Human in vivo database now on ACuteTox home page

Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...

Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...

Studies that assess how a drug is absorbed, distributed, metabolized, and excreted (ADME) at toxic doses are termed toxicokinetics. Understanding toxicokinetics helps predict adverse drug reactions (ADRs) and manage toxicity in humans.Toxicokinetics differs from pharmacokinetics mainly in the dose levels studied, with toxicokinetics focusing on higher toxic doses. The kinetics at these levels can be non-linear due to altered physiological processes. Toxicodynamics examines the relationship...

In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...

Acute pancreatitis is the sudden inflammation of the pancreas caused by the early activation of digestive enzymes, leading to the autodigestion of pancreatic tissue. This results in local inflammation and, in severe cases, systemic complications.EtiologyUnderstanding the underlying causes is crucial, as identifying the etiology guides treatment and anticipates complications. Acute pancreatitis can be triggered by various factors, typically grouped into the following clinical categories.Biliary...

Toxidromes are specific patterns of symptoms resulting from toxic substance exposure. They help in the identification and treatment of poisoning. The symptoms of each toxidrome group indicate poisoning by a certain class of chemicals or drugs.1. Sympathomimetic: Stimulates the sympathetic nervous system. Symptoms include agitation, increased heart rate (HR), blood pressure (BP), respiratory rate (RR), temperature, and pupil size. Drugs like cocaine and amphetamines, along with tremors and...