In vitro studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and its subdisciplines are traditionally done in labware such as test tubes, flasks, Petri dishes, and microtiter plates. Studies conducted using components of an organism that have been isolated from their usual biological surroundings permit a more detailed or more convenient analysis than can be done with whole organisms; however, results obtained from in vitro experiments may not fully or accurately predict the effects on a whole organism. In contrast to in vitro experiments, in vivo studies are those conducted in living organisms, including humans, known as clinical trials, and whole plants.
Pharmacology is a science of medical drug and medication, including a substance's origin, composition, pharmacokinetics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals.
Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating exposures to toxins and toxicants. The relationship between dose and its effects on the exposed organism is of high significance in toxicology. Factors that influence chemical toxicity include the dosage, duration of exposure, route of exposure, species, age, sex, and environment. Toxicologists are experts on poisons and poisoning. There is a movement for evidence-based toxicology as part of the larger movement towards evidence-based practices. Toxicology is currently contributing to the field of cancer research, since some toxins can be used as drugs for killing tumor cells. One prime example of this is ribosome-inactivating proteins, tested in the treatment of leukemia.
Physiologically based pharmacokinetic (PBPK) modeling is a mathematical modeling technique for predicting the absorption, distribution, metabolism and excretion (ADME) of synthetic or natural chemical substances in humans and other animal species. PBPK modeling is used in pharmaceutical research and drug development, and in health risk assessment for cosmetics or general chemicals.
Toxicogenomics is a subdiscipline of pharmacology that deals with the collection, interpretation, and storage of information about gene and protein activity within a particular cell or tissue of an organism in response to exposure to toxic substances. Toxicogenomics combines toxicology with genomics or other high-throughput molecular profiling technologies such as transcriptomics, proteomics and metabolomics. Toxicogenomics endeavors to elucidate the molecular mechanisms evolved in the expression of toxicity, and to derive molecular expression patterns that predict toxicity or the genetic susceptibility to it.
A toxicophore is a chemical structure or a portion of a structure that is related to the toxic properties of a chemical. Toxicophores can act directly or can require metabolic activation.
Johnson & Johnson Pharmaceutical Research and Development (J&JPRD) is a subsidiary of Johnson & Johnson that is responsible for discovering and developing pharmaceutical drugs. J&JPRD has research sites located in Raritan, New Jersey, Titusville, New Jersey, Spring House, Pennsylvania, La Jolla, California, Beerse, Belgium and Toledo, Spain.
Toxicology testing, also known as safety assessment, or toxicity testing, is the process of determining the degree to which a substance of interest negatively impacts the normal biological functions of an organism, given a certain exposure duration, route of exposure, and substance concentration. Toxicology testing is often conducted by researchers who follow established toxicology test protocosl for a certain substance, mode of exposure, exposure environment, duration of exposure, a particular organism of interest, or for a particular developmental stage of interest. Toxicology testing is commonly conducted during preclinical development for a substance intended for human exposure. Stages of in silico, in vitro and in vivo research are conducted to determine safe exposure doses in model organisms. If necessary, the next phase of research involves human toxicology testing during a first-in-man study. Toxicology testing may be conducted by the pharmaceutical industry, biotechnology companies, contract research organizations, or environmental scientists.
The Innovative Medicines Initiative (IMI) is a European initiative to improve the competitive situation of the European Union in the field of pharmaceutical research. The IMI is a joint initiative of the DG Research of the European Commission, representing the European Communities, and the European Federation of Pharmaceutical Industries and Associations (EFPIA). IMI is laid out as a Joint Technology Initiative within the Seventh Framework Programme. Michel Goldman was the first executive director, from September 2009 until December 2014.
Simcyp Limited is a research-based company which provides modelling and simulation software to the pharmaceutical industry for use during drug development. Simcyp is based in Sheffield, UK.
Safety pharmacology is a branch of pharmacology specialising in detecting and investigating potential undesirable pharmacodynamic effects of new chemical entities (NCEs) on physiological functions in relation to exposure in the therapeutic range and above.
Adverse event prediction is the process of identifying potential adverse events of an investigational drug before they actually occur in a clinical trial.
Biosimulation is a computer-aided mathematical simulation of biological processes and systems and thus is an integral part of systems biology. Due to the complexity of biological systems simplified models are often used, which should only be as complex as necessary.
Critical Path Institute (C-Path) is a non-profit organization created to improve the drug development process; its consortia include more than 1,600 scientists from government regulatory and research agencies, academia, patient organizations, and bio-pharmaceutical companies.
Sean Ekins is a British pharmacologist and expert in the fields of ADME/Tox, computational toxicology and cheminformatics at Collaborations in Chemistry, a division of corporate communications firm Collaborations in Communications. He is also the editor of four books and a book series for John Wiley & Sons.
The discipline of evidence-based toxicology (EBT) strives to transparently, consistently, and objectively assess available scientific evidence in order to answer questions in toxicology, the study of the adverse effects of chemical, physical, or biological agents on living organisms and the environment, including the prevention and amelioration of such effects. EBT has the potential to address concerns in the toxicological community about the limitations of current approaches to assessing the state of the science. These include concerns related to transparency in decision making, synthesis of different types of evidence, and the assessment of bias and credibility. Evidence-based toxicology has its roots in the larger movement towards evidence-based practices.
The non-profit Evidence-based Toxicology Collaboration (EBTC) comprises a group of scientists and experts with ties to governmental and non-governmental agencies, chemical and pharmaceutical companies, and academia that have banded together to promote the use of what are known as "evidence-based approaches" in toxicology. The discipline of evidence-based toxicology (EBT) is a process for transparently, consistently, and objectively assessing available scientific evidence in order to answer questions in toxicology. EBT has the potential to address concerns in the toxicological community about the limitations of current approaches. These include concerns related to transparency in decision making, synthesis of different types of evidence, and the assessment of bias and credibility. The evidence-based methods and approaches now being proposed for toxicology are widely used in medicine, which is the basis for their nomenclature. The need to improve how the performance of toxicological test methods is assessed was the main impetus for translating these tools to toxicology.
In vitro to in vivo extrapolation (IVIVE) refers to the qualitative or quantitative transposition of experimental results or observations made in vitro to predict phenomena in vivo, biological organisms.
An adverse outcome pathway (AOP) is structured representation of biological events leading to adverse effects and is considered relevant to risk assessment. The AOP links in a linear way existing knowledge along one or more series of causally connected key events (KE) between two points — a molecular initiating event (MIE) and an adverse outcome (AO) that occur at a level of biological organization relevant to risk assessment. The linkage between the events is described by key event relationships (KER) that describe the causal relationships between the key events.
Threshold dose is the minimum dose of drug that triggers minimal detectable biological effect in an animal. At extremely low doses, biological responses are absent for some of the drugs. The increase in dose above threshold dose induces an increase in the percentage of biological responses. Several benchmarks have been established to describe the effects of a particular dose of drug in a particular species, such as NOEL(no-observed-effect-level), NOAEL(no-observed-adverse-effect-level) and LOAEL(lowest-observed-adverse-effect-level). They are established by reviewing the available studies and animal studies. The application of threshold dose in risk assessment safeguards the participants in human clinical trials and evaluates the risks of chronic exposure to certain substances. However, the nature of animal studies also limits the applicability of experimental results in the human population and its significance in evaluating potential risk of certain substances. In toxicology, there are some other safety factors including LD50, LC50 and EC50.
