Reduced ossification

The previously mentioned feed restriction studies in rats and rabbits (13-16) also evaluated other effects than major malformations. The results in these studies are reviewed in some detail below. In rats, (13) feed restriction-induced reductions in maternal body weight gain (of approximately 50% compared to ab libitum-fed rats) resulted in reductions in fetal body weights. Fetal body weights were reduced to 95, 93, 90, and 76% of the control values at 20 g, 15 g, 10 g, and 7.5 g per day, respectively. There was also an increase in skeletal defects (wavy ribs and a reduced ossification at 7.5 g/day), but no major malformations. 

Sprague-Dawley rats and Swiss CD-I mice were exposed by inhalation to 0, 280, 1400 or 7000 ppm [800-19 530 mg/m ] isoprene for 6 h per day on seven days per week on gestational days 6-19 (rats) or 6-17 (mice) (lARC, 1994). There was no adverse effect on rat dams or other reproductive index at any dose level. The only fetal malformation observed in rats was reduced ossification of the vertebral centra, which occurred at 7000 ppm isoprene. In mice, there was reduced fetal body weight at all dose levels and decreased maternal weight gain in the 7000-ppm group. Also in the 7000-ppm group, there was an increased incidence of supernumerary ribs but no increase in fetal malformations. 

Mouse (albino) Gd 1-19 19 d (W) 46 (increased resorptions, reduced ossification, gross anomalies) Trivedi et al. 1989 K2Cr207 (VI)... 

Significant reduced ossification in nasal frontal, parietal, interparietal, caudal, and tarsal bones were observed only in the 152.4 mg chromium(VI)/kg/day-treated animals. 

In rats orally administered the compound cinnamaldehyde at doses of 5,25, or 250 mg/kg on days 7 to 17 of pregnancy, the incidence of poor cranial ossification was increased in all treated groups, while reduced ossification of the tympanic bulla was increased in the 25 and 250 mg/kg groups. Increases in the incidences of dilated pelvis/reduced papilla in the kidney, dilated ureters, and abnormal ster-nebrae were detected in the 25 mg/kg group, which had the highest overall prevalence of minor abnormalities. Increases in the incidences of reduced cranial ossification, dilated ureters, and renal variants were observed at 5 mg/ kg, a dose at which there was no detectable maternal toxicity (Mantovani et al. 1989). 

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