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

BISPHENOL A
Table 82
Summary of High Utility Developmental Toxicity Studies (Multiple Dose Levels)
Bisphenol A dose level (mg/kg bw/day) Reference
Model (treatment) Endpoint NOAEL LOAEL BMD 10 BMDL 10 BMD 1SD BMDL 1SD
Rat
Han–Wistar (drinking Male reproductive organ Z0.775–4.022 Cagen et al.
water from before weights, sperm production, (high dose) (1999b)
mating through testicular histopathology
gestation and lactation)
CD (gavage, 2-generations Prenatal or postnatal growth Z0.2 Ema et al.
exposure including or survival, developmental (high dose) (2001)
pre-and postnatal landmarks, anogenital distance,
development periods) age of puberty, fertility,
estrous cyclicity, or
sperm counts
Sprague–Dawley dam k Live fetuses/litter 300 1000 929 348 982 713 Kim et al.
(gavage GD 1–20) (2001b)
k Male body weight 100 300 456 339 694 497
k Female body weight 300 1000 439 328 682 490
k Ossification 300 1000
Sprague–Dawley dam Volume of SDN-POA, age or Z320 Kwon et al.
(gavage GD 11–PND 20) weight at vaginal opening (high dose) (2000)
or first estrous, estrous cyclicity,
mean lordosis intensity, prostate
weight, or histopathology in
ventral prostate, ovary, or uterus
CD dams (gavage Implantation sites, resorptions, Z640 Morrissey et al.
GD 6–15) body weight, viability, sex ratio, (high dose) (1987)
and malformations
Sprague–Dawley m Uterine epithelial cell nuclei 0.1 Schönfelder
dam (gavage (low dose) et al. (2004)
GD6–PND 21)
m Uterine epithelial nuclei with 0.1
condensed chromatin (low dose)
m Uterine epithelial cells 0.1
with cavities (low dose)
k ERb-positive cells in 0.1
uterine tissue (low dose)
kThickness of uterine 0.1 50
luminal epithelium
m ERa-positive cells in 0.1 50
uterine epithelium
Wistar-derived Delayed vaginal opening 0.1 50 68 51 35 16 Tinwell et al.
Alderley–Park (2002)
dams (gavage GD 6–21)
k Sperm count/testis 0.1 50 55 30 57 31
k Sperm count/g testis 0.1 50 81 41 68 34
k Daily sperm count/testis 0.1 50 56 31 59 31
k Daily sperm count/g testis 0.1 50 83 42 70 34
Sprague–Dawley (dietary, Live F1 pups/litter 47.5 475 268 192 559 394 Tyl et al.
multiple generations (2000b, 2002b)
with exposure during
pre-and post natal
development)
Live F2 pups/litter 47.5 475 422 152 459 294
Live F3 pups/litter 47.5 475 236 174 376 286
F1 body weight, PND 4 47.5 475 406 283 561 400
F1, F2, or F2 body weight, PND 7 47.5 475 217–328 183–257 265–410 218–313
F1, F2, or F2 body weight, PND 14 47.5 475 183–243 163–209 177–227 153–191
F1, F2, or F2 body weight, PND 21 47.5 475 208–252 166–226 223–267 175–220
m Age at F1 vaginal opening 47.5 475 394 343 206 176
m Age at F2 vaginal opening 47.5 475 404 336 277 228
m Age at F3 vaginal opening 47.5 475 471 401 396 203
m Age at F1 preputial separation 4.75 47.5 466 411 188 163
m Age at F2 preputial separation 47.5 475 300 255 241 203
m Age at F3 preputial separation 47.5 475 547 473 222 189
Mating, fertility, pregnancy, or Z475
gestational indices; (high dose)
precoital interval,
postimplantation loss,
estrous cyclicity,
and reproductive
organ histopathology;
sperm count, morphology
or motility;
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