Monograph on the Potential Human Reproductive and ... - OEHHA

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total. cholesterol,. triglycerides,. non-esterified.
fatty.acid.and.glucose..Body.weight.and.total.
cholesterol. were. significantly. increased. in.
female.offspring.in.both.dose.groups.although.
adipose.tissue.weight.and.leptin.levels.were.only.
significantly.increased.in.the.1.µg/ml.treatment.
group..Male.offspring.in.the.high.dose.group.
of.10.µg/ml.were.significantly.heavier.and.had.
increased.adipose.tissue.weight..Leptin.levels.
were.not.associated.with.either.of.these.effects.
in.males..Significantly.increased.triglycerides.
and. non-esterified. fatty. acid. and. decreased.
glucose.were.observed.in.male.offspring.in.the.
low.dose.group.of.1.µg/ml..Although.this.study.
addresses. the. hypothesis. that. developmental.
exposure.to.bisphenol.A.can.affect.carbohydrate.
and.lipid.metabolism.in.postnatal.life,.the.inconsistent.pattern.of.effects.on.serum.lipid.levels,.
leptin,.and.glucose.and.lack.of.control.for.litter.
effects 18 .makes.the.study.on.its.own.insufficient.
to.draw.any.conclusion..
More.research.in.this.area.is.warranted..Several.in
vitro studies.report.effects.of.bisphenol.
A.related.to.carbohydrate.and.lipid.regulation.
including.effects.on.pancreatic.cells.that.govern.
the.release.of.insulin.(β-cells).and.glucagon.(αcells),.altered.differentiation.of.fibroblast.cells.
into.adipocytes,.and.altered.glucose.transport.
in.adipocytes.(219 – 223)..Some.of.the.effects.
on.pancreatic.cells.are.very.rapid,.e.g.,.altered.
frequency.of.glucose-induced.calcium.oscillations.in.α-.and.β-cells,.activation.of.cAMP.
response.element.binding.protein,.and.appear.
to.be.mediated.by.ncmER.(63, 65, 224)..Effects.
mediated. through. the. ncmER. are. of. interest.
because.bisphenol.A.has.been.shown.to.activate.
this.receptor.in vitro at.a.concentration.of.1.nM,.
which.is.similar.to.the.active.concentration.of.
diethylstilbestrol.(63, 65).
18 16.–.25.males.or.females.were.reported.for.each.
treatment. group. however. these. animals. were.
derived.from.only.3.litters.per.treatment.group.
(215).
31
Decreased Sperm Count and Sperm Quality
There.is.currently.insufficient.evidence.to.conclude.that.bisphenol.A.exposure.during.development.or.adulthood.causes.decreased.sperm.count.or.sperm.quality..A.large.number.of.studies.have.addressed.this.issue.but.the.literature.is.
inconsistent.and.not.easily.reconciled.
Exposure during development
There.are.some.indications.that.treatment.with.
“high”.oral.doses.of.bisphenol.A.during.development.or.young.adulthood.can.impact.sperm.
quantity.in.laboratory.rats.(37, 42, 43)..Tan.et al.
(42).reported.that.33%.of.rats.did.not.show.any.
evidence.of.having.a.spermatogenic.cycle.after.
treatment.in.young.adulthood.with.100.mg/kg.
bw/day.of.bisphenol.A..Other.reported.decreases.
in.measures.of.testicular.or.epididymal.sperm.
count.and.sperm.production.were.more.modest.
and.ranged.from.10.to.19%.at.doses.of.50.and.
500.mg/kg.bw/day.(37, 43)..In.addition,.in.the.
three-generation.rat.study.conducted.by.Tyl.et
al. (37),.significant.decreases.in.sperm.parameters.were.only.observed.in.certain.generations.
of. similarly. exposed. males. in. the. high. dose.
group.of.500.mg/kg.bw/day:.~18%.decrease.in.
epididymal.sperm.concentration.in.F1.males,.
~19%.decrease.in.testicular.daily.sperm.production.in.F3.males.and.no.significant.effects.in.the.
F0.or.F2.generations..Testicular.or.epididymal.
histopathology.was.not.detected.in.any.treatment.
group.(37)..Significantly.decreased.sperm.motility.and.an.increased.percentage.of.abnormal.
sperm.was.also.reported.following.“high”.dose.
subcutaneous.injection,.~25.mg/kg.bw/day, 19 .to.
neonatal.mice.in.a.study.conducted.by.Aikawa.et
al. (225)..Again,.these.effects.were.not.associated.with.testicular.histological.alterations.
Effects.on.sperm.parameters.have.been.reported.
at.lower.doses.administered.orally.or.by.sub-
1 Administered.dose.was.0.050.mg/pup..This.is.
approximately.equal.to.25.mg/kg/day.assuming.
that.a.neonatal.mouse.weighs.0.002.kg