Introduction to Toxicology

Toxicology Basics

• Toxicology is the science dedicated to the study of poisons.
• Focuses on harmful effects of chemical substances on living organisms.
• Considers symptoms, mechanisms, treatments, and detection, especially regarding poisoning.
• Poison is anything causing injury, illness, or death after introduction.
• Paracelsus: "The dose makes the poison", meaning any substance can be toxic depending on the amount.
• Mathieu Orfila is viewed as the father of toxicology.
• Lex Cornelia is the 1st book regarding poisoning.

Branches of Toxicology

• Environmental toxicology examines chemicals which pollute to living organism harm
• Ecotoxicology studies toxic substances’ effects on populations within ecosystems.
• Occupational toxicology focuses on workplace chemicals, prevention harmful amounts
• Mechanistic toxicology researches toxic action mechanisms/toxicodynamics.
• Descriptive toxicology pertains to toxicity testing for safety and regulatory needs.
• Forensic toxicology concerns medico-legal aspects & chemical effects on humans/animals.
• Experimental toxicology investigates chemical toxicity in biologicals, including LD50 and NOAEL

Experimental Toxicology Parameters

• LD50 is the lethal dose for 50% of the test population.
• LC50 is the lethal concentration for 50% of the test population.
• TD50 is the toxic dose for 50% of the test population.
• TVL/TLC is the threshold limit value/concentration.
• NOAEL: No Observed Adverse Effect Level.

Regulatory & Clinical Toxicology

• Regulatory toxicology gathers toxicological data for "safe" exposure standards.
• Descriptive & Mechanistic toxicology decides a drug is safe.
• Clinical toxicology focuses on chemical effects in cases of accidental/intentional exposure.

Definitions

• Hazard is the possibility of injury in a setting.
• Risk is the expected rate of an undesirable exposure effect.
• Intoxication is toxicity due to any chemical substance,
• Poisoning: clinical toxicity related to accidental exposure.
• Overdose: intentional exposure to cause harm/death.

Evidence of Poisoning

• "Corpus delicti" includes evidence presented before a conviction.

Circumstantial Evidence

• Known as moral, deduced from circumstances; is weak, not factual evidence.
• Examples include motive, purchase, and possession of related materials.

Symptomatic Evidence

• Symptoms seen during poisoning, but symptoms are inconclusive due to disease similarities.
• Arsenic poisoning and diabetic coma are examples.

Chemical Evidence

• Obtained by analyzing substances suspected in the body.
• Chemical evidence alone unreliable due to the poison aging after death.

Post-mortem Evidence

• Noted from examens of tissues and organs obtained during autopsy.
• Examen after death.

Experimental Evidence

• Can be tested by administering substance to lab animals and noting the symptoms on a living man but tolerance varies.

Interactions of Poison

• Additive interactions: combined effect which equates to the sum of the effects were they given alone.
• Synergistic interactions: Combined effects > total sum on their own (1 + 1 = 3).
• Potentiation results in the chemical that is nontoxic adding to the toxicity of some other compound(1 + 0 = 2).
• Antagonism: When more than one chemicals are present, the co-administration can block or reverse the toxicity/effect (1 + 1 = 0).

Antagonism

• Functional antagonism: chemicals which counteract to exert influence on physiological function.
• Chemical antagonism (or inactivation) yields less number of toxic compounds when a reaction occurs such as with antivenoms.
• Dispositional antagonism: where disposition is changed in duration or conc, i.e PH change with pH alteraction
• Receptor antagonism is when chemicals compete for, and decreasing binding to the same receptor such as with Naloxone as an opiate binding antagonist

Poisoning Effects

• Local effects impact area of contact, i.e corrosives
• Remote effets occur elsewere, i.e blurred vision after ingesting atropine orally
• Combined presents remote & local, i.e arsenic

Poisoning Factors (Poison- & Patient-Related)

• Administration routes- injection, ingestion and inhalation
• Concentrations or Dosage increase toxicity likelihood
• IV toxicity potential > inhalation > subcutaneous > oral > dermal.
• Lipid-soluble poisons dermally absorb.
• Pediatric patients have immature livers for drug accumulation.
• Geriatric patients have drug metabolizing declines, alcohol tolerance

Duration & Frequency of Poisoning

• Acute poisoning results from 24 hour exposure, typically due to single dose of a strong, true poison.
• A repeated/protracted exposure to smaller toxicity amounts is chronic.
• "Cumulative" refers to sudden action increase once the limit is reached i.e metals

Metabolites Drug Toxicity

• Some parent drugs exhibit increase activity once they're metabolized
• Parathion > paraoxon
• Amitriptyline > nortriptyline

Terms For repeated exposure

• Subacute involves repeated exposure for a month or so
• Subchronic includes repeating exposure from 1-3 mos

Frequency Types of Poisoning

• Acute shows disturbance in function and or death in time that is quick, excessive or one time serving, or intake of strong true toxin
• Chronic is change in tissure fuction becaues small doses continue over long period, also that is gradual
• Cumulative is when after reach limit, intensity of action grows quickly, as with toxins based from metal

Effect Based Types of Poisoning

• Irritant presents tissure nercorisis upon context, like with acids
• Neurotics effects central nervous sustem, as with hallucinogens
• Carcinogens stimulate cancer cell growth, as from industrial poisoning
• lacrimators which stimulate tear follow- i.e organophosphates
• Asthenics are cause of Muscular weakness, i.e muscular block
• Narcotics induces metal weakess, ie sedatives

General poison deaths come

• CNS depression > coma
• Hypotenstion + shock
• Hypoxia ==
• Seizures
• Organ damage
• behavior changes