Teratogen, definition

Grossly elevated concentrations of dissolved copper produce teratogenicity in fish embryos. A significant number of malformed fish larvae came from eggs treated with 500 pg Cu/L (Birge and Black 1979). In studies with laboratory animals and elevated concentrations of copper salts, copper penetrates the placental barrier into the fetus intramuscular injection of 4 mg Cu/kg BW early in pregnancy adversely affects fetal central nervous system development (Aaseth and Norseth 1986). In humans, no definitive data are available on whether copper can cause birth defects however, incubation of human spermatozoa with metallic copper results in loss of sperm motility (Aaseth and Norseth 1986). 

C. Thalidomide caused a high incidence of pho-comelia, particularly in Europe, where it was approved as a sedative agent. There is no definitive evidence associating teratogenic activity with the other compounds. 

The widely cited FDA system for teratogenic potential (Table 59-2) is an attempt to quantify teratogenic risk from A (safe) to X (definite human teratogenic risk). This system has been criticized as inaccurate and impractical. For example, several drugs have been labeled "X" despite extensive opposite human safety data (eg, oral... 

The February 1987 update of the October 1985 RTECS list of chemicals which cause reproductive hazards, had 6,917 entries. We selected the following T codes T01-T09 (paternal effects), T25 (postimplantation mortality), T31-T59 (effects on embryo or fetus, and specific developmental abnormalities), and T65 (transplacental tumorigenesis). All but the first ones (T01-T09) would fit into a classical definition of teratogens. The paternal effects were included in line with the recommendation by Schardein (vide supra), and also to incorporate the newest data on this long neglected subject. 

In animals, THC crosses the placenta and is excreted in breast milk. There is conflicting evidence concerning teratogenicity in animals, but no definitive evidence in man. However, there have been many anecdotal reports of abnormalities. Although these were without consistent characteristics, the descriptions would readily fit the fetal alcohol syndrome (133-136) and clinical evaluation of the use of cannabis during pregnancy is complicated by the frequent concomitant use of alcohol and tobacco. 

Detection of teratogens. Anatomical abnormalities are the easiest to detect. Nonanatomical (functional) effects can also occur, though it is not appropriate to use the term teratogenesis (see definition above). They include effects on brain biochemistry which may have late behavioural consequences. 

Data from various studies in 1255 patients exposed to carbamazepine have been analysed to evaluate its potential teratogenicity (73). There was an increased rate of congenital anomalies, mainly neural tube defects, cardiovascular and urinary tract anomalies, and cleft palate. The combination of carbamazepine with other antiepileptic drugs was more teratogenic than carbamazepine monotherapy. Because this study was retrospective, the conclusions should not be seen as definitive. 

Some experimental data have suggested a possible teratogenic potential of nitrous oxide, the clinical relevance of which is unclear (41). The interaction with vitamin B12 causes changes in DNA synthesis that could be important in the first trimester of pregnancy. Nitrous oxide is the only inhalational anesthetic that has definitely been... 

No definite association has been demonstrated between habitual caffeine use and hypertension, myocardial infarction, carcinogenicity, or teratogenicity. Abrupt cessation of chronic caffeine ingestion may cause withdrawal headaches. 

The weight-of-evidence evaluation takes into account the human experience and the animal data. Interpretation of human data depends on the design of the study, definition of the cohort, quantification of exposure, validity of ascertainment, control for confounding factors, size of the study population, and appropriate statistical methods. In practice, identification of human teratogens has relied on answers to two questions ... 

Inhalation studies with mice and rats indicate that TCE is a developmental toxicant. Fetotoxicity is expressed mainly as skeletal ossification anomalies and other effects consistent with delayed maturation. Oral studies with rats and mice showed no trichloroethylene-related effects on fertility or other indicators of reproductive performance. No definitive teratogenic effects have been reported regarding exposure to TCE. 

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