Basic Toxicology Concepts for Pharmaceutical Toxicology Laboratory

- Livy

Pharmaceutical toxicology

focuses on the toxic effects of drugs and pharmaceutical compounds, including adverse drug reactions, drug overdoses, and safety assessments during drug development.

TOXICOLOGY

The study of adverse effects of chemicals on living organisms

TOXICANT

Used when talking about toxic substances produced by or byproducts of human-made activities.

TOXIN

A naturally occurring toxic substance (e.g., bacterial toxins, snake venom).

POISON

A substance that causes severe harm at low doses (e.g., cyanide).

TOXICITY

The degree to which a substance can harm an organism.

DOSE

The amount of a substance administered to an organism.

LETHAL DOSE 50

The dose that kills 50% of a test population.

THERAPEUTIC INDEX

The ratio of toxic dose to therapeutic dose (TI = TD₅₀ / ED₅₀).

Hazard

Potential to cause harm

Risk

Likelihood of exposure leading to harm.

No Effect Level

The highest dose that produces no observable toxic effects.

Threshold Dose

The minimum dose where toxic effects appear.

Acetaminophen

• Therapeutic dose: 500 mg to 1 g per dose (max 4 g/day).

• Toxic dose: >7.5 g/day → Liver damage due to NAPQI accumulation.

• Lethal dose: >15 g/day → Severe hepatotoxicity, liver failure.

Oral

This route of drug has a toxicity effects: Liver, gastrointestinal, and systemic toxicity

Inhalation

This route of drug has a toxicity effects: Rapid CNS toxicity, respiratory failure

Dermal

Systemic toxicity, skin irritation

Injection

Direct systemic effects, rapid toxicity

Absorption

It is the movement of a substance into the bloodstream.

Distribution

It is the transport of a toxicant to different tissues.

Metabolism

the chemical conversion of drugs/toxicants to enhance excretion.

Ames Test

In vitro (cell-based) tests, this detects mutagenic potential of chemicals.

Cytotoxicity Assays

In vitro (cell-based) tests, this measures cell viability in response to toxicants.

Reactive Oxygen Species Assay

In vitro (cell-based) tests, this evaluates oxidative stress caused by drugs.

Acute Toxicity

In vivo (animal) studies, this determines lethal dose

Chronic Toxicity Studies

In vivo (animal) studies, this evaluates longterm effects of exposure.

Reproductive & Developmental Toxicity Tests

In vivo (animal) studies, this identifies teratogenic effects.

drug-induced liver injury

What does the Liver Function Tests (ALT, AST, ALP, Bilirubin) detects?

nephrotoxicity

What does the Kidney Function Tests (Creatinine, BUN, GFR) detects?

cardiotoxicity

What does the ECG Monitoring identifies?

safe

Are High TI drugs (e.g., penicillin) safe or risky?

Risky

Are Low TI drugs (e.g., digoxin, warfarin) safe or risky?