DABT key terms

The principle that the size of a biological response generally rises as dose or exposure concentration increases, and that a dose often exists below which no measurable effect occurs.

A biphasic dose–response pattern in which low doses produce a stimulatory or beneficial effect while higher doses produce inhibition or toxicity, giving a U-shaped or inverted-U curve.

The statistically derived single dose of a substance expected to kill 50% of a defined test population under stated conditions; used to compare acute lethality, not chronic hazard.

The property of a chemical or drug that harms a target organism, cell, or process while sparing the host or non-target species, usually because of a biochemical difference between them.

An empirically supported sequence of key biological events that explains how a substance produces an observed effect at a given dose; less detailed than a full mechanism of action.

A framework linking a molecular initiating event through ordered key events to an adverse outcome at the organism or population level, used to organize mechanistic evidence for hazard assessment.

A chemical foreign to an organism-such as a drug, industrial chemical, or environmental contaminant-that is not normally produced by or expected in that organism.

The study of how a substance is absorbed, distributed, metabolized, and excreted over time, linking administered dose to internal concentration at target tissues.

The four processes determining a substance's fate in the body: absorption into blood, distribution among tissues, metabolism (biotransformation), and excretion; together they set the internal dose.

An apparent proportionality constant relating the amount of substance in the body to its plasma concentration; a large value indicates extensive tissue distribution rather than circulating drug.

The volume of plasma or blood from which a substance is completely removed per unit time; with volume of distribution it determines elimination half-life.

Metabolic conversion of a relatively unreactive parent compound into a reactive intermediate that can bind cellular macromolecules or generate oxidative stress, thereby producing toxicity.

A superfamily of heme-containing enzymes, most abundant in liver, that carry out oxidative phase I metabolism of many xenobiotics and can be induced or inhibited by exposures.

Conjugation reactions such as glucuronidation, sulfation, or glutathione conjugation that attach polar groups to a compound or its metabolite, usually increasing water solubility and excretion.

Metabolism of an orally absorbed substance in the intestinal wall and liver before it reaches systemic circulation, lowering oral bioavailability and sometimes generating toxic metabolites locally.

A mathematical model representing the body as interconnected tissue compartments with blood flows and partition coefficients, used to predict internal doses and extrapolate across species, routes, and doses.

The area under the concentration–time curve, an integrated measure of total systemic exposure over a defined period, used to compare internal doses across species or routes.

Chemical injury to the liver, shown as elevated liver enzymes, fat accumulation, cholestasis, necrosis, or fibrosis; patterns depend on the agent, dose, and duration of exposure.

Functional or structural kidney damage caused by toxicants, frequently affecting proximal tubular cells; detected by altered filtration, urinary biomarkers, or histopathology.

A condition in which oxidized hemoglobin (ferric iron) cannot carry oxygen, causing cyanosis and hypoxia; induced by nitrites, aniline, dapsone, and some local anesthetics.

A state in which reactive oxygen species exceed antioxidant defenses, damaging lipids, proteins, and DNA and contributing to many toxic endpoints.

An adverse reaction occurring in a small, unpredictable fraction of exposed people and not explained by the substance's known dose-related pharmacology; often immune-mediated or metabolic in origin.

A class of pesticides and nerve agents that phosphorylate acetylcholinesterase; poisoning produces cholinergic crisis with salivation, miosis, bronchoconstriction, bradycardia, and seizures.

Blocking of acetylcholinesterase so that acetylcholine accumulates at synapses and neuromuscular junctions, producing cholinergic overstimulation that can progress to respiratory failure.

A substance that interferes with the synthesis, secretion, transport, binding, or elimination of natural hormones, altering endocrine function and development in intact organisms or their offspring.

Combustion-derived organic compounds with two or more fused aromatic rings; some are bioactivated to diol epoxides that bind DNA and cause cancer.

A toxic secondary metabolite produced by fungi, such as aflatoxin B1, that can contaminate food and feed and cause acute or chronic disease in humans and animals.

The highest dose or exposure level in a study at which no statistically or biologically significant increase in adverse effects is seen compared with controls.

An estimate of daily oral exposure likely to be without appreciable lifetime risk of harmful effects, derived by dividing a NOAEL or benchmark dose by uncertainty factors.

A dose estimated by statistical modeling to give a predetermined small increase in response, such as 5% or 10%; its lower confidence limit often replaces a NOAEL.

A numerical divisor applied to an experimental point of departure to account for animal-to-human differences, human variability, and database deficiencies when deriving health-based guidance values.

The ratio of a point of departure, such as a NOAEL or benchmark dose, to estimated human exposure; smaller values indicate less separation between exposure and potentially harmful doses.

An estimate of increased cancer risk per unit dose, derived from linear extrapolation of animal or epidemiological data and used to calculate lifetime cancer risk.

Predicting the hazard of a data-poor substance from toxicity data on structurally or mechanistically similar substances, with documented justification for why the comparison is valid.

Distortion of an exposure–disease association by a third variable related to both exposure and outcome that is not on the causal pathway.

In case–control studies, the ratio of the odds of exposure among cases to the odds among controls; approximates relative risk when the disease is rare.

A quality system of management controls for how nonclinical laboratory studies are planned, performed, monitored, recorded, and reported, ensuring data integrity and regulatory acceptability.

Assigning experimental subjects to treatment groups by chance so that known and unknown confounders are distributed similarly across groups, reducing bias.

The highest dose allowed or required in a regulatory toxicity study, such as 1000 or 2000 mg/kg/day, tested when lower doses cause no toxicity.