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

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Model and exposure Husbandry a Adult ovariectomized Alpk:ApfSD, s.c. x 3 days Immature Crj:CD (SD), s.c. x 3 days Immature Crj:CD (SD), gavage x 3 days Adult ovariectomized Wistar, s.c. x 7 days Adult ovariectomized Sprague–Dawley, exposed in drinking water x 3 days Adult ovariectomized Sprague–Dawley, s.c. x 3 days Immature Alpk:ApfSD, s.c. x 3 days Immature Alpk:ApfSD, gavage x 3 days Immature Sprague– Dawley, s.c. x 3 days Immature Crj:CD (SD), s.c. x 3 days Immature Sprague– Dawley, s.c. x 3 days Pubertal Sprague– Dawley, gavage PND 22–42/43 Pregnant Sprague– Dawley, s.c. bisphenol A on GD 17–19 (17bestradiol s.c. x 1) Pregnant Sprague– Dawley, s.c. bisphenol A on GD 17–19 (17bestradiol s.c. x 1) Lactating Sprague– Dawley, s.c. bisphenol A x 5 days (17bestradiol s.c. x 1) Not indicated MF diet, steel cage MF diet, steel cage Not indicated Glass water bottles, plastic cage (negative E-Screen of ethanol cage washes) PMI Certified Rodent Diet, polycarbonate cage, elm bedding RM1 diet RM1 diet Soy-free diet, polycarbonate cage MF diet, steel cage Soy-free diet, polycarbonate cage, corncob bedding Purina 5002 diet, polycarbonate cage, chip bedding Soy-free diet, polycarbonate cage Soy-free diet, polycarbonate cage Soy-free diet Birth Defects Research (Part B) 83:157–395, 2008 BISPHENOL A Table 53 Continued Endpoint Molar potency/comparator b Uterine wet weight Uterine dry weight Wet and blotted uterine weight Wet and blotted uterine weight Blotted uterine weight Uterine wet weight Uterine wet weight Uterine dry weight Uterine wet weight Uterine dry weight Uterine wet weight Uterine dry weight Uterine wet weight Calbindin D9k expression ERa expression Uterine wet weight Blotted uterine weight Epithelial cell height Blotted uterine weight Vaginal opening Maternal uterine weight Maternal uterine calbindin D9k protein Maternal uterine calbindin D9k mRNA calbindin D9k protein [1.7 x 10 -4 ]/17b-estradiol [1.8 x 10 -4 ]/17b-estradiol Effect noted at Z8 mg/kg bw/day bisphenol A/no comparator Effect noted at Z160 mg/kg bw/day bisphenol A/no comparator Increased relative weight compared to placebo at Z11 mg/kg bw/day; uterus reached 83% of weight of sham-ovariectomized control at bisphenol A dose of 250 mg/kg bw/ day. No effect of bisphenol A at up to 16.9 mg/kg bw/day; estrone positive at 0.12 mg/kg bw/day [1.7 x 10 -6 ]/17b-estradiol [2.3 x 10 -6 ]/17b-estradiol [2.9 x 10 -4 ]/17b-estradiol No effect of bisphenol A at 800 mg/kg bw/day; 17b-estradiol positive at 0.4 mg/kg bw/day [2.3–5.5 x 10 -4 ]/17b-estradiol [2.4–7.1 x 10 -4 ]/17b-estradiol No effect of bisphenol A at r1000 mg/kg bw/day; 17bestradiol was positive at 0.04 mg/kg bw/day [8.4 x 10 -6 ]/17b-estradiol [3.4 x 10 -5 ]/17b-estradiol [5.1 x 10 -5 ]/ethinyl estradiol [8 x 10 -7 ]/ethinyl estradiol [1.2 x 10 -6 ]/ethinyl estradiol Absolute organ weight decreased with increase dose (400 and 600 mg/kg bw/day); no effect on relative organ weight No effect at 400 and 600 mg/kg bw/ day [1.8 x 10 -5 ]/17b-estradiol [1.7 x 10 -5 ]/17b-estradiol [2.2 x 10 -5 ]/17b-estradiol [6.9 x 10 -5 ]/17b-estradiol Reference Ashby et al. (2000) 215 Yamasaki et al. (2000) Goloubkova et al. (2000) Rubin et al. (2001) Kim et al. (2001a) Matthews et al. (2001) An et al. (2002) Yamasaki et al. (2002b) Wade et al. (2003) George et al. (2003) Hong et al. (2003) Hong et al. (2003) Hong et al. (2004)
216 CHAPIN ET AL. Model and exposure Husbandry a Immature and adult ovariectomized Wistar, gavage x 4 days Immature Sprague– Dawley, s.c. x 3 days Immature Sprague– Dawley, s.c. x 3 days Immature Alpk:ApfSD, gavage x 3 days Immature AP, s.c. x 3 days Adult ovariectomized Sprague–Dawley, diet x 3 months Immature Sprague– Dawley, s.c. x 3 days Adult ovariectomized Crj:CD (SD), s.c. x 3 days Adult Holzman, progesterone-treated to delay implantation, given test agent s.c. on GD 7 Rat vagina Adult ovariectomized F344, i.p. x 1 Adult ovariectomized Long Evans, bisphenol A by gavage x 11 days; 17b-estradiol by s.c. Long–Evans treated PND 21–35 by gavage Adult ovariectomized F344 and Sprague– Dawley, i.p. x 1 AO4C diet, wire cage Soy-free feed, polycarbonate cage Shinchon diet RM1 diet, polycarbonate cage RM1 diet, polypropylene cages, sawdust and shredded paper bedding Phytoestrogenfree diet PMI Certified Rodent Diet Estrogen-free NIH-07PLD diet, aluminum cage, paper bedding Unspecified Purina rodent chow, plastic cage, pine shavings Not indicated Purina 5001 diet Purina 5001 diet Not indicated Table 53 Continued Endpoint Molar potency/comparator b Uterine wet and dry weight Calbindin D9k protein Uterine wet weight Uterine wet weight relative to bw Glutathione peroxidase activity Blotted uterine weight Expression of: Progesterone receptor A Progesterone receptor B Complement C3 Lipocalcin Uterine wet weight Uterine dry weight Uterine weight, endometrial thickness, ERa, ERb expression Complement C3 expression Uterine wet weight Uterine dry weight Uterine wet weight, relative to bw Blotted uterine weight, relative to bw Implantation BrdU labeling cfos expression Vaginal cytology Vaginal opening BrdU labeling No effect in either model of bisphenol Aat r200 mg/kg bw/day/17bestradiol positive at 0.025– 0.035 mg/kg bw/day [5.1 x 10 -5 ]/17b-estradiol [1.5 x 10 -6 ]/17b-estradiol [1.3 x 10 -6 ]/17b-estradiol [4.2 x 10 -3 ]/17b-estradiol [2.5 x 10 -4 ]/17b-estradiol [3.8 x 10 -4 ]/17b-estradiol [4.2 x 10 -4 ]/17b-estradiol [1.8 x 10 -4 ]/17b-estradiol [2.3 x 10 -4 ]/17b-estradiol [1.0 x 10 -6 ]/ethinyl estradiol [1.2 x 10 -6 ]/ethinyl estradiol No bisphenol A effect at 0.37 mg/kg bw/day; estradiol benzoate positive control Bisphenol A and estradiol benzoate produced opposite effects [4.5 x 10 -7 ]/ethinyl estradiol [4.9 x 10 -7 ]/ethinyl estradiol [2.1 x 10 -5 ]/17b-estradiol [1.7 x 10 -6 ]/17b-estradiol [4–34 x 10 -6 ]/estrone Increased at bisphenol A dose of 37.5 but not 18.5 mg/kg bw/no comparator [1.3 x 10 -4 ]/17b-estradiol No effect at bisphenol A dose of 100 mg/kg bw/day; 17b-estradiol 0.005 mg/kg bw/day resulted in persistent estrus No effect at bisphenol A dose r400 mg/kg bw/day; ethinyl estradiol was active at 0.01 mg/kg bw/day F344: [4.5 x 10 -6 ]/17b-estradiol Sprague–Dawley: [1.4 x 10 -6 ]/17bestradiol Reference Stroheker et al. (2003) An et al. (2003) Kim et al. (2003a) Ashby and Odum (2004) Tinwell and Ashby (2004) Seidlová-Wuttke et al. (2004) Kim et al. (2005) Koda et al. (2005) Cummings and Laws (2000) Steinmetz et al. (1998) Laws et al. (2000) Laws et al. (2000) Long et al. (2000) Birth Defects Research (Part B) 83:157–395, 2008
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National Toxicology Program U.S. De
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[This page inTenTionally lefT blank
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NTP.will.transmit.the.NTP-CERHR.<st
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National Toxicology Program U.S. De
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nTp brief tainers.with.internal.epo
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Population Adult General. Populatio
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Table 3. Blood and Breast Milk Biom
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Figure 2b. The weight of evidence t
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in.considering.the.biological.plaus
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isphenol.A.as.efficiently.as.adult.
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isphenol.A..For.example,.this.raise
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laboRaToRy aNImal STudIeS In.contra
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of.normal.sex-based.differences.bet
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death.(168),.synaptic.plasticity.(1
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gland.carcinogen.or.that.bisphenol.
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understand.the.possible.long-term.c
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strategies.to.improve.the.sensitivi
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• • Howdeshell.et.al. (55).repo
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and.cystic.endometrial.hyperplasia.
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cutaneous. injection. 20 . vom. Saa
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are CurrenT exposures To bisphenol
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w/day;.95th.percentiles.0.289.-.0.2
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nTp ConClusions The.NTP.reached.the
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appendix a: inTerpreTaTion of blood
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µg/kg.bw/day.based.on.the.assumpti
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concentrations.from.maternal,.fetal
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12.. Padmanabhan. V,. Siefert. K,.
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In..Research.Triangle.Park,.NC:.RTI
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65.. Alonso-Magdalena. P,. Laribi.
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91.. Calabrese.EJ,.Baldwin.LA.(2003
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Thyroid.Function.in.Juvenile.Female
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droxylase.immunoreactivity..76:423.
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stanceschimiques.gc.ca/challenge-de
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Watanabe.H,.Ohta.Y,.Iguchi.T.(2006)
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226..vom. Saal. FS,. Cooke. PS,. Bu
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solid.phase.extraction-high.perform
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appendix i. nTp-Cerhr bisphenol a e
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158 CHAPIN ET AL. the CERHR Core Co
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160 CHAPIN ET AL. referred to as 4,
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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 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: 214 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 155 and 156: 232 CHAPIN ET AL. Table 64 Tissue R
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
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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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