TICToK | Tattoo Ink Chemicals and assocaited Toxicities Knowledgebase

Butylparaben

Associated High Confidence AOPs

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Associated AOPs with Level of Relevance 1

AOP Identifier	AOP Title	AO Classification	OECD Status	Coverage Score	KE Identifier	KE Name
AOP:15	Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations	Genetic Disease	WPHA/WNT Endorsed	0.25	KE:155	Inadequate DNA repair
AOP:17	Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leads to impairment of learning and memory	Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	0.1	KE:1392	Oxidative Stress
AOP:23	Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)	Unclassified	WPHA/WNT Endorsed	0.2	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:23		Unclassified	WPHA/WNT Endorsed	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:25	Aromatase inhibition leading to reproductive dysfunction	Unclassified	WPHA/WNT Endorsed	0.25	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:25	Aromatase inhibition leading to reproductive dysfunction	Unclassified	WPHA/WNT Endorsed	0.25	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:27	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)	Gastrointestinal System Disease	Under Development	0.12	KE:1115	Increase, Reactive oxygen species
AOP:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal System Disease	Under Development	0.2	KE:716	Increase, cell proliferation (hepatocytes)
AOP:39	Covalent Binding, Protein, leading to Increase, Allergic Respiratory Hypersensitivity Response	Respiratory System Disease	Under Development	0.2	KE:272	Activation/Proliferation, T-cells
AOP:40	Covalent Protein binding leading to Skin Sensitisation	Integumentary System Disease	WPHA/WNT Endorsed	0.2	KE:272	Activation/Proliferation, T-cells
AOP:73	Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity	Unclassified	-	0.15	KE:10059	Decreased LH surge for 24 hours
AOP:73		Unclassified	-	0.15	KE:531	Decreased, LH Surge
AOP:80	Nicotinic acetylcholine receptor activation contributes to accumulation of damaged mitochondrial DNA and leads to colony loss/failure	Unclassified	-	0.12	KE:664	Overwhelmed, Mitochondrial DNA repair mechanisms
AOP:102	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition	Reproductive System Disease	-	0.1	KE:690	Reduced, Luteinizing hormone (LH), plasma
AOP:103	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with spindle assembly checkpoint	Reproductive System Disease	-	0.1	KE:690	Reduced, Luteinizing hormone (LH), plasma
AOP:107	Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat	Cancer; Gastrointestinal System Disease	Under Review	0.2	KE:716	Increase, cell proliferation (hepatocytes)
AOP:110	Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine System Disease	-	0.14	KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:112	Increased dopaminergic activity leading to endometrial adenocarcinomas (in Wistar rat)	Reproductive System Disease; Cancer	-	0.17	KE:111	Agonism, Estrogen receptor
AOP:114	HPPD inhibition leading to corneal papillomas and carcinomas (in rat)	Cancer	-	0.17	KE:778	Increase, Regenerative cell proliferation (corneal cells)
AOP:115	Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)	Cancer	-	0.2	KE:781	Increase, Regenerative cell proliferation (forestomach epithelial cells)
AOP:117	Androgen receptor activation leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal System Disease	Under Development	0.25	KE:716	Increase, cell proliferation (hepatocytes)
AOP:118	Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal System Disease	-	0.25	KE:787	Increase, Regenerative cell proliferation (hepatocytes)
AOP:119	Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine System Disease	-	0.14	KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:120	Inhibition of 5α-reductase leading to Leydig cell tumors (in rat)	Cancer; Reproductive System Disease	-	0.4	KE:1690	Decrease, circulating testosterone levels
AOP:120		Cancer; Reproductive System Disease	-	0.4	KE:791	Increased, Leutinizing hormone (LH)
AOP:121	Urinary bladder calculi leading to urothelial papillomas and carcinomas (in mouse and rat)	Cancer; Urinary System Disease	-	0.2	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:122	Prolyl hydroxylase inhibition leading to reproductive dysfunction via increased HIF1 heterodimer formation	Unclassified	-	0.3	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
					KE:799	Increased, HIF-1 heterodimer
					KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:126	Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation	Unclassified	-	0.15	KE:10059	Decreased LH surge for 24 hours
AOP:126		Unclassified	-	0.15	KE:531	Decreased, LH Surge
AOP:136	Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors	Benign Neoplasm; Respiratory System Disease	Under Review	0.14	KE:870	Increase, Cell Proliferation
AOP:164	Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse	Cancer; Reproductive System Disease	-	0.17	KE:1042	Proliferation/Clonal Expansion, smooth muscle
AOP:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive System Disease	-	0.5	KE:1281	Increased, DNA Damage-Repair
					KE:1115	Increase, Reactive oxygen species
					KE:1262	Apoptosis
					KE:1280	Activation, HIF-1
AOP:213	Inhibition of fatty acid beta oxidation leading to nonalcoholic steatohepatitis (NASH)	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.17	KE:1115	Increase, Reactive oxygen species
AOP:219	Inhibition of CYP7B activity leads to decreased reproductive success via decreased sexual behavior	Unclassified	-	0.17	KE:1390	Sexual behavior, decreased
AOP:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal System Disease	WPHA/WNT Endorsed	0.2	KE:1392	Oxidative Stress
AOP:260	CYP2E1 activation and formation of protein adducts leading to neurodegeneration	Nervous System Disease	-	0.14	KE:1392	Oxidative Stress
AOP:271	Inhibition of thyroid peroxidase leading to impaired fertility in fish	Unclassified	Under Development	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	0.43	KE:870	Increase, Cell Proliferation
					KE:155	Inadequate DNA repair
					KE:1636	Increase, Chromosomal aberrations
AOP:275	Histone deacetylase inhibition leads to neural tube defects	Neural Tube Defect	-	0.2	KE:1239	Altered, Gene Expression
AOP:287	Mitochondrial complex III antagonism leading to growth inhibition (2)	Unclassified	-	0.25	KE:1825	Increase, Cell death
AOP:288	Inhibition of 17α-hydrolase/C 10,20-lyase (Cyp17A1) activity leads to birth reproductive defects (cryptorchidism) in male (mammals)	Endocrine System Disease	-	0.12	KE:1690	Decrease, circulating testosterone levels
AOP:289	Inhibition of 5α-reductase leading to impaired fecundity in female fish	Unclassified	Under Development	0.17	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:291	Mitochondrial ATP synthase antagonism leading to growth inhibition (2)	Unclassified	-	0.25	KE:1825	Increase, Cell death
AOP:293	Increased DNA damage leading to increased risk of breast cancer	Genetic Disease; Thoracic Disease; Cancer	Under Development	0.11	KE:1182	Increase, Cell Proliferation (Epithelial Cells)
AOP:294	Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer	Genetic Disease; Thoracic Disease; Cancer	Under Development	0.11	KE:1182	Increase, Cell Proliferation (Epithelial Cells)
AOP:299	Deposition of energy leading to population decline via DNA oxidation and follicular atresia	Unclassified	-	0.14	KE:1115	Increase, Reactive oxygen species
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	0.43	KE:1115	Increase, Reactive oxygen species
					KE:870	Increase, Cell Proliferation
					KE:1669	Increased, DNA damage and mutation
AOP:310	Embryonic Activation of the AHR leading to Reproductive failure, via epigenetic down-regulation of GnRHR	Unclassified	-	0.17	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
AOP:310		Unclassified	-	0.17	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:311	Deposition of energy leading to population decline via DNA oxidation and oocyte apoptosis	Unclassified	-	0.14	KE:1115	Increase, Reactive oxygen species
AOP:320	Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality	Unclassified	Under Development	0.11	KE:1750	Increased inflammatory immune responses
AOP:323	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone	Unclassified	-	0.17	KE:1758	Impaired, Spermatogenesis
AOP:335	AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment	Cancer; Urinary System Disease	-	0.2	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:346	Aromatase inhibition leads to male-biased sex ratio via impacts on gonad differentiation	Unclassified	WPHA/WNT Endorsed	0.2	KE:1789	Reduction, 17beta-estradiol synthesis by the undifferentiated gonad
AOP:348	Inhibition of 11β-Hydroxysteroid Dehydrogenase leading to decreased population trajectory	Unclassified	Under Development	0.4	KE:406	decreased, Fertility
AOP:348		Unclassified	Under Development	0.4	KE:1758	Impaired, Spermatogenesis
AOP:349	Inhibition of 11β-hydroxylase leading to decresed population trajectory	Unclassified	Under Development	0.5	KE:1836	Decreased plasma Cortisol level
					KE:1835	Cortisol and 11β-(OH) testosterone decreased
					KE:1798	Decreased spermatogenesis
					KE:406	decreased, Fertility
AOP:362	Immune mediated hepatitis	Gastrointestinal System Disease; Immune System Disease	-	0.12	KE:1817	Apoptotic cell death
AOP:368	Cytochrome oxidase inhibition leading to increased nasal lesions	Unclassified	-	0.33	KE:1825	Increase, Cell death
AOP:382	Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis	Musculoskeletal System Disease; Respiratory System Disease	Under Development	0.17	KE:1115	Increase, Reactive oxygen species
AOP:383	Inhibition of Angiotensin-converting enzyme 2 leading to liver fibrosis	Gastrointestinal System Disease	Under Development	0.17	KE:1115	Increase, Reactive oxygen species
AOP:384	Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease	Urinary System Disease	-	0.17	KE:1115	Increase, Reactive oxygen species
AOP:386	Deposition of ionizing energy leading to population decline via inhibition of photosynthesis	Reproductive System Disease	-	0.12	KE:1115	Increase, Reactive oxygen species
AOP:387	Deposition of ionising energy leading to population decline via mitochondrial dysfunction	Reproductive System Disease	-	0.12	KE:1115	Increase, Reactive oxygen species
AOP:388	Deposition of ionising energy leading to population decline via programmed cell death	Reproductive System Disease	-	0.2	KE:1864	Increase, Programmed cell death
AOP:397	Bulky DNA adducts leading to mutations	Genetic Disease	Under Development	0.33	KE:155	Inadequate DNA repair
AOP:409	Frustrated phagocytosis leads to malignant mesothelioma	Cancer	-	0.38	KE:1115	Increase, Reactive oxygen species
					KE:870	Increase, Cell Proliferation
					KE:1669	Increased, DNA damage and mutation
AOP:410	GSK3beta inactivation leading to increased mortality via defects in developing inner ear	Unclassified	-	0.1	KE:1825	Increase, Cell death
AOP:413	Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure	Unclassified	-	0.17	KE:1115	Increase, Reactive oxygen species
AOP:416	Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway	Cancer	-	0.33	KE:1669	Increased, DNA damage and mutation
AOP:416		Cancer	-	0.33	KE:1115	Increase, Reactive oxygen species
AOP:417	Aryl hydrocarbon receptor activation leading to lung cancer through AHR-ARNT toxicity pathway	Cancer	-	0.2	KE:1669	Increased, DNA damage and mutation
AOP:418	Aryl hydrocarbon receptor activation leading to impaired lung function through AHR-ARNT toxicity pathway	Respiratory System Disease	-	0.4	KE:1115	Increase, Reactive oxygen species
AOP:418		Respiratory System Disease	-	0.4	KE:1825	Increase, Cell death
AOP:419	Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway	Respiratory System Disease	-	0.25	KE:1262	Apoptosis
AOP:420	Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway	Cancer	-	0.25	KE:870	Increase, Cell Proliferation
AOP:431	Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)	Inherited Metabolic Disorder	-	0.2	KE:1952	Abnormal, Glucose homeostasis
AOP:432	Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia	Hematopoietic System Disease; Cancer	-	0.18	KE:870	Increase, Cell Proliferation
AOP:432		Hematopoietic System Disease; Cancer	-	0.18	KE:155	Inadequate DNA repair
AOP:437	Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity	Urinary System Disease	Under Development	0.2	KE:1392	Oxidative Stress
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic Disease; Cancer	Under Development	0.22	KE:1971	Increased, tumor growth
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic Disease; Cancer	Under Development	0.22	KE:1262	Apoptosis
AOP:441	Ionizing radiation-induced DNA damage leads to microcephaly via apoptosis and premature cell differentiation	Congenital Nervous System Abnormality; Nervous System Disease	-	0.14	KE:1262	Apoptosis
AOP:444	Ionizing radiation leads to reduced reproduction in Eisenia fetida via reduced spermatogenesis and cocoon hatchability	Unclassified	-	0.33	KE:1365	Increase, Apoptosis
					KE:1798	Decreased spermatogenesis
					KE:1392	Oxidative Stress
AOP:447	Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways	Urinary System Disease	-	0.17	KE:1365	Increase, Apoptosis
AOP:447		Urinary System Disease	-	0.17	KE:1392	Oxidative Stress
AOP:450	Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality	Nervous System Disease	-	0.14	KE:1392	Oxidative Stress
AOP:451	Interaction with lung resident cell membrane components leads to lung cancer	Cancer	-	0.33	KE:1115	Increase, Reactive oxygen species
					KE:870	Increase, Cell Proliferation
					KE:1669	Increased, DNA damage and mutation
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory System Disease	-	0.18	KE:1262	Apoptosis
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory System Disease	-	0.18	KE:1392	Oxidative Stress
AOP:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited Metabolic Disorder	-	0.17	KE:1392	Oxidative Stress
AOP:459	AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	-	0.11	KE:1392	Oxidative Stress
AOP:460	Antagonism of Smoothened receptor leading to orofacial clefting	Unclassified	Under Development	0.11	KE:1262	Apoptosis
AOP:464	Calcium overload in dopaminergic neurons of the substantia nigra leading to parkinsonian motor deficits	Nervous System Disease	-	0.11	KE:1825	Increase, Cell death
AOP:464		Nervous System Disease	-	0.11	KE:1392	Oxidative Stress
AOP:465	Alcohol dehydrogenase leading to reproductive dysfunction	Unclassified	-	0.12	KE:748	Increased, Estrogen receptor (ER) activity
AOP:468	Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)	Unclassified	-	0.12	KE:1825	Increase, Cell death
AOP:470	Deposition of energy leads to abnormal vascular remodeling	Cardiovascular System Disease	Under Review	0.25	KE:2244	Altered Stress Response Signaling
AOP:470	Deposition of energy leads to abnormal vascular remodeling	Cardiovascular System Disease	Under Review	0.25	KE:1392	Oxidative Stress
AOP:478	Deposition of energy leading to occurrence of cataracts	Nervous System Disease; Monogenic Disease	Under Review	0.4	KE:870	Increase, Cell Proliferation
					KE:1636	Increase, Chromosomal aberrations
					KE:155	Inadequate DNA repair
					KE:1392	Oxidative Stress
AOP:479	Mitochondrial complexes inhibition leading to left ventricular function decrease via increased myocardial oxidative stress	Cardiovascular System Disease; Thoracic Disease	Under Development	0.14	KE:1392	Oxidative Stress
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal System Disease	Under Review	0.29	KE:1825	Increase, Cell death
AOP:482	Deposition of energy leading to occurrence of bone loss	Musculoskeletal System Disease	Under Review	0.29	KE:1392	Oxidative Stress
AOP:483	Deposition of Energy Leading to Learning and Memory Impairment	Developmental Disorder Of Mental Health	Under Review	0.25	KE:2244	Altered Stress Response Signaling
AOP:483		Developmental Disorder Of Mental Health	Under Review	0.25	KE:1392	Oxidative Stress
AOP:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	0.17	KE:1262	Apoptosis
AOP:496	Androgen receptor agonism leading to reproduction dysfunction （in zebrafish）	Unclassified	-	0.2	KE:1690	Decrease, circulating testosterone levels
AOP:496		Unclassified	-	0.2	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:500	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis	Developmental Disorder Of Mental Health	-	0.29	KE:1115	Increase, Reactive oxygen species
AOP:500		Developmental Disorder Of Mental Health	-	0.29	KE:1262	Apoptosis
AOP:501	Excessive iron accumulation leading to neurological disorders	Nervous System Disease	-	0.25	KE:1392	Oxidative Stress
AOP:507	Nrf2 inhibition leading to vascular disrupting effects via inflammation pathway	Cardiovascular System Disease	-	0.17	KE:1392	Oxidative Stress
AOP:509	Nrf2 inhibition leading to vascular disrupting effects through activating apoptosis signal pathway and mitochondrial dysfunction	Cardiovascular System Disease	-	0.29	KE:1365	Increase, Apoptosis
AOP:509		Cardiovascular System Disease	-	0.29	KE:1392	Oxidative Stress
AOP:510	Demethylation of PPAR promotor leading to vascular disrupting effects	Cardiovascular System Disease	-	0.1	KE:1392	Oxidative Stress
AOP:521	Essential element imbalance leads to reproductive failure via oxidative stress	Unclassified	-	0.57	KE:1115	Increase, Reactive oxygen species
					KE:1758	Impaired, Spermatogenesis
					KE:2206	Increased, histomorphological alteration of testis
					KE:1392	Oxidative Stress
AOP:533	Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory	Developmental Disorder Of Mental Health	-	0.17	KE:1239	Altered, Gene Expression
AOP:535	Binding and activation of GPER leading to learning and memory impairments	Developmental Disorder Of Mental Health	-	0.33	KE:1262	Apoptosis
					KE:2233	Decreased, ERαβ heterodimers
					KE:1392	Oxidative Stress
AOP:549	Aromatase inhibition leads to reproductive toxicity (including growth and developmental toxicity) in adult female zebrafish	Unclassified	-	0.12	KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:550	Increased LMNA gene mutation leading to heart failure	Cardiovascular System Disease	-	0.2	KE:2066	Altered Signaling Pathways
AOP:563	Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis	Reproductive System Disease; Endocrine System Disease	-	0.33	KE:1262	Apoptosis
AOP:563		Reproductive System Disease; Endocrine System Disease	-	0.33	KE:1883	Decreased, size of the ovarian reserve
AOP:569	Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway	Developmental Disorder Of Mental Health	-	0.17	KE:1115	Increase, Reactive oxygen species
AOP:573	Inhibition, cytochrome oxidase leads to Increased, pulmonary edema	Respiratory System Disease	-	0.33	KE:1825	Increase, Cell death
AOP:574	Inhibition, cytochrome oxidase leads to Loss of olfactory function	Unclassified	-	0.33	KE:1825	Increase, Cell death

Associated AOPs with Level of Relevance 2

AOP Identifier	AOP Title	AO Classification	OECD Status	Coverage Score	KE Identifier	KE Name
AOP:6	Antagonist binding to PPARα leading to body-weight loss	Symptom	WPHA/WNT Endorsed	0.12	KE:864	Decreased, Body Weight
AOP:7	Aromatase (Cyp19a1) reduction leading to impaired fertility in adult female	Reproductive System Disease; Endocrine System Disease; Reproductive System Disease	Under Review	0.6	KE:406	decreased, Fertility
					KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
					KE:219	Reduction, Plasma 17beta-estradiol concentrations
AOP:18	PPARα activation in utero leading to impaired fertility in males	Reproductive System Disease	Under Review	0.25	KE:406	decreased, Fertility
AOP:18		Reproductive System Disease	Under Review	0.25	KE:1690	Decrease, circulating testosterone levels
AOP:43	Disruption of VEGFR Signaling Leading to Developmental Defects	Unclassified	WPHA/WNT Endorsed	0.2	KE:1001	Increased, Developmental Defects
AOP:64	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility	Reproductive System Disease	-	0.57	KE:406	decreased, Fertility
					KE:1690	Decrease, circulating testosterone levels
					KE:496	Increased apoptosis, decreased fetal/adult Leydig Cells
					KE:520	Decreased sperm quantity or quality in the adult, Decreased fertility
AOP:69	Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell	Reproductive System Disease	-	0.4	KE:645	Decreased Cholesterol, Decreased Testosterone Production by Adult Leydig Cells
AOP:69		Reproductive System Disease	-	0.4	KE:646	Decreased Cholesterol, Decreased sperm quantity and/or quality in the adult testis
AOP:124	HMG-CoA reductase inhibition leading to decreased fertility	Reproductive System Disease	-	0.33	KE:330	Decrease, Fertility
AOP:124	HMG-CoA reductase inhibition leading to decreased fertility	Reproductive System Disease	-	0.33	KE:1690	Decrease, circulating testosterone levels
AOP:139	Alkylation of DNA leading to cancer 1	Cancer	-	0.5	KE:885	Increase, Cancer
AOP:139	Alkylation of DNA leading to cancer 1	Cancer	-	0.5	KE:155	Inadequate DNA repair
AOP:205	AOP from chemical insult to cell death	Unclassified	-	0.17	KE:1262	Apoptosis
AOP:212	Histone deacetylase inhibition leading to testicular atrophy	Reproductive System Disease	WPHA/WNT Endorsed	0.33	KE:1506	Testicular atrophy
AOP:212		Reproductive System Disease	WPHA/WNT Endorsed	0.33	KE:1262	Apoptosis
AOP:296	Oxidative DNA damage leading to chromosomal aberrations and mutations	Genetic Disease; Chromosomal Disease	WPHA/WNT Endorsed	0.4	KE:155	Inadequate DNA repair
AOP:296		Genetic Disease; Chromosomal Disease	WPHA/WNT Endorsed	0.4	KE:1636	Increase, Chromosomal aberrations
AOP:322	Alkylation of DNA leading to reduced sperm count	Reproductive System Disease	-	0.6	KE:1757	Reduce, Sperm count
					KE:155	Inadequate DNA repair
					KE:1365	Increase, Apoptosis
AOP:345	Androgen receptor (AR) antagonism leading to decreased fertility in females	Endocrine System Disease; Reproductive System Disease; Reproductive System Disease	Under Development	0.17	KE:406	decreased, Fertility
AOP:398	Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogonia	Reproductive System Disease	Under Development	0.33	KE:406	decreased, Fertility
AOP:398		Reproductive System Disease	Under Development	0.33	KE:1883	Decreased, size of the ovarian reserve
AOP:474	Succinate dehydrogenase inactivation leads to cancer by promoting EMT	Cancer	Under Development	0.2	KE:885	Increase, Cancer
AOP:492	Glutathione conjugation leading to reproductive dysfunction via oxidative stress	Reproductive System Disease	-	0.4	KE:406	decreased, Fertility
AOP:492		Reproductive System Disease	-	0.4	KE:1115	Increase, Reactive oxygen species
AOP:504	SULT1E1 inhibition leading to uterine adenocarcinoma via increased estrogen availability at target organ level	Unclassified	-	0.67	KE:2251	Estradiol availability, increased
AOP:504		Unclassified	-	0.67	KE:1065	Activation, estrogen receptor alpha
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	0.5	KE:1115	Increase, Reactive oxygen species
					KE:885	Increase, Cancer
					KE:1392	Oxidative Stress
AOP:546	Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms	Cancer	-	0.2	KE:885	Increase, Cancer
AOP:561	Aromatase induction leading to estrogen receptor alpha activation via increased estradiol	Unclassified	-	0.6	KE:2251	Estradiol availability, increased
					KE:2294	Plasma estradiol, increased
					KE:1065	Activation, estrogen receptor alpha

Associated AOPs with Level of Relevance 3

AOP Identifier	AOP Title	AO Classification	OECD Status	Coverage Score	KE Identifier	KE Name
AOP:30	Estrogen receptor antagonism leading to reproductive dysfunction	Unclassified	Under Review	0.17	KE:112	Antagonism, Estrogen receptor
AOP:123	Unknown MIE leading to reproductive dysfunction via increased HIF-1alpha transcription	Unclassified	-	0.45	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
					KE:801	modulation, Unknown
					KE:802	Increased, HIF-1 alpha transcription
					KE:219	Reduction, Plasma 17beta-estradiol concentrations
					KE:799	Increased, HIF-1 heterodimer
AOP:167	Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.	Reproductive System Disease; Cancer	-	0.43	KE:1064	prepubertal increase, Estrogen receptor (ER) activity
					KE:1067	Proliferation/Clonal Expansion, aberrant basal cells
					KE:1065	Activation, estrogen receptor alpha
AOP:282	Adverse outcome pathway on photochemical toxicity initiated by light exposure	Unclassified	Under Review	0.25	KE:1115	Increase, Reactive oxygen species
AOP:298	Increase in reactive oxygen species (ROS) leading to human treatment-resistant gastric cancer via chronic ROS	Cancer; Gastrointestinal System Disease	Under Review	0.17	KE:1115	Increase, Reactive oxygen species
AOP:314	Binding to estrogen receptor (ER)-α in immune cells leading to exacerbation of systemic lupus erythematosus (SLE)	Immune System Disease; Musculoskeletal System Disease	Under Development	0.2	KE:1710	Binding to estrogen receptor (ER)-α in immune cells
AOP:324	Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and cell death	Unclassified	-	0.25	KE:1115	Increase, Reactive oxygen species
AOP:325	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and cell death	Unclassified	-	0.25	KE:1115	Increase, Reactive oxygen species
AOP:326	Excessive reactive oxygen species leading to growth inhibition via protein oxidation and cell death	Unclassified	-	0.25	KE:1115	Increase, Reactive oxygen species
AOP:327	Excessive reactive oxygen species production leading to mortality (1)	Unclassified	-	0.2	KE:1115	Increase, Reactive oxygen species
AOP:328	Excessive reactive oxygen species production leading to mortality (2)	Unclassified	-	0.2	KE:1115	Increase, Reactive oxygen species
AOP:329	Excessive reactive oxygen species production leading to mortality (3)	Unclassified	-	0.2	KE:1115	Increase, Reactive oxygen species
AOP:330	Excessive reactive oxygen species production leading to mortality (4)	Unclassified	-	0.4	KE:1115	Increase, Reactive oxygen species
AOP:330		Unclassified	-	0.4	KE:1365	Increase, Apoptosis
AOP:331	Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferation	Unclassified	-	0.17	KE:1115	Increase, Reactive oxygen species
AOP:332	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation	Unclassified	-	0.2	KE:1115	Increase, Reactive oxygen species
AOP:333	Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation	Unclassified	-	0.2	KE:1115	Increase, Reactive oxygen species
AOP:411	Oxidative stress Leading to Decreased Lung Function	Respiratory System Disease	-	0.25	KE:1392	Oxidative Stress
AOP:424	Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction	Respiratory System Disease	-	0.17	KE:1392	Oxidative Stress
AOP:425	Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1	Respiratory System Disease	-	0.17	KE:1392	Oxidative Stress
AOP:438	reactive oxygen species generation leading to increased cardiovascular morbidity and mortality	Cardiovascular System Disease	-	0.17	KE:1115	Increase, Reactive oxygen species
AOP:438		Cardiovascular System Disease	-	0.17	KE:1392	Oxidative Stress
AOP:440	Hypothalamus estrogen receptors activity suppression leading to ovarian cancer via ovarian epithelial cell hyperplasia	Benign Neoplasm; Endocrine System Disease; Reproductive System Disease; Reproductive System Disease; Cancer; Endocrine System Disease	Under Development	0.22	KE:1973	Increased, estrogens
AOP:440			Under Development	0.22	KE:1046	Suppression, Estrogen receptor (ER) activity
AOP:443	DNA damage and mutations leading to Metastatic Breast Cancer	Thoracic Disease; Cancer	Under Development	0.3	KE:1669	Increased, DNA damage and mutation
					KE:155	Inadequate DNA repair
					KE:112	Antagonism, Estrogen receptor
AOP:445	Estrogen Receptor Alpha Agonism leads to Impaired Reproduction	Reproductive System Disease	-	0.12	KE:1065	Activation, estrogen receptor alpha
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory System Disease	-	0.2	KE:1115	Increase, Reactive oxygen species
					KE:1262	Apoptosis
					KE:1239	Altered, Gene Expression
					KE:1392	Oxidative Stress
AOP:448	ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortality	Cardiovascular System Disease	-	0.12	KE:1115	Increase, Reactive oxygen species
AOP:448		Cardiovascular System Disease	-	0.12	KE:1392	Oxidative Stress
AOP:453	Reactive oxygen species and subsequent oxidative stress lead to increased incidence of digestive morbidity and mortality in the general population	Gastrointestinal System Disease	-	0.15	KE:1115	Increase, Reactive oxygen species
AOP:453		Gastrointestinal System Disease	-	0.15	KE:1392	Oxidative Stress
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal System Disease	-	0.27	KE:1115	Increase, Reactive oxygen species
					KE:1262	Apoptosis
					KE:1392	Oxidative Stress
AOP:469	Reactive oxygen speicies overproduction leading to increased digestive morbidity and mortality in generation population	Gastrointestinal System Disease	-	0.15	KE:1115	Increase, Reactive oxygen species
AOP:469		Gastrointestinal System Disease	-	0.15	KE:1392	Oxidative Stress
AOP:472	DNA adduct formation leading to kidney failure	Urinary System Disease	-	0.33	KE:1115	Increase, Reactive oxygen species
					KE:1392	Oxidative Stress
					KE:1825	Increase, Cell death
AOP:488	Increased reactive oxygen species production leading to decreased cognitive function	Cognitive Disorder	-	0.29	KE:1115	Increase, Reactive oxygen species
AOP:488		Cognitive Disorder	-	0.29	KE:1392	Oxidative Stress
AOP:503	Activation of uterine estrogen receptor-alfa leading to endometrial adenocarcinoma, via epigenetic modulation	Reproductive System Disease; Cancer	Under Review	0.17	KE:1065	Activation, estrogen receptor alpha
AOP:511	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects	Cardiovascular System Disease	-	0.12	KE:1115	Increase, Reactive oxygen species
AOP:511		Cardiovascular System Disease	-	0.12	KE:1392	Oxidative Stress
AOP:536	Estrogen receptor agonism leading to reduced survival and population growth due to renal failure	Unclassified	-	0.17	KE:111	Agonism, Estrogen receptor
AOP:537	Estrogen receptor agonism leads to reduced fecundity via increased vitellogenin in the liver	Unclassified	-	0.2	KE:111	Agonism, Estrogen receptor
AOP:540	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production	Unclassified	-	0.44	KE:3	Reduction, 17beta-estradiol synthesis by ovarian granulosa cells
					KE:1115	Increase, Reactive oxygen species
					KE:1262	Apoptosis
					KE:1392	Oxidative Stress
AOP:541	Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switching	Cardiovascular System Disease	-	0.15	KE:1115	Increase, Reactive oxygen species
AOP:541		Cardiovascular System Disease	-	0.15	KE:1392	Oxidative Stress

Associated AOPs with Level of Relevance 5

AOP Identifier	AOP Title	AO Classification	OECD Status	Coverage Score	KE Identifier	KE Name
AOP:423	Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway	Unclassified	-	0.33	KE:1115	Increase, Reactive oxygen species
AOP:423		Unclassified	-	0.33	KE:1817	Apoptotic cell death
AOP:493	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity	Acquired Metabolic Disease	-	0.2	KE:2126	Estrogen receptor alpha inactivation
AOP:493		Acquired Metabolic Disease	-	0.2	KE:2129	Metabolically unhealthy Obesity
AOP:497	ERa inactivation alters mitochondrial functions and insulin signalling in skeletal muscle and leads to insulin resistance and metabolic syndrome	Inherited Metabolic Disorder; Disease Of Metabolism	-	0.5	KE:1115	Increase, Reactive oxygen species
					KE:2126	Estrogen receptor alpha inactivation
					KE:2145	Metabolic syndrome
					KE:1392	Oxidative Stress
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	0.6	KE:1115	Increase, Reactive oxygen species
					KE:885	Increase, Cancer
					KE:1392	Oxidative Stress
AOP:513	Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway	Cancer	-	0.4	KE:1115	Increase, Reactive oxygen species
AOP:513		Cancer	-	0.4	KE:885	Increase, Cancer

Butylparaben

Associated AOPs with Level of Relevance 1

Associated AOPs with Level of Relevance 2

Associated AOPs with Level of Relevance 3

Associated AOPs with Level of Relevance 5

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