Fetus anomalies

Pregnant females were sacrificed by carbon dioxide anesthesia on day 21 of gestation the uterine horns were exteriorized through a midline incision in the abdominal wall, and the number and position of live, dead, and resorbed fetuses were noted. After being weighed and sexed, the fetuses were examined for external anomalies the crown-rump length was measured with a vernier caliper. Half of each litter was preserved in Bouin s solution and later examined for soft tissue anomalies (16) the other half was preserved in alcohol, cleared and stained with Alizarin red-S, and examined for skeletal abnormalities (2). 

OCDD. Signs of maternal toxicity were not observed in rats given 100 or 500 mg/kg/day OCDD. Examination of the fetuses did not reveal changes in fetal body measurements, incidence of fetal resorptions, or incidence of any fetal anomaly among litters or the fetal population. At 500 mg/kg/day, the incidence of subcutaneous edema was significantly increased among the fetal population (23/100 compared with 8/156 in controls) but not among litters (9/18 compared with 6/28 in controls). 

Exposure to the fetus in the first 2 weeks after conception may have an all or nothing effect (i.e., could destroy the embryo or have no ill effect). Exposure during the period of organogenesis (18 to 60 days postconception) may result in structural anomalies (e.g., methotrexate, cyclophosphamide, diethylstilbestrol, lithium, retinoids, thalidomide, certain antiepileptic drugs, and coumarin derivative). 

The 500-mg/kg/day dose also caused a significant decrease in maternal body weights. No effect on the number of fetuses with anomalies was observed, and no fetal or maternal effects were observed at lower doses. These studies suggest that in the absence of maternal effects, developmental effects in humans are unlikely. 

Visceral Fetal Examinations. The examination of the abdominal and thoracic viscera of fetuses is performed either fresh without fixation ( Staples technique ) or after Bouin s fixation by making freehand razor blade sections ( Wilson s technique Wilson, 1965). Both techniques have advantages. The fresh examination technique, which may require less training for thorough proficiency, provides a more easily interpreted view of heart anomalies. The examination must be performed on the day the dam is terminated, however, so having a large number of litters to examine in one day requires that a large team of workers be committed to the task. 

FIGURE 8.7. Litter effect with supernumerary rib in 1379 control litters. Between 1978 and 1988, fetal skeletons from 1379 litters of control rats were stained with alizarin red and examined for supernumerary rib in addition to other anomalies. The calculation of the expected number of fetuses with supernumerary rib in each litter was based on the assumption that each fetus had an equally likely chance of having supernumerary rib independent of the incidence among littermates (K. Soper, personal communication, 1990). 

Ellis WG, Semple JL, Hoogenboom JR, Kavlock RJ, Zeman FJ Benomyl-induced craniocerebral anomalies in fetuses of adequately nourished and protein-deprived rats. Teratog Carcinog Mutagen 8 377-391, 1988... 

Reproductive effects at the time of the incident included a 44% loss of fetuses in 865 pregnant women (15% expected), and the neonatal death rate increased from 3% to 15%. Reproductive toxicity of MIC has been confirmed in animal studies exposure has caused increased resorptions, reduced pup weight, and reduced neonatal survival. Terato-logical anomalies including wrist drop, everted claw, syndactyly, cleft palate formation, and unequal ribs were observed in rats exposed to concentrations of up to 0.353 ppm during gestation. ... 

In rats, inhalation exposure to 330-1,000 ppm during gestation caused maternal weight loss and clear maternal hepatotoxicity, but no effect on conception, number of implants, or number of resorptions (Schwetz et al. 1974). There were no gross anomalies, although fetal size was somewhat decreased. These data suggest that the fetus is not preferentially sensitive to carbon tetrachloride, and effects of carbon tetrachloride on fetal development and post-natal survival are likely secondary to maternal toxicity. 

Rats are sacrificed on gestation day 20. Fetuses are removed by cesarean section after noting the number of resorptions, implantations, and normal fetuses. The size, weight, and any abnormality of each fetus are noted. Two-thirds of the fetuses are eviscerated and then preserved in absolute alcohol for staining with Alizarin Red S for skeletal assessment. The other one-third of the fetuses is fixed in Allen s modification of Bonin s fluid for slicing with a razor blade (Wilson s Technique) to evaluate visceral anomalies. 

When performing external examination, special attention should be paid to positional anomalies of the limbs, since this is sometimes more complicated in fixed specimens, as well as subcutaneous hemorrhages, which can easily be induced during the further process of preparation. For ethical reasons, fetuses should be humanely killed as soon as possible after preparation ftom the uterus (e.g., by careful i.p. injection of 0.1 ml pentobarbitone). In general, care should be taken not to damage the fetuses. 

Visceral variations and anomalies occur in minipigs. In males the most frequent flnding is malpositioned testes which are seen in 12% of the males. Dilatation of the ventricles of the brain is seen approximately in 5% of all fetuses (12). 

Teratogenic activity. Resin, administered orally to pregnant rabbits at a dose of 1 mL/ kg, was active k Alcohol extract of the dried leaves, administered intragastrically to pregnant rats at a dose of 125 mg/kg from days 7 to 16 of gestation, was active. The fetuses showed several gross abnormalities, visceral anomalies, and skeletal mal-formations . Water extract of the dried... 

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