Embryo-fetal development toxicity of prenatal exposure to penequine hydrochloride intramuscularly in rats

• Published in: Food and chemical toxicology Vol. 45; no. 4; pp. 592 - 599
• Main Authors: Zhang, Zibo, Zhang, Qinglin, Wang, Zhiqiao, Wei, Jinfeng, Wang, Aiping
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.04.2007; New York, NY Elsevier Science
• Subjects: Abnormalities, Drug-Induced; Animals; Anticholinergic drug; Biological and medical sciences; Body Weight - drug effects; Bone and Bones - abnormalities; Cyclopentanes - toxicity; Embryo-fetal developmental toxicity; Embryology: invertebrates and vertebrates. Teratology; Embryonic Development - drug effects; Female; Fetal Development - drug effects; Fundamental and applied biological sciences. Psychology; Injections, Intramuscular; Male; Maternal toxicity; Medical sciences; No-Observed-Adverse-Effect Level; Penequine hydrochloride; Quinuclidines - toxicity; Rats; Rats, Wistar; Teratology. Teratogens; Toxicology; Wistar rats; Embryo-fetal developmental toxicity; Wistar rats; Anticholinergic drug; Maternal toxicity; Penequine hydrochloride; Drug; Embryonic development; Embryo; Rat; Toxicity; Rodentia; Prenatal; Teratogenesis; Vertebrata; Mammalia; Hydrochlorides; Animal; Fetus
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2006.10.004

The potential for penequine hydrochloride to induce maternal and embryo-fetal developmental toxicity was evaluated in Wistar rats. The drug was administered intramuscularly (i.m.) at dose levels of 0, 10, 30 or 50 mg/kg/day to groups of pregnant rats from day 6 to 15 of gestation. All dams were observed for maternal body weights, food consumption and any abnormal change, and subjected to caesarean-section on gestation day (GD) 20; all fetuses obtained from caesarean-section were assessed by external inspection, visceral and skeletal examinations. In the 50 mg/kg/day group, maternal toxicity included an increase in the incidence of abnormal clinical signs, and decrease in the body weight and body weight gain. Developmental toxicity included an increase in the postimplantation loss, a decrease in the litter size, and a reduction in the gravid uterus weight. In addition, a statistically non-significant increase in the incidence of fetal external, visceral, and skeletal alterations including malformations and variations were seen in high-dose group. There were no treatment-related findings in maternal clinical and intrauterine observations, and fetal morphological examinations in mid-, low-dose and control groups. Thus, under the conditions of this study, the no-observed-adverse-effect-level (NOAEL) and lowest-observed-adverse-effect-level (LOAEL) of penequine hydrochloride for both maternal and embryo-fetal toxicity in the Wistar rats were considered to be 30 mg/kg/day and 50 mg/kg/day, which are approximately 900 and 1500 above the therapeutic dosage, respectively.