Toxicology, Genotoxicity & Chronopharmacology – Key Vocabulary

A comprehensive set of vocabulary flashcards covering core concepts, agents, mechanisms and chronobiological terms from the lecture on toxicity, genotoxicity, antidotes, poisoning management and chronopharmacology.

Toxicology

The branch of science that studies the nature, effects and detection of poisons (xenobiotics) in living organisms.

Xenobiotic

Any foreign chemical substance not naturally produced by or expected to be present within an organism.

Acute Toxicity

Adverse effects occurring within 14 days after a single (or ≤24 h) exposure to a substance.

Sub-Acute Toxicity

Toxicity observed after repeated exposure for 14–28 days (≈1 month).

Sub-Chronic Toxicity

Toxicity resulting from exposure for 1–3 months.

Chronic Toxicity

Adverse effects produced by exposure lasting >3 months, often producing specific organ damage.

LD50

Median lethal dose: the single dose that kills 50 % of a test population (indicator of acute toxicity).

ED50

Median effective dose: dose at which 50 % of animals show a specified effect (may be therapeutic or toxic).

OECD Guidelines

International test protocols (e.g., TG 420, 423, 425) that standardise acute and repeat-dose toxicity studies.

Genotoxicity

Ability of an agent to damage genetic material, leading to mutations, cancer or birth defects.

Genotoxin

Chemical or physical agent capable of causing direct or indirect DNA damage.

Mutagenicity

Induction of heritable DNA changes (mutations); all mutagens are genotoxic, but not all genotoxins are mutagenic.

Mutagen

Agent that induces genetic events altering DNA or chromosomes, transmissible to progeny cells.

Carcinogenicity

Property of a substance to induce or increase the incidence of cancer.

Teratogenicity

Capacity of a substance to cause congenital malformations or developmental toxicity.

Teratogen

Agent that disrupts embryonic/fetal development, producing structural or functional defects.

Reactive Oxygen Species (ROS)

Highly reactive oxygen-containing molecules (e.g., superoxide, hydroxyl radical) that can damage DNA, proteins and lipids.

Free Radical

Molecule with an unpaired electron; often initiates oxidative damage (e.g., ROS, RNS).

Alkylating Agents

Chemotherapy drugs that modify DNA bases, interfering with replication (e.g., busulfan, carmustine).

Intercalating Agents

Planar molecules that wedge between DNA bases, disrupting replication/transcription (e.g., doxorubicin).

Enzyme Inhibitors (Genotoxic Chemo)

Drugs that block enzymes critical to DNA replication (e.g., etoposide, decitabine).

Carcinogen Category 1 (EU)

Known or presumed human carcinogen based on human/animal evidence.

Carcinogen Category 2 (EU)

Suspected human carcinogen; evidence mainly from animal studies and limited human data.

IARC Class 1

Agent is carcinogenic to humans.

IARC Class 2A

Agent is probably carcinogenic to humans.

Blastocyst

Early embryo (≈day 5) consisting of trophoblast and inner cell mass; very sensitive to cytotoxic drugs.

Organogenesis

Embryonic stage (≈days 17–60) when major organs form; peak period for teratogenic malformations.

Histogenesis

Stage of tissue differentiation & functional maturation occurring after organogenesis.

Phocomelia

Severe limb reduction defect famously linked to thalidomide exposure.

Frame-Shift Mutation

Insertion/deletion of nucleotides altering the reading frame of a gene.

Point Mutation

Single-nucleotide change in DNA (e.g., sickle-cell substitution).

Chromosome Mutation

Structural alteration of chromosomes (deletion, inversion, translocation, duplication, nondisjunction).

Deletion (Chromosomal)

Loss of a chromosome segment, removing genes.

Inversion

Reattachment of a chromosome segment in reversed orientation.

Translocation

Transfer of a chromosome part to a non-homologous chromosome.

Duplication

Repeated copy of a gene or chromosome segment.

Nondisjunction

Failure of chromosomes to separate during meiosis, causing aneuploidy.

Acridine Orange

Intercalating dye that induces frame-shift mutations by base insertions/deletions.

Nitrogen Mustard

Alkylating mutagen causing point mutations via base modification.

Cosmic Rays

High-energy space radiation acting as natural mutagens.

Activated Charcoal

Highly porous adsorbent used to bind ingested toxins in the gut and reduce absorption.

Gastric Lavage

Stomach washing to remove unabsorbed poison, ideally within 3–4 h of ingestion.

Emetic

Agent or method that induces vomiting to expel ingested poison.

Cathartic

Substance promoting bowel evacuation; used in whole-bowel irrigation for sustained-release overdoses.

Specific Antidote

Agent that counteracts a particular poison by a defined mechanism (e.g., naloxone for opioids).

Chelation Therapy

Use of ligands to bind metal ions forming non-toxic complexes excreted in urine or bile.

Dimercaprol (BAL)

Chelating agent for arsenic, mercury, lead; contains sulfhydryl groups that bind metals.

EDTA (CaNa2)

Polyaminocarboxylate chelator used mainly for lead poisoning.

Atropine

Muscarinic antagonist used to treat organophosphate-induced cholinergic excess.

Pralidoxime (2-PAM)

Oxime that reactivates phosphorylated acetylcholinesterase in organophosphate poisoning.

Organophosphate

Phosphoryl ester compound (often insecticide/nerve agent) that irreversibly inhibits acetylcholinesterase.

Acetylcholinesterase

Enzyme that hydrolyses acetylcholine; inhibition leads to cholinergic overstimulation.

DUMBELS

Mnemonic for muscarinic OP poisoning signs: Diarrhoea, Urination, Miosis, Bronchospasm/Bradycardia, Emesis, Lacrimation, Salivation.

SLUDGE

Alternate mnemonic: Salivation, Lacrimation, Urination, Diarrhoea, Gastrointestinal distress, Emesis.

Barbiturate

Sedative-hypnotic drugs that enhance GABA-mediated Cl– influx, causing CNS depression.

GABA Receptor

Neurotransmitter receptor whose activation opens Cl– channels producing neuronal inhibition.

Barbiturate Blister

Cutaneous bullae appearing over pressure points after barbiturate overdose.

Naloxone

Competitive opioid receptor antagonist reversing morphine/heroin respiratory depression.

Lead Colic

Severe intermittent abdominal pain characteristic of significant lead poisoning.

Burton’s Line

Bluish-black gingival line reflecting chronic lead sulfide deposition.

Mercury

Toxic heavy metal existing as elemental, inorganic or organic (methyl) forms.

Methyl Mercury

Highly neurotoxic organic mercury that bioaccumulates in fish and seafood.

Chronopharmacology

Science of optimising drug therapy by synchronising administration with biological rhythms.

Chronokinetics

Circadian variations in a drug’s pharmacokinetics (ADME).

Chronesthesy

Time-dependent changes in tissue sensitivity or receptor responsiveness to a drug.

Chronergy

Overall rhythmic change in therapeutic and toxic responses combining chronokinetics & chronesthesy.

Chronotoxicity

Time-related variation in the degree of toxic effect produced by a chemical.

Chronotherapy

Timed drug delivery or behavioural scheduling to align treatment with biological rhythms.

Circadian Rhythm

Approximately 24-hour endogenous cycle regulating physiology and behaviour (sleep–wake, hormones).

Ultradian Rhythm

Biological cycle shorter than 24 h (e.g., REM–NREM sleep phases, heartbeat).

Infradian Rhythm

Biological cycle longer than 24 h (e.g., menstrual cycle).

Suprachiasmatic Nucleus (SCN)

Hypothalamic cluster functioning as the master circadian pacemaker in mammals.

Biological Clock

Endogenous timing system, centred in the SCN, that coordinates peripheral rhythms across the body.

Auto-Induction

Drug-induced up-regulation of its own metabolising enzymes, increasing clearance over time.

Auto-Inhibition

Metabolite-mediated feedback inhibition that slows parent drug metabolism.

High-Alertness Circadian Phase

Morning period (~10 a.m.) of peak cognitive performance and reaction speed.

Triglyceride Circadian Peak

Early evening rise in serum triglycerides observed in normal human rhythm.

Hypertension Chronotherapy

Administering antihypertensives at bedtime to control early-morning BP surge.

Myocardial Infarction Chronotherapy

Targeting morning high-risk window when platelet aggregation and catecholamines peak.

CGRP Circadian Peak

Calcitonin gene-related peptide levels highest late night/early morning, influencing migraine timing.

Growth Hormone Peak

Pulsatile surge occurring soon after sleep onset, mainly during deep sleep.

Morning Platelet Aggregation

Enhanced thrombogenicity after awakening, contributing to higher AM cardiovascular events.

Night-Time Free Drug Fraction

Albumin nadir during sleep increases free levels of highly bound drugs (e.g., diazepam).

Organophosphate Aging

Irreversible process where phosphorylated AChE loses an alkyl group, preventing oxime reactivation.

Up-and-Down Procedure (OECD TG 425)

Sequential dosing method to estimate acute oral LD50 with fewer animals.

Fixed Dose Procedure (OECD TG 420)

Acute oral toxicity test using predetermined dose levels to identify toxicity class.

Acute Dermal Toxicity Study

OECD test assessing toxicity after single 24-h skin application of a substance.

Acute Inhalation Toxicity Study

OECD protocol evaluating effects of 4-h exposure to airborne chemicals.

TSH Circadian Peak

Thyroid-stimulating hormone reaches maximum during nocturnal sleep period.

Melatonin

Pineal hormone secreted during darkness; key signal of night phase to peripheral clocks.