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General Toxicology - The Essentials of Forensic Medicine & Toxicology (VV Pillai / KS Narayan Reddy, 36th Ed.)

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8.1 History of Toxicology

• Kautilya's Arthashastra (~2nd century BC): poisoning studied as a separate branch used offensively and defensively. Professional poisoners masked bitter tastes with sweet substances.
• 82 BC: Lex Cornelia issued by Sulla in Rome - the first law against poisoning, later a regulatory statute for careless drug dispensers.
• Hippocrates (4th century BC): added poisons to Greek medicine.
• Theophrastus (4th century BC): references to poisonous plants in De Historia Plantarum.
• Dioscorides: Greek physician in Emperor Nero's court; first classification of poisons that remained standard for 16 centuries.
• 7th-9th centuries: Arab pharmacologist-physicians Avicenna, Rhazes, and Jaber developed pharmacology and therapeutics.
• Bhojaprabandha (980 AD): reference to inhalation of medicaments before surgery; anesthetic "sammohini" used in the time of Buddha.
• Paracelsus: created the basic scientific discipline of toxicology in the late Middle Ages.
• Mathieu Joseph Bonaventure Orfila (Spanish chemist, 1787-1853): "Father of Toxicology." First to systematically correlate chemical and biological information of poisons, improved animal experimentation, pointed to necessity of chemical analysis for legal proof of lethal intoxication, devised poison detection methods.
• Contemporaries of Orfila: Marsh, Magendie, Tardieu, Ambrose Pare, Stas, Scheele, Reinsch.
• Robert Christison (1779-1882): major work on poisons (1845), influenced by Orfila.
• Rudolf Kobert: toxicology textbook in the style of Orfila (1893).

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8.2 Important Definitions

• Poison: Any substance which when introduced into or absorbed by a living body destroys life or injures health. Any substance in excess can be a poison (Paracelsus: "the dose makes the poison").
• Toxicology: The science of poisons.
• Forensic Toxicology: Application of toxicology to legal purposes.
• Clinical Toxicology: Medical management of patients poisoned by drugs or chemicals.
• Pharmacology: Study of drugs and their actions.
• Dose: Amount of a substance given at one time.
• LD50 (Lethal Dose 50): The dose that kills 50% of a group of experimental animals.
• TD50 (Toxic Dose 50): Dose producing a toxic effect in 50% of animals.
• Therapeutic Index (TI): LD50 / ED50. Indicates relative safety of a drug.
• Tolerance: Ability of an organism to show less response to a specific dose than it showed on a previous occasion - results from decreased reaction between the chemical and the biologic effector substance.
• Cumulative action: Poisons eliminated slowly accumulate in the body with repeated doses.
• Idiosyncrasy: An abnormal (usually unexpected) response to a drug or chemical at normal doses.
• Allergy/Hypersensitivity: Immunologically mediated adverse drug reaction; common examples - iodine, bromine, opium, belladonna, cocaine, aspirin, penicillin, mercury.
• Synergism: Combined effect of two drugs greater than the sum of each alone.
• Antagonism: One drug opposes the effect of another.
• Ecotoxicology: Toxic effects of chemical/physical agents on living organisms in populations and communities within defined ecosystems.

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8.3 Classification of Poisons

By Origin

1. Animal origin: Snake venom, scorpion venom, cantharides
2. Vegetable origin: Opium, strychnine, aconite, dhatura
3. Mineral origin: Arsenic, lead, mercury, phosphorus

By Action/Chemical Nature (Standard Classification)

By Medico-legal Aspect

1. Homicidal
2. Suicidal
3. Accidental
4. Self-administered for purpose of intoxication/addiction

Types of Poisoning

1. Fulminant: Massive dose; rapid death sometimes without symptoms
2. Acute: Excessive single dose or several doses over short interval
3. Subacute: Features of both acute and chronic
4. Chronic: Smaller doses repeated over long time

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Toxicokinetics (Fate of Poison in Body)

Routes of Administration

1. Ingestion (oral)
2. Intravenous (most rapid)
3. Intramuscular, subcutaneous, intradermal
4. Application to a wound
5. Application to serous surface
6. Bronchotracheal mucous membrane (inhalation)
7. Introduction into natural orifices (rectum, vagina, urethra)
8. Application to unbroken skin - organic phosphates, nicotine, organic solvents, lewisite gas, phenol, mercury, tetraethyl lead, cantharidin, HCN, estrogen, progesterone, methyl salicylate

Distribution and Fate

• Most poison is eliminated by vomiting and purging
• Absorbed portion deposited in liver (partial/complete metabolism)
• Unaltered portion enters general circulation and acts on target organs
• Inorganic poisons (arsenic, antimony) retained in nails, hair, bones for long periods
• Poisons destroyed in body (no trace after delayed PM): chloroform, phosphorus, nitrates, acetic acid

Effect on Putrefaction

Drugs Secreted into the Stomach (Important for Gastric Lavage)

• Acids: Salicylic acid, barbital, probenecid, thiopental
• Bases: Theophylline, antipyrine, quinine, acetanilid, aniline

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Factors Modifying Action of Poisons

• (A) Idiosyncrasy/Allergy: Abnormal or immunologic response
• (B) Habit/Tolerance: Requires increasing doses; opiates, alcohol, cocaine, morphine; limited tolerance for minerals (except arsenic)
• (C) State of Health: Diseased/debilitated persons more susceptible; CO can kill at only 25-30% blood saturation in debilitated; opium can be given in larger doses in tetanus, delirium tremens, mania
• (D) Sleep and Intoxication: Delay action of poison
• (E) Cumulative action: Slow elimination leads to buildup

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8.4 Laws in Relation to Poisons (India)

1. The Poisons Act, 1919: Regulates import, export, possession and sale of scheduled poisons.
2. The Pharmacy Act, 1948: Only registered pharmacists can compound, prepare, mix or dispense medicines on prescription. Does not apply to a doctor dispensing for their own patients.
3. The Drugs Control Act, 1950: Controls sale, supply and distribution of drugs; fixes maximum price.
4. The Drugs and Magic Remedies (Objectionable Advertisements) Act, 1954: Bans advertisements for abortion, contraception, sexual potency, menstrual disorders, and VD treatment.
5. The Medicinal and Toilet Preparations (Excise Duties) Act, 1956: Levy/collection of excise duties on medicinal/toilet preparations containing alcohol and narcotic drugs.
6. NDPS Act, 1985 (Narcotic Drugs and Psychotropic Substances Act): Repeals Opium Act 1857, Opium Act 1878, Dangerous Drugs Act 1930. Lists 77 psychotropic substances (LSD, amphetamine, barbiturates, benzodiazepines, methaqualone, ketamine, psilocybin, phencyclidine, mescaline, etc.)

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8.5 Medico-legal Autopsy in Poisoning - Viscera Preservation

Viscera to be Preserved

• Stomach and contents
• Small intestine and contents (1 metre)
• Liver (500 g)
• Kidney (one whole)
• Brain (half)
• Blood (50 mL from femoral vein)
• Urine (all available)
• Vitreous humor (alcohol cases)
• Lumps of hair and nails (arsenic/heavy metals)

Post-mortem Findings in Poisoning (Stomach)

• (A) Discoloration: Corrosive acids → brown/black eschar; alkalis → soft, white/grey soapy appearance
• (B) Hypertrophy of mucosa: Thickening with dilated vessels, from chronic irritant
• (C) Erosions: Corrosive/irritant - reddish-brown; pylorus most often involved
• (D) Ulcers: Thin friable margins, surrounding mucosa softened; disease ulcers have well-defined, thickened, indurated margins on lesser curvature
• (E) Perforation: Mainly from strong mineral acids (especially H₂SO₄); ammonia also causes perforation; stomach blackened, aperture irregular, sloughing edges
• (F) Autolysis vs. corrosive perforation: Autolysis - cardiac end of stomach, large irregular hole, gelatinous surroundings, no peritonitis; corrosive - irregular, sloughing, with peritonitis

Important: False Positive Results in Chemical Analysis

1. Environmental intake of many poisons via food/water/air
2. Decomposition products: gases (methane, H₂S, CO₂, mercaptan), alcohol, CO, cyanide
3. Anticoagulants in blood collection (methanol, formalin, EDTA, heparin)
4. Regular intake of arsenic, mercury, lead from food/water
5. Therapeutic use of arsenic, strychnine, sedatives
6. Nicotine in blood of smokers
7. Faulty technique of sample collection

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8.6 Symptomatology, Diagnosis and Management

Types of Drug Fatalities

1. Primary: Death due to toxic/adverse effect of the chemical agent
2. Secondary: Medical complications of drug abuse (viral hepatitis, bacterial endocarditis)
3. Drug-associated: Homicidal, accidental, suicidal violence related to obtaining/using illicit drugs

Drug Automatism

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8.7 Bedside Tests in Toxicology (TABLE 24.4)

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8.8 Methods of Decontamination, Enhanced Elimination and Antidotal Therapy

I. Gastric Lavage (Stomach Wash)

• Best performed within 4-6 hours of ingestion (up to 12 hours for some drugs)
• Use warm water or appropriate antidote solution
• Contraindications: Corrosive poisoning (risk of perforation), petroleum products/volatile hydrocarbons, unconscious patient (unless intubated), convulsions

II. Emesis (Induced Vomiting)

• Syrup of Ipecac: 30 mL adults; 15 mL (1-12 years); 10 mL (9-12 months); 5 mL (6-9 months) followed by several glasses of water. Induces vomiting in 90-95% within 20-30 min. Contains cephaeline and emetine.
• Acts by: local stimulation of GIT peripheral receptors + stimulation of vomiting centre
• Contraindications: Same as gastric lavage + severe heart/lung disease, advanced pregnancy, after CNS stimulants (risk of convulsions)
• Note: Salt water can cause fatal hypernatremia; copper sulfate, apomorphine, tartar emetic, zinc sulfate are obsolete.

III. Antidotes

1. Inert complex formation - chelating agents for heavy metals; dicobalt edetate for cyanide
2. Accelerated detoxification - thiosulfate for cyanide
3. Reduced toxic conversion - ethanol for methanol (competes for alcohol dehydrogenase)
4. Receptor site blockade - naloxone for opiates; atropine for organophosphates (muscarinic receptors)
5. Toxic effect bypass - 100% oxygen in cyanide poisoning

• Activated Charcoal: Fine, black, odorless, tasteless powder from destructive distillation of wood pulp + activation with steam/CO₂. Surface area = 1,000 sq meters per gram. Mixed as slurry (8 mL water per gram). NOT effective for iron, lithium, heavy metals, cyanide, alcohol, caustics.
  • Dose: 1 g/kg body weight; single dose or multi-dose
  • Multi-dose activated charcoal (MDAC) used for drugs with enterohepatic circulation
• Demulcents: Egg white, milk, olive oil, starch - soothe irritated mucosa

• Alkalis (for acid poisoning) - milk of magnesia, chalk, sodium bicarbonate
• Acids (for alkali poisoning) - diluted acetic acid, lemon juice
• Potassium permanganate (oxidizes alkaloids - morphine, strychnine, quinine, physostigmine)
• Tannic acid (precipitates alkaloids and heavy metals)
• Specific chelating agents - BAL, EDTA, D-penicillamine, desferrioxamine

Enhanced Elimination Methods

1. Forced diuresis (alkaline diuresis for salicylates, acidic diuresis for amphetamines)
2. Haemodialysis - for methanol, ethylene glycol, salicylates, lithium
3. Haemoperfusion - for barbiturates, theophylline, paraquat
4. Exchange transfusion - neonates, severe poisoning
5. Multi-dose activated charcoal - for drugs with enterohepatic circulation

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8.9 Police Intimation and Maintenance of Records

• All cases of suicidal, homicidal, or suspicious poisoning must be reported to police (Section 39 CrPC - duty to give information of certain offences)
• Hospital records of poisoning cases must be maintained carefully
• MLC (Medico-legal Case) documentation required
• Viscera should be labeled, sealed and sent to the Chemical Examiner/Forensic Science Laboratory
• Chain of custody must be maintained for legal validity

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8.10 Laboratory Tests (Analytical Toxicology)

Systematic Toxicological Analysis (STA) - Specimens

• Urine: Drug screening (immunoassay)
• Blood: Quantitative levels
• Vitreous humor: Alcohol (stable, resists decomposition)
• Hair: Chronic exposure (arsenic, heavy metals; 1 cm = 1 month's growth)
• Gastric contents: Highest concentration of ingested poison
• Liver: Metabolite detection
• Nails: Arsenic, heavy metals

Analytical Methods

1. Color/spot tests (Reinsch, Marsh, Trinder)
2. Immunoassay (ELISA, RIA) - rapid urine screening
3. Chromatography: TLC (thin layer), GC (gas), HPLC (high performance liquid)
4. Spectrophotometry: UV/Visible for metals, colorimetric
5. Atomic Absorption Spectrophotometry (AAS): Gold standard for heavy metals (arsenic, lead, mercury)
6. Mass Spectrometry (GC-MS): Confirmatory test

Poison Information Centers (India)

• National Poisons Information Centre: AIIMS, New Delhi (uses WHO's INTOX software)
• National Institute of Occupational Health: Ahmedabad
• Regional centers: Chennai and Cochin (POISINDEX)
• Available 24 hours for toxicity assessment and treatment recommendations

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