Teratogenicity types

The ability to form carbon—carbon bonds in a controlled manner around an alkene is the subject of continuing intense research [49,134—136], These compounds are stable and, due to the considerably different reactivities of the C—Zr and C—B bonds, allow for selective and sequential reactions with a variety of electrophiles. Temarotene 58 is a retinoid of interest [137] because it shows no sign of hypervitaminosis A and it is not teratogenic, presumably due to the lack of a polar group [138,139], The published synthesis of temarotene-type compounds is long and leads to mixtures of diastereo-isomers, from which the desired product is eventually isolated [140—142], However, the synthesis of temarotene 58 by the method of Srebnik et al. [130] is straightforward, as outlined in Scheme 7.18. 

Type D Delayed effects (e.g., carcinogenicity, teratogenicity) Low incidence... 

The structural features of the solanum alkaloids are based on two primary skeletal configurations solanidane, with or without glycoside functionalities, as featured by the toxic and teratogenic steroidal alkaloids a-chaconine and a-solanine with the indolizidine type E-F ring (Figure 2.7a) and the spirosolane... 

A particularly important type of developmental toxicity is called teratogenicity. After fertilization the ovum - a single cell - begins to proliferate, making more of its own kind by a series of divisions. In humans, at about the ninth day the remarkable process of cell... 

Type D (delayed) reactions are teratogenic or carcinogenic responses. 

D. Data on acute, subacute and chronic toxicity, teratogenicity and other types of toxicity... 

The practical consequence from this is that in the study type under consideration, always the dam/litter rather than the individual fetus is the basic statistical unit (see Chapters 23, 33, 34 and 35). Six malformed fetuses from six different litters in a treated group of dams is much more likely to constitute a teratogenic effect of the test substance than ten malformed fetuses all from the same litter. It is, therefore, important to report all fetal observations in this context and to select appropriate statistical tests (e.g., Fisher s exact test with Bonferroni correction) based on litter frequency. For continuous data, a procedure to calculate the mean value over the litter means (e.g., ANOVA followed by Dunnet s test) is preferred. An increase in variance (e.g., standard deviation), even without a change in the mean, may indicate that some animals were more susceptible than others, and may indicate the onset of a critical effect. 

Nevertheless, the rat is not always the appropriate species for the teratogenicity testing of all types of test item its pertinence needs to be justified for each study (see Note 1). 

Several published studies have demonstrated that minipig fetuses are sensitive to various known teratogens. In an early study with Pitman-Moore miniature pigs, it was found that this type of pig is sensitive to trypan blue, and a single injection on day 10 of... 

While there is no standard assay design for teratogenicity or developmental toxicity screening, there are many similarities in the types of assays that have been described in the literature (4-9, 22-25). One version of these (4) is described here, and an overview of the assay design is shown in Fig. 3. Variations on this assay (alone or in combination with other techniques) can also be used for more descriptive characterization of the effects of a test substance or evaluation of the mechanisms of developmental toxicity. 

The teratogenic potential of these three compounds was unequivocal in FETAX the incidence and type of malformations observed increased with the concentration in comparison with our historical data (Fig. 2). By contrast, the pertinence of the negative results in the mammalian tests could be open to question. 

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