Abstract |
Groups of 35 inseminated Wistar rats were dosed daily by gavage with YRC 2894 formulated in 0.5% aqueous carboxymethylcellulose suspension from gestation days 6 to 19. The doses were 0, 2, 10, and 50 mg/kg. The fetuses were delivered by cesarean section on day 20 of gestation. Appearance, behavior, and mortality of the dams were unaffected by treatment with YRC 2894. Feed consumption of the dams was distinctly decreased, especially during the first few days after initiation of treatment in the 50 mg/kg dose group. Water consumption and the amount of excreted feces were decreased during the first few days after initiation of treatment in the 50 mg/kg dose group, whereas increased water consumption and urine excretion were observed towards and during the second half of gestation in the 50 mg/kg dose group. Transient body weight loss was detected in the dams within the first few days after initiation of treatment and cumulative and corrected body weight gain during gestation were significantly decreased in the 50 mg/kg dose group. No test compound-related gross pathological findings were evident in any of the dose groups. At cesarean section, an increased incidence of late resorptions and one total resorption were observed in the 50 mg/kg dose group, resulting in a slightly decreased number of viable fetuses in the 50 mglkg dose group. Weight and appearance of the placentaswere not affected at any dose tested, whereas fetal weight was decreased in the 50 mg/kg dose group. Visceral examination of the fetuses revealed no treatment-related findings. External and skeletal evaluation revealed an increased incidence of extremital bone dysplasia, one fetus with multiple malformations, and an increased incidence of skeletal retardation (impaired ossification) and variation (wavy ribs and asymmetrical sternebrae) in the 50 mg/kg dose group. The data from this study are indicative of impaired embryonic or fetal development in the 50 mg/kg dose group, resulting in an increased incidence of postimplantation loss, retarded development, and an increase in common malformations and variations. No evidence for specific developmental toxicity potential of YRC 2894 was determined in this study, since all developmental effects observed were manifested only al a dose-level which also induced severe maternal toxicity andlor are common spontaneous malformations in the rat strain used. |