARACT (DINITROPHENOL)
» RETINA
» OPTIC NERVE - BLINDNESS (CS2 , METHANOL)
SYSTEMIC RESPONSES TO TOXIC AGENTS

NEPHROTOXIC AGENTS (KIDNEYS)
HEAVY METALS
MERCURY
LEAD
CADMIUM
BISMUTH
URANIUM
ARSENIC
SYSTEMIC RESPONSES TO TOXIC AGENTS

NEPHROTOXIC AGENTS (KIDNEYS)
MISCELLANEOUS CHEMICALS
ETHYLENE GLYCOL
CARBON TETRACHLORIDE
KEROSENE
SYSTEMIC RESPONSES TO TOXIC AGENTS

HEPATOTOXIC AGENTS (LIVER)
TOXICITY ASSOCIATED WITH LIPID
SOLUBLE AGENTS
DIRECT LIVER INJURY
» ALCOHOLIC TYPE
» TOXIC METABOLITE
CHRONIC HEPATOTOXICITY
SYSTEMIC RESPONSES TO TOXIC AGENTS

HEPATOTOXIC AGENTS (LIVER)
HEPATIC CHEMICAL CARCINOGENS
VINYL CHLORIDE
ARSENIC
PHENOBARBITAL
BUTTER YELLOW
TRICHLOROETHYLENE
DIOXANE
AFLATOXIN
NITROSAMINES
POLYHALOGENATED POLYCYCLIC HYDROCARBONS
TOXICOLOGY OF IONIZING
RADIATION

INTERACTIONS OF IONIZING RADIATION
WITH MATTER

EFFECTS ON BIOLOGICAL SYSTEMS
TOXICOLOGY OF IONIZING RADIATION

INTERACTIONS OF IONIZING RADIATION
WITH MATTER
INDIRECTLY IONIZING (PHOTONS)
» X-RAYS
» GAMMA RAYS
» NEUTRONS
» NEUTRAL MESONS
TOXICOLOGY OF IONIZING RADIATION

INTERACTIONS OF IONIZING RADIATION
WITH MATTER
DIRECTLY IONIZING (CORPUSCULAR)
»
»
»
»
»
»
POSITRONS
ALPHA PARTICLES
BETA PARTICLES
CHARGED MESONS
ACCELERATOR PARTICLES
FISSION FRAGMENTS
TOXICOLOGY OF IONIZING RADIATION

EFFECTS ON BIOLOGICAL SYSTEMS
ACUTE RESPONSE
» SKIN
» GASTROINTESTINAL SYSTEM
» HEMATOPOIETIC SYSTEM
» CENTRAL NERVOUS SYSTEM SYNDROME
TOXICOLOGY OF IONIZING RADIATION

EFFECTS ON BIOLOGICAL SYSTEMS
LOW LEVEL RESPONSE
» RADIATION CARCINOGENESIS

5 REM (ROENTGEN EQUIVALENT MAN)
GENERAL TOXICOLOGY OF
PESTICIDES

CHLORINATED HYDROCARBON
PESTICIDES

ORGANOPHOSPHATE & CARBAMATE
INSECTICIDES

HERBICIDES

PYRETHROID INSECTICIDES
GENERAL TOXICOLOGY OF PESTICIDES

CHLORINATED HYDROCARBON
PESTICIDES
LIPID SOLUBLE
BIO-ACCUMULATION
MANY ARE CARCINOGENIC
» ALDRIN
» DIELDRIN
GENERAL TOXICOLOGY OF PESTICIDES

ORGANOPHOSPHATE & CARBAMATE
INSECTICIDES
CHOLINESTERASE INHIBITORS
» ATROPINE
» PRALIDOXIME (2-PAM)
DELAYED NEUROPATHY
» TRI-ORTHO-CRESYL PHOSPHATE (TOCP)
GENERAL TOXICOLOGY OF PESTICIDES

HERBICIDES
GREATEST TOTAL VOLUME OF PRODUCTION
KILL PLANTS OR INHIBIT PLANT GROWTH
» AMINOTRIAZOLE
» 2,4-DICHLOROPHENOXYACETIC ACID (2,4-D)
GENERAL TOXICOLOGY OF PESTICIDES

PYRETHROID INSECTICIDES
NATURAL & SYNTHETIC ANALOGUES
POTENTIAL NEUROTOXICANTS
» FAIRLY LARGE DOSES REQUIRED
RELATIVELY SAFE INSECTICIDES
METAL TOXICITY

GENERAL FACTORS INFLUENCING
TOXICITY

TOXIC ACTION OF SPECIFIC METALS
METAL TOXICITY

ALKALINE EARTH METALS
Na, K, Ca, Fe

ESSENTIAL TRACE ELEMENTS
Zn, Mg, Cu, Ni, Mn, Co, Cr, I, Me, Se
METAL TOXICITY

GENERAL FACTORS INFLUENCING
TOXICITY
MOLECULAR SITE OF ACTION
ABSORPTION
ORGAN SELECTIVITY
METAL TOXICITY

GENERAL FACTORS INFLUENCING
TOXICITY
SOLUBILITY
ELECTROCHEMICAL NATURE
ABILITY TO FORM STABLE LIGANDS OR
CHELATES
METAL TOXICITY

TOXIC ACTION OF SPECIFIC METALS
GROUP IA (Li, Na, K, Rb, Cs)
» ESSENTIAL ELEMENTS
» EXCESSIVE INTAKE CAN INDUCE
TOXICITY
METAL TOXICITY

TOXIC ACTION OF SPECIFIC METALS
GROUP IB (Cu, Ag, Au)
» BASICALLY NON-TOXIC
METAL TOXICITY

TOXIC ACTION OF SPECIFIC METALS
GROUP IIA (Be, Mg, Ca, Sr, Ba)
» BASICALLY NON-TOXIC
» BERYLLIUM CAUSES LUNG FIBROSIS
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
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
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
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
METAL TOXICITY

TOXIC ACTION OF SPECIFIC METALS
GROUP IVB (Ti, Zr, Hf)
» LOW SOLUBILITY AND TOXICITY
» ZIRCONIUM PRODUCES HYPERSENSITIVITY IN SKIN & LUNG
 DEODORANTS
 HAIR
SPRAYS
METAL TOXICITY

TOXIC ACTION OF SPECIFIC METALS
GROUP V (ARSENIC [As])
» EXPOSURE MAINLY IN MANUFACTURING
 WEED
KILLERS
 WOOD
PERSERVATIVES
 INSECTICIDES
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
CLINICAL TOXICOLOGY
CLINICAL TOXICOLOGY
TEMPERATURE
INCREASED
DECREASED
AMPHETAMINES
COCAINE
BELLADONNA ALKALOIDS
FLUOROACETATE
HEXACHLOROBENZENE
SALICYLATES
TRICYCLIC ANTIDEPRESSANTS
ALCOHOLS
BARBITURATES
CLONIDINE
GLUTETHIMIDE
HALOPERIDOL
PHENOTHIAZINES
CLINICAL TOXICOLOGY
PULSE
BRADYCARDIA
ARRHYTHMIAS
ALCOHOLS
CARBAMATES
ORGANOPHOSPHATES
ARSENIC
CAFFEINE
SOLVENTS
CLINICAL TOXICOLOGY
RESPIRATORY RATE
INCREASED
DECREASED
CARBON MONOXIDE
CYANIDE
FLUOROACETATE
HEXACHLOROBENZENE
METHANOL
NITRITES
ALCOHOLS
CO
CYANIDE
PHENOTHIAZINES
CLINICAL TOXICOLOGY
BLOOD PRESSURE
INCREASED
DECREASED
AMPHETAMINES
BELLADONNA ALKALOIDS
COCAINE
PHENCYCLIDINE
BARBITURATES
CYANIDE
IRON
NITRITES
CLINICAL TOXICOLOGY
SKIN
DRY
ANTIHISTAMINES
BELLADONNA ALKALOIDS
GLUTETHIMIDE
MOIST
ALCOHOLS
ARSENIC
CARBAMATES
MERCURY
ORGANOPHOSPHATES
THALLIUM
CLINICAL TOXICOLOGY
SKIN COLOR
FLUSHED
CYANOTIC
ALCOHOLS
BORIC ACID
CARBON MONOXIDE
MSG
NITRITES
ANILINE DYES
CO
CYANIDE
NITRITES
CLINICAL TOXICOLOGY
SKIN COLOR
JAUNDICED
ANILINE DYES
ARSENIC
ARSINE GAS
CARBON TETRACHLORIDE
IRON
PHOSPHORUS
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
CLINICAL TOXICOLOGY
GASTROINTESTINAL TRACT
VOMITING
PAIN
ACIDS
ALKALI
ARSENIC
CAMPHOR
IRON
FLUORIDE
ARSENIC
IRON
BLACK WIDOW
CLINICAL TOXICOLOGY
CENTRAL NERVOUS SYSTEM
CONVULSIONS
COMA
CAMPHOR
CHLORINATED HYDROCARBONS
LEAD
NICOTINE
ORGANOPHOSPHATES
PHENOTHIAZINES
ALCOHOL
CARBAMATES
CO
CYANIDE
HYDROCARBONS
H2S
LEAD
ORGANOPHOSPHATES
CLINICAL TOXICOLOGY
CENTRAL NERVOUS SYSTEM
ATAXIA
ALCOHOLS
HYDROCARBONS
PHENYTOIN
PARALYSIS
CARBAMATES
THALLIUM
ORGANOPHOSPHATES
CLINICAL TOXICOLOGY
ANTIDOTES

COMPETITIVE ANTAGONIST
 OXYGEN FOR CARBON MONOXIDE POISONING

NONCOMPETITIVE ANTAGONIST
 ATROPINE FOR ORGANOPHOSPHATE POISONING
CLINICAL TOXICOLOGY
ANTIDOTES

CHEMICAL NEUTRALIZATION
 SODIUM THIOSULFATE FOR CYANIDE POISONING

METABOLIC INHIBITION
 ETHANOL FOR METHANOL POISONING
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