General Toxicology and Toxicologic Principles
Foundations
General toxicology provides the framework: exposure assessment, dose-response, toxicokinetics, mechanisms, target organ toxicity, and risk assessment. Candidates should be comfortable with terminology (LD50, NOAEL, LOAEL, therapeutic index, bioaccumulation, synergism) and with how studies are designed and interpreted.
Concepts to master
- Exposure routes and duration: acute vs chronic; dermal, inhalation, oral, parenteral. Route affects bioavailability and first-pass metabolism.
- Dose-response curves: sigmoidal shape, threshold, slope; steep curves imply narrow margins of safety.
- Toxicokinetics (ADME): absorption, distribution (volume of distribution, protein binding), metabolism (phase I oxidation, phase II conjugation; induction and inhibition), excretion (renal, biliary, enterohepatic recirculation).
- Mechanisms of injury: receptor-mediated, enzyme inhibition, oxidative stress, covalent binding, immune-mediated, carcinogenesis (initiation/promotion), teratogenesis (critical windows).
- Interactions: additive, synergistic, antagonistic; chemical vs functional antagonism.
- Risk assessment: hazard identification, dose-response, exposure assessment, risk characterization; safety factors applied to NOAEL.
Traps in questions
Do not confuse LD50 (median lethal dose) with LC50 (concentration) or with NOAEL. Remember that a high therapeutic index is safer. Watch for questions asking about first-pass effect or enterohepatic recirculation prolonging exposure.
Rule of thumb
If asked whether a substance is "safe," compare the exposure dose to the NOAEL and note the safety factor-never rely on a single LD50 value alone.
Worked example
A chronic exposure scenario: a dog eats a diet with a contaminant at 1 mg/kg body weight/day; the NOAEL is 0.5 mg/kg/day. The exposure exceeds the NOAEL, so risk characterization flags concern even without overt clinical signs.