Organogenesis period

The prolonged exposure period of animals to ziram caused adverse effects. For instance, female rats administered with low doses (2.5 mg/kg/day) in diets for 9 months showed a decreased antibody formation. Exposure of rats and dogs for a prolonged period with lower doses (1 to 5 mg/kg/day) of ziram showed no adverse effects, whereas treatment of pregnant rats with ziram (12.5 to 100 mg/kg/day) during the organogenesis period demonstrated embryotoxicity. 

Teratology studies cover the organogenesis period and usually end shortly thereafter, near or at term of delivery. 

The mentioned differences between the US, EEC and Japanese guidelines are only the major ones. Other differences concern the definition of organogenesis periods and the related treatment periods for the different species, as well as the type of recommended investigations. Depending on the regulating authority (e.g. for human or veterinary products) test recommendations can even vary within one country. 

No teratogenic effects of the compound D-camphor were observed in rats orally administered the compound at doses up to 1000 mg/kg daily during the organogenesis period of pregnancy, or in pregnant rabbits administered doses up to 681 mg/kg daily (Leuschner 1997). 

Exposure to the fetus in the first 2 weeks after conception may have an all or nothing effect (i.e., could destroy the embryo or have no ill effect). Exposure during the period of organogenesis (18 to 60 days postconception) may result in structural anomalies (e.g., methotrexate, cyclophosphamide, diethylstilbestrol, lithium, retinoids, thalidomide, certain antiepileptic drugs, and coumarin derivative). 

Globally, those experiments with knockout mice suggest that the implication of more than one member of the nuclear receptor family may have prominent effects in organogenesis, even if their expression is for a brief period during embryonic life. The mice with double or triple knock-outs, lacking two or three receptors, will surely contribute to finally clarifying the roles of each hormone and each receptor. 

Segment 11 teratogenicity study. This concentrates on the most sensitive part of gestation, from the time of implantation imtil major organogenesis is complete. This is the period during which a test substance is most likely to cause malformation of the embryo. Exposure of the mother to the test substance is usually confined to this period. Conventionally, the study is conducted in rats and rabbits. Rabbits are intolerant to antibiotics and the mouse is an acceptable alternative in most cases. 

Sulfuric acid mist was not teratogenic in mice or rabbits exposed 7 hours/day to 20mg/m during the period of major organogenesis. ... 

Most drugs and chemicals pose a threat to the developing fetus. An estimated 4 to 5% of developmental defects in humans result from prenatal exposure to drugs or environmental chemicals. This is particularly important, since women with irregular menstrual cycles may be exposed to teratogens and enter the sensitive period of organogenesis before pregnancy is suspected. 

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