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    Principles of Toxicology

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    Marie Sarangaya
    Toxicology is the study of the adverse effects of chemicals on living organisms. It examines how chemicals can cause injury, disease or death in humans, animals and the environment. Toxicologists are trained to evaluate and communicate the nature and extent of harmful effects from exposure to chemicals. They provide quantitative estimates of potential health effects on humans and environmental significance. Toxic agents can be classified based on their target organ, use, effects, source and other properties. Exposure to toxic substances can result in a wide spectrum of undesired effects ranging from allergic reactions and tolerance to irreversible toxicity, carcinogenicity, developmental toxicity and genetic toxicity.

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    Principles of Toxicology

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    Marie Sarangaya
    36 views64 pages
    Toxicology is the study of the adverse effects of chemicals on living organisms. It examines how chemicals can cause injury, disease or death in humans, animals and the environment. Toxicologists are trained to evaluate and communicate the nature and extent of harmful effects from exposure to chemicals. They provide quantitative estimates of potential health effects on humans and environmental significance. Toxic agents can be classified based on their target organ, use, effects, source and other properties. Exposure to toxic substances can result in a wide spectrum of undesired effects ranging from allergic reactions and tolerance to irreversible toxicity, carcinogenicity, developmental toxicity and genetic toxicity.

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    The Principles of Toxicology What is the Principles of Toxicology

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    Toxicology is the study of the adverse effects of chemicals on living organisms. It examines how chemicals can cause injury, disease or death in humans, animals and the environment. Toxicologists are trained to evaluate and communicate the nature and extent of harmful effects from exposure to chemicals. They provide quantitative estimates of potential health effects on humans and environmental significance. Toxic agents can be classified based on their target organ, use, effects, source and other properties. Exposure to toxic substances can result in a wide spectrum of undesired effects ranging from allergic reactions and tolerance to irreversible toxicity, carcinogenicity, developmental toxicity and genetic toxicity.

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    36 views64 pages

    Principles of Toxicology

    Uploaded by

    Marie Sarangaya
    Toxicology is the study of the adverse effects of chemicals on living organisms. It examines how chemicals can cause injury, disease or death in humans, animals and the environment. Toxicologists are trained to evaluate and communicate the nature and extent of harmful effects from exposure to chemicals. They provide quantitative estimates of potential health effects on humans and environmental significance. Toxic agents can be classified based on their target organ, use, effects, source and other properties. Exposure to toxic substances can result in a wide spectrum of undesired effects ranging from allergic reactions and tolerance to irreversible toxicity, carcinogenicity, developmental toxicity and genetic toxicity.

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    of 64

    TO X I C O L O G Y

    Toxicology
    • Study of the adverse effects of
    chemical or physical agents on living
    organisms
    • Any agent that may cause serious body injury,
    disease, or death

    • Trained to examine and communicate the nature


    of AE on human, animal and environmental health

    • Quantitative estimate of the potential effects on


    human health and environmental significance
    Topics
    Principles of Toxicology I and II

    General Management of Poisoned Patients

    Common Mechanisms of Toxicity

    Industrial and Household Toxicology

    Substances of Abuse

    Clinical Toxicology
    PRINCIPLES OF
    TOXICOLOGY I
    Areas of toxicology, Classification of toxic
    agents, Spectrum of undesired effects,
    Characteristics of exposure, Variations in toxic
    responses, Evidences of poisoning
    Toxicity
    • Intrinsic ability of an agent to harm
    living organisms
    • Adverse health effect associated with a
    change, reduction or loss of a vital
    function
    Definitions
    • Toxicity associated with any chemical
    substance

    • Clinical toxicity secondary to


    accidental exposure

    • Intentional exposure with the intent


    of causing self-injury or death
    Definitions
    • Likelihood that injury will
    occur in a given situation
    or setting

    • Expected frequency of
    occurrence
    AREAS OF TOXICOLOGY
    Areas of Toxicology
    • Realm of medical science that is concerned with
    Clinical disease caused by or uniquely associated with
    toxic substances

    • impacts of chemicals on nonhuman organisms


    Ecotoxicology such as fish, birds, terrestrial animals, and plants

    • Medico-legal aspects of harmful effects on


    Forensic humans and animals

    • Investigation of toxic effects of chemicals in


    Environmental biological system
    Areas of Toxicology
    • Concerned directly with toxicity testing,
    Descriptive which provides information for safety
    evaluation and regulatory requirements

    Mechanistic
    • Mechanism of toxic action of poisons
    Toxicology

    Regulatory • Decision whether drug is sufficiently low


    risk to be marketed
    CLASSIFICATION OF
    TOXIC AGENTS
    Classification of Toxic Agents
    • Liver, kidney, hematopoietic system,
    Target Organ etc.

    Use • Pesticide, solvent, food, additive, etc.

    Effects Cancer, mutation, liver injury, etc.

    Source • Animal and plant toxins


    Toxin VS Toxicant
    Toxin Toxicant
    From plants, animals, From humans
    fungi or bacteria
    Examples: Examples:
    Venoms: CVS Nerve gases
    Cobra: affect CNS Methyl Carbamate
    Vipers: affect Vessels Acetone
    (hemotoxic) Rugby
    Sea Snakes: affect Skeletal
    Muscles
    Zootoxins

    Tetrodotoxin Cantharidin Clupeotoxin

    Scromboid Ciguatoxin
    Zootoxins
    Source Toxin
    Puffer Fish Tetrodotoxin
    Blister Fly/Spanish Cantharidin
    Fly
    Oyster/Sardines Clupeotoxin
    Mackerel/Tuna Scromboid
    Fish Ciguatoxin
    Zootoxins

    Latrotoxin

    Apitoxin Hyaluronidase
    Zootoxins
    Source Toxin
    Black Widow Latrotoxin
    Bee Apitoxin

    Snake Hyaluronidase
    Phytotoxins
    Poison Source/s Effects
    Arecoline Betel nut Oral CA
    Brucine,
    Nux vomica Convulsion
    strychnine
    Fish berries
    Equimolar mixture of
    two
    Picrotoxin compounds, Seizures
    picrotoxinin and
    picrotin
    Myristicin Nutmeg Hallucinogen
    Phytotoxins
    Poison Source/s
    Colchicines Autumn crocus
    Lily of the valley Convallaria
    Convallarin
    majalis
    Poison hemlock Conium
    Coniine
    maculatum
    American mandrake, May
    Podophyllotoxin
    apple Podophyllum peltatum
    Mushroom Toxins
    Group Toxin Source/s
    Amanitotoxins,
    I Hepatotoxins
    cyclopeptides
    IA Orellanine, orelline Nephrotoxins
    Muscimo, Iboteric Hallucinogens, Anticholinergic
    II
    acid signs & symptoms
    III Gyrometrin Hepatotoxin
    IV Muscarine Cholinergic overstimulation
    V Coprine Disulfiram reaction
    VI Psilocin, psilocybin Hallucinogens
    Microbial Toxins
    Poison Source/s
    Saxitoxin Dinoflagellates Shellfish
    Aspergillus
    Aflatoxin Dried Peanuts
    flavus
    Ptomaine Bacterial decay Spoiled Food
    Milk and Dairy
    Tyrotoxicon Bacterial decay
    Products
    Microbial Toxins
    Poison Source/s
    Ergot Claviceps purpurea
    Exotoxins Mostly from Gram(+)
    Botulinum toxin C. botulinum
    Tetanospasmin C. tetani
    ALPHA toxin C. perfringens
    Erysipelas
    Devil’s Smile
    Ergotism
    Botox
    Gas Gangrene
    Classification of Toxic Agents
    Physical State • Gas, dust, liquid

    Chemical Stability • Explosive, flammable, oxidizer


    or Reactivity
    General Chemical • Aromatic amine, halogenated HC,
    Structure etc.

    Poisoning Potential • Extremely/very/slightly toxic

    Mechanism of • Alkylating agent, cholinesterase


    Action inhibitor, methemoglobin producer
    According to Effects
    CLASSIFICATION EFFECTS EXAMPLES
    cause tissue ACIDS AND
    Irritants necrosis on ALKALI
    contact
    Neurotoxin affect the cns HALLUCINOGEN
    stimulate INDUSTRIAL
    Carcinogens growth of POISONS
    cancer cells
    Asphyxiants cause dyspnea CO, METHANE
    mental SEDATIVE
    Narcotic weakness / HYPNOTICS
    depression
    SPECTRUM OF
    UNDESIRED EFECTS
    Spectrum of Undesired
    Effects
    • Immunologically mediated
    adverse reaction to a
    Allergic chemical resulting from
    previous sensitization to
    Reaction that chemical or to a
    structurally similar one
    Spectrum of Undesired
    Effects
    • State of decreased
    responsiveness to a toxic
    effect of a chemical resulting
    Tolerance from prior exposure to that
    chemical or to a structurally
    related chemical
    Spectrum of Undesired
    Effects

    •Genetically
    Idiosyncratic determined
    Reactions abnormal reactivity
    to a chemical
    Spectrum of Undesired
    Effects
    Immediate • Those that occur or develop
    rapidly after a single
    Toxicity administration of a substance

    Delayed • Those that occur after the


    lapse of some time
    Toxicity
    Spectrum of Undesired
    Effects
    Local • Those that occur at the site of first
    contact between the biological system
    Toxicity and the toxicant

    Systemic • Require absorption and distribution of


    a toxicant from its entry point to a
    distant site, at which deleterious effects
    Toxicity are produced
    Spectrum of Undesired
    Effects
    • Organophosphate insecticides
    Additive
    • Carbon tetrachloride + ethanol
    Synergism
    Potentiation • Carbon tetrachloride + isopropranol

    Antagonism • Basis of many antidotes


    Spectrum of Undesired
    Effects
    Reversible
    Toxicity •Injuries to liver

    Irreversible
    Toxicity •Injuries to CNS
    Irreversible Toxicity
    • Complex multistage process of
    Carcinogenicity abnormal cell growth

    Developmental • Adverse toxic effect to the


    Toxicity developing embryo or fetus

    • Results from damage to DNA


    Mutation and altered genetic expression
    Carcinogenicity
    Two Stages • Initiation, Promotion

    Tumors • Also known as Neoplasm

    Benign Tumors • Grow at the site of origin

    Malignant
    Tumors
    • Invade adjacent tissues
    Developmental Toxicity
    • Failure to conceive, spontaneous
    Embryolethality abortion or stillbirth

    • Growth retardation or delayed growth


    Embryotoxicity of specific organ systems

    • Irreversible conditions that leave


    Teratogenicity permanent birth defects in live
    offspring
    Common Teratogens
    Alcohol
    FDA Pregnancy Categories
    Genetic Toxicity
    Gene • Changes in DNA sequence
    Mutation within a gene

    Chromosome • Changes in chromosome


    Aberration structure

    Aneuploidy/ • Changes in chromosome


    Polyploidy number
    Genetic Toxicity
    Monoploidy • half of an entire set of chromosomes

    Euploidy • twice of an entire set of chromosomes

    • One or more chromosomes are missing or


    Aneuploidy present in more than their usual number
    Types of Aneuploidy
    Nullisomy •2N - 2

    Monosomy •2N - 1

    Trisomy •2N + 1

    Tetrasomy •2N + 2
    Chromosomal Alterations
    • Trisomy 21 (Down Syndrome)
    • Trisomy 13 (Patau Syndrome)
    • Trisomy 18 (Edward’s Syndrome)
    • 47, XXY Males (Klinefelter
    Syndrome)
    • Trisomy X (47, XXX Females)
    • Monosomy X (Turner’s Syndrome)
    CHARACTERISTICS OF
    EXPOSURE
    Characteristics of Exposure
    Acute • Exposure to a chemical for less than 24
    hours

    • Repeated exposure to a chemical for 1


    Sub-Acute month or less

    • Repeated exposure to a chemical for 1


    Sub-Chronic to 3 months

    • Repeated exposure to a chemical for


    Chronic more than 3 months
    VARIATIONS IN TOXIC
    RESPONSE
    Variations in Toxic Responses

    • Chemical produces injury to


    one kind of living matter
    Selective without harming another
    Toxicity form of life even though
    the two may exist in
    intimate contact
    EVIDENCES OF
    POISONING
    Evidences of Poisoning
    Circumstantial • Deducing from events or facts

    • Gathering information after an autopsy is


    Post-Mortem performed

    • Administering suspected substance to living


    Experimental animal and noting effect or symptom

    • Detecting of suspected substance via analysis


    Chemical of samples collected

    Symptomatic • Observing poisoning signs or effects


    Evidences of Poisoning
    Evidences of Poisoning

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