Delayed ossification

Mouse (CD-1) 11 d Gd 7-17 (GO) 0.5 1 (delayed ossification 38% increase in supraoccipital score 84% decrease in number of caudal vertebrae decreased fetal body weight) Kavlock et al. 1981 Endrin... 

Developmental Effects. Developmental effects associated with exposure of humans to endrin have not been reported. Prenatal exposure of animals to concentrations of endrin sufficient to cause maternal toxicity has resulted in a statistically significant increase in the incidence of fused ribs, cleft palate, exencephaly, microencephaloceles, and open eyes in hamsters and mice. Effects were not necessarily reproducible between studies. Adverse developmental effects generally have not been observed in rats (Kavlock et al. 1981) except for temporary increase in locomotor activity of pups (Gray et al. 1981) and delayed ossification at doses which resulted in maternal toxicity (Goldenthal 1978a). Developmental effects were found primarily in one species. It is unknown if these effects would occur in humans. 

In rat developmental studies, fetal effects including delayed ossification and decreased locomotor activity occurred at doses that also caused maternal toxicity. Cadmium sulfate injected into the lingual vein of female hamsters on day 8 of pregnancy caused a high incidence of resorption and malformed offspring. Acute necrosis of rat testes followed large doses orally or parenterally, but testicular effects have not been reported thus far in humans." ... 

Exposure of rats to 6000 ppm, 7 hours/day, on days 6-15 of gestation was associated with an increased incidence of delayed ossification of sternebrae. Maternal toxicity was limited to decreased weight gain. 

Oral exposure of pregnant rats to 750mg/kg/day for 10 gestational days induced slightly decreased fetal weight, delayed ossification of sternal and vertebral arches, and some early embryonic deaths. Maternal deaths also occurred at this dose, indicating that 2,4-DCP was not selectively toxic to embryos or fetuses. No effects were noted in dams or offspring exposed at 375 mg/kg/day. 

Pregnant mice exposed to 5000 ppm, 6 hours/day on days 6-15 of gestation had no overt maternal toxicity there was slightly delayed ossification of skull bones in the offspring. ... 

Limited animal studies bave suggested that methylene chloride is slightly fetotoxic at doses that also produce maternal toxicity in rats and mice exposed at 12 50 ppm on days 6-15 of gestation, delayed ossification of sternabrae and increased incidence of extra sternabrae were noted, respectively. " ... 

Exposure of pregnant mice to near-lethal levels of 15 00 ppm was maternally toxic and caused increased fetal mortality, reduced weight, delayed ossification, and an increased incidence of cleft palate. At 500 ppm there was reduced maternal and fetal weight gain. No developmental or maternal toxicity was seen at 100 ppm. Similar studies in rats reported developmental delays only at doses that were maternally toxic. No significant adverse effects on reproductive parameters were found in rats exposed for three generations at doses that produced severe toxicity. ... 

Diethanolamine was painted as an aqueous solution on the skin of CD rats on days 6-15 of gestation at dose levels of 0, 150, 500 and 1500 mg/kg bw per day. The two higher dose levels produced severe skin irritation. There was no effect of any treatments on fetal weight or on the incidence of external, visceral or skeletal abnormalities, but delayed ossification of the axial skeleton and distal appendages was observed in fetuses of the 1500-mg/kg bw group (Marty et al, 1999). 

Pregnant rats and mice exposed to 1250 ppm of CH2CI2 (gestation days 6 to 15, 7 hr. daily) showed a lower incidence of lumbar ribs than controls, and increased incidence of delayed ossification. A significant number of mouse pups had an extra center of sternal ossification (ref. 36). Exposure of rats to 4500 ppm of the dichloride for the 21 days prior to, and seven days during gestation altered environmental habituation rates. Preliminary observations indicate a possible behavioral effect on progeny of dams exposed to dichloromethane (ref. 37). 

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