Embryogenesis teratogenic effect

The timing of the interference with the process of embryogenesis would be very important to the final expression of the teratogenic effect. 

Gilani SH, Diaz A. 1986. The teratogenic effects of trichloroethane on the chick embryogenesis. Teratology 33 64C. 

As embryogenesis involves extensive cellular proliferation, any interference with this process is potentially teratogenic. Interference with spindle formation, inhibition or arrest of DNA synthesis or the incorrect separation of chromatids all fall into this category. Inhibition of DNA synthesis, such as that caused by cytosine arabinoside, slows or arrests mitosis, which cannot progress beyond the S-phase. Thus those areas of the embryo which show extensive cellular proliferation are the most susceptible to both necrosis and subsequent malformation from cytotoxic compounds such as cytosine arabinoside. Inhibition of spindle formation such as that caused by vincristine or colchicine stops separation of chromosomes at anaphase (see page 240). Proper separation of chromatids may not occur because of stickiness or bridging between the chromatids. Clearly interference with mitosis, and hence cell proliferation, is an important cause of teratogenic effects. 

Schuh TJ, Hall BL, Creech Kraft JM, Privalsky ML, Kimelman D (1993) V-erbA and citral reduce the teratogenic effects of d -trans retinoic acid and retinol, respectively, in Xenopus embryogenesis. Development 119 785-798... 

Hazard evaluation is used here to mean examination and evaluation of the hazards (adverse effects) observed in toxicity studies, including reproductive, teratogenic, and general toxicity studies plus other pertinent data. Because of the complexities of the reproductive system as well as embryogenesis and maturation of the conceptus, hazard evaluations must go beyond the mere determination of statistical effects, no observed effect levels (NOELS), relationships between dose and response, dose and effects, and the determination of margins of safety. Most... 

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