Example FlashCards
(30 cards)
What is 4-ipomeanol, and how does its toxicity differ between species?
4-ipomeanol: Fungal-derived toxicant catalyzed by CYP4B1 to a reactive intermediate. In animals, causes bronchiolar toxicity in lungs. In humans, hepatotoxic due to liver metabolism. Exam note: Species-specific metabolism is a key DABT concept.
What is the role of acetylcholine at nicotinic receptors, and name a toxicant affecting it?
Acetylcholine (nicotinic): Neurotransmitter at ganglia and neuromuscular junctions. Nicotine (agonist) causes muscle fibrillation and paralysis. Tubocurarine (antagonist, plant toxin) causes paralysis via poison arrows. Supplement: Alpha-bungarotoxin (snake toxin) also antagonizes nicotinic receptors.
Describe the effects of muscarinic M1 receptor agonists and antagonists.
M1 Agonists: Oxotremorine (plant chemical), organophosphate insecticides cause neuronal activation, convulsions. Antagonists: Atropine, belladonna cause hallucinations, decreased salivation. Supplement: Atropine is used in organophosphate poisoning treatment.
What are acute-phase proteins, and how are they used diagnostically?
Acute-phase proteins: Induced by interleukins, alter protein transcription/translation. Examples: C-reactive protein, hepcidin (diagnose tissue injury/inflammation), metallothionein (binds metals), opsonin (facilitates phagocytosis). Supplement: Increased RBC sedimentation due to fibrinogen is a clinical marker.
Define additive effect and provide an example.
Additive effect: Combined response of two chemicals equals the sum of individual responses. Example: Two organophosphate insecticides produce additive injury. Supplement: Common in pesticide exposure risk assessments.
What is the difference between hazard and risk?
Hazard: Intrinsic toxic property of a chemical (e.g., pesticide toxicity). Risk: Incorporates dose-response and exposure. Supplement: Risk = Hazard × Exposure is a key DABT formula.
What is REACH, and what data does it require?
REACH: EU program for Registration, Evaluation, Authorization, and Restriction of Chemicals. Data: Physical, chemical, toxicological, environmental fate/transport. Supplement: Uses read-across to estimate toxicity for similar chemicals.
What is the Ames test, and what does it detect?
Ames test: Bacterial assay (Salmonella typhimurium) for mutagenicity. Detects point mutations (TA100, TA1535) and frameshift mutations (TA98, TA1537). Requires S9 for pro-carcinogens. Supplement: High sensitivity for genotoxic carcinogens.
How is RfD (Reference Dose) calculated?
RfD: NOAEL ÷ UF (Uncertainty Factor, typically 100: 10 for interspecies, 10 for human variability). Supplement: If NOAEL unavailable, LOAEL ÷ 1000. Critical for pesticide regulation.
What is MOE (Margin of Exposure)?
MOE: NOAEL (rodents) ÷ Human exposure. Supplement: Higher MOE indicates safer exposure. Used in EPA risk assessments.
What are common toxic agents for blood toxicity?
Benzene, lead, arsenic, carbon monoxide, cyanide, nitrates, chloramphenicol, phenylhydrazine, 2-ethoxyethanol, radiation.
What is the mechanism of benzene-induced blood toxicity?
Damages bone marrow stem cells via reactive metabolites, leading to aplastic anemia and leukemia.
What is the mechanism of lead-induced blood toxicity?
Inhibits heme synthesis enzymes (ALA dehydratase, ferrochelatase), causing anemia.
What is the mechanism of carbon monoxide toxicity?
Binds hemoglobin (200x affinity over oxygen), forming carboxyhemoglobin, reducing oxygen transport.
What is the mechanism of cyanide-induced blood toxicity?
Inhibits cytochrome c oxidase, disrupting cellular respiration and causing hypoxia.
What are biomarkers for blood toxicity?
Decreased RBC count, low hemoglobin, increased methemoglobin, carboxyhemoglobin, pancytopenia.
What are testing methods for blood toxicity?
Complete blood count (CBC), hemoglobin levels, methemoglobin levels, bone marrow biopsy.
What are endpoints for blood toxicity?
Aplastic anemia, leukemia (e.g., AML), methemoglobinemia, cyanide poisoning, hemolytic anemia.
What is the role of nitrates in blood toxicity?
Converted to nitrites, oxidize hemoglobin to methemoglobin, impairing oxygen delivery.
How is 2-ethoxyethanol toxic to blood?
Suppresses red blood cell formation, causing hemolytic anemia and leukopenia.
What are common toxic agents for liver toxicity?
Acetaminophen, ethanol, carbon tetrachloride, aflatoxin B1, amoxicillin-clavulanate, isoniazid, valproate, halothane, herbal supplements, pyrrolizidine alkaloids.
What is the mechanism of acetaminophen-induced liver toxicity?
Metabolized to NAPQI by CYP2E1, depletes GSH, causes mitochondrial oxidative stress and necrosis.
What is the mechanism of ethanol-induced liver toxicity?
Induces CYP2E1, increases fatty acid synthesis, causes steatosis and fibrosis via stellate cell activation.
What is the mechanism of carbon tetrachloride toxicity?
Metabolized to trichloromethyl radical by CYP2E1, causes lipid peroxidation and hepatocyte damage.
