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Butylparaben

Associated curated AOPs from AOP-Wiki

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Associated AOPs with Level of Relevance 1
AOPs with at least 1 KE associated with chemical, where the KE(s) are neither MIE nor AO

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
AOPs with at least 1 AO associated with chemical, and no associated MIE

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
AOPs with at least 1 MIE associated with chemical, and no associated AO

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
AOPs with at least 1 MIE and AO associated with chemical, and there exists a directed path between that MIE and AO

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

Glossary of Terms

AOP: Adverse Outcome Pathway
MIE: Molecular Initiating Event
KE: Key Event
AO: Adverse Outcome
Coverage score: The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints
Level of relevance: Qualitative rank based on the kind of associated KEs within the corresponding AOP
AO classification: The disease category corresponding to the AO in the AOP obtained from Disease Ontology

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006974 - cellular response to DNA damage stimulus
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Oxidative stress in liver Oxidative stress in testis
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased estradiol levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased estradiol levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0072593 - reactive oxygen species metabolic process
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive regulation of cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive regulation of cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased LH levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased LH levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006974 - cellular response to DNA damage stimulus
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased LH levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive regulation of cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CCTE_Deisenroth_AIME_384WELL_LUC_Inactive - gain ATG_ERE_CIS - activatory ATG_ERa_TRANS - gain ACEA_ER_80hr - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive regulation of cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive regulation of cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive regulation of cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased testosterone levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Increased LH levels in offspring
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive regulation of cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_HIF1a_CIS - activatory

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive regulation of cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive regulation of cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006974 - cellular response to DNA damage stimulus
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Induce apoptosis of spermatogenic cells
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_HIF1a_CIS - activatory

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects sexual behavior
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D019457 - Chromosome Breakage
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects expression of androgen receptor (AR) in offspring Affects expression of estrogen receptor-beta (ER-beta) in offspring
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects implantation in offspring Induce apoptosis of spermatogenic cells
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive regulation of cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D019457 - Chromosome Breakage
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D010182 - Pancreatic Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects spermatogenesis Affects spermatogenesis in offspring
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased estradiol levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects fertility in offspring
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decrease in cortisol levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decrease in cortisol levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects spermatogenesis
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Induce apoptosis of spermatogenic cells
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Induce apoptosis of spermatogenic cells
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D006943 - Hyperglycemia
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Cancer phenotype
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Induce apoptosis of spermatogenic cells
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CCTE_Deisenroth_AIME_384WELL_LUC_Inactive - gain ATG_ERE_CIS - activatory ATG_ERa_TRANS - gain ACEA_ER_80hr - gain OT_ER_ERaERb_0480 - gain OT_ER_ERbERb_0480 - gain OT_ER_ERbERb_1440 - gain TOX21_ERa_LUC_VM7_Agonist - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Oxidative stress in liver Oxidative stress in testis
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased testis weights
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects estrogen signaling Affects expression of estrogen receptor-alpha (ER-alpha) in offspring Affects expression of estrogen receptor-beta (ER-beta) Affects expression of estrogen receptor-beta (ER-beta) in offspring
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects estrogen signaling
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects ovarian follicles population in offspring
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D015431 - Weight Loss
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CCTE_Padilla_ZF_144hpf_TERATOSCORE - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Alterations in number of leydig cells
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Reduced sperm counts Reduced sperm quality Reduced sperm counts in offspring
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased testosterone levels in offspring
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Reduced sperm quality
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Affects fertility in offspring
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Cancer phenotype
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Decreased testis weights
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Reduced sperm counts Reduced sperm counts in offspring
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Increased estradiol levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CCTE_Deisenroth_AIME_384WELL_LUC_Inactive - gain ATG_ERa_TRANS - gain OT_ER_ERaERb_0480 - gain TOX21_ERa_LUC_VM7_Agonist - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Increased estradiol levels
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CCTE_Deisenroth_AIME_384WELL_LUC_Shift - inhibitory NVS_NR_hER - loss NVS_NR_mERa - loss

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_HIF1a_CIS - activatory

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_HIF1a_CIS - activatory

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	TOX21_ERa_LUC_VM7_Agonist - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008284 - positive regulation of cell population proliferation
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	OT_ER_ERaERb_0480 - gain TOX21_ERa_LUC_VM7_Agonist - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	ATG_ERE_CIS - activatory ATG_ERa_TRANS - gain ACEA_ER_80hr - gain

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	CCTE_Deisenroth_AIME_384WELL_LUC_Shift - inhibitory NVS_NR_hER - loss

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	NVS_NR_hER - loss NVS_NR_mERa - loss

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	Lead to obesity in offspring Lead to obesity
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D006943 - Hyperglycemia
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

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DISCLAIMER

TICToK is a knowledgebase of chemicals found in tattoo inks, compiled from publicly available regulatory and scientific resources. The chemical classifications presented in this knowledgebase are derived from multiple publicly available resources and are provided solely for informational purposes, and they are neither authoritative nor binding. The chemical-AOP mappings compiled in this knowledgebase serve as plausible hypotheses for research, and further experimental validation is required to definitively establish these potential toxicity mechanisms. The authors bear no responsibility for any errors, omissions, or inconsistencies originating from these external sources. Users are advised to exercise independent judgment when interpreting chemical classifications and any other data provided in this resource. Importantly, our sole goal to build this resource on tattoo ink chemicals is to enable future basic research on this topic, and it does not necessarily reflect the views or objectives of our employers or funders.

Butylparaben

Associated AOPs with Level of Relevance 1 AOPs with at least 1 KE associated with chemical, where the KE(s) are neither MIE nor AO

Associated AOPs with Level of Relevance 2AOPs with at least 1 AO associated with chemical, and no associated MIE

Associated AOPs with Level of Relevance 3AOPs with at least 1 MIE associated with chemical, and no associated AO

Associated AOPs with Level of Relevance 5AOPs with at least 1 MIE and AO associated with chemical, and there exists a directed path between that MIE and AO