Skeletal ossification

Air concentrations of 28.5 mg/m3 for 4 h daily on days 9-12 of gestation caused fetotoxic effects and chromosomal damage to liver cells by day 18 effects included reduced survival, impaired growth, retarded limb ossification, and bone abnormalities. At 2.9 mg/m3, a 9.9% decrease in fetal weight was recorded at 0.26 mg/m3, a 3.1% decrease was measured Oral dosages of 400-600 mg/kg BW on days 7-16 of gestation produces fetal malformations (cleft palate), delayed skeletal ossification, and fetal weight reduction 200-600 mg/kg BW daily for 10 days (DMA) produced fetal and maternal toxicity... 

S decrease in fetal weight skeletal ossification in 59S of fetuses)... 

Developmental Effects. Oral developmental toxicity studies of deca-, octa-, and pentaBDE have shown no evidence of teratogenicity in animals. Gestational exposure to a high (1,000 mg/kg/day) but maternally nontoxic dose of decaBDE was fetotoxic in rats as shown by subcutaneous edema and delayed skull bone ossification. Commercial mixtures of octaBDE caused skeletal ossification variations in rats and rabbits at maternally toxic levels and other indications of fetotoxicity at lower doses. Effects of gestational exposure to octaBDE included minimally increased postimplantation loss in rats at >10 mg/kg/day, increased resorptions in rats at 25 mg/kg/day, and increased skeletal variations in rabbits at 15 mg/kg/day and rats at 50 mg/kg/day. No evidence of fetotoxicity was found in the only available study of pentaBDE in rats at maternally toxic doses < 200 mg/kg/day. No studies are available on developmental effects of PBDEs in humans. Based on the evidence in animals, PBDEs are unlikely to cause developmental toxicity at expected levels of exposure. 

Polybrominated Diphenyl Ethers. Oral developmental toxicity studies have shown no evidence of teratogenicity of deca-, octa-, and pentaBDE in rats and rabbits, although fetotoxic effects, including skeletal ossification variations at maternally toxic doses, have occurred (Argus Research Laboratories 1985b Breslin et al. 1989 Dow Chemical Co. 1975, 1985 Life Science Research Israel Ltd. 1987 Norris... 

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. 

Results from inhalation studies in animals also suggest that tetrachloroethylene is fetotoxic but not teratogenic at concentrations that are also maternally toxic (Schwetz et al. 1975). Fetotoxicity in rodents is usually expressed by decreased fetal weight and delayed skeletal ossification. These effects have been associated with exposure to 300 ppm, and NOAELs have not been reported. A gavage study in rats reported that tetrachloroethylene caused an increase in micro/anophthalmia in the offspring of rats treated... 

Titanocene dichloride effected a general embryotoxic influence when it was applied to pregnant mice. It caused diminution of the number of live fetuses per litter, a marked and dose-dependent reduction of mean fetal body weight after application on day 8 through day 16 of murine pregnancy, a dose-dependent delay of fetal growth and development and a distinct retardation of skeletal ossification (Fig. 66). At higher doses of I, abortions were induced within few hours after substance application. 

The effects of perfluorinated compounds on prenatal and postnatal endpoints have been evaluated in rodents for PFOA, PFNA, PFDA, perfluorooctadecanoic acid (PFOcDA), the 8-2 FTOH, and an FTOH mixture and in mice for PFOA. PFOA is the best-characterized of these compounds, having been assessed in both rats and mice. Mice appear to be far more sensitive to the effects of PFOA on development compared to rats, possibly due to the aforementioned species difference in pharmacokinetics. Adverse effects noted prenatally in mice and/or rats with the above-cited compounds include decreased implantation/number of corpora lutea (mixed FTOH and PFOcDA), increased percent litter loss and/or incidence of full litter resorption (FLR) reduced skeletal ossification and/or increased incidences of skeletal variations and decreased fetal body weights (Abbott et al. 2007 Lau et al. 

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