Periods of vertebral column sensitivity to boric acid treatment in CD-1 mice in utero.
Boric acid (BA) has many uses as an industrial compound and is widely distributed in the environment. BA has been shown to produce rib agenesis, a rare effect in laboratory animals. This study was conducted to determine if there is a period of sensitivity to this unusual effect. BA (500 or 750 mg/kg) was administered p.o. to pregnant CD-1 mice once daily on gestational days (GDs) 6-10. A reduction of 13th rib length occurred at both dose levels. BA 400mg/kg was also administered twice daily on GD 6, 7, 8, 9, or 10 or on GDs 6-8. A significant decrease in average fetal weight was observed in all treatment groups. Significant increases in the incidence of cervical ribs/ossifications resulted from treatments on GD 7 and GDs 6-8. Rib agenesis occurred with treatment on GD 8 and GDs 6-8. Reduced rib length, a decreased incidence of supernumerary ribs (SNR), and an increased incidence of fused and/or branched ribs occurred when dams were treated GDs 6-8. Doses of 750 mg/kg given twice on day 8 produced significant increases in several thoracic skeletal anomalies. Further studies of pathogenesis are necessary to determine the earliest perturbations and the processes that are affected. The sensitivity of embryos to treatment on GD 8 to rib agenesis suggests that BA is affecting early processes such as gastrulation and presomitic mesoderm formation and patterning in this area.
Cherrington
Jana W
JW
Department of Toxicology, North Carolina State University, Raleigh, NC 27695, USA. jana_cherrington@hotmail.com
Chernoff
Neil
N
D000014:Abnormalities, Drug-Induced; D000818:Animals; D001888:Boric Acids / Q000633:toxicity*; D002574:Cervical Vertebrae / Q000002:abnormalities / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D051379:Mice; D011247:Pregnancy; D012272:Ribs / Q000002:abnormalities / Q000187:drug effects; D013131:Spine / Q000002:abnormalities / Q000187:drug effects*; D013723:Teratogens / Q000633:toxicity*; D013997:Time Factors
D001888:Boric Acids; D013723:Teratogens; C032688:boric acid