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Teratogens

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Teratogens

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Teratogenesis is a medical term from the Greek, literally meaning monster-making, which derives from teratology, the study of the frequency, causation, and development of congenital malformations—misleadingly called birth defects. These include gross morphological abnormalities, such as cleft lip and/or palate, anencephaly, or ventricular septal defect, but may also include phenomena such as increased risk of cervical cancer or discoloration of tooth enamel. These malformations can arise from genetic abnormalities of the fetus, from adverse environmental circumstances (termed teratogens or tetragens), or a combination of these factors. Teratogenesis has gained a more specific usage for the development of abnormal cell masses during fetal growth (see pregnancy), causing physical defects in the fetus. The study of teratogenesis is called teratology.

Known teratogens

The American College of Occupational and Environmental Medicine recognizes the following teratogens.[1]

  • Ionizing radiation: atomic weapons, radioiodine, radiation therapy
  • Infections: cytomegalovirus, herpes virus hominis I and II, parvovirus B-19, rubella virus (German measles), syphilis, toxoplasmosis, Venezuelan equine encephalitis virus
  • Metabolic imbalance: alcoholism, endemic cretinism, diabetes, folic acid deficiency, hyperthermia, phenylketonuria, rheumatic disease and congenital heart block, virilizing tumors
  • Drugs and environmental chemicals: 13-cis-retinoic acid (isotretinoin, Accutane), aminopterin and methylaminopterin, androgenic hormones, busulfan, captopril and enalapril (ACE inhibitors), chlorobiphenyls (PCBs), cocaine, coumarin anticoagulants, cyclophosphamide, diethylstilbestrol, diphenylhydantoin (Phenytoin, Dilantin, Epanutin), etretinate, lithium, methimazole, organic mercury compounds, penicillamine, tetracyclines, thalidomide, trimethadione, and valproic acid.

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[1], nicotine[2], aspirin and other NSAIDs, and birth control pills. 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 Accutane), 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.[3][4]

References

  1. ^ Linnainmaa K (1983). "Sister chromatid exchanges among workers occupationally exposed to phenoxy acid herbicides 2,4-D and MCPA". Teratogenesis, Carcinogenesis, and Mutagenesis 3 (3): 269-79. ISSN:0270-3211. Retrieved on 2006-05-30. Note: Agent Orange contains 2,4-D
  2. ^ Vaglenova J, Birru S, Pandiella NM, Breese CR (April 2004). "An assessment of the long-term developmental and behavioral teratogenicity of prenatal nicotine exposure". Behavioural Brain Research 150 (1-2): 159-70. DOI:10.1016/j.bbr.2003.07.005. ISSN:0166-4328. Retrieved on 2006-05-30.
  3. ^ Rothman KJ, Moore LL, Singer MR, Nguyen US, Mannino S, Milunsky A (1995-11-23). "Teratogenicity of high vitamin A intake". The New England Journal of Medicine 333 (21): 1369-73. PMID: 7477116. Retrieved on 2006-06-04.
  4. ^ Hartmann S, Brors O, Bock J, Blomhoff R, Bausch J, Wiegand UW, Hartmann D, Hornig DH (May 2005). "Exposure to retinoic acids in non-pregnant women following high vitamin A intake with a liver meal" (abstract). International Journal for Vitamin and Nutrition Research 75 (3): 187-94. PMID: 16028634. Retrieved on 2006-06-04.

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