Handbook of Solvents - George Wypych - ChemTech - Ventech!

20.3 Pregnancy outcome following solvent exposure 1337
Effects of tetrachloroethylene on the dams varied between species. 11 In the mouse relative
liver weight was significantly increased and the absolute liver weight increased but not
significantly and with no effect on maternal body weight. In the rat there was a non-significant
decrease in absolute and relative liver weights and a significant 4-5% decrease in mean
body weight. Food consumption was unaffected.
Effects on the embryo and fetus also differed. 11 In the mouse there was no effect on implantation
sites, live fetuses or resorption rates but mean fetal weight was significantly reduced,
59% of litters containing runts (weight less than 3 standard deviations below the
mean) compared with 38% of control litters. Whereas in the rat, resorption rate was significantly
increased from 4% in controls to 9% in the exposed group, while fetal body was unaffected
(mean slightly higher than controls).
In the mouse, examination for anomalies revealed an increase in delayed ossification
of the skull bones (significant) and of the sternebrae (nonsignificant) as might be expected
from the fetal weight data. There were also significant increases in the incidence of split
sterenbrae and subcutaneous edema. No gross malformations were found. In the rat, gross
malformations (short tail) were reported but the incidence did not differ significantly from
that in controls. There were no other significant differences in soft tissue or skeletal abnormalities.
11
The results of this study are difficult to assess, partly because no indication of the numbers
of fetuses affected within affected litters is given and partly because of the uncertain
nature of the “subcutaneous edema” reported. 9,11 Exposure to tetrachloroethylene and the
concurrent controls were part of a large study on four different solvents. The incidence of
subcutaneous edema in the mouse ranged from 8-59% of litters affected which seems very
high and while the incidence in the tetrachloroethylene group was highest at 59%, it was as
high as 45% in nonconcurrent controls (27% in concurrent controls). 11 In the rat, the incidence
of this particular anomaly also varied enormously between groups from 0%
(tetrachloroethylene group) to 28% (trichloroethylene group). 11 It is therefore important to
know how strict were the criteria for designation of “subcutaneous edema” and in particular
whether the designation was made before or after fixing, subcutaneous edema being a common
fixative artifact. 9 However, the retardation of growth and ossification and the increased
incidence of split sternebrae in fetal mice exposed to tetrachloroethylene were clear effects
and in the absence of any effect on maternal body weight, suggest that tetrachloroethylene
has some maternal hepatotoxicity but has no effect in the rat where there is no
hepatotoxicity at 300 ppm. 11
The results of a behavioral teratology study in the rat by Nelson et al. have been reported.
12 Rats were exposed to 0 or 900 ppm tetrachloroethylene for 7 hours/day on days
7-13 or 14-20 of pregnancy (9-16 rats per group). The dams were affected by this level,
showing reduced food consumption and lower weight gain during exposure but
histopathological examination of the maternal liver and kidney in dams sacrificed on day 21
of pregnancy revealed no abnormalities. 12
Postnatally, offspring were tested for olfaction, neuromuscular ability, exploratory
and circadian activity, aversive and appetitive learning. 12 There was evidence of impaired
neuromuscular ability. 12 Offspring from dams exposed on days 7-13 were poorer than controls
in ascent of a wire mesh screen during the second week of life and were poorer than
controls on a rotorod test on one of the 3 days tested in the fourth week of life. 12 Offspring
from dams exposed on days 14-20 performed less well in ascent of a wire mesh screen.