In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a measure of the lethal dose of a toxin, radiation, or pathogen. The value of LD50 for a substance is the dose required to kill half the members of a tested population after a specified test duration. LD50 figures are frequently used as a general indicator of a substance's acute toxicity. A lower LD50 is indicative of increased toxicity.
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.
Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell (cytotoxicity) or an organ such as the liver (hepatotoxicity). By extension, the word may be metaphorically used to describe toxic effects on larger and more complex groups, such as the family unit or society at large. Sometimes the word is more or less synonymous with poisoning in everyday usage.
Chronic toxicity, the development of adverse effects as a result of long term exposure to a contaminant or other stressor, is an important aspect of aquatic toxicology. Adverse effects associated with chronic toxicity can be directly lethal but are more commonly sublethal, including changes in growth, reproduction, or behavior. Chronic toxicity is in contrast to acute toxicity, which occurs over a shorter period of time to higher concentrations. Various toxicity tests can be performed to assess the chronic toxicity of different contaminants, and usually last at least 10% of an organism's lifespan. Results of aquatic chronic toxicity tests can be used to determine water quality guidelines and regulations for protection of aquatic organisms.
In toxicology, the lethal dose (LD) is an indication of the lethal toxicity of a given substance or type of radiation. Because resistance varies from one individual to another, the "lethal dose" represents a dose at which a given percentage of subjects will die. The lethal concentration is a lethal dose measurement used for gases or particulates. The LD may be based on the standard person concept, a theoretical individual that has perfectly "normal" characteristics, and thus not apply to all sub-populations.
A reference dose is the United States Environmental Protection Agency's maximum acceptable oral dose of a toxic substance.Reference doses are most commonly determined for pesticides. The EPA defines an oral reference dose as:
[A]n estimate, with uncertainty spanning perhaps an order of magnitude, of a daily oral exposure to the human population that is likely to be without an appreciable risk of deleterious effects during a lifetime.
Aquatic toxicology is the study of the effects of manufactured chemicals and other anthropogenic and natural materials and activities on aquatic organisms at various levels of organization, from subcellular through individual organisms to communities and ecosystems. Aquatic toxicology is a multidisciplinary field which integrates toxicology, aquatic ecology and aquatic chemistry.
Acute toxicity describes the adverse effects of a substance that result either from a single exposure or from multiple exposures in a short period of time. To be described as acute toxicity, the adverse effects should occur within 14 days of the administration of the substance.
The dose–response relationship, or exposure–response relationship, describes the magnitude of the response of an organism, as a function of exposure to a stimulus or stressor after a certain exposure time. Dose–response relationships can be described by dose–response curves. This is explained further in the following sections. A stimulus response function or stimulus response curve is defined more broadly as the response from any type of stimulus, not limited to chemicals.
Measures of pollutant concentration are used to determine risk assessment in public health.
Phosmet is a phthalimide-derived, non-systemic, organophosphate insecticide used on plants and animals. It is mainly used on apple trees for control of codling moth, though it is also used on a wide range of fruit crops, ornamentals, and vines for the control of aphids, suckers, mites, and fruit flies.
Exposure assessment is a branch of environmental science and occupational hygiene that focuses on the processes that take place at the interface between the environment containing the contaminant of interest and the organism being considered. These are the final steps in the path to release an environmental contaminant, through transport to its effect in a biological system. It tries to measure how much of a contaminant can be absorbed by an exposed target organism, in what form, at what rate and how much of the absorbed amount is actually available to produce a biological effect. Although the same general concepts apply to other organisms, the overwhelming majority of applications of exposure assessment are concerned with human health, making it an important tool in public health.
The no-observed-adverse-effect level (NOAEL) denotes the level of exposure of an organism, found by experiment or observation, at which there is no biologically or statistically significant increase in the frequency or severity of any adverse effects of the tested protocol. In drug development, the NOAEL of a new drug is assessed in laboratory animals, such as mice, prior to initiation of human trials in order to establish a safe clinical starting dose in humans. The OECD publishes guidelines for Preclinical Safety Assessments, in order to help scientists discover the NOAEL.
In analytical chemistry, biomonitoring is the measurement of the body burden of toxic chemical compounds, elements, or their metabolites, in biological substances. Often, these measurements are done in blood and urine. Biomonitoring is performed in both environmental health, and in occupational safety and health as a means of exposure assessment and workplace health surveillance.
The maximum acceptable toxicant concentration (MATC) is a value that is calculated through aquatic toxicity tests to help set water quality regulations for the protection of aquatic life. Using the results of a partial life-cycle chronic toxicity test, the MATC is reported as the geometric mean between the No Observed Effect Concentration (NOEC) and the lowest observed effect concentration (LOEC).
The predicted no-effect concentration (PNEC) is the concentration of a chemical which marks the limit at which below no adverse effects of exposure in an ecosystem are measured. PNEC values are intended to be conservative and predict the concentration at which a chemical will likely have no toxic effect. They are not intended to predict the upper limit of concentration of a chemical that has a toxic effect. PNEC values are often used in environmental risk assessment as a tool in ecotoxicology. A PNEC for a chemical can be calculated with acute toxicity or chronic toxicity single-species data, Species Sensitivity Distribution (SSD) multi-species data, field data or model ecosystems data. Depending on the type of data used, an assessment factor is used to account for the confidence of the toxicity data being extrapolated to an entire ecosystem.
Tolerable weekly intake (TWI) estimates the amount per unit body weight of a potentially harmful substance or contaminant in food or water that can be ingested over a lifetime without risk of adverse health effects. TWI is generally preceded by "provisional" to indicate insufficient data exists, increasing uncertainty. The term TWI should be reserved for when there is a well-established and internationally accepted tolerance, backed by sound and uncontested data. Although similar in concept to tolerable daily intake (TDI), which is of the same derivation of acceptable daily intakes (ADIs), TWI accounts for contaminants that do not clear the body quickly and may accumulate within the body over a period of time. An example is heavy metals such as arsenic, cadmium, lead, and mercury. The concept of TWI takes into account daily variations in human consumption patterns.
Occupational toxicology is the application of toxicology to chemical hazards in the workplace. It focuses on substances and conditions that occur in workplaces, where inhalation exposure and dermal exposure are most important, there is often exposure to mixtures of chemicals whose interactions are complex, health effects are influenced or confounded by other environmental and individual factors, and there is a focus on identifying early adverse affects that are more subtle than those presented in clinical medicine.
Toxicological databases are large compilations of data derived from aquatic and environmental toxicity studies. Data is aggregated from a large number of individual studies in which toxic effects upon aquatic and terrestrial organisms have been determined for different chemicals. These databases are then used by toxicologists, chemists, regulatory agencies and scientists to investigate and predict the likelihood that an organic or inorganic chemical will cause an adverse effect on exposed organisms.
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.
