a ppendix II
a ppendix II
Utility (Adequacy) for CERHR Evaluation Process: These.reports.are.of.limited.utility.in.the.evalu-ation.process.
Hemminki et al. (73),.support.not.indicated,.gave.information.in.a.book.chapter.on.an.unpublished.
study.of.congenital.anomalies.in.women.in.the.plastics.industry..[The results may have been obtained as part of a spontaneous abortion study (74), reviewed in Section 4.1, to which there are method-ologic resemblances.] Women.who.were.members.of.the.Finnish.Union.of.Chemical.Workers.were.
identified.from.Union.records.and.information.on.congenital.malformations.was.obtained.from.the.
Finnish.Register.on.Congenital.Malformations.for.the.years.1973.–.1979.(this.registry.was.estimated.
to.have.“about.50%.coverage”)..Deliveries.were.identified.from.the.Hospital.Discharge.Registry..Each.
Union.member.who.was.identified.as.having.a.malformed.child.was.matched.to.two.Union.members.
according.to.date.of.delivery.(within.1.year).and.Union.chapter..The.cases.and.controls.were.evaluated.
to.determine.if.they.were.working.“at.the.time.of.early.pregnancy.”.For.women.in.the.plastics.industry,.
the.relative.risk.(95%.CI).based.on.9.exposed.cases.and.18.controls.was.1.0.(0.2.–.5.5)..There.was.no.
assessment.of.the.specific.chemicals.to.which.these.women.were.exposed.
Strengths/Weaknesses:.The.use.of.Union.records.to.identify.potentially.exposed.workers.and.the.use.
of.a.national.birth.registry.system.are.strengths.of.this.study;.however,.exposure.was.only.defined.by.
Union.status,.which.is.a.weakness..The.sample.size.was.small,.producing.a.wide.confidence.interval.
around.the.risk.estimate.for.plastics.work,.with.low.power.for.detection.of.an.effect.
Utility (Adequacy) for CERHR Evaluation Process:.This.study.is.of.limited.utility.in.the.evaluation.
process.
Härkönen et al. (75), support.not.indicated,.studied.the.incidence.of.congenital.malformations.among.
children.born.to.styrene-exposed.workers.in.Finland..Workers.were.identified.from.160.workplaces.
in.which.styrene.was.used.in.the.manufacture.of.reinforced.plastics,.with.inclusion.of.1698.men.
and.511.women..The.time.period.during.which.styrene.exposure.occurred.was.determined.[by an unspecified method].for.each.worker..Births.between.the.years.1963.and.1979.were.identified.from.
the. Population. Register,. and. malformations. were. ascertained. through. the. Register. of. Congenital.
Malformations..Children.were.assessed.as.having.been.born.during.or.before.the.period.of.exposure.
of.the.parent..Rates.of.malformation.obtained.in.children.born.within.and.outside.periods.of.parental.
styrene.exposure.were.compared.with.population.rates.calculated.as.total.malformations.in.the.Register.
divided.by.total.live.births.recorded.for.1963.–.1979..There.were.2.malformed.children.born.to.346.
female.workers.before.styrene.exposure,.and.there.was.1.malformed.child.(with.hydrocephalus).born.
to.79.female.workers.during.the.period.of.styrene.exposure..There.were.4.malformed.children.born.
to.771.male.workers.before.styrene.exposure,.and.7.malformed.children.born.to.630.male.workers.
during.styrene.exposure..All.of.the.rates.for.offspring.of.exposed.male.and.female.workers.were.
lower.than.the.expected.population.rates,.and.the.95%.confidence.intervals.based.on.the.Poisson.
distribution.were.overlapping..The.authors.concluded.that.the.results.of.the.study.were.inconclusive.
and.that.the.numbers.of.malformations.were.so.small.as.to.make.further.analysis.impossible.
Strengths/Weaknesses: The.use.of.national.registry.data.is.a.strength.of.this.study,.but.the.sample.size.
is.small.with.low.power,.especially.for.individual.defects..The.use.of.external.rates.for.comparison.
and.the.lack.of.individual.exposure.data.are.additional.weaknesses.
a ppendix II
Utility (Adequacy) for CERHR Evaluation Process: This.study.is.of.limited.utility.in.the.evaluation.
process.
Ahlborg et al. (76),.support.not.indicated,.reported.a.case-control.study.of.adverse.pregnancy.out-come.among.female.employees.of.Norwegian.and.Swedish.companies.producing.plastic.polymers..
Companies.were.asked.to.produce.records.of.women.who.were.employed.any.time.during.the.period.
1972.–.1980..Cooperation.was.obtained.from.43.Swedish.companies.and.35.Norwegian.companies.[the total number of companies approached was not indicated]..National.birth.registers.and.congenital.
malformation.registers.were.used.to.identify.cases,.defined.as.stillbirths,.postnatal.deaths.[not other-wise defined],.any.of.a.list.of.selected.malformations.[not specified],.or.low.birth.weight.(<.2000.g.in.
Sweden,.<1500.g.in.Norway)..Each.case.was.matched.to.2.controls.on.date.of.birth.within.2.months,.
maternal.age.within.5.years,.and.parity.(1,.2,.>.2)..In.“a.few”.cases,.date.of.birth.was.matched.within.
1.year.in.order.to.permit.selection.of.controls..One.Norwegian.woman.contributed.two.case.deliveries,.
and.one.Norwegian.woman.contributed.two.control.deliveries..For.each.case.and.control.woman,.a.
questionnaire.was.sent.to.the.employer.requesting.information.about.the.type.of.plastic.produced,.pro-duction.methods,.and.other.exposures.during.the.year.prior.to.the.delivery..Exposures.were.classified.
by.study.personnel.as.not.involving.plastics,.involving.unheated.plastics,.or.involving.heated.plastics..
Type.of.plastic.was.categorized.as.polyvinylchloride,.polyurethane,.or.styrene.(with.or.without.other.
components)..Odds.ratios.and.95%.confidence.intervals.were.calculated..[The women were not con-tacted and there was no mention of identification or evaluation of possible confounders.]
In.the.Swedish.sample,.there.were.1397.deliveries.of.which.there.were.18.liveborn.children.with.
congenital.malformations,.10.children.with.low.birth.weight,.and.16.dead.children.or.fetuses.(10.
stillbirths,.1.death.in.the.first.week.of.life,.and.1.death.after.the.first.week.of.life)..In.the.Norwegian.
sample,.there.were.282.pregnancies.of.which.there.were.4.liveborn.children.with.malformations,.2.
children.with.low.birth.weight,.and.4.dead.children.or.fetuses.(1.stillbirth.and.3.deaths.in.the.first.week.
of.life)..The.odds.ratio.for.adverse.outcomes.was.not.significantly.different.from.unity.for.any.gener-alized.plastic.work.category.(heated.plastics,.thermoplastics,.thermosetting.plastics)..There.were.18.
cases.in.which.styrene.exposure.was.determined,.giving.an.odds.ratio.(95%.CI).of.0.8.(0.4.–.1.6)..The.
authors.indicated.that.they.had.not.gotten.information.on.lifestyle.factors.or.social.characteristics,.
and.that.the.combining.of.diverse.perinatal.outcomes.was.a.weakness.of.their.approach..They.also.
indicated.that.the.size.of.their.sample.gave.a.less.than.50%.likelihood.of.identifying.a.2-fold.increase.
in.risk.of.adverse.pregnancy.outcome.associated.with.styrene.exposure.
Strengths/Weaknesses: The.use.of.national.pregnancy/birth.outcome.registries.and.the.use.of.company.
data.to.define.potential.exposure.are.strengths,.as.is.the.evaluation.of.multiple.outcomes..Weaknesses.
include.the.potential.for.selection.bias.by.company.participation,.the.lack.of.individual.exposure.data,.
mixed.exposures,.and.the.small.sample.size..Potential.confounding.factors.were.not.considered.
Utility (Adequacy) for CERHR Evaluation Process: This.study.is.of.limited.utility.in.the.evaluation.
process.
Lemasters et al. (77),.supported.by.the.EPA,.evaluated.birth.weight.in.children.born.to.women.work-ing.in.reinforced.plastics.companies.selected.based.on.type.of.process.and.products.and.number.of.
English-speaking.employees..Of.120.companies.contacted.by.the.authors,.36.agreed.to.participate,.
a ppendix II
and.2177.women.employees.of.these.companies.were.invited.to.be.interviewed..Inclusion.criteria.
included.age.<36.years.at.the.time.of.hiring,.employment.for.at.least.6.months.during.the.7-year.study.
period,.and.a.current.or.previous.marriage..There.were.1535.subjects.who.were.successfully.con-tacted.and.agreed.to.be.interviewed..The.642.non-participants,.most.of.whom.were.not.located.or.had.
no.telephone,.were.less.likely.than.the.participants.to.be.currently.employed.or.white..The.women.
who.were.interviewed.included.1050.women.who.were.considered.exposed.to.styrene.based.on.a.site.
visit.and.inspection.of.processes.and.work.records.by.one.of.the.investigators.(described.in.another.
paper.(20)).and.485.unexposed.individuals..Unexposed.women.were.selected.from.employees.of.the.
plastics.companies.and.other.local.companies.based.on.job.titles.such.as.secretary.or.typist..Because.
of.the.smaller.number.of.unexposed.than.exposed.women,.additional.births.were.included.from.pre-employment.pregnancies.of.women.who.contributed.no.exposed.births..As.a.result.of.information.
obtained.in.the.telephone.interview,.there.were.229.exposed.and.819.unexposed.births..Maternal.
diabetes,.infant.congenital.anomalies,.and.multiple.births.were.excluded,.and.only.one.birth.from.
each.woman.was.selected..
In.a.previously.published.study.on.spontaneous.abortion.(78).reviewed.in.Section.4.1,.exposure.was.
considered.high.if.the.individual.worked.in.open.molding.with.direct.styrene.contact.(weighted.mean.
exposure.52.ppm).and.low.if.involved.in.other.open.molding.work.or.in.press.molding.(weighted.
mean.exposure.13.ppm)..The.exposures.were.estimated.from.historically.collected.industrial.hygiene.
data..In.the.current.report,.low.exposure.was.considered.<30.ppm.and.high.exposure.was.≥ 30.ppm.in.
any.month.of.pregnancy..A.subset.of.50.women.who.worked.in.the.highest.styrene-exposed.jobs.was.
considered.in.an.additional.analysis..Styrene.exposures.in.these.women.averaged.82.ppm..
Telephone. interviews.were. conducted.by. professional.interviewers..Questions.sought.information.
on.occupational.and.reproductive.history.as.well.as.general.health.history.and.exposure.to.radia-tion,.medication,.cigarettes,.and.alcohol..Reproductive.histories.were.obtained.before.information.
on.exposures..Birth.weight.was.obtained.solely.from.the.telephone.questionnaire..The.reliability.of.
maternal.reporting.was.checked.by.re-asking.the.birth.weight.6.months.later.in.129.randomly.selected.
participants..Reliability.was.described.as.“good”.based.on.86%.agreement.within.1/2.pound..
Results. were. analyzed. using. multiple. regression.. Exposure. was. incorporated. in. the. analysis. as. a.
categorical.variable.(none,.low,.high).and.by.multiplying.mean.exposure.level.and.duration.of.exposure.
during. pregnancy. to. produce. three. categories. (cut-offs. not. given).. Month-. and. trimester-specific.
versions.of.this.cumulative.exposure.index.were.also.considered.in.the.regression..Gestational.age.
and.weight-for-gestational.age.were.also.considered..Results.are.shown.in.Table.24..
Table 24. Birth Weights in Pregnancies Exposed and Unexposed Occupationally to Styrene
Parameter Styrene exposure category
None (n = 819) Low (n = 154) High (n = 75) Birth.weight,.g.(mean.±.SD) 3298.±.595 3284.±.565 3253.±.594
Infants.<.2501.g,.n.(%) 67.(8.2) 13.(8.4) 3.(4.0)
From.Lemasters.et.al. (77)
a ppendix II
There.was.no.statistically.significant.effect.of.styrene.exposure.on.birth.weight.or.proportion.of.low.
birth-weight.babies..When.the.50.pregnancies.with.the.highest.exposures.were.considered.separately,.
there.was.a.4%.decrease.in.mean.birth.weight.(95%.CI.7.7%.to.+0.6%;.P=0.08)..The.authors.concluded.
that.this.effect.was.comparable.to.that.of.cigarette.smoking..They.cautioned,.however,.that.the.women.
who.were.the.most.highly.exposed.to.styrene.were.also.exposed.to.other.occupational.chemicals..In.
addition,.they.noted.that.exposure.estimates.were.based.on.historically.collected.industrial.hygiene.
data.and.were.not.specific.to.the.individual.pregnancy.
Strengths/Weaknesses: The.use.of.work.records.to.assess.individual.exposures.and.the.adjustment.
for.multiple.confounding.factors.are.strengths.of.this.study..Weaknesses.include.potential.selection.
bias.by.company.and.worker.participation,.the.small.sample.in.the.highest.exposure.category,.and.
potential.confounding.by.other.workplace.exposures..In.addition,.the.individual.exposure.assessments.
were.incomplete.
Utility (Adequacy) for CERHR Evaluation Process: This.study.is.of.moderate.utility.in.the.evaluation.
process.
3.2 Experimental Animal Data