Table 4.
Statistically Significant Pathways Identified in the 6 hr Time‐Point and Associated BMD Values
| Pathway | BMD Median unweighted dose (kJ/m2) | Fishers exact P‐value (%) | Number of significant genes | |
|---|---|---|---|---|
| Pyrimidine ribonucleotides interconversion | 21.7182 | 2.13 | 6 | Mode 1 |
| Pyrimidine ribonucleotides de novo biosynthesis | 21.7182 | 3.01 | 6 | |
| Nucleotide excision repair pathway | 25.98675 | 0.5 | 8 | |
| IGF‐1 signaling | 28.3745 | 0.3 | 17 | |
| DNA double‐strand break repair by homologous recombination | 32.1586 | 0.5 | 5 | |
| Telomere extension by telomerase | 37.9528 | 0.7 | 5 | |
| Assembly of RNA polymerase II complex | 40.5364 | 1.81 | 9 | |
| IL‐15 production | 40.788 | 3.52 | 6 | |
| Estrogen receptor signaling | 41.1082 | 0.88 | 18 | |
| Amyloid processing | 48.4955 | 3.51 | 9 | |
| Cell cycle: G2/M DNA damage checkpoint regulation | 49.1606 | 0 | 17 | |
| Adipogenesis pathway | 52.3224 | 0.2 | 20 | |
| Cell cycle control of chromosomal replication | 54.57425 | 0.16 | 8 | |
| Mitotic roles of polo‐like kinase | 57.38095 | 0 | 15 | Mode 2 |
| Cyclins and cell cycle regulation | 60.2006 | 0.04 | 17 | |
| PTEN signaling | 60.2006 | 0.05 | 21 | |
| Cell cycle: G1/S checkpoint regulation | 60.2006 | 0.3 | 13 | |
| Sonic Hedgehog signaling | 61.4501 | 3.01 | 6 | |
| Small cell lung cancer signaling | 61.80105 | 0.24 | 17 | |
| Semaphorin signaling in neurons | 62.47665 | 0.97 | 10 | |
| mTOR signaling | 63.20475 | 0.16 | 26 | |
| Oxidized GTP and dGTP detoxification | 63.97375 | 0.3 | 28 | |
| PDGF signaling | 64.06025 | 1.67 | 12 | |
| IL‐17A signaling in fibroblasts | 64.1084 | 0.36 | 9 | |
| Prostate cancer signaling | 64.4782 | 0.98 | 16 | |
| ERK5 signaling | 65.3988 | 0.16 | 13 | |
| Androgen signaling | 65.3988 | 0.84 | 25 | |
| Xenobiotic metabolism signaling | 65.4632 | 0.08 | 37 | |
| 14‐3‐3‐mediated signaling | 66.0496 | 0.5 | 18 | |
| Prolactin signaling | 67.1095 | 0.03 | 16 | |
| HIPPO signaling | 67.7237085 | 0.09 | 16 | |
| NGF signaling | 68.1574 | 0.06 | 20 | |
| Antiproliferative role of TOB in T cell signaling | 68.709575 | 2.13 | 6 | |
| Role of CHK proteins in cell cycle checkpoint control | 68.729567 | 0 | 15 | |
| Cell cycle regulation by BTG family proteins | 68.729567 | 2.82 | 7 | |
| PI3K/AKT signaling | 68.7426835 | 0.06 | 24 | |
| ERK/MAPK signaling | 68.7426835 | 1.11 | 28 | |
| Pancreatic adenocarcinoma signaling | 68.7558 | 0.02 | 23 | |
| Lymphotoxin? receptor signaling | 68.7558 | 0.05 | 13 | |
| VEGF family ligand‐receptor interactions | 68.7558 | 0.07 | 15 | |
| p70S6K signaling | 68.7558 | 0.11 | 21 | |
| Chronic myeloid leukemia signaling | 68.7558 | 0.3 | 17 | |
| Angiopoietin signaling | 68.7558 | 0.34 | 13 | |
| Anti‐inflammation and pro‐apoptotic mechanisms utilized by Yersinia pestis | 68.7558 | 2.09 | 7 | |
| G?12/13 signaling | 68.7558 | 2.63 | 17 | |
| UVB‐induced MAPK signaling | 68.7558 | 3.94 | 9 | |
| IL‐2 signaling | 68.7558 | 3.94 | 9 | |
| Pyridoxal 5‐phosphate salvage pathway | 68.7558 | 4.13 | 23 | |
| p53 signaling | 69.5671 | 0.02 | 20 | |
| Fc Epsilon RI signaling | 69.95905 | 0.13 | 18 | |
| RAR activation | 70.887025 | 0.01 | 30 | |
| Fc? receptor‐mediated phagocytosis in macrophages and monocytes | 71.1623 | 0.18 | 17 | |
| D‐myo‐inositol (1,4,5)‐trisphosphate degradation | 71.1623 | 1.24 | 5 | |
| D‐myo‐inositol (1,3,4)‐trisphosphate biosynthesis | 71.1623 | 1.6 | 5 | |
| 1D‐myo‐inositol hexakisphosphate biosynthesis II (Mammalian) | 71.1623 | 1.6 | 5 | |
| Superpathway of D‐myo‐inositol (1,4,5)‐trisphosphate metabolism | 71.1623 | 4.37 | 5 | |
| Docosahexaenoic acid (DHA) signaling | 71.7331 | 1.05 | 8 | |
| Mechanisms of viral exit from host cells | 72.60895 | 1.7 | 8 | |
| Ovarian cancer signaling | 72.6889 | 0.08 | 25 | |
| Wnt/?‐catenin signaling | 73.4417335 | 0.29 | 26 | |
| Transcriptional regulatory network in embryonic stem cells | 73.49585 | 1.96 | 8 | |
| Glioma signaling | 74.8883 | 0.16 | 20 | |
| Role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis | 75.479 | 0.01 | 44 | |
| Role of Wnt/GSK‐3? signaling in the pathogenesis of influenza | 75.479 | 3.17 | 12 | |
| LPS‐stimulated MAPK signaling | 76.061 | 0.47 | 14 | |
| IL‐12 signaling and production in macrophages | 76.061 | 0.54 | 18 | |
| IL‐17A signaling in airway cells | 76.061 | 1.12 | 12 | |
| Type II Diabetes mellitus signaling | 76.061 | 2.34 | 20 | |
| Effect of Bacillus anthracis toxins on macrophage function | 76.061 | 3.43 | 20 | |
| HGF signaling | 76.761775 | 2.3 | 18 | |
| PI3K signaling in B lymphocytes | 77.26425 | 0.02 | 24 | |
| SAPK/JNK signaling | 77.640775 | 1.77 | 16 | |
| Virus entry via endocytic pathways | 78.16795 | 1.72 | 14 | |
| Filoviral‐mediated alteration of cytokine production in innate immune responses | 78.27815 | 0.47 | 14 | |
| Role of pattern recognition receptors in recognition of bacteria and viruses | 78.94095 | 1.06 | 16 | |
| VDR/RXR activation | 79.41495 | 0.63 | 14 | |
| NRF2‐mediated oxidative stress response | 79.7547 | 0 | 37 | |
| Gap junction signaling | 79.7547 | 1.55 | 21 | |
| CTLA4 signaling in cytotoxic T lymphocytes | 81.2194 | 0.41 | 15 | |
| eNOS signaling | 81.5021 | 2.04 | 18 | |
| Molecular mechanisms of cancer | 81.77585 | 0.01 | 60 | |
| Glucocorticoid receptor signaling | 82.2928 | 0.01 | 42 | |
| Glioma invasiveness signaling | 82.5309 | 4.52 | 9 | |
| Heparan sulfate biosynthesis | 82.7629 | 0.27 | 24 | |
| Heparan sulfate biosynthesis (late stages) | 82.7629 | 0.58 | 22 | |
| Dopamine‐DARPP32 feedback in cAMP signaling | 82.8046335 | 3.53 | 22 | |
| Production of nitric oxide and reactive oxygen species in macrophages | 82.8388 | 0 | 30 | |
| PPAR signaling | 82.90845 | 0.26 | 16 | |
| Mitochondrial dysfunction | 83.3275 | 4.86 | 19 | |
| iNOS signaling | 83.3662 | 0.01 | 13 | |
| B cell receptor signaling | 83.3662 | 0.09 | 27 | |
| Antioxidant action of vitamin C | 83.3662 | 0.1 | 15 | |
| Induction of apoptosis by HIV1 | 83.3662 | 0.16 | 13 | |
| IL‐8 signaling | 83.3662 | 0.22 | 29 | |
| Protein Kinase A signaling | 83.3662 | 0.39 | 39 | |
| CD27 signaling in lymphocytes | 83.3662 | 0.59 | 11 | |
| RANK signaling in osteoclasts | 83.3662 | 1.15 | 15 | |
| TWEAK signaling | 83.3662 | 2.44 | 7 | |
| 4‐1BB signaling in T lymphocytes | 83.46785 | 0.61 | 8 | |
| Cholecystokinin/Gastrin‐mediated signaling | 83.5016 | 4.54 | 14 | |
| ILK signaling | 83.69635 | 0.03 | 30 | |
| RhoA signaling | 84.63145 | 0.54 | 18 | |
| Role of BRCA1 in DNA damage response | 84.76775 | 0 | 21 | |
| Hereditary breast cancer signaling | 84.76775 | 0.01 | 23 | |
| ATM signaling | 84.76775 | 0.08 | 13 | |
| Aryl hydrocarbon receptor signaling | 84.76775 | 0.4 | 23 | |
| AMPK signaling | 84.76775 | 0.46 | 27 | |
| Tec kinase signaling | 84.86515 | 1.93 | 24 | |
| NF‐?B activation by viruses | 85.2828 | 0.04 | 16 | |
| G?q signaling | 85.8799 | 0.07 | 26 | |
| April mediated signaling | 85.8799 | 1.7 | 8 | |
| IL‐3 signaling | 85.89915 | 1.53 | 12 | |
| Tight junction signaling | 86.3458 | 2.49 | 23 | |
| CD40 signaling | 86.4234 | 1.12 | 12 | |
| Insulin receptor signaling | 86.4285 | 0.13 | 21 | |
| Role of JAK2 in hormone‐like cytokine signaling | 86.4285 | 1.77 | 7 | |
| GDNF family ligand‐receptor interactions | 86.4285 | 2.81 | 11 | |
| Role of osteoblasts, osteoclasts and chondrocytes in rheumatoid arthritis | 86.43295 | 0.6 | 30 | |
| Systemic lupus erythematosus signaling | 86.56875 | 0.16 | 28 | |
| CDP‐diacylglycerol biosynthesis I | 86.85785 | 0.16 | 6 | |
| Phosphatidylglycerol biosynthesis II (Nonplastidic) | 86.85785 | 0.22 | 6 | |
| NF‐?B signaling | 86.86975 | 0.28 | 24 | |
| T cell receptor signaling | 87.1994 | 0.01 | 21 | |
| Natural killer cell signaling | 87.1994 | 3.32 | 15 | |
| Hypoxia signaling in the cardiovascular system | 88.3084 | 0.48 | 12 | |
| Role of NFAT in regulation of the immune response | 88.3936 | 0.01 | 31 | |
| PKC? signaling in T lymphocytes | 88.3936 | 0.37 | 23 | |
| B cell activating factor signaling | 88.3936 | 0.74 | 9 | |
| Colorectal cancer metastasis signaling | 89.4806 | 0.8 | 33 | |
| MIF‐mediated glucocorticoid regulation | 89.4806 | 1.49 | 7 | |
| Estrogen‐mediated S‐phase Entry | 89.508075 | 1.45 | 6 | |
| JAK/Stat signaling | 89.585875 | 3.17 | 12 | |
| Integrin signaling | 89.7925 | 2.82 | 26 | |
| Protein ubiquitination pathway | 90.1604 | 0 | 36 | |
| Serotonin degradation | 90.3392 | 3.98 | 10 | |
| Breast cancer regulation by Stathmin1 | 90.823725 | 1.17 | 26 | |
| Regulation of IL‐2 expression in activated and Anergic T lymphocytes | 91.6453 | 0.21 | 16 | |
| Induction of apoptosis by Francisella tularensis | 94.3216 | 0.41 | 15 | |
| Erythropoietin signaling | 95.8156 | 0.13 | 14 | |
| Sphingosine‐1‐phosphate signaling | 96.1025 | 0.98 | 16 | |
| Human embryonic stem cell pluripotency | 96.431 | 4.74 | 21 | |
| D‐myo‐inositol (3,4,5,6)‐tetrakisphosphate biosynthesis | 96.8797 | 0.01 | 43 | |
| D‐myo‐inositol (1,4,5,6)‐Tetrakisphosphate biosynthesis | 96.8797 | 0.01 | 43 | |
| 3‐phosphoinositide degradation | 96.8797 | 0.01 | 43 | |
| 3‐phosphoinositide biosynthesis | 96.8797 | 0.01 | 45 | |
| Phospholipase C signaling | 96.8797 | 0.04 | 37 | |
| Superpathway of inositol phosphate compounds | 97.9458 | 0.01 | 48 | |
| iCOS‐iCOSL Signaling in T helper cells | 98.3293 | 1.83 | 16 | |
| MIF regulation of innate immunity | 98.8728 | 1.7 | 8 | |
| D‐myo‐inositol‐5‐phosphate metabolism | 99.0119 | 0 | 45 | |
| Axonal guidance signaling | 99.172 | 0.23 | 53 | |
| Autophagy | 99.25395 | 0 | 14 | |
| p38 MAPK signaling | 99.822 | 1.27 | 17 | |
| Thrombopoietin signaling | 99.86325 | 0.14 | 12 | |
| Stearate biosynthesis I (Animals) | 100.69505 | 1.05 | 30 | |
| Basal cell carcinoma signaling | 100.948 | 4.52 | 11 | |
| Mismatch repair in eukaryotes | 101.06645 | 0.16 | 6 | |
| Endothelin‐1 signaling | 101.237 | 0.63 | 22 | |
| TREM1 signaling | 102.0385 | 3.14 | 10 | |
| Apoptosis signaling | 106.4305 | 2.2 | 14 | |
| Factors promoting cardiogenesis in vertebrates | 106.848 | 0.42 | 16 | |
| CD28 signaling in T Helper cells | 108.265 | 0.05 | 21 | |
| TNFR2 signaling | 108.265 | 1.03 | 7 | |
| Death receptor signaling | 108.4875 | 0.7 | 16 | |
| TNFR1 signaling | 108.4875 | 0.72 | 10 | |
| Neuropathic pain signaling in dorsal horn neurons | 109.432 | 2.64 | 15 | |
| Epithelial adherens junction signaling | 109.6895 | 1.93 | 20 | |
| Melatonin signaling | 111.394 | 4.88 | 11 | |
| Corticotropin releasing hormone signaling | 111.457 | 1.98 | 20 | |
| Purine nucleotides De Novo biosynthesis II | 113.154 | 0.08 | 5 | |
| Growth hormone signaling | 113.298 | 0.64 | 13 | |
| Oleate biosynthesis II (Animals) | 116.092 | 1.77 | 7 | |
| Calcium‐induced T lymphocyte apoptosis | 116.749 | 2.39 | 10 |