No abstract

Historical control data on rabbit prenatal developmental toxicity studies, performed between 1994-2010, were obtained from 20 laboratories, including 11 pharmaceutical and chemical companies and nine contract laboratories, in Japan. In this paper, data were incorporated from a laboratory if the information was based on 10 studies or more. Japanese White rabbits and New Zealand White rabbits were used for prenatal developmental toxicity studies. The data included maternal reproductive findings at terminal cesarean sections and fetal findings including spontaneous incidences of morphological alterations. No noticeable differences between strains or laboratories were observed in the maternal reproductive and fetal developmental data. The inter-laboratory variations in the incidences of fetal external, visceral, and skeletal alterations seem to be due to differences in the selection of observation parameters, observation criteria, and classification of the findings, and terminology of fetal alterations.

Historical control data from prenatal developmental toxicity studies in rats have been used to evaluate whether toxicology outcomes were induced by exposure to a chemical or were within the range of spontaneous variation. These data are also important for monitoring animal characteristics. As a follow-up to historical control data from 1998 to 2010, this study analyzed control data from prenatal developmental studies performed in rats from 2011 to 2015. Data were collected from studies performed by 24 Japanese laboratories, including 15 pharmaceutical and chemical companies and nine contract research organizations, in Sprague-Dawley and two-sub-strains of Wistar Hannover rats. The data included maternal reproductive findings at terminal cesarean section and fetal findings, including incidences of spontaneous external, visceral, and skeletal anomalies. No noticeable differences in maternal reproductive data were observed among laboratories. The inter-laboratory variations in the incidences of fetal anomalies seemed to be due to differences in the selection of observation parameters, observation criteria, and classification of the findings, as well as to differences in terminology of fetal alterations. These historical control data may be helpful for adequate interpretation of experimental results and for evaluating the reproductive and developmental toxicities of various chemicals.

High frequency of placental malformation was observed by the administration of GW501516. From GD 8 to 11, especially GD 10, is more sensitive period to induce the placental malformation.