Embryonic malformation

In laboratory tests, appHcation of DMAC to the skin of pregnant rats has caused fetal deaths when the dosages were close to the lethal dose level for the mother. Embryonal malformations have been observed at dose levels 20% of the lethal dose and higher. However, when male and female rats were exposed to mean DMAC concentrations of 31,101, and 291 ppm for 6 h per day over several weeks, no reproductive effects were observed (6). 

Karabulut AK, Ulger H, Pratten MK. Protection by free oxygen radical scavenging enzymes against salicylate-induced embryonic malformations in vitro. Toxicol In Vitro 2000 14(4) 297-307. 

Mercury exposures by immersion and oral administration have caused reproductive and behavioral modifications. Brief immersion of mallard eggs in solutions of methylmercury resulted in a significant incidence of skeletal embryoiuc aberrations at dosages of 1.0 trg Hg/egg, and higher no increases in embryonic malformations were noted at 0.3 trg Hg/egg. 

Vitamin A (retinol), a simple fat-soluble molecule discovered in 1913 by McCollum and Davis (/), is essential for proper development, growth, and maintenance of a normal adult vertebrate organism (2-4). Dietary deficiency of vitamin A results in structural and functional abnormalities of a multitude of organs and organ systems (5-7). Likewise, excess of vitamin A is deleterious to life, particularly in its early development where hypervitaminosis A leads to profound embryonic malformations (6,8,9). 

Up to 8% dead at dose range 0.01-1 mg As+5/embryo threshold for malformations at dose range 0.3-3 mg/embryo Teratogenic to embryos when injected at 1-2 mg/egg Developmental abnormalities at embryonic injected doses of 1-2 mg/egg... 

Treatment of rats with cypermethrin up to 8 mg/kg/day produced no malformations [140]. Maternally toxic dose level of bifenthrin did not produce adverse effects on embryonic development in rats [141], A rabbit teratology study with 30 or 90 mg/kg/day tetramethrin during fetal organogenesis demonstrated no adverse effects on skeletal or external development [137]. 

Embryonic zebra fish model was employed to study fullerene toxicity. This model is quite convenient because the embryos are transparent in the first week of life and their rate of development is rather fast. C60, C70, and C60(OH)24 have been tested on early embryogenesis (Usenko et al., 2007), presenting effects on this process with malformations, pericardial edema, and mortality. The results for fullerols are milder, but it is difficult to attribute this effect to the presence of the functionalizations themselves or to the easier solubilization, implying diminished cluster formations and avoiding the use of solvents as toluene or THF, the presence of which can play an important role in toxicity, as already demonstrated. 

Steroidal alkaloids found in the Filiaceae family, primarily Veratrum and Zygadenus, have been responsible for large losses in livestock. Fluman and livestock deaths have occurred from accidental ingestion of death camas (Panter et al., 1987). Thousands of lambs have died or been destroyed because of Veratrum-indvLCQd malformations, most notably a craniofacial defect called cyclopia (Binns et al., 1965 James, 1999 Figure 2.8). Tracheal stenosis, skeletal malformations and early embryonic death are also common (Keeler and... 

Anddewicz DS, Bums CG, Camey S A, Peterson RE, Heideman W (2005) Heart malformation is an early response to TCDD in embryonic zebrafish. Toxicol Sci 84 368-377... 

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

Folate play an important role in the biosynthesis of DNA bases and in amino acid metabolism. An adeguate intake of folate reduces the risk of abnormalities in early embryonic brain development, specifically the risk of malformations of the embryonic brain/spinal cord. Therefore a proper intake is strictly recommended for pregnant women. Megaloblastic anemia is the ultimate consequence of an inadequate folate intake. No adverse effects have been associated with the consumption of excess folate from foods [417]. 

Similar malformations should be treated as if they are the same, provided they are likely to have a common embryonic origin. In a small number of studies, the malformation rate increases because of a general, non-specific effect on the embryo. Examples of similar malformations are anencephaly, exencephaly and hydrocephaly. 

This study is performed in two species, a rodent (usually the rat) and a non-rodent (nearly always the rabbit). Pregnant females are fed the treated diet from the day of implantation of the embryo through to the end of gestation (i.e., through the embryonic and fetal periods). The females are euthanized shortly before they would have given birth and the femses are examined to detect any strucmral abnormalities. The dams unfortunately cannot be left to give birth namrally because they tend to eat any malformed pups before they can be examined. The fetuses are sampled and processed for detailed examinations of the soft tissues and the skeleton (see Chapters 16-21). 

---