Teratology
Encyclopedia
Teratology is the study of abnormalities of physiological development. It is often thought of as the study of human birth defects, but it is much broader than that, taking in other non-birth developmental stages, including puberty
; and other non-human life forms, including plants.
téras (genitive tératos), meaning monster or marvel, and lógos
, meaning the word or, more loosely, the study of .
As early as the 17th century, teratology referred to a discourse on prodigies and marvels of anything so extraordinary as to seem abnormal. In the 19th century, it acquired a meaning more closely related to biological deformities, mostly in the field of botany. Currently, its most instrumental meaning is that of the medical study of teratogenesis, congenital malformations
or individuals with significant malformations. There are many pejorative terms that have historically been used to describe individuals with significant physical malformations.
The term was popularized in the 1960s by Dr. David W. Smith
of the University of Washington
Medical School, one of the researchers who became known in 1973 for the discovery of Fetal alcohol syndrome
. With greater understanding of the origins of birth defects, the field of teratology now overlaps with other fields of basic science, including developmental biology
, embryology
, and genetics
.
It was previously believed that the mammalian embryo
developed in the impervious uterus of the mother, protected from all extrinsic factors. However, after the thalidomide
disaster of the 1960s, it became apparent and more accepted that the developing embryo
could be highly vulnerable to certain environmental agents that have negligible or non-toxic effects to adult individuals.
A review published in 2010 identified 6 main teratogenic mechanisms associated with medication use: folate antagonism, neural crest cell disruption, endocrine disruption, oxidative stress
, vascular
disruption and specific receptor- or enzyme-mediated teratogenesis.
vulnerability of the developing mammalian embryo
came the development and refinement of The Six Principles of Teratology which are still applied today. These principles of teratology were put forth by Jim Wilson
in 1959 and in his monograph Environment and Birth Defects. These principles guide the study and understanding of teratogenic agents and their effects on developing organisms:
Studies designed to test the teratogenic potential of environmental agents use animal model systems (e.g., rat, mouse, rabbit, dog, and monkey). Early teratologists exposed pregnant animals to environmental agents and observed the fetuses for gross visceral and skeletal abnormalities. While this is still part of the teratological evaluation procedures today, the field of Teratology is moving to a more molecular level, seeking the mechanism(s) of action by which these agents act. Genetically modified mice are commonly used for this purpose. In addition, pregnancy registries are large, prospective studies that monitor exposures women receive during their pregnancies and record the outcome of their births. These studies provide information about possible risks of medications or other exposures in human pregnancies.
Understanding how a teratogen causes its effect is not only important in preventing congenital abnormalities but also has the potential for developing new therapeutic drugs safe for use with pregnant women.
The status of some of the above substances (e.g. diphenylhydantoin) is subject to debate, and many other compounds are under varying degrees of suspicion. These include Agent Orange
, nicotine
, aspirin
and other NSAIDs. Other compounds are known as severe teratogens based on veterinary work and animal studies, but aren't listed above because they have not been studied in humans, e.g. cyclopamine
. Teratogenic effects also help to determine the pregnancy category
assigned by regulatory authorities; in the United States, a pregnancy category of X, D, or C may be assigned if teratogenic effects (or other risks in pregnancy) are documented or cannot be excluded.
Isotretinoin
(13-cis-retinoic-acid; brand name Roaccutane), which is often used to treat severe acne
, is such a strong teratogen that just a single dose taken by a pregnant woman may result in serious birth defects. Because of this effect, most countries have systems in place to ensure that it is not given to pregnant women, and that the patient is aware of how important it is to prevent pregnancy during and at least one month after treatment. Medical guidelines also suggest that pregnant women should limit vitamin A
intake to about 700 μg/day, as it has teratogenic potential when consumed in excess.
, anencephaly
, ventricular septal defect
. Exposure to a single agent can produce various abnormalities depending on the stage of development it occurs. Specific birth defects are not characteristic of any single agent.
, teratology investigates the theoretical implications of abnormal specimens. For example, the discovery of abnormal flowers—for example, flowers with leaves instead of petals, or flowers with staminoid pistils—furnished important evidence for the "foliar theory", the theory that all flower parts are highly specialised leaves.
Puberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
; and other non-human life forms, including plants.
Etymology
The term stems from the GreekGreek language
Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...
téras (genitive tératos), meaning monster or marvel, and lógos
Logos
' is an important term in philosophy, psychology, rhetoric and religion. Originally a word meaning "a ground", "a plea", "an opinion", "an expectation", "word," "speech," "account," "reason," it became a technical term in philosophy, beginning with Heraclitus ' is an important term in...
, meaning the word or, more loosely, the study of .
As early as the 17th century, teratology referred to a discourse on prodigies and marvels of anything so extraordinary as to seem abnormal. In the 19th century, it acquired a meaning more closely related to biological deformities, mostly in the field of botany. Currently, its most instrumental meaning is that of the medical study of teratogenesis, congenital malformations
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
or individuals with significant malformations. There are many pejorative terms that have historically been used to describe individuals with significant physical malformations.
The term was popularized in the 1960s by Dr. David W. Smith
David W. Smith
David Smith is a retired hammer thrower from Great Britain, who represented the United Kingdom in the men's hammer throw event at the 1996 Summer Olympics in Atlanta, Georgia...
of the University of Washington
University of Washington
University of Washington is a public research university, founded in 1861 in Seattle, Washington, United States. The UW is the largest university in the Northwest and the oldest public university on the West Coast. The university has three campuses, with its largest campus in the University...
Medical School, one of the researchers who became known in 1973 for the discovery of Fetal alcohol syndrome
Fetal alcohol syndrome
Fetal alcohol syndrome is a pattern of mental and physical defects that can develop in a fetus in association with high levels of alcohol consumption during pregnancy. Current research also implicates other lifestyle choices made by the prospective mother...
. With greater understanding of the origins of birth defects, the field of teratology now overlaps with other fields of basic science, including developmental biology
Developmental biology
Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
, embryology
Embryology
Embryology is a science which is about the development of an embryo from the fertilization of the ovum to the fetus stage...
, and genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
.
Teratogenesis
Birth defects are known to occur in 3-5% of all newborns. They are the leading cause of infant mortality in the United States, accounting for more than 20% of all infant deaths. Seven to ten percent of all children will require extensive medical care to diagnose or treat a birth defect. And although significant progress has been made in identifying the etiology of some birth defects, approximately 65% have no known or identifiable cause.It was previously believed that the mammalian embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
developed in the impervious uterus of the mother, protected from all extrinsic factors. However, after the thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
disaster of the 1960s, it became apparent and more accepted that the developing embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
could be highly vulnerable to certain environmental agents that have negligible or non-toxic effects to adult individuals.
A review published in 2010 identified 6 main teratogenic mechanisms associated with medication use: folate antagonism, neural crest cell disruption, endocrine disruption, oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
, vascular
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
disruption and specific receptor- or enzyme-mediated teratogenesis.
Wilson's 6 principles
Along with this new awareness of the in uteroIn utero
In utero is a Latin term literally meaning "in the womb". In biology, the phrase describes the state of an embryo or fetus. In legal contexts, the phrase is used to refer to unborn children. Under common law, unborn children are still considered to exist for property transfer purposes.-See also:*...
vulnerability of the developing mammalian embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
came the development and refinement of The Six Principles of Teratology which are still applied today. These principles of teratology were put forth by Jim Wilson
James G. Wilson
James G. Wilson was an embryologist and anatomist, known for his Six Principles of Teratology. In 1960 he co-founded The Teratology Society, and was since then one of its most active members....
in 1959 and in his monograph Environment and Birth Defects. These principles guide the study and understanding of teratogenic agents and their effects on developing organisms:
- Susceptibility to teratogenesis depends on the genotype of the conceptus and the manner in which this interacts with adverse environmental factors.
- Susceptibility to teratogenesis varies with the developmental stage at the time of exposure to an adverse influence. There are critical periods of susceptibility to agents and organ systems affected by these agents.
- Teratogenic agents act in specific ways on developing cells and tissues to initiate sequences of abnormal developmental events.
- The access of adverse influences to developing tissues depends on the nature of the influence. Several factors affect the ability of a teratogen to contact a developing conceptus, such as the nature of the agent itself, route and degree of maternal exposure, rate of placental transfer and systemic absorption, and composition of the maternal and embryonic/fetal genotypes.
- There are four manifestations of deviant development (Death, Malformation, Growth Retardation and Functional Defect).
- Manifestations of deviant development increase in frequency and degree as dosage increases from the No Observable Adverse Effect Level (NOAEL) to a dose producing 100% Lethality (LD100).
Studies designed to test the teratogenic potential of environmental agents use animal model systems (e.g., rat, mouse, rabbit, dog, and monkey). Early teratologists exposed pregnant animals to environmental agents and observed the fetuses for gross visceral and skeletal abnormalities. While this is still part of the teratological evaluation procedures today, the field of Teratology is moving to a more molecular level, seeking the mechanism(s) of action by which these agents act. Genetically modified mice are commonly used for this purpose. In addition, pregnancy registries are large, prospective studies that monitor exposures women receive during their pregnancies and record the outcome of their births. These studies provide information about possible risks of medications or other exposures in human pregnancies.
Understanding how a teratogen causes its effect is not only important in preventing congenital abnormalities but also has the potential for developing new therapeutic drugs safe for use with pregnant women.
Teratology education
It is estimated that 10% of all birth defects are caused by prenatal exposure to a teratogenic agent. These exposures include, but are not limited to, medication or drug exposures, maternal infections and diseases, and environmental and occupational exposures. Teratogen-caused birth defects are potentially preventable. Studies have shown that nearly 50% of pregnant women have been exposed to at least one medication during gestation. An additional study found that of 200 individuals referred for genetic counseling for a teratogenic exposure, 52% were exposed to more than one potential teratogen.Teratogenic agents
A wide range of different chemicals and environmental factors are suspected or are known to be teratogenic in humans and in animals. A selected few include:- Drugs and medications: tobaccoTobaccoTobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines...
, caffeineCaffeineCaffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
, drinking alcoholAlcoholIn chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
(ethanolEthanolEthanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
) (see fetal alcohol spectrum disorderFetal alcohol spectrum disorderFetal Alcohol Spectrum Disorders describes a continuum of permanent birth defects caused by maternal consumption of alcohol during pregnancy, which includes, but is not limited to fetal alcohol syndrome...
), isotretinoinIsotretinoinIsotretinoin, INN, is a medication used mostly for cystic acne. It was first developed for brain, pancreatic and other cancers. It is used to treat harlequin-type ichthyosis, a usually lethal skin disease, and lamellar ichthyosis. Its effects are systemic and nonselective...
(13-cis-retinoic acid, Roaccutane), temazepamTemazepamTemazepam is an intermediate-acting 3-hydroxy benzodiazepine. It is mostly prescribed for the short-term treatment of sleeplessness in patients who have difficulty maintaining sleep...
(Restoril; Normisson), nitrazepamNitrazepamNitrazepam is a type of benzodiazepine drug and is marketed in English-speaking countries under the following brand names: Alodorm, Arem, Insoma, Mogadon, Nitrados, Nitrazadon, Ormodon, Paxadorm, Remnos, and Somnite...
(Mogadon), nimetazepamNimetazepamNimetazepam is an intermediate-acting hypnotic drug which is a benzodiazepine derivative. It was first synthesized by a team at Hoffmann-La Roche in 1962. It possesses hypnotic, anxiolytic, sedative, and skeletal muscle relaxant properties. Nimetazepam is also an anticonvulsant. It is sold in 5 mg...
(Ermin), aminopterinAminopterinAminopterin , a 4-amino analog of folic acid, is an antineoplastic drug with immunosuppressive properties used in chemotherapy. Aminopterin is a synthetic derivative of pterin. Aminopterin works as an enzyme inhibitor by competing for the folate binding site of the enzyme dihydrofolate reductase...
or methotrexateMethotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
, androgenic hormones, busulfanBusulfanBusulfan is a cancer drug, in use since 1959.Busulfan is a cell cycle non-specific alkylating antineoplastic agent, in the class of alkyl sulfonates...
, captoprilCaptoprilCaptopril is an angiotensin-converting enzyme inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first ACE inhibitor developed and was considered a breakthrough both because of its novel mechanism of action and also because of the...
, enalaprilEnalaprilEnalapril is an angiotensin converting enzyme inhibitor used in the treatment of hypertension and some types of chronic heart failure. ACE raises blood pressure by constricting blood vessels. ACE inhibitors like enalapril prevent this effect. Enalapril has been shown to lower the death rate in...
, coumarinCoumarinCoumarin is a fragrant chemical compound in the benzopyrone chemical class, found in many plants, notably in high concentration in the tonka bean , vanilla grass , sweet woodruff , mullein , sweet grass , cassia cinnamon and sweet clover...
, cyclophosphamideCyclophosphamideCyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
, diethylstilbestrolDiethylstilbestrolDiethylstilbestrol is a synthetic nonsteroidal estrogen that was first synthesized in 1938. Human exposure to DES occurred through diverse sources, such as dietary ingestion from supplemented cattle feed and medical treatment for certain conditions, including breast and prostate cancers...
, phenytoinPhenytoinPhenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
(diphenylhydantoin, Dilantin, Epanutin), etretinateEtretinateEtretinate is a medication developed by Hoffmann–La Roche that was approved by the FDA in 1986 to treat severe psoriasis...
, lithiumLithiumLithium is a soft, silver-white metal that belongs to the alkali metal group of chemical elements. It is represented by the symbol Li, and it has the atomic number 3. Under standard conditions it is the lightest metal and the least dense solid element. Like all alkali metals, lithium is highly...
, methimazoleMethimazoleMethimazole is an antithyroid drug, and part of the thioamide group.-Indications:...
, penicillaminePenicillaminePenicillamine is a pharmaceutical of the chelator class. It is sold under the trade names of Cuprimine and Depen. The pharmaceutical form is D-penicillamine, as L-penicillamine is toxic...
, tetracyclines, thalidomideThalidomideThalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
, trimethadioneTrimethadioneTrimethadione is an oxazolidinedione anticonvulsant. It is most commonly used to treat epileptic conditions that are resistant to other treatments.-Fetal trimethadione syndrome:...
, methoxyethyl ethers, FlusilazoleFlusilazoleFlusilazole is an organosilicon fungicide invented by DuPont, which is used to control fungal infections on a variety of fruit and vegetable crops. It is moderately toxic to animals and has been shown to produce birth defects and embryotoxicity at high doses....
, valproic acidValproic acidValproic acid is a chemical compound that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, major depression. It is also used to treat migraine headaches and schizophrenia...
, and many more. - Environmental chemicals: polycyclic aromatic hydrocarbons (polynuclear aromatic hydrocarbons), polychlorinated biphenylPolychlorinated biphenylPolychlorinated biphenyls are a class of organic compounds with 2 to 10 chlorine atoms attached to biphenyl, which is a molecule composed of two benzene rings. The chemical formula for PCBs is C12H10-xClx...
s (PCBs), polychlorinated dibenzodioxins a.k.a dioxin, polychlorinated dibenzofuransPolychlorinated dibenzofuransPolychlorinated dibenzofurans are a group of halogenated organic compounds which are toxic environmental pollutants. They are known teratogens, mutagens, and suspected human carcinogens. PCDFs tend to co-occur with polychlorinated dibenzodioxins...
(PCDFs), hexachlorobenzeneHexachlorobenzeneHexachlorobenzene, or perchlorobenzene, is a chlorocarbon with the molecular formula C6Cl6. It is a fungicide formerly used as a seed treatment, especially on wheat to control the fungal disease bunt...
hexachloropheneHexachloropheneHexachlorophene, also known as Nabac, is a disinfectant. The compound occurs as a white to light-tan crystalline powder, which either is odorless or produces a slightly phenolic odor. In medicine, hexachlorophene is very useful as a topical anti-infective, anti-bacterial agent, often used in soaps...
, organic mercuryMercury (element)Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...
, ethidium bromideEthidium bromideEthidium bromide is an intercalating agent commonly used as a fluorescent tag in molecular biology laboratories for techniques such as agarose gel electrophoresis. It is commonly abbreviated as "EtBr", which is also an abbreviation for bromoethane...
, etc. - Ionizing radiation: atomic weapons fallout (Iodine-131Iodine-131Iodine-131 , also called radioiodine , is an important radioisotope of iodine. It has a radioactive decay half-life of about eight days. Its uses are mostly medical and pharmaceutical...
, uraniumUraniumUranium is a silvery-white metallic chemical element in the actinide series of the periodic table, with atomic number 92. It is assigned the chemical symbol U. A uranium atom has 92 protons and 92 electrons, of which 6 are valence electrons...
), background radiationBackground radiationBackground radiation is the ionizing radiation constantly present in the natural environment of the Earth, which is emitted by natural and artificial sources.-Overview:Both Natural and human-made background radiation varies by location....
, diagnostic x-rayX-rayX-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
s, radiation therapyRadiation therapyRadiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control... - Infections: cytomegalovirusCytomegalovirusCytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...
, herpes virusHerpes virusIn colloquial use, herpes virus refers to the herpes simplex virus, particularly when transmitted sexually.In scientific use, herpesvirus refers to a virus of the taxonomic family herpesviridae....
, parvovirus B19Parvovirus B19The B19 virus, generally referred to as parvovirus B19 or sometimes erythrovirus B19, was the first known human virus in the family of parvoviruses, genus erythrovirus...
, rubella virusRubellaRubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...
(German measles), syphilisSyphilisSyphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...
, toxoplasmosisToxoplasmosisToxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. The parasite infects most genera of warm-blooded animals, including humans, but the primary host is the felid family. Animals are infected by eating infected meat, by ingestion of feces of a cat that has itself...
, Venezuelan equine encephalitis virusVenezuelan equine encephalitis virusVenezuelan equine encephalitis virus is a mosquito-borne viral pathogen that causes Venezuelan equine encephalitis or encephalomyelitis . VEE can affect all equine species, such as horses, donkeys, and zebras. After infection, equines may suddenly die or show progressive central nervous system...
. (An easy way to remember maternal infections is TORCH: Toxoplasmosis, Other agents, Rubella, CMV and HSV. - Metabolic imbalance: alcoholismAlcoholismAlcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...
, endemic cretinismCretinismCretinism is a condition of severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones usually due to maternal hypothyroidism.-Etymology and use of cretin:...
, diabetes, folic acid deficiency, iodine deficiencyIodine deficiencyIodine is an essential trace element; the thyroid hormones thyroxine and triiodotyronine contain iodine. In areas where there is little iodine in the diet—typically remote inlandareas where no marine foods are eaten—iodine deficiency gives rise to...
, hyperthermiaHyperthermiaHyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...
, phenylketonuriaPhenylketonuriaPhenylketonuria is an autosomal recessive metabolic genetic disorder characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase , rendering it nonfunctional. This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine...
, rheumatic disease and congenital heart blockHeart blockA heart block can be a blockage at any level of the electrical conduction system of the heart .* Blocks that occur within the sinoatrial node are described as SA nodal blocks....
, virilizing tumorsVirilizationIn biology and medicine, virilization refers to the biological development of sex differences, changes that make a male body different from a female body. Most of the changes of virilization are produced by androgens...
The status of some of the above substances (e.g. diphenylhydantoin) is subject to debate, and many other compounds are under varying degrees of suspicion. These include Agent Orange
Agent Orange
Agent Orange is the code name for one of the herbicides and defoliants used by the U.S. military as part of its herbicidal warfare program, Operation Ranch Hand, during the Vietnam War from 1961 to 1971. Vietnam estimates 400,000 people were killed or maimed, and 500,000 children born with birth...
, nicotine
Nicotine
Nicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
, aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
and other NSAIDs. Other compounds are known as severe teratogens based on veterinary work and animal studies, but aren't listed above because they have not been studied in humans, e.g. cyclopamine
Cyclopamine
Cyclopamine is a naturally occurring chemical that belongs to the group of steroidal jerveratrum alkaloids. It is a teratogen isolated from the corn lily that causes usually fatal birth defects. It can prevent the fetal brain from dividing into two lobes and cause the development of a single eye...
. Teratogenic effects also help to determine the pregnancy category
Pregnancy category
The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does not include any risks conferred by pharmaceutical agents or their metabolites that are present in breast...
assigned by regulatory authorities; in the United States, a pregnancy category of X, D, or C may be assigned if teratogenic effects (or other risks in pregnancy) are documented or cannot be excluded.
Isotretinoin
Isotretinoin
Isotretinoin, INN, is a medication used mostly for cystic acne. It was first developed for brain, pancreatic and other cancers. It is used to treat harlequin-type ichthyosis, a usually lethal skin disease, and lamellar ichthyosis. Its effects are systemic and nonselective...
(13-cis-retinoic-acid; brand name Roaccutane), which is often used to treat severe acne
Acne vulgaris
Acne vulgaris is a common human skin disease, characterized by areas of skin with seborrhea , comedones , papules , pustules , Nodules and possibly scarring...
, is such a strong teratogen that just a single dose taken by a pregnant woman may result in serious birth defects. Because of this effect, most countries have systems in place to ensure that it is not given to pregnant women, and that the patient is aware of how important it is to prevent pregnancy during and at least one month after treatment. Medical guidelines also suggest that pregnant women should limit vitamin A
Vitamin A
Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
intake to about 700 μg/day, as it has teratogenic potential when consumed in excess.
Teratogenic outcomes
Exposure to teratogens can result in a wide range of structural abnormalities such as cleft lip, cleft palate, dysmeliaDysmelia
Dysmelia is a congenital disorder referring to the limbs. -Types:Dysmelia can refer to*missing limbs: amelia, oligodactyly, congenital amputation...
, anencephaly
Anencephaly
Anencephaly is a cephalic disorder that results from a neural tube defect that occurs when the cephalic end of the neural tube fails to close, usually between the 23rd and 26th day of pregnancy, resulting in the absence of a major portion of the brain, skull, and scalp...
, ventricular septal defect
Ventricular septal defect
A ventricular septal defect is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart.The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively innervated with conducting cardiomyocytes.The membranous...
. Exposure to a single agent can produce various abnormalities depending on the stage of development it occurs. Specific birth defects are not characteristic of any single agent.
Plantae
In botanyBotany
Botany, plant science, or plant biology is a branch of biology that involves the scientific study of plant life. Traditionally, botany also included the study of fungi, algae and viruses...
, teratology investigates the theoretical implications of abnormal specimens. For example, the discovery of abnormal flowers—for example, flowers with leaves instead of petals, or flowers with staminoid pistils—furnished important evidence for the "foliar theory", the theory that all flower parts are highly specialised leaves.
External links
- Society of Teratology
- European Teratology Society
- Organization of Teratology Information Specialists
- March of Dimes Foundation
- A Telling of Wonders: Teratology in Western Medicine through 1800 (New York Academy of Medicine Historical Collections)
- List of known and suspected Teratogens (Hazard Database)