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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cutaneous. injecti<strong>on</strong>. 20 . vom. Saal. et al. (226).<br />
reported. a. ~19%. decrease. in. testicular. daily.<br />
sperm.producti<strong>on</strong>.in.adult.male.mice.exposed.<br />
to.bisphenol.A.as.fetuses.via.maternal.dosing.<br />
with. 0.02. mg/kg. bw/day. (higher. dose. levels.<br />
were.not.tested)..Toyama.et al. (227).observed.<br />
increased.incidences.of.several.measures.of.<br />
abnormal.sperm.morphology.(40.–.80%.compared.to..0.17.mg/kg.or.rats.treated.with.>.0.33.mg/kg.by.<br />
subcutaneous.injecti<strong>on</strong>. 21 .of.bisphenol.A.every.<br />
o<strong>the</strong>r.day.during.postnatal.days.2.to.12.<br />
However,.a.number.of.larger.studies.have.not.<br />
reported.effects.<strong>on</strong>.sperm.parameters.following.<br />
exposure.during.development.at.“high”.or.“low”.<br />
dose.levels.(0.0002.–.600.mg/kg.bw/day).(41,<br />
107, 199 – 201, 228).<br />
Exposure during adulthood <strong>on</strong>ly<br />
Several.studies.have.reported.effects.<strong>on</strong>.sperm.<br />
parameters.in.mice.or.rats.exposed.to.“low”.<br />
doses.of.bisphenol.A.<strong>on</strong>ly.during.adulthood..In.<br />
rats,.<strong>the</strong>se.effects.are.reported.following.oral.<br />
dosing.of.0.02.–.200.mg/kg.bw/day.for.six.days.<br />
(~24.–.32%.decreased.daily.sperm.producti<strong>on</strong>.<br />
per. gram. tissue). (229),. 0.0002.–.0.02. mg/kg.<br />
bw/day.for.45.days.(~23–41%.decrease.in.epididymal.sperm.motility;.~18.–.27%.decrease.in.<br />
epidiymal.sperm.count.at.0.002.–.0.02.mg/kg.<br />
20 .Talsness. et al. (217). reported. effects. <strong>on</strong>. sperm.<br />
quantity. in. rats. exposed. during. gestati<strong>on</strong>. to. 0.1.<br />
<strong>and</strong>.50.mg/kg.bw/day.but.this.study.is.not.included.in.<strong>the</strong>.discussi<strong>on</strong>.because.(1).reported.effects.<br />
included.an.increase.in.sperm.number.which.was.<br />
opposite.<strong>the</strong>.effect.observed.in.<strong>the</strong>.positive.c<strong>on</strong>trol.<br />
group,.<strong>and</strong>.(2).effects.<strong>on</strong>.daily.sperm.producti<strong>on</strong>.<br />
appeared.inc<strong>on</strong>sistent.over.time.<strong>and</strong>.across.dose.<br />
21 Administered.doses.were.≥.0.001.mg/pup.in.<strong>the</strong>.<br />
mouse.<strong>and</strong>.≥.0.01.mg/pup.in.<strong>the</strong>.rat..These.doses.<br />
are. approximately. equal. to. 0.17. to. 0.5. mg/kg.<br />
in. <strong>the</strong>. mouse. <strong>and</strong>. 0.33.–.1.33. mg/kg. in. <strong>the</strong>. rat.<br />
assuming.that.body.weight.between.postnatal.<br />
days.2.to.12.ranges.from.0.002.to.0.006.kg.in.<br />
<strong>the</strong>.mouse.<strong>and</strong>.0.0075.<strong>and</strong>.0.03.kg.in.<strong>the</strong>.rat.<br />
32<br />
bw/day).(230),.<strong>and</strong>.0.0002.–.0.02.mg/kg.bw/day.<br />
for.60.days.(~30–45%.decrease.in.epididymal.<br />
sperm.motility;.~12.–.40%.decrease.in.epidiymal.sperm.count.at.0.002.–.0.02.mg/kg.bw/<br />
day).(231)..In.adult.mice,.“low”.dose.effects.<strong>on</strong>.<br />
sperm.are.observed.at.oral.doses.of.0.025.–.0.1.<br />
mg/kg.bw/day.for.30.days.(~16.–.37%.decrease.<br />
in. weight. corrected. testicular. or. epididymal.<br />
sperm.count).(108).<strong>and</strong>.subcutaneous.dosing.<br />
with. 0.02. <strong>and</strong>. 0.2. mg/kg. bw/day. for. 6. days.<br />
(abnormal.sperm.morphology).(232)..<br />
O<strong>the</strong>r.larger.studies.have.not.reported.effects.<br />
in.adult.animals.at.<strong>the</strong>se.doses..The.2-generati<strong>on</strong>.mouse.study.c<strong>on</strong>ducted.by.Tyl.et<br />
al. (41).<br />
reported.a.15%.decrease.in.epididymal.sperm.<br />
c<strong>on</strong>centrati<strong>on</strong>.in.F0.generati<strong>on</strong>.animals.at.<strong>the</strong>.<br />
highest.dose.tested.of.600.mg/kg.bw/day.but.<br />
not.at.lower.doses.of.0.003.to.50.mg/kg.bw/day..<br />
Ema.et al. (107).also.did.not.detect.an.effect.<br />
<strong>on</strong>.sperm.measures.in.<strong>the</strong>.F0.generati<strong>on</strong>.in.a.rat.<br />
multigenerati<strong>on</strong>.study.at.oral.doses.of.0.0002.to.<br />
0.2.mg/kg.bw/day..The.finding.by.Sakaue.et al.<br />
(229).of.a.~24.–.32%.decrease.in.sperm.producti<strong>on</strong>.in.adult.Sprague-Dawley.rats.(obtained.from.<br />
CLEA.Japan,.Inc.).was.not.reproduced.in.a.study.<br />
using.larger.sample.sizes.of.Sprague-Dawley.rats.<br />
obtained.from.Charles.River.UK.(233)..<br />
The.basis.for.<strong>the</strong>.inc<strong>on</strong>sistent.findings.is.not.<br />
clear..One.proposed.explanati<strong>on</strong>.is.that.rodent.<br />
species,.strains,.<strong>and</strong>.breeding.stocks.differ.in.<br />
<strong>the</strong>ir.resp<strong>on</strong>siveness.to.estrogens.(59)..Species.<br />
<strong>and</strong>.strain.differences.in.resp<strong>on</strong>se.to.estrogen.<br />
have. been. documented,. but. animal. model.<br />
sensitivity.varies.depending.up<strong>on</strong>.<strong>the</strong>.specific.<br />
trait.being.assessed.[discussed.in.(2, 59, 200)]..<br />
Studies.that.include.sperm.assessment.in.<strong>the</strong>.<br />
bisphenol.A.literature.are.too.varied.in.terms.of.<br />
periods.of.dosing,.use.of.positive.c<strong>on</strong>trol,.e.g.,.<br />
n<strong>on</strong>e.used,.ethinyl.estradiol,.or.17β-estradiol,.<br />
<strong>and</strong>.o<strong>the</strong>r.aspects.of.experimental.c<strong>on</strong>duct.to.<br />
determine. if. differences. in. sensitivity. of. <strong>the</strong>.<br />
animal.model.can.account.for.<strong>the</strong>.inc<strong>on</strong>sistent.<br />
findings.<strong>on</strong>.sperm.quantity.<strong>and</strong>.quality..<br />
nTp brief
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