DEDUCT | Database of Endocrine Disrupting chemicals and their Toxicity profiles

Hexabromocyclododecane

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	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
AOP:8	Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Nervous system disease	Under Development	Rat	0.33	KE:961	Increased, Clearance of thyroxine from serum
						KE:280	Thyroxine (T4) in neuronal tissue, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:15	Alkylation of DNA in male pre-meiotic germ cells leading to heritable mutations	Genetic disease	WPHA/WNT Endorsed	Mus musculus, Drosophila melanogaster, Oryzias latipes, Syrian golden hamster	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	Zebrafish, Medaka, Gallus gallus	0.2	KE:317	Altered, Cardiovascular development/function
AOP:37	PPARα activation leading to hepatocellular adenomas and carcinomas in rodents	Cancer; Gastrointestinal system disease	Under Development	Mouse, Rat	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	Human, Mouse	0.2	KE:272	Activation/Proliferation, T-cells
AOP:40	Covalent Protein binding leading to Skin Sensitisation	Integumentary system disease	WPHA/WNT Endorsed	Mouse, Human	0.2	KE:272	Activation/Proliferation, T-cells
AOP:41	Sustained AhR Activation leading to Rodent Liver Tumours	Cancer; Gastrointestinal system disease	Under Review	Rattus sp. ABTC 42503, Mus sp. 2000082	0.6	KE:854	Alterations, Cellular proliferation / hyperplasia
						KE:853	Changes/Inhibition, Cellular Homeostasis and Apoptosis
						KE:139	N/A, Hepatotoxicity, Hepatopathy, including a constellation of observable effects
AOP:42	Inhibition of Thyroperoxidase and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	WPHA/WNT Endorsed	Human, Rat, Mouse	0.25	KE:280	Thyroxine (T4) in neuronal tissue, Decreased
AOP:42		Cognitive disorder	WPHA/WNT Endorsed	Human, Rat, Mouse	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:58	NR1I3 (CAR) suppression leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-	Human, Mouse, Rat	0.06	KE:454	Increased, Triglyceride formation
AOP:60	NR1I2 (Pregnane X Receptor, PXR) activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.08	KE:454	Increased, Triglyceride formation
AOP:64	Glucocorticoid Receptor (GR) Mediated Adult Leydig Cell Dysfunction Leading to Decreased Male Fertility	Reproductive system disease	-	Rattus norvegicus	0.29	KE:496	Increased apoptosis, decreased fetal/adult Leydig Cells
AOP:64		Reproductive system disease	-	Rattus norvegicus	0.29	KE:495	Repressed expression of steroidogenic enzymes
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:77	Nicotinic acetylcholine receptor activation contributes to abnormal foraging and leads to colony death/failure 1	Unclassified	-	Honey bee	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	-	Honey bee	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	-	Honey bee	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	-	Honey bee	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	-	Honey bee	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	-	Honey bee	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	-	Honey bee	0.12	KE:341	Impairment, Learning and memory
AOP:99	Histamine (H2) receptor antagonism leading to reduced survival	Unclassified	-	Zebrafish	0.14	KE:341	Impairment, Learning and memory
AOP:102	Cyclooxygenase inhibition leading to reproductive dysfunction via interference with meiotic prophase I /metaphase I transition	Reproductive system disease	-	Goldfish, Human, Rat, Mouse	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	-	Goldfish, Human, Rat, Mouse	0.1	KE:690	Reduced, Luteinizing hormone (LH), plasma
AOP:104	Altered ion channel activity leading impaired heart function	Unclassified	-		0.25	KE:699	Increased, cardiac arrthymia
AOP:105	Alpha2u-microglobulin cytotoxicity leading to renal tubular adenomas and carcinomas (in male rat)	Cancer; Urinary system disease	-	Rattus norvegicus	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	Rattus norvegicus, Mus musculus	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	-	Mus musculus, Rattus norvegicus	0.17	KE:768	Increase, Cytotoxicity
AOP:109	Cytotoxicity leading to bronchioloalveolar adenomas and carcinomas (in mouse)	Cancer; Respiratory system disease	-	Mus musculus	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	-	Rattus norvegicus, Mus musculus	0.43	KE:1023	Increased, Thyroid-stimulating hormone (TSH)
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:739	Increase, Hypertrophy and proliferation (follicular cell)
AOP:114	HPPD inhibition leading to corneal papillomas and carcinomas (in rat)	Cancer	-	Rattus norvegicus	0.17	KE:778	Increase, Regenerative cell proliferation (corneal cells)
AOP:115	Epithelial cytotoxicity leading to forestomach tumors (in mouse and rat)	Cancer	-	Mus musculus, Rattus norvegicus	0.2	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	-	Rattus norvegicus	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	Mus musculus, Rattus norvegicus	0.25	KE:716	Increase, cell proliferation (hepatocytes)
AOP:119	Inhibition of thyroid peroxidase leading to follicular cell adenomas and carcinomas (in rat and mouse)	Cancer; Endocrine system disease	-	Rattus norvegicus, Mus musculus	0.43	KE:1023	Increased, Thyroid-stimulating hormone (TSH)
						KE:281	Thyroxine (T4) in serum, Decreased
						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	-	Mus musculus, Rattus norvegicus	0.2	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:124	HMG-CoA reductase inhibition leading to decreased fertility	Reproductive system disease	-	Rattus rattus	0.17	KE:807	Decreased, cholesterol
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:128	Kidney dysfunction by decreased thyroid hormone	Urinary system disease	Under Development	Sprague-Dawley, Homo sapiens	0.09	KE:281	Thyroxine (T4) in serum, Decreased
AOP:134	Sodium Iodide Symporter (NIS) Inhibition and Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Homo sapiens	0.22	KE:280	Thyroxine (T4) in neuronal tissue, Decreased
AOP:134		Cognitive disorder	-	Rat, Homo sapiens	0.22	KE:281	Thyroxine (T4) in serum, Decreased
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:150	Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF	Unclassified	WPHA/WNT Endorsed	Chicken, Zebrafish, Mouse, Rattus norvegicus	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	Zebrafish, Fathead minnow	0.12	KE:281	Thyroxine (T4) in serum, Decreased
AOP:164	Beta-2 adrenergic agonist activity leading to mesovarian leiomyomas in the rat and mouse	Cancer; Reproductive system disease	-	CD-1 mouse, SD rat	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	-	Mouse, Homo sapiens	0.14	KE:1067	Proliferation/Clonal Expansion, aberrant basal cells
AOP:175	Thyroperoxidase inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:176	Sodium Iodide Symporter (NIS) Inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.2	KE:281	Thyroxine (T4) in serum, Decreased
AOP:188	Iodotyrosine deiodinase (IYD) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.2	KE:281	Thyroxine (T4) in serum, Decreased
AOP:190	Type II iodothyronine deiodinase (DIO2) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.17	KE:1023	Increased, Thyroid-stimulating hormone (TSH)
AOP:191	Type III iodotyrosine deiodinase (DIO3) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.25	KE:1154	Increased, Triiodothyronine (T3) in tissues
AOP:192	Pendrin inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:193	Dual oxidase (DUOX) inhibition leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.25	KE:281	Thyroxine (T4) in serum, Decreased
AOP:194	Hepatic nuclear receptor activation leading to altered amphibian metamorphosis	Unclassified	-	African clawed frog	0.33	KE:961	Increased, Clearance of thyroxine from serum
AOP:194		Unclassified	-	African clawed frog	0.33	KE:281	Thyroxine (T4) in serum, Decreased
AOP:207	NADPH oxidase and P38 MAPK activation leading to reproductive failure in Caenorhabditis elegans	Reproductive system disease	-	Caenorhabditis elegans	0.25	KE:1281	Increased, DNA Damage-Repair
AOP:207		Reproductive system disease	-	Caenorhabditis elegans	0.25	KE:1262	Apoptosis
AOP:245	Reduction in photophosphorylation leading to growth inhibition in aquatic plants	Unclassified	-	Lemna minor, Lemna gibba	0.09	KE:40	Decrease, Mitochondrial ATP production
AOP:258	Renal protein alkylation leading to kidney toxicity	Urinary system disease	Under Development	Human, Rat, Mouse	0.2	KE:40	Decrease, Mitochondrial ATP production
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	Human, Rat, Mouse	0.29	KE:155	Inadequate DNA repair
AOP:272	Deposition of energy leading to lung cancer	Cancer	WPHA/WNT Endorsed	Human, Rat, Mouse	0.29	KE:870	Increase, Cell Proliferation
AOP:275	Histone deacetylase inhibition leads to neural tube defects	Neural tube defect	-		0.2	KE:1239	Altered, Gene Expression
AOP:286	Mitochondrial complex III antagonism leading to growth inhibition (1)	Unclassified	-	Lemna minor, Daphnia magna, Danio rerio	0.5	KE:1821	Decrease, Cell proliferation
AOP:286		Unclassified	-	Lemna minor, Daphnia magna, Danio rerio	0.5	KE:1771	Decrease, Adenosine triphosphate pool
AOP:287	Mitochondrial complex III antagonism leading to growth inhibition (2)	Unclassified	-	Lemna minor, Daphnia magna, Danio rerio	0.25	KE:1771	Decrease, Adenosine triphosphate pool
AOP:290	Mitochondrial ATP synthase antagonism leading to growth inhibition (1)	Unclassified	-	Daphnia magna	0.5	KE:1821	Decrease, Cell proliferation
AOP:290		Unclassified	-	Daphnia magna	0.5	KE:1771	Decrease, Adenosine triphosphate pool
AOP:291	Mitochondrial ATP synthase antagonism leading to growth inhibition (2)	Unclassified	-	Daphnia magna	0.25	KE:1771	Decrease, Adenosine triphosphate pool
AOP:293	Increased DNA damage leading to increased risk of breast cancer	Genetic disease; Thoracic disease; Cancer	Under Development	Rattus rattus, Mus musculus	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:296	Oxidative DNA damage leading to chromosomal aberrations and mutations	Genetic disease; Chromosomal disease	WPHA/WNT Endorsed	Human, Mice, Rat, Fish	0.2	KE:155	Inadequate DNA repair
AOP:303	Frustrated phagocytosis-induced lung cancer	Cancer	Under Development	Mammals	0.14	KE:870	Increase, Cell Proliferation
AOP:321	Reduced environmental pH leading to thinner shells in Mytilus edulis	Unclassified	-		0.09	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	-	Teleost fish	0.17	KE:807	Decreased, cholesterol
AOP:328	Excessive reactive oxygen species production leading to mortality (2)	Unclassified	-	Daphnia magna	0.2	KE:1771	Decrease, Adenosine triphosphate pool
AOP:329	Excessive reactive oxygen species production leading to mortality (3)	Unclassified	-	Daphnia magna, Paracyclopina nana	0.2	KE:1771	Decrease, Adenosine triphosphate pool
AOP:331	Excessive reactive oxygen species leading to growth inhibition via oxidative DNA damage and reduced cell proliferation	Unclassified	-	Daphnia magna, Daphnia middendorffiana, Daphnia pulex, Daphnia pulicaria, Daphnia parvula	0.17	KE:1821	Decrease, Cell proliferation
AOP:332	Excessive reactive oxygen species leading to growth inhibition via lipid peroxidation and reduced cell proliferation	Unclassified	-		0.2	KE:1821	Decrease, Cell proliferation
AOP:333	Excessive reactive oxygen species leading to growth inhibition via uncoupling of oxidative phosphorylation	Unclassified	-		0.6	KE:1821	Decrease, Cell proliferation
						KE:1771	Decrease, Adenosine triphosphate pool
						KE:1446	Decrease, Coupling of oxidative phosphorylation
AOP:335	AOP for urothelial carcinogenesis due to chemical cytotoxicity by mitochondrial impairment	Cancer; Urinary system disease	-	Rat	0.2	KE:795	Increase, Regenerative cell proliferation (urothelial cells)
AOP:363	Thyroperoxidase inhibition leading to altered visual function via altered retinal layer structure	Unclassified	Under Review	Zebrafish	0.12	KE:281	Thyroxine (T4) in serum, Decreased
AOP:364	Thyroperoxidase inhibition leading to altered visual function via decreased eye size	Unclassified	Under Development		0.12	KE:281	Thyroxine (T4) in serum, Decreased
AOP:365	Thyroperoxidase inhibition leading to altered visual function via altered photoreceptor patterning	Unclassified	Under Development		0.12	KE:281	Thyroxine (T4) in serum, Decreased
AOP:366	Competitive binding to thyroid hormone carrier protein transthyretin (TTR) leading to altered amphibian metamorphosis	Unclassified	-		0.29	KE:961	Increased, Clearance of thyroxine from serum
AOP:366		Unclassified	-		0.29	KE:281	Thyroxine (T4) in serum, Decreased
AOP:367	Competitive binding to thyroid hormone carrier protein thyroid binding globulin (TBG) leading to altered amphibian metamorphosis	Unclassified	-		0.29	KE:961	Increased, Clearance of thyroxine from serum
AOP:367		Unclassified	-		0.29	KE:281	Thyroxine (T4) in serum, Decreased
AOP:387	Deposition of ionising energy leading to population decline via mitochondrial dysfunction	Reproductive system disease	-	Lemna minor	0.12	KE:40	Decrease, Mitochondrial ATP 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	-	Zebrafish	0.12	KE:1821	Decrease, Cell proliferation
AOP:409	Frustrated phagocytosis leads to malignant mesothelioma	Cancer	-		0.12	KE:870	Increase, Cell Proliferation
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:432	Deposition of Energy by Ionizing Radiation leading to Acute Myeloid Leukemia	Hematopoietic system disease; Cancer	-	Homo sapiens, Mus musculus	0.18	KE:155	Inadequate DNA repair
AOP:432		Hematopoietic system disease; Cancer	-	Homo sapiens, Mus musculus	0.18	KE:870	Increase, Cell Proliferation
AOP:438	reactive oxygen species generation leading to increased cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.08	KE:1919	Increased, Cardiac Dysregulation
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic disease; Cancer	Under Development	Humans, Mice	0.22	KE:1971	Increased, tumor growth
AOP:439	Activation of the AhR leading to metastatic breast cancer	Thoracic disease; Cancer	Under Development	Humans, Mice	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	-	Homo sapiens, Mus musculus musculus, Rattus norvegicus	0.14	KE:1262	Apoptosis
AOP:443	DNA damage and mutations leading to Metastatic Breast Cancer	Thoracic disease; Cancer	Under Development	Human and other cells in culture, Human, Mice, Rat, Canine heartworm nematode, Yeast	0.1	KE:155	Inadequate DNA repair
AOP:448	ROS, inflammation, and activation of nAChR lead to increased incidence of cardiovascular morbidity and mortality	Cardiovascular system disease	-		0.06	KE:2001	Cardiac hypertrophy
AOP:451	Interaction with lung resident cell membrane components leads to lung cancer	Cancer	-	Human	0.11	KE:870	Increase, Cell Proliferation
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory system disease	-		0.18	KE:2013	Airway remodeling
AOP:452	Adverse outcome pathway of PM-induced respiratory toxicity	Respiratory system disease	-		0.18	KE:1262	Apoptosis
AOP:456	Aryl hydrocarbon receptor activation leading to early life stage mortality via sox9 repression induced cardiovascular toxicity	Unclassified	Under Review	Zebrafish, Mouse, Human, Chicken	0.17	KE:317	Altered, Cardiovascular development/function
AOP:458	AhR activation in the liver leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Rat, Mouse, Monkey, Human	0.38	KE:961	Increased, Clearance of thyroxine from serum
						KE:280	Thyroxine (T4) in neuronal tissue, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
AOP:459	AhR activation in the thyroid leading to Subsequent Adverse Neurodevelopmental Outcomes in Mammals	Cognitive disorder	-	Human, Mouse, Rat	0.22	KE:280	Thyroxine (T4) in neuronal tissue, Decreased
AOP:459		Cognitive disorder	-	Human, Mouse, Rat	0.22	KE:281	Thyroxine (T4) in serum, Decreased
AOP:460	Antagonism of Smoothened receptor leading to orofacial clefting	Unclassified	Under Development	Mouse	0.22	KE:1821	Decrease, Cell proliferation
AOP:460		Unclassified	Under Development	Mouse	0.22	KE:1262	Apoptosis
AOP:478	Deposition of energy leading to occurrence of cataracts	Nervous system disease; Monogenic disease	Under Review	Human, Mouse, Rat, Rhesus monkeys, Rabbit, Guinea pig	0.2	KE:155	Inadequate DNA repair
AOP:478	Deposition of energy leading to occurrence of cataracts	Nervous system disease; Monogenic disease	Under Review	Human, Mouse, Rat, Rhesus monkeys, Rabbit, Guinea pig	0.2	KE:870	Increase, Cell Proliferation
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	Mouse	0.33	KE:1821	Decrease, Cell proliferation
AOP:491		Unclassified	Under Development	Mouse	0.33	KE:1262	Apoptosis
AOP:493	ERa inactivation alters AT expansion and functions and leads to insulin resistance and metabolically unhealthy obesity	Acquired metabolic disease	-	Mus musculus, Homo sapiens	0.2	KE:2119	Insulin resistance, increased
AOP:493		Acquired metabolic disease	-	Mus musculus, Homo sapiens	0.2	KE:2125	Increased fat mass
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.22	KE:854	Alterations, Cellular proliferation / hyperplasia
AOP:495	Androgen receptor activation leading to prostate cancer	Reproductive system disease; Cancer	-		0.22	KE:1183	Decreased, Apoptosis (Epithelial Cells)
AOP:521	Essential element imbalance leads to reproductive failure via oxidative stress	Unclassified	-	Murinae gen. sp.	0.14	KE:2206	Increased, histomorphological alteration of testis
AOP:532	Retinoic acid receptor agonism during cerebellar development leading to impaired locomotor function	Unclassified	-		0.2	KE:2230	Cerebellar hypoplasia
AOP:540	Oxidative Stress in the Fish Ovary Leads to Reproductive Impairment via Reduced Vitellogenin Production	Unclassified	-		0.11	KE:1262	Apoptosis
AOP:563	Aryl hydrocarbon Receptor (AHR) activation causes Premature Ovarian Insufficiency via Bax mediated apoptosis	Reproductive system disease; Endocrine system disease	-	Rat, Mouse, Zebra fish, Human	0.17	KE:1262	Apoptosis
AOP:564	DBDPE-induced inhibition of mitochondrial complex Ⅰ leading to population decline via neurotoxicity and metabotoxicity.	Unclassified	-	Zebrafish	0.09	KE:40	Decrease, Mitochondrial ATP production

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	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
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	Monkey, Rat, Human, Mouse, Zebrafish	0.12	KE:341	Impairment, Learning and memory
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	Human, Mouse, Monkey sp., Rat	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	Rat, Mouse, Human	0.1	KE:341	Impairment, Learning and memory
AOP:34	LXR activation leading to hepatic steatosis	Gastrointestinal system disease; Inherited metabolic disorder	-		0.08	KE:345	N/A, Liver Steatosis
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	Human, Mouse, Rat	0.11	KE:341	Impairment, Learning and memory
AOP:54	Inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment	Developmental disorder of mental health	WPHA/WNT Endorsed	Homo sapiens, Rattus sp.	0.3	KE:280	Thyroxine (T4) in neuronal tissue, Decreased
						KE:281	Thyroxine (T4) in serum, Decreased
						KE:341	Impairment, Learning and memory
AOP:139	Alkylation of DNA leading to cancer 1	Cancer	-	Homo sapiens, Mus musculus	0.5	KE:885	Increase, Cancer
AOP:139	Alkylation of DNA leading to cancer 1	Cancer	-	Homo sapiens, Mus musculus	0.5	KE:155	Inadequate DNA repair
AOP:205	AOP from chemical insult to cell death	Unclassified	-	Vertebrates	0.17	KE:1262	Apoptosis
AOP:212	Histone deacetylase inhibition leading to testicular atrophy	Reproductive system disease	WPHA/WNT Endorsed	Rat, Human, Mouse	0.33	KE:1506	Testicular atrophy
AOP:212		Reproductive system disease	WPHA/WNT Endorsed	Rat, Human, Mouse	0.33	KE:1262	Apoptosis
AOP:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal system disease	WPHA/WNT Endorsed	Rodents, Homo sapiens	0.4	KE:1395	Liver Cancer
AOP:220	Cyp2E1 Activation Leading to Liver Cancer	Cancer; Gastrointestinal system disease	WPHA/WNT Endorsed	Rodents, Homo sapiens	0.4	KE:1393	Hepatocytotoxicity
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:457	Succinate dehydrogenase inhibition leading to increased insulin resistance through reduction in circulating thyroxine	Inherited metabolic disorder	-	Human	0.33	KE:2119	Insulin resistance, increased
AOP:457		Inherited metabolic disorder	-	Human	0.33	KE:281	Thyroxine (T4) in serum, Decreased
AOP:463	The AOP framwork on silica nanopariticles induced hepatoxicity	Gastrointestinal system disease	-		0.18	KE:2034	liver dysfunction
AOP:463		Gastrointestinal system disease	-		0.18	KE:1262	Apoptosis
AOP:474	Succinate dehydrogenase inactivation leads to cancer by promoting EMT	Cancer	Under Development	Human and other cells in culture	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	Mouse, Rat, Human, Caenorhabditis elegans	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	Mouse, Rat, Rabbit, Dog, Pigs, Cow, Human	0.12	KE:341	Impairment, Learning and memory
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: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	-		0.12	KE:2119	Insulin resistance, increased
AOP:498	Increased LCN2/iron complex leading to neurological disorders	Nervous system disease	-	Homo sapiens	0.25	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	-	Rattus norvegicus, Mus musculus, Homo sapiens	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	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.29	KE:1262	Apoptosis
AOP:500		Developmental disorder of mental health	-	Rattus norvegicus, Mus musculus, Homo sapiens	0.29	KE:341	Impairment, Learning and memory
AOP:501	Excessive iron accumulation leading to neurological disorders	Nervous system disease	-	Homo sapiens	0.25	KE:2150	Neurological disorder
AOP:505	Reactive Oxygen Species (ROS) formation leads to cancer via inflammation pathway	Cancer	-	Human, Mouse, Rat	0.2	KE:885	Increase, Cancer
AOP:513	Reactive Oxygen (ROS) formation leads to cancer via Peroxisome proliferation-activated receptor (PPAR) pathway	Cancer	-	Human, Mouse, Rat	0.4	KE:885	Increase, Cancer
AOP:513		Cancer	-	Human, Mouse, Rat	0.4	KE:1060	Alteration, lipid metabolism
AOP:520	Retinoic acid receptor agonism during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-	Mouse, Rat, Human	0.4	KE:2204	Altered brain morphology
AOP:520		Developmental disorder of mental health	-	Mouse, Rat, Human	0.4	KE:341	Impairment, Learning and memory
AOP:525	Reduced oligodendrocyte differentiation during neurodevelopment leading to impaired learning and memory	Developmental disorder of mental health	-		0.15	KE:2115	Altered, cholesterol metabolism
AOP:525		Developmental disorder of mental health	-		0.15	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	-		0.33	KE:1239	Altered, Gene Expression
AOP:533		Developmental disorder of mental health	-		0.33	KE:341	Impairment, Learning and memory
AOP:534	Succinate dehydrogenase (SDH) inhibition leads to cancer through oxidative stress	Cancer	-	Vertebrates	0.33	KE:885	Increase, Cancer
AOP:534		Cancer	-	Vertebrates	0.33	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	-	Mouse, Human	0.22	KE:1262	Apoptosis
AOP:535		Developmental disorder of mental health	-	Mouse, Human	0.22	KE:341	Impairment, Learning and memory
AOP:546	Succinate dehydrogenase inactivation leads to cancer through hypoxic-like mechanisms	Cancer	-	Human and other cells in culture	0.2	KE:885	Increase, Cancer
AOP:551	Increased Muscarinic M2 Receptor leading to Arrhythmia	Symptom	-	Human, Mouse, Rat	0.2	KE:1106	Occurrence, cardiac arrhythmia
AOP:554	β-adrenergic receptor agonists leading to arrhythmias.	Symptom	-	Human and other cells in culture, Rodents, Macaca mulatta, Zebrafish, Gallus gallus	0.25	KE:1106	Occurrence, cardiac arrhythmia
AOP:559	Inhibition of acetylcholinesterase (AChE) leading to arrhythmias	Symptom	-	Human and other cells in culture, Rattus norvegicus, Dogs, Sus scrofa, Zebrafish, Insecta sp. BOLD:AAN5199	0.2	KE:1106	Occurrence, cardiac arrhythmia
AOP:560	Inhibition of Funny current (If) leading to Arrhythmias	Symptom	-	Human and other cells in culture, Rodents, Dogs, Zebrafish	0.25	KE:1106	Occurrence, cardiac arrhythmia
AOP:562	HCN Channel Inhibition leading to Arrhythmias	Symptom	-	Human and other cells in culture, Dogs, Zebrafish, Rodents, Pigs	0.2	KE:1106	Occurrence, cardiac arrhythmia

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	Taxonomic applicability	Coverage Score ⓘ The fraction of KEs within the AOP, that are mapped to the chemical-associated toxicological endpoints.	KE Identifier	KE Name
AOP:69	Modulation of Adult Leydig Cell Function Subsequent to Decreased Cholesterol Synthesis or Transport in the Adult Leydig Cell	Reproductive system disease	-	Rattus norvegicus, Homo sapiens	0.2	KE:642	Decreased Cholesterol, Decreased De Novo Biosynthesis of Choleseterol
AOP:118	Chronic cytotoxicity leading to hepatocellular adenomas and carcinomas (in mouse and rat)	Cancer; Gastrointestinal system disease	-	Mus musculus, Rattus norvegicus	0.5	KE:786	Increase, Cytotoxicity (hepatocytes)
AOP:118		Cancer; Gastrointestinal system disease	-	Mus musculus, Rattus norvegicus	0.5	KE:787	Increase, Regenerative cell proliferation (hepatocytes)
AOP:263	Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation	Unclassified	WPHA/WNT Endorsed	Zebrafish, Mouse, Rat, Lemna minor, Human, Caenorhabditis elegans	0.75	KE:1771	Decrease, Adenosine triphosphate pool
						KE:1446	Decrease, Coupling of oxidative phosphorylation
						KE:1821	Decrease, Cell proliferation
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:446	PM-related Adverse outcome pathway frameworks on various systems	Respiratory system disease	-		0.1	KE:1239	Altered, Gene Expression
AOP:446		Respiratory system disease	-		0.1	KE:1262	Apoptosis

No associated AOPs with Level of Relevance 5

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We have built a comprehensive resource which compiles potential endocrine disrupting chemicals (EDCs) based on the observed adverse effects or endocrine-mediated endpoints in published experiments on humans or rodents to support basic research. We are not responsible for any errors or omissions in the published research articles or supporting literature on potential EDCs compiled in this resource. Users are advised to exercise their own judgement on the weight of evidence for potential EDCs compiled in this resource. Importantly, our sole goal to build this resource on potential EDCs is to enable future basic research towards better understanding of the systems-level perturbations upon chemical exposure rather than influencing regulatory advice on chemical use.