Influence of nicotine and caffeine on skeletal development in the rat.

The effects of nicotine and caffeine at dose levels approximating human consumption on skeletal development was investigated in Sprague-Dawley rats. One group of animals received nicotine administered subcutaneously by an Alzet miniosmotic pump from gestational d 6 through 12 (25 mg over 7 d; rate 149 micrograms/h). Control animals received physiological saline in a similar manner. A2. group received a single intravenous injection of caffeine (25 mg/kg) on gestational d 6. Control animals were treated with physiological saline. A further group received both nicotine and caffeine on gestational d 6 as described for the 2 previous groups. Evaluation of the fetal skeletal system on gestational d 20 revealed a significant decrease in the number of complete sternal ossification centers, as well as delays in the ossification of the skull and face, following combined nicotine and caffeine treatment. Other skeletal anomalies and variations were frequently observed, but their incidences were not significantly increased in any of the treatment groups, compared to the corresponding controls. A coteratogenic effect is evident between nicotine and caffeine on account of the increased incidence of delayed and abnormal skeletal development.