Monograph on the Potential Human Reproductive and ... - OEHHA
Monograph on the Potential Human Reproductive and ... - OEHHA
Monograph on the Potential Human Reproductive and ... - OEHHA
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c<strong>on</strong>centrati<strong>on</strong>s.from.maternal,.fetal,.<strong>and</strong>.ne<strong>on</strong>atal.tissues.or.fluids.(i.e.,.placenta,.amniotic.fluid,.<br />
breast.milk,.urine,.serum)..These.data.would.<br />
provide.fur<strong>the</strong>r.insight.into.<strong>the</strong>.roles.of.metabolism.<strong>and</strong>.exposure.route.<strong>on</strong>.internal.dose.<strong>and</strong>.<br />
provide.a.firmer.foundati<strong>on</strong>.for.extrapolati<strong>on</strong>s.of.<br />
risks.to.humans.from.<strong>the</strong>.wealth.of.animal.studies.available..Available.data.dem<strong>on</strong>strate.that.a.large.fracti<strong>on</strong>.of.children.<strong>and</strong>.adults.have.detectable.levels.of.bisphenol.A,.or.its.metabolites,.<br />
in.<strong>the</strong>ir.urine..Duplicate.diet.studies.to.identify.<br />
in. detail. <strong>the</strong>. sources. <strong>and</strong>. routes. of. exposure.<br />
of.bisphenol.A.would.be.useful..For.example,.<br />
while.research.suggests.diet.is.<strong>the</strong>.major.source.<br />
of.bisphenol.A.for.infants.<strong>and</strong>.young.children.<br />
in.<strong>the</strong>.United.States,.<strong>the</strong>.detailed.analysis.of.<br />
bisphenol.A.levels.has.primarily.focused.<strong>on</strong>.<br />
polycarb<strong>on</strong>ate.baby.bottle.leachates.<strong>and</strong>.canned.<br />
food..The.c<strong>on</strong>tributi<strong>on</strong>s.of.n<strong>on</strong>-canned.food.<strong>and</strong>.<br />
drinking.water.routes.of.exposure.for.youth.<strong>and</strong>.<br />
adults.not.occupati<strong>on</strong>ally-exposed.to.bisphenol.<br />
A.remain.unknown.<strong>and</strong>.in.need.of.fur<strong>the</strong>r.study..<br />
Levels.of.bisphenol.A.in.residential.drinking.<br />
water.wells.<strong>and</strong>.community.water.sources.have.<br />
not.been.systematically.studied..Also.unknown.<br />
is.<strong>the</strong>.impact.of.l<strong>and</strong>fill.leachates.<strong>on</strong>.levels.of.<br />
bisphenol.A.in.U.S..drinking.well.waters.<strong>and</strong>.<br />
whe<strong>the</strong>r.chlorinated.c<strong>on</strong>geners.of.bisphenol.A.<br />
are.found.in.municipal.water.supplies..<br />
More.research.is.needed.to.characterize.<strong>the</strong>.toxicokinetics.of.bisphenol.A.in.developing.animals.<br />
under.exposure.scenarios.that.better.mimic.<strong>the</strong>.<br />
low-level. chr<strong>on</strong>ic. exposures. experienced. by.<br />
humans..Currently,.<strong>on</strong>ly.single.or.“acute”.dosing.<br />
kinetic. studies. in. laboratory. animals. are.<br />
44<br />
available.for.predicting.<strong>the</strong>.metabolism.<strong>and</strong>.fate.<br />
of.bisphenol.A.following.l<strong>on</strong>g-term,.daily.exposure,.or.for.comparing.apparent.differences.in.<strong>the</strong>.metabolism.<strong>and</strong>.fate.of.bisphenol.A.in.laboratory.rodents.<strong>and</strong>.humans..Repeated.administrati<strong>on</strong>.of.many.compounds.has.been.shown.to.<br />
alter.<strong>the</strong>.capacity.of.<strong>the</strong>.animal.to.metabolize.<strong>and</strong>.<br />
excrete.<strong>the</strong>.compound..Fur<strong>the</strong>r.characterizati<strong>on</strong>.<br />
of.<strong>the</strong>.ability.of.repeated.exposures.to.bisphenol.<br />
A.to.change.rates.<strong>and</strong>.extent.of.metabolism.<strong>and</strong>.<br />
excreti<strong>on</strong>.in.laboratory.animals.<strong>and</strong>.humans.is.<br />
a.critical.research.need..<br />
In.additi<strong>on</strong>,.it.is.clear.that.<strong>the</strong>re.are.differences.<br />
in.<strong>the</strong>.pharmacokinetics.of.bisphenol.A,.particularly.between.rats.<strong>and</strong>.humans,.which.complicate.using.<strong>the</strong>.rat.data.to.interpret.<strong>the</strong>.human.<br />
biom<strong>on</strong>itoring.data..For.example,.<strong>the</strong>.excreti<strong>on</strong>.<br />
profiles. of. bisphenol.A. differ. in. rodents. <strong>and</strong>.<br />
humans..In.humans,.<strong>the</strong>.major.route.of.eliminati<strong>on</strong>.is.via.<strong>the</strong>.urine.in.<strong>the</strong>.form.of.bisphenol.<br />
A. glucur<strong>on</strong>ide. (261).. In. c<strong>on</strong>trast,. <strong>the</strong>. major.<br />
eliminati<strong>on</strong>.routes.in.rodents.are.as.bisphenol.<br />
A.in.<strong>the</strong>.feces,.as.bisphenol.A.glucur<strong>on</strong>ide.in.<strong>the</strong>.<br />
bile,.<strong>and</strong>.to.a.lesser.extent,.in.<strong>the</strong>.urine.[reviewed.<br />
in.(2)]..Also,.in.rats.bisphenol.A.glucur<strong>on</strong>ide.<br />
can.remain.in.<strong>the</strong>.bile.<strong>and</strong>.be.recirculated.back.<br />
to.<strong>the</strong>.liver.(“enterohepatic.circulati<strong>on</strong>”)..To.<br />
address.<strong>the</strong>se.uncertainties.<strong>the</strong>.NTP.is.pursuing.<br />
studies.of.absorpti<strong>on</strong>,.distributi<strong>on</strong>,.metabolism,.<br />
<strong>and</strong>.excreti<strong>on</strong>.in.experimental.animals.(rodents.<br />
<strong>and</strong>.n<strong>on</strong>.human.primates).as.well.as.<strong>the</strong>.kinetics.<br />
associated.with.<strong>the</strong>se.processes,.following.exposures.to.bisphenol.A.from.<strong>the</strong>.perinatal.period.<br />
through.adulthood,.over.a.wide.range.of.doses,.<br />
by.multiple.routes.of.administrati<strong>on</strong>.<br />
nTp brief
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