Fetal malformation

Administration of trimethadione (Tridione) may result in hematologic changes, such as pancytopenia (decrease in all the cellular components of the blood), leukopenia, aplastic anemia, and thrombocytopenia Also reported are various types of skin rashes, diplopia (double vision), vomiting, changes in blood pressure, CNS depression, photosensitivity, and fatal nephrosis. Because these dm have been associated with serious adverse reactions and fetal malformations, they should be used only when other less toxic dm are not effective in controlling seizures. The oxazolidinediones may precipitate a tonic-clonic seizure... 

Monooctyltin/ dioctyltin Mouse DOT stabilizer mix (DOT(IOMA) MOT(IOMA) 80 20) Gestation days 6-17 at 0,20, 30, 45, 67, and 100 mg/kg body weight Embryo/fetal malformations Maternal thymus weight LOAEL = 67 NOAEL = 45 LOAEL = 45 NOAEL = 30 Faqi et al. (2001)... 

Developmental Effects. There are no data available on developmental effects of acrylonitrile in humans however, two well-conducted studies in rats have shown that acrylonitrile is teratogenic in animals by both inhalation and oral exposure (Murray et al. 1978). Fetal malformations occurred in a dose-related manner. When administered orally, malformations were present even at doses in which no maternal or fetal toxicity was apparent. 

Single intraperitoneal injection of 900-1000 mg/kg during midgestation results in some maternal deaths and increased incidences of fetal malformations... 

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... 

The hemolytic anemia caused in pregnant rabbits by diflunisal was severe enough to explain the concomitant axial skeletal malformations (Clark et ah, 1984). Acetazolamide-induced fetal malformations in mice are apparently related to maternal hypercapnia (Weaver and Scott, 1984a, b) and hypokalemia (Ellison and Maren, 1972). The increased resorption rate induced in rabbits by the antibiotic norfloxacin depends on exposure of the maternal gastrointestinal tract (Clark et ah,... 

Khera, K.S. (1984). Maternal toxicity-A possible factor in fetal malformations in mice. 

It has been demonstrated that At is embryotoxic in pregnant mice, and there also exists a dose-related occurrence of associated fetal malformations (29, 30). Long-term studies in female rats that had received 0.5 /tCi g At systemically indicated a significant incidence of radiation-induced mammary carcinomata (39/45 44%) and endometrial polyps (43/55 76.4%) at 14 months after treatment. No thyroid tumors were found (50). Detailed macroscopic radiation dosimetric studies related to the biodistribution of At in animal models have been reported (29, 33, 39). 

Intra-amniotic administration of acrolein in rats induced a significant number of fetal malformations, whereas intravenous administration was embryo lethal. Pregnant rabbits given 4.0 and 6.0mg/kg/day on days 7 through 19 of gestation had high incidences of mater-... 

Single intravenous injection of InCh in pregnant rats caused reduced fetal weights and fetal malformations primarily in the tail." In mice similarly treated, indium did not cause fetal malformations although it reduced fetal weight and caused fetal mortality. 

No treatment-related increases in embryo/fetal mortality or fetal malformations were observed in rats after exposures of up to 100 ppm, 6 hour/day, during days 6-20 of gestation. Fetal and maternal toxicity were evidenced by reduced weights. 

Administered by injection or inhalation during gestation nickel carbonyl caused fetal mortality, reduced pup weights, and fetal malformations including anophthalmia, microphthalmia, cystic lungs, and hydronephrosis in rats and hamsters. ... 

Parental injection of TMSN caused some fetal malformation and embryonic death but only at doses that caused severe maternal toxicity. ... 

A high rate of fetal malformations in sheep offspring occurs following grazing on Veratrum califomicum growing in the mountains of North America. Plants that induce abortion, such as bitter melon seeds, have a long history of use of in humans. 

This knowledge has been reinforced numerous times through tragic experience with thalidomide, alcohol, methyl mercury, lead, and many other agents. Our knowledge has progressed from concern only over chemicals that cause physical fetal malformation to recognition that chemicals can cause much more subtle but still harmful effects. 

N3. Norgaard-Pedersen, B., Bagger, R, et al., Maternal-serum-alphafetoprotein screening for fetal malformations in 28,062 pregnancies. A four-year experience from a low-risk area. Acta Obstet. Gynecol. Scand. 64(6), 511-514 (1985). 

Azathioprine can be administered both orally and intravenously. It is well absorbed orally and after its rapid conversion to 6-mercaptopurine it is inactivated by xanthine oxidase which converts 6-mercaptopurine to 6-thiouric acid. This final metabolite is then excreted in the urine. In combination with the xanthine oxidase inhibitor allopurinol dose adjustments of azathioprine are needed. Renal disease also raises 6-mercaptopurine concentrations and can make dose adjustments necessary. Azathioprine is still used in organ transplantation programs and for the management of several autoimmune diseases. Its adverse effects include nausea, vomiting, diarrhea and, more seriously, bone marrow suppression and hepatotoxicity. Azathioprine is not thought to cause fetal malformation. 

As for the rat, large litter sizes and extensive background data in the rabbit are valuable criteria for an optimal assessment of in utero development of the embryo or fetus and for the detection of potential external or internal fetal malformations. 

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