Toxic Chemical Exposure, Dose & Response

These flashcards cover key concepts from the lecture on toxic chemical exposure, including exposure routes and durations, bioavailability, first-pass effect, dose definitions, graded and quantal dose-response relationships, LD50/ED50, margin of safety, variability, and mixture interactions.

What five environmental media are common sources of toxic chemical exposure?

Air, water, food, soil, and consumer products.

What six overall sources of chemical exposure were listed in the lecture?

Environmental, occupational, therapeutic (medical), dietary, accidental, and deliberate sources.

Name the four primary routes by which poisons can enter the human body.

Ingestion (digestive tract), inhalation (respiratory tract), dermal/topical absorption (skin), and injection/bite.

Which exposure route is typically the most effective at delivering a toxicant into systemic circulation?

Intravenous (IV) injection.

State the typical effectiveness ranking of exposure routes from most to least effective.

IV > inhalation > intraperitoneal (IP) > intramuscular (IM) > ingestion > topical (dermal).

Define bioavailability in pharmacokinetics.

The fraction of an administered dose that reaches the systemic circulation.

What is the bioavailability of an intravenous dose?

100%.

What phenomenon reduces bioavailability after oral administration by metabolising a drug before it reaches systemic circulation?

The first-pass effect (first-pass metabolism).

During the first-pass effect, which organ is primarily responsible for pre-systemic metabolism?

The liver.

List the four exposure-duration categories used in toxicology studies.

Acute (

How is "dose" normally expressed in toxicology?

Milligrams of chemical per kilogram of body weight (mg/kg).

What three conditions must be met for a toxic effect to occur?

The chemical must reach the target site, at a sufficient concentration, for a sufficient duration.

What is meant by a threshold concentration in toxicity?

The lowest concentration that can produce a harmful effect or toxic response.

Which type of toxic response is unpredictable, genetically determined, and does not involve the immune system?

An idiosyncratic reaction.

Differentiate between local and systemic toxic effects.

Local effects occur at the site of contact; systemic effects involve absorption and impact distant organs.

What kind of dose-response curve relates dose to magnitude of effect in a single individual?

A graded dose-response curve.

What kind of dose-response curve relates dose to the proportion of a population that responds?

A quantal dose-response curve.

What does NOAEL stand for?

No Observable Adverse Effect Level.

On a log dose-response curve, what does the slope indicate?

How rapidly the response changes with dose (steep = greater change per dose increment).

Define ED50.

The dose that produces the desired (effective) response in 50% of the population.

Define LD50.

The dose that is lethal to 50% of the population.

When comparing two toxicants, which one is more potent?

The one with the lower LD50 (it kills at a smaller dose).

Provide the formula for calculating the margin of safety.

Margin of Safety = LD1 ÷ ED99.

Why is therapeutic index alone not sufficient to judge drug safety?

It only compares median doses (ED50 vs LD50) and ignores the shapes of the full therapeutic and toxic dose-response curves.

Name three biological factors that cause variability in individual drug responses.

Body weight/size, age and sex, genetic differences (others: health status, tolerance, placebo effect).

List three administration-related factors that influence drug or toxicant response.

Dose and formulation, route of administration, and drug interactions (absorption, protein binding, metabolism, excretion, receptor effects).

In mixture toxicity, what term describes a combined effect equal to the sum of individual effects?

Additive interaction.

In mixture toxicity, what term describes a combined effect greater than the sum of individual effects?

Synergistic interaction.

In mixture toxicity, what term describes a combined effect less than expected from individual effects?

Antagonistic interaction.

Which drug administration route is generally considered most convenient for patients?

Oral administration.

Give two examples of injection routes mentioned other than intravenous.

Intramuscular (IM) and intraperitoneal (IP).

How does a long biological half-life affect chemical accumulation during chronic exposure?

It allows the chemical to build up in the body over time, increasing potential toxicity.

Why are animal models used to collect toxicokinetic data instead of human volunteers?

Ethical and safety reasons—deliberate high-dose exposure cannot be performed in humans.

Name the two related scientific disciplines that study how chemicals move through the body for drugs and toxins, respectively.

Pharmacokinetics (drugs) and toxicokinetics (toxins).

Why must bioavailability be considered when calculating non-IV dosages?

Because less than 100 % of the administered dose reaches systemic circulation, so the dose must be adjusted accordingly.

What is the relationship between dose and response according to the fundamental toxicology principle discussed?

As the dose of a toxicant increases, the magnitude of the response also increases (dose determines the biological response).

Which exposure category involves a single exposure lasting less than 24 hours?

Acute exposure.

What graphical distribution illustrates variability in individual responses to the same dose?

A normal (Gaussian) distribution curve.

What is the practical implication of individual variability for setting exposure guidelines?

Guidelines must protect the most sensitive individuals, not just the average.