United States
Environmental Protection
Agency
Health Effects Research
Laboratory
Research Triangle Park NC 27711
Research and Development
EPA-600/S1-81-057 Sept. 1981
Project Summary
Association Between Birth
Defects and Exposure to
Ambient Vinyl Chloride
Gilles P. Theriault, Hilda Iturra, and Suzanne Gingras
To better define the association
between exposure to vinyl chloride
monomer (VCM) and the occurrence
of birth defects, this epidemiological
study was made in Shawinigan,
Quebec, Canada, where a vinyl chloride
polymerization plant has operated
since 1943. Birth-defect rates in
Shawinigan during the last 15 years
were compared with rates in three
other communities, and seasonal and
spatial variations in Shawinigan's
birth-defect rate were correlated with
estimated VCM concentrations in the
environment.
Shawinigan had an excess of birth
defects which fluctuated seasonally in
a way that could correspond to
changes in VCM concentration in the
environment. Mothers who gave birth
to malformed children were younger
on average in Shawinigan than in the
comparison communities. However,
there was no excess of stillbirths in
Shawinigan, the excess in birth defects
involved most systems, and variation
in birth-defect rates among school
districts could not be accounted for by
estimates of VCM in the atmosphere.
The occupational and residential
histories of parents who gave birth to
malformed infants were compared
with those of parents of normal
infants. The two groups did not differ
in occupational exposure or closeness
of residence to the vinyl chloride
polymerization plant.
This Project Summary was devel-
oped by EPA's Health Effects Research
Laboratory, Research Triangle Park,
NC, to announce key findings of the
research report that is fully docu-
mented in a separate report of the
same title (see Project Report ordering
information at back).
Introduction
Vinyl chloride monomer (VCM) is
carcinogenic in man and other animals
and mutagenic in microbial assays,
Drosophila, yeast, mammalian cells,
and man. VCM generates mutations
primarily through one of its metabolites,
chloroethylene oxide, and with the
involvement of liver microsomal
enzymes. Although miscarriages and
fetal losses among the wives of workers
exposed to VCM have been studied,
such effects remain undocumented.
VCM was found in the fetal and
maternal blood and the amniotic fluid of
pregnant rats after exposure to air
containing VCM; two studies of VCM
teratogenicity in animals failed to
demonstrate fetal malformations, but
showed increased fetal death rates.
At normal temperature and pressure,
VCM is a gas; it liquifies at -13° C. It is
processed into polyvinyl chloride (PVC; a
plastic) through polymerization reac-
tions in autoclaves. The gas is released
into the environment during unloading,
processing, and autoclave-cleaning
operations. The concentration of VCM
-------
to which people in the community are
exposed depends on production rate,
wind direction, wind velocity, and
distance from the plant.
In Shawinigan (population 27,000), a
vinyl chloride polymerization plant
(owned by B.F. Goodrich Co., Ltd.) has
operated since 1943 and currently
produces 25,000 tons/yr of PVC. Ten
cases of angiosarcoma of the liver have
been reported among workers at this
plant. In addition to the PVC plant,
Shawinigan has two chemical plants,
one aluminum electrolysis plant, one
carbide plant, and one pulp and paper
mill. A great number of pollutants are
discharged into its environment. Fur-
thermore, prevailing winds tend to blow
from the pollution sources towards the
town's residential areas.
In 1975, a high birth-defect incidence
(mostly central nervous system abnor-
malities) was found in three Ohio towns
with PVC plants. However, two sub-
sequent studies failed to find any
association between birth defects and
either work at or proximity of residence
to these plants. In a 1977 study, a higher
birth-defect rate was found in Shawinigan
than in Drummondville (a town without
a PVC plant); the highest rates in
Shawinigan were in the vicinity of the
plant. The present study was an attempt
to associate this high frequency of birth
defects with exposure to VCM.
One objective of this study was to
establish birth-defect and stillbirth rates
in Shawinigan and to compare these
rates with those for other communities,
in an attempt to confirm the high birth-
defect rates previously observed. An-
other objective was to try to correlate
seasonal and spatial variations in the
birth-defect rate with variations in VCM
concentration in the environment. The
final objective was to compare a group
of parents who gave birth to malformed
infants with a control group of parents
of normal children with respect to
residential and occupational history and
several birth-defect risk factors.
In determining birth-defect rates in
Shawinigan, the study included all
stillbirths and malformed children born
of mothers who resided within the city
limits of Shawinigan at the time of
delivery and who delivered between
January 1, 1966, and December 31,
1979. The case-control study was
limited to a shorter period (January
1973 to December 31,1979), because it
required information based on the
mothers' recollection of events during
their pregnancies. A birth defect was
defined as a gross physical or anatomic
developmental anomaly present at birth
or detected at the hospital during the
first days after delivery.
To assess the importance of the
excess of birth defects in Shawinigan,
three comparison communities were
chosen, based on their similarity to
Shawinigan in population size and
structure, socioeconomic level, and
medical-care facilities. To take into
account the influence of environmental
pollution, one town with an aluminum
plant but no VCM-emitting plant (Baie-
Comeau—Hauterive) and two towns
with neither a VCM nor an aluminum
plant (Drummondville and Rimouski)
were chosen as control communities.
The Quebec Population Registry
provided the annual numbers of births
and stillbirths in the communities; as
the 1979 data were not available,
numbers were estimated from the three
preceding years. Birth-defect children
and controls were identified and data
were collected from several medical
files and hospital rosters (delivery-room
daybooks, birth-defect rosters, discharge
lists, mothers' and children's medical
files, and birth rosters). Shawinigan's
14 school districts were used as the unit
of spatial distribution of birth defects.
For the case-control study, the mothers
of affected infants and matched controls
were interviewed at home. Cases and
controls were matched by maternal age
within two years, sex of the infant, and
place of residence of the mother.
Two studies were conducted to
assess vinyl chloride concentration in
the air in Shawinigan. The first was a
study of the feasibility of measuring
VCM in the air at several locations in
Shawinigan using air sampling and
analysis techniques (summarized in an
appendix to the report of the present
study). Its conclusion was that environ-
mental VCM concentrations could be
assessed by ambient air sampling at
various sites in Shawinigan; depending
on location, sampling detected levels up
to 45 ppb. During winter, VCM tended to
accumulate in the snow in the vicinity of
the plant, and VCM concentrations
differed between indoor and outdoor
samples. The report recommended a
continuous one-year sampling program
with special attention to meteorologic,
topographic, and demographic data to
establish the true VCM concentrations
to which the Shawinigan population is
exposed.
Considering the high cost of such a
sampling program, it was decided that
for the present study, ambient vinyl \
chloride concentrations in Shawinigan
would be estimated using a dispersion
model based on production records and
the results of previous air-monitoring
activities. This study was conducted by a
subcontractor. The dispersion model
used the Pasquill-Gifford equation, and
its variables included wind direction and
velocity, rainfall, humidity, tempera-
ture, topography, and estimated VCM
production and emissions. The model
allowed construction of isopleths of
estimated vinyl chloride concentration
over Shawinigan.
Results
From January 1966 through Decem-
ber 1979, there were 4534 live births
and 33 stillbirths in Shawinigan. Of the
live infants, 150 had birth defects, and
of the stillbirths, 9 had birth defects. The
birth defects reported most frequently
were those of the musculoskeletal
system, followed by the cardiovascular,
central nervous, and urogenital sys-
tems. The ages of the mothers did not
differ significantly among the various
types of birth defect. Defects of the
central nervous system (CNS) were
particularly frequent among malformed
infants with short gestation periods. '
The yearly numbers of malformed
children per 100 births varied from 1.68
(in 1969) to 6.84 (in 1973), with an
overall rate of 3.48. Detailed analysis of
the monthly distribution of birth defects
and the distribution by affected system
for the year 1973 showed no single
large increase that could account for the
high rate in that year. Nor did the yearly
distribution by system show any par-
ticular feature that could account for the
annual variation in the overall rates.
Furthermore, birth-defect rates did not
consistently increase or decrease with
time.
The observed number of malformed
children in Shawiniganwashigherthan
would be expected based on the rate for
each comparison community or for all
three comparison communities together
(see Table 1). The excess birth defects in
Shawinigan occurred in the central
nervous, cardiovascular, urogenital,
and musculoskeletal systems, the eye
and ear, and the chest. As the types of
defects found in excess in Shawinigan
were also the most common types o1
defects overall, it can be concluded thai
birth defects in general were in excess
in Shawinigan. The proportion of mat
formed infants was greater in Shawinigar
than in the comparison communities ir
-------
Table 1 . Number of Malformed Children Observed in Shawinigan Compared with
Comparison Communities (1966-1979)"
Affected
System
Central nervous
Cardiovascular
Gastrointestinal
Urogenital
Musculoskeletal
Mouth and upper
airways
Eye and ear
Chest
Syndromes and
other defects
Total
Observed
in
Shawinigan
30
37
11
30
49
17
6
3
6
159
Expected
Based on
Drummondville
19.69*
19.69**
9.04
19.15*
36.71
6.92**
1.06**
0.53*
6.92
102.68**
Expected
Based on
Baie-Comeau —
Hauterive
18.18*
13.94**
9.70
13.94**
27.88**
13.33
1.82*
—
9.70
98.80**
Expected Numbers Based on Rates for the
Expected
Based on
Rimouski
15.33**
43.06
10.95
13.14**
40.14
13.14
—
0.73
10.95
124.08**
Expected
Based on All
Comparison
Communities
17.96*
24.29*
9.80
15.72**
34. 70*
10.82
1.02**
0.41*
8.98
107.36**
"Ratio of Poisson variable to its expectation (36); * indicates p < 0.05;
** indicates p< 0.01.
all years except 1969 and 1972 (see
Table 2).
The number of stillbirths differed only
• between Shawinigan and Drummond-
ville, where the number of stillbirths
was significantly higher. The proportion
of malformed children among the still-
born was higher in Shawinigan than in
the comparison communities. This is
consistent with previous findings of an
excess of birth defects in Shawinigan.
Mothers who gave birth to malformed
children were significantly younger in
Shawinigan than in the comparison
communities for all malformations
combined and for defects of the CNS,
mouth and upper airways, and eye and
ear. Children in Shawinigan did not
differ from those in the comparison
communities in mean gestational age at
birth, except in the case of chest
malformation, for which the sample size
was very small.
Figure 1 compares the monthly birth-
defect rates for Shawinigan with those
for Drummondville and Rimouski The
Shawinigan curve is V-shaped, with the
lowest rates in the summer, whereas
the curve for the comparison communi-
ties is flatter. The seasonal variation in
birth-defect rates was statistically
significant for Shawinigan, but not for
the comparison communities.
The spatial distribution of birth
defects in Shawinigan with respect to
the PVC plant was analyzed; in no
Table 2, Distribution of Malformed Children for Each Year (1966-1979)
Year
1966
1967
1968
1969
1970
1971
1972
1973
1974
1975
1976
1977
1978
1979
Total
Shawinigan
16
13
8
6
15
6
6
18
8
15
13
14
11
10
159
Ratea
3.54
3.52
2.30
1.68
4.70
2.08
2.19
6.84
2.97
4.40
3.98
4.56
3.33
3.11
3.48
Comparison
Communities
31
33
24
27
24
30
34
44
43
51
36
50
52
47
526
Rates
1.82
1.96
1.51
1.78
1.66
2.05
2.43
3.17
2.81
3.10
2.20
2.76
2.88
2.69
2.35
SH/ Comparison
Communities*'
1.95*
1.80
1.52
0.94
2.83*
1.01
0.90
2.16*
1.06
1.42
1.81
1.65
1.16
1.16
1.48*
95% Confidence
Interval
(1.08, 3.52}
(0.96, 3.391
(0.69, 3.341
(0.41, 2.18)
(1.55. 5.1 7 j
10.53, 1.94)
(0.36. 2.20)
(1.28, 3.65)
(0.48. 2.33)
(0.81. 2.49)
(0.93, 3.51)
(0.93, 2.93)
(0.61, 2.20)
(0.60. 2.26)
(1.24. 1.75)
"^Number of malformed children per 100 births.
"""' indicates p < 0.05.
-------
f)-
OQ
^
-3
I
CJ
0)
3-
2-
co
1-
Shawinigan (1966-1979) •
Drummondville and
Rimouski (1971-1977)
JAN FEB MAR APR MAY JUN JUL AUG SEP OCT
Month of Birth
Figure 1. Monthly distribution of birth-defect rates.
\ \
NOV DEC
school district did the ratio of observed
to expected number of birth defects
differ significantly from 1. The four
districts with the highest rates are
located on the north-south axis passing
through the vinyl chloride plant; the
district in which the plant is located had
abcut the expected number of birth
defects. The yearly average concentra-
tion of vinyl chloride was estimated for
each school district, based on data from
a study entitled "Dispersion Patterns of
Vinyl Chloride Emitted by B.F. Goodrich
Co., Ltd., Shawinigan, Clue." (which is
appended to the report of the present
study). Birth-defect rates did not differ
between school districts with high and
low VCM exposure, either for all birth
defects or for CNS defects (see Table 3).
Likewise, school districts adjacent to
the plant did not differ from the other
school districts in numbers of birth
defects (total or CNS), nor did districts
differ within and beyond a one-mile
radius of the vinyl chloride plant.
For the period January 1973 to
December 1979, 68 cases of birth
defects were identified in Shawinigan
and matched with controls (42 male and
26 female pairs). Five of the cases were
stillborn; all of the controls were born
alive. There was no significant difference
between cases and controls in number
of weeks' gestation at delivery. The
frequencies of previous birth defects in
the families of cases and controls did
not differ significantly, nor was there a
significant difference between case and
control mothers in number of previous
pregnancies.
Mothers of malformed infants reported
no excess of diseases during pregnancy;
however, the following diseases sus-
pected to bear a high risk of birth defect
were reported more frequently by case
than by control mothers: rubella,
hydramnios, epilepsy, nonpsychotic
mental disorders, and psychosis. There
was no significant difference between
case and control mothers in number of
previous abortions. There was one
pievious stillbirth among the control
mothers and none for the case mothers;
there was one previous malformed child
in each of the two groups. There was no
significant difference between cases
and controls in the father's age. No
mother (case or control) was exposed to
X-rays during the first trimester of
pregnancy, and only one case mother
was exposed during the second third of
pregnancy; exposure during the third
trimester did not differ significantly
between case and control mothers.
Table 4 summarizes the mothers'
occupations before and during their
pregnancies. None of the women were
ever exposed to VCM at work before or
during pregnancy. The working experi-
ences of the case and control mothers
before and during pregnancy did not
differ, nor did their smoking habits or
alcohol consumption. Two mothers of
defective infants reported having used
the drug LSD before their pregnancies.
There was no significant difference
between cases and controls in the
father's occupational exposure to
chemicals, and no fathers were ever
exposed to vinyl chloride (see Table 5).
The distance between each mother's
place of residence and the VCM plant
was measured to ± 100 m, using a map
of the city; there was no significant
difference between the two groups in
distance from the VCM plant.
Table 3.
Discussion
Some observations of this study
support the existence of an association
between VCM in the air and birth
defects in the exposed community,
Comparison of Total Birth Defects* and CNS Birth Defects* Between
School Districts with High and Low Atmospheric Vinyl Chloride
Concentration
School Districts
School Districts
Births with
defects
Births without
defects
Births with CNS
defects
Births without
CNS defects
Total births
With High VCM Levels*
87
2285
16
2356
2372
With Low VCM Levels
70
2125
13
2182
2195
Total
1'57
4410
29
4538
4567
aX2i = 0.80; p> 0.35.
t>X^^ =0.10; p> 0.70.
"School districts nos. 1. 3, 5, 6, 7, and 8.
-------
Table 4. Distribution of Cases and Controls by Mother's Occupation*
Cases Control
Mother's Before
Occupation Pregnancy
Work outside home without
exposure to chemicals
Work in VCM industry
Work outside home with
exposure to chemicals
Stay at home
Total
41
0
2
25
68
During
Pregnancy
22
0
1
45
68
Before
Pregnancy
42
0
2
24
68
During
Pregnancy
20
0
1
47
68
^Partitioning stay at home vs. work outside home before pregnancy:
X2,=0.03; p>0.85. Partitioning stay at home vs. work outside home during pregnancy:
X2, =0.13;p>0.71.
while others tend to contradict such an
association. High birth-defect rates in
Shawinigan were confirmed for a 15-
year period, and women who gave birth
to malformed children were, on average,
younger in Shawinigan than in the
comparison communities. These results
are consistent with previous findings for
three Ohio towns with PVC plants.
The present study revealed seasonal
variation in birth-defect rates that could
correspond to variation in atmospheric
VCM concentrations. VCM could not be
measured in air samples during Decem-
ber, January, and February. It is
believed that during these months, VCM
tends to accumulate near the plant as a
liquid, because the outdoor temperature
is below its liquefaction point; this VCM
would be released into the air in the
spring. Birth-defect rates were lowest in
September, which is eight months after
midwinter, corresponding to the time
between the first third of pregnancy and
delivery. This observation would tend to
support an association between VCM
concentration in the air and birth
defects in the community. One con-
sultant believed that below its liquefac-
tion point, VCM would remain in the air
in droplets, at a concentration similar to
that found at higher temperatures.
However, because people spend more
time indoors during the winter than the
rest of the year, winter exposure would
tend to be low in any case.
On the other hand, several observa-
tions of the present study tend to argue
against any association between VCM
concentration in the air and birth
defects in the community. The spatial
distribution of birth defects in Shawinigan
cannot be explained on the basis of
estimates of VCM concentrations in the
community. Malformation rates were
not relatively high either near the plant
or in the area where VCM concentrations
were estimated to be highest, and the
school district with the highest birth-
defect rate was far from the plant.
However, VCM concentrations were not
measured directly, but estimated by a
theoretical dispersion model based on
approximate production and emission
values, because the B.F. Goodrich Co.
would not release the actual values.
Table 5. Distribution of Cases and Controls by Father's Occupation*
Father's Occupation Cases Controls
Ever worked in vinyl
chloride industry
Ever worked in industries
with exposure to chemicals
0
20
0
25
Never worked in industries
with exposure to chemicals
Unknown
Total
43
5
68
39
4
68
"X2! =0.73;p>0.39.
There was no difference in occupa-
tional or residential history between the
parents who gave birth to malformed
infants and the control parents. Both
groups resided at similar distances from
the plant, and none of the parents had
worked at the plant. Furthermore, all
types of birth defects were in excess in
Shawinigan, rather than those of any
particular system. These results agree
with those for the three Ohio cities;
however, agents known to be teratogenic
in humans and experimental animals
have very specific effects, and it seems
unlikely that any agent would produce
the variety of malformations found in
excess in Shawinipan.
Possible explanations of the results
as artifactual are not convincing. It is
unlikely that Shawinigan's physicians
were'more inclined to diagnose birth
defects than were physicians in the
comparison communities. Birth defects
were included in this study on the basis
of their obviousness, and the birth-
defect rates were the same in the three
comparison communities. Furthermore,
for severe birth defects like those of the
CNS, which cannot be misdiagnosed,
rates were much higher in Shawinigan
than in any of the comparison com-
munities. The method by which the data
were collected made it very unlikely that
a bias in the quality of the information
from the archives of the regional
hospitals could have influenced the
results.
The possibility remains that pregnant
mothers residing outside of Shawinigan
who were at risk of having a malformed
child migrated to the city for delivery,
thereby increasing the birth-defect rate
for that town. In the case-control study,
six mothers (6.7%) were rejected
because they had moved to the city of
Shawinigan after the first third of
pregnancy, and four more cases were
untraceable. Thus, as many as 11% of
the birth-defect cases observed in
Shawinigan might actually have come
from elsewhere, reducing the number
of observed cases to 142. However,
birth-defect rates would still be sig-
nificantly higher than in the comparison
communities, leading us to believe that
the excess noted in Shawinigan was
real.
Animal studies have shown that
exposure to high levels of VCM during
pregnancy results more often in high
rates of fetal loss and miscarriage than
in birth defects. However, stillbirth rates
were no higher in Shawinigan than in
the comparison communities, and m the
-------
case-control study, abortion rates were
not higher for case than for control
mothers.
Several industries in Shawinigan
emit pollutants into the atmosphere,
and several of the pollutants may
interact to generate potent mutagenic
or teratogenic chemicals in the com-
munity. The analysis of such an envi-
ronment and its association with the
excess of birth defects was beyond the
scope of the present study. However, in
the case-control study, there was no
difference between the numbers of case
and control parents who worked at the
aluminum plant, and the comparison
community with an aluminum elec-
trolysis plant (Baie-Comeau—Hauterive)
had lower birth-defect rates than did
Shawinigan. Thus, the aluminum in-
dustry probably was not solely respon-
sible for the excess of birth defects in
Shawinigan.
Among risk factors (other than occu-
pational or environmental exposure to a
pollutant) known to be associated with
birth defects, epilepsy and mental
disorders before and during pregnancy
and the use of the drug LSD before
pregnancy were reported more fre-
quently by mothers of malformed
children than by control mothers. Drugs
prescribed to control epilepsy have been
reported to be associated with birth
defects and could account for a few birth
defects observed in Shawinigan, as
could LSD. No other risk factor was
reported more frequently by the case
than by the control mothers.
An association between VCM in the
air and birth defects in the exposed
community cannot be substantiated at
the present time. If the association
exists, it cannot be measured by the
methods used in this and in previous
studies or in populations of the sizes
studied so far.
Conclusions
The conclusions of this study can be
summarized as follows:
1. For the years 1966 through 1979,
there was an excess of birth
defects in the population of
Shawinigan, Quebec. This result
is similar to the findings for
several U.S. cities where vinyl
polymerization plants operate.
2. Birth-defect rates underwent a
seasonal variation that could cor-
respond to variation in the con-
centration of VCM in ambient air.
3. Mothers from Shawinigan who
gave birth to malformed infants
were younger than mothers from
the comparison communities who
also gave birth to malformed
infants.
4. The excess malformations involved
not only the central nervous
system, but almost all body sys-
tems.
5. No correlation was found between
the spatial distribution of birth
defects in the town and estimates
of VCM concentrations in the air.
(These estimates were based on
approximate data, since informa-
tion on PVC production and VCM
emissions was not available.)
6. Occupational exposure as a causal
agent was ruled out, because
none of the parents in the study
had ever worked at the VCM plant.
7. Cases and controls did not differ in
distance of residence from the
plant.
8. No excess of stillbirths was ob-
served in Shawinigan, and abortion
rates were no higher for mothers
of malformed infants than for
mothers of normal infants.
Some observations of this study
support an association between VCM in
the air and birth defects in the exposed
community, while others tend to indi-
cate that no such association exists. As
the present results are inconclusive, the
possibility that VCM generates birth
defects in human communities requires
further consideration. This would best
be accomplished through a program
during the next five to ten years to
monitor VCM concentration in the air
and birth defects in the exposed
communities.
Cities P. Theriault, Hilda Iturra, and Suzanne Gingras are with the Department of
Social and Preventive Medicine, Faculty of Medicine, Laval University,
Ste-Foy, Quebec, Canada G1K 7P4.
Jeff Beaubier and Gregg Wilkinson are the EPA Project Officers (see below).
The complete report, entitled "Association Between Birth Defects and Exposure
to Ambient Vinyl Chloride," (Order No. PBS 1-238 883; Cost: $11.00, subject
to change) will be available only from:
National Technical Information Service
5285 Port Royal Road
Springfield, VA 22161
Telephone- 703-487-4650
The EPA Project Officers can be contacted at:
Health Effects Research Laboratory
U.S. Environmental Protection Agency
Research Triangle Park, NC 27711
•h US GOVERNMENT PRINTING OFFICE, 1981 —757012 7327
-------
United States
Environmental Protection
Agency
Center for Environmental Research
Information
Cincinnati OH 45268
Postage and
Fees Paid
Environmental
Protection
Agency
EPA 335
Official Business
Penalty for Private Use $300
K^Vlf, H^uToflTUM
u * 5 T J.RKAKY
6 D ^ H F ti Q H *> S t' P h P* ^t
IU IT, 6ofio4
------- |