Prenatal smokeless tobacco effects on the rat fetus.
The objective of this study was to examine the effect of an aqueous extract of smokeless tobacco (ST) on the development and bone ossification of the Sprague Dawley rat fetus at known nicotine blood levels. Dams were intubated with the ST extract three times daily on gestational days (GD) 6-18 with one of the following: ST equivalent to either 1.33 mg nicotine/kg body weight (STD-1), 6 mg nicotine/kg body weight (STD-2), or equal amounts of distilled water (sham-treated controls). Parallel groups of rats were used for nicotine-blood-level determinations. Dams were killed on GD 19, fetuses and placentas were weighed, and resorptions, deaths, and/or malformations were noted. Two thirds of the fetuses were further examined by Wilson's method, and the remaining one third was stained and cleared for skeletal examinations. Mean plasma nicotine levels, determined in a parallel group of nonpregnant/pregnant rats, were 220.4/283.3 ng/ml in the STD-1 group and 869.1/846.3 ng/ml in the STD-2 group. At these ST dosages, weight gain of dams was reduced in comparison with sham-treated controls (P < .05), but fetal weights were reduced in the STD-2 group only. Placental weights, litter size, resorptions, deaths, and malformations were not significantly affected. Skeletal examinations revealed several dose-related differences between the ST-treated and sham-treated control groups. In the STD-1 group, reductions in ossification were seen in the nasal and femur width measurements only. In the STD-2 group, reductions in ossification were seen in femur length and width, in the number of ossification centers in the forelimb, in the maxillary, mandibular, and nasal bone measurements. We conclude that under these experimental conditions the effects of ST at the low dose are minimal, whereas the high ST dose resulted in significant growth retardation and decreased ossification levels (P < .05).