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Zinc

Associated High Confidence AOPs

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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:21	Aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2	Unclassified	WPHA/WNT Endorsed	0.2	KE:317	Altered, Cardiovascular development/function
AOP:27	Cholestatic Liver Injury induced by Inhibition of the Bile Salt Export Pump (ABCB11)	Gastrointestinal System Disease	Under Development	0.25	KE:149	Increase, Inflammation
AOP:27		Gastrointestinal System Disease	Under Development	0.25	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	0.4	KE:1496	Increased, secretion of proinflammatory mediators
AOP:39		Respiratory System Disease	Under Development	0.4	KE:272	Activation/Proliferation, T-cells
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal System Disease	Under Review	0.4	KE:854	Alterations, Cellular proliferation / hyperplasia
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal System Disease	Under Review	0.4	KE:853	Changes/Inhibition, Cellular Homeostasis and Apoptosis
AOP:58	NR1I3 (CAR) suppression leading to hepatic steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.06	KE:458	Increased, De Novo FA synthesis
AOP:64	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility	Reproductive System Disease	-	0.14	KE:496	Increased apoptosis, decreased fetal/adult Leydig Cells
AOP:73	Xenobiotic Inhibition of Dopamine-beta-Hydroxylase and subsequent reduced fecundity	Unclassified	-	0.08	KE:531	Decreased, LH Surge
AOP:77	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1	Unclassified	-	0.14	KE:341	Impairment, Learning and memory
AOP:78	Nicotinic acetylcholine receptor activation contributes to abnormal role change within the worker bee caste leading to colony death failure 1	Unclassified	-	0.12	KE:341	Impairment, Learning and memory
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:87	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure	Unclassified	-	0.12	KE:341	Impairment, Learning and memory
AOP:88	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony loss/failure via abnormal role change within caste	Unclassified	-	0.14	KE:341	Impairment, Learning and memory
AOP:89	Nicotinic acetylcholine receptor activation followed by desensitization contributes to abnormal foraging and directly leads to colony loss/failure	Unclassified	-	0.12	KE:341	Impairment, Learning and memory
AOP:90	Nicotinic acetylcholine receptor activation contributes to abnormal roll change within the worker bee caste leading to colony loss/failure 2	Unclassified	-	0.12	KE:341	Impairment, Learning and memory
AOP:99	Histamine (H2) receptor antagonism leading to reduced survival	Unclassified	-	0.14	KE:341	Impairment, Learning and memory
AOP:105	Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary System Disease	-	0.17	KE:710	Increase, Regenerative cell proliferation (tubular epithelial cells)
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:108	Inhibition of pyruvate dehydrogenase kinase leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal System Disease	-	0.17	KE:768	Increase, Cytotoxicity
AOP:109	Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)	Cancer; Respiratory System Disease	-	0.2	KE:734	Increase, Regenerative cell proliferation (terminal bronchiolar epithelial cells)
AOP:110	Inhibition of iodide pump activity leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine System Disease	-	0.29	KE:277	Thyroid hormone synthesis, Decreased
AOP:110		Cancer; Endocrine System Disease	-	0.29	KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:114	HPPD inhibition leading to corneal papillomas and carcinomas (in rat)	Cancer	-	0.33	KE:777	Increase, Inflammation (corneal cells)
AOP:114		Cancer	-	0.33	KE:778	Increase, Regenerative cell proliferation (corneal cells)
AOP:115	Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)	Cancer	-	0.4	KE:149	Increase, Inflammation
AOP:115		Cancer	-	0.4	KE:781	Increase, Regenerative cell proliferation (forestomach epithelial cells)
AOP:116	Cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary System Disease	-	0.25	KE:710	Increase, Regenerative cell proliferation (tubular 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	-	0.29	KE:277	Thyroid hormone synthesis, Decreased
AOP:119		Cancer; Endocrine System Disease	-	0.29	KE:739	Increase, Hypertrophy and proliferation (follicular cell)
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:126	Alpha-noradrenergic antagonism leads to reduced fecundity via delayed ovulation	Unclassified	-	0.08	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	0.29	KE:768	Increase, Cytotoxicity
AOP:136		Benign Neoplasm; Respiratory System Disease	Under Review	0.29	KE:870	Increase, Cell Proliferation
AOP:144	Endocytic lysosomal uptake leading to liver fibrosis	Gastrointestinal System Disease	Under Review	0.33	KE:1494	Leukocyte recruitment/activation
					KE:68	Accumulation, Collagen
					KE:1493	Increased Pro-inflammatory mediators
AOP:150	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF	Unclassified	WPHA/WNT Endorsed	0.14	KE:317	Altered, Cardiovascular development/function
AOP:159	Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation	Unclassified	WPHA/WNT Endorsed	0.12	KE:277	Thyroid hormone synthesis, Decreased
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:167	Early-life estrogen receptor activity leading to endometrial carcinoma in the mouse.	Reproductive System Disease; Cancer	-	0.14	KE:1067	Proliferation/Clonal Expansion, aberrant basal cells
AOP:173	Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis	Musculoskeletal System Disease; Respiratory System Disease	WPHA/WNT Endorsed	0.38	KE:68	Accumulation, Collagen
					KE:1497	Increased, recruitment of inflammatory cells
					KE:1496	Increased, secretion of proinflammatory mediators
AOP:175	Thyroperoxidase inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:176	Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.2	KE:277	Thyroid hormone synthesis, Decreased
AOP:188	Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.2	KE:277	Thyroid hormone synthesis, Decreased
AOP:192	Pendrin inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:193	Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis	Unclassified	-	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:206	Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis	Musculoskeletal System Disease; Respiratory System Disease	Under Development	0.17	KE:149	Increase, Inflammation
AOP:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive System Disease	-	0.38	KE:1281	Increased, DNA Damage-Repair
					KE:1115	Increase, Reactive oxygen species
					KE:1262	Apoptosis
AOP:212	Histone deacetylase inhibition leading to testicular atrophy	Reproductive System Disease	WPHA/WNT Endorsed	0.33	KE:1262	Apoptosis
AOP:212		Reproductive System Disease	WPHA/WNT Endorsed	0.33	KE:1503	Histone acetylation, increase
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:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal System Disease	WPHA/WNT Endorsed	0.2	KE:1394	Induction, persistent proliferation/sustained proliferation
AOP:237	Substance interaction with lung resident cell membrane components leading to atherosclerosis	Cardiovascular System Disease	Under Development	0.2	KE:1496	Increased, secretion of proinflammatory mediators
AOP:241	Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis	Musculoskeletal System Disease; Respiratory System Disease	-	0.17	KE:68	Accumulation, Collagen
AOP:245	Reduction in photophosphorylation leading to growth inhibition in aquatic plants	Unclassified	-	0.09	KE:40	Decrease, Mitochondrial ATP production
AOP:271	Inhibition of thyroid peroxidase leading to impaired fertility in fish	Unclassified	Under Development	0.2	KE:277	Thyroid hormone synthesis, Decreased
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	0.29	KE:870	Increase, Cell Proliferation
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	0.29	KE:155	Inadequate DNA repair
AOP:275	Histone deacetylase inhibition leads to neural tube defects	Neural Tube Defect	-	0.2	KE:1503	Histone acetylation, increase
AOP:277	Impaired IL-1R1 signaling leading to Impaired T-Cell Dependent Antibody Response	Immune System Disease	WPHA/WNT Endorsed	0.25	KE:202	Inhibition, Nuclear factor kappa B (NF-kB)
AOP:280	α-diketone-induced bronchiolitis obliterans	Musculoskeletal System Disease; Respiratory System Disease	-	0.14	KE:149	Increase, Inflammation
AOP:286	Mitochondrial complex III antagonism leading to growth inhibition (1)	Unclassified	-	0.5	KE:1821	Decrease, Cell proliferation
AOP:286		Unclassified	-	0.5	KE:1771	Decrease, Adenosine triphosphate pool
AOP:287	Mitochondrial complex III antagonism leading to growth inhibition (2)	Unclassified	-	0.25	KE:1771	Decrease, Adenosine triphosphate pool
AOP:290	Mitochondrial ATP synthase antagonism leading to growth inhibition (1)	Unclassified	-	0.5	KE:1821	Decrease, Cell proliferation
AOP:290		Unclassified	-	0.5	KE:1771	Decrease, Adenosine triphosphate pool
AOP:291	Mitochondrial ATP synthase antagonism leading to growth inhibition (2)	Unclassified	-	0.25	KE:1771	Decrease, Adenosine triphosphate pool
AOP:296	Oxidative DNA damage leading to chromosomal aberrations and mutations	Genetic Disease; Chromosomal Disease	WPHA/WNT Endorsed	0.2	KE:155	Inadequate DNA repair
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:1497	Increased, recruitment of inflammatory cells
					KE:870	Increase, Cell Proliferation
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:315	Inhibition of JAK3 leading to impairment of T-Cell Dependent Antibody Response	Immune System Disease	Under Development	0.2	KE:1716	Blockade of STAT5 phosphorylation
AOP:320	Binding of SARS-CoV-2 to ACE2 receptor leading to acute respiratory distress associated mortality	Unclassified	Under Development	0.33	KE:1847	Increased SARS-CoV-2 production
					KE:1750	Increased inflammatory immune responses
					KE:1496	Increased, secretion of proinflammatory mediators
AOP:321	Reduced environmental pH leading to thinner shells in Mytilus edulis	Unclassified	-	0.18	KE:10041	Altered metabolic rate
AOP:321		Unclassified	-	0.18	KE:10042	Abnormal development
AOP:322	Alkylation of DNA leading to reduced sperm count	Reproductive System Disease	-	0.2	KE:155	Inadequate DNA repair
AOP:323	PPARalpha Agonism Leading to Decreased Viable Offspring via Decreased 11-Ketotestosterone	Unclassified	-	0.17	KE:807	Decreased, cholesterol
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:362	Immune mediated hepatitis	Gastrointestinal System Disease; Immune System Disease	-	0.12	KE:1633	Increase in inflammation
AOP:363	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure	Unclassified	Under Review	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:363		Unclassified	Under Review	0.25	KE:1877	Altered, retinal layer structure
AOP:364	Thyroperoxidase inhibition leading to altered visual function via decreased eye size	Unclassified	Under Development	0.12	KE:277	Thyroid hormone synthesis, Decreased
AOP:365	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning	Unclassified	Under Development	0.12	KE:277	Thyroid hormone synthesis, Decreased
AOP:374	Binding of Sars-CoV-2 spike protein to ACE 2 receptors expressed on brain cells (neuronal and non-neuronal) leads to neuroinflammation resulting in encephalitis	Nervous System Disease	Under Development	0.25	KE:352	N/A, Neurodegeneration
AOP:379	Binding to ACE2 leading to thrombosis and disseminated intravascular coagulation	Cardiovascular System Disease	Under Development	0.29	KE:1847	Increased SARS-CoV-2 production
AOP:379		Cardiovascular System Disease	Under Development	0.29	KE:1869	Diminished protective oxidative stress response
AOP:382	Angiotensin II type 1 receptor (AT1R) agonism leading to lung fibrosis	Musculoskeletal System Disease; Respiratory System Disease	Under Development	0.67	KE:1115	Increase, Reactive oxygen species
					KE:68	Accumulation, Collagen
					KE:1496	Increased, secretion of proinflammatory mediators
					KE:1172	Increased activation, Nuclear factor kappa B (NF-kB)
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: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	-	0.25	KE:40	Decrease, Mitochondrial ATP production
AOP:387		Reproductive System Disease	-	0.25	KE:1115	Increase, Reactive oxygen species
AOP:394	SARS-CoV-2 infection of olfactory epithelium leading to impaired olfactory function (short-term anosmia)	Endocrine System Disease	Under Development	0.14	KE:1847	Increased SARS-CoV-2 production
AOP:397	Bulky DNA adducts leading to mutations	Genetic Disease	Under Development	0.33	KE:155	Inadequate DNA repair
AOP:399	Inhibition of Fyna leading to increased mortality via decreased eye size (Microphthalmos)	Unclassified	-	0.12	KE:1821	Decrease, Cell proliferation
AOP:409	Frustrated phagocytosis leads to malignant mesothelioma	Cancer	-	0.5	KE:1115	Increase, Reactive oxygen species
					KE:870	Increase, Cell Proliferation
					KE:1497	Increased, recruitment of inflammatory cells
					KE:1496	Increased, secretion of proinflammatory mediators
AOP:413	Oxidation and antagonism of reduced glutathione leading to mortality via acute renal failure	Unclassified	-	0.33	KE:1115	Increase, Reactive oxygen species
AOP:413		Unclassified	-	0.33	KE:759	Increased, Kidney Failure
AOP:416	Aryl hydrocarbon receptor activation leading to lung cancer through IL-6 toxicity pathway	Cancer	-	0.17	KE:1115	Increase, Reactive oxygen species
AOP:420	Aryl hydrocarbon receptor activation leading to lung cancer through sustained NRF2 toxicity pathway	Cancer	-	0.25	KE:870	Increase, Cell Proliferation
AOP:422	Binding of SARS-CoV-2 to ACE2 in enterocytes leads to intestinal barrier disruption	Gastrointestinal System Disease	Under Development	0.2	KE:1847	Increased SARS-CoV-2 production
AOP:430	Binding of SARS-CoV-2 to ACE2 leads to viral infection proliferation	Viral Infectious Disease	Under Development	0.2	KE:1847	Increased SARS-CoV-2 production
AOP:432	Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia	Hematopoietic System Disease; Cancer	-	0.36	KE:155	Inadequate DNA repair
					KE:870	Increase, Cell Proliferation
					KE:1493	Increased Pro-inflammatory mediators
					KE:403	Suppression, Immune system
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic Disease; Cancer	Under Development	0.33	KE:149	Increase, Inflammation
					KE:1971	Increased, tumor growth
					KE:1262	Apoptosis
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:1052	Hyperplasia, ovarian epithelium
AOP:440			Under Development	0.22	KE:1050	Increased, secretion of LH from anterior pituitary
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:443	DNA damage and mutations leading to Metastatic Breast Cancer	Thoracic Disease; Cancer	Under Development	0.2	KE:155	Inadequate DNA repair
AOP:443		Thoracic Disease; Cancer	Under Development	0.2	KE:1172	Increased activation, Nuclear factor kappa B (NF-kB)
AOP:450	Inhibition of AChE and activation of CYP2E1 leading to sensory axonal peripheral neuropathy and mortality	Nervous System Disease	-	0.14	KE:352	N/A, Neurodegeneration
AOP:451	Interaction with lung resident cell membrane components leads to lung cancer	Cancer	-	0.44	KE:1115	Increase, Reactive oxygen species
					KE:870	Increase, Cell Proliferation
					KE:1497	Increased, recruitment of inflammatory cells
					KE:1496	Increased, secretion of proinflammatory mediators
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory System Disease	-	0.09	KE:1262	Apoptosis
AOP:456	Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity	Unclassified	Under Review	0.17	KE:317	Altered, Cardiovascular development/function
AOP:460	Antagonism of Smoothened receptor leading to orofacial clefting	Unclassified	Under Development	0.33	KE:1821	Decrease, Cell proliferation
					KE:1262	Apoptosis
					KE:2043	Decrease, Sonic Hedgehog second messenger production
AOP:465	Alcohol dehydrogenase leading to reproductive dysfunction	Unclassified	-	0.12	KE:2050	Increase, developmental abnormalities
AOP:467	Knickkopf leading to mortality	Unclassified	-	0.11	KE:2050	Increase, developmental abnormalities
AOP:470	Deposition of energy leads to abnormal vascular remodeling	Cardiovascular System Disease	Under Review	0.12	KE:1493	Increased Pro-inflammatory mediators
AOP:478	Deposition of energy leading to occurrence of cataracts	Nervous System Disease; Monogenic Disease	Under Review	0.2	KE:870	Increase, Cell Proliferation
AOP:478	Deposition of energy leading to occurrence of cataracts	Nervous System Disease; Monogenic Disease	Under Review	0.2	KE:155	Inadequate DNA repair
AOP:480	Mitochondrial complexes inhibition leading to heart failure via decreased ATP production	Cardiovascular System Disease; Thoracic Disease	Under Development	0.2	KE:40	Decrease, Mitochondrial ATP production
AOP:491	Decrease, GLI1/2 target gene expression leads to orofacial clefting	Unclassified	Under Development	0.5	KE:1821	Decrease, Cell proliferation
					KE:1262	Apoptosis
					KE:2043	Decrease, Sonic Hedgehog second messenger production
AOP:492	Glutathione conjugation leading to reproductive dysfunction via oxidative stress	Reproductive System Disease	-	0.2	KE:1115	Increase, Reactive oxygen species
AOP:493	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity	Acquired Metabolic Disease	-	0.4	KE:1633	Increase in inflammation
					KE:1497	Increased, recruitment of inflammatory cells
					KE:2125	Increased fat mass
					KE:2119	Insulin resistance, increased
AOP:518	Liver X Receptor (LXR) activation leads to liver steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.2	KE:89	Synthesis, De Novo Fatty Acid (FA)
AOP:521	Essential element imbalance leads to reproductive failure via oxidative stress	Unclassified	-	0.14	KE:1115	Increase, Reactive oxygen species
AOP:544	Inhibition of neuropathy target esterase leading to delayed neuropathy via increased inflammation	Nervous System Disease	-	0.17	KE:149	Increase, Inflammation
AOP:563	Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis	Reproductive System Disease; Endocrine System Disease	-	0.17	KE:1262	Apoptosis
AOP:564	DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.	Unclassified	-	0.09	KE:40	Decrease, Mitochondrial ATP production
AOP:569	Decreased DNA methylation of FAM50B/PTCHD3 leading to IQ loss of children via PI3K-Akt pathway	Developmental Disorder Of Mental Health	-	0.33	KE:1115	Increase, Reactive oxygen species
AOP:569		Developmental Disorder Of Mental Health	-	0.33	KE:2195	Increase, CNS Neural 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:12	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development leads to neurodegeneration with impairment in learning and memory in aging	Nervous System Disease; Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	0.25	KE:341	Impairment, Learning and memory
AOP:12			WPHA/WNT Endorsed	0.25	KE:352	N/A, Neurodegeneration
AOP:13	Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities	Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	0.1	KE:341	Impairment, Learning and memory
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	0.3	KE:1492	Tissue resident cell activation
					KE:1493	Increased Pro-inflammatory mediators
					KE:341	Impairment, Learning and memory
AOP:34	LXR activation leading to hepatic steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.15	KE:89	Synthesis, De Novo Fatty Acid (FA)
AOP:34	LXR activation leading to hepatic steatosis		-	0.15	KE:345	N/A, Liver Steatosis
AOP:40	Covalent Protein binding leading to Skin Sensitisation	Integumentary System Disease	WPHA/WNT Endorsed	0.6	KE:827	sensitisation, skin
					KE:826	Activation, Keratinocytes
					KE:272	Activation/Proliferation, T-cells
AOP:42	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	WPHA/WNT Endorsed	0.25	KE:277	Thyroid hormone synthesis, Decreased
AOP:42		Cognitive Disorder	WPHA/WNT Endorsed	0.25	KE:402	Cognitive function, decreased
AOP:48	Binding of agonists to ionotropic glutamate receptors in adult brain causes excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment.	Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	0.22	KE:341	Impairment, Learning and memory
AOP:48		Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	0.22	KE:352	N/A, Neurodegeneration
AOP:54	Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment	Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	0.2	KE:277	Thyroid hormone synthesis, Decreased
AOP:54		Developmental Disorder Of Mental Health	WPHA/WNT Endorsed	0.2	KE:341	Impairment, Learning and memory
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:807	Decreased, cholesterol
AOP:134	Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	-	0.22	KE:277	Thyroid hormone synthesis, Decreased
AOP:134		Cognitive Disorder	-	0.22	KE:402	Cognitive function, decreased
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:148	EGFR Activation Leading to Decreased Lung Function	Respiratory System Disease	Under Development	0.25	KE:1250	Decrease, Lung function
AOP:149	Peptide Oxidation Leading to Hypertension	Cardiovascular System Disease	Under Development	0.3	KE:927	KE1 : S-Glutathionylation, eNOS
					KE:952	Hypertension
					KE:933	KE6 : Depletion, Nitric Oxide
AOP:151	AhR activation leading to preeclampsia	Cardiovascular System Disease	Under Development	0.14	KE:1893	increase, Preeclampsia
AOP:196	Volatile Organic Chemicals Activate TRPA1 Receptor to Induce Sensory Pulmonary Irritation	Respiratory System Disease	-	0.11	KE:1226	Increased Respiratory irritability and Chronic Cough,
AOP:205	AOP from chemical insult to cell death	Unclassified	-	0.17	KE:1262	Apoptosis
AOP:227	NSAID induced PTGS1 inactivation to gastric ulcer	Gastrointestinal System Disease	-	0.14	KE:1385	Activated, gastric ulcer formation
AOP:228	NSAID induced PTGS2 inactivation to gastric ulcer	Gastrointestinal System Disease	-	0.2	KE:1385	Activated, gastric ulcer formation
AOP:260	CYP2E1 activation and formation of protein adducts leading to neurodegeneration	Nervous System Disease	-	0.14	KE:1514	Neurodegeneration
AOP:261	L-type calcium channel blockade leading to heart failure via decrease in cardiac contractility	Cardiovascular System Disease	Under Development	0.12	KE:1535	Heart failure
AOP:269	Elevated ATP demand for detoxification and repair mechanisms leading to impaired growth and development	Unclassified	-	0.17	KE:10013	Impaired growth and development
AOP:278	IKK complex inhibition leading to liver injury	Unclassified	-	0.25	KE:1549	Liver Injury
AOP:278	IKK complex inhibition leading to liver injury	Unclassified	-	0.25	KE:202	Inhibition, Nuclear factor kappa B (NF-kB)
AOP:281	Acetylcholinesterase Inhibition Leading to Neurodegeneration	Nervous System Disease	-	0.1	KE:352	N/A, Neurodegeneration
AOP:293	Increased DNA damage leading to increased risk of breast cancer	Genetic Disease; Thoracic Disease; Cancer	Under Development	0.56	KE:1193	N/A, Breast Cancer
					KE:1492	Tissue resident cell activation
					KE:1182	Increase, Cell Proliferation (Epithelial Cells)
					KE:1494	Leukocyte recruitment/activation
					KE:1493	Increased Pro-inflammatory mediators
AOP:294	Increased reactive oxygen and nitrogen species (RONS) leading to increased risk of breast cancer	Genetic Disease; Thoracic Disease; Cancer	Under Development	0.56	KE:1193	N/A, Breast Cancer
					KE:1492	Tissue resident cell activation
					KE:1182	Increase, Cell Proliferation (Epithelial Cells)
					KE:1494	Leukocyte recruitment/activation
					KE:1493	Increased Pro-inflammatory mediators
AOP:300	Thyroid Receptor Antagonism and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	Under Development	0.2	KE:402	Cognitive function, decreased
AOP:302	Lung surfactant function inhibition leading to decreased lung function	Respiratory System Disease	Under Development	0.2	KE:1250	Decrease, Lung function
AOP:384	Hyperactivation of ACE/Ang-II/AT1R axis leading to chronic kidney disease	Urinary System Disease	-	0.33	KE:1115	Increase, Reactive oxygen species
AOP:384		Urinary System Disease	-	0.33	KE:1603	Chronic kidney disease
AOP:392	Decreased fibrinolysis and activated bradykinin system leading to hyperinflammation	Unclassified	Under Development	0.6	KE:1868	Hyperinflammation
					KE:1497	Increased, recruitment of inflammatory cells
					KE:1496	Increased, secretion of proinflammatory mediators
AOP:405	Organo-Phosphate Chemicals induced inhibition of AChE leading to impaired cognitive function	Cognitive Disorder	-	0.2	KE:402	Cognitive function, decreased
AOP:406	SARS-CoV-2 infection leading to hyperinflammation	Unclassified	-	0.5	KE:1868	Hyperinflammation
					KE:1847	Increased SARS-CoV-2 production
					KE:1869	Diminished protective oxidative stress response
AOP:411	Oxidative stress Leading to Decreased Lung Function	Respiratory System Disease	-	0.25	KE:1250	Decrease, Lung function
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:1250	Decrease, Lung function
AOP:419	Aryl hydrocarbon receptor activation leading to impaired lung function through P53 toxicity pathway	Respiratory System Disease	-	0.5	KE:1250	Decrease, Lung function
AOP:419		Respiratory System Disease	-	0.5	KE:1262	Apoptosis
AOP:424	Oxidative stress Leading to Decreased Lung Function via CFTR dysfunction	Respiratory System Disease	-	0.17	KE:1250	Decrease, Lung function
AOP:425	Oxidative Stress Leading to Decreased Lung Function via Decreased FOXJ1	Respiratory System Disease	-	0.17	KE:1250	Decrease, Lung function
AOP:431	Increased tumor necrosis factor (TNF) leading to increased risk of gestational diabetes mellitus (GDM)	Inherited Metabolic Disorder	-	0.4	KE:1953	Gestational diabetes mellitus
AOP:431		Inherited Metabolic Disorder	-	0.4	KE:1952	Abnormal, Glucose homeostasis
AOP:433	hERG channel blockade leading to sudden cardiac death	Cardiovascular System Disease	-	0.17	KE:1964	Sudden cardiac death
AOP:442	Binding to voltage gate sodium channels during development leads to cognitive impairment	Cognitive Disorder	Under Review	0.14	KE:402	Cognitive function, decreased
AOP:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited Metabolic Disorder	-	0.33	KE:277	Thyroid hormone synthesis, Decreased
AOP:457		Inherited Metabolic Disorder	-	0.33	KE:2119	Insulin resistance, increased
AOP:458	AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	-	0.12	KE:402	Cognitive function, decreased
AOP:459	AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive Disorder	-	0.22	KE:277	Thyroid hormone synthesis, Decreased
AOP:459		Cognitive Disorder	-	0.22	KE:402	Cognitive function, decreased
AOP:468	Binding of SARS-CoV-2 to ACE2 leads to hyperinflammation (via cell death)	Unclassified	-	0.5	KE:1847	Increased SARS-CoV-2 production
					KE:1868	Hyperinflammation
					KE:1497	Increased, recruitment of inflammatory cells
					KE:1496	Increased, secretion of proinflammatory mediators
AOP:474	Succinate dehydrogenase inactivation leads to cancer by promoting EMT	Cancer	Under Development	0.2	KE:885	Increase, Cancer
AOP:475	Binding of chemicals to ionotropic glutamate receptors leads to impairment of learning and memory via loss of drebrin from dendritic spines of neurons	Developmental Disorder Of Mental Health	Under Development	0.12	KE:341	Impairment, Learning and memory
AOP:483	Deposition of Energy Leading to Learning and Memory Impairment	Developmental Disorder Of Mental Health	Under Review	0.25	KE:1492	Tissue resident cell activation
AOP:483		Developmental Disorder Of Mental Health	Under Review	0.25	KE:341	Impairment, Learning and memory
AOP:485	Thyroid hormone antagonism leading to impaired oligodendrocyte maturation during development and subsequent decreased cognition	Cognitive Disorder	-	0.14	KE:402	Cognitive function, decreased
AOP:486	Binding to the extracellular protein laminin leading to decreased cognitive function	Cognitive Disorder	-	0.14	KE:402	Cognitive function, decreased
AOP:490	Co-activation of IP3R and RyR leads to reduced IQ through non-cholinergic mechanisms	Developmental Disorder Of Mental Health	-	0.09	KE:341	Impairment, Learning and memory
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive System Disease; Cancer	-	0.33	KE:854	Alterations, Cellular proliferation / hyperplasia
					KE:1183	Decreased, Apoptosis (Epithelial Cells)
					KE:2135	Prostate cancer
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	-	0.38	KE:1115	Increase, Reactive oxygen species
					KE:2145	Metabolic syndrome
					KE:2119	Insulin resistance, increased
AOP:498	Increased LCN2/iron complex leading to neurological disorders	Nervous System Disease	-	0.5	KE:191	Neuronal dysfunction
AOP:498		Nervous System Disease	-	0.5	KE:2150	Neurological disorder
AOP:499	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via disrupted neurotransmitter release	Developmental Disorder Of Mental Health	-	0.25	KE:341	Impairment, Learning and memory
AOP:500	Activation of MEK-ERK1/2 leads to deficits in learning and cognition via ROS and apoptosis	Developmental Disorder Of Mental Health	-	0.57	KE:1115	Increase, Reactive oxygen species
					KE:1262	Apoptosis
					KE:341	Impairment, Learning and memory
					KE:352	N/A, Neurodegeneration
AOP:501	Excessive iron accumulation leading to neurological disorders	Nervous System Disease	-	0.25	KE:2150	Neurological disorder
AOP:520	Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory	Developmental Disorder Of Mental Health	-	0.2	KE:341	Impairment, Learning and memory
AOP:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental Disorder Of Mental Health	-	0.08	KE:341	Impairment, Learning and memory
AOP:533	Retinoic acid receptor antagonism during neurodevelopment leading to impaired learning and memory	Developmental Disorder Of Mental Health	-	0.17	KE:341	Impairment, Learning and memory
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:1446	Decrease, Coupling of oxidative phosphorylation
AOP:535	Binding and activation of GPER leading to learning and memory impairments	Developmental Disorder Of Mental Health	-	0.22	KE:1262	Apoptosis
AOP:535		Developmental Disorder Of Mental Health	-	0.22	KE:341	Impairment, Learning and memory
AOP:539	Decreased Sodium/Potassium ATPase activity leads to Heart failure	Cardiovascular System Disease	-	0.29	KE:2261	Decreased, blood plasma volume
AOP:539		Cardiovascular System Disease	-	0.29	KE:1535	Heart failure
AOP:546	Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms	Cancer	-	0.2	KE:885	Increase, Cancer
AOP:550	Increased LMNA gene mutation leading to heart failure	Cardiovascular System Disease	-	0.2	KE:1535	Heart failure
AOP:552	Inhibiton of L-Type Calcium Channels leading to heart failure via QT interval prolongation and Torsades de Pointes (TdP)	Cardiovascular System Disease	-	0.17	KE:1535	Heart failure
AOP:553	Inhibition of Voltage-gated sodium channels (Na⁺ channels) leading to heart failure	Cardiovascular System Disease	-	0.25	KE:1535	Heart failure
AOP:555	Inhibition, Ether-a-go-go (ERG) Voltage-Gated Potassium Channel leading to heart failure	Cardiovascular System Disease	-	0.2	KE:1535	Heart failure
AOP:556	Decreased Na/K ATPase activity leading to heart failure	Cardiovascular System Disease	-	0.17	KE:1535	Heart failure
AOP:558	Phosphodiesterase inhibition leading to heart failure	Cardiovascular System Disease	-	0.17	KE:1535	Heart failure

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:38	Protein Alkylation leading to Liver Fibrosis	Gastrointestinal System Disease	WPHA/WNT Endorsed	0.57	KE:1492	Tissue resident cell activation
					KE:68	Accumulation, Collagen
					KE:1493	Increased Pro-inflammatory mediators
					KE:244	Alkylation, Protein
AOP:62	AKT2 activation leading to hepatic steatosis	Gastrointestinal System Disease; Inherited Metabolic Disorder	-	0.25	KE:486	systemic inflammation leading to hepatic steatosis
AOP:69	Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell	Reproductive System Disease	-	0.2	KE:642	Decreased Cholesterol, Decreased De Novo Biosynthesis of Choleseterol
AOP:128	Kidney dysfunction by decreased thyroid hormone	Urinary System Disease	Under Development	0.09	KE:277	Thyroid hormone synthesis, Decreased
AOP:209	Perturbation of cholesterol and glutathione homeostasis leading to hepatotoxicity: Integrated multi-OMICS approach for building AOP	Gastrointestinal System Disease	-	0.38	KE:1287	Glutathione synthesis
					KE:1286	Down Regulation, GSS and GSTs gene
					KE:1285	Up Regulation, Unsaturated fatty acid
AOP:258	Renal protein alkylation leading to kidney toxicity	Urinary System Disease	Under Development	0.4	KE:40	Decrease, Mitochondrial ATP production
AOP:258	Renal protein alkylation leading to kidney toxicity	Urinary System Disease	Under Development	0.4	KE:244	Alkylation, Protein
AOP:263	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation	Unclassified	WPHA/WNT Endorsed	0.75	KE:1821	Decrease, Cell proliferation
					KE:1771	Decrease, Adenosine triphosphate pool
					KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:264	Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death	Unclassified	Under Development	0.5	KE:1771	Decrease, Adenosine triphosphate pool
AOP:264		Unclassified	Under Development	0.5	KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:265	Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cytosolic calcium	Unclassified	Under Development	0.25	KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:266	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased Na-K ATPase activity	Unclassified	Under Development	0.33	KE:1771	Decrease, Adenosine triphosphate pool
AOP:266		Unclassified	Under Development	0.33	KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:267	Uncoupling of oxidative phosphorylation leading to growth inhibition via glucose depletion	Unclassified	Under Development	0.4	KE:1821	Decrease, Cell proliferation
AOP:267		Unclassified	Under Development	0.4	KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:268	Uncoupling of oxidative phosphorylation leading to growth inhibition via mitochondrial swelling	Unclassified	Under Development	0.25	KE:1446	Decrease, Coupling of oxidative phosphorylation
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	0.33	KE:1115	Increase, Reactive oxygen species
AOP:298		Cancer; Gastrointestinal System Disease	Under Review	0.33	KE:1753	Chronic reactive oxygen species
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	-	0.4	KE:1115	Increase, Reactive oxygen species
AOP:328		Unclassified	-	0.4	KE:1771	Decrease, Adenosine triphosphate pool
AOP:329	Excessive reactive oxygen species production leading to mortality (3)	Unclassified	-	0.4	KE:1115	Increase, Reactive oxygen species
AOP:329		Unclassified	-	0.4	KE:1771	Decrease, Adenosine triphosphate pool
AOP:330	Excessive reactive oxygen species production leading to mortality (4)	Unclassified	-	0.2	KE:1115	Increase, Reactive oxygen species
AOP:331	Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferation	Unclassified	-	0.33	KE:1821	Decrease, Cell proliferation
AOP:331		Unclassified	-	0.33	KE:1115	Increase, Reactive oxygen species
AOP:332	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation	Unclassified	-	0.4	KE:1821	Decrease, Cell proliferation
AOP:332		Unclassified	-	0.4	KE:1115	Increase, Reactive oxygen species
AOP:333	Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation	Unclassified	-	0.8	KE:1821	Decrease, Cell proliferation
					KE:1115	Increase, Reactive oxygen species
					KE:1771	Decrease, Adenosine triphosphate pool
					KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:423	Toxicological mechanisms of hepatocyte apoptosis through the PARP1 dependent cell death pathway	Unclassified	-	0.17	KE:1115	Increase, Reactive oxygen species
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:1919	Increased, Cardiac Dysregulation
AOP:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory System Disease	-	0.4	KE:1262	Apoptosis
					KE:149	Increase, Inflammation
					KE:1496	Increased, secretion of proinflammatory mediators
					KE:1115	Increase, Reactive oxygen species
					KE:1250	Decrease, Lung function
					KE:1993	Increase, Pneumonia
					KE:1497	Increased, recruitment of inflammatory cells
					KE:1198	Activation, Macrophages
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:1198	Activation, Macrophages
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:1198	Activation, Macrophages
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:1198	Activation, Macrophages
AOP:511	The AOP framework on ROS-mediated oxidative stress induced vascular disrupting effects	Cardiovascular System Disease	-	0.06	KE:1115	Increase, Reactive oxygen species
AOP:540	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production	Unclassified	-	0.22	KE:1115	Increase, Reactive oxygen species
AOP:540		Unclassified	-	0.22	KE:1262	Apoptosis
AOP:541	Excessive ROS generation leading to increased incidence of vascular calcification by VSMC phenotype switching	Cardiovascular System Disease	-	0.23	KE:1115	Increase, Reactive oxygen species
					KE:1493	Increased Pro-inflammatory mediators
					KE:1198	Activation, Macrophages

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:447	Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways	Urinary System Disease	-	0.25	KE:1633	Increase in inflammation
					KE:202	Inhibition, Nuclear factor kappa B (NF-kB)
					KE:759	Increased, Kidney Failure
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal System Disease	-	0.36	KE:149	Increase, Inflammation
					KE:1115	Increase, Reactive oxygen species
					KE:1262	Apoptosis
					KE:2034	liver dysfunction
AOP:472	DNA adduct formation leading to kidney failure	Urinary System Disease	-	0.33	KE:149	Increase, Inflammation
					KE:1115	Increase, Reactive oxygen species
					KE:759	Increased, Kidney Failure
AOP:488	Increased reactive oxygen species production leading to decreased cognitive function	Cognitive Disorder	-	0.43	KE:1115	Increase, Reactive oxygen species
					KE:1869	Diminished protective oxidative stress response
					KE:402	Cognitive function, decreased
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	0.6	KE:149	Increase, Inflammation
					KE:1115	Increase, Reactive oxygen species
					KE:885	Increase, Cancer
AOP:513	Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway	Cancer	-	0.6	KE:1115	Increase, Reactive oxygen species
					KE:1060	Alteration, lipid metabolism
					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 GO:0070914 - UV-damage excision repair
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:D002318 - Cardiovascular Diseases MESH:D009202 - Cardiomyopathies
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0002523 - leukocyte migration involved in inflammatory response GO:0006954 - inflammatory response
CTD - Disease	MESH:D007249 - Inflammation
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0072593 - reactive oxygen species metabolic process GO:1903428 - positive regulation of reactive oxygen species biosynthetic 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 GO:0008283 - 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:1900017 - positive regulation of cytokine production involved in inflammatory response
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 GO:0008283 - 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:0008283 - cell population proliferation
CTD - Disease	MESH:D006965 - Hyperplasia
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0045454 - cell redox homeostasis GO:0006915 - apoptotic 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:0006633 - fatty acid biosynthetic 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:0043065 - positive regulation of apoptotic process GO:0006915 - apoptotic 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:0032275 - luteinizing hormone secretion
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0007614 - short-term memory GO:0007611 - learning or memory GO:0007613 - memory GO:0007612 - learning
CTD - Disease	MESH:D007859 - Learning Disabilities
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	GO:0008283 - 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:D011041 - Poisoning
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008283 - 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:0042403 - thyroid hormone 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 GO:0008283 - 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:0002523 - leukocyte migration involved in inflammatory response GO:0006954 - inflammatory response
CTD - Disease	MESH:D005128 - Eye Diseases
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 GO:0008283 - 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 GO:0008283 - 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 GO:0008283 - 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 GO:0008283 - 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 GO:0008283 - 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:0006955 - immune response
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0032964 - collagen biosynthetic 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:0006954 - inflammatory response
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 GO:0008283 - 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 GO:0008283 - 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:0002523 - leukocyte migration involved in inflammatory response GO:0006954 - inflammatory response
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	GO:0043065 - positive regulation of apoptotic process GO:0006915 - apoptotic 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:0036211 - protein modification 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:0006979 - response to oxidative stress
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006754 - ATP biosynthetic process GO:0046034 - ATP 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:0035556 - intracellular signal transduction GO:0007249 - I-kappaB kinase/NF-kappaB signaling
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008285 - negative regulation of cell population proliferation GO:0008283 - 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:0006754 - ATP biosynthetic 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:0036211 - protein modification process
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:D000086382 - COVID-19
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D001847 - Bone Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:C538178 - Acrodermatitis enteropathica
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D000013 - Congenital Abnormalities
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006695 - cholesterol biosynthetic process
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:D000169 - Acrodermatitis
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D012162 - Retinal Degeneration
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D000544 - Alzheimer Disease MESH:D009410 - Nerve Degeneration
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006979 - response to oxidative stress
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0043123 - positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0007249 - I-kappaB kinase/NF-kappaB signaling
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:D007676 - Kidney Failure, Chronic
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D007154 - Immune System Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D002294 - Carcinoma, Squamous Cell MESH:D000230 - Adenocarcinoma MESH:D010051 - Ovarian Neoplasms MESH:D004938 - Esophageal Neoplasms
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D010051 - Ovarian Neoplasms
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0032275 - luteinizing hormone secretion
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0035556 - intracellular signal transduction
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:D011297 - Prenatal Exposure Delayed Effects
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D005234 - Fatty Liver
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D003924 - Diabetes Mellitus, Type 2
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006633 - fatty acid biosynthetic process
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:D009410 - Nerve Degeneration
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D015431 - Weight Loss MESH:D000855 - Anorexia
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006955 - immune response
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:D005234 - Fatty Liver
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D003872 - Dermatitis
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:1900017 - positive regulation of cytokine production involved in inflammatory response
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0007611 - learning or memory GO:0007613 - memory GO:0007612 - learning
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:D013733 - Testicular Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D002294 - Carcinoma, Squamous Cell MESH:D001943 - Breast Neoplasms MESH:D011471 - Prostatic Neoplasms MESH:D000077277 - Esophageal Squamous Cell Carcinoma MESH:D000230 - Adenocarcinoma MESH:D008325 - Mammary Neoplasms, Experimental MESH:D009369 - Neoplasms MESH:D011230 - Precancerous Conditions MESH:D014062 - Tongue Neoplasms
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D012140 - Respiratory Tract Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0036211 - protein modification process
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:D006973 - Hypertension MESH:D006975 - Hypertension, Portal
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0046209 - nitric oxide 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	-
CTD - Disease	MESH:D011225 - Pre-Eclampsia
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0002523 - leukocyte migration involved in inflammatory response GO:0006954 - inflammatory response
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:D016481 - Helicobacter Infections
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D000544 - Alzheimer Disease MESH:D009410 - Nerve Degeneration MESH:C566627 - Ceroid Lipofuscinosis, Neuronal, 6
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D006333 - Heart Failure
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D006130 - Growth Disorders
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D064420 - Drug-Related Side Effects and Adverse Reactions
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D001943 - Breast Neoplasms
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 GO:0008283 - 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:D007674 - Kidney Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0032731 - positive regulation of interleukin-1 beta production GO:0006954 - inflammatory response
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:D003920 - Diabetes Mellitus
DEDuCT - endocrine-mediated endpoint	-
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	MESH:D003643 - Death
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006915 - apoptotic process
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:D011471 - Prostatic Neoplasms
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D006943 - Hyperglycemia MESH:D024821 - Metabolic Syndrome MESH:C538178 - Acrodermatitis enteropathica
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D010300 - Parkinson Disease MESH:D009410 - Nerve Degeneration MESH:D001930 - Brain Injuries
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D010300 - Parkinson Disease MESH:D001321 - Autistic Disorder MESH:D000067877 - Autism Spectrum Disorder MESH:D012608 - Scrapie MESH:D009422 - Nervous System Diseases MESH:D001930 - Brain Injuries MESH:D008569 - Memory Disorders MESH:D014202 - Tremor MESH:D013226 - Status Epilepticus
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0051881 - regulation of mitochondrial membrane potential
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008217 - regulation of blood pressure
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0036211 - protein modification 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:0002523 - leukocyte migration involved in inflammatory response GO:0006954 - inflammatory response
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006695 - cholesterol biosynthetic 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:0006750 - glutathione biosynthetic 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:0004364 - glutathione transferase activity
CTD - Disease	-
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0006633 - fatty acid biosynthetic process GO:0006636 - unsaturated fatty acid biosynthetic 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:0006979 - response to oxidative stress
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:D006331 - Heart Diseases
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	-
CTD - Disease	MESH:D011014 - Pneumonia
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0001774 - microglial cell activation
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:D008106 - Liver Cirrhosis, Experimental MESH:D006501 - Hepatic Encephalopathy
DEDuCT - endocrine-mediated endpoint	-
NeurotoxKb - neurotoxic endpoints	-
REACH Dossier - experimental data	-
ToxCast invitrodb v4.2	-

Source	Evidence
AOP-Wiki	-
CTD - Phenotype	GO:0008610 - lipid biosynthetic process GO:0016042 - lipid catabolic process
CTD - Disease	-
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.

Zinc

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