General Toxicology: Principles & Classification
Forensic Medicine · Toxicology · lean revision notes
General Toxicology: Principles & Classification
General toxicology is the foundation on which every poison-specific MCQ rests. It deals with what a poison is, how it enters and acts, what modifies its toxicity, and how the medicolegal system investigates a suspected poisoning. Master these principles and a large slice of forensic toxicology becomes pattern recognition.
Definition and basic terms
A poison is any substance which, when administered into or applied to the body in any quantity, through any route, is capable of causing injury, deranging health, or destroying life by its physical, chemical, or physiological action. The classic dictum, attributed to Paracelsus ("the father of toxicology"), is "Sola dosis facit venenum" — only the dose makes the poison. Water, oxygen and even common salt are toxic at extreme doses; conversely a few drops of a potent alkaloid can kill.
Related definitions worth memorising:
- Toxicology — science dealing with the source, properties, action, lethal dose, symptoms, treatment, detection and medicolegal aspects of poisons.
- Toxinology — study of toxins produced by living organisms (snake venom, bacterial toxins).
- Toxin — a poison of biological origin (plant, animal or microbial).
- Venom — a toxin actively injected by a specialised apparatus (fangs, sting).
- Fulminant poisoning — massive overdose causing death so rapidly that classic symptoms have no time to develop.
High-yield: "Sola dosis facit venenum" — only the dose differentiates a poison from a remedy. Paracelsus is the father of toxicology; Mathieu Orfila is the father of modern/analytical toxicology.
Key quantitative terms (toxicokinetic cut-offs)
| Term | Meaning |
|---|---|
| Fatal dose (FD) | Smallest amount likely to cause death |
| Fatal period (FP) | Time interval between intake and death |
| LD50 | Dose killing 50% of a test population (statistical measure of acute toxicity) |
| TD50 | Dose producing a toxic effect in 50% of population |
| ED50 | Dose producing the desired (effective) response in 50% |
| Therapeutic index | TD50/ED50 (or LD50/ED50) — higher = safer drug |
| Margin of safety | LD1/ED99 — a stricter, more clinically useful safety margin |
High-yield: LD50 is inversely proportional to toxicity — a lower LD50 means a more potent poison. LD50 is expressed in mg/kg body weight. Botulinum toxin has one of the lowest LD50 values known.
A stepwise way to think about dose–response: threshold dose → ED50 (therapeutic) → TD50 (toxic) → LD50 (lethal). The closer these values cluster, the more dangerous the agent.
Classification of poisons
Poisons can be grouped by mode of action (most examined), by intent, or by physical form.
A. Based on mode of action
- Corrosives — destroy tissue locally by chemical action.
- Strong acids: sulphuric, nitric, hydrochloric.
- Strong alkalis: caustic soda (NaOH), caustic potash (KOH), ammonia.
- Metallic salts/organic corrosives: oxalic acid, phenol (carbolic acid).
- Irritants — cause pain, vomiting and purging by local inflammation.
- Inorganic: non-metallic (phosphorus, chlorine, bromine, iodine) and metallic (arsenic, mercury, lead, copper).
- Organic — vegetable: castor (ricin), croton, abrus (jequirity), calotropis.
- Organic — animal: snake venom, insect stings, cantharides.
- Mechanical: powdered glass, diamond dust, chopped hair.
- Neurotics (systemic) — act chiefly on the nervous system:
- Cerebral: somniferous (opium), inebriant (alcohol, ether, chloroform), deliriant (dhatura, belladonna, cannabis, cocaine).
- Spinal: excitant (strychnine/nux vomica), depressant (gelsemium).
- Peripheral: conium, curare.
- Cardiac poisons — aconite, digitalis, oleander, nicotine, quinine.
- Asphyxiants — carbon monoxide, carbon dioxide, hydrogen sulphide, war/irritant gases.
- Miscellaneous — analgesics, antipyretics, hypnotics, agrochemicals.
B. Based on intent / medicolegal context
- Homicidal (used to murder): the "ideal homicidal poison" should be cheap, easily available, colourless, odourless, tasteless, highly toxic, mimic natural disease, and leave no characteristic post-mortem signs. Arsenic and thallium approach this ideal.
- Suicidal: organophosphates, aluminium phoside, barbiturates, opium, carbolic acid (in India, agrochemicals dominate).
- Accidental: CO, kerosene, drug overdose, food poisoning, snakebite.
- Stupefying (for robbery/abduction): dhatura, cannabis, chloral hydrate, belladonna.
- Abortifacient: ergot, lead, quinine.
- Cattle poison / arrow poison: abrus, aconite.
High-yield: The ideal homicidal poison = arsenic (signs mimic gastroenteritis/cholera). The ideal suicidal poison = opium/barbiturates (painless). Dhatura = "poison of thieves" / "Devil's trumpet" — the classic stupefying agent.
Routes of absorption and speed of action
The rate of action depends heavily on the route of entry. Stepwise, from fastest to slowest:
Inhalation (gases/vapours) → Intravenous → Intramuscular → Subcutaneous → Intraperitoneal → Oral/ingestion → Rectal/vaginal → Skin (transdermal, slowest)
| Route | Relative speed | Notes |
|---|---|---|
| Inhalation | Fastest | Huge alveolar surface, direct to systemic circulation (e.g., CO, HCN, anaesthetic gases) |
| Intravenous | Very fast | Bypasses absorption entirely |
| Intramuscular / subcutaneous | Fast–moderate | Depends on vascularity |
| Oral | Moderate | First-pass metabolism in liver reduces effect; presence of food delays |
| Skin / mucosa | Slowest | Lipid-soluble agents (organophosphates, phenol, aniline) can still be lethal transdermally |
High-yield: A poison acts fastest when inhaled (after IV). Empty stomach, finely divided/dissolved poison, and combination with alcohol all hasten absorption.
Factors modifying the action of a poison
Examiners love this list. Group them mentally as dose, form, route, host factors, and combinations.
- Dose — large doses act faster; but corrosives in concentrated form may coagulate the surface and paradoxically delay deeper penetration.
- Physical form — gaseous > liquid > powder > tablet > lump. Soluble salts act faster than insoluble forms (e.g., barium sulphate is inert; barium chloride is toxic).
- Chemical combination — inert combinations reduce toxicity (silver nitrate + NaCl → inert silver chloride).
- Route of administration — as above.
- Condition of the body:
- Age — children and the elderly are more susceptible; some exceptions exist (children tolerate belladonna/opium poorly).
- State of health — diseased kidneys/liver impair excretion → enhanced toxicity.
- Sleep & metabolism — slow metabolism in sleep delays action.
- Idiosyncrasy — abnormal individual response (e.g., quinine, aspirin).
- Tolerance — repeated exposure raises the lethal threshold (opium, alcohol, arsenic — the arsenic-eaters of Styria).
- Cumulation — slowly excreted poisons (arsenic, lead, strychnine, digitalis) accumulate even at sub-toxic doses.
- Hypersensitivity / allergy — immune-mediated reactions (penicillin anaphylaxis).
- Synergism & antagonism — alcohol + barbiturates is synergistic; pilocarpine antagonises atropine.
High-yield: Tolerance (need for higher dose for same effect) and cumulation (small repeated doses build up) are opposite concepts frequently paired in MCQs. Classic cumulative poisons: arsenic, lead, strychnine, mercury, digitalis.
Diagnosis of poisoning
In the living
Suspect poisoning when:
- Symptoms appear abruptly in a previously healthy person, often after food/drink.
- Several people sharing the same food fall ill together (food poisoning / mass poisoning).
- Symptoms are rapidly progressive and don't fit a single natural disease.
- A known prior suicidal/homicidal context exists.
In the dead (post-mortem)
A confident diagnosis rests on circumstantial + post-mortem + chemical evidence:
- Circumstantial — history, container/tablets at scene, suicide note, occupation.
- Post-mortem findings — corrosion of lips/mouth, characteristic stains, smell of stomach contents (bitter almond = cyanide; garlic = phosphorus/organophosphate/arsenic; kerosene smell).
- Chemical analysis of viscera — the definitive proof.
High-yield smells (eponymic clues):
- Bitter almonds → cyanide
- Garlicky → phosphorus, organophosphates, arsenic, thallium
- Rotten eggs → hydrogen sulphide
- Shoe-polish / nitrobenzene → almond-like, plus chocolate-brown blood (methaemoglobinaemia)
Viscera preservation — the heart of medicolegal toxicology
When poisoning is suspected, the autopsy surgeon preserves viscera and sends them to the Forensic Science Laboratory (FSL). This is the single most examined practical topic.
What to preserve (standard "Bottle" scheme)
| Bottle | Contents | Preservative |
|---|---|---|
| Bottle 1 | Stomach + first 30 cm of small intestine + their contents | Saturated saline (or rectified spirit) |
| Bottle 2 | ~½ each of liver, spleen, kidney; 200 g | Saturated saline / rectified spirit |
| Bottle 3 | Blood (10–20 mL) | Sodium fluoride + potassium oxalate |
| Bottle 4 | Urine | Sodium fluoride / no preservative |
| Bottle 5 | Control sample of preservative used | — |
Preservatives — what to use when
- Routine viscera (most poisons): saturated solution of common salt (NaCl) is the preservative of choice.
- Rectified spirit (ethyl alcohol): alternative — but contraindicated when alcohol, phosphorus, paraldehyde, chloroform, ether or acetic acid poisoning is suspected (it interferes with detection / dissolves phosphorus).
- Sodium fluoride (1% w/v) + potassium oxalate: for blood — fluoride is an enzyme inhibitor that prevents fermentation/alcohol production and decomposition (vital for alcohol & carbon monoxide estimation); oxalate is an anticoagulant.
- Saturated NaCl is contraindicated when looking for chloride/heavy-metal halide poisons.
High-yield: Saturated common salt = routine preservative for viscera. Sodium fluoride = preservative of choice for blood (especially for alcohol estimation, because it stops yeast/bacteria from generating or destroying ethanol). For suspected alcohol/phosphorus poisoning, do NOT use rectified spirit.
Special samples
- Suspected heavy-metal (arsenic, thallium, lead) chronic poisoning: preserve skin, hair, nails and bone — these store metals long-term.
- Suspected organophosphate: preserve blood for cholinesterase, plus stomach + liver.
- Decomposed bodies: preserve bone, hair, nail, muscle, maggots (entomotoxicology).
- In exhumation, additionally collect soil samples from above, below and around the coffin plus control soil for comparison.
The completed bottles are sealed, labelled, and dispatched with a forwarding letter and sample of the seal to the FSL, maintaining an unbroken chain of custody.
Management — general principles of treatment
Stepwise emergency approach to any acute poisoning:
- Resuscitation (ABC) — secure airway, breathing, circulation; this always precedes antidotes.
- Decontamination —
- Skin/eye: copious water irrigation, remove clothing.
- GI: gastric lavage (most effective within 1 hour; contraindicated in corrosive and hydrocarbon poisoning and in unprotected airway). Activated charcoal 1 g/kg adsorbs most poisons (ineffective for the PHAILS group — Pesticides? no; better mnemonic below).
- Elimination enhancement — forced diuresis, urine alkalinisation (salicylates, phenobarbitone), haemodialysis (methanol, ethylene glycol, lithium, salicylates).
- Antidote — specific where available.
- Supportive & symptomatic care.
High-yield — activated charcoal does NOT bind ("PHAILS"): Pesticides poorly; truly: Metals (iron, lithium), Alcohols/glycols, Acids/alkalis (corrosives), Hydrocarbons, Cyanide, Potassium. Charcoal is most useful within 1 hour and for repeated dosing in carbamazepine, theophylline, phenobarbitone, dapsone, quinine.
Antidotes — classification
| Type | Example |
|---|---|
| Physical/mechanical | Activated charcoal (adsorbent), demulcents |
| Chemical | Sodium thiosulphate for cyanide; tannic acid for alkaloids |
| Physiological/pharmacological | Atropine for organophosphates; naloxone for opioids; flumazenil for benzodiazepines |
| Chelating agents | BAL (dimercaprol) for arsenic/mercury; calcium disodium EDTA & DMSA for lead; penicillamine for copper |
| Universal antidote | (Largely obsolete) activated charcoal + magnesium oxide + tannic acid — now replaced by activated charcoal alone |
High-yield antidote pairs: OP poisoning → atropine + pralidoxime (oxime); paracetamol → N-acetylcysteine; methanol/ethylene glycol → fomepizole/ethanol; iron → desferrioxamine; heparin → protamine; warfarin → vitamin K; cyanide → sodium nitrite + sodium thiosulphate / hydroxocobalamin; benzodiazepine → flumazenil; opioid → naloxone.
Complications and sequelae
- Aspiration pneumonia (after lavage or hydrocarbon ingestion).
- Oesophageal/pyloric stricture following corrosive ingestion.
- Acute kidney injury (ethylene glycol, heavy metals, paraquat).
- Hepatic failure (paracetamol, phosphorus, amanita mushrooms).
- Aspiration & ARDS with paraquat (progressive pulmonary fibrosis).
- Peripheral neuropathy / encephalopathy (lead, arsenic, thallium).
- Death — from respiratory failure, arrhythmia, shock, or organ failure depending on the agent.
Key differentials — poisoning vs natural disease
Distinguishing poisoning from disease is a recurring exam theme:
| Feature | Poisoning | Natural disease |
|---|---|---|
| Onset | Sudden, often post-meal | Usually gradual |
| Multiple persons | Common (shared food) | Uncommon |
| Course | Rapidly progressive, uniform | Variable, fluctuating |
| Response to history | Container/note/occupation clue | Past medical history |
| Confirmation | Chemical analysis of viscera | Histopathology/clinical |
Important mimics: arsenic mimics cholera/gastroenteritis; organophosphate mimics medical coma; CO mimics cardiac/neurological events; aconite/oleander mimics MI/arrhythmia.
Statutory and ethical points
- Section 39 CrPC obliges every person aware of certain offences to inform; poisoning deaths are medicolegal and require police intimation before/at autopsy.
- A registered medical practitioner who treats a suspected poisoning is not obliged to inform the police if it appears accidental or suicidal in a private setting, but must report homicidal poisoning.
- Poisons Act 1919 and Drugs and Cosmetics Act 1940 regulate sale and storage of poisons in India.
- Sale of schedule poisons requires entry in a Poison Register (name, address, quantity, purpose, signature).
High-yield: Every suspected poisoning death is a medicolegal autopsy; viscera must be preserved even if cause seems obvious, because chemical confirmation alone is admissible proof.
Recently asked / exam angle
- Father of toxicology = Paracelsus; father of modern (analytical) toxicology = Orfila. Frequently confused — Orfila wrote the first systematic treatise.
- LD50 definition and its inverse relationship to toxicity — a near-guaranteed one-liner MCQ.
- Preservative of choice: "viscera → saturated common salt; blood for alcohol → sodium fluoride." Repeatedly asked in NEET PG/INI-CET.
- Rectified spirit is contraindicated in alcohol & phosphorus poisoning — classic "which preservative NOT to use" question.
- Ideal homicidal poison = arsenic; stupefying poison = dhatura. Single-best-answer staple.
- Activated charcoal ineffective substances (metals, alcohols, hydrocarbons, corrosives, cyanide) — image/clinical vignette format.
- Smell associations (bitter almond = cyanide, garlic = OP/phosphorus/arsenic) — often as a clinical autopsy scenario.
- Therapeutic index = TD50/ED50; margin of safety = LD1/ED99 — pharmacology–forensic overlap.
- Chelating agents matched to metals (BAL→arsenic/mercury, EDTA→lead, penicillamine→copper/Wilson).
Rapid revision
- Poison = any substance harming health/life through chemical or physiological action; only the dose makes the poison (Paracelsus).
- LD50 = dose lethal to 50% of a population; lower LD50 = more toxic.
- Therapeutic index = TD50/ED50; margin of safety = LD1/ED99.
- Routes by speed: inhalation > IV > IM > SC > oral > skin.
- Ideal homicidal poison = arsenic; ideal suicidal poison = opium/barbiturate; stupefying = dhatura.
- Cumulative poisons: arsenic, lead, mercury, strychnine, digitalis; tolerance is the opposite concept.
- Saturated common salt = routine viscera preservative; rectified spirit alternative (avoid in alcohol/phosphorus poisoning).
- Sodium fluoride + potassium oxalate = blood preservative, essential for alcohol/CO estimation.
- Preserve hair, nail, skin, bone in chronic heavy-metal poisoning; soil samples in exhumation.
- Activated charcoal works best within 1 hour; useless for metals, alcohols, hydrocarbons, corrosives, cyanide.
- Smells: bitter almond = cyanide; garlic = OP/phosphorus/arsenic; rotten egg = H₂S.
- Management order: ABC → decontamination → elimination → antidote → supportive care.