TOXICOLOGY

Latin toxicus (poisonous) Greek toxikon (poisons)

The science of poisons.

The science that deals with the study of the nature, properties, effects and detection of poisons, and the treatment of poisoning; and regulation of poisons.

DEFINITION OF TERMS
Toxic having the characteristic of producing undesirable or adverse health effect. Toxicity any toxic (adverse) effect that a chemical or physical agent might produce within a living organism. Poison any substance applied to the body, ingested, inhaled or developed within the body that causes or may cause disturbance of functions. Symptoms any evidence of disease or change of state

DEFINITION OF TERMS
Exposure the means by which an organism comes in contact with the substance
Acute single exposure to repeated exposures within a short period of time Subacute repeated exposure at greater duration Subchronic exposure repeated or spread over an intermediate time range Chronic repeated or continuous exposures over a long period of time

Poisoning a morbid condition produced by a poison. Posology the study of doses.

Minimum dose Average or customary dose Maximum dose Toxic dose Lethal dose

Treatment management of a patients condition, overcoming or combating a disorder.

Rigor mortis or cadaveric rigidity stiffening of the muscles of the body throughout the entire extent Coma state of profound insensibility Asphyxia condition of more or less complete suspension of respiration. Syncope- suspended animation due to failure in the heart action. Tolerance state of decreased responsiveness to a toxic effect of a chemical. Antidote substance that neutralizes a poison or its effects

Lets explore the science of poisons!

HISTORY
Job 6:4 1400 BC
For the arrows of the Ruler of all are present within me, and their poison goes deep into my spirit: his army of fears is put in order against me

Ebers papyrus 1500 BC Hippocrates (400 BC) Theophrastus (370 286 BC) De historia plantarum Dioscorides De Materia Medica King Mithridates VI of Pontus

HISTORY
Galen 131 200 BC Paracelsus 1493 1541 BC, Father of Toxicology All substances are poisons; there is none that is not a poison. The right dose differentiates a poison and a remedy. Recognition of Hg and Pb in goldsmithing industry
If the dust has corrosive qualities, it eats away the lungs, and implants consumption in the body; hence in the mines of the Carpathian Mountains women are found who have married 7 husband, all of whom this terrible consumption has carried off to a premature death. de Re Metallica, 1556

Ramazini 1700 Diseases of Workers, Father of Occupational medicine Percival Pott 1775 chimney sweepers and scrotal cancer Hill 1761 nasal cancer and snuff use

Age of enlightenment (19th century) Development of organic chemistry

Chemical analysis and autopsy Radioactive materials and vitamins - bioassays Health and occupational regulations Toxicology journals WW I chlorine gas, mustard gas and other human pesticides Arsenicals for tx of syphillis Discovery of DDT US FDA Federal insecticide, fungicide and rodenticide act

HISTORY
Orfilla 1815 Toxicology is a separate science, Father of Modern Toxicology Claude Bernard 1813 1878 Site of action of Curare Rachel Carson 1962 The Silent Spring

AREAS OF TOXICOLOGY
Mechanistic (chemical, biochemical, molecular events)
Biochemical Behavioral Nutritional Carcinogenesis Teratogenesis Mutagenesis Organ toxicity

AREAS OF TOXICOLOGY
Measurement of toxicants and toxicity
Analytical Toxicity testing Toxicologic pathology SA studies Biomathematics/statistics Epidemiology

AREAS OF TOXICOLOGY
Applied toxicology
Clinical Veterinary Forensic Environmental Industrial

AREAS OF TOXICOLOGY
Chemical classes
Agricultural Clinical drugs Drugs of abuse Food additives Industrial chemicals Naturally occurring substances Combustion products

AREAS OF TOXICOLOGY
Regulatory toxicology
Legal aspect Risk assessment

EFFECTS OF POISONS
Adverse, deleterious or toxic effects* Allergic reactions Immediate vs delayed toxicity Reversible vs irreversible toxicity Local vs systemic toxicity

CHEMICAL INTERACTIONS
Additive effect (1 + 1 =2) Synergistic effect (1 + 1 = 10) Potentiation (0 + 1 = 10) Antagonism (1 + 1 = 0)
Functional (physiological) antagonism Chemical antagonism (inactivation) Dispositional antagonism (ADME) Receptor antagonism (blockers)

ORIGIN OF POISONS
Vegetable/plant morphine, atropine, nicotine, etc Animal snake venom, epinephrine, insulin etc Minerals arsenic, mercury, lead etc Synthetic barbiturates, antihistamines etc Microbial bacterial toxins

CLASSIFICATION OF POISONS
Autenrieth classification
Volatile Non-volatile Metallic poisons

Physiological classification
Corrosives Irritants Asphyxiants Anesthetics and narcotics Neurotic Tetanics Deliriants Depressants or sedatives Asthenics or exhaustive

Chemical
Inorganic Organic

Kind of poisons
Corrosive True poison Cumulative

Effects
Local Remote Combined

Conditions influencing absorption of poisons

Solubility of the poison Characteristic of the surface to which the poison is applied Quantity of the blood in the blood vessels

STAGES IN THE INDUCTION OF POISON

Exposure

Delivery

Interaction

Clinical consequences

Factors that modify the effects of a poison

Those related to the organism
Age, gender, idiosyncracy, health, sleep, exhaustion, condition of the stomach and character and amount of stomach content

Those related to the poison

Physical state or form, mode of administration, size of dose, association with other poisons, dilution

ROUTES/SITES OF EXPOSURE
Parenteral Enteral
Oral/peroral

Others
Topical Inhalation/intranasal

TYPES OF POISONING
Medical point of view
Acute Chronic

Legal point of view

Accidental Suicidal Homicidal Undetermined

ELIMINATION OF POISON
Saliva Sweat Urine Feces Respiration Tears Bile Pancreatic juice Vomitus

When can I suspect that a person is being poisoned?

Circumstantial evidence Symptomatic evidence Chemical evidence Post mortem evidence Experimental evidence

CAUSES OF DEATH
Death beginning at the brain (coma) Death beginning at the heart (syncope) Death beginning at the lungs (asphyxia or apnea)

DOSE-RESPONSE DATA
Lethal dose mortality Toxic dose a serious adverse effect other than lethality Sentinel dose non or minimally adverse effect

RANK OF ORAL LETHAL DOSE IN HUMANS

Practically nontoxic - >15,000 mg/kg Slightly toxic 5000 to 15,000 mg/kg Moderately toxic 50 to 5000 mg/kg Very toxic 50 to 500 mg/ kg Extremely toxic 5 to 50 mg/kg Supertoxic - <5 mg/kg

Movement of poisons across membranes

PASSIVE DIFFUSION 1) concentration of substances on the two sides of the membrane 2) ease with which a molecule of the chemical can move through the membrane Factors Partition coefficient Molecular size Degree of ionization

FACILITATED DIFFUSION - Requires a carrier protein - Carrier proteins are finite - Faster than passive diffusion

ACTIVE TRANSPORT - Carrier mediated - Expends energy - Against concentration gradient

FILTRATION relies on the movement through pores PHAGOCYTOSIS

GI facilitated and active transport SKIN passive diffusion LUNG -