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

More documents

Recommendations

Info

Table 98 Treatment-Related Effects in Adult Mice Fed Bisphenol A Through Diet in a Multigeneration Reproductive Toxicity Study Dose, ppm diet [mg/kg bw/day based on target intakes provided by study authors] 30 [5] 300 [50] 3500 [600] BMD10 BMDL10 BMD1SD BMDL1SD Endpoint 0.018 [0.003] 0.18 [0.03] 1.8 [0.3] 2 2 m2.2–fold 249 [42.2] 150 [25.4] 4258 [722] 2941 [498] 2 2 k10% 3455 [586] 2388 [405] 3503 [594] 2608 [442] 2 2 m17% 2189 [371] 1820 [308] 2021 [343] 1668 [283] 2 m5% m22% 1662 [282] 1425 [242] 1637 [277] 1389 [235] 2 2 m23% 1584 [268] 1383 [234] 1685 [286] 1405 [238] 2 2 m17% 2524 [428] 1595 [270] 3014 [511] 2155 [365] 2 2 m10% 3424 [580] 2438 [413] 3551 [602] 3024 [513] Birth Defects Research (Part B) 83:157–395, 2008 2 m8% m20% 1861 [315] 1536 [260] 2100 [356] 1723 [292] m11% m10% m21% 2079 [352] 1913 [324] 862 [146] 773 [131] 2 2 m27% 1501 [254] 1229 [208] 1978 [335] 1610 [273] 2 2 m13% 3568 [605] 2504 [424] 4326 [733] 3041 [515] 2 2 m8% 3629 [615] 2976 [504] 3702 [627] 3393 [575] BISPHENOL A 2 m9% m19% 1899 [322] 1548 [262] 2249 [381] 1825 [309] m13% m10% m22% 2074 [352] 1650 [280] 2547 [432] 2020 [342] 2 m11% m28% 1466 [248] 1205 [204] 1937 [328] 1582 [268] 2 2 m11% 3746 [635] 2550 [432] 4773 [809] 3258 [552] 2 2 m10% 3413 [578] 2087 [554] 3627 [615] 3182 [539] 2 2 m16% 2678 [454] 1934 [328] 3476 [589] 2512 [426] 2 2 m9% 2678 [454] 1934 [328] 3476 [589] 2512 [426] 0/10 4/10 10/10 122 [20.7] 70 [11.8] 2/10 1/10 6/10 879 [149] 578 [98.0] 2/10 5/10 7/10 656 [111] 442 [74.9] 0/10 1/10 6/10 1348 [228] 947 [161] 0/10 3/11 7/10 962 [163] 679 [115] 2/10 1/10 4/10 1556 [264] 750 [127] 2/10 0/10 4/10 1418 [240] 838 [142] 2/10 0/10 3/10 1991 [337] 992 [168] 1/10 1/11 4/11 1646 [279] 847 [144] 1/12 3/14 7/17 1328 [225] 833 [141] 2/10 2/11 7/15 1193 [202] 708 [120] 2 2 k15% 3343 [567] 1884 [319] 3581 [607] 3241 [549] Body weight gain during lactation, F0 2 2 2 Terminal body weight F1 retained males 2 2 2 Relative liver to body weight F0 males 2 2 2 F1 parental males 2 2 2 F1 retained males 2 2 2 F0 females 2 2 2 F1 females 2 2 2 Relative right kidney to body weight F0 males 2 2 2 F1 parental males 2 2 2 F1 retained males 2 2 2 F0 females 2 2 2 F1 females 2 2 2 Relative left kidney to body weight F0 males 2 2 2 F1 parental males 2 2 2 F1 retained males 2 2 2 F0 females 2 2 2 Relative pituitary to body weight a F1 parental males 2 2 2 F1 retained males a 2 2 2 a Relative brain to body weight F1 retained males 2 2 2 Hepatocyte centrilobular hypertrophy incidence (control incidence in parentheses) F0 males (6/56) 1/10 2/10 2/10 F1 parental males (7/55) 0/10 0/10 4/10 F1 retained males (4/50) 1/10 3/10 2/10 F0 females (1/56) 0/10 0/10 0/10 F1 females (2/55) 0/10 0/10 0/10 Renal nephropathy incidence (control incidence in parentheses) F0 males (12/56) 0/10 3/10 2/10 F1 parental males (6/55) 2/10 0/10 1/10 F1 retained males (8/50) 1/10 0/10 0/10 F1 females (10/55) 1/10 3/10 0/10 Paraovarian cysts (control incidence in parentheses) F0 (9/56) 1/11 2/12 1/11 F1 (14/55) 1/11 1/11 1/10 a Epididymal sperm concentration, F0 2 2 2 Gestational length 2 2 m2% 21,351 [3619] 3770 [639] 6749 [1144] 3536 [599] 2 2 m2% 17,820 [3020] 3784 [641] 4552 [772] 3134 [531] F0 2 2 2 F1 2 2 2 365 a Not considered a treatment-related effect by study authors. m,k Statistically significant increase, decrease; 2 no statistically significant effect compared to controls.
366 CHAPIN ET AL. Table 99 Treatment- or Dose-Related Effects in Developing Mice in a Multigeneration Reproductive Toxicity Study With Bisphenol A Dose, ppm diet [mg/kg bw/day based on target intakes provided by study authors] a End point 0.018 [0.003] 0.18 [0.03] 1.8 [0.3] 30 [5] 300 [50] 3500 [600] BMD10 BMDL10 BMD1SD BMDL1SD Body weight F1, PND 7 2 2 2 2 2 k13% 3304 [560] 1849 [313] 3433 [582] 2403 [407] F1, PND 14 2 2 2 2 2 k11% 3453 [585] 2256 [382] 3639 [617] 2988 [506] F1, PND 21 2 2 2 2 2 k17% 3236 [548] 1577 [267] 3421 [580] 2342 [370] F1 male, PND 21 necropsy 2 2 2 2 2 k12% 3325 [564] 1845 [313] 3776 [640] 3536 [599] F1 female, PND 21 necropsy 2 2 2 2 2 k18% 2284 [387] 1501 [254] 4577 [776] 3529 [598] Lactational survival indices (control index, %, in parentheses) F2 PND 21 survival (100%) c 2 2 2 2 k to 86.6% 2 F2 Lactational index (97.2%) c 2 2 2 2 k to 86.6% 2 Relative thymus to body 2 2 2 2 m 13% b m 10% b weight, F1 male, PND 21 b Relative spleen to body weight F1 male, PND 21 2 k 12% 2 2 2 k 30% 3123 [529] 1074 [182] 3538 [600] 3148 [534] F2 male, PND 21 2 2 2 2 2 k 20% 2148 [364] 1425 [242] 7013 [1189] 3560 [603] F1 female, PND 21 2 2 2 2 2 k 23% 3168 [537] 647 [110] 4571 [775] 3677 [623] F2 female, PND 21 2 2 2 2 2 k 21% 1787 [303] 1311 [222] 5022 [851] 3517 [596] Relative paired testes weight to body or brain weight F1, PND 21 (body weight) 2 2 2 2 2 k 8% 3578 [606] 2720 [461] 3861 [654] 3550 [602] F2, PND 21 (brain weight) 2 2 2 2 2 k 11% 3316 [562] 2003 [339] 5342 [905] 3571 [605] Relative paired epididymides 2 m 18% 2 2 2 2 b to body weight, F1 Relative brain to body weight 2 2 2 2 2 m 17% b 2219 [376] 1415 [240] 3576 [606] 2825 [479] F1 female, PND 21 b Relative left kidney to body 2 2 2 2 2 m 6% 6664 [1129] 3540 [600] 8501 [1441] 3589 [608] weight, F2 male, PND 21 Relative seminal vesicles with 2 2 2 2 k 15% k 16% 2389 [405] 1315 [223] 11,294 [1914] 3631 [615] b coagulating gland to brain weight, F2 Uterus with cervix and vagina 2 2 2 2 k16% 2 weight relative to bodyweight, F2 PND 21 b b Relative paired ovary weights, F1 2 2 m 2 2 2 Birth Defects Research (Part B) 83:157–395, 2008
Page 1:
National Toxicology Program U.S. De
Page 4 and 5:
[This page inTenTionally lefT blank
Page 6 and 7:
Page 8 and 9:
NTP.will.transmit.the.NTP-CERHR.<st
Page 10:
National Toxicology Program U.S. De
Page 13 and 14:
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:
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:
Page 155 and 156:
232 CHAPIN ET AL. Table 64 Tissue R
Page 157 and 158:
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 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: 364 CHAPIN ET AL. Table 97 Effects
Page 291 and 292: 368 CHAPIN ET AL. Therefore the NTP
Page 293 and 294: 370 CHAPIN ET AL. weeks before mati
Page 297 and 298: 374 Table 101 Summary of High Utili
Page 299 and 300: 376 Table 102 Summary of Limited Ut
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 and 318: 394 CHAPIN ET AL. Thomas P, Dong J.
Page 319 and 320: [This page inTenTionally lefT blank
Page 321: appendix iii. publiC CommenTs and p
show all

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

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?