Rb. Paulson et al., PRENATAL SMOKELESS TOBACCO EFFECTS ON THE RAT FETUS, Journal of craniofacial genetics and developmental biology, 14(1), 1994, pp. 16-25
The objective of this study was to examine the effect of an aqueous ex
tract of smokeless tobacco (ST) on the development and bone ossificati
on of the Sprague Dawley rat fetus at known nicotine blood levels. Dam
s 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). Para
llel groups of rats were used for nicotine-blood-level determinations.
Dams were killed on GD 19, fetuses and placentas were weighed, and re
sorptions, deaths, and/or malformations were noted. Two thirds of the
fetuses were further examined by Wilson's method, and the remaining on
e third was stained and cleared for skeletal examinations. Mean plasma
nicotine levels, determined in a parallel group of nonpregnant/pregna
nt 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 darns was r
educed in comparison with sham-treated controls (P < .05), but fetal w
eights were reduced in the STD-2 group only. Placental weights, litter
size, resorptions, deaths, and malformations were not significantly a
ffected. Skeletal examinations revealed several dose-related differenc
es between the ST-treated and sham-treated control groups. In the STD-
1 group, reductions in ossification were seen in the nasal and femur w
idth measurements only. In the STD-2 group, reductions in ossification
were seen in femur length and width, in the number of ossification ce
nters in the forelimb, in the maxillary, mandibular, and nasal bone me
asurements. We conclude that under these experimental conditions the e
ffects of ST at the low dose are minimal, whereas the high ST dose res
ulted in significant growth retardation and decreased ossification lev
els (P < .05).