Fundamentals of Toxicology - Vocabulary Flashcards

A set of vocabulary-style flashcards covering key terms and concepts from Lecture 2: Fundamentals of toxicology, including spectrum of effects, exposure, dose–response, interactions, risk metrics, and systems toxicology.

Adverse effects (toxic effects)

Effects of a drug that are never desirable and are harmful (adverse or toxic effects).

Allergic reaction

Adverse immune response to a chemical requiring prior exposure (sensitization).

Sensitization

Prior exposure to a chemical that enables a subsequent toxic or allergic response.

Idiosyncratic reaction

Abnormal reactivity to a chemical based on genetics or other individual sensitivity factors.

Agranulocytosis

Life-threatening reduction in neutrophils due to bone marrow suppression.

Aplastic anemia

Bone marrow failure leading to insufficient production of neutrophils and erythrocytes.

Immediate toxicity

Toxic effects that are observable soon after exposure.

Delayed toxicity

Toxic effects that take months or years to become evident after exposure.

Reversible toxicity

Toxic effects that tissue can adapt to, repair, or recover from.

Irreversible toxicity

Toxic effects that cause permanent damage (e.g., cancers, birth defects).

Local toxicity

Toxic effects that occur at the site of first contact with the toxicant.

Systemic toxicity

Toxic effects that occur after absorption and distribution to distant sites.

Antagonism

Interaction where combined effects are less than the sum of individual effects.

Receptor antagonism

Two chemicals compete for the same receptor, reducing each other's effect.

Chemical antagonism

Direct chemical reaction between two compounds producing a less toxic product.

Dispositional antagonism

Alteration of absorption, distribution, metabolism, or excretion reducing target site exposure.

Functional antagonism

Two chemicals counterbalance each other by affecting the same physiological function.

Additivity

Combined effect equals the sum of individual effects.

Toxicity Equivalence Factor (TEF)

A relative potency factor that compares dioxin-like compounds to a reference (TCDD).

Dioxins

Family of structurally related persistent environmental pollutants (e.g., TCDD) with toxic properties.

Total Toxic Equivalents (TEQ)

Sum of (concentration × TEF) for dioxin-like compounds in a mixture.

Aryl hydrocarbon receptor (AhR)

Ligand-activated transcription factor activated by dioxins/PAHs/PCBs that regulates gene expression linked to toxicity and cancer.

AhR-ARNT complex

Dimer of AhR with ARNT that binds to AHREs to initiate transcription of target genes.

Xenobiotic-metabolizing enzymes

Enzymes (e.g., CYP1A1, CYP1A2, CYP1B1) induced by AhR signaling to metabolize xenobiotics.

Detoxification pathway (NQO1)

Phase II/detox genes that help neutralize oxidative stress, potentially involved in cancer risk when overactivated.

Immunosuppression via AhR

Chronic AhR activation can promote regulatory T cells and dampen anti-tumor immunity.

Dose–response relationship

Association between the amount of toxic exposure and the extent of biological change.

ED50

Dose that induces a response in 50% of a population.

LD50/LC50

Lethal dose/ lethal concentration for 50% of a population.

TD1

Toxic dose that produces a specified effect in 1% of a population (example metric).

NOAEL

No Observed Adverse Effect Level—the highest dose with no significant adverse effects observed.

LOAEL

Lowest Observed Adverse Effect Level—the lowest dose at which adverse effects are observed.

MOE (Margin of Exposure)

Exposed dose divided by NOAEL; used for chemicals without beneficial effects.

Margin of Safety (MOS)

TD1 to ED99 or similar comparison; alternative metric to gauge safety margins.

Therapeutic Index (TI)

Ratio of toxic dose to therapeutic dose; wider TI indicates safer drug.

Margin of Safety (MOS) (environmental contaminants)

MOE-type concept applied when no beneficial effect exists; compares exposure to NOAEL/LOAEL.

Potency

Amount of substance needed to produce a given effect; lower dose for same effect means higher potency.

Efficacy

Maximum effect a substance can produce, regardless of dose.

Synergism

Combined effect of two chemicals is greater than the sum of their separate effects.

Potentiation

One chemical increases the toxicity of another without sharing the same toxic effect.

Dose extrapolation across species

Using body surface area (not body weight) to convert doses when translating from animals to humans.

MRSD (Maximum Recommended Starting Dose)

Highest dose tested in animals that does not cause significant toxicity, used to start human trials.

Therapeutic index vs margin of safety

TI compares TD50 to ED50; MOS/ MOE compare exposure to NOAEL or ED99 to assess safety.

Quantal vs graded dose–response

Quantal: population-level all-or-none responses; Graded: continuous response in individuals.

Monotonic dose–response curve

Response increases (or decreases) steadily with dose.

Nonmonotonic dose–response curve (hormesis)

Curve with multiple inflection points; low-dose stimulation with high-dose toxicity.

Threshold model

Toxicity appears only above a certain dose; no effects below threshold.

Linear, nonthreshold model

Proportional dose–response without a safe threshold; used for genotoxic carcinogens and ionizing radiation.

AOP (Adverse Outcome Pathway)

Framework linking molecular initiating events to adverse outcomes through a chain of key events.

Systems toxicology

Integrates toxicology with systems biology (genomics, proteomics, metabolomics) to study toxicity pathways.

Transcriptome

All mature mRNA species present in a cell at a given time.

Epigenome

Heritable changes in gene expression without altering DNA sequence (e.g., methylation, histone modification).

Proteome

Complete set of proteins expressed in a cell, tissue, or organism.

Metabonomics/Metabolomics

Analysis of small-molecule metabolites to assess biochemical pathways and responses.

DDT eggshell thinning hypothesis

DDT/DDE disrupt calcium metabolism causing thinner eggshells and reproductive failures in birds.

Selective toxicity

Ability of a chemical to affect a target organism or tissue while sparing others.

Species differences in toxicity

Different species can show different toxicokinetic and toxicodynamic responses to the same chemical.

Biomagnification

Increase in concentration of a toxin as it moves up the food chain.