Evaluation of a core battery of tests for detecting behavioral dysfunction of rat offspring induced by retinoic acid: Collaborative work II of the Japanese behavioral teratology committee

The Japanese Behavioral Teratology Meeting, a satellite meeting of the Japanese Teratology Society, proposed a core battery of tests to detect behavioral teratogens in animals in 1992. The core battery consists of examining maternal body weight, offspring weight, external anomalies, viability, preweaning landmarks of physical development (pinna, incisor and eyelids), preweaning reflex tests (surface righting, negative geotaxis and mid-air righting), an open-field test at 5 weeks of age, a water-filled multiple T-maze (Biel-type water maze) test at 6 weeks, a shuttlebox test at 7 weeks and brain weight at termination on postnatal day 56. In order to evaluate the detectability of behavioral dysfunction in rat offspring by this core battery, the first collaborative study was carried out in 1993 using phenytoin. The present, second collaborative study using retinoic acid (RA) was performed in twenty-eight laboratories to further evaluate the proposed core test battery. Pregnant SD rats received 5 mg/kg RA orally from days 14 to 16 of gestation, and postnatal development of their offspring was evaluated. The effects of RA on offspring were detected as lower viability, increased incidence of minor anomalies in the paw and nail, delayed pinna detachment, negative geotaxis and air righting, and less frequent rearing and grooming behaviors in the open-field test. However, no effects were observed in the Biel-type maze and shuttlebox tests. These results suggest that our proposed core battery of tests is useful as a screening method to detect postnatal development disorders, including behavioral dysfunction, in SD rat offspring exposed to RA in utero.