The intraperitoneal median lethal dose i. Decreased locomotor activity, piloerection, weight loss, and decreased food and water consumption are the most notable physical signs appearing after acute aluminum intoxication. Median lethal dose LD 50 values, which may differ based on route of exposure and species exposed, can be used to compare the toxicity of trichothecenes Table For example, the LD 50 values for ip exposure in the mouse are 5.
For T-2 toxin, oral LD 50 values are not markedly different across species; however, T-2 toxin was to fold more toxic when inhaled than when administered orally. The pig is one of the most sensitive species to all trichothecenes. While human data are limited, the anatomical and physiological similarity of pigs and humans should be considered in extrapolation of data across species. Recent research has focused on DON due to its common occurrence in cereal-based food.
All monogastric species, such as pigs, dogs, cats, mice, and rats, are sensitive to DON-induced reduction in weight gain following chronic low-level exposure, with pigs being the most sensitive. Ruminants, horses, rabbits, and poultry are relatively resistant species. This is presumably due to their inability to excrete T-2 toxin and its metabolites via glucuronide conjugation. Drug toxicity is a major issue in development. Beyond toxicity attributable to relative overdosing from variable metabolism, genetically related adverse events can arise from drug target or related pathway polymorphisms, immunologic predisposition e.
Sorting out the mechanistic bases of drug adverse events will be straightforward in some cases and highly complicated in others.
The size of most drug development programs will only allow elucidation of the most clear-cut genetic association. Regulatory issues do not complicate such investigations, except in the rare instance where the drug is not safe enough to be approved absent the test. In these cases, sponsors should discuss with FDA the amount of evidence needed to demonstrate that use of the test confers an adequate level of safety.
Drug toxicity can develop at normal therapeutic doses of a drug or as a result of an acute overdose.
LD 50 figures are frequently used as a general indicator of a substance's acute toxicity. A lower LD 50 is indicative of increased toxicity.
The test was created by J. LD 50 is usually determined by tests on animals such as laboratory mice. LD values for humans are best estimated by extrapolating results from human cell cultures.
One form of measuring LD is to use animals like mice or rats, converting to dosage per kilogram of biomass, and extrapolating to human norms. The degree of error from animal-extrapolated LD values is large. The biology of test animals differs in important aspects to that of humans. For instance, mouse tissue is approximately fifty times less responsive than human tissue to the venom of the Sydney funnel-web spider [ citation needed ].
The square-cube law also complicates the scaling relationships involved. Researchers are shifting away from animal-based LD measurements in some instances. Food and Drug Administration has begun to approve more non-animal methods in response to animal welfare concerns. The LD 50 is usually expressed as the mass of substance administered per unit mass of test subject, typically as milli grams of substance per kilogram of body mass, but stated as nanograms suitable for botulinum , micrograms, milligrams, or grams suitable for paracetamol per kilogram.
Stating it this way allows the relative toxicity of different substances to be compared, and normalizes for the variation in the size of the animals exposed, although toxicity does not always scale simply with body mass. However, this also means that LD 50 is not the lethal dose for all subjects; some may be killed by much less, while others survive doses far higher than the LD Lethal dosage often varies depending on the method of administration ; for instance, many substances are less toxic when administered orally than when intravenously administered.
For this reason, LD 50 figures are often qualified with the mode of administration, e. These measures are used more commonly with radiation , as survival beyond 60 days usually results in recovery. The median infective dose ID 50 is the number of organisms received by a person or test animal qualified by the route of administration e.
Because of the difficulties in counting actual organisms in a dose, infective doses may be expressed in terms of biological assay, such as the number of LD 50 's to some test animal. The Material Safety Data Sheets for toxic substances frequently use this form of the term even if the substance does follow Haber's Law.
For disease-causing organisms, there is also a measure known as the median infective dose and dosage. The median infective dose ID 50 is the number of organisms received by a person or test animal qualified by the route of administration e. Because of the difficulties in counting actual organisms in a dose, infective doses may be expressed in terms of biological assay, such as the number of LD 50 's to some test animal.
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. The name LD50 is an abbreviation for "Lethal Dose, 50%" or median lethal dose. It is the amount of the substance required (usually per body weight) to kill 50%.
In biological warfare infective dosage is the number of infective doses per cubic metre of air times the number of minutes of exposure e. As a measure of toxicity, LD 50 is somewhat unreliable and results may vary greatly between testing facilities due to factors such as the genetic characteristics of the sample population, animal species tested, environmental factors and mode of administration.
There can be wide variability between species as well; what is relatively safe for rats may very well be extremely toxic for humans cf. For example, chocolate, comparatively harmless to humans, is known to be toxic to many animals. When used to test venom from venomous creatures, such as snakes , LD 50 results may be misleading due to the physiological differences between mice, rats, and humans.
Many venomous snakes are specialized predators on mice, and their venom may be adapted specifically to incapacitate mice; and mongooses may be exceptionally resistant. While most mammals have a very similar physiology, LD 50 results may or may not have equal bearing upon every mammal species, such as humans, etc. Comparing substances especially drugs to each other by LD 50 can be misleading in many cases due in part to differences in effective dose ED Therefore, it is more useful to compare such substances by therapeutic index , which is simply the ratio of LD 50 to ED Animal-rights and animal-welfare groups, such as Animal Rights International,  have campaigned against LD 50 testing on animals.
From Wikipedia, the free encyclopedia.
For other uses, see LD50 disambiguation. Archived from the original on 26 June A Textbook of Modern Toxicology. Toxicological Information for the LD 50 verification.
The Journal of Nutrition. Drug and Chemical Toxicology. Archived from the original on Archived from the original PDF on Aleksandryan, "Toxicological characteristics of melamine cyanurate, melamine and cyanuric acid", Zhurnal Eksperimental'noi i Klinicheskoi Meditsiny, Vol. Original article in Russian.
Toxicology and Applied Pharmacology. Journal of Psychoactive Drugs. Human and Veterinary Medicine. Tracing back the generally accepted lethal dose to dubious self-experiments in the nineteenth century".
Easy-to-read, question-and-answer fact sheets covering a wide range of workplace health and safety topics, from hazards to diseases to ergonomics to workplace promotion. While most mammals have a very similar physiology, LD 50 results may or may not have equal bearing upon every mammal species, including humans. However, this information does not tell us if A or B is more toxic because we do not know which damage is more critical or harmful. As an aid in developing emergency procedures in case of a major spill or accident. The median infective dose ID 50 is the number of organisms received by a person or test animal qualified by the route of administration e.
Chemical Safety Information from Intergovernmental Organizations: Elsevier — via Google Books.