Handbook of Solvents - George Wypych - ChemTech - Ventech!

1338 Kristen I. McMartin, Gideon Koren
However, the latter group were consistently superior to controls on the rotorod later in development.
12 Both exposed groups were generally more active in open field tests than controls
but only those exposed on days 14-20 of gestation differed significantly from
controls. 12 Biochemical analyses of whole brain neurotransmitter levels showed no effects
in newborns but significant reductions in acetylcholine levels at 21 days of age in both exposed
groups of offspring and reduced dopamine levels at 21 days of age in those from dams
exposed on days 7-13. 12 There were no significant differences between exposed and control
groups on any other of the tests. 12 Exposure of offspring to 100 ppm on days 14-20 of gestation
showed no significant differences from controls on any of the above behavioral tests. 12
It was not stated whether neurotransmitter levels were measured in this low-dose group. 9,12
In view of these results, suggesting some fetotoxicity in the mouse but not the rat at
300 ppm and postnatal effects in the rat at 900 ppm but not 100 ppm, there is a need for further
studies at low levels between 900 and 100 ppm to establish a more accurate no-effect-level.
9
20.3.3 PREGNANCY OUTCOME FOLLOWING MATERNAL ORGANIC
SOLVENT EXPOSURE: A META-ANALYSIS OF EPIDEMIOLOGIC
STUDIES
[Adapted, by permission, from K.I. McMartin, M. Chu, E. Kopecky, T.R. Einarson and G.
Koren, Am. J. Ind. Med., 34, 288 (1998) Copyright 1998 John Wiley & Sons, Inc. Reprinted
by permission of Wiley-Liss, Inc. a division of John Wiley & Sons, Inc.]
Introduction
Evidence of fetal damage or demise from organic solvent levels that are not toxic to the
pregnant woman is inconsistent in the medical literature. A mathematical method has been
previously developed and utilized to help overcome bias and arrive at a single overall value
that describes the exposure-outcome relationship; namely, meta-analysis. 15
The risk for major malformations and spontaneous abortion from maternal
inhalational organic solvent exposure during pregnancy is summarized using meta-analysis.
31 Besides being more objective than the traditional methods of literature review, it has
the ability to pool research results from various studies thereby increasing the statistical
strength/power of the analysis. This is especially useful in epidemiologic studies, such as
cohort studies or case control studies since very often large numbers of subjects are required
in order for any problem to be significantly addressed. This is particularly true for
teratogenic studies where the frequencies of malformation are often very low.
Methods
A literature search was conducted to collect studies for the meta-analysis. Using Medline,
Toxline and Dissertation Abstracts databases spanning 1966-1994, literature was identified
concerning the problem in question. In addition, external colleagues were consulted (regarding
unpublished studies) whose area of interest is in occupational exposure and reproductive
toxicology. All references from the extracted papers and case reports were
investigated. Standard textbooks containing summaries of teratogenicity data were consulted
for further undetected references.
Inclusion criteria consisted of human studies of any language which were 1) case control
or cohort study in design; 2) included maternal inhalational, occupational, organic solvent
exposure; 3) had an outcome of major malformation and/or spontaneous abortion; and
4) included first trimester pregnancy exposure. Exclusion criteria consisted of animal studies,
non-inhalational exposure, case reports, letters, editorials, review articles and studies