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Tetrachlorodibenzodioxin
2,3,7,8-Tetrachlorodibenzo-''p-''dioxin (TCDD) is a polychlorinated dibenzo''-p-''dioxin (sometimes shortened, though inaccurately, to simply 'dioxin')Tuomisto, Jouko (2019) Dioxins and dioxin-like compounds: toxicity in humans and animals, sources, and behaviour in the environment. WikiJournal of Medicine 6(1): 8 , https://doi.org/10.15347/wjm/2019.008 with the chemical formula CHClO. Pure TCDD is a colorless solid with no distinguishable odor at room temperature. It is usually formed as an unwanted product in burning processes of organic materials or as a side product in organic synthesis. TCDD is the most potent compound ( congener) of its series (polychlorinated dibenzodioxins, known as PCDDs or simply dioxins) and became known as a contaminant in Agent Orange, a herbicide used in the Vietnam War. TCDD was released into the environment in the Seveso disaster. It is a persistent organic pollutant. Mechanism of action TCDD and dioxin-like compounds act via a specific ...
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Polychlorinated Dibenzodioxins
Polychlorinated dibenzodioxins (PCDDs), or simply dioxins, are a group of long-lived polyhalogenated compound, polyhalogenated organic compounds that are primarily anthropogenic, and contribute toxic, Persistent organic pollutant, persistent organic pollution in the environment. They are commonly but inaccurately referred to as dioxins for simplicity, because every PCDD molecule contains a dibenzo-1,4-dioxin skeletal structure, with 1,4-Dioxin, 1,4-dioxin as the central Ring (chemistry), ring. Members of the PCDD family bioaccumulation, bioaccumulate in humans and wildlife because of their lipophilicity, lipophilic properties, and may cause developmental disturbances and cancer. Because dioxins can persist in the environment for more than 100 years, the majority of PCDD pollution today is not the result of recent emissions, but the cumulative result of synthetic processes undertaken since the beginning of the 20th century, including organochloride-related manufacturing, incinera ...
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Dioxins And Dioxin-like Compounds
Dioxins and dioxin-like compounds (DLCs) are a group of chemical compounds that are persistent organic pollutants (POPs) in the environment. They are mostly by-products of burning or various industrial processes - or, in case of dioxin-like PCBs and PBBs, unwanted minor components of intentionally produced mixtures. Some of them are highly toxic, but the toxicity among them varies 30,000-fold. They are grouped together because their mechanism of action is the same. They activate the aryl hydrocarbon receptor (AH receptor), albeit with very different binding affinities, leading to high differences in toxicity and other effects. They include: * Polychlorinated dibenzo''-p-''dioxins (PCDDs), or simply dioxins. PCDDs are derivatives of dibenzo''-p-''dioxin. There are 75 PCDD congeners, differing in the number and location of chlorine atoms, and 7 of them are specifically toxic, the most toxic being 2,3,7,8-tetrachlorodibenzodioxin (TCDD). * Polychlorinated dibenzofurans (PCDFs), or ...
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Teratogenic
Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. The related term developmental toxicity includes all manifestations of abnormal development that are caused by environmental insult. These may include growth retardation, delayed mental development or other congenital disorders without any structural malformations. Teratogens are substances that may cause birth defects via a toxic effect on an embryo or fetus. Known teratogens include: retinol, thalidomide, Mercury (element), mercury, Alcohol (drug), alcohol, lead, polychlorinated biphenyls (PCBs), and 2,3,7,8-tetrachlorodibenzodioxin. Etymology The term was borrowed in 1842 from the French , where it was formed in 1830 from the Greek language, Greek (word stem ), meaning "sign sent by the gods, portent, marvel, monster", and (''-ology''), used ...
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Estrogenic
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal activity: estrone (E1), estradiol (E2), and estriol (E3). Estradiol, an estrane, is the most potent and prevalent. Another estrogen called estetrol (E4) is produced only during pregnancy. Estrogens are synthesized in all vertebrates and some insects. Their presence in both vertebrates and insects suggests that estrogenic sex hormones have an ancient evolutionary history. Quantitatively, estrogens circulate at lower levels than androgens in both men and women. While estrogen levels are significantly lower in males than in females, estrogens nevertheless have important physiological roles in males. Like all steroid hormones, estrogens readily diffuse across the cell membrane. Once inside the cell, they bind to and activate estrogen receptors (ER ...
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Anti-estrogenic
Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or inhibiting or suppressing estrogen production., Antiestrogens are one of three types of sex hormone antagonists, the others being antiandrogens and antiprogestogens. Antiestrogens are commonly used to stop steroid hormones, estrogen, from binding to the estrogen receptors leading to the decrease of estrogen levels. Decreased levels of estrogen can lead to complications in sexual development. Antiandrogens are sex hormone antagonists which are able to lower the production and the effects that testosterone can have on female bodies. Types and examples Antiestrogens include selective estrogen receptor modulators (SERMs) like tamoxifen, clomifene, and raloxifene, the ER silent antagonist and selective estrogen receptor degrader (SERD) fulvestr ...
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Oxidative Stress
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily Detoxification, detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. Oxidative stress from Cellular respiration, oxidative metabolism causes base damage, as well as DNA damage (naturally occurring), strand breaks in DNA. Base damage is mostly indirect and caused by the reactive oxygen species generated, e.g., O2− (superoxide radical), OH (hydroxyl radical) and H2O2 (hydrogen peroxide). Further, some reactive oxidative species act as cellular messengers in redox signaling. Thus, oxidative stress can cause disruptions in normal mechanisms of cellular signaling. In humans, oxidative stress is thought to be involved in the ...
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Genotoxic
Genotoxicity is the property of chemical agents that damage the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with Mutagen, mutagenicity, all mutagens are genotoxic, but some genotoxic substances are not mutagenic. The alteration can have direct or indirect effects on the DNA: the induction of mutations, mistimed event activation, and direct DNA damage leading to mutations. The permanent, heritable changes can affect either somatic cells of the organism or germ cells to be passed on to future generations. Cells prevent expression of the genotoxic mutation by either DNA repair or apoptosis; however, the damage may not always be fixed leading to mutagenesis. To bioassay, assay for genotoxic molecules, researchers assay for DNA damage in cells exposed to the toxic substrates. This DNA damage can be in the form of single- and double-strand breaks, loss of excision repair, cross-linking, alkali-labile sites, point mutat ...
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Mutagenic
In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in animals, such mutagens can therefore be carcinogens, although not all necessarily are. All mutagens have characteristic mutational signatures with some chemicals becoming mutagenic through cellular processes. The process of DNA becoming modified is called mutagenesis. Not all mutations are caused by mutagens: so-called "spontaneous mutations" occur due to spontaneous hydrolysis, errors in DNA replication, repair and recombination. Discovery The first mutagens to be identified were carcinogens, substances that were shown to be linked to cancer. Tumors were described more than 2,000 years before the discovery of chromosomes and DNA; in 500 B.C., the Greek physician Hippocrates named tumors resembling a crab ''karkinos'' (from which the ...
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Spina Bifida
Spina bifida (Latin for 'split spine'; SB) is a birth defect in which there is incomplete closing of the spine and the membranes around the spinal cord during early development in pregnancy. There are three main types: spina bifida occulta, meningocele and myelomeningocele. Meningocele and myelomeningocele may be grouped as spina bifida cystica. The most common location is the lower back, but in rare cases it may be in the middle back or neck. Occulta has no or only mild signs, which may include a hairy patch, dimple, dark spot or swelling on the back at the site of the gap in the spine. Meningocele typically causes mild problems, with a sac of fluid present at the gap in the spine. Myelomeningocele, also known as open spina bifida, is the most severe form. Problems associated with this form include poor ability to walk, impaired bladder or bowel control, accumulation of fluid in the brain (hydrocephalus), a tethered spinal cord and latex allergy. Learning problems are rela ...
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Neural Tube Defects
Neural tube defects (NTDs) are a group of birth defects in which an opening in the Vertebral column, spine or cranium remains from early in human development. In the third week of pregnancy called gastrulation, specialized cells on the dorsal side of the embryo begin to change shape and form the neural tube. When the neural tube does not close completely, an NTD develops. Specific types include: spina bifida which affects the Human vertebral column, spine, anencephaly which results in little to no brain, encephalocele which affects the skull, and iniencephaly which results in severe neck problems. NTDs are one of the most common birth defects, affecting over 300,000 births each year worldwide. For example, spina bifida affects approximately 1,500 births annually in the United States, or about 3.5 in every 10,000 (0.035% of US births), which has decreased from around 5 per 10,000 (0.05% of US births) since #Prevention, folate fortification of grain products was started. The num ...
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Meta-analysis
A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting measurements that are expected to have some degree of error. The aim then is to use approaches from statistics to derive a pooled estimate closest to the unknown common truth based on how this error is perceived. Meta-analytic results are considered the most trustworthy source of evidence by the evidence-based medicine literature.Herrera Ortiz AF., Cadavid Camacho E, Cubillos Rojas J, Cadavid Camacho T, Zoe Guevara S, Tatiana Rincón Cuenca N, Vásquez Perdomo A, Del Castillo Herazo V, & Giraldo Malo R. A Practical Guide to Perform a Systematic Literature Review and Meta-analysis. Principles and Practice of Clinical Research. 2022;7(4):47–57. https://doi.org/10.21801/ppcrj.2021.74.6 Not only can meta-analyses provide an estimate of the un ...
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