Monograph on the Potential Human Reproductive and ... - OEHHA
Monograph on the Potential Human Reproductive and ... - OEHHA
Monograph on the Potential Human Reproductive and ... - OEHHA
Create successful ePaper yourself
Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.
nTp brief<br />
use.of.a.positive.c<strong>on</strong>trol.to.be.a.required.study.<br />
design.comp<strong>on</strong>ent.particularly.in.animal.model.<br />
systems.that.are.well.characterized.regarding.<strong>the</strong>.<br />
background.incidence.of.“effects”.<strong>and</strong>.<strong>the</strong>ir.variability..For.bisphenol.A.studies,.potent.estrogens,.such.as.diethylstilbestrol,.ethinyl.estradiol,.17βestradiol,.<strong>and</strong>.estradiol.benzoate,.are.<strong>the</strong>.most.<br />
comm<strong>on</strong>ly.used.positive.c<strong>on</strong>trol.chemicals.given.<br />
bisphenol.A’s.historical.classificati<strong>on</strong>.as.a.weak.<br />
estrogen..Failure.to.obtain.predicted.resp<strong>on</strong>ses.<br />
with.<strong>the</strong>se.chemicals.is.generally.interpreted.as.a.<br />
“failed”.experiment,.perhaps.reflecting.<strong>the</strong>.selecti<strong>on</strong>.of.a.relatively.insensitive.animal.or.experimental.model.or.insufficient.chemical.challenge..<br />
Studies.where.no.resp<strong>on</strong>ses.are.observed.in.<strong>the</strong>.<br />
positive.c<strong>on</strong>trol.group.have.generally.c<strong>on</strong>tributed.less.weight.to.evaluati<strong>on</strong>s.of.bisphenol.A.<br />
(2, 60)..The.significance.of.a.“failed”.positive.<br />
c<strong>on</strong>trol.for.bisphenol.A.varies.from.endpoint.<br />
to.endpoint.<strong>and</strong>.reflected.more.negatively.<strong>on</strong>.a.<br />
study.in.<strong>the</strong>.NTP.evaluati<strong>on</strong>.when.<strong>the</strong>.predicted.<br />
effect.<strong>on</strong>.reproductive.tissue.or.functi<strong>on</strong>.was.not.<br />
observed.at.dose.levels.that.should.be.sufficiently.<br />
high.to.produce.an.effect..In.additi<strong>on</strong>,.although.<br />
potent.estrogens.are.used.as.positive.c<strong>on</strong>trols.for.<br />
bisphenol.A,.as.discussed.earlier.an.increasing.<br />
number.of.molecular.or.cell-based.studies.suggest.that.interpreting.<strong>the</strong>.toxicological.effects.of.<br />
bisphenol.A.solely.within.<strong>the</strong>.c<strong>on</strong>text.of.<strong>the</strong>ir.<br />
c<strong>on</strong>sistency.with.a.classic.estrogenic.mechanism.<br />
of.acti<strong>on</strong>.is.overly.simplistic..<br />
HumaN STudIeS<br />
Only.a.very.small.number.of.studies.have.looked.<br />
at.associati<strong>on</strong>s.between.bisphenol.A.exposure.<br />
<strong>and</strong>.disorders.of.reproducti<strong>on</strong>.or.developmental.<br />
effects.in.humans.[(12, 99, 100),.studies.prior.to.<br />
mid-2007.reviewed.in.(2, 3)]..The.human.studies.<br />
have.looked.at.<strong>the</strong>.relati<strong>on</strong>ship.between.urine.or.<br />
blood.c<strong>on</strong>centrati<strong>on</strong>s.of.total.or.free.bisphenol.A.<br />
<strong>and</strong>.a.variety.of.health.measures.including.levels.<br />
of.certain.horm<strong>on</strong>es.that.help.regulate.reproducti<strong>on</strong>.<br />
(32, 101),. markers. of. DNA. damage.<br />
(102),.miscarriage.(103),.chromosomal.defects.<br />
in.fetuses.(104),.fertility.<strong>and</strong>.obesity.in.women.<br />
15<br />
(16, 99, 105),.effects.<strong>on</strong>.<strong>the</strong>.tissue.that.lines.<strong>the</strong>.<br />
uterus.(“endometrium”).(99, 106),.polycystic.<br />
ovary.syndrome.(101, 105),.<strong>and</strong>.birth.outcomes.<br />
<strong>and</strong>.length.of.gestati<strong>on</strong>.(12, 100)..<br />
In.<strong>the</strong>se.studies,.<strong>the</strong>re.are.reports.of.associati<strong>on</strong>s.<br />
between.higher.urine.or.blood.c<strong>on</strong>centrati<strong>on</strong>s.of.<br />
bisphenol.A.<strong>and</strong>.lower.levels.of.follicle.–.stimulating.<br />
horm<strong>on</strong>e. in. occupati<strong>on</strong>ally. exposed.<br />
men.(32),.higher.levels.of.testoster<strong>on</strong>e.in.men.<br />
<strong>and</strong>.women.(101, 105),.polycystic.ovary.syndrome.(101,<br />
105),.recurrent.miscarriage.(103),.<br />
<strong>and</strong>.chromosomal.defects.in.fetuses.(104)..In.<br />
additi<strong>on</strong>,.<strong>on</strong>e.study.reported.that.patients.with.<br />
endometrial.cancer.<strong>and</strong>.complex.endometrial.<br />
hyperplasia.had.lower.blood.levels.of.bisphenol.<br />
A.than.healthy.women.<strong>and</strong>.women.with.simple.<br />
endometrial. hyperplasia. (106).. Bisphenol.A.<br />
was.not.associated.with.decreased.birth.weight.<br />
or. several. o<strong>the</strong>r. measures. of. birth. outcome.<br />
in.two.recent.studies.(12, 100)..Drawing.firm.<br />
c<strong>on</strong>clusi<strong>on</strong>s. about. potential. reproductive. or.<br />
developmental.effects.of.bisphenol.A.in.humans.<br />
from.<strong>the</strong>se.studies.is.difficult.because.of.factors.<br />
such.as.small.sample.size,.cross-secti<strong>on</strong>al.design,.<br />
lack.of.large.variati<strong>on</strong>s.in.exposure,.or.lack.of.<br />
adjustment.for.potential.c<strong>on</strong>founders..However,.<br />
<strong>the</strong>.CERHR.Expert.Panel.<strong>on</strong>.Bisphenol.A.(2)<br />
c<strong>on</strong>cluded.that.several.studies.collectively.suggest.horm<strong>on</strong>al.effects.of.bisphenol.A.exposure.<br />
(32, 101, 105).including.<strong>on</strong>e.in.occupati<strong>on</strong>ally.<br />
exposed.male.workers.likely.exposed.through.<br />
multiple.routes.including.inhalati<strong>on</strong>.(32)..<br />
The.NTP.c<strong>on</strong>curs.with.findings.of.<strong>the</strong>.recent.<br />
evaluati<strong>on</strong>s.(2, 3).that.while.<strong>the</strong>se.studies.may.<br />
suggest.directi<strong>on</strong>s.for.future.research,.<strong>the</strong>re.is.<br />
currently.insufficient.evidence.to.determine.if.<br />
bisphenol.A.causes.or.does.not.cause.reproductive.<br />
toxicity. in. exposed. adults..There. is. also.<br />
insufficient.evidence.from.studies.in.humans.to.<br />
determine.if.bisphenol.A.does.or.does.not.cause.<br />
developmental.toxicity.when.exposure.occurs.<br />
prenatally.or.during.infancy.<strong>and</strong>.childhood.
Change language