to pentachlorophenol, bisphenol-A, <strong>and</strong> n<strong>on</strong>ylphenol at home <strong>and</strong> daycare. Envir<strong>on</strong> Res 103:9–20. Wistuba J, Brinkworth MH, Schlatt S, Chahoud I, Nieschlag E. 2003. Intrauterine bisphenol A exposure leads to stimulatory effects <strong>on</strong> Sertoli cell number in rats. Envir<strong>on</strong> Res 91:95–103. Wolff MS, Teitelbaum SL, Windham G, Pinney SM, Britt<strong>on</strong> JA, Chelimo C, Godbold J, Biro F, Kushi LH, Pfeiffer CM, Calafat AM. 2006. Pilot study of urinary biomarkers of phytoestrogens, phthalates, <strong>and</strong> phenols in girls. Envir<strong>on</strong> Health Perspect 115: 116–121. Wozniak AL, Bulayeva NN, Wats<strong>on</strong> CS. 2005. Xenoestrogens at picomolar to nanomolar c<strong>on</strong>centrati<strong>on</strong>s trigger membrane estrogen receptoralpha-mediated Ca21 fluxes <strong>and</strong> prolactin release in GH3/B6 pituitary tumor cells. Envir<strong>on</strong> Health Perspect 113:431–439. Xu J, Osuga Y, Yano T, Morita Y, Tang X, Fujiwara T, Takai Y, Matsumi H, Koga K, Taketani Y, Tsutsumi O. 2002. Bisphenol A induces apoptosis <strong>and</strong> G2-to-M arrest of ovarian granulosa cells. Biochem Biophys Res Commun 292:456–462. Xu L-C, Sun H, Chen J-F, Q. B, Qian J, S<strong>on</strong>g L, Wang X-R. 2005. Evaluati<strong>on</strong> of <strong>and</strong>rogen receptor transcripti<strong>on</strong>al activities of bisphenol A, octylphenol <strong>and</strong> n<strong>on</strong>ylphenol in vitro. Toxicology 216:197–203. Yamada H, Furuta I, Kato EH, Kataoka S, Usuki Y, Kobashi G, Sata F, Kishi R, Fujimoto S. 2002. Maternal serum <strong>and</strong> amniotic fluid bisphenol A c<strong>on</strong>centrati<strong>on</strong>s in <strong>the</strong> early sec<strong>on</strong>d trimester. Reprod Toxicol 16:735–739. Yamaguchi A, Ishibashi H, Kohra S, Ariz<strong>on</strong>o K, Tominaga N. 2005. Shortterm effects of endocrine-disrupting chemicals <strong>on</strong> <strong>the</strong> expressi<strong>on</strong> of estrogen-resp<strong>on</strong>sive genes in male medaka (Oryzias latipes). Aquat Toxicol 72:239–249. Yamaguchi H, Zhu J, Yu T, Sasaki K, Umetsu H, Kidachi Y, Ryoyama K. 2006. Low-level bisphenol A increases producti<strong>on</strong> of glial fibrillary acidic protein in differentiating astrocyte progenitor cells through excessive STAT3 <strong>and</strong> Smad1 activati<strong>on</strong>. Toxicology 226: 131–142. Yamamoto T, Yasuhara A, Shiraishi H, Nakasugi O. 2001. Bisphenol A in hazardous waste l<strong>and</strong>fill leachates. Chemosphere 42:415–418. Yamasaki K, Sawaki M, Noda S, Imatanaka N, Takatsuki M. 2002a. Subacute oral toxicity study of ethynylestradiol <strong>and</strong> bisphenol A, based <strong>on</strong> <strong>the</strong> draft protocol for <strong>the</strong> "Enhanced OECD Test Guideline no. 407". Arch Toxicol 76:65–74. Yamasaki K, Sawaki M, Takatsuki M. 2000. Immature rat uterotrophic assay of bisphenol A. Envir<strong>on</strong> Health Perspect 108:1147–1150. Yamasaki K, Takeyoshi M, Sawaki M, Imatanaka N, Shinoda K, Takatsuki M. 2003. Immature rat uterotrophic assay of 18 chemicals <strong>and</strong> Hershberger assay of 30 chemicals. Toxicology 183:93–115. Yamasaki K, Takeyoshi M, Yakabe Y, Sawaki M, Imatanaka N, Takatsuki M. 2002b. Comparis<strong>on</strong> of reporter gene assay <strong>and</strong> immature rat uterotrophic assay of twenty-three chemicals. Toxicology 170:21–30. Yang FX, Xu Y, Wen S. 2005. Endocrine-disrupting effects of n<strong>on</strong>ylphenol, bisphenol A, <strong>and</strong> p,p 0 -DDE <strong>on</strong> Rana nigromaculata tadpoles. Bull Envir<strong>on</strong> C<strong>on</strong>tam Toxicol 75:1168–1175. Yang M, Kim SY, Chang SS, Lee IS, Kawamoto T. 2006. Urinary c<strong>on</strong>centrati<strong>on</strong>s of bisphenol A in relati<strong>on</strong> to biomarkers of sensitivity <strong>and</strong> effect <strong>and</strong> endocrine-related health effects. Envir<strong>on</strong> Mol Mutagen 47:571–578. Yang M, Kim SY, Lee SM, Chang SS, Kawamoto T, Jang JY, Ahn YO. 2003. Biological m<strong>on</strong>itoring of bisphenol a in a Korean populati<strong>on</strong>. Arch Envir<strong>on</strong> C<strong>on</strong>tam Toxicol 44:546–551. Ye X, Bishop AM, Reidy JA, Needham LL, Calafat AM. 2007. Temporal stability of <strong>the</strong> c<strong>on</strong>jugated species of bisphenol A, parabens, <strong>and</strong> Birth Defects Research (Part B) 83:157–395, 2008 BISPHENOL A 395 o<strong>the</strong>r envir<strong>on</strong>mental phenols in human urine. J Expo Sci Envir<strong>on</strong> Epidemiol 17: 567-572. Ye X, Kuklenyik Z, Needham LL, Calafat AM. 2005. Quantificati<strong>on</strong> of urinary c<strong>on</strong>jugates of bisphenol A, 2,5-dichlorophenol, <strong>and</strong> 2hydroxy-4-methoxybenzophen<strong>on</strong>e in humans by <strong>on</strong>line solid phase extracti<strong>on</strong>-high performance liquid chromatography-t<strong>and</strong>em mass spectrometry. Anal Bioanal Chem 383:638–644. Ye X, Kuklenyik Z, Needham LL, Calafat AM. 2006. Measuring envir<strong>on</strong>mental phenols <strong>and</strong> chlorinated organic chemicals in breast milk using automated <strong>on</strong>-line column-switching-high performance liquid chromatography-isotope diluti<strong>on</strong> t<strong>and</strong>em mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 831:110–115. Yokota H, Iwano H, Endo M, Kobayashi T, Inoue H, Ikushiro SI, Yuasa A. 1999. Glucur<strong>on</strong>idati<strong>on</strong> of <strong>the</strong> envir<strong>on</strong>mental oestrogen bisphenol A by an isoform of UDP-glucur<strong>on</strong>osyltransferase, UGT2B1, in <strong>the</strong> rat liver. Biochem J 340:405–409. Yokota H, Tsuruda Y, Maeda M, Oshima Y, Tadokoro H, Nakaz<strong>on</strong>o A, H<strong>on</strong>jo T, Kobayashi K. 2000. Effect of bisphenol A <strong>on</strong> <strong>the</strong> early life stage in Japanese medaka (Oryzias latipes). Envir<strong>on</strong> Toxicol Chem 19:1925–1930. Yoo SD, Shin BS, Lee BM, Lee KC, Han SY, Kim HS, Kwack SJ, Park KL. 2001. Bioavailability <strong>and</strong> mammary excreti<strong>on</strong> of bisphenol A in Sprague-Dawley rats. J Toxicol Envir<strong>on</strong> Health A 64:417–426. Yoshida M, Shimomoto T, Katashima S, Watanabe G, Taya K, Maekawa A. 2004. Maternal exposure to low doses of bisphenol A has no effects <strong>on</strong> development of female reproductive tract <strong>and</strong> uterine carcinogenesis in D<strong>on</strong>ryu rats. J Reprod Dev 50:349–360. Yoshida T, Horie M, Hoshino Y, Nakazawa H. 2001. Determinati<strong>on</strong> of bisphenol A in canned vegetables <strong>and</strong> fruit by high performance liquid chromatography. Food Addit C<strong>on</strong>tam 18:69–75. Yoshihara S, Makishima M, Suzuki N, Ohta S. 2001. Metabolic activati<strong>on</strong> of bisphenol A by rat liver S9 fracti<strong>on</strong>. Toxicol Sci 62:221–227. Yoshihara S, Mizutare T, Makishima M, Suzuki N.Fujimoto N, Igarashi K, Ohta S. 2004. Potent estrogenic metabolites of bisphenol A <strong>and</strong> bisphenol B formed by rat liver S9 fracti<strong>on</strong>: <strong>the</strong>ir structures <strong>and</strong> estrogenic potency. Toxicol Sci 78:50–59. Yoshino H, Ichihara T, Kawabe M, Imai N, Hagiwara A, Asamoto M, Shirai T. 2002. Lack of significant alterati<strong>on</strong> in <strong>the</strong> prostate or testis of F344 rat offspring after transplacental <strong>and</strong> lactati<strong>on</strong>al exposure to bisphenol A. J Toxicol Sci 27:433–439. Yoshino S, Yamaki K, Li X, Sai T, Yanagisawa R, Takano H, Taneda S, Hayashi H, Mori Y. 2004. Prenatal exposure to bisphenol A upregulates immune resp<strong>on</strong>ses, including T helper 1 <strong>and</strong> T helper 2 resp<strong>on</strong>ses, in mice. Immunology 112:489–495. Zalko D, Soto AM, Dolo L, Dorio C, Rathahao E, Debrauwer L, Faure R, Cravedi JP. 2003. Biotransformati<strong>on</strong>s of bisphenol A in a mammalian model: answers <strong>and</strong> new questi<strong>on</strong>s raised by low-dose metabolic fate studies in pregnant CD1 mice. Envir<strong>on</strong> Health Perspect 111:309–319. Zoeller RT, Bansal R, Parris C. 2005. Bisphenol-A, an envir<strong>on</strong>mental c<strong>on</strong>taminant that acts as a thyroid horm<strong>on</strong>e receptor antag<strong>on</strong>ist in vitro, increases serum thyroxine, <strong>and</strong> alters RC3/neurogranin expressi<strong>on</strong> in <strong>the</strong> developing rat brain. Endocrinology 146: 607–612. Zsarnovszky A, Le HH, Wang H-S, Belcher SM. 2005. Ontogeny of rapid estrogen-mediated ERK1/2 signaling in <strong>the</strong> rat cerebellar cortex in vivo: potent n<strong>on</strong>-genomic ag<strong>on</strong>ist <strong>and</strong> endocrine disrupting activity of <strong>the</strong> xenoestrogen bisphenol A. Endocrinology 146: 5388–5396.
[This page inTenTi<strong>on</strong>ally lefT blank]
- Page 1:
National Toxicology Program U.S. De
- Page 4 and 5:
[This page inTenTionally lefT blank
- Page 6 and 7:
[This page inTenTionally lefT blank
- Page 8 and 9:
NTP.will.transmit.the.NTP-CERHR.<st
- Page 10:
National Toxicology Program U.S. De
- Page 13 and 14:
[This page inTenTionally lefT blank
- 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 and 50:
w/day;.95th.percentiles.0.289.-.0.2
- 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
- Page 99 and 100:
176 CHAPIN ET AL. Table 13 Summarie
- Page 101 and 102:
178 CHAPIN ET AL. Table 15 Estimate
- Page 103 and 104:
180 CHAPIN ET AL. Table 17 Maximum
- Page 105 and 106:
182 CHAPIN ET AL. 2.0 GENERAL TOXIC
- Page 107 and 108:
184 CHAPIN ET AL. fetuses (3.572.7
- Page 109 and 110:
186 CHAPIN ET AL. Secondary sources
- Page 111 and 112:
188 CHAPIN ET AL. Table 25 Maternal
- Page 113 and 114:
190 CHAPIN ET AL. Table 27 Bispheno
- Page 115 and 116:
192 CHAPIN ET AL. Table 31 Qualitat
- Page 117 and 118:
194 CHAPIN ET AL. Table 33 Toxicoki
- Page 119 and 120:
196 CHAPIN ET AL. Table 36 Toxicoki
- Page 121 and 122:
198 CHAPIN ET AL. appeared to occur
- Page 123 and 124:
200 CHAPIN ET AL. Table 43 Biliary
- Page 125 and 126:
202 CHAPIN ET AL. suggesting that 4
- Page 127 and 128:
204 CHAPIN ET AL. low following ora
- Page 129 and 130:
206 CHAPIN ET AL. scaling and speci
- Page 131 and 132:
208 CHAPIN ET AL. 60-100% in each d
- Page 133 and 134:
210 CHAPIN ET AL. related. No histo
- Page 135 and 136:
212 CHAPIN ET AL. Table 52 Continue
- Page 137 and 138:
214 CHAPIN ET AL. Model and exposur
- Page 139 and 140:
216 CHAPIN ET AL. Model and exposur
- Page 141 and 142:
218 Model and exposure Husbandry a
- Page 143 and 144:
220 CHAPIN ET AL. Table 54 Differen
- Page 145 and 146:
222 CHAPIN ET AL. Table 56 Anti-And
- Page 147 and 148:
224 Table 57 In Vitro Genetic Toxic
- Page 149 and 150:
226 CHAPIN ET AL. Table 58 In Vivo
- Page 151 and 152:
228 CHAPIN ET AL. Table 59 Developm
- Page 153 and 154:
230 CHAPIN ET AL. Table 62 Toxicoki
- Page 155 and 156:
232 CHAPIN ET AL. Table 64 Tissue R
- Page 157 and 158:
234 CHAPIN ET AL. Table 68 Toxicoki
- Page 159 and 160:
236 CHAPIN ET AL. treatment conditi
- Page 161 and 162:
238 CHAPIN ET AL. clinical signs, b
- Page 163 and 164:
240 CHAPIN ET AL. Table 71 Benchmar
- Page 165 and 166:
242 CHAPIN ET AL. group, 5 from 1 l
- Page 167 and 168:
244 CHAPIN ET AL. least significant
- Page 169 and 170:
246 CHAPIN ET AL. group was a reduc
- Page 171 and 172:
248 CHAPIN ET AL. 100-151 g for fem
- Page 173 and 174:
250 CHAPIN ET AL. 3.2.3.2 Developme
- Page 175 and 176:
252 CHAPIN ET AL. weights, bispheno
- Page 177 and 178:
254 CHAPIN ET AL. 120 mg/kg bw/day
- Page 179 and 180:
256 CHAPIN ET AL. comparisons condu
- Page 181 and 182:
258 CHAPIN ET AL. the findings of t
- Page 183 and 184:
260 CHAPIN ET AL. analyzed.] Anogen
- Page 185 and 186:
262 CHAPIN ET AL. purposeful confou
- Page 187 and 188:
264 CHAPIN ET AL. increased lordosi
- Page 189 and 190:
266 CHAPIN ET AL. that there was a
- Page 191 and 192:
268 CHAPIN ET AL. duration of adver
- Page 193 and 194:
270 CHAPIN ET AL. doses of potent e
- Page 195 and 196:
272 CHAPIN ET AL. Table 74 Effects
- Page 197 and 198:
274 CHAPIN ET AL. reproductive orga
- Page 199 and 200:
276 CHAPIN ET AL. tyrosine-hydroxly
- Page 201 and 202:
278 CHAPIN ET AL. include small sam
- Page 203 and 204:
280 CHAPIN ET AL. males/group. [It
- Page 205 and 206:
282 CHAPIN ET AL. termination, whic
- Page 207 and 208:
284 CHAPIN ET AL. provided a reliab
- Page 209 and 210:
286 CHAPIN ET AL. grooming, and out
- Page 211 and 212:
288 CHAPIN ET AL. method of oral do
- Page 213 and 214:
290 CHAPIN ET AL. reared by their d
- Page 215 and 216:
292 CHAPIN ET AL. has been informed
- Page 217 and 218:
294 CHAPIN ET AL. buffered paraform
- Page 219 and 220:
296 CHAPIN ET AL. unit. Further, th
- Page 221 and 222:
298 CHAPIN ET AL. PND 21 and housed
- Page 223 and 224:
300 CHAPIN ET AL. Tando et al. (200
- Page 225 and 226:
302 CHAPIN ET AL. Purina Certified
- Page 227 and 228:
304 CHAPIN ET AL. high-doses of bis
- Page 229 and 230:
306 CHAPIN ET AL. born to those dam
- Page 231 and 232:
308 CHAPIN ET AL. average weight we
- Page 233 and 234:
310 CHAPIN ET AL. study authors con
- Page 235 and 236:
312 CHAPIN ET AL. used for extracti
- Page 237 and 238:
314 CHAPIN ET AL. jar, and there we
- Page 239 and 240:
316 CHAPIN ET AL. of testes and com
- Page 241 and 242:
318 CHAPIN ET AL. differentiation o
- Page 243 and 244:
320 CHAPIN ET AL. Table 81 Summary
- Page 245 and 246:
322 CHAPIN ET AL. Table 82 Continue
- Page 247 and 248:
324 CHAPIN ET AL. Table 84 Summary
- Page 249 and 250:
326 CHAPIN ET AL. Table 85 Summary
- Page 251 and 252:
328 CHAPIN ET AL. 600 mg/kg bw/day)
- Page 253 and 254:
330 CHAPIN ET AL. (Nagao et al., 19
- Page 255 and 256:
332 CHAPIN ET AL. antinuclear antib
- Page 257 and 258:
334 CHAPIN ET AL. least 6 animals.
- Page 259 and 260:
336 CHAPIN ET AL. Utility (Adequacy
- Page 261 and 262:
338 CHAPIN ET AL. stomach weight wa
- Page 263 and 264:
340 CHAPIN ET AL. Schirling et al.
- Page 265 and 266:
342 CHAPIN ET AL. Endpoint Table 88
- Page 267 and 268: 344 CHAPIN ET AL. different diets b
- Page 269 and 270: 346 CHAPIN ET AL. with 40 mg vitami
- Page 271 and 272: 348 CHAPIN ET AL. the bisphenol A v
- Page 273 and 274: 350 CHAPIN ET AL. and determining t
- Page 275 and 276: 352 CHAPIN ET AL. expression [to B6
- Page 277 and 278: 354 CHAPIN ET AL. indicated] at 0 (
- Page 279 and 280: 356 CHAPIN ET AL. concentrations us
- Page 281 and 282: 358 CHAPIN ET AL. animals were non-
- Page 283 and 284: 360 CHAPIN ET AL. following adjustm
- Page 285 and 286: 362 CHAPIN ET AL. Table 94 Treatmen
- Page 287 and 288: 364 CHAPIN ET AL. Table 97 Effects
- Page 289 and 290: 366 CHAPIN ET AL. Table 99 Treatmen
- Page 291 and 292: 368 CHAPIN ET AL. Therefore the NTP
- Page 293 and 294: 370 CHAPIN ET AL. weeks before mati
- Page 295 and 296: 372 CHAPIN ET AL. Table 100 Summary
- Page 297 and 298: 374 Table 101 Summary of High Utili
- Page 299 and 300: 376 Table 102 Summary of Limited Ut
- Page 301 and 302: 378 CHAPIN ET AL. Table 103 Summary
- Page 303 and 304: 380 CHAPIN ET AL. from other suppli
- Page 305 and 306: 382 CHAPIN ET AL. U.S. populations.
- Page 307 and 308: 384 CHAPIN ET AL. 10. Critical desi
- Page 309 and 310: 386 CHAPIN ET AL. Engel SM, Levy B,
- Page 311 and 312: 388 CHAPIN ET AL. alpha and beta ex
- Page 313 and 314: 390 CHAPIN ET AL. Murray TJ, Maffin
- Page 315 and 316: 392 CHAPIN ET AL. Ryan BC, Vandenbe
- Page 317: 394 CHAPIN ET AL. Thomas P, Dong J.
- Page 321: appendix iii. publiC CommenTs and p