Handbook of Solvents - George Wypych - ChemTech - Ventech!

20.3 Pregnancy outcome following solvent exposure 1343
When a chemical or any other environmental factor caused a malformation in the experimental
animals and/or the biological mechanism is understood, the observation of an
association in humans becomes more plausible. Although the statistical association must be
present before any relationship can be said to exist, only biological plausible associations
can result in “biological significance”.
The mechanisms by which many solvents exert their toxicity are unclear and may vary
from one solvent to another. Halogenated hydrocarbons such as carbon tetrachloride may
generate free radicals. 27 Simple aromatic compounds such as benzene may disrupt
polyribosomes, whereas some solvents are thought to affect lipid membranes and to penetrate
tissues such as the brain. 27
In 1979 a syndrome of anomalies (hypertonia, scaphocephaly, mental retardation and
other CNS effects) was suggested in two children in a small American Indian community
where gasoline sniffing and alcohol abuse are common. 28 Four other children had similar
abnormalities, however, in these cases it was impossible to verify gasoline sniffing. Also, it
is unclear what was the contribution of the lead in the gasoline or the alcohol abuse in producing
these abnormalities. It is important to remember that the mothers in many of these
cases showed signs of solvent toxicity indicating heavy exposure. This is not the case in
most occupational exposures during pregnancy. While fetal toxicity is biologically sensible
in cases of intoxicated mothers, the evidence of fetal damage from levels that are not toxic to
the mother is scanty and inconsistent.
7. Proof in an experimental system that the agent acts in an unaltered state.
8. Important information for prevention.
Several lists of criteria for human teratogenicity have included the dose (or concentration)
response relationship. 1 Although a dose response may be considered essential in establishing
teratogenicity in animals it is extremely uncommon to have sufficient data in human
studies. Another criterion which is comforting to have but not very often fulfilled is biologic
plausibility for the cause. Shepard states that at present there is no biologically plausible explanation
for thalidomide embryopathy and that at least one half of all human teratogens do
not fit this criterion. 26
B. Spontaneous abortion
Estimates for clinically recognized spontaneous abortions as a proportion of all pregnancies
vary markedly. In ten descriptive studies reviewed by Axelsson, 29 the proportion of spontaneous
abortions varied from 9% to 15% in different populations. The variation depended
not only on the characteristics of the population but on the methods used in the study, i.e.,
the selection of the study population, the source of pregnancy data, the definition of spontaneous
abortion, the occurrence of induced abortions and their inclusion or otherwise in the
data. The weaknesses of the studies using interviews or questionnaires pertain to the possibility
of differential recognition and recall (or reporting) of spontaneous abortions and of
differential response. Both exposure and the outcome of pregnancy may influence the willingness
of subjects to respond to a study. One advantage of interview data is that it is more
likely to provide information on early spontaneous abortion than medical records. However,
the validity of information on early abortion which may be difficult to distinguish
from a skipped or delayed menstruation has been suspect. Spontaneous abortions which
have come to medical attention are probably better defined than self-reported abortions.
The feasibility of using medical records as a source of data depends on the pattern of
use of medical facilities in the community and the coverage and correctness of the records.