Table 2:
Significant BPA and EE effects observed across multiple experiments, target organs and doses in CLARITY-BPA
|
TARGET ORGANS |
BPA DOSE (μg/kg BW/day) |
Ethinyl Estradiol (μg/kg BW/day) |
|||||||
|---|---|---|---|---|---|---|---|---|---|
| TREATMENT GROUPS | ENDPOINTS ASSESSED | 2.5 | 25 | 250 | 2,500 | 25,000 | 0.05 EE | 0.5 EE | |
| BRAIN | |||||||||
| SD1 | Stop-dose; PND 28 examined | AVPV size increase; females | <0.01 | <0.05 | ne | <0.001 | ne | ne | O |
| SD2 | AVPV size increase; males | O | <0.001 | ne | <0.001 | O | ne | O | |
| SD3 | MePD volume; males | O | O | ne | <0.01 | O | ne | O | |
| G1 | G6 to DOB: PND 1 examined | Hypothalamic ERα increase; females only | <0.01 | O | <0.01 | O | <0.01 | O | O |
| G2 | Hypothalamic ERß increase; females only | <0.01 | O | <0.05 | O | <0.05 | O | O | |
| G3 | Hippocampus ERß increase; males only | O | O | O | O | <0.01 | <0.01 | O | |
| G4 | Amygdala ERß increase; males | O | <0.01 | O | O | O | O | O | |
| G5 | Amygdala ERß increase; females | O | O | <0.05 | O | O | O | O | |
| G6 | Amygdala oxytocin receptor increase; males | O | <0.01 | <0.05 | O | O | O | O | |
| G7 | Amygdala oxytocin receptor increase; females | <0.05 | <0.01 | <0.05 | O | <0.05 | O | <0.01 | |
| G8 | Amygdala vasopressin increase; males | O | <0.01 | <0.05 | O | O | O | <0.05 | |
| G9 | Amygdala genes for GABA/glutamate signaling; females | <0.01 | <0.01 | <0.01 | <0.01 | <0.01 | <0.01 | <0.01 | |
| HEART | |||||||||
| SD1 | Stop-dose | Heart weight decrease; females at 6 months | <0.02 | O | O | O | O | O | O |
| SD2 | Heart weight/body weight decrease; females at 6 months | <0.06 | O | O | O | O | O | O | |
| SD3 | LV wall thickness decrease; females at 3 months | <0.05 | O | O | O | O | O | <0.01 | |
| SD4 | Cardiomyopathy, increase severity; females at PND 21 | <0.05 | O | <0.05 | O | <0.02 | <0.0005 | O | |
| CD1 | Continuous-dose | LV wall thickness increase; females at 6 months | O | O | O | O | O | <0.05 | O |
| CD2 | Heart weight/body weight increase; females at 6 months | O | <0.05 | O | O | O | O | <0.001 | |
| PROSTATE | |||||||||
| SD+1 | Stop-dose: T+E at PND 90 | Lateral high-grade prostate intraepithelial neoplasia (HGPIN) at 1 year | <0.01 | na | <0.05 | na | <0.05 | ne | <0.05 |
| SD+2 | Dorsolateral ductal adenocarcinoma, multiplicity increase at 1 year | <0.01 | O | O | O | O | ne | O | |
| CD1 | Continuous-dose: 6 months | Stem cell # increase | <0.02 | O | O | ne | ne | ne | <0.02 |
| CD2 | Progenitor cell proliferation increased | O | <0.01 | <0.02 | ne | ne | ne | <0.01 | |
| CD3 | Stem cell lineage commitment shift to basal cells | O | <0.001 | <0.01 | ne | ne | ne | <0.001 | |
| OVARY | |||||||||
| SD1 | Stop-dose: PND 21 effects | Primordial follicle # decrease | O | O | <0.05 | O | O | O | O |
| SD2 | Primary follicle # decrease | <0.05 | O | <0.05 | O | O | O | O | |
| SD3 | Preantral follicle # decrease | <0.05 | O | O | O | O | O | O | |
| SD4 | Healthy follicle # decrease | <0.05 | O | <0.05 | O | O | O | O | |
| CD1 | Continuous-dose: 1 year | Serum estradiol | O | P=0.08 | O | <0.05 | <0.05 | <0.05 | <0.05 |
| IMMUNE | |||||||||
| CD1 | Continuous-dose: Spleenic effects | Myoid cDC cell increase; males at 3 months | <0.05 | O | O | O | O | O | O |
| CD2 | cDC cell decrease; males at 6 months | <0.01 | O | O | O | <0.01 | O | <0.001 | |
| CD3 | B-cell decrease; females at 6 months | O | <0.05 | O | O | O | O | O | |
| CD4 | APC cell decrease; males at 1 year | <0.05 | <0.05 | O | O | O | O | O | |
| CD5 | Macrophage decrease; males at 1 year | O | O | O | <0.05 | O | O | O | |
| CD6 | CD8 T cells and NKT cell increase; males at 1 year | O | O | O | O | <0.05 | O | O | |
| CD+1 | Continuous-dose: Spleenic response to activating stimuli ex vivo | Proliferation increase (to PWM); females at 6 months | O | <0.01 | O | <0.0001 | O | <0.001 | O |
| CD+2 | Proliferation decrease (to PWM); males at 6 months | <0.05 | O | <0.05 | <0.01 | O | O | <0.001 | |
| CD+3 | Proliferation increase (to PWM); males at 1 year | <0.01 | <0.05 | O | <0.01 | <0.01 | <0.01 | <0.001 | |
| CD+4 | Proliferation increase (to LPS); females at 1 year | O | O | O | O | <0.05 | O | O | |
| CD+5 | Proliferation increase (to LPS); males at 1 year | <0.05 | O | O | <0.05 | <0.01 | O | <0.0001 | |
| CD+6 | Proliferation decrease (to anti-CD3); females at 1 year | <0.05 | O | O | O | O | <0.01 | O | |
| CORE STUDY | |||||||||
| SD1 | Stop-dose | Mammary adenocarcinoma incidence increase; females at 2 years | <0.02 | O | O | O | O | O | O |
| SD2 | Ovarian follicular cysts; 1 year | O | O | O | O | <0.001 | O | <0.001 | |
| SD3 | Aberrant estrous cycle, early onset | O | O | O | <0.03 | O | O | O | |
| SD4 | Liver infiltration with mononuclear cells; females at 1 year | <0.05 | O | O | O | <0.05 | O | O | |
| SD5 | Kidney tubule cyst increase; females at 2 years | <0.01 | O | O | O | O | O | O | |
| SD6 | Serum protein and total bile acids decrease; males at 1 year | O | <0.05 | O | O | O | O | O | |
| SD7 | Platelets decrease; females at 1 year | O | O | O | O | <0.05 | <0.002 | O | |
| SD8 | Pancreas pigmentation increase; males at 1 year | O | O | X | O | O | O | O | |
| SD9 | Adrenal hyperplasia; males at 2 years | O | O | O | X | O | O | O | |
| SD10 | Pituitary cysts; males at 2 years | O | O | O | O | <0.05 | O | O | |
| SD11 | Pituitary gland hyperplasia; males at 2 years | O | O | O | O | <0.05 | <0.05 | O | |
| SD12 | Bone marrow hypercellularity; males at 2 years | O | O | X | O | X | O | O | |
| SD13 | Spleen lymphoid hyperplasia; males at 2 years | O | O | X | O | O | O | O | |
| SD14 | Thyroid cysts; females at 2 years | O | O | <0.05 | O | <0.05 | O | O | |
| SD15 | Epididymis, exfoliated germ cells increase; 2 years | O | O | O | <0.05 | O | O | O | |
| CD1 | Continuous-dose | Mammary gland alveoli dilation; females at 2 years | X | O | O | O | O | O | O |
| CD2 | Uterine apoptosis increase | O | O | O | O | <0.05 | O | <0.001 | |
| CD3 | Vaginal epithelial hyperplasia increase; females at 2 years | O | <0.05 | O | <0.05 | <0.05 | O | O | |
| CD4 | Vaginal epithelial hyperplasia increase; females at 1 year | O | O | O | O | O | O | <0.001 | |
| CD5 | Liver weight decrease; males at 1 year | <0.05 | O | O | O | O | O | O | |
| CD6 | Liver angiectasis incidence increase; males at 2 years | X | O | O | O | O | O | O | |
| CD7 | Liver mononuclear infiltration; males at 1 year | <0.05 | O | <0.05 | <0.05 | <0.05 | O | O | |
| CD8 | Liver mononuclear infiltration; males at 2 years | O | O | O | O | O | <0.05 | O | |
| CD9 | Liver fatty acid increase; males at 1 year | O | <0.05 | O | O | O | O | <0.05 | |
| CD10 | Kidney tubule cysts; females at 1 year | <0.02 | O | O | O | O | <0.05 | O | |
| CD11 | Kidney tubule cysts; males at 1 year | O | O | X | X | O | X | O | |
| CD12 | Kidney epithelial hyperplasia, males at 2 years | O | <0.01 | O | O | O | O | O | |
| CD13 | Hemoglobin increase; females at 1 year | O | <0.01 | O | O | O | O | O | |
| CD14 | Hemoglobin increase; males at 1 year | O | O | O | O | <0.05 | <0.05 | O | |
| CD15 | Body weight increase; females at 2 years | O | O | <0.05 | O | O | O | O | |
| CD16 | Pituitary hyperplasia; males at 2 years | O | <0.05 | O | O | <0.05 | O | <0.05 | |
| CD17 | Parathyroid gland hyperplasia; males at 2 years | O | <0.01 | O | O | O | O | <0.05 | |
| CD18 | Thyroid hyperplasia; males at 2 years | O | O | O | <0.01 | O | <0.01 | O | |
| CD19 | Eosinophil decrease; males and females at 1 year | O | O | <0.05 | O | O | O | <0.05 | |
| CD20 | Epididymis, exfoliated germ cells & lymphocytic infiltration increase; 1 year | O | O | O | O | <0.05 | O | <0.05 | |
| CD21 | Fat pad, retroperitoneal; females at 1 year | <0.05 | O | O | O | O | O | O | |
| CD22 | Prostate DLP chronic lymphocytic inflammation increase; 1 year | <0.05 | O | O | O | O | O | O | |
| CD23 | Prostate DLP chronic intraluminal inflammation increase; 2 years | <0.05 | O | O | O | O | O | O | |
Significant effects observed for each organ system were sequentially numbered (column at left): (SD) Stop-dose; (CD) Continuous-dose; (G) Gestation exposure only; (+) indicates secondary exposures in vivo or in vitro as described in the text. (na) not available; (ne) not examined; (O) no significant effect; (X) significant effect noted on Core Study Overview Table; data not available.