Peri-/postnatal toxicity

Reproduction studies (fertility and general reproductive performance, embryo-toxicity and peri/postnatal toxicity) ... 

If peri-postnatal tests, developmental neurotoxicity smdies, or specific male or female fertility studies are available they can be used to identify a substance as being toxic to reproduction. Data from such studies alone cannot be used to identify a substance as being of no concern in relation to reproduction. 

Hellwig J, Liberacki AB Evaluation of the pre-, peri-, and postnatal toxicity of mono-ethanolamine in rats following repeated oral administration during organogenesis. Fundam Appl Toxicol 40 158-162, 1997... 

PYAP Tablet coatings/ink component for capsules Single dose in various species, repeat dose (oral gavage or diet and up to 2 yrs in duration in rat and dog) and reproduction (fertility study in rat, embryo-fetal studies in rat and rabbit, and peri-postnatal study in rat) toxicity Well tolerated [limited extreme high-dose effects seen (Table 3)]... 

These study protocols combine the design of a fertility study and of a peri- and postnatal toxicity study. The study element of an embryo-fetal toxicity study can be included. In both cases, provided clearly negative results at sufficiently high doses or exposure are achieved, no further reproduction studies in rodents are required. Such a combination of all the study designs mentioned would provide all examinations required in a most probable option using considerably fewer animals. But an embryo-fetal toxicity study in a second species is expected. 

Peri- and postnatal toxicity studies commence before mating or in early pregnancy and observe the effects during pregnancy, at delivery and during the entire lactation period until weaning. 

In all reproduction toxicity studies at least three doses (minimally toxic, intermediate, non-toxic) should be given, preferrably by the proposed clinical route of application. Fertility and peri- and postnatal toxicity studies require tests in only one species (usually rats or mice), the teratology segment must be tested in two species (e.g. rodents and rabbits). Pharmacokinetic data and differences in the placentation may suggest other modes of application and/or other test species, e.g. primates. Of course the minimum animal numbers for the standard tests do not apply to studies in primates. 

Peri- and postnatal toxicity studies are recommended as a continuation of a part of the fertility or teratology studies, thus the treatment periods vary. At least 12 (-20) pregnant mice or rats per group are examined during pregnancy, delivery and during the lactation... 

Reproductive toxicity studies in animals provide important information for evaluating the potential developmental toxicity in children. Developmental toxicity effects assessed in reproductive toxicity studies include fetal growth retardation, malformations, fetal loss, decreases in peri- and postnatal growth and survival, retarded... 

The complete reproductive toxicity package, including the rodent peri-and postnatal studies, must be submitted with the marketing application. 

Delgado, I.F., A.C. Nogueira, C.A. Souza, et al. 1993. Peri- and postnatal developmental toxicity of beta-myrcene in the rat. 

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