Toxicology is the study of the adverse effects of chemicals on living organisms.
In drug development, toxicological studies assess the potential harmful effects of drug candidates.
Types of Toxicity Studies
Acute Toxicity
Objective: Determine the effects of a single dose.
Endpoints: Lethal dose (LD50), clinical signs, organ toxicity.
Repeated Dose Toxicity
Subacute (up to 28 days) and Subchronic (up to 90 days)
Objective: Assess effects of repeated dosing over time.
Endpoints: Clinical observations, hematology, clinical chemistry, histopathology.
Chronic Toxicity
Duration: Typically, longer than 90 days, up to 1 year or more.
Objective: Identify long-term effects.
Genotoxicity
Tests: Ames test, micronucleus test, chromosomal aberration tests.
Objective: Detect mutations, chromosomal damage.
Carcinogenicity
Objective: Assess potential to cause cancer.
Duration: Long-term studies, often in rodents.
Reproductive and Developmental Toxicity
Segments:
Segment I: Fertility and early embryonic development.
Segment II: Embryo-fetal development (teratogenicity).
Segment III: Pre- and postnatal development.
Immunotoxicity
Objective: Evaluate effects on the immune system.
Local Tolerance
Objective: Assess irritation or sensitization at administration sites.
Regulatory Guidelines
ICH M3(R2): Guidance on non-clinical safety studies.
OECD Guidelines: Standardized methods for toxicology testing.