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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<strong>and</strong>.cystic.endometrial.hyperplasia.were.statistically.significant.in.<strong>the</strong>.100.µg/kg.dose.group.but.<br />
not.at.1000.µg/kg..N<strong>on</strong>-statistically.significant.<br />
increases.in.<strong>the</strong>.incidence.of.a.variety.of.o<strong>the</strong>r.<br />
ovarian. <strong>and</strong>. uterine. proliferative. lesi<strong>on</strong>s. <strong>and</strong>.<br />
cysts.were.also.reported..Replicati<strong>on</strong>.of.<strong>the</strong>se.<br />
findings.<strong>and</strong>.fur<strong>the</strong>r.study.of.<strong>the</strong>.linkage.of.early.<br />
<strong>and</strong>.late.occurring.events.will.be.important.in.<br />
establishing.a.better.underst<strong>and</strong>ing.of.any.l<strong>on</strong>gterm.c<strong>on</strong>sequences.of.exposures.of.<strong>the</strong>.developing.organism.to.bisphenol.A.<br />
As.menti<strong>on</strong>ed.earlier,.NTP.Briefs.are.not.meant.<br />
to.serve.as.comprehensive.reviews.of.<strong>the</strong>.scientific.literature..Only.key.study.findings.<strong>and</strong>.issues.that.relate.to.NTP.c<strong>on</strong>clusi<strong>on</strong>s.<strong>on</strong>.c<strong>on</strong>cerns.for.potential.reproductive.<strong>and</strong>.developmental.health.effects.in.humans.are.typically.<br />
presented..However,.three.reported.“low”.dose.<br />
health.effects.(obesity,.decreased.sperm.count.<br />
or.quality,.<strong>and</strong>.abnormalities.of.meiosis).that.<br />
ultimately.had.less.impact.in.determining.<strong>the</strong>.<br />
NTP’s.c<strong>on</strong>clusi<strong>on</strong>s.are.briefly.discussed.below.<br />
in.order.to.illustrate.<strong>the</strong>.interpretive.challenges.<br />
associated.with.this.literature..Two.examples.<br />
of.such.effects,.obesity.<strong>and</strong>.impacts.<strong>on</strong>.sperm,.<br />
dem<strong>on</strong>strate.findings.that.are.not.reported.c<strong>on</strong>sistently.enough.to.be.c<strong>on</strong>sidered.reproducible..<br />
The.third.example.relates.to.abnormalities.of.<br />
meiosis.<strong>and</strong>.is.presented.to.dem<strong>on</strong>strate.that.<br />
effects.predicted.from.in vitro studies.are.not.<br />
necessarily.observed.in.<strong>the</strong>.in vivo.studies..<br />
Obesity<br />
There.is.currently.insufficient.evidence.to.c<strong>on</strong>clude.that.bisphenol.A.exposure.during.development.predisposes.laboratory.animals.to.develop.<br />
obesity.or.metabolic.diseases.such.as.diabetes,.<br />
later.in.life..Obesity.<strong>and</strong>.metabolic.disrupti<strong>on</strong>.<br />
have.become.a.research.focus.for.bisphenol.A.<br />
based.<strong>on</strong>.several.reports.of.increased.postnatal.<br />
growth.following.“low”.dose.exposure.during.<br />
development.<strong>and</strong>.several.in vitro <strong>and</strong>.in vivo.<br />
studies.that.report.effects.related.to.altered.carbohydrate.<strong>and</strong>.lipid.regulati<strong>on</strong>.<br />
30<br />
The.NTP.c<strong>on</strong>curs.with.<strong>the</strong>.CERHR.Expert.Panel.<br />
<strong>on</strong>.Bisphenol.A.that.<strong>the</strong>.effects.of.bisphenol.A.<br />
<strong>on</strong>.body.weight.at.“low”.doses.are.inc<strong>on</strong>sistent.<br />
(2)..A.number.of.studies.in.rats.<strong>and</strong>.mice.report.<br />
increases.in.postnatal.growth.following.developmental.exposure.to.bisphenol.A.at.oral.doses.<br />
of.0.0024.–.1.2.mg/kg.bw/day. (55, 155, 173,<br />
215).or.a.subcutaneous.dose.of.0.5.mg/kg.bw/<br />
day.(179)..O<strong>the</strong>r.“low”.dose.(≤.5.mg/kg.bw/day).<br />
studies.in.rats.<strong>and</strong>.mice.have.ei<strong>the</strong>r.not.detected.<br />
any.significant.effect.<strong>on</strong>.body.weight.(43, 48,<br />
50, 52, 107, 116, 122, 200, 214, 216).or.reported.<br />
growth. reducti<strong>on</strong>s. (37, 115, 146, 189, 217)..<br />
Differences.in.study.outcomes.cannot.easily.be.<br />
attributed.to.<strong>the</strong>.use.of.a.potentially.insensitive.<br />
rodent.model.or.experimental.protocol.because.<br />
several.studies.that.did.not.detect.any.significant.<br />
difference.in.body.weight.reported.o<strong>the</strong>r.effects.<br />
at.“low”.dose.levels.(48, 50, 52, 122, 217)..The.<br />
bases.for.<strong>the</strong>.inc<strong>on</strong>sistent.findings.are.unclear,.<br />
but.may.relate.to.factors.such.as.diet.<strong>and</strong>.differences.in.experimental.design.or.analysis.<br />
The.data.are.currently.too.limited.to.c<strong>on</strong>clude.<br />
that. developmental. exposure. to. bisphenol.A.<br />
causes. diabetes. or. o<strong>the</strong>r. metabolic. disorders.<br />
later.in.life..Two.studies.in.laboratory.animals.<br />
have.assessed.endpoints.related.to.carbohydrate.<br />
or.lipid.regulati<strong>on</strong>..In.adult.male.mice,.a.single.<br />
subcutaneous.dose.of.0.010.or.0.100.mg/kg.bw/<br />
day.bisphenol.A.caused.decreased.blood.glucose.<br />
<strong>and</strong>.increased.plasma.insulin.(218)..Additi<strong>on</strong>ally,.increased.pancreatic.insulin.c<strong>on</strong>tent.<strong>and</strong>.<br />
insulin.resistance.were.reported.at.0.100.mg/kg.<br />
bw/day.(administered.orally.or.by.subcutaneous.<br />
injecti<strong>on</strong>).after.a.slightly.l<strong>on</strong>ger.period.of.dosing.<br />
(4-.days).(218)..A.recent.study.by.Miyawaki.et<br />
al. (215).assessed.a.variety.of.endpoints.related.<br />
to.carbohydrate.<strong>and</strong>.lipid.regulati<strong>on</strong>.in.1-m<strong>on</strong>th.<br />
old.mice.that.were.exposed.through.maternal.<br />
treatment.during.gestati<strong>on</strong>.<strong>and</strong>.lactati<strong>on</strong>.with.<br />
0.001.or.0.010.µg/ml.bisphenol.A.in.drinking.<br />
water.(~0.26.<strong>and</strong>.2.42.mg/kg.bw/during.gestati<strong>on</strong>)..Endpoints.included.body.weight,.adipose.<br />
tissue.weight,.<strong>and</strong>.blood.c<strong>on</strong>centrati<strong>on</strong>s.of.leptin,.<br />
nTp brief
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