ABSTRACT At the Behavioral Teratology Meeting (BTM) of the Japanese Teratology Society in 1992, a core test battery was proposed from a practical and simple point of view as an estimation of developmental neurobehavioral toxicity for use in pharmaceutical drug screening. The validity of the core test battery is being examined in a new series of collaborative studies. The present study is the first such study; phenytoin, a well-known behavioral teratogen, was selected as the test compound, and 32 laboratories took part in a behavioral teratology study of phenytoin using the new test battery. Sprague-Dawley strain rats from four breeds were used. Phenytoin (200 mg/kg) was administered orally to pregnant rats from days 10 to 14 of gestation (sperm detection = day 0), and in the male offspring, the survival rate, development of physical landmarks, functional developments, open field test scores, and Biel water maze test results were assessed and the brain weights were measured. The shuttle box conditioned avoidance test was also performed in some laboratories. In the present collaborative study, by taking an aggregate of the relative values converted from the measured values of each breed (providing a much larger sample size than that recommended by reproduction toxicity study guidelines), a high detectability level for phenytoin's effects was established. Under these conditions, the effects of phenytoin on eye opening, incisor eruption, the surface righting reflex, the negative geotaxis reflex, and perfoImance of the open field test, Biel water maze test and shuttle box conditioned avoidance test were observed. It was found that present collaborative study made it possible to evaluate the detectable capacity of each of these test battery items. In addition, the critical period of abnormalities demonstrated in many test items was identified, and the results of several previous reports were confirmed. Furthermore, a breed difference in the effect of phcnytoin for several test items was found. The present results established that the core test battery accurately detected the effects of phenytoin.
ABSTRACT We studied the pathogenesis of congenital posterolateral diaphragmatic hernia induced by bisdiamine in rats. The frequency of live fetuses with left congenital diaphragmatic hernia (which resembles a hernia through the foramen of Bochdalek in man) was high (78.4%) when pregnant rats were administered bisdiamine by gavage once at a dose of 400 mg/kg on day 9 of pregnancy. Then the bisdiamine-treated rat fetuses were examined at successive developmental stages. Histopathological observation revealed that 1) in the control fetus on day 14 of pregnancy, the mesothelial cells lining the pleural aspect of the pleuroperitoneal fold were eventually clustered close to the pleuroperitoneal opening, giving the appearance of a high wave lapping the shore; 2) in the affected fetus on day 14 of pregnancy, the mesothelial cells of the pleural aspect of the fold were scarce; 3) in the affected fetuses during days 14-16 of pregnancy, primary lung hypoplasia was seen. On day 19 of pregnancy, no remarkable differences in the gross appearance of the right lung were found between the affected and control fetuses. Each lung (right and left) of the affected embryos may be considered to have the potential for further growth and development. The development of the mesothelium of the pleura may be greatly influenced by the growth and enlargement of the thorax (mainly the lung), and a retardation of lung growth near the time of pleuroperitoneal canal closure may induce the hernia in diaphragm.
ABSTRACT This paper is the first version of a Japanese glossary of terms for structural developmental abnormalities in laboratory animals, mainly rats, mice and rabbits. This is a translation of the glossary entitled Terminology of Developmental Abnormalities in Common Laboratory Mammals that was edited by the International Federation of Teratology Societies (IFTS) Committee on International Harmonization of Nomenclature in Developmental Toxicology (IFTS glossary). The purpose of the present Japanese glossary is to provide a common vocabulary, terms and definitions in the description of abnormalities observed in reproductive and developmental toxicity studies. The glossary contains 868 observations, synonyms, related terms, definitions of the abnormalities and non-preferred terms for external, visceral and skeletal abnormalities in fetuses or neonates of laboratory animals. Modifying terms used repeatedly in the glossary (e.g., absent, atresia) are listed separately in Appendix A, and syndrome names that are generally known are listed in Appendix B. Translation was made into Japanese based on the following: 1) Observations are translated in order of orgadfinding (e.g., thymudabsent, maxilldfused) with exception of the terms in common use, 2) Words are appended where appropriate. when literal translation does not provide an adequate description, 3) A supplementary explanation is appended as an “annotation”, where appropriate, 4) Among the synonyms or related terms. the terms listed in Appendix A or the same Japanese translations as the observations are not described repeatedly, and 5) Non-preferred terms are not literally translated, and only those terms which are considered as adequate as Japanese are described. Suggestions, questions. and additions are welcomed on the Japanese terms and translations in the glossary. Revisions of the Japanese glossary are planned based on the comments received.