Effect of smokeless tobacco on the development of the CD-1 mouse fetus

The objective of this study was to examine the effect of smokeless tobacco (ST) on the development of the CD-1 mouse fetus. ST was administered continuously via Alzet osmotic minipumps during the critical gestational days 7-14 and 6-13. Two ST dosages were administered, 3.2 mg/ml (Dosage I) and 6.4 mg/ml (Dosage II), which yielded plasma nicotine levels within the range comparable to those of an average ST user or smoker (36.0 ng/ml). Plasma nicotine levels were maintained in the range of 29.4 +/- 4.8 ng/ml to 44.3 +/- 16.0 ng/ml for the Dosage I group of dams, and in the range of 34.6 +/- 10.9 ng/ml of 75.5 +/- 19.9 ng/ml for the Dosage II group of dams. The main effect on the fetus was weight reduction, with Dosage I producing a tendency toward weight reduction (p = .08). Dosage II produced a significant 8.6% weight reduction from normal (p less than .0001) and an increase in fetal deaths (p less than .03). Dosage I produced an increase in the incidence of hemorrhages and supernumerary ribs, and a significant delay (p less than .05) in ossification of the supraoccipital bone, the sacrococcygeal vertebrae, and the bones of the forefoot and hindfoot. There were no significant differences between placental weights. Weights of dams were significantly reduced only at the higher ST exposure levels. We conclude that at plasma nicotine levels comparable to those of an average ST user, ST produces weight reduction, delayed ossification, and increase in hemorrhages and fetolethality in the CD-1 mouse fetus.