Embryo-fetal development

These components would normally be evaluated in a rodent species (preferably rats) and, in addition, embryo-fetal development would be evaluated in a second species, typically the rabbit. The most probable option in the ICH guideline is the case where three rodent studies would be conducted that separately addressed each of the components listed above. These study designs are described below. The day of insemination or detection of evidence of mating is considered Day 0 of gestation and the day of birth is considered postpartum and postnatal Day 0. Figure 8.1 presents line charts for the ICH Stage-Study Designs. 

With the possible exception of combining the female fertility component with the embryo-fetal development component, the combined-study approach is used often. The female fertility and embryo-fetal development components are needed to... 

The critical period for the induction of hypospadias by finasteride in rats is Days 16 to 17 of gestation (Clark et al., 1990a). It is unlikely that other agents would have a much earlier critical period since testosterone synthesis, which is required for the development of the penile urethra, begins in the rat on Day 15 of gestation (Habert and Picon, 1984). Thus, if treatment in the embryo-fetal development study... 

Food consumption Toxicokinetics For fertility studies In-life observations Terminal and necroscopic evaluations For embryo-fetal development studies In-life observations... 

Varsho BJ et al (2000) A study of the effects of restraint duration for nose-only inhalation exposure on embryo/fetal development in rats. Toxicologist 54 204... 

Key words Rat, Teratology, Developmental toxicity, Embryo-fetal development, Embryo-toxicity... 

Key words DART, Teratology, Fertility, Preclinical methods. Embryo-fetal development, Embryotoxicity. 

The combined fertility and embryo-fetal development study is described as a two study design in the ICH S5(R2) guideline (1) and is anticipated for use in rodents (usually rat but also the mouse) embryo-fetal development must still be evaluated in a second, nonrodent, species. 

However, combining different phases of the reproductive cycle into a single study design increases the risk of an adverse event compromising the evaluation of subsequent stages, e.g., any impact on fertility of the male or female could result in too few litters for the embryo-fetal development evaluation. Under such circumstances, a separate embryo-fetal development study would have to be scheduled with the associated added cost and use of animals. Further, a separate embryo-fetal development study is recommended if the test item is poorly tolerated with repeated dosing in order to limit the duration of the administration period. 

Embryo fetal Development Studies in Nonhuman Primates... 

Key words Embryo fetal development. Nonhuman primate, Cynomolgus monkey, Fetus, Marmoset, Teratology... 

Synopsis of parameters collected in cynomolgus and marmoset monkeys embryo fetal development studies... 

In addition when it is necessary to process a large number of specimens per day, taking hours over a single specimen is clearly not a practical approach. The use of MRI to examine fresh, unfixed fetal rat and rabbit heads from embryo-fetal development (EFD) studies has already been proposed (6) (see Note 1) and the compromise between image quality and speed of acquisition that is necessary under these circumstances examined. MRI is now considered to have the potential to be an acceptable alternative to current methods after throughput was increased by scanning multiple specimens in parallel with careful optimization of scan parameters. 

French Jet al (2010) Use of magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) in the morphological examination of rat and rabbit fetuses from embryo-fetal development studies. Reprod Toxicol 30 292-300... 

Type of study, e.g., prenatal or embryo fetal development ... 

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