Significance of Supernumerary Ribs in Rodent Developmental Toxicity Studies: Postnatal Persistence in Rats and Mice

Significance of Supernumerary Ribs in Rodent Developmental ToxicityStudies: Postnatal Persistence in Rats and Mice. CHERNOFF, N.,ROGERS, J. M., TURNER, C. I., AND FRANCIS, B. M. (1991). Fundam.Appl Toxicol 17, 448–453. Pregnant Sprague-Dawley ratsand Swiss-Webster mice were gavaged with bromoxynil at 15 and96.4 mg/kg/day, respectively, on Days 6–15 of gestation.The frequency of supernumerary ribs (SNR), which are here definedas any degree of ossification lateral to the first lumbar vertebrae,was determined in fetuses at term and offspring on PostnatalDays 6, 20, and 40. Bromoxynil induced significant increasesin the incidence of SNR in fetuses of both species. In rats,SNR occurred in 62% of treated fetuses as compared to 14% incontrols; in mice these values were 45% and 11%, respectively.The postnatal incidence and persistence of SNR was species dependent.In the rat, postnatal SNR incidence in treated animals did notdiffer significantly from controls. In contrast, in mice thebromoxynil-induced elevated incidence of SNR persisted throughDay 40(42.3% in treated vs 0% in controls). Analysis of SNRwas also done on the basis of their length (greater or lessthan the length of the 13th rib). In the mouse, the incidenceof smaller SNR was much lower on Day 40 as compared to Day 20;in contrast the incidence of larger SNR persisted through Day40. In the rat, the incidence of larger SNR was too small todraw conclusions as to the postnatal fate of these structures.As in the mouse, however, the incidence of smaller SNR was significantlylower by Day 40. The significance of SNR in developmental toxicityremains problematic. The impact of this anomaly on animals isdifficult to assess. While it appears to be a transient effectin rats, detailed examination of the adjacent vertebrae to determinetheir normalcy has not yet been accomplished. While the effectappears to be transient in the rat, data reported here suggestthat this may be a species/strain specific phenomenon ratherthan a general finding.