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

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nTp brief ing.sources.of.exposure.(Table.1)..No.biomonitoring.data,.i.e.,.blood.or.urine.concentration.of. bisphenol.A,.are.available.for.these.life.stages. [reviewed.in (2)]..An.estimated.daily.intake.of.~1. µg/kg.bw/day.for.both.breast-fed.and.formulafed.infants.was.calculated.by.the.CERHR.Expert. Panel.for.Bisphenol.A.(2)..Higher.“worst.case”. daily.intake.estimates.of.11.–.13.µg/kg.bw/day. during.the.first.year.of.life.have.been.calculated. for.infants.(25)..In.children.1.5.to.6.years.of.age,. the.range.of.estimated.daily.intakes.based.on. aggregating.sources.of.exposure.is.0.043.–.14.7. µg/kg.bw/day,.with.14.7.µg/kg.bw/day.representing.a.worst.case.scenario.(27, 29). Although.biomonitoring.data.are.not.available. for.infants.and.children.less.than.6.years.of.age,. blood.and.urine.levels.of.free.bisphenol.A.are. predicted.to.be.higher.in.these.age.groups.compared.to.pregnant.women.or.other.adult.populations..This.is.based.on.information.related.to.age-specific.differences.in.daily.intake.of.bisphenol.A.and.in.the.ability.to.metabolize.the.chemical..More.specifically,.it.is.based.on.observations.of.(1).higher.urinary.measurements. of.total.bisphenol.A.in.children.(6.–.11.years.of. age).compared.to.adolescents.and.adults.(8),.(2). higher.estimated.daily.intakes.of.bisphenol.A. for.infants.and.children.(2, 25, 27).compared. to.estimated.daily.intakes.for.adults.(2, 25, 35),. and.(3).predicted.higher.blood.concentrations.of. free.bisphenol.A.in.infants.compared.to.adults. at.a.given.daily.intake.level.based.on.less.efficient.metabolism.of.bisphenol.A.in.rat.fetuses. and.neonates.(18 – 20),.and.very.low.or.absent. activities.in.human.fetuses.and.premature.or. full-term.infants.of.the.isozymes.that.govern. glucuronidation.(246 – 248). adults and children aged 6 years and above Daily.intake.estimates.for.adults.and.children. aged.6.years.and.older.are.based.on.(1).back.calculations.from.the.most.recent.CDC.NHANES. 35 data.on.urinary.concentrations.of.total.bisphenol. and.(2).aggregating.sources.of.exposure.(Table. 1.and.Table.3)..Of.these.estimates,.the.NTP.has. more.confidence.in.the.estimates.based.on.back. calculating. from. urinary. biomonitoring. data. because.all.sources.of.exposure.are.integrated. into.the.fluid.measurement.and.thus.do.not.have. to.be.identified.in.advance..However,.it.is.worth. noting.that.the.estimates.for.non-occupationally. exposed.adults.based.on.aggregating.sources. of. exposure. encompass. the. range. estimated. from.back.calculating.from.urine.[aggregating. sources.of.exposure:.0.008.–.1.5.µg/kg.bw/day. (Table.1);.and.back.calculating.based.on.urine:. 0.233.–.0.289.µg/kg.bw/day.for.various.categories.of.adults.ages.20+.at.the.95th.percentile. (35)]..Fewer.studies.have.estimated.daily.intakes. for.children.older.than.6.years.of.age.and.adolescents..In.Japanese.children.and.adolescents. between.the.ages.of.7.and.19.years,.the.range. of.estimated.daily.intakes.based.on.aggregating. sources.of.exposure.is.0.36.to.0.55.µg/kg.bw/day. (30),.which.is.only.slightly.higher.than.the.estimated.range.of.daily.intakes.for.American.children.and.adolescents.based.on.back.calculating. from.urinary.concentration.of.total.bisphenol.A. [0.311.–.0.348.µg/kg.bw/day.for.children.ages. 6.–.11.and.12.–.19.at.the.95th.percentile.(35)]. Estimated daily intake based on blood biomonitoring The.NTP.also.considered.the.appropriateness.of. estimating.daily.intake.based.on.back.calculations.from.free.bisphenol.A.measured.in.human.blood.and.concluded.that.the.scientific.uncertainties.are.currently.too.large.to.support.this. exercise.(see.Appendix.A)..In.brief,.estimated. daily.intakes.in.adults.based.on.this.approach. are.much.greater.(~500.µg/kg.–.1.54.mg/kg.bw/ day.for.a.65.kg.human).(3, 249).than.estimates. of.daily.intake.based.on.aggregating.routes.of. exposure.(0.008.–.1.5.µg/kg.bw/day).(25, 31).or. from.back.calculating.from.urinary.data.(adults. aged.20.–.60.+:.medians.0.0563.–.0.0334.µg/kg.
w/day;.95th.percentiles.0.289.–.0.233).(35)..In. addition,.data.from.an.intentional.dosing.study. conducted.by.Tsukioka.et al. (250) 22 .provides. further.support.for.daily.intakes.in.humans.of.
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: are CurrenT exposures To bisphenol
Page 51 and 52: nTp ConClusions The.NTP.reached.the
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
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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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