Monograph on the Potential Human Reproductive and ... - OEHHA
Monograph on the Potential Human Reproductive and ... - OEHHA
Monograph on the Potential Human Reproductive and ... - OEHHA
You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
nTp brief<br />
higher,.as.much.as.~3000.times.greater,.than.<br />
<strong>the</strong>.estimated.peak.c<strong>on</strong>centrati<strong>on</strong>s.in.laboratory.<br />
animals.where.biological.changes.are.observed.<br />
is.a.point.of.intense.scientific.c<strong>on</strong>troversy..In.<br />
brief,. although. <strong>the</strong>. <strong>the</strong>oretical. plausibility. of.<br />
receptor-mediated.effects.at.“low”.doses.has.<br />
been. described. (259, 260),. many. scientists.<br />
expect.that.a.compound.with.a.significant.degree.<br />
of.biological.“activity”.at.low.doses.would.show.<br />
more.profound.impacts.<strong>on</strong>.overall.toxicity.at.<br />
lower.doses.than.that.observed.for.bisphenol.A..<br />
With.bisphenol.A,.“low”.dose.developmental.<br />
effects.can.be.observed.at.0.0024.to.0.010.mg/kg.<br />
bw/day.but.indicati<strong>on</strong>s.of.severe.developmental.<br />
toxicity.in.rats.<strong>and</strong>.mice,.i.e.,.fetal.or.ne<strong>on</strong>atal.<br />
death.are.not.observed.except.when.doses.are.<br />
used.that.are.50,000.–.200,000-.times.higher.at.<br />
≥.500.mg/kg.bw/day.(36 – 40).<br />
Estimated daily intake based <strong>on</strong> back<br />
calculating from blood <strong>and</strong> urine<br />
Based.<strong>on</strong>.parameters.derived.from.laboratory.<br />
animal.studies,.estimated.daily.intakes.based.<br />
<strong>on</strong>. back. calculati<strong>on</strong>s. from. free. bisphenol. A.<br />
measured. in. human. blood. are. much. greater.<br />
(~500.µg/kg.–.1.54.mg/kg.bw/day.for.a.65.kg.<br />
human).(3, 249).than.estimates.based.<strong>on</strong>.any.<br />
o<strong>the</strong>r.approach..In.c<strong>on</strong>trast,.<strong>the</strong>re.is.a.degree.of.<br />
c<strong>on</strong>cordance.in.estimates.of.daily.intake.based.<br />
<strong>on</strong>.o<strong>the</strong>r.approaches..For.<strong>the</strong>se.reas<strong>on</strong>s,.<strong>the</strong>.NTP.<br />
has. less. c<strong>on</strong>fidence. in. daily. intake. estimates.<br />
based.<strong>on</strong>.blood.biom<strong>on</strong>itoring.data.compared.<br />
to.o<strong>the</strong>r.estimates,.particularly.those.based.<strong>on</strong>.<br />
urine.biom<strong>on</strong>itoring.data.<br />
Estimates.of.daily.bisphenol.A.intake.in.adults.<br />
based.<strong>on</strong>.aggregating.routes.of.exposure.fall.<br />
within.<strong>the</strong>.range.of.0.008.–.1.5.µg/kg.bw/day.<br />
(25, 31).(Table.1).with.most.estimates.falling.<br />
within.a.range.that.spans.<strong>on</strong>e.order.of.magnitude,.<br />
0.183.–.1.5. µg/kg. bw/day. (24 – 27, 30)..<br />
Daily.intakes.estimated.from.<strong>the</strong>.CDC.NHANES.<br />
biom<strong>on</strong>itoring.data.are.similar.<strong>and</strong>.range.from.<br />
0.289.–.0.233. µg/kg. bw/day. for. adults. aged.<br />
20.–.60+.years.at.<strong>the</strong>.95th.percentile.(35)..The.<br />
43<br />
NTP.c<strong>on</strong>sidered.<strong>the</strong>.possibility.that.<strong>the</strong>.assumpti<strong>on</strong>s.used.to.derive.<strong>the</strong>se.intakes.could.underestimate.human.exposures..For.estimates.based.<strong>on</strong>.aggregating.sources.of.exposure,.<strong>on</strong>e.c<strong>on</strong>cern.is.that.too.much.emphasis.has.been.placed.<br />
<strong>on</strong>.diet.as.<strong>the</strong>.predominant.route.of.exposure..<br />
For.estimates.based.<strong>on</strong>.<strong>the</strong>.total.c<strong>on</strong>centrati<strong>on</strong>.<br />
of.bisphenol.A.in.urine,.it.is.assumed.that.<strong>the</strong>.<br />
daily.excreti<strong>on</strong>.of.bisphenol.A.is.a.reas<strong>on</strong>able.<br />
surrogate.for.daily.intake..Deviati<strong>on</strong>s.from.<strong>the</strong>.<br />
assumpti<strong>on</strong>s.used.to.derive.current.estimates.<br />
could.increase.<strong>the</strong>.daily.intake.estimates,.but.<br />
still.result.in.estimated.intakes.in.<strong>the</strong>.very.low.<br />
µg/kg.bw/day.range.ra<strong>the</strong>r.than.near.1.mg/kg.<br />
bw/day.as.predicted.from.<strong>the</strong>.blood.biom<strong>on</strong>itoring.data.in.adult.humans.<br />
Data.from.an.intenti<strong>on</strong>al.dosing.study.c<strong>on</strong>ducted.<br />
by.Tsukioka.et al. (250).provides.fur<strong>the</strong>r.support.<br />
for.daily.intakes.of.
Change language