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

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nTp brief exPoSuRe ComPaRISoNS baSed oN blood CoNCeNTRaTIoNS of fRee bISPHeNol a No.studies.in.laboratory.animals.have.measured. circulating. levels. of. free. bisphenol.A. in. the. blood.following.a.dosing.schedule.that.mimics. human.exposures,.i.e.,.long-term.dietary.lowdose.exposure.occurring.numerous.times.during.the.day..However,.a.number.of.studies.have. detected.quantifiable.levels.of.free.bisphenol.A. in.the.blood.of.adult.rodents.following.a.single. oral.administration.of.bisphenol.A,.typically.at. doses.considered.high.when.compared.to.estimated. human. daily. intakes. (500.–.1,000,000. µg/kg.for.rodents.versus.
nTp ConClusions The.NTP.reached.the.following.conclusions.on. the.possible.effects.of.exposure.to.bisphenol.A. on.human.development.and.reproduction..Note. that.the.possible.levels.of.concern,.from.lowest.to. highest,.are.negligible.concern,.minimal.concern,. some.concern,.concern,.and.serious.concern. The NTP has some concern for effects on the brain, behavior, and prostate gland in fetuses, infants, and children at current human exposures to bisphenol A. The.NTP.concurs.with.the.conclusion.of.the. CERHR.Expert.Panel.on.Bisphenol.A.that.the. scientific. evidence. supports. a. conclusion. of. some concern.for.exposures.in.fetuses,.infants,. and.children.based.on.a.number.of.laboratory. animal.studies.reporting.that.“low”.level.exposure. to. bisphenol.A. during. development. can. cause.changes.in.the.brain.and.behavior..In.addition,.the.NTP.has.some concern.for.exposures. to. these. populations. based. on. effects. on. the. prostate.gland.observed.in.laboratory.animals.. This.level.of.concern.for.effects.on.the.prostate. gland.is.higher.than.that.expressed.by.the.Expert. Panel.and.is.based.primarily.on.new.supportive. data.related.to.(1).the.interpretation.of.studies. that.use.a.non-oral.route.of.administration.in. neonatal.rodents,.and.(2).an.additional.publication.reporting.subtle.cellular.changes.in.the. prostate.gland..These.reports.were.not.published. when.the.Expert.Panel.completed.its.deliberations..These.studies.in.laboratory.animals.provide.only.limited.evidence.for.adverse.effects. on.development.and.more.research.is.needed.to. better.understand.their.implications.for.human. health..However,.because.these.effects.in.animals. occur.at.bisphenol.A.exposure.levels.similar.to. those.experienced.by.humans,.the.possibility. that.bisphenol.A.may.alter.human.development. cannot.be.dismissed. 38 The NTP has minimal concern for effects on the mammary gland and an earlier age for puberty for females in fetuses, infants, and children at current human exposures to bisphenol A. The.NTP.concurs.with.the.conclusion.of.the. CERHR. Expert. Panel. on. Bisphenol. A. that. the.scientific.evidence.supports.a.conclusion. of.minimal concern.for.exposures.in.fetuses,. infants,. and. children. based. on. a. number. of. laboratory.animal.studies.reporting.that.“low”. level.exposure.to.bisphenol.A.during.development.can.alter.the.timing.of.events.related.to. sexual.maturation.in.females..In.addition,.the. NTP.has.minimal concern.for.exposures.to.these. populations.based.on.effects.on.the.mammary. gland. observed. in. laboratory. animals.. This. level.of.concern.for.effects.on.the.mammary. gland.is.higher.than.that.expressed.by.the.Expert. Panel.and.is.based.primarily.on.(1).information. received. through. public. comments. and. (2). a. new.supportive.study.reporting.subtle.changes. in.the.undifferentiated.structures.of.the.mammary.gland..These.studies.in.laboratory.animals. provide.only.limited.evidence.for.adverse.effects. on.development.and.more.research.is.needed.to. better.understand.their.implications.for.human. health..However,.because.these.effects.in.animals. occur.at.bisphenol.A.exposure.levels.similar.to. those.experienced.by.humans,.the.possibility. that.bisphenol.A.may.alter.human.development. cannot.be.dismissed. The NTP has negligible concern that exposure of pregnant women to bisphenol A will result in fetal or neonatal mortality, birth defects, or reduced birth weight and growth in their offspring. The.NTP.concurs.with.the.conclusion.of.the. CERHR.Expert.Panel.on.Bisphenol.A.that.there. is.negligible concern.that.exposure.of.pregnant. nTp brief
Page 1: National Toxicology Program U.S. De
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Page 8 and 9: NTP.will.transmit.the.NTP-CERHR.<st
Page 10: National Toxicology Program U.S. De
Page 15 and 16: nTp brief tainers.with.internal.epo
Page 17 and 18: Population Adult General. Populatio
Page 19 and 20: Table 3. Blood and Breast Milk Biom
Page 21 and 22: Figure 2b. The weight of evidence t
Page 23 and 24: in.considering.the.biological.plaus
Page 25 and 26: isphenol.A.as.efficiently.as.adult.
Page 27 and 28: isphenol.A..For.example,.this.raise
Page 29 and 30: laboRaToRy aNImal STudIeS In.contra
Page 31 and 32: of.normal.sex-based.differences.bet
Page 33 and 34: death.(168),.synaptic.plasticity.(1
Page 35 and 36: gland.carcinogen.or.that.bisphenol.
Page 37 and 38: understand.the.possible.long-term.c
Page 39 and 40: strategies.to.improve.the.sensitivi
Page 41 and 42: • • Howdeshell.et.al. (55).repo
Page 43 and 44: and.cystic.endometrial.hyperplasia.
Page 45 and 46: cutaneous. injection. 20 . vom. Saa
Page 47 and 48: are CurrenT exposures To bisphenol
Page 49: w/day;.95th.percentiles.0.289.-.0.2
Page 53 and 54: appendix a: inTerpreTaTion of blood
Page 55 and 56: µg/kg.bw/day.based.on.the.assumpti
Page 57 and 58: concentrations.from.maternal,.fetal
Page 59 and 60: 12.. Padmanabhan. V,. Siefert. K,.
Page 61 and 62: In..Research.Triangle.Park,.NC:.RTI
Page 63 and 64: 65.. Alonso-Magdalena. P,. Laribi.
Page 65 and 66: 91.. Calabrese.EJ,.Baldwin.LA.(2003
Page 67 and 68: Thyroid.Function.in.Juvenile.Female
Page 69 and 70: droxylase.immunoreactivity..76:423.
Page 71 and 72: stanceschimiques.gc.ca/challenge-de
Page 73 and 74: Watanabe.H,.Ohta.Y,.Iguchi.T.(2006)
Page 75 and 76: 226..vom. Saal. FS,. Cooke. PS,. Bu
Page 77 and 78: solid.phase.extraction-high.perform
Page 79 and 80: appendix i. nTp-Cerhr bisphenol a e
Page 81 and 82: 158 CHAPIN ET AL. the CERHR Core Co
Page 83 and 84: 160 CHAPIN ET AL. referred to as 4,
Page 85 and 86: 162 CHAPIN ET AL. concentrations in
Page 87 and 88: 164 CHAPIN ET AL. Food (no. sampled
Page 89 and 90: 166 CHAPIN ET AL. Table 6 Continued
Page 91 and 92: 168 CHAPIN ET AL. comparison of the
Page 93 and 94: 170 CHAPIN ET AL. Table 8 Urinary C
Page 95 and 96: 172 CHAPIN ET AL. the blood of male
Page 97 and 98: 174 CHAPIN ET AL. Table 11 Bispheno
Page 99 and 100: 176 CHAPIN ET AL. Table 13 Summarie
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178 CHAPIN ET AL. Table 15 Estimate
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180 CHAPIN ET AL. Table 17 Maximum
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182 CHAPIN ET AL. 2.0 GENERAL TOXIC
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184 CHAPIN ET AL. fetuses (3.572.7
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186 CHAPIN ET AL. Secondary sources
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188 CHAPIN ET AL. Table 25 Maternal
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190 CHAPIN ET AL. Table 27 Bispheno
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192 CHAPIN ET AL. Table 31 Qualitat
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194 CHAPIN ET AL. Table 33 Toxicoki
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198 CHAPIN ET AL. appeared to occur
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200 CHAPIN ET AL. Table 43 Biliary
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202 CHAPIN ET AL. suggesting that 4
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204 CHAPIN ET AL. low following ora
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206 CHAPIN ET AL. scaling and speci
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208 CHAPIN ET AL. 60-100% in each d
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210 CHAPIN ET AL. related. No histo
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212 CHAPIN ET AL. Table 52 Continue
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214 CHAPIN ET AL. Model and exposur
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216 CHAPIN ET AL. Model and exposur
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218 Model and exposure Husbandry a
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220 CHAPIN ET AL. Table 54 Differen
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222 CHAPIN ET AL. Table 56 Anti-And
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224 Table 57 In Vitro Genetic Toxic
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226 CHAPIN ET AL. Table 58 In Vivo
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228 CHAPIN ET AL. Table 59 Developm
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232 CHAPIN ET AL. Table 64 Tissue R
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236 CHAPIN ET AL. treatment conditi
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238 CHAPIN ET AL. clinical signs, b
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240 CHAPIN ET AL. Table 71 Benchmar
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242 CHAPIN ET AL. group, 5 from 1 l
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244 CHAPIN ET AL. least significant
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246 CHAPIN ET AL. group was a reduc
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248 CHAPIN ET AL. 100-151 g for fem
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250 CHAPIN ET AL. 3.2.3.2 Developme
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252 CHAPIN ET AL. weights, bispheno
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254 CHAPIN ET AL. 120 mg/kg bw/day
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256 CHAPIN ET AL. comparisons condu
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258 CHAPIN ET AL. the findings of t
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260 CHAPIN ET AL. analyzed.] Anogen
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262 CHAPIN ET AL. purposeful confou
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264 CHAPIN ET AL. increased lordosi
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266 CHAPIN ET AL. that there was a
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268 CHAPIN ET AL. duration of adver
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270 CHAPIN ET AL. doses of potent e
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272 CHAPIN ET AL. Table 74 Effects
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274 CHAPIN ET AL. reproductive orga
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276 CHAPIN ET AL. tyrosine-hydroxly
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278 CHAPIN ET AL. include small sam
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280 CHAPIN ET AL. males/group. [It
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282 CHAPIN ET AL. termination, whic
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284 CHAPIN ET AL. provided a reliab
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286 CHAPIN ET AL. grooming, and out
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288 CHAPIN ET AL. method of oral do
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290 CHAPIN ET AL. reared by their d
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292 CHAPIN ET AL. has been informed
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294 CHAPIN ET AL. buffered paraform
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296 CHAPIN ET AL. unit. Further, th
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298 CHAPIN ET AL. PND 21 and housed
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300 CHAPIN ET AL. Tando et al. (200
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302 CHAPIN ET AL. Purina Certified
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304 CHAPIN ET AL. high-doses of bis
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306 CHAPIN ET AL. born to those dam
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308 CHAPIN ET AL. average weight we
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310 CHAPIN ET AL. study authors con
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312 CHAPIN ET AL. used for extracti
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314 CHAPIN ET AL. jar, and there we
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316 CHAPIN ET AL. of testes and com
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318 CHAPIN ET AL. differentiation o
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320 CHAPIN ET AL. Table 81 Summary
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322 CHAPIN ET AL. Table 82 Continue
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328 CHAPIN ET AL. 600 mg/kg bw/day)
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330 CHAPIN ET AL. (Nagao et al., 19
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332 CHAPIN ET AL. antinuclear antib
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334 CHAPIN ET AL. least 6 animals.
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336 CHAPIN ET AL. Utility (Adequacy
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338 CHAPIN ET AL. stomach weight wa
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340 CHAPIN ET AL. Schirling et al.
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342 CHAPIN ET AL. Endpoint Table 88
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344 CHAPIN ET AL. different diets b
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346 CHAPIN ET AL. with 40 mg vitami
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348 CHAPIN ET AL. the bisphenol A v
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350 CHAPIN ET AL. and determining t
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352 CHAPIN ET AL. expression [to B6
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354 CHAPIN ET AL. indicated] at 0 (
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356 CHAPIN ET AL. concentrations us
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358 CHAPIN ET AL. animals were non-
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360 CHAPIN ET AL. following adjustm
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362 CHAPIN ET AL. Table 94 Treatmen
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364 CHAPIN ET AL. Table 97 Effects
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366 CHAPIN ET AL. Table 99 Treatmen
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368 CHAPIN ET AL. Therefore the NTP
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370 CHAPIN ET AL. weeks before mati
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374 Table 101 Summary of High Utili
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376 Table 102 Summary of Limited Ut
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380 CHAPIN ET AL. from other suppli
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382 CHAPIN ET AL. U.S. populations.
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384 CHAPIN ET AL. 10. Critical desi
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386 CHAPIN ET AL. Engel SM, Levy B,
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388 CHAPIN ET AL. alpha and beta ex
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390 CHAPIN ET AL. Murray TJ, Maffin
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392 CHAPIN ET AL. Ryan BC, Vandenbe
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394 CHAPIN ET AL. Thomas P, Dong J.
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appendix iii. publiC CommenTs and p
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