Teratogenic studies, definition

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 ... 

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). 

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. 

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. 

Conventional animal developmental studies in rats and rabbits exposed to CS aerosols at a concentration of around 10 mg m-3 for 5 min have shown that CS is not embryotoxic and teratogenic in rats and rabbits (Upshall, 1973). However, the exposure conditions, meant to simulate riot control situations, do not allow for definitive... 

---