Toxicity Tests, Acute
Toxicity Tests
Toxicity Tests, Subchronic
Toxicity Tests, Chronic
Toxicity Tests, Subacute
Lethal Dose 50
Morinda
Darier Disease
Water Pollutants, Chemical
Daphnia
Skin Irritancy Tests
Amphipoda
Toxicology
Artemia
Plant Extracts
Preclinical safety evaluation of human gene therapy products. (1/1374)
Human gene therapy products include naked DNA and viral as well as non-viral vectors containing nucleic acids. There is limited experience on the preclinical toxicity studies necessary for the safety evaluation of these products, which have been outlined in several recently released guidelines. Requirements for the preclinical safety evaluation of human gene therapy products are both specific and non-specific. All key preclinical studies should be performed in compliance with Good Laboratory Practices. Non-specific requirements are in fact common to all pharmaceutical products. Critical specific issues to be addressed are: the safety evaluation of the vector and the toxicity of the expressed protein(s), which are the two components of gene therapy products, the quality of the test article, the selection of animal species, and the verification that the administration method successfully transports the gene of interest, with the vector, to the target site(s). The treatment schedule should mimic the intended human therapeutic design. The host's immune response against the gene therapy product has to be evaluated to detect possible adverse effects and immune neutralization by antibodies. The biodistribution of the gene of interest is also essential and can be evaluated by molecular biology techniques, such as PCR. Specific confinement is required for the safe manipulation of viral vectors. (+info)The contribution of acute toxicity in animals to occupational exposure limits of chemical substances. (2/1374)
The correlations of lethal doses of various industrial chemicals for rats and mice with occupational exposure limit values were investigated. 50% lethal dose (LD50) values obtained by oral (p.o.) and intraperitoneal (i.p.) injection and 50% lethal concentration (LC50) values obtained by inhalation exposure were collected from Registry of Toxic Effects of Chemical Substances (RTECS). Threshold Limit Value (Time-Weighted Average) (TLVs-TWA) and Threshold Limit Value (Short Term Exposure Limit) (TLVs-STEL) recommended by American Conference of Governmental Industrial Hygienists (ACGIH) were used as exposure limits. TLVs-TWA or TLVs-STEL and LD50 or LC50 values obtained for the rats were plotted on logarithmic scales on the ordinate and abscissa, respectively. High correlations were obtained between these parameters. The order of correlations was: TLVs-STEL vs. LC50s > TLVs-TWA vs. LC50s > TLVs-TWA vs. LD50s i.p. > TLVs vs. LD50s p.o. The same calculations for the relationship between TLVs and lethal doses in mice were also performed. The order of the three types of correlations was same as that of the rats; however, correlation coefficients for TLVs-STEL vs. LC50s and for TLVs-TWA vs. LC50s obtained in mice were smaller than those in rats. TLVs-TWA are, therefore, well correlated with LC50 values rather than LD50 values, particularly with those in rats. High correlations between TLVs-STEL vs. LC50s were also obtained, as had been expected before calculation. The equation: TLV-TWA = 10b x (LC50)a can be obtained from these plottings, where the values a and b are taken from each linear regression line. TLV-TWA for each chemical can be calculated by using LC50 and the equation. The upper and lower 95% confidence limits for calculated TLV-TWA were TLV-TWA (calculated from LC50) x 22.9 and TLV-TWA (calculated)/22.9, respectively, where LC50 for rats expressed in ppm x hr was used. (+info)The marginalization of hormesis. (3/1374)
Despite the substantial development and publication of highly reproducible toxicological data, the concept of hormetic dose-response relationships was never integrated into the mainstream of toxicological thought. Review of the historical foundations of the interpretation of the bioassay and assessment of competitive theories of dose-response relationships lead to the conclusion that multiple factors contributed to the marginalization of hormesis during the middle and subsequent decades of the 20th Century. These factors include the following: (a) the close association of hormesis with homeopathy, which led to the hostility of modern medicine toward homeopathy, thereby creating a guilt-by-association framework, and the carryover influence of that hostility toward hormesis in the judgements of medically based pharmacologists/toxicologists; (b) the emphasis of high-dose effects linked with a lack of appreciation of the significance of the implications of low-dose stimulatory effects; (c) the lack of an evolution-based mechanism(s) to account for hormetic effects; and (d) lack of appropriate scientific advocates to counter aggressive and intellectually powerful critics of the hormetic perspective. (+info)Chemical hormesis: its historical foundations as a biological hypothesis. (4/1374)
Despite the long history of hormesis-related experimental research, no systematic effort to describe its early history has been undertaken. The present paper attempts to reconstruct and assess the early history of such research and to evaluate how advances in related scientific fields affected the course of hormesis-related research. The purpose of this paper is not only to satisfy this gap in current knowledge but also to provide a foundation for the assessment of how the concept of hormetic dose-response relationships may have affected the nature of the bioassay, especially with respect to hazard assessment practices within a modern risk assessment framework. (+info)Serum vitellogenin levels and reproductive impairment of male Japanese Medaka (Oryzias latipes) exposed to 4-tert-octylphenol. (5/1374)
The induction of synthesis of the "female" yolk precursor protein vitellogenin (VTG) in male fish by estrogenic chemicals in the environment has been demonstrated in many recent reports. However, little is known about the organismal and biological significance of this phenomenon. To examine the relationship between VTG production in male fish and reproductive impairment, adult male medaka were exposed to 4-tert-octylphenol (OP), a known environmental estrogen, in concentrations ranging from 20 to 230 ppb for 21 days, under flow-through conditions. Following exposure, male fish were mated, in the absence of OP, with unexposed females. Breeding groups composed of exposed males and control females produced about 50% fewer eggs than control groups. VTG levels in serum of male fish increased with increasing OP exposure concentration and decreased after OP exposure was discontinued. Nevertheless, significant correlations (p<0.01) were observed between VTG levels in exposed male fish and 1) OP exposure concentrations, 2) percent of fertilized eggs, and 3) survival of embryos. OP-induced VTG synthesis and reproductive impairment appear to be closely linked phenomena. Histological examination indicated spermatogenesis in OP-exposed fish was inhibited, and some exposed fish had oocytes in their testes. Finally, OP caused a significant increase in the number of abnormally developing embryos, suggesting that OP may be genotoxic as well as estrogenic. (+info)Demonstration of the pathogenic effect of point mutated keratin 9 in vivo. (6/1374)
A wild type keratin 9 (K9) cDNA and a point mutated keratin 9 cDNA were injected subcutaneously into mouse skin. The hemagglutinin tag staining of the wild type K9 cDNA injected specimens mainly showed a homogeneous pattern, whereas the point mutated K9 cDNA injected specimens mainly showed a granular pattern in the suprabasal cells. Double staining of K9 and the endogenous keratin revealed the incorporation of de novo synthesized K9 into the keratin network. These results demonstrate that (1) a naked DNA transfection into mouse skin can detect the pathogenic changes of point mutated keratin in vivo and (2) the keratin 9 mutation disrupts the keratin network formation in the suprabasal cells in vivo. (+info)Changes in thyroid gland morphology after acute acrylamide exposure. (7/1374)
High exposure to the acrylamide monomer has been associated with neuropathy and neurotoxic effects. Chronic lower exposure causes endocrine disruption associated with thyroid, testicular, and mammary tumors. To investigate mechanisms of endocrine disruption, short-term, low-level oral dosing studies were conducted. Weanling female Fischer 344 rats were acclimatized for two weeks before dosing. Controls were given distilled water by gavage and rats in other groups were given acrylamide at doses of 2 mg/kg/day and 15 mg/kg/day for 2 or 7 days by gavage. Twenty-four h after the last dose, the rats were killed by decapitation. Trunk blood was collected for hormone analyses and tissues for histopathological examination. There were no toxicity-related deaths, no clinical signs of toxicity, and no significant difference in the mean body weight of animal groups. Histopathological examination of select tissues showed no lesions of pathologic significance. Plasma thyroxine (T4), thyroid stimulating hormone (TSH), prolactin (PRL), and pituitary TSH and PRL analyses did not reveal significant changes between control vs. treated rats. In the 7-day study, however, there was a slight dose-dependent increase in plasma T4 and a slight dose-dependent decrease in plasma TSH. Thyroid gland morphometry showed a significant (p < 0.05) decrease in the colloid area and a significant increase (p < 0.05) in the follicular cell height of treated rats as compared to controls. The follicular area shrinkage was similar in both studies. These results show a very early endocrine response to very low levels of toxic insult and opens other venues to further investigate the mechanisms of endocrine disruption by acrylamide. (+info)Effects of acute exposure to PCBs 126 and 153 on anterior pituitary and thyroid hormones and FSH isoforms in adult Sprague Dawley male rats. (8/1374)
3,3'4,4',5-Pentachlorobiphenyl (PCB 126) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) were administered to adult male rats in order to identify sensitive indicators of endocrine disruption. We tested the hypothesis that PCB exposure modifies follicle-stimulating hormone (FSH) pituitary isoforms, as well as the pituitary and serum concentrations of FSH, luteinizing hormone (LH), growth hormone, prolactin, and thyroid-stimulating hormone (TSH). Effects on serum levels of thyroxine (T4) and testosterone (T), and prostate androgen receptor content, were also tested. In one experiment, 5 groups of 8 rats each received two i.p. injections, one day apart, of either corn oil or 6.25, 25, 100 or 400 micrograms/kg/day of PCB 126. Decreases (p < 0.05) in the serum concentrations of T4 and LH started at doses of 25 and 100 micrograms/kg/day, respectively. Serum FSH concentrations were reduced (p = 0.07) in the highest dose group. In contrast, pituitary content of FSH and LH increased with PCB-126 doses (p = 0.004, p = 0.002, respectively). Despite changes in reproductive hormones, PCB-126 had no effect on the androgen receptor content of the prostate. The effect of PCB-126 was tested in the hemicastrated rat, and suggested adverse effects on testosterone secretion. To test the effects of PCB exposure on FSH pituitary isoforms, 4 groups of 10 male rats received two i.p. injections, one day apart, of either corn oil, PCB 153 (25 mg/kg/day), estradiol-17 beta (E2; 20 micrograms/kg/day), or PCB 126 (0.1 mg/kg/day). Serum T4 levels were higher (p < 0.01) in the E2 and PCB 153 groups, and slightly reduced in the PCB 126-treated groups, compared to controls. Simultaneous purification of pituitary FSH and TSH isoforms was performed by HPLC, using two chromatofocusing columns in series. In contrast to TSH isoforms, the distribution of FSH isoforms over the chromatography run differed slightly between treatment groups; the amounts of FSH isoform eluted during the pH gradient were lower (p < 0.05) in E2 and PCB 153-treated rats than in control or PCB 126-treated rats. The similarity between the effects of E2 and PCB 153 on T4 and FSH isoforms supports the contention that PCB 153 possesses estrogenic properties. Serum LH and T4 concentrations were the most sensitive and practical endocrine indicators of PCBs 126 and 153 exposure in male rats. (+info)Acute toxicity tests are a category of medical or biological testing that measure the short-term adverse effects of a substance on living organisms. These tests are typically performed in a laboratory setting and involve exposing test subjects (such as cells, animals, or isolated organs) to a single high dose or multiple doses of a substance within a short period of time, usually 24 hours or less.
The primary objective of acute toxicity testing is to determine the median lethal dose (LD50) or concentration (LC50) of a substance, which is the amount or concentration that causes death in 50% of the test subjects. This information can be used to help assess the potential health hazards associated with exposure to a particular substance and to establish safety guidelines for its handling and use.
Acute toxicity tests are required by regulatory agencies around the world as part of the process of evaluating the safety of chemicals, drugs, and other substances. However, there is growing concern about the ethical implications of using animals in these tests, and many researchers are working to develop alternative testing methods that do not involve the use of live animals.
Toxicity tests, also known as toxicity assays, are a set of procedures used to determine the harmful effects of various substances on living organisms, typically on cells, tissues, or whole animals. These tests measure the degree to which a substance can cause damage, inhibit normal functioning, or lead to death in exposed organisms.
Toxicity tests can be conducted in vitro (in a test tube or petri dish) using cell cultures or in vivo (in living organisms) using animals such as rats, mice, or rabbits. The results of these tests help researchers and regulators assess the potential risks associated with exposure to various chemicals, drugs, or environmental pollutants.
There are several types of toxicity tests, including:
1. Acute toxicity tests: These tests measure the immediate effects of a single exposure to a substance over a short period (usually 24 hours or less).
2. Chronic toxicity tests: These tests evaluate the long-term effects of repeated exposures to a substance over an extended period (weeks, months, or even years).
3. Genotoxicity tests: These tests determine whether a substance can damage DNA or cause mutations in genetic material.
4. Developmental and reproductive toxicity tests: These tests assess the impact of a substance on fertility, embryonic development, and offspring health.
5. Carcinogenicity tests: These tests evaluate the potential of a substance to cause cancer.
6. Ecotoxicity tests: These tests determine the effects of a substance on entire ecosystems, including plants, animals, and microorganisms.
Toxicity tests play a crucial role in protecting public health by helping to identify potentially harmful substances and establish safe exposure levels. They also contribute to the development of new drugs, chemicals, and consumer products by providing critical data for risk assessment and safety evaluation.
Subchronic toxicity tests are a type of medical study used to evaluate the potential adverse health effects resulting from repeated exposure to a substance over a relatively short period of time, usually lasting between 28 and 90 days. These tests are designed to identify the dosage levels at which a substance may cause harm, as well as any patterns of toxicity that may emerge with repeated exposure.
The tests typically involve administering the substance to groups of animals, such as rats or mice, at different dose levels. The animals are then closely monitored for signs of toxicity, including changes in body weight, food and water intake, clinical chemistry parameters, hematology, urinalysis, and histopathological examinations of major organs.
The data collected from these tests can be used to establish a no-observed-adverse-effect level (NOAEL) or a lowest-observed-adverse-effect level (LOAEL), which can help inform regulatory decisions about the safe use of the substance in question. Subchronic toxicity tests are an important part of the overall risk assessment process for many chemicals, pharmaceuticals, and other substances that may be used in consumer products or industrial applications.
Chronic toxicity tests are a type of experimental procedure in toxicology that are conducted over an extended period to evaluate the potential adverse health effects resulting from repeated exposure to low levels of chemical substances or physical agents. These tests are designed to assess the long-term effects of these agents on living organisms, including humans, and typically span a significant portion of the lifespan of the test species.
The primary objective of chronic toxicity testing is to identify potential health hazards associated with prolonged exposure to chemicals or physical agents, such as heavy metals, pesticides, pharmaceuticals, nanomaterials, and ionizing radiation. The tests provide information on the nature and severity of toxic effects, including cancer, reproductive and developmental toxicity, neurological damage, and other chronic health issues.
Standardized protocols for conducting chronic toxicity tests are established by regulatory agencies such as the US Environmental Protection Agency (EPA), the European Chemicals Agency (ECHA), and the Organisation for Economic Cooperation and Development (OECD). These guidelines typically involve testing on two or more species, often including rodents and non-rodents, to ensure the results are applicable across different taxonomic groups.
The data generated from chronic toxicity tests contribute significantly to risk assessment and help regulatory agencies establish safe exposure limits for chemical substances and physical agents in various settings, such as occupational, consumer, and environmental contexts.
Subacute toxicity tests are a type of toxicity test used in preclinical safety evaluation of new pharmaceuticals, chemicals, or medical devices. These tests are conducted over a longer period than acute toxicity tests, typically lasting between 14 and 28 days, to evaluate the potential adverse effects of repeated exposure to the substance.
The test involves administering the substance to animals, usually rodents, at specified doses and observing them for signs of toxicity. The parameters evaluated during subacute toxicity tests include clinical observations, body weight changes, food and water consumption, hematology, blood chemistry, urinalysis, and necropsy findings.
The primary objective of subacute toxicity testing is to identify the no-observed-adverse-effect level (NOAEL) or the lowest observed adverse effect level (LOAEL), which helps in determining safe starting doses for subsequent long-term toxicity studies and human clinical trials. It also provides information on potential target organs of toxicity, which is useful in risk assessment and safety evaluation.
Medical Definition:
Lethal Dose 50 (LD50) is a standard measurement in toxicology that refers to the estimated amount or dose of a substance, which if ingested, injected, inhaled, or absorbed through the skin by either human or animal, would cause death in 50% of the test population. It is expressed as the mass of a substance per unit of body weight (mg/kg, μg/kg, etc.). LD50 values are often used to compare the toxicity of different substances and help determine safe dosage levels.
"Morinda" is a botanical term that refers to a genus of tropical shrubs and trees in the family Rubiaceae, which includes several species with medicinal properties. One of the most well-known species is Morinda citrifolia, also known as noni, which has been used in traditional medicine for various health purposes.
The fruit, leaves, bark, and roots of Morinda plants have been used in traditional medicine to treat a variety of conditions such as infections, inflammation, fever, skin disorders, and digestive problems. Some studies suggest that Morinda extracts may have antioxidant, anti-inflammatory, analgesic, and immune-boosting properties, but more research is needed to confirm these effects and establish recommended dosages and safety guidelines.
It's important to note that while Morinda has a long history of use in traditional medicine, it should not be used as a substitute for professional medical advice or treatment. Before taking any herbal supplements, including Morinda, it's always best to consult with a healthcare provider to ensure safety and effectiveness.
Darier Disease is a genetic skin disorder, also known as Keratosis Follicularis. It is characterized by the formation of greasy, crusted, keratotic papules and plaques that typically appear on the upper arms, torso, and scalp. The lesions may also affect the nasolabial folds, central face, and mucous membranes. Darier Disease is caused by mutations in the ATP2A2 gene, which encodes a calcium pump protein involved in keratinization. It is an autosomal dominant disorder, meaning that a person has a 50% chance of inheriting the disease if one of their parents is affected. The onset of symptoms typically occurs during adolescence or early adulthood. Treatment options include topical medications, oral retinoids, and photodynamic therapy.
Chemical water pollutants refer to harmful chemicals or substances that contaminate bodies of water, making them unsafe for human use and harmful to aquatic life. These pollutants can come from various sources, including industrial and agricultural runoff, sewage and wastewater, oil spills, and improper disposal of hazardous materials.
Examples of chemical water pollutants include heavy metals (such as lead, mercury, and cadmium), pesticides and herbicides, volatile organic compounds (VOCs), polychlorinated biphenyls (PCBs), and petroleum products. These chemicals can have toxic effects on aquatic organisms, disrupt ecosystems, and pose risks to human health through exposure or consumption.
Regulations and standards are in place to monitor and limit the levels of chemical pollutants in water sources, with the aim of protecting public health and the environment.
'Daphnia' is not a medical term, but rather it refers to a group of small, planktonic crustaceans commonly known as water fleas. They are widely distributed in various freshwater environments and play an important role in the aquatic food chain as they serve as a food source for many larger animals such as fish.
While Daphnia may not have a direct medical definition, there has been some research into their potential use in biomedical applications due to their sensitivity to environmental changes. For instance, they have been used as indicators of water quality and toxicity levels in ecotoxicological studies. However, it is important to note that Daphnia itself is not a medical term or concept.
Skin irritancy tests are experimental procedures used to determine the potential of a substance to cause irritation or damage to the skin. These tests typically involve applying the substance to intact or abraded (damaged) skin of human volunteers or animals, and then observing and measuring any adverse reactions that occur over a specified period. The results of these tests can help assess the safety of a substance for use in consumer products, pharmaceuticals, or industrial applications. It is important to note that the ethical considerations and regulations surrounding animal testing have led to an increased focus on developing alternative methods, such as in vitro (test tube) tests using reconstructed human skin models.
Amphipoda is an order of crustaceans characterized by a laterally compressed body and a distinctive jointed swimming leg, making them well-adapted for swimming in open water. They are commonly known as "sand fleas" or "beach fleas," although they are not actually fleas. Amphipods can be found in various aquatic habitats, including marine, freshwater, and brackish environments. Some species live on the seafloor, while others are planktonic or associate with other organisms. They vary greatly in size, ranging from less than a millimeter to over 30 centimeters in length.
The medical definition of 'Amphipoda' is not typically used since amphipods do not have direct relevance to human health or medicine. However, they can serve as bioindicators of environmental quality and may be involved in the transmission of certain diseases between aquatic organisms.
Toxicology is a branch of medical science that deals with the study of the adverse effects of chemicals or toxins on living organisms and the environment, including their detection, evaluation, prevention, and treatment. It involves understanding how various substances can cause harm, the doses at which they become toxic, and the factors that influence their toxicity. This field is crucial in areas such as public health, medicine, pharmacology, environmental science, and forensic investigations.
'Artemia' is a genus of aquatic branchiopod crustaceans, also known as brine shrimp. They are commonly found in saltwater environments such as salt lakes and highly saline ponds. Artemia are known for their ability to produce cysts (also called "resting eggs") that can survive extreme environmental conditions, making them an important organism in research related to survival in harsh environments and space exploration.
In a medical context, Artemia is not typically used as a term but may be referenced in scientific studies related to biology, genetics, or astrobiology. The compounds derived from Artemia, such as astaxanthin and other carotenoids, have been studied for their potential health benefits, including antioxidant properties and support for eye and heart health. However, these applications are still under research and not yet considered part of mainstream medical practice.
A plant extract is a preparation containing chemical constituents that have been extracted from a plant using a solvent. The resulting extract may contain a single compound or a mixture of several compounds, depending on the extraction process and the specific plant material used. These extracts are often used in various industries including pharmaceuticals, nutraceuticals, cosmetics, and food and beverage, due to their potential therapeutic or beneficial properties. The composition of plant extracts can vary widely, and it is important to ensure their quality, safety, and efficacy before use in any application.
A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.
The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.
The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.
In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.